AMERICAN ACADEMY OF PEDIATRICS IMPROVING THE AVAILABILITY OF PEDIATRIC DEVICES Washington, D.C. Monday, June 28, 2004 2 1 PARTICIPANTS: 2 JON S. ABRAMSON, M.D. 3 JOANNE R. LESS, PH.D. 4 BRAM D. ZUCKERMAN, M.D. 5 SUSAN MEADOWS, M.S. 6 LYNNE RICE 7 MARLENE HAFFNER, M.D. 8 ROSEMARY ROBERTS, M.D. 9 TERRIE L. CRESCENDI 10 KHODAYAR RAIS-BAHRAMI, M.D. 11 ROBERT M. CAMPBELL, JR., M.D. 12 LOU QUATRANO 13 ANDRE A. MUELENAER, JR., M.D. 14 ALFRED L. WICKS 15 JOHN H. GREINWALD, M.D. 16 ROBERT H. O'HOLLA 17 PATRICIA B. SHRADER, Esquire 18 TOM CONNAUGHTON 19 TODD ENGLANDER 20 MARIBETH SAYRE, M.D. 21 SUSAN ALPERT, M.D. 22 KATHY JENKINS, M.D. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 3 1 PARTICIPANTS (CONT'D): 2 MURRAY M. LUMPKIN, M.D. 3 ELAINE VINING 4 JEANNE IRELAND 5 DIANE DORMAN 6 STEVEN GROSSMAN 7 ELIZABETH JACOBSON 8 TARN FEDERICI 9 BENJAMIN H. WALLFISCH 10 MARILYN J. FIELD 11 ANN LANGLEY 12 LISA KAESER 13 SARAH LINDEFOYT, M.D. 14 15 16 17 * * * * * 18 19 20 21 22 BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 4 1 P R O C E E D I N G S 2 (8:57 a.m.) 3 DR. ABRAMSON: We'll start out by 4 just everybody introducing themselves, 5 talking about what their affiliation is; if 6 they want to say a sentence or two and what 7 their interest is. 8 I'll start out. I'm John 9 Abramson. I'm Chair of the Department of 10 Pediatrics at Wake Forest and I just am the 11 past head of the Committee on Infectious 12 Disease Redbook where issues of both drugs 13 and devices come up repeatedly and we asked 14 the Academy to think about both. Initially, 15 they took on the issue of drugs and now 16 we're about to take on the issue of devices, 17 and also I'll also talk about a little bit 18 the issue of tests; lab tests, those kind of 19 things. 20 Mac, do you want to go around? 21 DR. LUMPKIN: Sure. Hi. Good 22 morning, everybody. I'm Mac Lumpkin. I am BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 5 1 the Acting Deputy Commission at FDA for 2 International and Special Programs. My 3 background is pediatric infectious diseases 4 and I'm here with a fairly large delegation 5 from FDA and people who will introduce 6 themselves as we get around to that part of 7 the table. 8 DR. JENKINS: I'm Kathy Jenkins. 9 I'm a pediatric cardiologist at the 10 Children's Hospital in Boston and I've been 11 involved with sponsoring pediatric device 12 trials for a number of years through my 13 hospital. 14 DR. ALPERT: I'm Susan Alpert. 15 I'm a chief quality and regulatory officer 16 at Medtronic in Minneapolis, and I used to 17 be with FDA. I'm also a pediatrician, 18 pediatric-infectious disease, two careers 19 ago. 20 DR. SAYRE: I'm Maribeth Sayre. 21 I'm with Masimo Corporation. We make pulse 22 oximeters and are based in Irvine, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 6 1 California, and I'm a neonatologist by 2 training. 3 MR. ENGLANDER: My name is Todd 4 Englander. I'm a retail sales manager for 5 Cook Critical Care, one of the companies and 6 this is my first meeting. 7 MR. CONNAUGHTON: I'm Tom 8 Connaughton, Vice President of Legislative 9 Affairs 컴컴 pediatrics product, 10 particularly for critical care, and I'm 11 happy to be here. 12 MS. SHRADER: Good morning. I'm 13 Pat Shrader, with 컴컴 Dickinson & Company. 14 I'm Vice President for Public Policy and 15 Regulatory Affairs. For those of you who 16 are not familiar, we make a lot of low-risk 17 devices, but encounter, I think some of the 18 same issues, with devices for the pediatric 19 population that some of the other companies 20 do. 21 MR. O'HOLLA: Good morning. I'm 22 Bob O'Holla, Vice President of Regulatory BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 7 1 Affairs for the Device Businesses, within 2 Johnson & Johnson, and going back to our 3 history, we care about babies, and so we're 4 very interested in defining the topic here 5 this morning so we have a clear direction 6 forward. 7 MR. WICKS: Good morning. I'm Al 8 Wicks. I'm a professor of mechanical 9 engineering, Virginia Tech. My area is 10 instrumentation signal processing. We have 11 a strong relationship with Wake Forest now 12 and 컴컴 Biomedical, where we try to 13 integrate the activities in the chemical 14 engineer department with medical needs and I 15 have an interest in that area. 16 DR. MUELENAER: I'm Andy 17 Muelenaer. I'm from the 컴컴 Biomedical 18 Institute, but I'm also a practicing 19 pediatric pulmonologist in critical care and 20 I went in the military, did neonatology 21 also. I'm the medical director for the 컴컴 22 Biomedical Institute, which is a partnership BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 8 1 between an integrated health system, the 2 University of Virginia, and Virginia Tech, 3 and I've worked with Al on projects. 4 My reason for being here is I'm 5 involved in technology transfer from the 6 universities and the development of medical 7 devices. I'm also an inventor and I also 8 own my own small company. So I have several 9 perspectives today. 10 MR. QUATRANO: My name's Louis 11 Quatrano. I'm with the National Institutes 12 of Child Health and Community Development, 13 and in particular, the National Center for 14 Medical Rehabilitation Research and involved 15 in supporting device development and so 16 forth as the program 컴컴. 17 MR. CAMPBELL: I'm Bob Campbell, a 18 pediatric orthopedist at the University of 19 Texas outside San Antonio. I'm very 20 interested in 컴컴 surgical devices; I 21 helped developed one, and I'm on the 22 National Organization of Rare Disorders BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 9 1 Medical Advisory Committee. 2 DR. RAIS-BAHRAMI: Good morning. 3 I'm Rais-Bahrami Khodayar. I'm a 4 neonatologist at Children's National Medical 5 Center at the George Washington School of 6 Medicine. 7 MS. ROBERTS: I'm Rosemary 8 Roberts. I am from the Center from Drugs. 9 I am the Deputy Director of the Office of 10 Counterterrorism and Pediatric Drug Czar. 11 (?) 12 (Laughter) 13 DR. LUMPKIN: Also known as bombs 14 and babies. 15 (Laughter) 16 DR. HAFFNER: Hi. I'm Marlene 17 Haffner. I'm the I think sole internist in 18 the group here, so I'm delighted that you 19 allow me to be here. I have, for the last 20 almost 18 years, been responsible for the 21 FDA's Office of Orphan Products Development, 22 just finding ways to develop particularly BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 10 1 drugs, but also devices for folks with rare 2 diseases. We have long targeted pediatrics, 3 so we're really pleased to see emphasis from 4 the device arena coming here and we worked 5 closely with Dr. Campbell in the development 6 of his device. So I'm delighted to be here. 7 I have one other thing to say and 8 that is that -- and I think I can say this 9 in a pediatric group -- I have a bit of ADD 10 and so I do needlepoint during meetings. 11 It's the only way I can concentrate, 12 otherwise, I'm not here. So I hope I don't 13 bother you. 14 (Laughter) 15 MS. RICE: I'm Lynn Rice. I'm 16 with the Center for Devices and Radiological 17 컴컴. I'm also Director of the Office of 18 Communication, Education and Radiation 19 Programs and so we're here to work on how we 20 can put the education piece as well as 21 working on the report to Congress. 22 MS. MEADOWS: I'm Susan Meadows. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 11 1 I work with Lynn in the Office of 2 Communication, Education and Radiation 3 programs. I'm an advisor in that office and 4 I work in the area of constituent relations 5 and human factors. Our role here is to 6 coordinate the development of the report 7 back to Congress. 8 DR. ZUCKERMAN: Good morning. I'm 9 Bram Zuckerman. I'm the Director, FDA 10 Division of Cardiovascular Devices, so I'm 11 here as a representative of one of the 12 pre-market divisions that regulates medical 13 devices. We're currently responsible for 14 the pre-market review of cardiovascular 15 devices, cardiothoracic surgery devices, and 16 peripheral vascular devices that are used to 17 treat arterial disease. I'm an adult 18 cardiologist by background. 19 MS. LESS: I'm Joanne Less from 20 the Center from Devices and 컴컴 Help. 21 Normally, I work in investigational and 22 humanitarian devices. I've been on detail BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 12 1 for the last year and a half directing the 2 implementation of MDUFMA, the Medical Device 3 User Fee Modernization Act, of which this 4 report is so-called the technical amendment. 5 Thank you. 6 DR. LINDEFOYT: I'm Sarah 7 Lindefoyt. I also work at FDA in the Office 8 of Work and Products Development. I'm a 9 family physician and I direct 컴컴 device 10 program in our office, which is part of 11 Joanne's program to develop devices for 12 conditions that affect 컴컴. 13 MS. VINING: I'm Elaine Vining. 14 I'm with the American Academy of Pediatrics 15 and I want to welcome everybody and thank 16 you for the long trips you've taken and give 17 you a couple of housekeeping items while I 18 have the floor. 19 (Laughter) 20 MS. VINING: One is please help 21 yourself to coffee and breakfast across the 22 way. Lunch will be served there as well. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 13 1 The ladies' room and men's room require a 2 key, which you get at the front desk here. 3 The men's room is on this side through our 4 glass doors. The women have to go across 5 the elevator banks and then you'll find the 6 restrooms there and please speak up. This 7 is going to be recorded. We have a 8 transcriber here, but also there is an 9 individual from the FDA on the phone and it 10 will be helpful for him to hear the 11 conversation as well and yourselves as well 12 because the air-conditioning gets a little 13 bit loud here, and if it's hot or cold or if 14 it's comfortable, please let us know and 15 we'll try to do whatever we can. 16 Thank you. 17 MS. IRELAND: I'm Jeanne Ireland 18 with the Elizabeth Glaser Pediatric AIDS 19 Foundation for 컴컴 Public Policy. We're 20 thrilled to be co-hosting the meeting and 21 want to thank AAP for putting together a 22 lovely meeting, as always, and it's just BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 14 1 wonderful to see everybody from so many 2 different areas all in the same room. 3 MS. DORMAN: I'm Diane Dorman, 4 National Organization for Rare Disorders; 5 Vice President for Public Policy, and I'd 6 like to mirror Jeanne's comments. Welcome, 7 everyone. 8 Thank you. 9 MS. JACOBSON: I'm Liz Jacobson. 10 I'm Executive 컴컴 and Regulatory Affairs at 11 컴컴, which is the largest trade association 12 of medical device manufacturers in the 13 world. Our manufacturers make about 90 14 percent of the dollar value of the devices 15 that are sold in this country and our 16 members range from small companies to very 17 large companies and about 70 percent of our 18 members are small companies. So this is a 19 very exciting meeting and 컴컴. 20 MS. FEDERICI: I'm Tara Federici, 21 컴컴 Vice President of 컴컴 Regulatory 22 Affairs 컴컴. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 15 1 MR. WALLFISCH: I'm Ben Wallfisch 2 with the Medical Device Manufacturers 3 Association. In general, we 컴컴 to talk 4 about access to the 컴컴. 5 MS. KAESER: I'm Lisa Kaeser. I'm 6 the 컴컴 Director at the National Institute 7 of Child Health and Human Development. 8 MS. FIELD: I'm Marilyn Field at 9 the Institute of Medicine, National Academy 10 of Sciences and we're in the process of 11 undertaking a legislatively requested study 12 of post-market surveillance and pediatric 13 medical devices on the study for 컴컴. 14 MS. KELLY: I'm Claire Kelly. I'm 15 the Associate Director of Public Policy at 16 the National Association of Children's 17 Hospital and we're also 컴컴. 18 DR. ABRAMSON: Thank you. This 19 is -- oh; I'm sorry. I didn't mean to. 20 SPEAKER: I was blocking his view 21 here. 22 MS. BUTTERFIELD: I'm Christian BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 16 1 Butterfield. I'm here at the Academy of 2 Pediatrics and I'm also representing the 3 Pediatrics Academic Society, APS SPR, 컴컴, 4 and also the Society for 컴컴. 5 MS. ROSENFELD: Hi. I'm Taren 6 Rosenfeld. (?) I'm actually here with the 7 Academy of Pediatrics. 8 MS. MATTHEWS: I'm Katie Matthews. 9 I'm here also with the Academy and I'm here 10 if you need anything. 11 (Laughter) 12 DR. ABRAMSON: Anybody else I 13 missed? 14 SPEAKER: On the phone. 15 DR. ABRAMSON: Oh; on the phone. 16 I'm sorry. Yes. Can the person on the 17 phone introduce themselves? 18 MR. RUDOLPH: Yes; Paul Rudolph. 19 I'm with the FDA, Office of the 20 Commissioner, Office of Policy. 21 DR. ABRAMSON: Thank you. When we 22 took on the issue of drugs, we did this in a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 17 1 collaborative manner with companies, the 2 FDA, and others, and I think came out with a 3 set of rules and regulations that markedly 4 improve our ability to use drugs that are 5 safe and efficaciously for children; the 6 same thing here. That's exactly what we 7 want to do. We want to work 8 collaboratively. We're having to spend 9 time, about four years ago, getting into 10 this with Susan Alpert, when she was at the 11 FDA, I came to realize that it's a very 12 different beast, but still the aim, the 13 final aim, is to create devices and tests 14 that can be used with children safely and 15 efficaciously. 16 The goal of the meeting is to 17 generate some consensus around action steps 18 that stakeholders can independently or 19 collaboratively build on or institute to 20 improve the availability of pediatric 21 devices. It's to also encourage 22 participation, but need to limit the length BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 18 1 of responses, so I will at times ask you to 2 speak and please do so, but I am going to 3 have to limit so that we can get through 4 this in a day so that we don't take on any 5 one particular device or issue to any large 6 extent. 7 As groups, we're going to talk 8 largely about issues, not get weighed down 9 on the specifics, and how do we turn the 10 specific successes that we've had with 11 devices into a broader solution for children 12 and I want to encourage creative ideas and 13 solutions. The Dammer Act, the regulations 14 and legislation that goes with it were 15 creative. They were a new way of doing 16 things and I think very good. 17 Mac, do you want to say anything 18 and then we'll get on to a few of the 19 presentations and then we'll open up to 20 discussion. 21 DR. LUMPKIN: Yes. Thanks, Jon. 22 I feel very good sitting next to Jon here. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 19 1 As some of you might know, Jon was a 2 resident when I was a medical student at 3 Wake Forest, so we've been side by side 4 before. It goes back than either of us care 5 to remember. 6 I would like to take this 7 opportunity, on behalf of the senior 8 political and senior career leadership at 9 FDA and all of my colleagues who are here to 10 thank all of you for being here today and 11 especially one more time to be able to say 12 publicly a great deal of thanks to Elaine 13 and the American Academy and the Glaser 14 Foundation and NORD and others who clearly 15 were the catalyst and the instrument that 16 made the situation occur with 17 pharmaceuticals that did occur over the past 18 seven or eight years of struggle to get us 19 to the position that Jon was just talking 20 about. 21 I mean, there was clearly no other 22 group, other than AAP, that was as tenacious BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 20 1 and as committed to seeing that particular 2 effort be taken forward, through all the ups 3 and the downs and two pieces of legislation 4 and court cases and all kinds of things that 5 we had to go through. I mean, every time it 6 seemed very bleak or that this was going to 7 be taken off course, Elaine would rally the 8 forces of good and once again it would come 9 forward. 10 So Elaine again, thank you for 11 what you did then and thank you very much 12 for what we're trying to do here and your 13 role and the role of all your colleagues 14 here in trying to make it happen when it 15 comes to devices. 16 I think when we were looking at 17 the pharmaceutical situation and trying to 18 figure out how could we make that a better 19 situation for children, not only in our 20 country, but ultimately to spill over to 21 children around the world, there were really 22 two fundamental principles that I think all BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 21 1 of us were unwilling to give on, and one was 2 the reality that children are not just 3 little adults, and because of that, that 4 makes a difference and no one is better than 5 pediatricians and caregivers of children to 6 know what those differences are and to try 7 to make the laws and the regulations and 8 public policy recognize those differences. 9 The second was that children are 10 not second-class citizens and if there are 11 scientific standards for safety and efficacy 12 for adults, there has to be a good 13 explanation if we don't use those same 14 standards in children as to why we are not 15 using those same standards; that indeed 16 children are not second- class citizens. 17 They should be our first among equal 18 citizens, and if we're going to be 19 responsible for them as adults, they deserve 20 the best from a scientific perspective that 21 we can get. 22 So I think, you know, those two BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 22 1 principles served us very, very well as we 2 went forward, looking at how, as Jon said, 3 very collaboratively try to figure out what 4 we could do to make the pharmaceutical world 5 better for children. 6 I think that's why we're here 7 today. As people have already said, we have 8 a very tight deadline from the FDA to 9 produce a report to Congress that will 10 hopefully be the foundation for a public 11 policy debate on how this country can go 12 forward in the world of devices and in order 13 to put that report together, we need to 14 identify what barriers exist today to 15 getting well-studied, well-developed, 16 well-manufactured, well- understood products 17 or devices available to our children. 18 There might be regulatory 19 barriers. There might be clinical barriers. 20 There might be ethical barriers. There 21 might be legal barriers. There might be 22 economic barriers. These were all barriers BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 23 1 that existed as far as the pharmaceutical 2 situation was concerned and they were all 3 ones that we had to identify and deal with 4 and many of which we continue to deal with 5 as we go forward. 6 So I think our goal here today is 7 to try to identify those barriers and also 8 to begin to put forward solutions to getting 9 us beyond those barriers and I know I and my 10 colleagues very much look forward to hearing 11 your perspectives on this so we can go 12 forward with this initiative. 13 Unfortunately, I'm going to have 14 to leave at ten this morning to go to a 15 meeting at the Department, but unless things 16 change, I should be back after lunch and I 17 plan to be here all afternoon to hear the 18 afternoon discussion. 19 So I do look forward to this 20 meeting. Again, thank you all for being 21 here and again thanks, Elaine, for 22 everything. Thank you. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 24 1 DR. ABRAMSON: I'm going to give 2 the first presentation. I promise you I'll 3 be done by 9:30 with mine. 4 I was at the Institute of Medicine 5 last week and I think the Institute of 6 Medicine heard a lot of information and a 7 very vibrant discussion of things that 8 pediatricians in various specialties need to 9 get better devices and I think they heard 10 from epidemiologists and others the 11 scientific problems in trying to get those 12 regulations and things that are necessary to 13 do these studies underway and find out what 14 the safety issues are. I'm even going to 15 try to highlight a few issues for you. 16 (Discussion off the record) 17 DR. ABRAMSON: While we're 18 waiting, let me make a few points. We're 19 going to concentrate on devices, but there 20 are issues also surrounding tests. A good 21 example of this, from my standpoint, is that 22 for many, many years, there were rapid 컴컴 BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 25 1 tests on cerebral spinal fluids that were 2 available that were being used and these 3 tests are neither sensitive or specific 4 enough to be useful, but they will be used 5 to make decisions and I think really to 6 adverse outcomes in children, some of them 7 not being treated inappropriately; some of 8 them being treated 컴컴. 9 So there are a whole lot of issues 10 that surround the issue of testing that 11 we're not going to get to today; maybe 12 another day. 13 So these are the new 컴컴 14 technologies. These are considered -- I 15 think we should make the point that there's 16 an ethical responsibility to assure that we 17 have safe and effective devices for use in 18 children for the various diseases that they 19 have. 20 Next slide. These are the number 21 of new devices. These are not what I'm 22 going to call "me-too devices," which I'll BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 26 1 show you in the next slide, but these are a 2 number of new devices that have been 3 approved by the FDA since 1993. 4 Next slide. These are a number of 5 what I would call "me-too devices," so you 6 have an 컴컴 and now you have an improvement 7 or alleged improved in an 컴컴 monitor and 8 those do not require the same degree of 9 safety and efficacy testing that the new 10 devices do. 11 Next slide. These are some of the 12 things that are here coming out predicted in 13 the next five years and as you can see, if 14 they work, they're going to be remarkable 15 improvements in our ability to take care of 16 patients. So there's a lot of promise out 17 there in the world of devices. 18 Next. So there are steps towards 19 컴컴 pediatric device needs that 2001 컴컴 20 the protection of pediatric 컴컴 research 21 studies were extended. In 2002, there were 22 medical device user fees, 컴컴 Act of 2002. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 27 1 So 컴컴 the Dammer Act, and they include 2 provisions for the 컴컴 to conduct a study 3 and report back to Congress by October 2006 4 on 컴컴 surveillance of pediatric medical 5 devices. 6 Next. 컴컴 updated and now the 7 FDA has a report due to Congress by 8 October 1, 2004, on various availability of 9 devices intended for the treatment and 10 diagnosis of diseases that affect children, 11 and then the Federal Registry Notice 12 requesting public comment on 컴컴 13 availability. 14 Next. So the points that many of 15 you 컴컴 not overall, you know, is that 16 infants and children suffer from many of the 17 same diseases and conditions as adults, 18 similar to adults. The pediatric population 19 need devices that 컴컴 long and prudent 20 life, 컴컴, establish effective and 컴컴 21 safety, will shorten hospital stays, reduce 22 basic procedures, and to me, there's a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 28 1 burgeoning world of in-home devices, 2 ventilators being used at home. 3 We experienced extreme frustration 4 during the past decade, trying to get any 5 child who needs a long-term ventilator out 6 of your hospital and what was created 7 because these institutions or hospitals that 8 specialize in this don't exist and the 9 reimbursement's inadequate is these patients 10 go home. They go home on home ventilators. 11 They go home without any power supply 12 back-up except for batteries. 13 There are pumps that we use in 14 homes to deliver drugs. There are many 15 reports of 컴컴 drugs being given too fast 16 to 컴컴. These are all problems that have 17 been created and I think this is a 18 particular area that people have not paid 19 attention to. 20 Next. There are diseases and 21 conditions that are unique to children and 22 there are adult diseases and conditions that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 29 1 occur in children for which children 컴컴. 2 So there's a whole category of 3 devices that you just can't shorten the 4 length of the decatheter and fix the problem 5 for the child. 6 Next. There are dynamic growth in 7 potential devices that impact growth; 8 potential migration of titanium devices when 9 they're used in plastic surgery and they 10 sort of don't stay in the same position as 11 they would in an adult who's not growing. 12 There are differences in 컴컴 13 sizes. The biochemistry of a child is 14 different from adults and I'll try to give 15 you a few examples of these. 16 There's an active lifestyle of 17 infants, children and adolescents that 18 markedly affect devices. For instance, if 19 you go close to a playground where there are 20 particular types of plastic, it can 21 deprogram a Cochlear implant. This was 22 something I was unaware of prior to the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 30 1 컴컴. 2 There are infections triggered by 3 pediatric-specific considerations. In other 4 words, urine contamination of a catheter in 5 the stomach and groin area of a baby who 6 wears diapers. That's not a problem, 7 particularly in adults, but it is a problem 8 in children. 9 Next. The impact of devices on 10 organ growth for infants and children, again 11 another example is undersized heart valves 12 used in children. We have to keep replacing 13 these. Is there not a way that we can come 14 up with that would allow the device to grow 15 as the child grows? 16 The impact of long-term device 17 implementation of children, the absorption 18 rate of 컴컴 cranial/facial devices, the 19 leaking of the gastrostomy tubes; those are 20 all just some of the examples that we really 21 don't know the long-term effect of. 22 Now, I sit there day and day BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 31 1 fighting the issue of giving 25 micrograms 2 of mercury and influenza vaccines. These, 3 to me, are much more long-term and much more 4 reasonable issues; efficacy and/or adverse 5 컴컴 in children may not be predicted from 6 the adult experience and there are many 7 examples of that, such as 컴컴 of 컴컴. So 8 no one can really predict it going in. 9 Next. There is a lack of 10 pediatric-specific information about a 11 device and diagnostic test. You know, the 12 Pharmaceutical Act, you only had to make one 13 point to get everybody's attention: At the 14 point where we 컴컴 for drug studies, 15 specifically for children. We were able to 16 tell people that 80 percent of the drugs 17 they were using at that time would be used 18 for an indication and/or age for which the 19 FDA did not approve. We don't even know 20 that in the 컴컴. We have no clue. We have 21 very little denominated 컴컴. 22 Lack of appropriate pediatric BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 32 1 devices may require more and basic treatment 2 whereas physicians' hospital staff have 3 gerry- rigged devices to make them work for 4 children. You have no idea how 컴컴 those 5 work, and again I want to bring home the 6 safety and efficacy of home devices. 7 Next. I'll stick to my own area 8 because I want to make several points for a 9 minute. There are lots of shunts, lines and 10 catheters. We accept high infection rates 11 now. We don't even know what the 컴컴 are, 12 but we all know that they're fairly high 13 because we're dealing with them every single 14 day, but we don't have denominated data. 15 So I think it is not okay to 16 accept them. We need to be able to create 17 catheters and lines that resist the 18 adherence of these bacteria to the lines and 19 make the rates of infection much lower. 20 VP shunts are a great example. I 21 can't tell you how many VP shunts I've seen 22 fail because either the shunt is no longer BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 33 1 worker or they get infected, and once they 2 get infected, boy, it's hard to treat them 3 with 컴컴 and often you don't even have to 4 replace the shunt. 5 Now, I've seen kids who no longer 6 have the ability to put them into their 7 ventricular perineum and you have to put 8 them into the heart and that's a huge 9 problem because those hearts later on get 10 all sorts of problems with the shunt being 11 in there. 12 Next. So we've talked about the 13 high rate of infection. 14 We've talked about the need for 15 better design, so the design issue; this is 16 not an issue that, per se, says that isn't 17 safe and effective. These lines are 18 effective, but they're not safe. They are 19 not safe at all. 20 Next. There are issues around 21 critical care and cardiology that 22 Dr. Jenkins may talk about. Left BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 34 1 ventricular cyst devices, we do not have 2 these for children less than five years of 3 age. That's a big problem. 4 Next. The ones for five to 5 seventeen are under protocol, is my 6 understanding, is under research protocol. 7 컴컴 infants and children less than five 8 years of age who have critical failure of 9 their ventricle have to be supported on 컴컴 10 extra corporeal membrane oxygenation until 11 they can be transported. 12 These systemizers are a much 13 better way of bridging that gap. All right. 14 There are these available 컴컴 that can 15 support pediatric patients in small infants. 16 They're in Germany. They ought to be in the 17 United States or at least we ought to know 18 that they're not safe and effective and 19 we're not going to 컴컴. 20 Next. So mere partnership among 21 all the stakeholders to improve the 22 availability of devices in neonates, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 35 1 infants, children, and adolescents, I think 2 will create many more devices and more 3 opportunity for business if we can work 4 together and come up with ways of creating 5 the devices, but making sure they're safe 6 and effective. 7 We need tracking and reporting 8 mechanisms. The IOM heard a ton about this. 9 We have essentially no numerated 10 data and no 컴컴. Eight or ten clinicians 11 there were told that there are mechanisms 12 for reporting failures; none of the 13 commissions knew these, knew how to do 14 these. Where we do know how to do them for 15 drugs and vaccines. Expansion of 컴컴 16 systems to encourage development of devices. 17 Next. I'm going to move out of 18 the way here and, Joanne, you will talk 19 about the FDA's -- 20 MS. LESS: I have to go behind 21 you? 22 (Laughter) BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 36 1 MS. LESS: Can we do it sitting? 2 DR. ABRAMSON: Say it again. 3 MS. LESS: Is there a reason, when 4 we talk, not to do it sitting? 5 DR. ABRAMSON: No. 6 MS. LESS: Before I get started, 7 again I wanted to thank the American Academy 8 of Pediatrics and the other 컴컴 -- Diane 9 and Jeannie -- for all of your help in 10 pulling this meeting together. FDA, 11 obviously, couldn't do it, as quickly as 12 they did, and we really appreciate you 13 taking this on and doing it for us. 14 When Wayne and Jeannie and Diane 15 and I were talking about the agenda, one of 16 the things that we thought we should spend a 17 few minutes on is FDA's regulations. We 18 have three basic mechanisms to get 컴컴 19 devices to market, and we thought it was 20 important that everybody start on the same 21 page and understand the difference between 22 a 510(k) and an HDE, not, you know, to kill BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 37 1 you with it, but at least to give you some 2 basic information on that. 3 The first process that we have -- 4 and this is for the lower risk devices -- is 5 what we call a 510(k) and it's called that 6 because that's the section of the law that 7 it comes from. These are basically Class II 8 devices and unlike the patent process, a 9 company's goal here is to say that you're 10 just like something else that's already been 11 approved for marketing. 12 So you don't want to say yours is 13 unique or different. You want to say you're 14 just like something else that's out there 15 and most of these go through without 16 clinical data. There's usually marketing 17 that's just based on description 18 information, some performance testing, bench 19 testing, bio comparability, but only 20 about 10 to 15 percent actually include 21 clinical data and we see about 4,000 of 22 these per year. So it's our biggest BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 38 1 program. 2 The device we have here -- it took 3 me forever to figure out what it was and I 4 finally had to go ask somebody; I borrowed 5 this picture from someone. It's actually a 6 palm-held device for ECG. So it's one of 7 our newer things and it's kind of neat and 8 it did go through the 510(k) process. So it 9 goes to show that it's not just old 10 technology being found equivalent to old 11 technology. There's a lot of advances that 12 go through in the 510(k) process. 13 Premarket approval process is 14 reserved for our higher- risk devices; life 15 sustaining, life supporting, substantial 16 importance in treating disease. In this 17 process, the company needs to establish 18 reasonable assurance of safety and 19 effectiveness. That doesn't mean it has to 20 be absolutely safe and effective, but 21 reasonable assurance. 22 For these types of applications, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 39 1 we see bench, animal, human data, and it's 2 important to find out that although all of 3 our PMAs do have clinical data in them, 4 they're not all randomized in full trials. 5 A lot of times we have historical data, 6 literature, crossover signs, patient 컴컴 7 their own control. 8 About 40 percent of the time we do 9 require post- approval studies. That really 10 depends on whether there's some unanswered 11 questions that we still feel that the 12 company needs to address in a post-market. 13 They should not be safety and effectiveness 14 related. It's usually long-term or a 15 specific question maybe that our advisory 16 panel 컴컴, and we see about 50 of these a 17 year. So it's a much smaller program, but 18 the bigger the device is, the higher the 19 risk. 20 Now I'm going to talk about the 21 HDE program, since this is the focus of so 22 much of their current discussion down on the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 40 1 Hill. In 1990, with SMBA 90, Congress added 2 the humanitarian device exemption provision 3 to our statute and that was aimed at devices 4 that are supposed to be treating or 5 diagnosing diseases of which there's less 6 than 4,000 patients in the U.S. per year. 7 God only knows where the 4,000 came from. 8 It started as 8,000, if you look in the 9 legislative history, but when it was passed, 10 it was changed to 4,000. So there isn't 11 really a lot of discussion on where 12 the 8,000 came from or why it got cut 13 to 4,000. 14 For these devices, the idea was 15 that the company could not do a 컴컴 16 clinical trial to support safety and 17 effectiveness or reasonable terms of safety 18 and effectiveness and so because of that, 19 Congress added this provision to say that 20 the device could be exempt from 21 effectiveness as long as there's no other 22 alternative device out there and the company BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 41 1 would not otherwise bother to bring the 2 device to market. There was not enough of a 3 financial incentive to do that. 4 At the bottom, I have a couple of 5 the ones that we approved. The first one 6 over here is a cultured skin substitute for 7 컴컴 deformities. We have two heart valves 8 that have gone through; one Medtronic and 9 one from 컴컴, and again, these were aimed 10 at pediatric subjects for which there's a 11 higher rate of calcification to the heart 12 value is specially treated and try to slow 13 down that calcification rate. The last one 14 is the LVAD, that we just approved in 15 February for pediatrics from 5 to 16. 16 The approval threshold for an HDE 17 is completely different than what you see 18 for an PMA. Unlike a PMA, where you're 19 trying to show reasonable assurance of 20 safety and effectiveness, this is basically 21 what the statute says. It's a long 컴컴 22 threshold. The device will not expose BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 42 1 patients to an unreasonable or significant 2 risk of illness or injury. The probable 3 benefit outweighs the risk of illness or 4 injury, taking into account the probable 5 risks and benefits of alternative devices or 6 other treatments. 7 So unlike PMA, where a company 8 needs to show that their antibodies has 9 reasonable assurance and safety and 10 effectiveness, this is more of a comparison 11 where we're looking at the safety, we're 12 looking at probable benefit, but we're also 13 taking into account what else is on the 14 market for that patient population, and 15 that's the critical piece, because all of 16 these come in. There's almost nothing else 17 out there. We don't have a lot of data, but 18 when you look to see what the course of the 19 disease and what's going to happen to that 20 subject without the device, that's what 21 helps you make the decision. 22 For an HDE, the statute requires BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 43 1 IRB approval. Congress thought that even 2 though it's an improved device and 컴컴 3 marketing that the IRB should be involved, 4 it makes it complicated for the IRBs because 5 there's no protocol and there's also no 6 informed consent requirement under the 7 statute. So it's tough for the IRBs. 8 They're not exactly sure what they're 9 supposed to be looking at since we already 10 made that 컴컴. For an HDE, you can't make 11 a profit and you can recover your cost, just 12 like for an IDE. You can recoup your cost 13 of research development and your 컴컴 14 distribution. 15 So an HDE is sort of like a cross 16 between an IDE and a PMA as far as the 17 approval. The threshold is more like an 18 IDE, except 컴컴 approval. You can't make a 19 profit, but it is marketing 컴컴). 20 We only get about five or ten of 21 these per year. It's a fairly new program. 22 We didn't have any regulations until the mid BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 44 1 to late nineties; 1996, so we only get about 2 five per year. So it does sort of seem like 3 a new program to us. 4 It's a two-step process. We work 5 with Marlene Haffner's group and the Office 6 of Products Development makes these 7 decisions for us as to whether or not 8 there's less than 4,000 patients in the U.S. 9 per year, with that 컴컴. 10 Well, when we wrote the 11 regulation, what we wanted to do was make 12 sure the companies didn't waste their time 13 putting together an HDE that wouldn't either 14 meet the 4,000 threshold or wouldn't meet 15 our threshold for approval, and so we 16 divided up into two steps, and so the first 17 piece is to go to the Office of Orphan 18 Products Development. They make the 19 decision whether or not there's less 20 than 4,000 subjects in the U.S. from here. 21 If they meet that threshold, then they can 22 submit their HDE to us and the HDE BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 45 1 application looks like an PMA. It's 2 actually formatted just like that as far as 3 contents go, but it's different, since there 4 is no requirement for clinical trial, it's 5 mostly bench testing, animal testing, 컴컴 6 and some clinical experience. 7 I think we were at 컴컴' process, 8 the bottom of the statistics slide, HD 9 process and approvals. So far we've 10 approved 34 HDEs; 6 of these were 11 pediatrics, including the LVAD, a couple of 12 heart valves, water simulator. That's an 13 urgent stimulator 컴컴 for children with 14 spinobifida and also the 컴컴 stems. That 15 was originally the 컴컴 came from the 16 co-group and it came in as a PMA. We 17 concerted it over to an THE when the 18 regulation went into effect. It went to 19 panel as a PMA. The panel thought it was a 20 very promising device, but they didn't think 21 there was enough data to show reasonable 22 signs of safety effectiveness that we BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 46 1 converted it to an HDE. 2 We have 18 HDEs that we've 3 approved for both a coronary graft for 4 patients undergoing cabbage that don't have 5 enough 컴컴. Two finger joints, the 컴컴 6 and MCP and also from a descending aortal 7 section. 8 Then we have ten 컴컴 for both; 9 the gastric simulator. Medtronic 컴컴 10 nauseam, vomiting, due to gastric 컴컴. 11 That was actually again under IV for a very 12 long time, slow enrollment. A lot of 컴컴 13 requests. We actually had 컴컴 requests 14 that went to President Clinton asking that 15 that device be made available. 16 The company was about to give up. 17 They didn't think that they could do the 18 trial to support the PMA and then 컴컴 come 19 under the agency provision, and then one 20 that I mentioned 컴컴. 21 Now I have my slide with the 22 little 컴컴 patients and they move. You BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 47 1 can't see those. 2 (Laughter) 3 DR. ABRAMSON: We'll wait. 4 MS. LESS: It's worth waiting for, 5 let me tell you. 6 DR. ABRAMSON: We'll need to see 7 that. Why can't we use adult devices in 8 children? I think Dr. Abramson was talking 9 about this; Dr. Lumpkin, and all of you are 10 familiar with these reasons. 11 I wanted to give you an example 12 though. If you look at that list, the 13 disease or condition may be limited to 14 children the sizes of the device, the growth 15 of the patient, hormonal influences, 16 activity level of the children and the 17 maturity level of the patient. 18 The deep brain simulator that we 19 recently improved under the HD process pulls 20 in almost all of those. The deep brain 21 simulator was for chronic, intractable 22 primary dystonia, a little neurosimulator BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 48 1 that gets implanted 컴컴 in the abdomen, the 2 컴컴 up through the back of the neck into 3 the brain. 4 Well, in children, it makes it 5 more difficult because if you have two 6 neurosimulators, you can get crossed talked. 7 You don't have to worry about the size of 8 the neurosimulators, where you're implanting 9 it, whether or not you get some erosion 10 through the chest wall. As the child grows, 11 you don't have to worry about the 컴컴, 12 whether or not they need to have extensions 13 or lengthening; whether they're going to 14 migrate due to the activity level of the 15 child, and also that in simulators, usually 16 컴컴 under general anesthesia as opposed to 17 sedation for adults. So there's a lot of 18 different risks and a lot of different 19 things to think about just in that one 20 device. 21 The next one. Why do we need to 22 get the clinical data? Again, we've talked BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 49 1 about this a little bit already. Ensure the 2 device is properly designed. There is a 3 tendency, when a device comes in, that's 4 already approved for an adult indication, if 5 it's going to be changed or used in the 6 pediatric population, we say, well, we know 7 a lot about it, you know. It's really not 8 all that different. It's pretty similar. 9 Maybe if we can just get a little bit of 10 data, but if we have actual pediatric 11 clinical data, we can make sure that it is 12 properly designed if there are some unknown 13 risks that were not taken into account. 14 We want to also want to ensure the 15 safety and effectiveness is demonstrated, 16 again, that it's not presumed that we don't 17 just think that it's going to work okay 18 because you know it looks like it from the 19 adult data; that we get an accurate risk and 20 adverse event assessment. We've been 21 surprised by some adverse events when the 22 device goes into clinical trials, 컴컴 that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 50 1 you don't necessarily think about, and if 2 you know what these risks and adverse events 3 are, you can address them through the 4 labeling. So hopefully even if there are 5 some events out there, you can mitigate the 6 risks through proper labeling. 7 The last thing I wanted to mention 8 under age appropriate instructions or use, 9 not just that you get the data so that you 10 know whether it's appropriate for infants or 11 pre- adolescents or whatever sub-population 12 you're indicating the device for, but also 13 if there's human factors issues; if the 14 advice is actually going to be used by the 15 child, that you make sure that you write the 16 instructions for use so that the child can 17 understand them. 18 When do we ask for pediatric 19 clinical data? There is no hard and fast 20 rule. We look at the device. We look at 21 the indications for use, and we look to see 22 whether obviously if the device is indicated BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 51 1 for children, do we have any adult data and 2 if we do, is it relevant or is it sufficient 3 in the case of the fetal bladder 컴컴, 4 obviously we weren't going to have any adult 5 data. We did use data though from a lung 6 study where that 컴컴 had been used to drain 7 fluid in the lung and we decided that 컴컴 8 could drain fluid in the lung that that 9 supported, then you could also drain urine. 10 So although it wasn't adult pediatric, it 11 was sort of a different type of study that 12 was done. 13 But we do look first to see 14 whether or not we can use the adult data. 15 Under the Food and Drug Modernization Act 16 of 1997, we were charged with making sure 17 that we look at the least 컴컴 for a company 18 to demonstrate effectiveness to get advice 19 on the market and we would consider this to 20 be part of that to look to see what data we 21 already have, whether we really do need to 22 have clinical data, whether we can 컴컴, and BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 52 1 a lot of times if a device is being 2 modified, that's what we can use. 3 In the case of the LVAD that we 4 approved in February, we had the old data. 5 The device was modified. There were two 6 basic modifications to go into the pediatric 7 population. One had to do with an 컴컴 of 8 the tubing coming off the LVAD, the other 9 with the diameter of the tubing, and main 10 concerns we had with that were the flow and 11 turbulence and so we could use some basic 12 animal testing to address that. 13 We also had some clinical 14 experience from Europe, and then we asked 15 for a post-approval study to make sure that 16 we do exactly what was going on and that we 17 had all of our bases covered. 18 The last is approval methods for 19 pediatrics. What we saw with the brain 20 stimulator was the level of stimulation for 21 pediatrics 컴컴 slightly different than what 22 you would expect for an adult. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 53 1 When you look at marketing the 2 pediatric devices, they basically fall in 3 three categories. The first one is the 4 easiest: That adult device, you can use in 5 adults, you can use in pediatrics. There's 6 no special issues. These tend to be the 7 lower risk devices, the ones that 8 컴컴 510(k). Syringes, wound dressings, 9 컴컴, and 컴컴, manual surgical instruments, 10 monitoring and imaging devices. We don't 11 usually have clinical data to support those 12 and those are 컴컴 that are easier ones to 13 컴컴. 14 The second category are devices 15 that are limited to pediatric use: The 16 infant heel warmer and newborn hearing 17 screener -- those both in 510(k). I just 18 wanted to mention for the infant heel 19 warmer, that device is actually exempt 20 from 510(k), meaning a company can go to 21 market without coming into the agency if 22 it's for adults. If it's for infants, they BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 54 1 do have to 컴컴 submit a 510(k) to us, but 2 all we're really looking at is this 컴컴 3 device to make -- it's basically a heat 4 pack. You crumble it up and it generates 5 heat and we we're just looking at this 6 excellent device and making sure it gets to 7 the right temperature, doesn't get too hot, 8 doesn't stay there too long. 9 The fetal bladder stent went 10 through an HDE and we did have 컴컴 on that 11 and the occluder for PDA. Again, that went 12 through a PMA process so we did have a 13 clinical trial for that. 14 We tried to use bench and animal 15 testing as much as we can to answer at least 16 the basic safety and effectiveness questions 17 and then reserve the clinical data for 18 specific either risk questions or things 19 that the panel might raise. 20 Then we have sort of the adult 21 devices that get sized down or modified for 22 pediatrics and again this can be more BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 55 1 difficult because you have the adult device 2 out there and the tendency is to say well, 3 it's probably okay for pediatrics. We'll 4 get a little bit of data to make sure that 5 everything's okay, but how much is that 6 little data? Is it five or ten patients? 7 Is it a hundred patients? Sometimes it's 8 hard to decide how much you actually need to 9 identify 컴컴 make sure that you have a good 10 risk assessment for the device. 11 We have lots of examples of the 12 heart valves. Not only are they a different 13 size, like I mentioned, they're treated 14 differently to reduce the calcification 15 rates in pediatrics. We have orthopedic 16 implants, Cochlear implants, so you have 17 different issues with the Cochlear implant 18 that's for a 컴컴 the risk of a child versus 19 an adult, and the ventricular devices again; 20 there's different in 컴컴 rates, questions 21 that we have to be sure that we take into 22 account. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 56 1 Again, mostly we've tried to start 2 with the bench and animal testing to address 3 these special issues and then turn to 4 clinical data when we need it. 5 I put up here a list of the 6 difficulties that we see in collecting 7 pediatrics clinical data and this isn't 8 necessarily everything obviously and it's 9 not -- it might not even be accurate -- but 10 this is what we're hearing from clinicians 11 and from 컴컴. 12 First, that doing a clinical trial 13 in children is unethical and we actually 14 have one clinical trial now that the IRB had 15 a difficult time reviewing and bumped it up 16 to FDA, and so there's one example and way 17 where the IRB thought it was unethical to do 18 the trial. 19 We also hear that there's problems 20 in enrollment by the prevalence of a disease 21 or condition, reluctance of the parents. 22 They don't want to put their child in a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 57 1 clinical trial either because of the risks 2 or the inconvenience or just not knowing 3 enough about the device. 4 Same thing from clinical 5 investigators and IRBs; these are a little 6 bit reluctant to enroll children in clinical 7 trials, and a lot of that has to do with the 8 additional testing. They don't want to 9 expose their kids to whatever additional 10 things might go into the clinical trial that 11 they were getting 컴컴. Ensuring protocol 12 compliance can be much more difficult with 13 children, and lastly, the limited financial 14 incentive for industry. If the patient 15 population is small, the cost of the trial 16 is large, you have to use multiple sites to 17 get enough patients in a trial, it's going 18 to cost the company a lot more to do it and 19 maybe they won't bother; they'll just stick 20 with the adults. 21 The last thing that I wanted to 22 mention is if you don't have a pediatric BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 58 1 device available, what are the options for 2 an investigator or a physician 컴컴? 3 The first obviously would be to 4 use the device off label, and rather than 5 컴컴 different indications, I should have 6 also included devices that are labeled for 7 adult- patient populations, but then are 8 used in pediatrics. 9 So it's either adult devices that 10 are completely different indications, which 11 we do see a lot, or if it's a different 12 patient population by age, and under our 13 law, under Section 906 of the practice of 14 medicine, physicians are free to use an 15 approved device in any way they want and FDA 16 is not supposed to limit that or interfere 17 with that practice. 18 The only thing that we can do is 19 look at the company and make sure that 20 they're not promoting or advertising for 21 that 컴컴 indication. We see a lot of 22 emergency and compassionate use. Under BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 59 1 emergency use, the physician makes the 2 decision that as the best alternative for 3 his or her patient, under compassionate use, 4 they have to 컴컴 FDA and we make that 5 decision based on what we know about the 6 device, and again we're talking about 7 investigational devices or devices that are 8 being imported from overseas. 9 So we don't necessarily know a lot 10 about that device. We have some basic 11 information on it, the 컴컴, sometimes we'll 12 ask you for some testing. We might know 13 that it's on the market in Europe or it's 14 been CE marked, but it's not like a full- 15 blown kind of 컴컴 know a lot about that 16 device, so it's hard to make that decision 17 컴컴 compassionate 컴컴. So usually we'll 18 try to make that decision within a couple of 19 days. Emergency use of 컴컴 within minutes 20 or hours, so it's a tough decision to make 21 without much information. 22 The last is custom devices. We've BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 60 1 had some cases -- we had one recently -- 2 where an infant was involved in a car 3 accident and the physician went to a company 4 and said could you make a stabilizer for the 5 컴컴. So the company made it and it was 6 shipped out and the physician used it. 7 So there are these mechanisms 8 available, but there's not improved 9 pediatric device, but I would argue that 10 they're for the short term or they're good 11 for case-by-case, but it's certainly not 12 going to 컴컴 see on a larger scale. 13 Our challenge today: To encourage 14 the government 컴컴 new pediatric devices 15 without increasing the risk to pediatric 16 subjects. We don't necessarily want to 17 lower the threshold to get more pediatric 18 devices out there, just so that we have them 19 available. If we don't really know what the 20 risk profile is, we've done nothing more but 21 get 컴컴 out there that don't actually help 22 the subject, but our patients at risk. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 61 1 Unduly increasing the burden on 2 컴컴 for FDA and 컴컴 proven for adults and 3 so trying to do all of this, I think is 4 going to be a challenge and we really 5 appreciate all the help that you can give us 6 since we have such a short time frame to 7 pull it all together. 8 (Laughter) 9 MS. LESS: Thank you. 10 DR. ALPERT: As you already heard, 11 many medical device companies already 12 address issues that are important in the 13 development and availability of pediatric 14 devices or devices for the pediatric 15 population; in fact, in a lot. As Joanne 16 pointed out, particularly for certain types 17 of devices, and that includes some of the 18 lower risk devices, it's a foregoing 19 conclusion, at the beginning of device 20 development, that is going to be for all 21 ages and all sizes and all groups of 22 patients and that development takes place, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 62 1 making sure that all of the patients who are 2 in need of certain therapy are bracketed. 3 That doesn't mean that there 4 aren't challenges, and I'm going to talk a 5 little bit about them, but I wanted to make 6 a couple of introductory remarks, I think, 7 before I actually start the formal 8 presentation. One is to emphasize, as 9 Joanne pointed out, about four to five 10 thousand medical devices a year go through a 11 process called the 510(k) process, premarket 12 notification, and if you're not familiar, it 13 sounds like gee, those devices have no 14 understanding or there's no understanding of 15 the safety and effectiveness of those 16 devices, so why are they going to market and 17 that's been talked about in the press over 18 the last couple of years. 19 In reality, those devices may be 20 different and are compared on the basis of 21 their design in engineering, but their 22 safety and effectiveness is related to the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 63 1 safety and effectiveness of the earlier 2 devices. So it's an assumption and a 3 movement of safety and effectiveness data 4 from one device to another. I didn't want 5 anybody to walk out of the room thinking 6 that there are 4,000 devices a year and 7 there's no information about whether they're 8 safe or effective because there is. It just 9 happens to be linked to an earlier device 10 and in many cases, those devices that go 11 through that process are actually linked to 12 an earlier device by the same company. So 13 we're talking about changes, modifications, 14 and improvements, and that's important to 15 understand about the device industry. 16 When it comes to existing 17 technologies, this is an evolutionary 18 process. Devices, engineers -- and there 19 are about three engineers in the room and 20 you will know and for those who don't know, 21 engineers don't leave anything alone. So as 22 things are evolved, by the time they get to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 64 1 market, somebody's already been making 2 changes, making improvements, trying to make 3 it better, easier to use, less expensive, 4 and to address new diseases and new 5 conditions. So this is an evolving process. 6 When it comes to brand-new 7 technologies, most really revolutionary, 8 really novel technologies in the medical 9 device arena, come from work between someone 10 who's in need of the product. Someone who's 11 identified a specific new need and maybe an 12 engineer, maybe a big company, but it really 13 comes -- but the novel devices generally 14 come from someone's idea, from working with 15 someone who's in need. 16 So I think this particular group 17 getting together, where we have a lot of 18 people from different areas of pediatrics, 19 who can talk about needs is going to be 20 extremely helpful for the discussion. 21 I put a question mark after 22 barriers because I don't think that they're BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 65 1 really barriers. I think they're challenges 2 and they're challenges for all of us who are 3 physicians in neat- looking and in need of 4 certain kinds of devices, challenges for 5 industry to come up with the technologies 6 and the appropriate way of developing those 7 technologies and challenges for the 8 regulators as well to figure out how do we 9 do this while we don't increase the burden 10 so much that there's no one who can, in 11 fact, manufacture and -- design and 12 manufacture -- devices for special needs 13 populations, and I think of pediatrics as a 14 special need, although for many diseases, 15 it's really not so different, and also not 16 inordinately increasing the burdens that are 17 in place and the true barriers to putting 18 something in the market that would prevent 19 them being available even once they're 20 developed and manufactured. 21 I know we're not going to talk 22 about it today, but Jon did mention BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 66 1 reimbursement and I want to make sure that 2 we don't lose that thought that there is -- 3 there are the issues of design and 4 development of products through the issues 5 of the regulatory market entry and then 6 there are issues about reimbursement and 7 those also impact the availability of these 8 technologies. So if we increase the cost of 9 development being then too high and 10 reimbursement's a problem, we're not going 11 to have them available for the populations 12 as well. 13 So I just wanted to keep in mind 14 that these are challenges and they're 15 broader than just specifically identifying 16 what device is needed and who might develop 17 it. 18 These have already been talked 19 about. Identification of needs. I'm going 20 to come back to that in a moment. Research 21 needs for pediatric uses. I think Joanne 22 pointed out a lot of the issues that face us BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 67 1 as companies when it comes to developing 2 devices for use in the pediatric population. 3 I'll come back to that, and then the 4 development issues, which I want to spend a 5 little bit of time on so that we both have a 6 common understanding of some of the 7 challenges that are in place for companies 8 in developing devices for the pediatric 9 population. 10 Again, this ground has already 11 been gone over. There are issues about 12 products already in the market being used in 13 adults. Difference of size, which usually 14 comes to mind first, but is not the big 15 issue. The issue of performance, which 16 comes up much more often in the pediatric 17 population. The number of times that that 18 fluid is cycled, the rates at which pumps 19 and pacemakers still work; all those things 20 that challenge in terms of actual 21 performance measures and then risks, and 22 Joanne talked about those already. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 68 1 If products are unavailable, 2 there's a real question about how do we get 3 that communication? How do we get the 4 communication from the population -- 5 clinical population -- and the physician 6 population, well enough recognized and the 7 industry population so that there is an 8 understanding of what the needs are, who's 9 in need, which pediatric population, which 10 age? 11 You already heard it's not about 12 adults in pediatrics, as all of you know. 13 It's about adults and newborns, infants, 14 small children, older children, adolescents. 15 There's lots of ways with breaking down the 16 pediatric population and the need to 17 understand where is this product in need, 18 what age group, what specific disease groups 19 and therefore what will be needed to get 20 into that population. 21 The next slide, please. I want to 22 spend most of my time right here, on this BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 69 1 slide, and that is because this points out 2 some of the challenges -- again, not 3 barriers -- but challenges to developing 4 devices in the pediatric population. One is 5 designed. 6 The infants for design development 7 really come best to us as industry from the 8 clinical population, from the clinical user, 9 from you, from the physicians. In 10 understanding what this population at need 11 is -- as I said, which of the pediatric 12 populations is in need; what are the special 13 issues for that population? What are the 14 special changes? What are the unique things 15 that happen to children as they grow and 16 mature that are important to understand and 17 design because it's not about size? It's 18 really about overall design, and going 19 back -- if you have already have a product 20 in market -- going back to develop that 21 device for pediatrics frequently means a new 22 device developed; a really new development BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 70 1 process, and that development process needs 2 a lot of information from the use of a 3 potential user community. 4 Another issue is materials. There 5 are materials that are perfectly safe for 6 use in adults that may not be as safe for 7 use in children and, therefore, for those of 8 us developing those devices, we need to go 9 back and do the materials testing. New 10 materials testing can be a four- or 11 five-year process. We're talking about long 12 lead times and understanding the needs for 13 materials to be tested, but that the bench 14 and lots of animal testing and some of that 15 animal testing is long-term testing in order 16 to be sure that the materials are 17 appropriate for pediatrics. 18 Again, when you go back, even if 19 you have a product in the market, never mind 20 the brand-new product, sometimes, as is 21 pointed out, the older product may be more 22 difficult because you're going to have to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 71 1 reevaluate materials and change them and 2 that could change all device design. 3 On bench testing, bench testing is 4 done on the actual product most often so you 5 have to get through a lot of testing before 6 you can get to actually doing bench work, 7 but bench testing in the medical device 8 arena is extremely useful. It addresses not 9 only the performance of the device, but many 10 issues that are focused on safety and 11 effectiveness can, in fact, be evaluated at 12 the bench in engineering testing for medical 13 devices, and I'm emphasizing that because 14 it's not only about clinical testing. 15 Clinical testing in medical 16 devices pretty much is the confirmation that 17 you got it right and that you do understand 18 the issues of safety and effectiveness well 19 enough, but it's not from scratch because 20 bench testing -- and then the animal testing 21 that's done -- can get you significantly 22 down the road on the issues of safety and BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 72 1 effectiveness when you're talking about a 2 medical device. 3 Again, the devices are designed to 4 address a specific need, so they're created, 5 designed, developed, and built to meet those 6 specific needs. Therefore, knowing what the 7 end goal is allows the development of 8 testing and evaluation at the bench and then 9 in animals that is very specific to the 10 issues of safety effectiveness for the 11 product so that by the time you get to any 12 needed clinicals, it's really confirmation 13 testing and not putting something in and 14 saying you're not really sure how this 15 works, what it's going to do. It's really 16 quite a different process when we talk about 17 medical devices. 18 Animal testing has some challenges 19 in it as well. I think Joanne mentioned a 20 little bit about what's needed for doing 21 testing for medical devices if you are going 22 to be using them in infants or are you going BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 73 1 to be using them in small children? 2 Frequently that testing, there will be a 3 need for testing in appropriate aged animal 4 populations. 5 Again, it's a challenge to do 6 that, to design devices that you can 7 actually test in that way because animals 8 are not the same size obviously as the 9 populations we're trying to address 10 clinically. 11 So a lot of assumptions need to be 12 made in order for animal testing to be 13 appropriate. It really is a challenge for 14 the medical device developer. 15 When these are insufficient, when 16 design materials testing, bench testing and 17 animal testing don't get you all of the 18 information you need and when you've figured 19 out what you don't know and what needs 20 confirmation, you go into human clinicals. 21 A lot can be gained from doing 22 human clinicals and non- pediatric BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 74 1 populations where it's appropriate to have a 2 device used in an adult population. There 3 are situations where if a disease obviously 4 is only one condition, is only in the 5 pediatric population, there's no option, all 6 of the testing needs to be done or whatever 7 clinical testing needs to be done must be 8 done in the pediatric population, but for 9 many devices, the clinical information 10 developed in testing and use in an adult 11 population is extremely useful and very 12 informative for the use of pediatrics. 13 Again, pediatric clinical testing 14 isn't starting from scratch. We need to be 15 sure that we are more open to understanding 16 what can in fact be understood and used from 17 adult testing and what small amounts of 18 information might need confirmation, 19 particularly on issues of a particular 20 safety concern, an issue in pediatrics that 21 has to do with growth and maturing of the 22 pediatric patient versus the adult patient, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 75 1 but a tremendous amount of safety and 2 effective information can, in fact, come 3 from the adult experience. So where and 4 when needed are really critical challenges 5 as well as questions for the medical device 6 developer. 7 Then an area of manufacturing, 8 when we talk about the manufacturing of 9 devices that are different from what is 10 already being manufactured, what we're 11 talking about has a couple of aspects. One 12 is when you manufacture devices, obviously 13 you have to develop the equipment that can 14 manufacture the device you're talking about, 15 although in the device industry, a lot of 16 work is done by operators, by humans. A lot 17 of people do a lot of handwork in the 18 development of medical devices. 19 There's still a lot of equipment 20 that's used and, therefore, moving from the 21 manufacture of a device for adults to a 22 different size or a different capacity, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 76 1 different rate capacity, different engines, 2 different software, all of that, 3 manufacturing needs to be changed. So 4 that's a big area for us and understanding 5 what we're going to need to do for medical 6 devices. 7 There are shelf life issues. That 8 has to do with what's the size of the 9 population and how much of the device will 10 be used. It has to do with how we rate our 11 manufacturing, how we make sure that devices 12 of all of the different sizes can be 13 available appropriately in time, not just in 14 design and in development and through FDA, 15 but also continue to make them available 16 appropriately in the pediatric population 17 where you've had a range of different sizes 18 and performance issues across the pediatric 19 population, so that has to do with how we 20 manufacture and then there are times when 21 creating particular devices for the 22 pediatric population is going to have BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 77 1 challenges in manufacturing that don't exist 2 for the adult device. A lot of that may be 3 related to size. Some of it may be related 4 to use. 5 Again, I just want to point out 6 that the issues of developing a device for a 7 specific population in need, in particular 8 the pediatric population where there are 9 issues of size, development, change over 10 time, pose real significant challenges to 11 the manufacturing community. 12 Next slide. So what do we need? 13 Talking about barriers and challenges; we 14 have some from the device industry side and 15 I wanted to take on two. One is what we 16 need from the clinical community and then 17 I'm going to talk a little about what we 18 need from the regulatory community. 19 As I said, one of the issues that 20 comes up most often in devices and the way 21 in which most devices are developed is by 22 good communication between the use -- the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 78 1 potential user -- and the individuals 2 designing -- trying to design -- the product 3 and therefore the input, design input, from 4 the clinical community is a critical need. 5 One of the things that I found 6 though from when I was at the FDA and 컴컴 7 industry is that although we'll know some of 8 the things, some of the needs, some of the 9 products, I am unaware of a good compendium 10 that identifies a good listing or website or 11 anyplace to go to find out what the critical 12 needs are for pediatric devices. Where are 13 the gaps, and that's got to come from the 14 clinical community. 15 We need the specialty societies 16 and practicing pediatrics in all areas of 17 pediatrics to identify the areas where there 18 are needs because without that gap, without 19 understanding what those gaps are and where 20 the needs are, it's really not possible for 21 us as manufactures to understand where we 22 need to go, understand where the critical BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 79 1 issues are, and understand how to move our 2 processes. 3 As I already pointed out, those 4 processes need lead time, so we need to have 5 an understanding from the community where 6 the real needs are, where the critical 7 issues are so that we can address them and 8 figure out do we have technologies already 9 available that need some modification to 10 work in pediatrics and where are the places 11 where really new development needs to take 12 place in order to meet pediatric needs. We 13 don't know what all those needs are. 14 As was already pointed out, many 15 companies already address pediatric needs 16 when they're making devices. The LVAD are 17 now down to five years old. Pacemakers go 18 all the way to infancy. All different types 19 of direct delivery devices are available for 20 all ages. There's lots of places where that 21 work is already being done. So we need to 22 understand better where are the gaps, where BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 80 1 are the leads so that we can address them. 2 I want to put in one comment, 3 although I know Pat will take this up later, 4 and that has to do with the development of 5 diagnostics. Most diagnostics do go 6 through -- come to market -- through 7 the 510(k) process that Joanne described; 8 the free market notification process, but 9 let me assure you that those 510(k)s contain 10 clinical data, but they're not new clinical 11 studies. 12 510(k)s on the diagnostic side 13 contain large numbers -- large amounts -- of 14 data that was developed with samples already 15 available to the manufacture and samples 16 from all different populations so that the 17 availability of testing -- I think one of 18 the issues that we'll face, and I'll let Pat 19 speak to the issues in diagnostics -- but 20 one of the issues is what are norms? In 21 order to understand the sensitivity and 22 specificity of a diagnostic test, you need BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 81 1 to understand what the norms are in that 2 population. Again, a place where we need 3 information, input, and cooperation from the 4 clinical community. 5 We also need the clinical 6 community to participate as we move forward 7 in helping us understand testing, in 8 participating in the appropriate trials and 9 data-gathering, whether they are pre-market 10 or post-market. We need a lot of 11 cooperation from the clinical community in 12 order to get the information and this is not 13 a one-size fits all, well, we're just 컴컴. 14 There are some real issues here about what's 15 the right kind of data to capture, how is 16 that data collected, how is it brought 17 forward, and whose data is it. 18 So we have a lot of issues where 19 we're going to need help from the clinical 20 community to take a leadership role in 21 defining what's needed and then moving on 22 and developing the bridge that will be BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 82 1 participants in whatever human testing is 2 needed and in capturing information 3 post-market. 4 Next slide. What we need from the 5 regulators -- Joanne talked about some of 6 these, but I'm going to reemphasize them. 7 One of the challenges here that I already 8 talked about, Joanne talked about, and Jon 9 mentioned it as well, is understanding what 10 amount of data is needed to move products 11 into use of pediatrics. If products are 12 already available for other populations -- 13 for the adult population maybe; for the 14 elderly population, which is not -- for 15 those not in devices who may not be aware -- 16 our devices also have to be evaluated in the 17 elderly frequently because they 18 physiologically are also not like people 19 between the ages of 18 and perhaps 컴컴. So 20 we do need to understand from the regulator 21 and need the regulator to understand how 22 current data can be used and the amounts of BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 83 1 current data that are already available that 2 can, in fact, be used to help move products 3 into the market specifically for pediatrics. 4 Reasonable requirements for 5 sufficient data development 컴컴 pediatrics. 6 Joanne talked about it a little as well and 7 from an industry perspective, one of the 8 critical needs from the regulator is 9 advanced understanding of what is going to 10 be necessary to put a product into the 11 market. 12 I already spoke several times 13 about the fact that device companies need 14 long lead times to do this development. If 15 we get through development and FDA has 16 changed the requirements, we're set back. 17 We're set back, we can't move our products 18 forward and we can't get them. So we need 19 to be sure that the regulator identifies 20 what the real data needs are, what's going 21 to be expected so we can move products 22 efficiently into the markets. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 84 1 DR. ABRAMSON: You've been hooked. 2 DR. ALPERT: Is that the hook? 3 (Laughter) 4 DR. ABRAMSON: Yes. 5 DR. ALPERT: The next point, which 6 is almost visible, I think is the most 7 critical. As we go through this process 8 together, we need to be sure that we are not 9 creating additional barriers that are going 10 to prevent rather than promote the 11 development of devices for pediatrics. This 12 is a real challenge. 13 There are many things that sound 14 simple; they sound simple on their face. 15 Well, let's require certain kinds of 16 communications from companies about their 17 devices. They sound simple, but they create 18 barriers that may, in fact, not only prevent 19 new devices from being developed, but may, 20 in fact, have the unanticipated effect of 21 removing devices from available to 22 pediatricians that are already in the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 85 1 market. 2 So I'm putting a caution on the 3 table that we don't in this process create 4 new barriers that are going to adversely 5 impact what is currently in the market and 6 adversely impact the capacity to have new 7 products in the market. 8 Let me look and see what was at 9 the bottom of that slide, and then pathways 10 to market with clear expectations. 11 There are different requirements 12 for different types of medical devices, and 13 as Joanne pointed out, there are three 14 major -- actually four major -- ways in 15 which medical devices can move into the 16 market through the regulatory process. One 17 of the things that we need from FDA is clear 18 understanding of which devices will qualify 19 for HDE, which devices can be developed 20 through pediatrics and still go through the 21 pre-market notification of the 510(k) 22 process. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 86 1 What specific devices might need 2 pre-market approval; PMA devices? Which can 3 be done as supplements which are changes to 4 currently available products that can go 5 through a more abbreviated process. 6 We need very clear pathways from 7 the regulators. So we need the information 8 from them as to what's going to be needed in 9 the pathway as well. The regulatory 10 mechanisms that will be available and 11 perhaps we might need new mechanisms to make 12 these devices more readily available in a 13 faster way in the marketplace. 14 So, in summary, there are lots of 15 challenges for the medical device 16 manufacture, designer and manufacturer, 17 based on the needs of the pediatric 18 population and the specific physiology of 19 pediatrics. These are not trivial and they 20 take time, energy, and obviously money to 21 make these developments so that the products 22 will be available, but before we can BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 87 1 initiate those development programs, we need 2 information about where the gaps are and 3 what the real needs are for the pediatric 4 population and we need the regulators to be 5 clear as to what the pathways and what their 6 needs will be so we can move pediatric 7 devices more readily into the market. 8 Again, a final reminder: Many, 9 many, many medical device companies already 10 have products in the market for the 11 pediatric population. Many are interested 12 and are working on developing new products 13 and many more could come in if they knew 14 what the gaps and needs were. 15 I look forward to the discussion. 16 I'm pleased to see people from all different 17 aspects of the pediatric needs in the room 18 together and I hope that we can come up with 19 an approach that will work for all of us. 20 Thanks. 21 MR. ABRAMSON: Susan, thank you. 22 I'm going to ask everybody to come back BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 88 1 at 10:30; take a break, come back at 10:30. 2 We'll start the discussion, the whole rest 3 of the day will be open discussion through 4 our sets of questions and I very much look 5 forward to the input. 6 Thank you. 7 (Discussion off the record) 8 DR. ABRAMSON: 컴컴 which we'll 9 get to before lunch and the others we'll get 10 to later on, but what we want to end up 11 today is potentially one or more proposals 12 that might pull all of these problems that 13 have been highlighted for you today; how we 14 might work together better and a lot of us 15 have been thinking about this for a while 16 and we'll come to discuss this later on. 17 So this morning, what I hope to do 18 is to take on the following questions: What 19 are the unmet medical device needs across 20 the pediatric population? Is the need for 21 pediatric medical devices concentrated in 22 certain medical specialties? Is there a way BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 89 1 to prioritize the kind of devices needed for 2 the pediatric population and how does the 3 lack of availability of appropriate devices 4 impact 컴컴? 5 Those are further declining 6 problem questions. You'll see it's 7 inevitable that we won't cleanly answer all 8 questions though. We'll move back and forth 9 between these four questions. In the 10 afternoon, we're going to talk about how to 11 put this problem together with a workable 12 solution. 13 So let's take on the issue of what 14 of the unmet medical device needs across 15 pediatric population and a subset 컴컴 occur 16 컴컴 condition of pediatric specific and 17 those that affect both children and adults. 18 So does anybody want to answer any 19 of those questions? 20 (No response) 21 DR. ABRAMSON: All right; then I 22 will start them off. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 90 1 (Laughter) 2 SPEAKER: I think you need to 컴컴 3 those questions. 4 DR. ABRAMSON: We need medical 5 devices that can actually allow us not to 6 use 컴컴, and a good example of one that's 7 been created already is the 컴컴. So we do 8 a lot less blood 컴컴, but we're still 9 having to get electrolytes. We're still 10 having to go in after the vein to get that. 11 This is probably an issue I'm sure 12 that also adults would like. 13 SPEAKER: Excuse me. We really 14 can't hear back here. I don't know if you 15 can speak up or not. 16 DR. ABRAMSON: Sure; I'll try to 17 speak up. So the question we're on is what 18 are the unmet medical device needs across 19 pediatric populations? I've started off 20 with one that I think is fairly obvious and 21 fairly simple and that is the ability to 22 monitor more things without having to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 91 1 actually stick a vein to draw blood. We've 2 had pulse ox's for a good piece of time. I 3 know people have tried to create CLQ 4 equivalents, and not successfully. 5 I know no one who has created 컴컴 6 we can measure sodium potassium; those kinds 7 of things, and I think the glucose one, 8 though there are a couple of devices that 9 have been created to do that, do not 10 specifically measure the exact glucose 11 there. When you compare, you know, somebody 12 to draw blood and say its one/a hundred and 13 you look at the sensor and say -- the 14 sensors are better at looking at, you know, 15 gross changes than they are what is the 16 specific number. 17 So I'll throw out that one. Now 18 I'll let perhaps Dr. Jenkins talk about 19 cardiology. What do you have? 20 DR. JENKINS: I mean, I think the 21 obvious answer to the question is there's 22 lots of different kinds of unmet medical BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 92 1 needs. I think one that I would just sort 2 of throw out for consideration, from an 3 illustrative perspective, is I think almost 4 anything in cardiology that requires 5 algorithms or a computer software component 6 is very underdeveloped in children and often 7 it is more of, you know, a death to the use 8 of the technology, even then issues related 9 to miniaturization. I think a good example 10 is that the American Heart Association can't 11 endorse uses of ADDs in kids less than a 12 year of age because there's no 13 evidence-based algorithm supporting their 14 use except -- there may be one new product 15 on the market that's going to move it down 16 to the lower level, but it's a long time 17 coming for a lifesaving device. 18 DR. ABRAMSON: Marilyn -- you look 19 like you're straining to hear that. 20 MS. FIELD: I can't hear her. 21 DR. ABRAMSON: Can you just speak 22 a little bit louder, please? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 93 1 MS. FIELD: I heard computer 2 algorithms and nothing much after that. 3 DR. JENKINS: Yes, computer 4 algorithms to support technologies 컴컴 into 5 pediatrics are often very underdeveloped and 6 don't work. Simple things like EKG-reading 7 algorithms don't work at all. The example I 8 used was AED algorithms, which the HA, at 9 least for many yeas, couldn't endorse in 10 children because there were no algorithms 11 developed to support the uses of the 12 technology, even if the same products were 13 saving kids, much less when you had to move 14 down the 컴컴. So I'll just throw that out 15 as an example; the unmet need in cardiology. 16 DR. ABRAMSON: Andre, would you 17 talk about some of the pulmonary issues that 18 you might have? 19 DR. MUELENAER: Sure. Yes. I'm 20 sitting here trimming the list. I kind of 21 look at what I can do -- respiratory control 22 disorders and then all the other mechanical BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 94 1 kind of things, but respiratory control 2 just, you know, starting from the top: 3 Sleep diagnostics for infants and children. 4 Pulmonary functions: We have pretty good 5 devices down to about age four and below 6 that. Most of it is still somewhat 7 experimental. You know, you just can't tell 8 a two- year-old to blow into a device 9 reliably. 10 On our list serve just last week, 11 we had a tremendous discussion about airway 12 stents and we're using coronary stints and 13 babies' airways with good, immediate results 14 and terrible long-term results, and so we're 15 still, you know, using the old- fashion way, 16 doing trach's and putting babies on CPAP and 17 there's no CPAP for use in the home that's 18 reliable. I mean, I've been beating my head 19 against the wall about this for the last 20 20 years 컴컴. Other needs: Home monitoring, 21 which we do a fair amount of now, the 22 ability to wirelessly, you know, eliminate BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 95 1 the leads. I mean, that's the number one 2 request from parents when we do focus 3 groups, looking at home monitoring in 4 infants. Can you get rid of that darn cable 5 so I can carry the baby to the grocery store 6 and not slam the door on the cable line, put 7 them in the car and make my baby more 8 normal. 9 In the hospital, the same thing: 10 Use of wireless technology, just talking to 11 physicians in general and other caregivers, 12 and I think sometimes we forget who really 13 touches the technology. It's not 14 physicians. It's nurses and therapists; 15 anything that will eliminate paperwork and 16 get clinicians back at the bedside is also 17 of great need and I'm sure I'll think of 18 other things as we move along here. 19 DR. ABRAMSON: Would anybody else 20 have any thoughts about other things they'd 21 like to mention? We're just not trying to 22 fix everything, but get some ideas. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 96 1 Yes? 2 DR. CAMPBELL: I'm a pediatric 3 orthopedist. I'm in the trenches. 4 Generally, I use hundred-year-old 5 operations, treatment of diseases of kids. 6 The devices are usually 60 years old or a 7 little bit of an improvement over 컴컴, and 8 there are a lot of areas that we go around 9 jury-rigging the seat of our pants. I'm 10 really concerned because what hasn't been 11 mentioned so far is people are improving 12 jury-rigging as a safety valve in the 13 situation and with the malpractice crisis, 14 which hasn't been talked about, that may 15 close. 16 People like me in their fifties, 17 we're sort of old guard, but this new 18 generation is much less risk adverse. So 19 I'm really concerned long term about my 20 specialty. 21 There's roughly 700 pediatric 22 orthopedists in Canada and the U.S., and BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 97 1 we're not getting 컴컴 fellowships. 2 Probably one reason is because we're high 3 risk. We're liable until a patient reaches 4 maturity, plus the statute of limitations. 5 That's a real issue for us. 6 I wanted to talk about several 7 areas. In particular, children don't have 8 joint prosthesis. Adults have them, but 9 they're very special issues; the drug 10 concerns and everything. There are 11 conditions -- I can't reconstruct the joint 12 and expect it to grow and I just don't have 13 anything. There's little work, if any, on 14 this, except maybe 컴컴 reconstruction. 15 I'm a pediatric orthopedist. You 16 know, I bend over backwards not to harm 17 growth anywhere in the body. A baby with 18 club feet, I do soft tissue releases at age 19 six month to try to realign the foot and let 20 the growth take over and hopefully have as 21 good a foot as possible by 컴컴 maturity, 22 but I put a different hat on when I'm an BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 98 1 orthopedic surgeon with a six-month- old 2 baby with a spine problem. 3 I've used the spine. I stop 4 growth. What does that do long-term? I 5 absolutely do not know. So our specialty 6 needs to have the ability to develop new 7 treatments to spine deformity that nurtures 8 growth 컴컴 thorax and it's very frustrating 9 because it's very hard to do this. 10 Trauma is a tremendous problem. I 11 put in implants that were developed in the 12 early part of the last century. We need to 13 design new implants that are biocervical; 14 safe, strong, and absorbent because when 15 children grow, you know, long bones 16 incorporate the metal devices. I've got to 17 go back in and pull them out. Second 18 operation, more morbidity. It seems that it 19 ought to be a way to solve this with a 20 one-time procedure. 21 I'm a surgeon so there's always 22 risks; there's always complications. My job BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 99 1 is to minimize that and make it better. 2 Growth disturbances: We're still 3 using techniques pioneered in the 1930s to 4 컴컴. Screws the wires through the leg 5 lengthening them. There needs to be 6 research into a mechanical equivalent for a 7 growth bite, and to my knowledge, no one's 8 ever even looked into that. 9 Your comment earlier is well 10 taken. You were talking about shunts on 11 encephalitis, but as a surgeon, I have seen 12 untreated hydrocephalus. The heads are 13 twice normal size. The cerebral cortex is 14 crushed by the fluid. So 컴컴 said it's 15 very frustrating, changing out shunts 16 constantly, treating the infections, but 17 it's much lesser than the other 컴컴. 18 So whenever you look at these 19 problems, think about what happens 컴컴. 20 DR. ABRAMSON: Just let me be 21 clear. I wasn't trying to say that we 22 should get rid of shunts. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 100 1 DR. CAMPBELL: No, sir. 2 DR. ABRAMSON: That we should make 3 them better. 4 DR. CAMPBELL: Right. I agree and 5 if there's a way to put antibiotics on, you 6 know, that's a struggle in orthopedics, 7 trying to get that through regulatory. 8 DR. ABRAMSON: Well, that issue 9 has actually been looked at and there's a 10 great controversy about resistance and then 11 with the things like silver, that have been 12 컴컴 and some of the adults still don't use 13 them for the most part because of concerns. 14 We need better, and that's all I'm saying. 15 I'm not saying the manufacturers 16 are bad, because I haven't done it. I'm 17 just saying we need to clearly get the 18 message out that it's not good enough. 19 DR. CAMPBELL: I understand and I 20 agree. I've had my say. Thank you. 21 DR. ABRAMSON: Good. Great. Yes? 22 DR. ZUCKERMAN: Yes. Thank you. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 101 1 I'd like to build upon what you've just said 2 and apply it back to perhaps the 3 cardiovascular device situation. Perhaps 4 one way to approach this question is to ask 5 Kathy and others when you're in the 6 pediatric cath lab, are any of the pediatric 7 devices you're using unlabeled devices or is 8 it all off-labeled use? I think to a large 9 extent, it's all off-labeled. I can't think 10 of a coronary stent approved for pediatrics. 11 Can you? 12 DR. JENKINS: Well, actually, I'm 13 not an interventionist, but I work a lot 14 with our interventional groups and there is 15 sort of an anecdotal joke that one of our -- 16 my chair mentioned, 컴컴 told where he had 17 done a very complicated interventional 18 procedure. I think he put six or seven 19 stents in pulmonary arteries and on the way 20 out actually noticed that one of the iliac 21 arteries had been damaged and put a stent in 22 the iliac artery on the way out and said it BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 102 1 was the first time ever that we'd used a 2 stent in the 20 years in our cath lab for an 3 improved indication, which is an iliac 4 artery, and it's that core technology that 5 we use every day. 6 Pulmonary artery dilation, balloon 7 dilation catheters, all of the -- almost 8 every single product that we use is not 9 approved for use in the kids that we use 10 them in for congenital heart 컴컴. 11 DR. ZUCKERMAN: Right. So I think 12 that really helps us understand the problem 13 now; what is the big need? What are the 14 incentives that are going to make industry 15 perhaps fill that need, but certainly in the 16 pediatric cath lab, similar to a 컴컴. 17 DR. ABRAMSON: There's one more 18 that I'd like to bring up and that is 컴컴 19 monitors. When I talked to Susan Alpert 20 about four years ago, five years ago, she 21 informed me that they're grandfathered in. 22 The problem with them is they don't work. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 103 1 Ninety percent of parents within 2 one month stop using them because they're 3 going off all the time in sort of false- 4 positives and so I don't know where we have 5 to go, and I'll ask the FDA that, but we 6 have a product out there that there are many 7 "me-too" generations of, but they're still 8 not adequate. They don't do what we're 9 asking them to do. 10 Susan? 11 DR. ALPERT: It seems to me that 12 one of the things that we need to be talking 13 about is -- 14 SPEAKER: Susan, please speak up. 15 DR. ALPERT: One of the things we 16 need to be talking about is a process. I 17 think these are very helpful examples, but I 18 think if we're going to suggest that 19 something be done, it seems to me we need a 20 process. How do we capture this 21 information? Who does the capturing and how 22 is this captured in the clinical and BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 104 1 pediatric community to get some better idea 2 and then be able to do some prioritizing and 3 some risk assessment because I think that's 4 got to be done. 5 I mean, that's what the question 6 is. The question is, you know, what's 7 missing? In order to do the what's missing, 8 somebody's got to, you know, sort of 9 undertake the process of figuring out how do 10 you identify in each of the areas where the 11 needs are and then prioritize those needs 12 and then we can figure out, you know, how do 13 we establish the communication with the 14 industry. 15 So I think, you know, the examples 16 are very helpful because they highlight 17 things like where there's nothing or where 18 there's something, but maybe unlabeled and I 19 think that's an issue to be discussed as to 20 what's unlabeled simply because it's 21 unlabeled, but actually it's tested? What 22 needs testing and labeling? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 105 1 Then there are the issues where 2 improvements are needed, but those are very 3 different -- they're very different areas 4 and I think we need to figure out what the 5 process to get there and I'm going to do 6 that and then unfortunately I have to duck 7 out for a minute for a telephone meeting and 8 then I'll be back. 9 DR. ABRAMSON: All right. Well, 10 let's just say that after lunch, we're going 11 to get -- we are going to propose one 12 potential solution, kick that around and 13 have others propose other potential 14 solutions to address some of these issues. 15 DR. HAFFNER: Yes. I just wanted 16 to follow on, Susan, what you were saying 17 and it's what's missing and why was it 18 missing and what will it take to change that 19 because, you know, nature pours a vacuum, 20 so, you know, if there were a reason to 21 commend that, industry probably would have, 22 and there's a reason why they haven't. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 106 1 So are there incentives that are 2 needed clearly coming from orphan drugs. 3 You know, that's my vested interest of 4 knowing something about incentives, but they 5 work, and, you know -- and they certainly 6 worked initially in pediatric drug 7 development. So that needs to be part of 8 the 컴컴. 9 DR. ABRAMSON: Yes? 10 MS. IRELAND: Before we move to 11 the discussion this afternoon about what 12 systems and what solutions we might want to 13 have in place, it might be helpful for all 14 of us to hear from those of you who 15 communicated with the device companies in 16 the past and have had even some of these 17 examples. When has it worked, because 18 clearly sometimes pediatric devices are 19 being monitored by the 컴컴? 20 We've talked about where there are 21 some gaps, but do people have examples of 22 where they've communicated and gaps have BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 107 1 been filled? Maybe that gives us something 2 to build on for this afternoon. 3 DR. JENKINS: Sure. I mean, 4 there's a lot to say in answer to that. I 5 think interestingly there are products where 6 there's a natural trajectory for the product 7 to be miniaturized. I think pacemakers are 8 a good example, where if there's just a 9 natural push for things to be smaller, then 10 when industry goes to make things smaller, 11 it's a little bit easier for them to want to 12 move downward to the pediatric market. I 13 think it's a little bit less true in areas 14 where the miniaturization of the product 15 isn't part of the adult uses. 16 So we've approached industry a 17 lot. I mean, the usual way -- 18 interventional cardiology is very dependent 19 on technology and so our innovative 20 clinicians want the latest and greatest new 21 toys all the time and so I've actually 22 personally been in the situation of BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 108 1 approaching industries on a number of 2 occasions to say can you help us use your 3 product in children and occasionally the 4 door is open, but usually the door is closed 5 and the usual reason that the door is closed 6 is that people are afraid that the pathway 7 to a pediatric use might somehow interfere 8 with an adult labeling indication and so 9 they'd be very, very, fearful of that and 10 not want to go muddy the waters with the 11 pediatric use. 12 Sometimes, especially lately, with 13 the FDA encouraging the use, we've had the 14 door be more open, but usually they'd be 15 very unwilling to devote the infrastructure 16 that would be necessary to support pediatric 17 labeling indications and if we can provide 18 that for them a little bit on the 19 shoestring, then we can often find that the 20 door is open and start to get trials moving 21 forward through the FDA process for kids, 22 but it's with us sort of playing a big piece BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 109 1 of the action where the companies wouldn't 2 be willing to devote their resources from 3 their own machinery, which is aimed towards 4 the profit-moving indications to those types 5 of trials. 6 DR. ABRAMSON: Well, someone from 7 the companies wanted to speak to the issue 8 of being afraid. If you do it for a 9 pediatric indication, it actually makes it 10 harder for you. 11 MR. O'HOLLA: I was going to ask 12 the question is there a specific -- I'm 13 having a hard time understanding that 14 because if, you know, I'm looking at brand, 15 I'm not sure that pursuing a pediatric at 16 the same time you're pursuing an adult would 17 get in the way of your major indication. 18 I could see where it would be more 19 work, and I'm not sure how it would hurt the 20 approval. 21 DR. JENKINS: Yes. Well, an 22 example is that a study that we're doing BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 110 1 right now, which actually successfully move 2 forward, but with some difficulty for a 컴컴 3 technology, which is a pulmonary artery 4 dilation. We're using it in pulmonary 5 artery dilation procedures. 6 There's blades on the balloon, and 7 there's fear of this balloon, you know, 8 perhaps being a risky product and the 9 company that was pursuing this technology 10 was not through their own FDA process and 11 they didn't want to be using this technology 12 in small pulmonary arteries in young 13 children, even though those children had no 14 other potential therapeutic uses because 15 they felt that if, you know, a few babies 16 died and did badly with that technology, 17 that would not look well for them. 18 MR. O'HOLLA: It would kill the 19 technology. 20 DR. JENKINS: It could kill the 21 technology. 22 MR. O'HOLLA: So it's that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 111 1 emotional thing of God forbid I have a dead 2 child. 3 DR. JENKINS: Well, I think people 4 do try to pick relatively safe indication, 5 you know -- 6 MR. O'HOLLA: Yes. 7 DR. JENKINS: -- which doesn't 8 sort of merge itself well with their 9 life-threatening pediatric diseases with no 10 other solutions. 11 MR. O'HOLLA: Well, do you think 12 that's a real problem to getting the 13 approval or is it more of a public 14 relations, public opinion? 15 DR. ZUCKERMAN: I should hope that 16 it's a PR problem on the side of the 17 regulatory affairs person at this particular 18 company. It's a great example where the 19 cutting balloon has kind of knives on the 20 end. It has a difficult risk-benefit 21 profile to assess in adults, but the 22 question of pulmonary stenosis in kids, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 112 1 where we don't have anything approved, where 2 there are major- league problems, has a very 3 different risk-benefit profile and, you 4 know, we would look at it as a separate 5 application, you know, as Bob is suggesting, 6 but I can appreciate where the industry 7 would be worried, but I would encourage you 8 to pursue it. 9 DR. JENKINS: Oh; it's being 10 pursued. 11 MR. O'HOLLA: Is that one of the 12 barriers we need to make sure it gets 13 identified? You know, I think we heard a 14 couple of times this morning this whole 15 thing about it's unethical to do studies on 16 kids or it's problematic to do studies on 17 kids. A lot of that seems to me to be 18 related to the emotion attached with 19 technology not being perfect and it seems 20 between the practitioners, the Food and Drug 21 Administration and the industry, as we focus 22 on that issue and help -- I think we have BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 113 1 the ability to make that issue go away if we 2 can put those things in perspective. 3 DR. ABRAMSON: We did for drugs. 4 I mean, the same issues were raised for 5 drugs and we made it go away because they're 6 just great examples of where you don't study 7 it and the very bad side effects that occur 8 when you don't do that. 9 DR. JENKINS: This actually 10 example brought up another barrier, so to 11 speak, and I thought personally the FDA was 12 very hopeful with this particular one, which 13 is that often the studies in adults are very 14 incremental. So, for example, if you want 15 to study a new, novel technology in 16 pulmonary arteries, you're going to base 17 that on the core technologies that are 18 already approved. So if nothing's approved 19 in kids, there's nothing to base it on. 20 So we were in this odd situation 21 where we were looking for approval of a new, 22 novel technology where the core technologies BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 114 1 of simple 컴컴 dilations in pulmonary 2 arteries had never been through an FDA 3 process. It was all off- label and it was 4 really very important for the agency to work 5 with us around that issue and actually it 6 was FDA reps who came up with suggestions 7 for how to bridge that barrier from their 8 perspective and from the perspective of 9 getting the product labeled. 10 So it's successful example 11 actually. 12 MR. O'HOLLA: What did you use as 13 you control, just to be curious? 14 DR. JENKINS: Well, this is 15 randomized to an non- approved technology 16 that is also widely used, but unproven, but 17 what the FDA suggested that we do -- which 18 we are doing, in the process of doing -- is 19 gather data about the core technology on the 20 way to the labeling study that we were doing 21 so that we would potentially be building 22 that background data set that should have BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 115 1 been built 20 years ago that never was 2 built 20 years ago so we could move forward, 3 and that was an excellent solution. 4 MR. O'HOLLA: I think that's going 5 to be a huge issue for a lot of pediatrics 6 and products as you move forward. 7 DR. JENKINS: It was a great 8 solution. 9 MR. O'HOLLA: I have an 10 established practice, but I don't have 11 approved practice. 12 DR. JENKINS: Right. But I 13 personally found that because the FDA has 14 been very interested in trying to do 15 pediatric studies, they've been very open to 16 understanding that from practitioners. 17 DR. ABRAMSON: I think there's 18 also something else -- 19 MR. O'HOLLA: But that's -- I'm 20 sorry. 21 DR. ABRAMSON: -- lost here and 22 that is there are times when pediatric BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 116 1 technologies are -- well, technologies are 2 first developed in pediatrics and then 3 expand out to the adults and 컴컴 -- who is 4 probably one of the best examples of that -- 5 created initially specifically for a 6 neonatal pulmonary hypertension and then it 7 develops its whole full spectrum based on 8 very, very finite -- very, you know, 9 designated group of patients. 10 MR. O'HOLLA: While we're on 11 clinical trials, I'd like to say two more 12 things: I think that's a great solution, 13 but I think if we -- and I'll direct my 14 comments to the FDA folks -- if we always 15 look to establishing the background on the 16 established practice moving forward, you're 17 going to get companies that are going to 18 start to balk because that becomes a very 19 extensive part of the study. 20 So I would suggest that there are 21 times where that may be appropriate, but we 22 also have to look at perhaps making BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 117 1 decisions without controls and looking 2 towards labeling to inform the physicians 3 that we've studied this in children and here 4 are the results we get in these patient 5 populations so that you have more 6 information to base your practice decisions 7 on where we don't have comparisons, and that 8 may not be always necessary, particularly 9 when we have these unapproved established 10 practices. 11 The other thought that occurred 12 several times to me this morning during 13 presentations is this whole issue of 14 clinical studies. I think Joanne and Susan 15 outlined it very well. I think the question 16 is when do you do it and I think there were 17 some very clear rules, kind of thought 18 processes, that were on your slide, but some 19 of the earlier questions before the 20 presentations were related to special things 21 about pediatrics like growth. 22 If we are going to wait for those BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 118 1 answers from those clinical studies, we're 2 not going to see new devices get to market 3 because those studies would never get 4 completed, so we need to figure out how do 5 we balance off knowing what's appropriate to 6 get the technology out 컴컴 in children and 7 then what do we do it once it's out there, 8 and that's not -- and it's going to be real 9 easy to say, oh, we'll do post-market 10 surveillance, but that's not going to be so 11 easy either because the technologies are 12 going to change by the time you finish your 13 post-market surveillance. 14 For example, looking at growth 15 phenomenon, you're going to be on the fifth 16 technology and that data's not going to be 17 valuable anymore except to those groups of 18 patients that got that product. So I think 19 that's going to be a very complex issue and 20 we're going to have to strike an even 21 balance and figure out how to use the 22 information and get those products out there BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 119 1 at the same time. 2 DR. ABRAMSON: Well, you're 3 actually into the efficacy question, so 4 let's take that, and that is the lack of 5 efficacy information or problems in the 6 pediatric populations. Would others like to 7 comment on that? 8 Yes, sir? 9 DR. ZUCKERMAN: Yes. I believe 10 Bob has hit the heart of the matter on 11 several aspects in pediatrics. 12 DR. ABRAMSON: Okay. 13 DR. ZUCKERMAN: That's correct. 14 We have a situation where we don't have a 15 lot of approved FDA controls so we have to 16 venture into that territory carefully 17 because then when we make our comparison of 18 new product to unapproved control, if the 19 unapproved control is very bad in a clinical 20 trial then ideally what you've learned from 21 that is both the new product and unapproved 22 control are problematic. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 120 1 It's not that we can't work in 2 this area. The adult companies have 3 examples where we don't have unapproved 4 controls. It's just that we have to be more 5 careful in terms of the planning upfront and 6 that's why I would disagree with your 7 statement that we can't compare a new device 8 to anything. We always need to make a 9 comparison. It's just that we have to 10 accept something that might not be optimal 11 for making that comparison. 12 Certainly the agency, when it's 13 faced with a certain risk benefit profile 14 for new device technology is willing to 15 consider that option. It just underlines 16 the need for good strategic, upfront 17 planning very early in the process to be 18 realistic. 19 Comment No. 2: Susan gave a great 20 talk about the problems faced by industry 21 for market development and it's a very 22 difficult challenge, but perhaps the one BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 121 1 component that we're missing that Bob has 2 pointed out is that there's -- for most of 3 these chronic implants, the agency needs to 4 develop the appropriate pre, post-market 5 balance because these are chronic implants. 6 Certainly, we're not suggesting 7 that we need to wait ten years, Bob, before 8 we approve the next PDA, but if we make 9 approval decisions with one year of chronic 10 implant data, we have to follow these 11 devices long term. 12 Now, the approach used by the 13 agency generally is not to be most 14 burdensome, but to look for usual clinical 15 foul-up such that we can get certain signals 16 back into our feedback loop that mechanical 17 characteristics of these devices may be less 18 than sub-optimal, but I think it is part of 19 the developmental framework. The challenge 20 for your group is to tell us how to do it so 21 it doesn't cost an arm and a leg. 22 The final point about cost and BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 122 1 development and what's really necessary I 2 think is to ask the question, given that 3 this is such a difficult field, what really 4 is appropriate for industry to be the engine 5 and where's the place of NIH? Perhaps later 6 we can get back to Jon Abramson's initial 7 questions. He asked why isn't there a 8 pediatric VAD for kids under five. It's an 9 extremely difficult research project. It's 10 going to take millions of dollars. 11 The NIH is committed to that 12 particular program right now and it would 13 behoove us to better understand how that 14 program was initiated, how we can make sure 15 it's an efficient one, et cetera, and are 16 there certain other program/project areas 17 that are going to take NIH money to really 18 jumpstart? 19 MR. O'HOLLA: Bram, do you know 20 anything -- I think Dr. Abramson mentioned 21 that product was approved. There is one in 22 Germany? Do we know anything about that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 123 1 because it kind of piqued my interest to see 2 why there's 컴컴. 3 DR. ZUCKERMAN: Okay. So let's go 4 back to a very -- do you mind, Doctor? 5 DR. ABRAMSON: No, please. 6 DR. ZUCKERMAN: Let's go back to 7 the situation where we have a very 8 complicated device technology, the left 9 ventricular assist device, which is used as 10 a bridge for patients with severe end-stage 11 heart failure, either as a bridge to 12 transplant or as a permanent destination 13 therapy device. 14 Let's go over the data, first of 15 all, in the supposedly easier situation, 16 which is the adult category. The NIH has 17 really needed to put a lot of money into the 18 development here because we're dealing with 19 small device companies with very creative 20 engineers. A lot of good work has been 21 done, but I would underline the need to look 22 at our two most recent FDA advisory panel BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 124 1 meetings where LVADs were discussed: The 2 syncardia device and most recently the world 3 heart device. 4 Even in the simpler world of 5 adults, the data are extremely problematic; 6 number one. 7 Number two, I think there's a 8 general problem with device clinical data as 9 opposed to drug clinical data in that the 10 standards in Europe for drug approval are 11 more similar to U.S. Standards. It was 12 interesting at both these panel meetings 13 European LDVAD data tried to bring -- 14 companies tried to bring it into the 15 process. As you might imagine, Bob, the 16 foul-up and lack of clinical protocols, et 17 cetera, make these data very problematic and 18 it's a real question mark as to why we can't 19 do worldwide device trials when you're 20 company's leading the way. Then you ratchet 21 up the problems more than one notch when you 22 get to pediatric LVAD development. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 125 1 Certainly the newer device 2 technology has the potential, given that 3 it's much smaller, et cetera. You heard the 4 example of the micro med device where we 5 tried to leverage adult data, bench data, et 6 cetera, but there comes a point where the 7 risk benefit profile still can become 8 questionable. That's why Joanne mentioned 9 the need for good, post-approval data in 10 this particular situation, but for many 11 other applications, there is going to be 12 probably a need for limited pre-approval 13 data for pediatric VADs. 14 MR. O'HOLLA: By the way, I wasn't 15 suggesting that we not do post-market 16 surveillance data because I think, 17 particularly in this case, it would be a 18 valuable tool in that risk benefit balance. 19 What I'm not clear on in my own mind is 20 because the technology moved so quickly, how 21 long do you do that for and when? When is 22 appropriate and how long is appropriate to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 126 1 do it for? 2 If I'm going to come out with 3 something in a cardiovascular area, an 4 implant, and I'm going to come out with a 5 new implant four years from now that is -- 6 maybe it's not based on the technology that 7 I've just gotten approved. How much longer 8 do I do that post-marketing 컴컴? I think 9 it's really a question -- it's not just a 10 regulatory question or a question of cost 11 for the companies. It's a question of let's 12 keep looking at the patient. 13 What's important for practitioners 14 to know for that group of patients they 15 implanted and how long do we have to follow 16 that? Those are going to be very critical 17 questions and they may differ from device to 18 device, but we should have kind of a general 19 framework in our own minds about, you know, 20 what kind of logic do we use as we answer 21 that question. 22 MS. LESS: Could I just ask a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 127 1 question? 2 DR. ABRAMSON: Yes, please. 3 MS. LESS: I wanted to say with 4 post-approval studies, it's really difficult 5 for the agency because a lot of times when a 6 device goes to panel, the advisory committee 7 will vote as an approvable application, but 8 then tack on some conditions and sometimes 9 there's a post-approval study and the agency 10 will agree with that, but then the track 11 record for companies actually doing those 12 post-approval studies is not that good and, 13 like Bob said, a lot of times there's a very 14 good reason; the newest device has come out 15 and so doing a post-approval study on the 16 old technology doesn't really matter and the 17 agency isn't all that concerned about it. 18 In other cases though, as that 19 technology keeps advancing, you move them 20 further and further, but you still don't 21 have that basic information that you were 22 looking for three years ago. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 128 1 MR. O'HOLLA: Right. 2 MS. LESS: So I think, like Bob 3 was saying, the pre- and post-market balance 4 is very important, but we're also going to 5 need a commitment from industry to follow up 6 on those studies because otherwise, in some 7 cases, we're going to be in trouble as we 8 get further and further out. 9 MS. SHRADER: I think also, to add 10 to that, this is an area where we could 11 really use the support of both the agency 12 and the practitioners because in my 13 experience, one of the challenges with the 14 post-approval studies is that the longer you 15 run the study and the more successful the 16 device is, the smaller and smaller your 17 follow-up cohort becomes. 18 MS. LESS: Right. 19 MS. SHRADER: So for a device that 20 very well may be functioning the way that 21 it's intended to function, the majority of 22 the information you get back may be the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 129 1 anecdotal bad experiences rather than a 2 good, solid body of positive evidence. 3 MS. LESS: Right. 4 MS. SHRADER: I think that to a 5 certain extent, maybe just publicity and 6 education could help to overcome that 7 though. That's a real important thing to 8 take into consideration. 9 DR. ABRAMSON: Let me add one 10 thing that was actually pointed out to me at 11 the Institute of Medicine. They brought in 12 four epidemiologists and the question that 13 was asked of them is just this question: 14 How do you do these things that are 15 particularly difficult? They all agreed 16 they are, but we have one major advantage, 17 and that is in adults, there are 18 subspecialists out in the community in 19 almost everything that happens. In 20 pediatrics, that's not true. There are very 21 few pediatric oncologists, for instance, out 22 in the community, with small numbers of BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 130 1 exceptions. 2 So if you wanted to know, for 3 instance, what the rate of line infections 4 are, you don't have to go very far. There's 5 a very concentrated group -- the Cancer 6 Oncology Group -- that could answer that 7 question well. If you then change something 8 about lines, thinking that it might decrease 9 the infection rate, there's a very small 10 group -- again the Cancer Oncology Group -- 11 that could do it. 12 There aren't a ton of pediatric 13 cardiologists out there. So we have huge 14 advantage over the adults that we need to 15 think about and use. 16 Did I ask the person from the 17 NICHD to comment about what role they see? 18 MR. QUATRANO: You mean in terms 19 of some of the areas that were mentioned? 20 DR. ABRAMSON: Yes. 21 MR. QUATRANO: Well, first of all, 22 the comments -- I can't respond to the NIH BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 131 1 in general, though, you know, I do know that 2 there are, for example, several different 3 institutes involved in some of the 4 activities. For example, in cardiovascular, 5 you know obviously NHLBI would be a 컴컴. 6 Also there's a new institute, which some of 7 you're familiar with, the Bioengineering 8 Institute, currently an institute that's 9 interested in obviously device development. 10 Of course NICHD has been interested in 11 device development also in terms of some of 12 these areas, but it is difficult and some of 13 the suggestions that were brought up, just 14 in terms of getting people interested; 15 investigators interested in pursuing some of 16 these different topics. 17 Also you have industry. There 18 were a couple of conferences relative to 19 device retrieval, for example. When you 20 mentioned this issue about post-market, I'm 21 not sure what that refers to and obviously 22 with a consensus of one of the conferences BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 132 1 put on by the Bioengineering Institute about 2 device retrieval, there's issues about that 3 relative to industry; retrieving the device 4 and looking at its functions and so forth as 5 well as what you mentioned in terms of the 6 new generations of the device which go 7 beyond that. 8 So I think there are challenges 9 and I think if we could get investigators 10 willing to address some of those areas, I 11 think that, you know, they'll be people 12 willing to invest in those things, but I 13 think -- 14 DR. ABRAMSOM: That's great 15 because we'll be proposing something along 16 that line that may help this discussion. 17 All right. Is the need for 18 pediatric medical devices concentrated in 19 certain medical specialties or pediatric 20 subspecialties? Does anybody want to 21 comment on this? 22 I think we've talked a lot about BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 133 1 it. I don't think there's any subspecialty 2 that doesn't have some wish list, but 3 cardiology, pulmonary -- you know, there are 4 some that are much more than others -- 5 neonatology; great example. 6 Anybody want to comment on it? 7 Yes? 8 DR. RAIS-BAHRAMI: Before we go 9 into that, can I bring up something about 10 regulation and I will speak up. 11 Speaking of post-market evaluation 12 and post-market studies, we've been 13 challenging this for years now to see how 14 can use -- data from off-label use of a 15 device for a product -- to be effectively 16 used for getting that product approved? 17 For example, when you brought up 18 the need for 컴컴 life support, we have -- 19 in neonates alone, there are over 20 years 20 of experience, over the years 컴컴 15,000 21 newborns' data collection and their 22 registered data and still we are faced with BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 134 1 a good mix that have not changed 2 over 20-plus years and 컴컴 for certainly 3 컴컴 that they're still using it on labels. 4 For example, the membrane is 5 labeled for -- to be used for 48 hours and 6 currently, am I going to go to the intensive 7 care unit and change that membrane on 8 occasion or is it 컴컴 well every 48 hours? 9 Of course, not. Am I liable for not doing 10 that? Of course, I am, but we have data 11 showing that this membrane has been 12 functional and working and nearly 13 over 10,000 newborns for over 20-plus years. 14 Why can't that data be used to relabel this 15 product or we look at it and be extrapolated 16 as a post-market evaluation, post-market 17 컴컴, without putting it to trial again? 18 MS. LESS: Actually, that exact 19 issue came up a few years ago when a company 20 took some data from 컴컴 that had been 21 gathered off label and bundled it up and 22 submitted it in a 510(k) and it became a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 135 1 huge issue for the agency because informed 2 consent wasn't obtained, 컴컴 approval 3 wasn't obtained because it wasn't done as a 4 study. It was done as off-label use, but 5 then when all the data was gathered up and 6 you came into the agency, we felt like we 7 needed to go out and do some inspections to 8 verify the data, look at patient records. 9 Without informed consent and IRB 10 approval, we didn't really have access to 11 that and then there was sort of the dilemma 12 that the agency was having by saying if we 13 take the data and we clear the 510(k), we're 14 doing it, recognizing that the data wasn't 15 gathered under our regulations and so it 16 makes it hard for us because, according to 17 our statute, under 520(g), you do have to 18 get IRB approval and informed consent to do 19 a study. 20 We're supposed to base our 21 marketing applications in accordance with 22 those regs and we we've gotten into the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 136 1 debate internally between should we take the 2 data, are we going to be liable, and we have 3 had cases where we have let devices go to 4 market where our regulations have not been 5 followed and then we've been sued by 6 competitors saying you let them use the 7 device off-label. We had to do it under 8 your regulation so how could you let their 9 device go out when we're trying to do it the 10 right way? 11 So we got stuck in that situation 12 and ultimately we decided to clear 13 the 510(k). We decided it was the best 14 thing to do and we put a letter -- a note 15 in -- I think to the manufacturer saying, 16 you know, in the future, you should follow 17 our regulations, but we did accept the data, 18 but it comes down to that tension between do 19 you accept it, knowing that it wasn't done 20 as a study, but not wanting to ignore the 21 data. 22 DR. RAIS-BAHRAMI: If you're BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 137 1 talking about the population that is less 2 than 2,000 a year, and if anyone wants to 3 collect that data, it's going to take 4 another 20 years to collect it for what we 5 already have in the data. 6 MS. LESS: Right. It's the same 7 in the IVD world, too. 8 MR. O'HOLLA: I think Joanne 9 raises a good question and your example 10 raises a good question and that's another 11 barrier, which is probably a statutory 12 barrier, but that is is there a way to 13 provide FDA some assurance that the data 14 that they're going to base the decision on 15 is valid and good data without having to 16 have all the things you would have in a 17 normal trial, and I'm way out of the box, 18 Bram, so don't worry about it, but I'm way 19 out of the box. 20 (Laughter) 21 MR. O'HOLLA: It's really a matter 22 of public policy as opposed -- right now, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 138 1 FDA's hands basically are tied in that area. 2 The question is did the policymakers leave 3 their hands tied in that area or should they 4 loosen them up so that data that's gathered 5 in the scientific community can be used and 6 they can rely on that data. 7 So that's I think a good question 8 for us to explore as a barrier and how do we 9 overcome that. 10 DR. ABRAMSON: Other questions? 11 DR. CAMPBELL: Well -- 12 DR. ABRAMSOM: Oh; I'm sorry. Go 13 ahead. 14 DR. CAMPBELL: I think the big 15 hold here is we don't know where we're at on 16 controls, treatment. I think NIH or FDA 17 needs to survey all the pertinent clinical 18 societies and Peds Ortho would be the 19 Pediatric Orthopedic Society, the Scoliosis 20 Research Society, and let the boards poll 21 their members and get a feel for what is the 22 off-label standard of care. Is there a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 139 1 standard of care? There are multiple 2 things, and just get a feel for what's going 3 on in the real world out there. 4 I know we're talking about in-base 5 interventional cardiology, but in surgery, 6 everything's very interventional. Getting 7 surgical controls in children is a 8 nightmare, you know. Ethically, the 9 population -- especially rare diseases -- is 10 so diverse and heterogeneous that it may 11 take 50 years to get an adequate control 12 population if you really fragmented the 13 various criteria. 14 So there has to be a fine line of 15 balance between, you know, scientific 16 regulatory concerns and, you know, the guys 17 out there making decisions and trying to 18 take care of kids. 19 MR. O'HOLLA: I think Dr. Campbell 20 raises a good point because I was going to 21 tell Bram that he and I were going to agree 22 to disagree for a while on the issue of BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 140 1 control. If you look at the agency's 2 definitions of valid scientific evidence in 3 their own regulations, it doesn't 4 necessarily require a control trial. 5 However, if I put myself in Bram's 6 seat and I'm going to make a decision to let 7 a device go on the market, I'm going to be 8 much more comfortable with that if I have a 9 control. So the question I have is given 10 the breadth of FDA's definition of valid 11 scientific evidence -- and I'm sorry. I 12 should have thought to bring that table; we 13 should look at that definition -- is there a 14 way that the things you just mentioned can 15 give the regulators the other hook they need 16 so that their neck isn't way out in making 17 those decisions and that it is both the 18 practitioners, the company, and FDA who have 19 banded together to provide the kinds of 20 hooks necessary to get that approval because 21 it is a pretty broad definition. 22 It includes even, for example, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 141 1 series of case histories, case studies, so 2 it's not always a well-control trial. 3 That's the goal standard, but there may be 4 other avenues for these kinds of products to 5 get there. 6 MS. LESS: Let me just clarify 7 that though. The definition of valid 8 scientific evidence is a hierarchy and at 9 the top is a well-controlled trial, then 10 it's partially controlled. 11 MR. O'HOLLA: Right. 12 MS. LESS: But well controlled 13 doesn't necessarily mean randomized control. 14 MR. O'HOLLA: That's right. 15 MS. LESS: Well controlled just 16 means you would have objective criteria and 17 you're following patients and monitoring 18 them. 19 MR. O'HOLLA: That's a good point. 20 MS. LESS: There's a tendency 21 within FDA to say well, well controlled 22 means randomized; that you have to have that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 142 1 randomized 컴컴 trial and we try to make 2 sure that our staff recognizes that they're 3 not necessarily just saying and like you 4 said, it goes all the way down to case 5 histories and reports. 6 DR. ABRAMSOM: Kathy? 7 DR. JENKINS: I was just going to 8 respond to, you know, the issue that you 9 raised before about using registered-typed 10 data, retrospective data, and looking for 11 some verification. There is a customary way 12 to get IRB approvals and waivers of consent, 13 but retrospective studies -- 14 MS. LESS: You can't waive consent 15 under FDA regs. Under NIH, you can waive 16 informed consent, but under our statute, the 17 only time informed consent can be waived is 18 if it's a life- threatening situation and 19 that's sort of the tension we have right now 20 with the in vitro community is that they are 21 using a lot of samples from databanks where 22 informed consent wasn't obtained and if it BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 143 1 is linked back to the patient, the agency's 2 getting nervous that consent wasn't 3 obtained. 4 I'm saying that when the IRB 5 waives consent. I mean, the whole 6 retrospect and chart review idea where 7 consent is rarely obtained is a waiver of 8 consent under Federal regulations. So I'd 9 be surprised that you all couldn't follow 10 those Federal IRB regulations. 11 DR. JENKINS: NIH has that 12 provision. FDA doesn't. It's something our 13 two 컴컴. 14 DR. ABRAMSON: That's potentially 15 something again that's -- 16 DR. JENKINS: It's something that 17 should be addressed, yes. That's a problem. 18 MS. LESS: Right. 19 DR. JENKINS: That's a huge 20 problem, if it's true. 21 MS. LESS: Yes. 22 DR. JENKINS: They know. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 144 1 MS. LESS: We know. 2 (Laughter) 3 DR. JENKINS: But you said they 4 didn't have IRB approval. 5 MS. LESS: They didn't, because it 6 was just off-label use. 7 DR. JENKINS: But they could have 8 gotten IRB approval for their retrospective 9 study though and made your problem smaller. 10 (Laughter) 11 SPEAKER: Gotten rid of one of the 12 issues. 13 DR. JENKINS: Yes. 14 MR. GREINWALD: I apologize for 15 being late. My name is John Greinwald, by 16 the way. I'm a pediatric otologist at 17 Cincinnati's Children's Hospital. We have a 18 great interest in 컴컴 hearing in our center 19 컴컴 a number of manufacturers and research 20 protocols and one of the things that -- I 21 guess there are two things that kind of came 22 to mind was-- and it was touched on BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 145 1 earlier -- was about the longevity issue and 2 biocompatibility, and actually bio-tissue 3 engineering is a huge issue that I think is 4 now just maybe being touched by the NIH. 5 My colleagues who do 컴컴 6 reconstruction and I can understand the 7 comments made earlier about that indicate a 8 huge problem that needs to be addressed on 9 several levels. The NIH, I think, is the 10 critical one, but I think Dr. Campbell's 11 컴컴 and I think it's the responsibility, 12 too, of our individual societies, similar to 13 pediatric orthopedics, to 컴컴 as a 14 relatively small society and I think it 15 would be very easy for us that it should be 16 kind of a society by society initiative that 17 we want to foster pediatric device 18 development. 19 Now, in our academy, broad academy 20 of 컴컴, we've had a huge explosion in the 21 last ten years with technology device and 22 we've been very blessed to have many BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 146 1 advances in our field. In fact, 15 years 2 ago, when I started doing 컴컴 research, it 3 was hammer and chisel kind of stuff. So 4 we've been very -- and it's been very good 5 and the reason we've done that, I think, is 6 that from the academy level, so all 10, 15 7 thousand 컴컴 have partnered and 컴컴; 8 excuse me -- is one and many have been 9 partnered with them directly to perform 10 studies and we've had symposiums to figure 11 out what are the needs and what are the -- 12 and so that kind of gets down to grassroots 13 and that's really the only way to do that, 14 but the whole society sponsored. The whole 15 society made that happen, but that's how you 16 get some guy in Little Rock, Arkansas, who's 17 got a great idea, who's maybe just not going 18 to be able to do that kind of study or do 19 that kind of trial; nothing against 20 Arkansas, by the way. 21 So that I think is critical, and 22 certainly there are other barriers to that, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 147 1 but unless you can get the group of 2 specialists who wants to develop it to pool 3 their data, particularly in smaller kinds of 4 patients, I think you're going to have an 5 extremely challenging -- as opposed to 6 getting more common diseases, which we all 7 sometimes do take care of. 8 DR. ABRAMSON: I just want to make 9 the point that when we use drug, devices, 10 off-label, somebody is at risk. When it's 11 the physician using it off-label, which is 12 almost always the case -- the physician 13 who's at risk, the patient who's at risk, 14 and potentially the company -- if we don't 15 fix this problem, all we're going to do is 16 컴컴 someplace. If we fix the problem, then 17 either we'll share the risk better or we'll 18 get rid of the risk. 19 Bob? 20 MR. O'HOLLA: Dr. Abramson? 21 DR. ABRAMSOM: Yes? 22 MR. O'HOLLA: This BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 148 1 on-label/off-label issue is very important 2 and I think it's going to require us to 3 define something. The fact that a 4 particular product doesn't say it's 5 indicated for pediatrics doesn't mean it's 6 not. 7 MS. LESS: Right. 8 MR. O'HOLLA: We're going to have 9 to define which devices or categories of 10 devices need a definitive pediatric 11 indication and which -- for example, many 12 surgical tools; a scalpel, is used across a 13 wide range. We know -- that's kind of 14 intuitive. We don't need a pediatric 15 indication there, but where does that line 16 start to blur and where do we make that line 17 definitive because where we make that line 18 definitive will have obvious FDA 19 ramifications, but it's going to have 20 ramifications on the risks that individual 21 practitioners take on then and it will also 22 have ramifications in the reimbursement BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 149 1 areas, which we can do everything we want to 2 do to get the product through the approval 3 process, but if by putting that indication 4 on there or putting it on there 5 inappropriately or saying it needs it and 6 not having it, we may adversely affect the 7 ability to have payers pay for the 8 technologies that they've always paid for 9 because we suddenly said oh, we 컴컴 10 pediatric 컴컴. 11 So we have to be very careful to 12 define when do we want to say that, when is 13 it absolutely necessary. 14 DR. ABRAMSON: All right. Is 15 there a way to -- the next question is -- is 16 we're minutes away from lunch -- this is 17 great; this is a great discussion -- and 18 again, after lunch, we will try to take on 19 solutions, proposed solutions. 20 Is there a way to prioritize the 21 kind of device needed for the pediatric 22 populations, diagnostic, life-threatening BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 150 1 conditions, quality of life, et cetera? 2 In the drug world, we still have 3 to prioritize. Even though everything going 4 forward had to be studied if it could be 5 used for pediatrics. There were tons of 6 drugs back that hadn't been studied that we 7 had to prioritize and this -- I see us both 8 having prioritized going forward and going 9 back. So let's have some discussions about 10 prioritization. 11 MR. O'HOLLA: I'll start. One 12 example, I think, was brought up by several 13 down at this end of the table is to have the 14 societies take some ownership in identifying 15 those areas because it's certainly something 16 that -- I've been involved in several of 17 these debates regarding pediatric devices. 18 To have that clarified with a list from the 19 societies would be a tremendous asset, not 20 only, I think, to the policymakers, but 21 certainly industry would welcome those kinds 22 of lists. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 151 1 DR. ABRAMSOM: Just to be clear: 2 That's what happened with drugs. The 3 Pediatric Infectious Disease Society was 4 asked to prioritize antibiotics. The 5 Pediatric Neurologists were asked to 6 prioritize 컴컴. So that is a potential -- 7 a root way of getting some prioritization. 8 Others? 9 MR. MUELENAER: Well, that's what 10 I would see from, you know, having practiced 11 as a general pediatrician, a pulmonologist, 12 critical care. Within our subspecialties, 13 most of us have subspecialty societies or 14 subsections of larger societies. You know, 15 in our case, the American Thoracic Society 16 has a pediatric subsection. The American 17 College of Chest Physicians; the same thing. 18 So certainly that's where I would 19 look for the needs assessment, you know. 20 What do we mean as practicing clinicians? 21 Where are our frustrations that we just deal 22 with every day and just again, because most BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 152 1 practicing physicians are not entrepreneurs 2 or inventors. We're just, you know -- we 3 take the technology that's handed to us and 4 do the best we can do, and wish there was a 5 better solution sometimes. 6 We just don't have the time and 7 the wherewithal to move on and get something 8 done. 9 DR. ABRAMSOM: Yes? 10 DR. ROBERTS: The one caution I 11 would make about individual societies, 12 making a list of priorities is the 13 difficulty we had was how does one make an 14 overall framework-size list because to the 15 pulmonologist, there are some things in the 16 pulmonology area that are 컴컴 and that was 17 one of the difficulties we had is we had all 18 these sort of 컴컴 of priorities, but how 19 does one do an overall prioritization? 20 MR. MUELENAER: Well, when you 21 talk to -- and I've talked to large groups 22 of physicians from diverse backgrounds in my BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 153 1 function with my institute, and there are 2 common things that -- common themes -- that 3 come up when you start polling large groups. 4 It may not be I need a device, but for 5 patient care, you know, I asked a 6 cardiovascular surgeon, you know, what do 7 you need and I thought they'd say valves or 8 stents and things like that and he said you 9 know, I really need a better way of managing 10 diabetics postoperatively; to manage their 11 blood sugars real time. 12 You know, you talk to medical 13 folks, surgical folks. The number one need 14 that's been voiced to me is an objective 15 measure of pain. 16 So there are things that cover all 17 the disciplines that when you start asking 18 the question, it depends on how -- if you 19 ask for devices, you're going to get 20 devices, but if you ask for patient care, 21 you may get a different answer and it will 22 cover other specialties and there's a lot. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 154 1 MR. CONNAUGHTON: Does it involve 2 relevant -- specialty- by-specialty 컴컴 3 various companies work with various 4 specialties knowing the 컴컴 any one 5 specialty 컴컴. 6 MR. GREINWALD: But it depends on 7 what you do with the prioritized list. I 8 mean, you don't -- you wouldn't go to 9 society and say give us your prioritized 10 list, and just to give you an example of the 11 two -- the common disorders. You take 12 deafness, which is what I do. I think 13 deafness is very important obviously, and 14 from a quality of life standpoint, restoring 15 somebody's hearing and all of the benefits 16 of that, versus my colleagues who do airway 17 reconstruction. 18 Clearly those children are going 19 to die if they don't get their intervention, 20 so it's a mortality 컴컴. So I think that 21 the initial thrust should be not as a 22 prioritization -- that's probably a bad word BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 155 1 maybe -- it should just be an identification 2 of one of the needs, then marry that up with 3 the industry and regulatory partners to find 4 out what's the low- hanging fruit? What can 5 we attack and bring to market and help the 6 greatest number of patients right off? 7 The prioritization is almost from 8 what can we attack first. Whatever's second 9 or third is how it would get prioritized, 10 which I think you have a hard time giving 11 the definition of what's important. 12 DR. ABRAMSOM: Yes? 13 MS. JACOBSON: Yes. I just wanted 14 to echo that. Not only is what you say 15 exactly right, but also you have different 16 sectors of the industry that will be working 17 on different products and you don't really 18 have to do a lot of 컴컴. 19 I agree; that'd be very difficult 20 to do. 21 DR. ABRAMSOM: Bram, you wanted to 22 say something? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 156 1 DR. ZUCKERMAN: No. I agree 2 exactly with Liz. The FDA is organized 3 along medical product lines so we can do 4 things in parallel, 컴컴 and cardiovascular 5 at the same time. There's an 컴컴 and so 6 forth. 7 DR. ABRAMSOM: Anybody else want 8 to talk? Yes, Kathy? 9 DR. JENKINS: I was just thinking 10 you would have to be pretty clear as you 11 went though to clarify what the question 12 was. Is the question unmet device need? Is 13 it unapproved for use in pediatrics? Is it 14 not sufficiently tested because I think the 15 various societies would answer differently, 16 depending on exactly how you posed the 17 question. 18 I suspect most of your examples 19 were regarding new technology that we don't 20 have right now. 21 MR. GREINWALD: Well, yes. It 22 could be, but the comment was made earlier BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 157 1 that is it really -- let's get down to 2 what's the patient problem and build up from 3 there. 4 DR. JENKINS: Uhm-hm. 5 MR. GREINWALD: That patient 6 problem might have all four of those. So I 7 don't think you should limit it to one new 8 device or modification or diagnostics or 9 drugs. I think it's better if you would -- 10 what's the patient problem and then identify 11 what one or all four of those need to be 12 fixed and maybe that's a better way to look 13 at it. 14 DR. ABRAMSOM: That is the 15 difference between drugs, where it was 16 regulated that new drug development would be 17 studied in children. So we have a whole 18 separate problem here than the drug part 19 that the FDA dealt with. 20 Yes? 21 DR. HAFFNER: You know, one of the 22 things -- and I may be na땦e in this because BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 158 1 I don't deal with kids so much -- but one of 2 the things that's been bothering me about 3 this discussion is that in addition to the 4 device itself, Jon, in your presentation, 5 you talked about materials and about 6 absorption and about movement and obviously 7 about growth, and those are cross- cutting 8 that have not to do necessarily with 9 specific specialties, but have to do with 10 the length of time that the product will be 11 used and so that needs to fit into this 12 equation as well. 13 DR. ABRAMSOM: Absolutely. Yes? 14 DR. CAMPBELL: I think about 15 devices if you're going to poll the guys 16 that use it, but the short-term problems, 17 long-term problems, advantages, 18 disadvantages, don't just ask what do you 19 use, but let us criticize what we're trying 20 to use. Let us tell you what the problems 21 are. We'd be glad to tell you. 22 (Laughter) BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 159 1 DR. ABRAMSOM: But just to be 2 clear, in the end, somebody's got to take 3 this whole list of devices and given a 4 certain amount of money that will be used to 5 study -- wherever 컴컴 source the money -- 6 we are going to have to prioritize, either 7 by numbers or devices that are out there for 8 a particular device; life-saving, not 9 life-saving. I mean, those are the things 10 that you end up having to look at and we 11 need to think about that carefully. 12 I think drugs did pretty good, the 13 prioritizing. I wouldn't say I agree with 14 everything, but they incorporated all those 15 things when they went back and said of all 16 these drugs, which ones were we going to 17 study or not, and they went through 18 subspecialty groups, but then somebody 19 over-optioned and I'm not still clear how 20 much the FDA did this alone versus the FDA 21 and the NIH and maybe Bram or somebody from 22 the FDA can tell us that. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 160 1 How did you in the end come up 2 with a prioritization list after all this 3 feedback? 4 (Laughter) 5 DR. JENKINS: I don't know. 6 DR. ZUCKERMAN: I guess 7 Dr. Lumpkin, when he returns, can answer 8 that. 9 DR. ROBERTS: Well, now, with 10 FDAMA, we were mandated to develop and 11 prioritize a list of products that were 12 approved in adults that 컴컴 with children. 13 So these were basically products that were 14 on the market and these are the 80 percent 15 that had no information on use in pediatrics 16 and if you'll recall that initial list 17 was 400-plus and the reason it was 400-plus 18 is because that's how difficult it was to 19 try to prioritize so we ended up having a 20 large list and then just saying all of these 21 are on the priority list and then we asked 22 industry to step to the plate and send in a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 161 1 proposal to study this and so if they were 2 on the list or if they wanted to be on the 3 list -- they could also petition us to get 4 on the list -- and indicate the basis as to 5 why they should be on the list. 6 So that's why we had such a long 7 list. 8 DR. ABRAMSOM: Well, I actually 9 work with the NIH and we sat with them and 10 gone through sets of drugs and they're 11 asking 10 of us, on conference calls, and 2 12 of us who reviewed these drugs, to say yes 13 or no, and so there are other things in 14 place to try to get -- I realize that's a 15 long list, but not all 400 are being studied 16 at once. 17 DR. ROBERTS: We're talking about 18 the 컴컴 process -- 19 DR. ABRAMSOM: Yes. 20 DR. ROBERTS: -- which is the 21 process that is currently where the list has 22 to be updated every year by NIH. I was BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 162 1 talking about the original list back 2 in '97, '98. 3 DR. ABRAMSOM: Gotcha. 4 DR. JENKINS: Yes. I just wanted 5 to build on what Rosemary was saying. 컴컴 6 Pharmaceutical Act did mandate that the NIH, 7 with FDA, work-up a priority list and we 8 have a fairly extensive description of how 9 we attempted to, you know, hone down that 10 original list down to the ones that needed 11 immediate prioritization and it brought in a 12 lot of the things you all had mentioned 13 about what's the low-hanging fruit, what's 14 something we can do right away, what just 15 needs little tweaks, but what might be a 16 very long-term, but very important product; 17 that kind of thing. 18 So there is -- I'd be happy to 19 share it with everyone -- there is a 20 description of that process. It actually 21 took us a long time and working, you know, 22 between the two agencies to come up with BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 163 1 that. I do think -- I mean, I totally agree 2 with what you were saying before about, you 3 know, marrying the specific industry with 4 the specific needs, but I am concerned that 5 if there isn't an overarching sort of 6 weaning out of all this, it just may not 7 happen. 8 I mean, we got input from 9 industry. We sent out letters to literally 10 hundreds of non-profit groups to ask for 11 input, but it took all of that and it took 12 kind of one cooperatively central place to 13 put that together and there have been three 14 lists published in the Federal Register so 15 far. 16 DR. ABRAMSOM: Anybody else want 17 to add to this conversation? 18 MS. SHRADER: I guess one question 19 I'd like to add is, you know, in the device 20 industry, we always stress the big 21 differences between devices and drugs and 22 certainly a process like you followed with BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 164 1 drugs where you go looking at products that 2 were already on the market, but lacking 3 pediatric application where in-patients were 4 used, might be helpful as a starting point, 5 but the fact that the device is out there 6 for use in adults doesn't necessarily mean 7 that the process of getting a device for use 8 in children will be simpler or will be just 9 confined to doing studies, you know, and I 10 think a number of people made very good 11 points that not only might we have to go 12 back and reengineer a product, but, in fact, 13 it might not be feasible to go back and 14 reengineer some products to make them 15 appropriate for use in kids. 16 So just sort of an addition to 17 your comment, we do need to keep in mind 18 some of the unique aspects of medical 19 devices. 20 DR. ABRAMSOM: Good. Any other 21 comments? All right. The final question 22 for this morning, before we take our lunch BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 165 1 break, is how does the lack of availability 2 in 컴컴 devices impact the health of 3 children and what are the potential negative 4 outcomes associated with using a device not 5 designed for children, altruistic children, 6 lack of insurance coverage, liability 7 considerations, et cetera? 8 Now, Dr. Campbell, you started out 9 with some of the liability issues, so I'll 10 let you have at it. 11 DR. CAMPBELL: All right. I 12 think, you know, availability cost, 13 especially in children, a lot of kids are on 14 small programs for state or Medicaid. 15 There's a limited piece of the pie. So we 16 don't have a whole lot of availability and 17 maybe you need something that's very 18 expensive, but it's just not possible with 19 this arrangement. 20 I think -- see, you go to an 21 alternative and then we get back to 22 jerry-rigging and improvising, which -- it's BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 166 1 very scary. None of this was ever 2 published. You really don't find out what's 3 going on and the pediatric orthopedist, we 4 do a lot of that. The Pediatric General 5 Surgeons did just as much. I don't know if 6 the Pediatric Neurosurgeons do this, but I 7 think you just really have to work toward 8 approved, recognized usage indication and 9 컴컴 devices because, you know, the 10 undercurrent just might disappear, like I 11 said, because of, in the liability 12 situation, it may get worse before it gets 13 better. 14 So we don't know what we're doing 15 right now in terms of all this alternative 16 therapy we're forced to do because the 17 devices aren't approved. 18 DR. ABRAMSOM: Does the FDA want 19 to talk about efforts they're trying to make 20 to get some denominated and numerated data 21 that would help us in dealing with this 22 issue? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 167 1 DR. ZUCKERMAN: Well -- 2 MS. LESS: Oh. Were you going to 3 go first? 4 DR. ZUCKERMAN: I will very gladly 5 let you go first. 6 (Laughter) 7 MS. LESS: Let me just say 8 currently our databases don't capture a lot 9 of information on pediatrics and, in fact, 10 we didn't have any pediatric flag in our 11 database until the medical device user fee 12 went into effect and then because pediatric 13 devices are exempt from user fees, we had to 14 add a flag so that when a device is 15 submitted for pediatric indication, the 16 company doesn't have to pay for the review 17 of that. 18 So we do have that flag, but we're 19 in the process of going through -- I think 20 it's a four- or five-year revamping program 21 of our databases to try to capture links 22 between the IDE and the PMA process, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 168 1 pediatric things, other types of flags that 2 currently the way all this information is 3 captured is when it goes through the review 4 process, the reviewer is responsible for 5 checking a flag that it's a pediatric 6 indication, it's a combination product, it's 7 a 컴컴 device or drugs. So if they flag it, 8 it's in the database. If they don't flag 9 it, it's not there. 10 So the data right now that we have 11 is pretty poor, but we are trying to redo 12 those databases to try to capture more of 13 this information and it would give us a much 14 better denominator as well as, you know, we 15 could link it then to our adverse event 16 database so that we would have the 17 denominator and a new order, but it's going 18 to be a few years before we have that 19 available. 20 Bram? 21 DR. ZUCKERMAN: The problems 22 expressed with off-label use are certainly BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 169 1 not unique to the pediatric field. It's a 2 tremendous problem in adult cardiology. 3 Certainly the industry has taken some steps 4 and the American College of Cardiology 5 certainly is, I think, pushing folks to move 6 forward in the post- market arena for a 7 better collection of data. 8 Some practical steps that have 9 been taken are, one, to really try to become 10 serious about the need for more post- 11 approval data. During the actual review 12 process of the PMA for, say, a drug 컴컴 13 stent, we're now starting the post- approval 14 study so that we can get some momentum 15 going. We're including long-term follow-up 16 of the original IDE cohort in this 17 post-approval study. 18 I think though the bottom line is 19 that without some frankly professional 20 responsibility taken by pediatricians or 21 adult cardiologists in recognition of this 22 problem, it's very hard to move forward. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 170 1 Bob, your company has really set a 2 bar though for moving forward. How would 3 you respond to that? 4 MR. O'HOLLA: Well, you know, I 5 think your point is well taken about getting 6 the cooperation of the practitioner in that 7 post-market follow-up because I think what 8 tends to happen is the new technology gets 9 out there and everybody's really interested 10 in following it for six months and after six 11 months, it's a big yawn. Everybody's 12 looking for the next technology and it 13 becomes very difficult for us to satisfy 14 FDA's requirements on post-market when we 15 can't the cooperation of the practitioners. 16 That is the one missing link and 17 if you were going to deliver a message 18 through your societies, that would be the 19 one message that would be helpful, not only 20 for new technology, but as Joanne points 21 out, in getting that denominator data for 22 adverse events on medical devices. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 171 1 We often have a hard time finding 2 out what hospital it occurred in, let alone 3 whether the patient was a pediatric or an 4 adult or a geriatric patient. So those 5 kinds of attention to detail, from the 6 practitioners, will help make our databases 7 collectively so much more valuable to work 8 from and then maybe we'll be facing some of 9 the issues of, you know, what do I do 10 with 20 years worth of data? It's got to be 11 good for something kind of thing. 12 DR. ABRAMSOM: Others? Elaine? 13 MS. VINING: I'd just like to ask 14 at what point in time is there -- is it 15 appropriate to perhaps make an assumption 16 that since children and adults suffer from 17 many of the same indications, that the 18 device is likely to be needed for that 19 indication in children? 20 I mean, if we know the children 21 have a series of issues that a device is 22 being designed for an adult, we're using BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 172 1 sort of a dynamic of the drug here, but is 2 it reasonable to think about how that use 3 may be appropriate in children and what 4 kinds of devices they may need? 5 DR. ABRAMSOM: Let me try to add 6 question or rephrase the question a little 7 bit. The way the down loader works is that 8 it says that if a disease exist in children 9 and you're creating a drug, you have to 10 create the drug both for -- if you're 11 creating it for adults, you have to create 12 it for children. 13 Now, your point is some of those 14 things -- and I agree with you a hundred 15 percent -- some devices it just doesn't 16 matter where, with drugs, it does. You have 17 to always worry about the size, whether 18 you're creating a scalpel to make an 19 incision, it probably doesn't matter and we 20 know it's going to use, you know, a big 21 blade on a neonate. 22 So how do we figure out -- how do BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 173 1 we help the FDA decide whether we're going 2 to demand that it be also studied in 3 children? That's the question that I think 4 Elaine and 컴컴 had. 5 MR. O'HOLLA: Is that also the 6 question we want to ask at the first line of 7 the survey after prioritization? Is that 8 the first thing we want to know? I mean, 9 because we've heard a lot about -- some of 10 the things I heard this morning about some 11 of the needs -- our needs are in adult 12 populations, too. They're technology needs. 13 Certainly, that would be on a 14 long-term list for everybody, but I'm 15 struggling with the question you both put 16 out and that is, okay, I have a device and I 17 treat adults. How do I know I need this 18 device for pediatrics? 19 DR. ABRAMSOM: Or how do you know 20 that it needs to be studied in pediatrics? 21 MR. O'HOLLA: If I say yes, I need 22 it in pediatrics, that is do I need to study BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 174 1 or is there something -- the thing that 2 makes devices different is this engineering 3 analysis. 4 DR. ABRAMSOM: I mean there are a 5 set of questions one could ask. Is there a 6 growth and development issue with that 7 particular device? Is there a biochemistry 8 issue that -- at a trial that might make 9 that device work or not work? 10 I can see a set of questions that 11 won't get asked. I guess the group will 12 have to get together and think about so that 13 with the FDA, sort of the FDA will have a 14 set of questions before that it thinks about 15 that says this actually needs studies in 16 children or adult and we'll accept that 17 adult data as adequate. 18 DR. JENKINS: But your question 19 wasn't just about studying it in kids. It 20 was actually creating the technology for 21 kids; right, and if I'm understanding, you 22 have sort of an implicit mandate. Perhaps BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 175 1 there could be a mandate to companies to do 2 that under certain circumstances, but I 3 think though it sounds very simple. That's 4 very, very complicated because the device is 5 used for a specific indication, okay, which 6 usually disease specific. 7 So the question could be that it's 8 a disease that also occurs in children, but 9 it may be that it's a device that could be 10 used for a similar disease in children, but 11 I it's really not at all from a regular 12 employee perspective, the same study, for 13 the same device or the same use. Then if 14 you turn it around and you say well, what if 15 you just take the opposite, problem, which 16 is miniaturization. 17 You know, the technical issues, is 18 the biotechnical -- no; the bio engineering 19 issues of making something the size of a 20 neonate that you've managed to work out for 21 the size of a 70-kilo man, maybe you'd 22 really insurmountable. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 176 1 So to crack -- try to create 2 mandates around what sounds like a simple 3 question like that, I don't think would be 4 very easy at all. 5 MS. VINING: It's not a mandate so 6 much as it is can we have a presumption 7 where we have a need because I think what 8 we're talking about here is trying to 9 understand that there is a need and at some 10 point is there an ability have a presumption 11 that there would be a need in children. 12 MR. GREINWALD: You'd would almost 13 need like a very diverse working, but not, 14 too, but similar to this; working with both 15 the FDA and the NIH as these things come 16 through, speaking for adults, not specific 17 needs, could this have any particular use 18 and then somebody would have to -- and then 19 somebody would have to -- a group like this 20 would have to look and go up; this maybe has 21 potential, and then through that agency, 22 then recommendations re made and the RFU or, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 177 1 you know, what ever happens that we want to 2 stimulate that because I think what happens 3 a lot, and the RPF is written? 4 You know, whatever happens that we 5 want to stimulate that -- b k think what 6 happens was things go on and the other 7 people, you know, God love them, they don't 8 want to deal with this. 9 (Laughter) 10 DR. ABRAMSOM: That's the last 11 thing -- they're trying to get this thing to 12 market and do their trial. They don't want 13 to worry about oh, I have a pediatrician 14 now. They don't want to hear about that. 15 That's the last thing. They're trying to 16 get this thing to market and do their trial. 17 They don't want to worry about oh, I have to 18 talk to a pediatrician now. They don't want 19 to do that. So I think you're almost -- we 20 would have to take the bull by the horns and 21 try to foster that information as coming out 22 of the adult world that we don't maybe don't BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 178 1 believe and have access to. 2 I mean, I know, but from a 3 cardiology standpoint, I know you've 4 interacted with your adult cardiologist, 5 but, you know, maybe that information's a 6 little delayed. Maybe you're not getting -- 7 I don't know. I don't know what that 8 relationship is that you have with new 9 advances in the adult world. 10 MS. IRELAND: I was going to 11 suggest something very similar. I mean, 12 taking -- I think Elaine's idea was do you 13 want to have a similar presumption as we 14 have in the drug world so the drug world 15 devices coming out of the market, if the 16 컴컴 occurs in kids and adults, you have to 17 study, it's a mandate, it's very clear. 18 I think you're suggesting perhaps 19 it's a little more complicated here, but 20 maybe the direction to go is something like 21 that where, as a device is moving through 22 the approval process at the FDA, there's the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 179 1 FDA that had the ability maybe looking at 2 the information gathered about needs -- 3 that's identified needs -- to say looks like 4 this product, you know -- they each want to 5 identify the three for a cardiologist, 6 something to be said to pediatrics here. 7 They can then think of are there 8 some ways to talk to the manufacture about 9 the fastest cath ways. Neither the 10 manufacturer has the thought or they thought 11 they had to do 컴컴 than they actually have 12 to do. Maybe it's some clarity of the 13 process. 14 As the device is coming through 15 for adults -- your conversations going on 16 earlier in the process about what's a 17 pediatrics need, what's the fastest pathway 18 to getting pediatric approval, so when the 19 device comes on the market for kids, maybe 20 the change for pediatrics isn't too far 21 behind. 22 But it seems like earlier BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 180 1 conversations and that process might be -- 2 DR. ABRAMSOM: Well, remember for 3 the drugs, it was never the intention to 4 slow down the development of drugs for 5 adults. That was never the intention. What 6 was created was that we used to say here's 7 our plant to study it in children at the 8 time of it being approved for adults. 9 There are two levels to your 10 question. Does it need to be studied, which 11 is a question; that's fair enough, and if it 12 does need -- if the group agrees that though 13 the FDA agrees, it does need to be studied, 14 how will it be studied? 15 The idea is never to make an adult 16 not get something. 17 MS. IRELAND: The law is very 18 clear on that. 19 MR. O'HOLLA: I think the issue -- 20 that presumption at least raised a flag in 21 my mind of when -- if you were to adopt that 22 presumption -- when would you kick it in? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 181 1 When I have a hundred cases, pediatric cases 2 a year? When I have 50? When I have 2,000? 3 When would you kick in that presumption to 4 have a manufacturer do something because if 5 it's 50, you may be misspending value 6 research dollars. So I think it's going to 7 be more complicated for devices than it was 8 for drugs. 9 MR. CONNAUGHTON: I think Bob's 10 exactly right and when you used the word 11 mandated, it's very complex in this area. 12 MS. VINING: I don't I ever used 13 the word "Band-Aid." 14 MR. CONNAUGHTON: No, no, no. 15 MS. VINING: I don't want to ever 16 presume that that is what's on the table. 17 MR. CONNAUGHTON: But I think what 18 Jeannie was talking about, working with 19 companies and calling to their attention 20 this -- and see if there's a solution in 21 pediatrics use. 22 Another way to go is say okay, but BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 182 1 I've got to do this then. Spend it and make 2 sense. 3 MS. LESS: I think the other thing 4 that we have to think about though is that a 5 lot of times when a PMA comes in, if there's 6 more than one indication, that can slow the 7 process down if the data doesn't look good 8 for all those indications, and so what we've 9 told companies to do is focus on this one, 10 get it out there, and then we'll review the 11 other one as a supplement, and that would be 12 my concern when you do this; that the 13 pediatric indication could slow down the 14 adult approval. 15 DR. ABRAMSOM: All right. 16 It's 11:59. This afternoon at 1, if 17 everyone would come back, I will put on the 18 table one proposed mechanism for dealing 19 with all the issues, including those raised 20 by Susan about how does the clinician and 21 the industry talk to each other so that the 22 device is that automated, everybody knows BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 183 1 about it. 2 That is not the only proposed 3 solution though. There are many others and 4 we want to hear from you. 5 (Whereupon, at 11:59 a.m., a 6 luncheon recess was taken.) 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 184 1 A F T E R N O O N S E S S I O N 2 (1:00 p.m.) 3 DR. ABRAMSON: Elaine just quickly 4 typed out some of the barriers that we 5 talked about this morning, and what I'm 6 going to do is put in front of you a 7 potential framework that we might then think 8 about and discuss whether these would help 9 some of these barriers or not, and I'll tell 10 you that we actually thought about two ideas 11 and we went with one, and I'll explain the 12 reasons why. 13 I think all of you are aware that 14 there is a pediatric pharmaceutical network 15 and it's now -- it started out, I think, 16 seven academic centers; it's now at 17 thirteen -- and that network looks at drugs 18 and does some NIH studies with pediatric -- 19 you know, drugs were used in pediatric 20 population, does some industry studies, and 21 gives the NIH and industry the ability to 22 access children to get drugs studied that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 185 1 need to be studied. 2 I'm going to propose that as a 3 framework to discuss a lot of these 4 barriers, except obviously it wouldn't be a 5 drug network. It would be a device network. 6 So you would have -- well, let's just say we 7 start out with ten academic centers where 8 you could come and study devices and the NIH 9 would have support from NIH and industry, 10 industry could do studies there. NIH could 11 do studies there, et cetera. 12 I'll get more into those in a 13 minute, but just say that we did think about 14 something similar using sub-specialty 15 groups, but in knowing a lot about 16 sub-specialty groups, a lot of them function 17 in different ways. So there's COG, the 18 Cancer Oncology Group, where I think this 19 kind of thing could be done in a heartbeat. 20 They're always collecting data. They're 21 always having their children on protocol. 22 That would be ideal, but a lot of BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 186 1 the sub-specialty groups don't function that 2 way and it's not just the surgery sub- 3 specialty groups. Infectious disease 4 sub-specialty group doesn't function in that 5 kind of manner. 6 So what we will be proposing to 7 you is that you would actually have a place 8 where other pediatricians or family -- 9 whoever -- could come and send e-mails or 10 send ideas that say this is the device I 11 need or I'm thinking about. 12 This group would then pick 13 representatives from their ten academic 14 centers. This is what happens in 컴컴, and 15 they meet quarterly and they process those 16 ideas. 17 They'd also be meeting with 18 industry and saying these are the things 19 that we see out there as needs in 20 pediatrics. These are studies that need to 21 be done; some of them best belong sponsored 22 by NIH because they're really hypothesis BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 187 1 testing. Some of them are far enough along 2 that they really would best be sponsored by 3 industry. 4 This doesn't solve all problems, 5 but I want to bring this up as a potential 6 place to then start discussing barriers and 7 does this work or not work or do others have 8 other potential solutions that might work 9 better? But it does get to some of Susan's 10 questions to me or early on to the group 11 that says we got no place -- we don't have a 12 place -- where we interact with the 13 clinicians, in a not one-on-one way. 14 It also allows studies to occur 15 that if you have ten centers, you may 16 have -- Cochlear implants might be a good 17 example of this -- you might not have enough 18 Cochlear implants, even in Cincinnati to 19 really do safety and efficacy data, but ten 20 centers might, and though it won't take care 21 of the really rare diseases, it might take 22 care of the relatively rare diseases. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 188 1 So with that as the proposal in 2 front of you -- and please feel free to 3 suggest other proposals -- we can start to 4 discuss does this help or not and is this a 5 way forward that industry can support; that 6 the FDA can support, that the NIH would 7 think about supporting? 8 As I said, the NICHD often joins 9 with other groups; it might join with the 10 Bioengineering Institute. It might join 11 with the FDA in doing some of this work with 12 us. 13 So let me throw that out and open 14 it up for discussion. Yes? 15 MR. WICKS: Can we define what a 16 center -- what this academic center -- 17 really is? What's the specifications for 18 it? 19 DR. ABRAMSON: Well, no; I 20 haven't. 21 MR. WICKS: I said can we? 22 DR. ABRAMSON: Yes. When we close BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 189 1 out, you might want -- instead of -- all the 2 pharmaceutical units have people with 3 expertise in pharmacy. You might want an 4 academic center that had a bioengineering 5 school. So it had expertise in engineering, 6 in addition to it. That might be one of the 7 things that gets you high priority as you 8 apply to be one of these centers, but I 9 don't have any preconceived notion. 10 I am not suggesting that the 14 11 centers -- that in the pharmaceutical 12 centers -- all 14 of the centers, that this 13 be done by a peer review process. 14 DR. JENKINS: Is this for getting 15 new technology or is this for studying 16 existing technology? 17 DR. ABRAMSON: This would be both. 18 This would be just like in the drugs. The 19 NIH could say, you know what? This drug or 20 patent needs further study and because the 21 companies are patent, companies might or 22 might not support it. The NIH, as it is BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 190 1 right now, is prioritizing these and giving 2 money to support studies. 3 One that we just recently did in 4 pediatrics and infectious disease is suggest 5 컴컴 and DP shots. We use it a lot. We 6 have no clue to how well it works. 7 MR. ENGLANDER: Are you suggesting 8 academic centers -- 9 DR. ABRAMSON: Yes. 10 MR. ENGLANDER: -- because of 11 volume? 12 DR. ABRAMSON: Yes, and because 13 the 컴컴 where these devices mainly are have 14 the sub-specialists. 15 MR. ENGLANDER: If you're looking 16 at pediatric intensive care units -- 17 DR. ABRAMSON: Yes. 18 MR. ENGLANDER: -- they may not be 19 solely 컴컴 on to an academic center, which, 20 for many reasons, tends to bring costs up 21 because of just all these insularly issues. 22 MR. ABRAMSON: You're saying to me BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 191 1 that this is a children's hospital that's 2 not a part of an academic center, but is 3 affiliated or not affiliated, it would stand 4 a peer review; could it do it or could it 5 not do it, but there's certainly no -- no 6 one can stop anybody from applying to be 7 part of this, just like in other cases. 8 DR. HAFFNER: Would each of these 9 centers have clinical research centers; 10 children's CRC? I think that would be a 11 requisite. 12 DR. ABRAMSON: Yes. I mean, I 13 would imagine that would make it a high 14 priority in the assessment of whether it 15 gets funded as a center. 16 DR. HAFFNER: Right. 17 DR. MUELENAER: For the pediatric 18 funds and network, how is it 19 administratively structured? Who's in 20 charge of that? 21 DR. ABRAMSON: I don't know all 22 the details of it. We can bring somebody BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 192 1 forth. This is an idea that -- 2 MS. KAESER: Excuse me. 3 SPEAKER: Right here. 4 DR. ABRAMSON: Great; great. Go 5 ahead. 6 MS. KAESER: We run it; administer 7 it. I mean -- 8 DR. ABRAMSON: Can you speak up, 9 please? 10 MS. KAESER: We administer the 11 network and support the network. That's 12 been a key issue to their support work 13 funding. We do hold those quarterly 14 meetings. You know, we bring the 15 investigators together and they have a huge 16 amount of input, although I think our 17 director has the final say on which things 18 get tested ultimately, but we get input from 19 everybody about what the needs are and what, 20 you know, their experiences are. 21 Is that what you were getting at? 22 DR. MUELENAER: Yes; to understand BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 193 1 that would be -- how it's structured; if it 2 got 13 -- 3 MS. KAESER: It's pretty virtual, 4 in a sense. I mean, we do bring people in 5 face to face, but we have a -- NSAT runs 6 actually a large number of networks in 7 different areas and we may want to speak to 8 his own experience, but we do that for the 9 whole, the maternal fetal medicine network; 10 getting neonatal research networks, which 11 y'all may be familiar with. 12 Same sort of thing: We do bring 13 people together face to face, but most of it 14 is done with uniform data collection and, 15 you know, 컴컴. 16 DR. MUELENAER: I guess where I'd 17 see this a little difference for 18 pharmaceuticals is -- you know, we're 19 talking about medical devices and not only 20 are we talking about clinical trials, but 21 the development of devices, needs 22 assessments, engineers, and other life BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 194 1 sciences people. We can follow 컴컴. I 2 have a sense it will be a lot more complex 3 than the pharmaceutical -- 4 DR. ABRAMSON: Well, again, just 5 to be clear, that may make it a 컴컴. If 6 you are an academic medical center with a 7 bioengineering school, that might give you 8 very high priority as you're peer reviewed 9 to be part of this process. 10 Yes? 11 MR. O'HOLLA: I'm unclear what 12 role this would play. Is this to circumvent 13 the normal commercial process of getting 14 ideas into manufacturers and manufacturers 15 develop new products? Is this to set a 16 research agenda for pediatrics for the 17 United States that then companies can either 18 opt into or opt out of? 19 The reason I ask the question is 20 this morning I heard from many of the folks 21 down at this end of the table that the 22 societies haven't been very good at BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 195 1 identifying the needs and I guess this 2 proposal seems to be a good proposal, if we 3 had good identified needs and people weren't 4 responding. It seems that we haven't even 5 taken the first step, but I'm wondering if 6 we had good identified needs from the 7 societies, if then maybe we wouldn't need a 8 bigger infrastructure to get things moving. 9 DR. ABRAMSON: As we toyed 10 around -- and this was also mentioned -- if 11 you talk about individual subspecialties, 12 you then talk about subspecialties in those 13 subspecialties, and as the physician from 14 Cincinnati mentioned, a new Cochlear implant 15 may be his highest priority. Somebody 16 else's in the 컴컴 may be stents. This 17 doesn't stop anybody from coming to -- 18 there's no prohibition from anybody coming 19 directly to a company, putting in a proposal 20 directly to the NIH. None of that is 21 stopped. 22 This is a central place where good BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 196 1 ideas can come and projects or studies could 2 be done if appropriate. If a company thinks 3 it's appropriate or the NIH thinks it's 4 appropriate. 5 Susan? 6 DR. ALPERT: I want to raise an 7 issue that I think we need to discuss and 8 that is that one of the things that was 9 brought up this morning is the ability to 10 get clinical trials done in pediatrics, and 11 having -- so what I'm thinking is there 12 aren't, to my knowledge, places that would 13 be readily identified by people in the 14 industry as places where you would go to 15 take your medical device to be studied, and 16 I think one of the questions that comes up 17 is are these places that have -- I mean, 18 current research in pediatrics doesn't have 19 a lot of focus on medical devices. 20 So are the centers that would be 21 coming forward going to have to develop a 22 whole new set of expertise, and maybe we're BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 197 1 a little ahead of -- maybe this is a little 2 ahead of where it needs to be, in terms of 3 trying to figure out how do you develop the 4 expertise to do medical device trials 5 because they are different, and as Jon 6 already said, the input to development, the 7 support that's needed to try to both develop 8 and move the devices along in that 9 environment, and I'm just wondering if there 10 are places or if it's really, you know, 11 academic institutions or it may be different 12 departments within pediatrics and different 13 places that actually would bring the 14 expertise to the table. 15 DR. ABRAMSON: Let me try that 16 because having reviewed one of the cycles or 17 these pharmaceutical ones, you are not 18 looking -- University of Colorado -- you're 19 not looking for them to have expertise in 20 pharmacy in every single area, but they 21 might bring asthmatics to the group. They 22 might bring neonates to the group; you know, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 198 1 neonatology. They might bring a series of 2 patients where they have particular 3 expertise. Another one, Boston Children's, 4 might be cardiac. 5 So it's building this ten centers 6 and, again, I'm not saying it should be ten 7 centers. It's building this whole group 8 together that allows you to put everything 9 together and have the needed expertise and 10 you still may not have all the needed 11 expertise, but it still may be the next 12 major step forward in trying to create 13 something where a lot of this will be done. 14 Kathy? 15 DR. JENKINS: Did I look like I 16 wanted to say something? 17 DR. ABRAMSON: Oh; I thought you 18 were raising your hand. 19 DR. JENKINS: No; I was actually. 20 I mean, I just think -- you read my mind. I 21 mean, I see a lot of difference issues here 22 and I think what the specific purpose of BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 199 1 this would be designed to do would be very, 2 very important. I'm not sure that -- if 3 it's at the device design level, that it 4 would necessarily be the same groups, except 5 for maybe the identification of a need of a 6 device design that would necessarily be the 7 best infrastructure to run out a clinical 8 trial in a reasonable period of time. 9 So I was saying to someone just 10 while we were having lunch that there's a 11 little model now because everyone's 12 recognized that there's a real lack of 13 pediatric clinical trial research 14 infrastructure in the country. So the NHLBI 15 just funded a seven-center pediatric heart 16 network to do studies and they have been 17 done -- they have really struggled to find 18 studies that they could do at seven centers 19 in two years, you know, and that's partially 20 because the way you got to be a center was 21 by going through a competitive process and 22 it wasn't that you would necessarily be able BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 200 1 to supply enough patients. 2 So I would be worried that if you 3 were doing an ortho trial, you're going to 4 need some of the largest orthocenters to run 5 another study in a reasonable period of 6 time, and it may not look the same as a 7 neuro search trial or a cardiology trial or 8 drug trials. 9 So if you're talking about common 10 pediatric conditions, that's one thing. If 11 you're talking about some of the things 12 we've been talking about here, which are 13 niche devices for rarer problems, you don't 14 go after these centers based on the numbers 15 of patients 컴컴. You'll end up with a lot 16 of failed studies or studies that just take 17 too long. 18 So I don't know how to balance all 19 that because I do think a need for an 20 infrastructure, you could just go into the 21 infrastructure and it's there already, would 22 be ideal. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 201 1 DR. ABRAMSON: Okay. 2 DR. CAMPBELL: At NORD, the 3 medical advisory committee reviews grants 4 and rare diseases and it always amazes me 5 that the expertise often is not at the large 6 academic centers. The patients go to the 7 person who has taken on the disease as a 8 life goal and these investigators are 9 oftentimes are very small places. 10 So I get concerned about forming, 11 you know, probably large academic centers. 12 A lot of the rare diseases would be left out 13 of the network because the people won't be 14 there to attract the patients. The centers 15 are probably not going to build 컴컴 16 department 컴컴 license storage disease to 17 get expertise in those. 18 DR. HAFFNER: You know, you have 19 the experience from NORD, but the Office of 20 Rare Diseases at NIH recently let, I think, 21 eight 컴컴 centers of excellence and 컴컴 22 triggered my thoughts because that's BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 202 1 where -- you know, one of them is the urea 2 cycle disorders and these are all pretty 3 rare situations and they all went to very 4 academic centers who had the capability, not 5 for the development, because I think you're 6 right; I think it's individuals who get the 7 idea to do development. That's not 8 necessarily something that goes on in a 9 CRCT-type setup, but in an engineering 10 setup. 11 But then the actual carrying out 12 of a significantly powered clinical trial 13 will go on under the auspices of the center. 14 That may be a multi-centered center. 15 MR. GROSSMAN: In fact, I'm pretty 16 sure 컴컴 in terms of the application 17 process. I remember when I worked at five 18 centers, the lead center -- I remember the 19 five 컴컴 proposal 컴컴. That's the way the 20 small 컴컴. 21 DR. ABRAMSON: So what I'm hearing 22 is that somehow or another, we'd have to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 203 1 create a whole another mechanism. We'll 2 have to create the flexibility to deal with 3 these rare diseases so catheters probably 4 can be easily done in this group. I can't 5 imagine ten centers that don't have enough 6 컴컴 shunts, but some of these rare 7 diseases, we may have to think about 8 flexibility, to either allow studies outside 9 the network agree the investigator or 10 investigators that created the device into 11 the centers where there are patients or to 12 have the ability to create a quasi-center at 13 that place. 컴컴 them out. 14 I mean, if I thought we could sell 15 a lot of drugs and devices at the same time, 16 which I did at one time, we wouldn't be here 17 today. 18 DR. JENKINS: That central group 19 could offer a lot of advantages. They could 20 be the repository for the high-level 21 political trials, design experience. They 22 could do the central data coordination BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 204 1 collection, and they could also, you know, 2 be the body that's really used to dealing 3 with the FDA, the regulatory process, or the 4 컴컴 and the funding processes or whatever, 5 you know. 6 So there could be a lot of kind of 7 centralization of expertise, but I would 8 just be nervous about having the sites all 9 be pre-named and not being the right ones to 10 run out anyone's studies. 11 DR. ABRAMSON: Okay. Other 12 thoughts? Other proposed mechanisms? 13 Yes? 14 MS. IRELAND: I think the other 15 concern that we would have about this is 16 that we are talking about when PDR uses an 17 existing program and gets money from NICHD, 18 which is great, but it sounds like we're 19 talking about something that would require 20 new money. You know, to the extent that's 21 hard to get or it would just be taken from 22 other programs at NICHD, you know, I think BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 205 1 we need -- I guess I'm asking that we 2 maybe -- in addition to thinking about the 3 network concept, which would address some of 4 the capacity issues 컴컴 we were talking 5 about this morning, what are some other 6 mechanisms we could talk about that aren't 7 going to take new money so while we're 8 fighting to get those funds in Congress, 9 other things are moving forward in terms of 10 pediatric devices. 11 DR. ABRAMSON: Thank you. 12 MS. IRELAND: So we talked this 13 morning about not -- difficulty in 14 identifying what devices need to be studied, 15 so what mechanisms do you want to have in 16 place for that? Conversations between 17 manufacturers and the FDA about the quickest 18 pathways 컴컴, what mechanisms should we 19 have in place for that? 20 We have this HDE process now, 21 which Joanne talked for quite a long time 22 about. I'm not entirely clear how the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 206 1 issues raised around the table. People are 2 saying we have small numbers of patients, 3 difficult to get the studies; you know, 4 difficult to get clinical trials, 컴컴 kinds 5 of studies, why is HDE not working in those 6 circumstances? Does HDE need to be fixed? 7 I mean, some other mechanisms, in 8 addition, I think 컴컴. 9 DR. ABRAMSON: It is my intention 10 to go through these barriers and ask you to 11 list other ones that we aren't listing and 12 see what solutions you have, and they don't 13 necessarily have to -- and please -- they 14 don't have to come back to this idea of a 15 central network. We are listening to any 16 solutions that you have. 17 I just put that out as a proposal 18 to think of it because it does deal with 19 some of the issues that are facing all of us 20 and I think in a collaborative way, all of 21 us could benefit, including, in particular 22 the children, you know, to have devices that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 207 1 are better studied and for whom we 2 understand what the safety and efficacy 3 issues are. 4 MR. O'HOLLA: Yes. I want to echo 5 the comments. I think there are a lot of 6 things that can be done without a new 7 network or funding and you enumerated most 8 of the ones that were on my mind, but I keep 9 going back to -- this idea of the network is 10 a good idea if we had really well-defined 11 issues that haven't been acted on, but as I 12 see the problem, we don't have well-defined 13 issues yet and so I would like to see us, 14 besides doing the things you had talked 15 about -- talking about approval mechanisms, 16 et cetera -- is get a clear definition from 17 the societies of what are the needs because 18 I suspect that if there are needs there -- I 19 mean, companies don't turn down market 20 opportunities, and so if they're 21 well-defined market opportunities, companies 22 are going to pursue that and then we're BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 208 1 going to have a whole host of others; these 2 kind of orphan problems that aren't 3 commercially viable. 4 It seems to me that then a network 5 or HDEs or something other than the normal 6 commercial process can be focused on and get 7 taken care of, but in my mind, at least, I 8 don't think we've picked the low hang of the 9 fruit because we haven't identified the low 10 hang of the fruit. 11 MS. IRELAND: I'd just add to 12 that. I think it's important -- I think the 13 network is a wonderful idea and something to 14 be supportive of, but it is true; we will 15 not get congressional support for something 16 like that if they believe it's a planning 17 industry effort. So what can the industry 18 do on its own? What can government take up 19 that's not going to be handled otherwise? 20 DR. ABRAMSON: Other comments 21 because otherwise I'm going to take on 22 exactly the issue that she raised and ask BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 209 1 people to respond. 2 The comment was made that if 3 there's a real need out there, industry will 4 go at it and fix it. My feeling is that 5 that's not always true, the 컴컴. Maybe 6 it's because it's out-of-the-box thinking 7 and I don't understand the engineering well 8 enough to even complain about infection 9 rates in 컴컴 and shunts and 컴컴 shunts 10 that have to be replaced every year for a 11 long, long time; not rare diseases. 12 MR. O'HOLLA: Yes. Well, let 13 me -- actually, I can talk to that because 14 there are a couple of things in that 15 particular example. First of all, we'd love 16 to make a shunt that doesn't 컴컴 and we 17 look for those opportunities all the time. 18 It's not as easy as saying we're going to 19 make a shunt that doesn't 컴컴. 20 The idea of reducing infection 21 rates -- and this is something that I think 22 FDA has been very creative on and should be BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 210 1 commended on -- to make a shunt and say I 2 reduced the infection rates would be a very 3 difficult thing to get approved. To, 4 however, make a shunt that says I have these 5 antibiotics on the shunt and these 6 antibiotics prevent adherence of 7 microorganisms to the shunt is a much easier 8 and, in fact, doable thing to get approved. 9 You'll never get "I reduced the infection 10 rate." 11 In fact, there are shunts that 12 have various antibiotics on them approved -- 13 we're in the 510(k) process, by the way -- 14 that do that, but you pointed out the other 15 issues: There's a lot of controversies over 16 what are the right antibiotics? What is 17 right for this patient versus that patient? 18 I think in that particular area, 19 you're not -- those are technical issues 20 that may or may not get resolved, but I 21 think that the hurdle to get those products 22 to market, you know, were overcome. It took BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 211 1 us a long time, working with FDA, to figure 2 out how do you get these antibiotic products 3 through without doing thousands of patients 4 to show a reduction in the infection because 5 that's what it takes to get the claim 6 approved and I think the creative way was to 7 say well we won't make an outcomes claim. 8 We'll make a claim about the device 9 properties, and that's something that FDA 10 has done. 11 DR. ABRAMSON: But the problem is 12 they're not being used. 13 MR. O'HOLLA: Well, but isn't that 14 a different issue versus they're there, but 15 not being used? 16 DR. ABRAMSON: No. 17 MR. O'HOLLA: Or if they're not 18 there? 19 DR. ABRAMSON: No, because no one, 20 at least in my specialty, is convinced that 21 they were or that the downside doesn't 22 outweigh the upside. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 212 1 MR. O'HOLLA: That -- particularly 2 with infection -- that will be the issue 3 because the studies are so large that if you 4 needed to do that study for a shunt, you 5 wouldn't be able to -- a company couldn't 6 afford to do that study. So maybe that's a 7 study that should be funded through NIH, but 8 the studies are huge. 9 To do that, for any one company, 10 that's a real problem and there's a real 11 problem with it; antibiotic 컴컴. That was 12 exactly the issue and it will be the issue 13 with every antibiotic 컴컴. So we've got to 14 figure out what information do we want 15 versus what information is realistic to get 16 the technology out there, and maybe that 17 requires some leaps of scientific faith; 18 maybe. 19 DR. ALPERT: Then those kinds 20 of -- 21 DR. ABRAMSON: All right. Yes, 22 Susan; I'm sorry. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 213 1 DR. ALPERT: Then those kinds of 2 issues -- and we started with 컴컴 and VP 3 shunts when I was still reviewing drugs 4 in 1991 and '92. The issues of -- the kinds 5 of studies that need to be done in advance, 6 the combinations that need to be evaluated 7 to prevent resistance emergence, and then 8 the issues of which -- whose combination -- 9 and we all are aware that there's at least 10 three difference groups around the country 11 that think that their combination is the 12 right combination. So then you're in to 13 comparative studies, which get even bigger. 14 Now, those are the kinds of 15 studies that maybe a network can help 16 resolve, maybe today's network could help 17 resolve, because these are not uniquely 18 engineering and device- type questions that 19 are being asked. They're the kinds of 20 questions that -- there's a lot of 21 competency all ready to do infectious 22 disease trials around the country. So we've BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 214 1 got to look at all different kinds of 2 things. I mean, those kinds of things; 3 that, I mean, for us as companies would be 4 more post- market. 5 I worked for a company before. I 6 worked for Medtronic that had worked -- done 7 a lot of work -- on different kinds of 8 catheters and infection control issues and 9 it's a constant. It's a constantly evolving 10 set of criteria, constantly changing 11 environment of organisms and alternatives 12 that raise a lot of questions. So there are 13 some things that maybe, as Bob points out -- 14 maybe that's post-market kinds of trial 15 issues. 16 I think one of the things that 17 differentiate devices and pharmaceuticals in 18 some sense is, in fact, the reliance on the 19 device side a bit more on post-market data, 20 not as -- as Joanne pointed out -- not to 21 establish the initial safety and 22 effectiveness and, in fact, you know, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 215 1 there's a lot of work that's been done; we 2 do shunts as an example -- on the small 3 trials that are needed to get you there, the 4 animal work, the bench work, and the small 5 trials. 6 But those big trials can be done 7 more in a post-market comparative way if 8 they're set up right and the center has done 9 some work on a number of different devices 10 where, through NIH or others, combining 11 multiple companies' products into large 12 enough trials to answer those kinds of 13 questions have been done with FDA's support 14 and NIH's, but that's just one -- that's a 15 difference problem. So I think that's a 16 problem of more data and more use as opposed 17 to unmet needs; original unmet needs. 18 So we've got a lot of different 19 categories and I think that's why this issue 20 of doing different mechanisms right now, to 21 look at different aspects of what's on the 22 table and be very flexible about it; not go BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 216 1 to one answer because it may not be the 2 answer for all these areas of questions. So 3 I think, you know, we need to pay a little 4 different attention and maybe make use of 5 some of what's already out there for some 6 kinds of questions where they lend 7 themselves to the networks and to the 8 already existing structures, and think about 9 where do we still need them. 10 DR. ABRAMSON: All right. Well, 11 let's go to your first question, which is 12 what you raised anyway, and this goes back 13 to the identified various and morning 14 discussions. The question that Susan raised 15 and others have raised is where does a 16 company go to get the information about what 17 devices are needed or if they're thinking 18 about a device, to say is this useful or 19 not? What I've heard as an alternative is 20 the pediatric subspecialty use, which are 21 relatively finite. 22 I mean, they're not adult BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 217 1 sized; 10,000. Does everybody think that's 2 a reasonable way that companies are going to 3 get their information and the FDA or, in 4 this case, is really the FDA within 컴컴 5 potential device that came forward that way, 6 but it isn't going to be in at that point. 7 So you're proposing an 8 alternative, which is just go to the 9 subspecialty. 10 DR. ALPERT: I think one of the 11 things -- Liz, can you talk a little bit 12 about the industry and the way it exists in 13 terms of large and small companies and the 14 number of companies that we're talking about 15 because I think that that makes it -- it's 16 not about a single company. I mean, 17 Medtronic knows how to go into hospital and 18 look at the areas in which we work, but I 19 felt we were trying to look at unmet needs 20 in broad areas and trying to bring them to 21 visibility for the industry, for the 22 industry as a whole, and so I think a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 218 1 little -- 2 MS. JACOBSON: Yes. One of the 3 things we were talking about a little bit at 4 lunchtime was how to get the word out from 5 this kind of a conference and what role 6 could 컴컴 play. Part of that is looking at 7 the industry, which is very heterogeneous 8 compared to the pharmaceutical industry. 9 Some big companies -- but lots and 10 lots of little companies -- I said before; 11 almost 70 percent of the 컴컴 members are 12 small companies and it's probably a bigger 13 percentage of that of the 컴컴 industry. 14 We cover most of the products 15 that, in terms of dollar value, that are 16 sold in this country; something like 90 17 percent. Our members 컴컴, but there are 18 lots of other companies; in addition, little 19 tiny companies, that may be making one 20 product or two products where they don't 21 have a huge dollar value that they're 22 adding, but they might be making a very BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 219 1 critical and very important product 컴컴. 2 So the idea of trying to get this 3 message to those companies is going to be a 4 very interesting challenge because they 5 don't have the regulatory affairs 6 departments, you know, 50 or 100 people that 7 are sitting there, just churning out 8 regulatory affairs documentation and being 9 able to work with FDA. 10 In fact, the FDA has recognized 11 that and they have actually 컴컴 a statute. 12 They have a whole group that does nothing 13 but try to explain a regulatory framework 14 and the regulatory pathway toward this 컴컴. 15 Lynn Rice is here. That group is in her 16 office and it's a constant challenge to try 17 to make sure that those folks get the 18 message and that they are not disadvantaged 19 by very, very complicated statutory 20 requirements. 21 DR. ALPERT: Those are the 22 companies that aren't connected in the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 220 1 medical community because those companies 2 may have 25 people; period. 3 MS. JACOBSON: Exactly. 4 MR. O'HOLLA: But they may be the 5 companies. As you mentioned earlier, the 6 commercial model doesn't always 컴컴. If 7 you came to J&J and said, you know, I got 8 this great pediatric product and it will 9 be $15 million a year in sales, J&J's not 10 going to be interested in that in the scheme 11 of things, but it's exactly those companies 12 that that financial model may be encouraging 13 to them to pursue those kinds of products. 14 So they're different financial hurdles, 15 depending on your size where I think, you 16 know, 컴컴 and the societies need to try to 17 focus because even those companies are not 18 going to go to a broad list. They don't 19 read the Federal Register. 20 So you have to figure out how do 21 you reach out to them, both the medical 22 societies and the trade associations, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 221 1 because they have to be brought in. They 2 don't come in easily. 3 MS. JACOBSON: Let me just put 4 some numbers to what Bob just said. Last 5 year, there were about 42 PMAs, which 6 actually is a relatively low year. The PMA 7 numbers tend to jump around a little bit. 8 So last year there were 42 PMAs. 14 of 9 those were from small companies' first-time 10 PMAs. So that's pretty -- I mean, the 11 innovative folks and people that are coming 12 up with some of the ideas that are going to 13 be needed to answer some of these questions, 14 you know, are these guys, 컴컴; companies 15 that have never done a PMA before. 16 DR. ABRAMSON: Bram? 17 DR. ZUCKERMAN: These may be just 18 the companies that will interact with your 19 centers; your academic centers. 20 DR. ABRAMSON: A point I want to 21 make: I still haven't heard where they're 22 going to go; one place they're going to go BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 222 1 to get the information and the feedback. 2 Bram? 3 DR. ZUCKERMAN: Okay. I think, 4 Jon, you've made the point that one size 5 doesn't fit all here. You're going to need 6 multiple models. I do think, from the FDA's 7 perspective, your idea would be useful. 8 Let's take a pilot. If the 9 society could first of all just identify 10 what are the key interventional pediatric 11 products that we should put some resource 12 utilization into, I would suspect it'll come 13 out treatments for pulmonary stenosis, aorta 14 컴컴. Once that's identified, certainly 15 from the agency's perspective, we would be 16 willing to work with small device companies 17 to develop appropriate trial designs in 18 these areas. 19 We don't have unlimited resources, 20 but as you heard, I think for this area, 21 it's not going to necessarily be randomized 22 trials, which makes it more challenging. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 223 1 There's need for more interaction. So one 2 is identification by the Pediatric Society. 3 Two is then to get the word out; we need 4 subsequent conferences. I hope this isn't 5 the last conference and although there's a 6 lot of heterogeneity in these medical device 7 manufacturers out there, through your 8 society, I do think you have good contacts 9 for finding out which companies need to be 10 brought to the table so that this is an 11 inclusive product and I think there's a lot 12 of merit for trying to do this strategic 13 piloting this way. 14 DR. ABRAMSON: Okay. 15 DR. LUMPKIN: I have no idea and I 16 appreciate the feedback from you guys on 17 whether one of the lessons that we learned 18 on the pharmaceutical side is applicable 19 here, but when we were looking at the needs 20 assessment approach, on the pharmaceutical 21 side, it really kind of divided into two 22 groups, and one was the group of trying to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 224 1 figure out what are the needs involving 2 products that are already available. That 3 was kind of the off-label use issue, and 4 after much ado and struggle, I think 5 ultimately the Academy and other groups of 6 professionals, like you're talking about, 7 were able to prioritize and able to look and 8 able to talk about needs when it comes to 9 what do I need with the product that I'm 10 using off-labels already available? 11 Then the second group is new 12 products, you know; kind of the whole blue 13 sky issue. We would need a drug to cure 14 cancer or we need a drug to cure AIDS or we 15 need a drug to do something; something that 16 doesn't really exist now. That was a whole 17 different kettle of fish and that was very 18 difficult and impossible to prioritize 19 because it depended on a subspecialty. The 20 oncologist thought the cure for cancer was 21 most important. The infectious disease 22 thought the cure was the most important and BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 225 1 so forth and so on. 2 Now, you know, I don't know 3 whether in the world of devices, Susan and 4 the rest of you all, would it work for 5 people who are in the society to concentrate 6 on what needs to be done with products that 7 are presently available or are your products 8 so swiftly being developed and coming along 9 that even in the blue sky world, do you 10 think they would be able to prioritize and 11 give you what you need, thinking about de 12 novo products? 13 DR. ALPERT: I think it's a 14 mixture because the issue in devices is -- 15 you're right; they're constantly evolving, 16 but it's not about one company's product 17 because unlike pharmaceuticals, there's no 18 patent protection so we all make a lot of 19 the same things so that it's -- I think that 20 the idea of what's currently in the market 21 that's being jerry-rigged for use is a very 22 fruitful area. That would be helpful. It BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 226 1 may not be the company who's got it out 2 there, who's going to wind up doing that 3 because we're not restricted from getting 4 into each other's kind of areas in quite the 5 same way that the pharmaceutical companies 6 are in terms of patents and worrying about 7 that. 8 So I think that there is a great 9 deal of work that could be done in focusing 10 on what's in the market that's being used 11 off-label or that's being jerry-rigged where 12 that's a need versus where the needs -- the 13 gaps -- that exist totally; again, 14 pediatrics versus, as Bob pointed out 15 before, you know, things that are new, 16 technologies that are kind of broadly 17 needed, adults and pediatrics. 18 I think one of the things we've 19 been struggling here with is this issue of a 20 lot on one side with a lot of unknowns and a 21 lot of players on the other side, not 22 knowing even where to begin to look because BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 227 1 most companies, most medical device 2 companies don't have physicians, never mind 3 pediatricians, that are in the companies. 4 It's a very different kind of industry and 5 so trying to figure out how to bring, how to 6 get things identified and then bring them to 7 notice; you know, there's two different 8 pieces there that still need, I mean maybe, 9 some kind of a network to identify gaps 10 would work, but it would be very different, 11 and that goes to the issue of maybe it 12 doesn't even need funding because it's 13 really a gap identifier as opposed to a 14 clinical trials network that needs to be 15 paid for and staffed with an infrastructure. 16 DR. HAFFNER: It sounds to me 17 like, if what Bram said is true and it might 18 be 컴컴 that if we're looking at, for 19 instance, devices for 컴컴, devices for 20 pulmonary hypertension, these are all going 21 to be rarely used devices. They would all 22 then fall in an orphan-type arena of HDEs BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 228 1 and 컴컴 every one of them, and then we need 2 to look at, you know, why hasn't that worked 3 to bring forward these products? 4 Is it an engineering issue? Is it 5 an incentive issue? Is it that the 6 companies don't know that it's needed? 7 What's going on here? Because I mean they 8 sound to me like they're all pretty zebra; 9 uniform-type -- 10 DR. ABRAMSON: I want to finish 11 out this whole issue and get to your issue 12 second because it's listed on our question: 13 What is it about orphan devices that's 14 stopping, and we have our guesses, but we'll 15 let you talk to it; then stopping the 16 development of those, short of simply not 17 having the ideas put forward. 18 Yes? 19 DR. RAIS-BAHRAMI: Just a 20 suggestion. Maybe rather than every company 21 having a pediatrician on board, maybe AAP 22 should have a committee on 컴컴 that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 229 1 collects ideas from practicing 2 subspecialties 컴컴 and share it with the 3 industries like smaller organizations do and 4 like 컴컴 twice a year. It has internal 5 committee for 컴컴 devices and looks into 6 what it needs to be modified, to be changed, 7 to be upgraded, to be redesigned and a 8 members of manufacturing devices and 9 industry devices join those meetings and 10 share ideas and within a year, they did get 11 approach to relook at this device because we 12 tested this device. 13 It was very quickly advanced. 14 컴컴 15 DR. ABRAMSON: It sounds to me 16 that I'm not hearing any disagreement; that 17 there needs to be the creating of a central 18 repository, receptive or projective, for the 19 ideas and how to do that is then the 20 question in front of us. 21 DR. RAIS-BAHRAMI: The only other 22 thing -- I'm sorry. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 230 1 MR. WALLFISCH: I'm with the metal 2 device manufacturers association. I'm just 3 following up on some of 컴컴 comments about 4 different characteristics or devices because 5 컴컴 and the important role the small 6 companies play, especially the really small 7 ones with 25 employees, that are headed up 8 by the entrepreneurs and the inventors who 9 are 컴컴 and they're not as aware of the 10 컴컴 process as the challenges ahead and the 11 recovery and gaining access to the market 12 that you guys have and we really tried to 13 컴컴 communication 컴컴 let you know what's 14 going on in Washington; what the 15 opportunities are. 16 So to the extent that we can be 17 helpful with our membership, 컴컴 nearly 200 18 members 컴컴, small companies, we might do 19 that. 20 DR. ABRAMSON: Great. Thank you. 21 DR. SAYRE: I'd like to follow up. 22 Again, I'm Maribeth Sayre with Massimo BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 231 1 Corporation and we are not quit that small, 2 not quite 25 people, but I think maybe an 3 illustration of another problem that really 4 hasn't been touched on and that has to do 5 with market access; once a company has 6 identified a need and has even developed a 7 product. 8 We're a 15-year-old company. 9 About six years ago, we came up with a 10 break-through product in pulse oximetry and 11 we were shut out of the market because 12 general purchase organizations and we were 13 lucky because we got a lot of focus from The 14 New York Times, from the Senate hearings. 15 Our founder refused to let, you know, that 16 stopping. So there have been some voluntary 17 agreements in the GPOs to say, okay; rather 18 than single source, there will not be dual 19 source and that's been helpful for us, but 20 there needs to be a more permanent solution 21 that will help the smaller companies. 22 There are a host of -- Ben can BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 232 1 speak to this better than I, I'm sure -- a 2 whole host of small companies who developed 3 products that worked. They went through all 4 the processes. They were approved. There 5 were clinical trials and the companies 6 folded because they didn't have access to 7 the market and so the devices are no longer 8 available because of lack of market access, 9 so this is a problem that I think also needs 10 to be looked at. 11 I also think when we talk about 12 your sample focus or whatever, somehow we 13 have to figure out a good way to get a new 14 institute at NIH, the bioengineering 15 institute, engaged in this because they're 16 brand-new. They're setting their research 17 agenda, and I can see this. Societies can 18 help with their various pieces of the 19 puzzle, from their perspective of what's 20 needed. 21 There may very well be overarching 22 advances in software or whatever that NIH BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 233 1 could target that would really be of benefit 2 to a great number of companies if they 3 wanted to take advantage of some of those 4 research 컴컴. I don't see a way right now. 5 There is no really good mechanism for 6 getting -- that I see -- for getting that 7 컴컴 back to them and I don't see 컴컴. 8 DR. ABRAMSON: The Institute 9 hasn't heard a lot of this; not knowing 10 where to send your ideas and not knowing 11 where to report your ideas, so I think you 12 raise a very good additional issue about 13 컴컴. 14 DR. SAYRE: Because once the ideas 15 are out there, once the product is there, if 16 the company can't make it and it's not 17 commercially viable, then the company's 18 going to go under and again, another thing 19 that has an impact on us as small companies 20 especially is a lot of us depend on venture 21 capital. If the venture capitalist don't 22 see that there's a possibility for profit BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 234 1 somewhere down the line, then they're not 2 going to be willing to 컴컴 for the research 3 and development. 4 DR. ABRAMSON: So this is the 5 third bullet. Does anybody else want to 6 talk to this question; how the stakeholders 7 accomplish getting the product developed, 8 particularly as it pertains to that 9 question? 10 MR. ENGLANDER: I think one thing 11 that unified this question of trying to get 12 products developed in the marketplace with 13 trying to get the initial clinical needs met 14 in the first place, is that a network would 15 be able to demonstrate a way to collect data 16 for submission to a peer review journal, 17 which is one way, Maribeth, that we see that 18 you can try to combat a GPO and bind groups 19 that are going to look at your product from 20 a commercial interest 컴컴. 21 But if you have that sort of 22 published data, which we see 컴컴 medicine BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 235 1 as being very strong advocates of use, 2 that's why this network may really have some 3 컴컴 muscle in that regard and that goes to 4 both questions. 5 DR. ABRAMSON: Okay. Great. 6 There was a very interesting question 7 brought up about devices and drugs. We 8 wouldn't let a drug go to use after just 9 animal studies. That wasn't going to 10 happen. But in devices, there may well be a 11 time where all you need is the bench data. 12 You may only need the bench and the animal 13 data or you may need all three and clarity 14 to that doesn't exist, if I understand the 15 question. I guess I'll ask the FDA to talk 16 about that and what things we can do as a 17 group, as recommendations, that would help 18 there or is this just a 컴컴 in a black 19 hole? 20 MS. LESS: I guess I would say 21 it's better than a black hole; much better, 22 in fact. If it's a 510(k) product, it's BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 236 1 going to be basically 컴컴 some animal 2 testing unless there's some other issue 3 that's driving a clinical question and only 4 about like I mentioned 10 percent being a 5 clinical trial or some type of clinical 6 data, out of the 4,000 that are going to 7 market, but then most are going with bench 8 animal testing bio- compatibility. 9 If it's a PMA, there's going to be 10 clinical data, but we do have a lot of 11 device specific-guidance documents that 12 we've developed, particularly for the 510(k) 13 product, and so we put those out there, 14 developed in concert with industry and other 15 컴컴 organizations to say if you're 16 developing pulse oximeters, this is the kind 17 of testing you're looking for and it covers 18 the whole gamut and the same thing for a lot 19 of the PMA products. 20 So we've come a long way in the 21 last five years or so, especially since we 22 now have third-party reviewers that can BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 237 1 review 510(k)'s. We've developed a lot of 2 guidance documents to outline that, so it's 3 not as hazy as it was a few years ago. 4 DR. ABRAMSON: Let's hear from the 5 industry and the clinicians about things 6 that they're uncomfortable with, if at all, 7 about what the FDA has in front of you right 8 now. 9 MR. O'HOLLA: I'm never 10 uncomfortable with FDA though. 11 (Laughter) 12 DR. ABRAMSON: You don't get any 13 points for that. 14 MR. O'HOLLA: No points for that? 15 SPEAKER: A get out of jail free 16 card. 17 MR. O'HOLLA: I think that 18 Joanne's answer to the question is kind of 19 the answer for new technology, but I think 20 there's a particular subgroup of 컴컴 we've 21 been talking about today that we may want to 22 get out of the box a little bit on; that is, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 238 1 those products that have a bona fide adult 2 use that do not have a pediatric indication, 3 but need one, and the question there 4 becomes -- and let's assume for a minute 5 that it's the PMA product where you're 6 automatically, if you're in a PMA, the 7 answer is usually clinical data. 8 The question I see though for 9 those devices, as opposed to a drug is what 10 have I learned from the engineering and the 11 adult experience and is it enough? Does it 12 answer or get close to answering -- you 13 know, I don't know what I mean by close to 14 answering -- the questions that are in my 15 mind about the pediatric use and, therefore, 16 do I really need clinical data for the 17 pediatric use or can I craft my engineering 18 and 컴컴 base into reasonable assurance and 19 safety and efficacy for a device for 20 pediatrics 컴컴. 21 DR. LUMPKIN: Yes. I guess I 22 would -- see, I don't think that's so BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 239 1 different from the drug side of it. 2 MR. O'HOLLA: Well, we just like 3 to say we're different though, Mac. 4 DR. LUMPKIN: Yes, but I think, 5 you know, in fairness here, the whole issue 6 of the 컴컴 ability of adult pharmaceutical 7 data to the children is one of the 8 fundamental things that the drug side of it 9 has to deal with and I think 컴컴 to deal 10 with. I mean, I think what you're putting, 11 you know, actually goes to one of the other 12 major lessons that we learned and I have no 13 idea again whether this is going to be 14 applicable, but one of the things over the 15 years was the need to have a fundamental, 16 philosophical shift when it comes to 17 developing a product. 18 Now, on the drug side, the idea 19 was, you know, if you're developing a new 20 product now under the law, you cannot choose 21 not to think about pediatrics. That's a 22 fundamental, you know, sine qua non and it BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 240 1 might be that it's totally inappropriate for 2 the product to be used in children, if it's 3 for prostate cancer or something; fine, you 4 get a waiver. It might be inappropriate to 5 develop them simultaneously, you know, so 6 you get a deferral, but you have to at least 7 go through the thought process and you have 8 to defend why am I not thinking about 9 children as I develop this product because 10 when it gets on the market, you know 11 somebody's going to jerry-rig it and use it 12 for a kid until such time as the appropriate 13 product and the appropriate data are 14 developed. 15 So that was the idea behind the 16 third in the legislative pieces that came 17 out that set in statute for pharmaceutical 18 on new products, going forward with new 19 products, you have to think about children 20 upfront and decide when is it going -- if 21 it's going to be appropriate to develop for 22 children, when is it going to be BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 241 1 appropriate, and put that forward as part of 2 your development plan. The question is is 3 that something that we ought to do for 4 devices like we did for drugs? 5 DR. ALPERT: That's not good. 6 What I think you've been trying to say is 7 that the issue is where are their needs, 8 because it's very unclear today in what 9 areas would that make sense and areas where 10 that may not make sense, and given that 11 there are I don't know how many thousands 12 of, you know -- we've got somewhere 13 around 5,000 products a year going to 14 market -- it, to me, from both my FDA 15 experience and my industry experience, 16 trying to plug that into the 510(k) process 17 or 5,000 510(k)'s a year is a burden that's 18 probably not -- doesn't have the benefit 19 risks, you know, of 컴컴. 20 DR. LUMPKIN: What about for PMAs? 21 DR. ALPERT: I think that's a 22 question of where and what and one of the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 242 1 goals I think that we ought to be working 2 on -- that's why I think -- we've been 3 pushing a lot about identify the areas of 4 need. Identify the issues of need, and 5 maybe in those areas, it may make sense to 6 push for pediatric development, but until 7 you know, you're creating a tremendous 8 burden for both the industry and the FDA in 9 an environment of unknowns and I think -- 10 let's figure out what the unknowns -- you 11 know, where the gaps are and help kind of 12 focus this work before we jump to that model 13 because that model, I think, you know, for 14 companies -- again, a lot of these little 15 companies with one product have to spend the 16 time and energy to justify and FDA would 17 have to give them the waiver when there's no 18 way that this makes any sense, but have to 19 go through the process of developing the 20 information. 21 If we can identify the areas where 22 it doesn't make sense, the areas where there BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 243 1 are needs, I mean, it seems to me that 2 there's some background work that needs to 3 be done before it's applied broadly because 4 it's a very different -- 5 DR. ABRAMSON: Are these simply a 6 컴컴 set of questions to be created that 7 would identify whether a company had to 8 justify not doing pediatrics? 9 DR. ALPERT: A threshold that sort 10 of lines up here, if this were to be 11 considered, where should it be considered 12 appropriately as opposed to blanket the way 13 it is with drugs, everything going forward, 14 because we're talking about very difference 15 industries and very different volumes of 16 products and very different kinds of 17 submissions to the FDA. 18 DR. LUMPKIN: But it would still 19 be an upfront thought process, somewhere 20 along the line. The children aren't going 21 to be a secondary thought. 22 DR. ALPERT: Somewhere along BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 244 1 the -- 2 DR. LUMPKIN: Somewhere in here, 3 you think about it as you go forward and it 4 draws 컴컴 level. 5 DR. ALPERT: Where that is, I 6 think, is what we keep pushing back. Help 7 us understand where. 8 MR. O'HOLLA: Well, that's what we 9 said, and I'm sorry you weren't here for 10 part of the discussion this morning. The 11 automatic assumption that because I do it 12 for adults, I'm going to do it for peds 13 doesn't hold for devices because, for some 14 devices -- and if there be a 15 device-by-device decision, it's not going to 16 be easy to do categorically, and it may be 17 manufacturer to manufacturer for the same 18 device, depending on what technologies they 19 used in the device. 20 For some device designs, it may be 21 just a matter of kind of reengineering the 22 smaller. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 245 1 SPEAKER: Right. 2 MR. O'HOLLA: Well, that's an easy 3 one, but for other device designs, you may 4 not be able to get there with that design 5 and so what do you do to that company? You 6 know, if you were taking an extreme position 7 and say you need to pediatrics and I know 8 you did it for adults and you now need to do 9 it for pediatrics, even though it means 10 you've got to spend a gazillion dollars to 11 redesign the device for pediatrics, well, 12 that model doesn't work very well either. 13 So it's not just a matter of kind 14 of saying well, if I treat the adults, I can 15 treat the child. It may be beyond the 16 technical feasibility for that particular 17 company to do that. 18 Some other company may be able to 19 do it, but that particular company may not 20 be able to do it and that's where it kind of 21 gets muddy for devices. 22 DR. ABRAMSON: Again, there are BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 246 1 exceptions in drugs, and with their 2 formulation, you prove that you cannot make 3 that 컴컴. 4 DR. ALPERT: My clinical 컴컴. 5 DR. ABRAMSON: You need to think 6 long and hard about that because we as 7 pediatricians don't like the idea that we 8 have a device that could be effective in a 9 kid and not know whether it's safe or not. 10 Kathy? 11 DR. JENKINS: Yes. I was going to 12 say I'm a little confused, I guess, because 13 we're talking about -- you keep talking 14 about that you need to go to the physicians 15 and ask about these unmet needs, but on the 16 other hand, I suspect that most companies, 17 whether they're big or small, know if 18 they're selling products to pediatricians. 19 So, you know, I guess I a little 20 bit think that people do know that they're 21 selling their product occasionally for use 22 in pediatrics for which it's unlabeled and, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 247 1 you know, they don't really need a medical 2 specialty group to go through a long process 3 to tell them that that's nothing. 4 DR. ALPERT: That goes to Bob's 5 question; the difference between needing it 6 for a hundred kids a year, needing it for 7 five hundred kids a year, needing it for a 8 thousand kids, or needing it for much 9 broader numbers. That was a question that 10 Bob raised. 11 MR. O'HOLLA: We sell our 12 products, for example, to a cath lab. We 13 don't sell to an individual physician. 14 DR. JENKINS: But if you sold it 15 to my cath lab, you could guess it's being 16 used in children. 17 (Laughter) 18 MR. CONNAUGHTON: We sell lots of 19 products to pediatrics critical care centers 20 and we know that that's there and we are 21 marketing directly to those centers, but I 22 mean, no; the problems that we run into are BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 248 1 when you have that PMA requirement and the 2 cost to the medical 컴컴. 3 DR. ALPERT: Those aren't so much 4 the unmet needs because those are the ones 5 that are being designed and sold into the 6 environment. The question is where the 7 컴컴. 8 DR. JENKINS: I guess it depends 9 on how you define unmet need because we 10 don't really know what's safe and someone 11 has to jerry-rig it to get it to work. That 12 is an unmet need. 13 DR. ALPERT: That's why we're 14 trying to separate them. 15 DR. JENKINS: But you're doing it 16 based on volume and then volume of sales 17 really gets back to the small pediatric 18 marketplace and the halfway thing to 19 approval thing being very expensive. 20 DR. ALPERT: Now, I took 컴컴 when 21 you raised the question about if I sell to 22 you, then I know that there's either a need BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 249 1 or an unmet need. I don't know. I know 2 that I sell -- let's say I know that I sell 3 to, you know, a small number to a couple of 4 pediatric hospitals. It doesn't tell me, 5 without better input, as to whether you're 6 buying it because it works, but it only 7 works in a small number of patients, or 8 you're buying it and doing something to it 9 to jerry-rig, and part of that is 10 communications because, I mean, we're a big 11 company. We communicate and we hear all 12 this stuff, but we've been talking about the 13 fact that a lot of these industries are very 14 small companies and they may not be having 15 that ongoing communication with a children's 16 hospital or to find out those issues. 17 So I don't think that's the issue 18 we're talking about right here. I think 19 what we're trying to, I think, figure out is 20 is there a mechanism that would put 21 pediatrics on to the radar for certain kinds 22 of products so that that would be, as Mac BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 250 1 puts it, an upfront thought as the product 2 is being developed? I'm just 컴컴 that to 3 say we're -- how do we make sure that we're 4 doing that appropriately so that it's not a 5 burden on either the agency or the industry 6 and really get you the benefit of developing 7 products in the areas where you really need 8 them because you're going to get them. 9 DR. LUMPKIN: I think, Susan -- I 10 mean, it was interesting. I wasn't here 11 this morning and I did miss the last hour 12 and half of discussion, but coming back here 13 and identifying these barriers, maybe I just 14 didn't read it right, but clearly the 15 biggest barrier than we've heard from 컴컴 16 was the economic incentive barrier, and 17 that's what I think I've been hearing all 18 the way around. 19 When people talk about volume and 20 size and all this -- 21 DR. ALPERT: That's one of the 22 benefits. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 251 1 DR. LUMPKIN: I mean, we're in a 2 brainstorming situation here. I mean, if 3 there were a way to create for devices what 4 was created for the pharmaceutical side, as 5 one piece of answering the pediatric 6 question, of creating an economic incentive, 7 when the market doesn't have an economic 8 incentive, then what would that be? 9 I mean, we figured out the 10 pharmaceuticals a way to do it, but again, 11 in devices, perhaps the same things don't 12 exist, but is there a -- I mean, so the 13 solution might not be the same, but if the 14 issue is the same, how would somebody go 15 about creating an economic incentive for you 16 guys when you've got small populations and 17 small uses to say well, this is worth my 18 while to try to meet this need if we think 19 really for children it's important from a 20 public policy perspective. 21 DR. ABRAMSON: Let me throw out 22 the specific question that's on here. So BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 252 1 today I've learned, and am learning all the 2 time, that if you have what I would call an 3 orphan device and you develop it, you can't 4 make a profit. I mean, that's -- does doing 5 away -- if we change that regulation -- I'm 6 not saying we can -- but if we change -- 7 DR. LUMPKIN: Change the law. 8 DR. JENKINS: Change the law. 9 DR. LUMPKIN: That's not a reg. 10 That's a law. 11 (Laughter) 12 DR. ABRAMSON: If we got that law 13 changed, how much of that fixes -- does that 14 fix this problem? 15 MR. CONNAUGHTON: It would be 16 helpful, but it wouldn't fix it. 17 DR. LUMPKIN: Right. 18 MR. CONNAUGHTON: It would be 19 helpful. 20 DR. ABRAMSON: Please speak to 21 that because we've got to find a way to fix 22 this problem. We as pediatricians will keep BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 253 1 hammering at you about vices and safe 2 devices so we're not going away and you've 3 got to figure out how to fix it. 4 MR. CONNAUGHTON: In my opinion, I 5 think one of the reasons we're seeing so few 6 uses 컴컴 is that you can't make a promise. 7 Most of them turn their backs on their 8 products immediately. 9 DR. ABRAMSON: I can't hear you. 10 MR. CONNAUGHTON: So many 11 companies will turn their back on it and if 12 you allowed them to make a profit, it seems 13 to me that we would look very carefully at 14 can we go forward at this point. Just give 15 them some other areas that we didn't think 16 we had, and we had lots of pediatric 17 devices, but most of them are 510(k) 18 products and from time to time, there is 19 that 컴컴 product that comes up and 20 generally we have to turn away from it 21 unless it's a real lifesaver. I'm not going 22 to 컴컴. If we had this other avenue, we BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 254 1 would have something else we could examine 2 and a way to rationalize going forward with 3 them. 4 We think it would be a good thing. 5 DR. ABRAMSON: So 컴컴 doing all 6 the 컴컴? 7 MR. CONNAUGHTON: Right. 8 DR. ABRAMSON: Let's assume for a 9 moment they have a pediatric need; I'm not 10 arguing that, okay. What's stopping you if 11 you can make a profit? 12 MR. CONNAUGHTON: Well, the 13 question is can you make a profit period 14 with a lot of these stuff, even though 15 someone could have larger markers and cost 16 is taking something through the clinical 17 trials 컴컴 approval 컴컴. You're talking 18 seven figures or eight figures to do that 19 and how big is that market. 20 As you know, 컴컴 pediatric 컴컴 21 is small. It might be 5,000 instead 22 of 4,000; it might be 7,000, but 컴컴 BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 255 1 catheter, you can't do it. You just can't 2 do it. So I think that's an issue for all 3 those markets and I'm not sure 컴컴. 4 DR. ABRAMSON: Khodayar? 5 DR. RAIS-BAHRAMI: As you 6 mentioned, when you are making any adult 7 devices, you have to think about pediatrics, 8 but it's not the other way around. If there 9 are devices that are 컴컴 used in 10 pediatrics, I think newborns and infants, it 11 has no other applicability and it's sold 12 like $150 a year, I don't think anybody's 13 going to make it. That's basically, it, you 14 know, and there are examples of that. 15 DR. LUMPKIN: I think that's the 16 question we're putting to you; why wouldn't 17 that happen? If for those 150 children this 18 is an important condition, and for those 19 taking care of those children or the parents 20 of those children, this is an important 21 issue, I think we've found from a public 22 policy perspective, you just can't go to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 256 1 them and say sorry, you can't make any money 2 on this; tough. 3 I mean, you know, as a society who 4 cares about children, the answer's got to be 5 okay; well, what can we do? I mean, it 6 sounds like the general market incentives 7 are not there for that product. We all 8 agree. How do we create an incentive for 9 the companies to do what needs to be done 10 right by those children to make the product 11 and study it appropriately so that there is 12 some appropriate incentive and, you know, 13 that's what we need some feedback on. 14 DR. RAIS-BAHRAMI: Absolutely. I 15 agree with you, but it has to be a very 16 attractive incentive to drive that cause. 17 MR. O'HOLLA: I'm sorry; even the 18 approval mechanisms are a product 19 that's $150 a year and couldn't generate 20 enough gator in a reasonable period of time 21 to get it approved. So not only the 22 incentive -- BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 257 1 DR. LUMPKIN: We've approved drugs 2 that have been used in five people, and so, 3 I mean, it can be done. 4 MR. O'HOLLA: That's the kind of 5 thinking that would have to apply. 6 DR. LUMPKIN: So it can be done, I 7 mean, I think, but that's not going to give 8 you the financial incentives and I think 9 we've found -- it's the nice thing about 10 living in a free country. I mean, we can, 11 you know, think about these things and if 12 they make sense, you know, you've got people 13 that can push for this to happen, but we 14 don't know. I mean, I would say from the 15 academic view and from the FDA view, we do 16 not understand your business practices. We 17 do not know your business practices. That 18 is where industry has to at least come to 19 the table and say if we had this over here, 20 it might help us over here do something that 21 from a public policy perspective is good. 22 Now, if Congress buys it or not BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 258 1 remains to be seen; they are the ultimate 2 arbitrator of it, but at least we need to 3 put on the table what some ideas might be. 4 MR. O'HOLLA: Right. 5 DR. ALPERT: One of the things I 6 need for people who aren't in the industry 7 to understand is that on the drug side, some 8 of the incentives are patent term extensions 9 and things like that. We don't have those 10 devices. 11 DR. LUMPKIN: Right. 12 DR. ALPERT: They just don't 13 exist. 14 DR. LUMPKIN: Right. 15 DR. ALPERT: So that the same 16 kinds of incentives don't work. 17 To answer John's question, the 18 idea -- even under HDE, if you could make 19 profit on HDE, that still might not be 20 viable because a very small number, even 21 with profit, the profit would have to be so 22 large that nobody could afford the product. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 259 1 So, you know, you've got to -- but there may 2 be things that could be done that would 3 benefit the company as opposed to that 4 particular product. 5 DR. LUMPKIN: Right. 6 DR. ALPERT: So one of the 7 challenges is trying to figure out what's 8 the benefit to the company that they would 9 get that might provide some incentive, some 10 capacity for that company to do the 11 investing because this is not without need. 12 Many of us already invest and do -- we have 13 a large number of products that are used in 14 orphan-sized pediatric populations. We put 15 the money to the investment and have done it 16 because we have the wherewithal to do that 17 and so we pick and choose and do that, but 18 there are lots of companies who don't have 19 that flexibility, who don't have large 20 revenue streams from somewhere else that can 21 be used to support -- you know, if you're a 22 two-device company, you don't have big BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 260 1 revenue streams from other things that can 2 help you do that. 3 So I think the issue here is to 4 try to figure out what kinds of incentives 5 can you put in front of a company for other 6 products, for other benefits, that could 7 work where the patent term extension stuff 8 that protects you doesn't work on a device 9 like that. 10 DR. LUMPKIN: Right. 11 DR. ALPERT: But if we could come 12 up with the kinds of things that reward, 13 that might help. I don't think that any of 14 these are going to be the final answer 15 because a lot of these products will not fit 16 the small product area. They are products 17 that are going to be used more broadly. 18 They won't fit under HDE. Then you get into 19 the issue of the investment and development 20 that requires the full clinical trials and 21 all the rest of it. 22 So whatever these incentives are, BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 261 1 they have to address what's had to be done 2 to do that development and what the market's 3 going to look like. I think it's going to 4 be very complicated. I don't think it's 5 impossible, but it's going to be very 6 different and very complicated to reward 7 companies for making that effort and it 8 can't all be in financial. 9 MS. JACOBSON: Susan, I think the 10 other thing that complicates it more -- and 11 a gain I just think people need to be aware 12 of this -- is that the industry -- and we're 13 talking like it's a 컴컴 -- there are 14 companies that are electronics industries. 15 There are companies that are really material 16 fabrication types of industries. There are 17 companies that make in vitros; there are 18 biological chemical industries. 19 So there's this broad range of 20 different types of technologies that 21 companies see as their whole strength or 22 whatever and what is an incentive for one BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 262 1 type of manufacturing sector may, in fact, 2 not be an incentive for another type of 3 manufacturing sector. 4 So if we get into those types of 5 discussions now which I think is really an 6 interesting idea -- we've got to make sure 7 that we're tailoring it to the various 8 sectors of the various manufacturing 9 capabilities so that it doesn't become a 10 disincentive for one part of the industry 11 whereas it might be an incentive for 12 another. 13 DR. ABRAMSON: That's right. 14 DR. CAMPBELL: We've got a lot of 15 manufacturing representation here, but most 16 of them are the giants. All the little guys 17 aren't here. Getting back to the point, 18 well, why don't we survey everybody, the 19 little guys, and get a feel. 20 We're arguing in absence of data 21 here. I don't know what incentives are 22 needed. I've heard a few ideas here, maybe BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 263 1 tax incentives and everything, but if a 2 device has to cost a million bucks to be 3 built, well, it's never going to be built. 4 I'm not sure that profit is the 5 best way to go. 6 MR. WALLFISCH: With the 7 humanitarian devices specifically, the 8 no-profit requirement would be an 9 improvement, but still that provides 10 coverage for the device -- that's part of 11 it -- but it doesn't have funding for the 12 downstream costs, like going to payers in 13 the future and going on to different reasons 14 and getting the product actually adopted, 15 which is very challenging for the little 16 guys, but in terms of incentives, I'd 컴컴 17 it more in terms of breaking down barriers 18 and we talked about EPOs a little bit 19 before, which is an ongoing frustration that 20 we hear from our members and the other thing 21 we hear about is concerns about the 컴컴 22 program and this is somewhere where costs BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 264 1 for filing a 510(k) and application 2 applications are going up pretty drastically 3 just in the first two years of the program 4 and we hear continually from small 5 manufacturers. You see, this is a burden 6 where paying, you know, a large fee just to 7 get reviewed by the FDA is a concern. 8 So our perspective on that is that 9 going forward, if that's going to help 10 streamline the FDA's review processes and 11 speed it up, great, but it needs to be done 12 with an eye towards preventing and 컴컴 of 13 innovations and allowing new companies to 14 컴컴. 15 DR. LUMPKIN: But, you know, 16 again, I think those are the kind of things 17 that are some of the more specific things we 18 can think about because -- correct me if I'm 19 wrong, Rosemary -- I mean, on the 20 pharmaceutical side, orphan applications and 21 pediatric applications are exempted from the 22 drug user fees. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 265 1 DR. ROBERTS: Yes. 2 DR. LUMPKIN: Okay; good. Well, 3 that's good. You know, but I think there 4 are -- you know, people have brought up tax 5 issues; you know, other things people have 6 brought up and 컴컴 liability issues, 7 extending patent issues, guaranteed loans. 8 You know, the kinds of programs that we 9 have. 10 There are some things that I 11 think, Liz, that might be, you know, 12 interesting to all companies on some of the 13 tax and liability issues and those kinds of 14 things. I mean, there are ways that I think 15 you guys can make a pitch on this to deal 16 with some of the issues that plague you, you 17 know. At least what we've learned on the 18 pharmaceutical side is that I don't think 19 you're going to get a good hearing if what 20 you're trying to do is say, look, we don't 21 want to take risks in the marketplace. 22 I mean, we're talking to people BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 266 1 who say that's the way the marketplace 2 works. If you're not willing to take the 3 risks, you know, you shouldn't be in this 4 game. You shouldn't play the game. But if 5 there are situations where the general 6 market incentives do not give you any 7 rational reasons to take the risk, then you 8 can come forward with well, you know, I'm 9 willing to do it over here because I know 10 I'm going to take a hit, but I can get an 11 advantage over here, and those are the kinds 12 of things I think we need from you guys, 13 maybe not today, but as we go through this 14 process; things that you're willing to put 15 on the table from a public policy 16 perspective that might be a tradeoff to say, 17 well, you know, it's worth it to our kids to 18 do this and we think it's important and this 19 is a way to begin to address the issue. 20 DR. ABRAMSON: The only other 21 thing I want to add to this before, to make 22 sure that everybody understands, that for BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 267 1 the drug, we link together -- all 2 together -- the same message. If we ever 3 fractured, it never would have occurred, and 4 so we've got to find the common ground that 5 will allow us to go together, hand and hand, 6 and say we're all in agreement. 7 MR. O'HOLLA: I just had a 8 question for Joanne. You know, we talked 9 about the 4,000 HD number. It started out 10 as 8,000. If you're thinking about allowing 11 an HD to make a profit, is it worth thinking 12 about what a realistic number would be under 13 the HDE for pediatrics? Maybe you don't 14 want to increase HDEs for all devices, but 15 for pediatric devices, the HDE is -- I don't 16 know what an appropriate number would be -- 17 but if there were some way to get a better 18 feel for that, maybe those two things 19 combined could be synergistic. 20 MS. LESS: That's what I wanted to 21 say. When you asked for complaints from the 22 industry as to -- for the HDE process and BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 268 1 Tom mentioned one -- we actually got a lot 2 of complaints from J&J for the 컴컴 kit, 3 when that went to market. 4 (Laughter) 5 MS. LESS: I did a presentation 6 with one of your people and they said that 7 one of the 컴컴 is the IRB approval. You 8 know, every single site is supposed to give 9 IRB approval where the device is used. 10 MR. WALLFISCH: That's right. 11 MS. LESS: So that's a big hurdle. 12 GMPs, I mean, maybe it's not a big issue for 13 something like Medtronic or for J&J, but for 14 the little guy -- and most of our HDEs are 15 coming from single product companies -- to 16 comply with GMPs is a big issue and 17 the 4,000. I mean, even though they get 18 cleared for 4,000 under a HUD designation, 19 what we're seeing in the annual reports is 20 that they're selling 150 or 200. 21 So even if you could make a 22 profit, is that really going to make a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 269 1 difference? 2 DR. ABRAMSON: Others on this 3 issue and then we're going to move the IRB 4 issue. 5 MS. LESS: Okay. 6 MR. WICKS: As I'm sitting here 7 listening to this discussion, being an 8 academic, coming from an academic 9 institution, I don't work for profit. You 10 know, the State of Virginia pays me; not 11 well, but they pay me. 12 (Laughter) 13 MR. WICKS: One of the things that 14 has come up -- I listened to industry and 15 they talk about market. I listen to the 16 pediatricians and they talk about needs. 17 Market and needs are not equivalent 18 statements, at least in my opinion, but one 19 of the things that we might want to think 20 about trying to achieve is that if I have 21 design problems, I can throw them out to my 22 students and graduate students, who most of BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 270 1 you know -- as most of you've been one at 2 one time or another -- work very cheaply. 3 So it's very inexpensive to do this kind of 4 stuff. 5 But one of the big issues that 6 prevents me as an academic from working a 7 lot with industry is intellectual property 8 issues and, essentially the State of 9 Virginia -- I'm on the intellectual property 10 committee for Virginia Tech, so I have some 11 feelings in that regard -- the State of 12 Virginia interprets anything that I develop 13 or come up with, 24-7, belongs to the State 14 of Virginia. 15 If you're a company -- Johnson & 16 Johnson comes and funds a research project 17 that I'm working at -- all that money goes 18 to, from the State of Virginia's 19 perspective, is the right for you to 20 negotiate. You don't own any of it. You 21 have a right to negotiate. 22 So what I might throw out here is BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 271 1 kind of maybe an interim between the budgets 2 that you're looking at to make a profit and 3 truly if it's an industry, a company, 4 they're there to make a profit whether 5 you've got venture capitalists or whether 6 you've a chairman of the board or whatever 7 looking down. It's profit. I mean, let's 8 call it what it is. 9 Is it possible that we can create 10 some legislation for something that will 11 allow the intellectual property that is 12 developed in a university-funded program, go 13 to some of these companies, inexpensively, 14 so that we can make devices, fill this void 15 for the needs issue, for the profit 16 margin -- or the market -- 컴컴 I used the 17 term loosely there -- to maybe fill some of 18 this in. Taking advantage of the great 19 minds of the 18- to-25-year old crowd that I 20 deal with on a day-to-day basis, and 21 capitalizing on that to fill some of these 22 intermediate needs and then using that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 272 1 development tool -- inexpensive, cheap 2 development tool -- to kind of foster the 3 devices being developed within industrial 4 컴컴. 5 I'm not a developer. I'm not a 6 marketing person. I'm good at prototypes, 7 but that's about as far as it goes. So it 8 seems to me that there's room here for some 9 컴컴 where we can kind of fill in some of 10 these voids that industry can't afford to 11 do, you don't want to pay for it yourself 12 obviously, but maybe it's time for academia 13 to kind of get in bed -- and I use the term 14 loosely -- with industry and with the FDA 15 and say that, you know, there's some common 16 ground there, especially common interest 17 with our children. 18 I just throw that out as a 19 possibility. 20 DR. ABRAMSON: It's another 21 mechanism obviously to potentially 컴컴. 22 MR. WICKS: Well, it's a different BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 273 1 model, I guess is what I'm saying, from what 2 we've been discussing. 3 DR. ABRAMSON: Yes? 4 MR. GROSSMAN: I'm just going to 5 say about ten years ago, I worked with a 6 group a lot similar to this 컴컴 creation 7 and addiction drugs and they had the 8 addiction drugs, and what we tried to do 9 was -- we're all looking at where you are 10 rather than where the policymakers are going 11 to sit is that we tried to divide the 12 centers. They're what you might want to 13 call ordinary incentives, like the R&D tax 14 credits. You know, ordinary and then 15 upgraded might be -- FDA sets up a special 16 office to make sure these things go as 17 quickly as they can. 18 They're advanced, like marketing 19 exclusivity, and then the fourth category 20 was extraordinary, such as -- I think I'm 21 your first person to bring this up -- to 22 give a company the ability to extend a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 274 1 patent on a product that was not the one 2 they're getting the goodwill for. 3 So I think that as you start to 4 look at -- and unfortunately, from a public 5 point of view, it's how little incentive on 6 that change you have to give up in order to 7 get the desired action, and I think that at 8 some point it may make sense to 9 systematize -- because I heard some 10 different things that people thought would 11 work, but, you know, it's hard to do that 12 until you -- you start to 컴컴 13 systematically and then start asking 14 companies what would it take. 15 DR. ABRAMSON: Thank you. I want 16 to get to the issue of IRB approval for 17 컴컴. There's a demand on you to collect 18 data on your devices and that database, if 19 well done, has a wealth of information in 20 it. Do we need to change the -- I don't 21 know if it's the 컴컴 regulation -- so that 22 you could go and get an expedited review of BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 275 1 an IRB or no review, to go use that data to 2 look and see if a product is safe? 3 What needs to be done under that 4 issue or fixed? 5 MS. LESS: Our statute requires 6 that if you're doing clinical studies, 7 according to 컴컴 applications, you have to 8 get IRB approval and you have to get 9 informed consent and the only waiver for the 10 informed consent piece is if it's a life- 11 threatening situation and you can't 12 communicate or there's not time to get 13 consent from the subject. 14 NIH is -- and so our regulations 15 are written around that. There is no waiver 16 for informed consent under our regulations 17 and 컴컴 there's no waiver for IRB under our 18 regs, if it's a pre-market setting. 19 Post-market is a slightly different issue. 20 Under NIH's or OPOC's regulations, 21 they do have a provision where they can 22 waive informed consent if the IRB determines BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 276 1 that it's a minimal risk study. It's not 2 practical to do the study without the waiver 3 and a couple of other requirements, but 4 those are the two papers that most companies 5 refer to. 6 So for most of our studies, that's 7 not an issue. It does become at issue with 8 some of the cardiovascular studies when they 9 can't get consent, but we do have a right 10 for that, but when you look at IVD and some 11 of the other, say, like imaging studies, 12 where a company wants to go back into a 13 patient record and get a bunch of MRIs and 14 submit them in support of a 510(k) for a 15 different indication, we've said that they 16 have to go back and get informed consent to 17 go into those records, and so there can be a 18 barrier, you know, to doing that research 19 obviously. 20 In some cases, if you're doing 50 21 patients, 100, it's not a big deal to go 22 back. In other cases, patients might be BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 277 1 dead. It is burdensome to do it if you're 2 spread across the country; it gets 3 expensive, and so there is that piece that 4 becomes a big issue which is driven mostly 5 by the IUD industry right now because it's 6 come up in a number of your studies where, 7 under NIH'S regs, a company will go -- the 8 IRB to waive consent, then the information 9 will come into us and we'll say, you know, 10 the IRB shouldn't have waived consent. They 11 should have followed our regulations under 12 the 컴컴. 13 So we're trying to look at 컴컴 14 that, but in the meantime, that had become a 15 big issue. 16 DR. ABRAMSON: So if I understand 17 you correctly, you would like to see the 18 ability to do what the NIH does? 19 MS. LESS: We're looking into that 20 to see; yes. I think there's a lot of 21 concern within the agency that that is 22 stifling research, but the counter to that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 278 1 is that if you go back and you look at when 2 we promulgated IRB and informed consent 3 regulations, there's a big discussion in 4 there about, aha, even though there's no 5 risk to these studies, that the patient 6 should have the right to say no, I don't 7 want to be in the study and so there's sort 8 of a back and forth between people that say 9 there's no risk, just let them, you know, 10 delink the sample and it's not actually 11 clinical research, versus people saying no, 12 it is clinical research. We're just 13 artificially saying it's not a specimen by 14 컴컴. 15 DR. ABRAMSON: Okay. 16 MS. SHRADER: Could I just add one 17 thing to that? We're finding this to be a 18 problem with many of our IUD studies, but 19 most particularly, where you're looking at, 20 for example, infectious disease and you're 21 looking at organisms that are 컴컴 greater, 22 because if we can't go back and use the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 279 1 bank's samples -- and we just recently had 2 this experience, as a matter of fact. 3 We were able to find the total of 4 eight prospective samples worldwide over a 5 whole 컴컴 -- a yearlong 컴컴 cycle. We 6 can't get FDA approval for that process. 7 MS. LESS: Right, but it's 8 difficult because if we say okay, go back in 9 those patient records, you don't get 10 consent, is the public going to like having 11 FDA trouncing through their records without 12 their permission? 13 DR. LUMPKIN: I think part of it 14 gets to the issue it's not only an issue of 15 risks and a person -- you know, the 16 traditional informed consent of saying, you 17 know, I'm willing to undergo what risk it 18 is. This becomes a privacy issue, and it 19 gets not only into that, but it gets into 20 the privacy laws and in many situations, I 21 know it's not only us and the privacy laws 22 we have to enforce, when it comes to state BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 280 1 privacy laws sitting here, who lives in 2 Minnesota, with some of the toughest privacy 3 laws, you know, that there are. 4 The other thing that I think would 5 help -- and I'd be interested to hear what 6 you guys think on this issue -- one of the 7 things that we constantly struggle with is 8 this kind of gray area, and this goes more 9 to the 컴컴 authorization, but this gray 10 area between what is surveillance and what 11 is research and the issue of traditionally 12 we in this country have not required IRB 13 oversight or informed consents for 14 surveillance activities versus what we have 15 required for research activities and I think 16 in terms of what you were talking about; 17 you're going through and looking. 18 Are you really looking for the 19 patients, you know, or are you surveying the 20 data to try and get an overview of what 21 exists, you know, for the community at 22 large, and I think it's something that might BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 281 1 help clarify where that line is; might help 2 answer the question that you put forward. 3 DR. ALPERT: The other IRB issue 4 is on HDE and it's a difference issue. 5 MS. LESS: Right. 6 DR. ALPERT: It's the issue that 7 because HDEs go to market with limited, if 8 any, effectiveness data, a requirement was 9 put in for IRB and consent -- 10 MS. LESS: IRB. 11 DR. ALPERT: IRB. It was IRB and 12 consent originally and they just kept IRB so 13 that the hospital recognizes that this is a 14 very different kind of device. This is not 15 a fully-approved product, but one that has 16 some risks because of the way in which it's 17 felt on stage, actually, at which -- the 18 stage of development that it is in, and so 19 the question there is, you know, would 20 hospitals be willing and would the public be 21 willing to give that up as an issue for the 22 hospital knowing that a product is being BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 282 1 used that didn't go through the full common 2 FDA evaluation safety effectiveness, but was 3 something less because of the nature of the 4 product, and that is a burden. 5 IRB's 컴컴 is a real burden, 6 product by product, facility by facility, 7 and almost patient by patient because the 8 patients will be scattered, and that's 9 another one. If we're talking about IRB and 10 consent issues, that one ought to be in the 11 collection. 12 DR. LUMPKIN: Susan, you know, one 13 thing we've talked about, trying to compare 14 this figure to the process with, you know, 15 on the pharmaceutical site, with our 16 accelerated approval regs, which are kind of 17 the same thing where you're giving a full 18 approval to a product based on an 19 invalidated surrogated end- point, those are 20 for approval. There is no limit to the 21 profit a company can make on it. There's no 22 requirement for an IRB or informed consent. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 283 1 There is a requirement for 2 post-authorization follow-up and a process 3 for doing further evaluation and removing 4 the product if, indeed, the 5 post-authorization follow-up doesn't go, but 6 I think one of the questions might be, if 7 you want to put forward, on the device side, 8 you know, if we can treat it more like an 9 accelerated approval on pharmaceuticals, 10 we'd be willing for the follow-up kind of 11 situation, but I don't know. I don't know. 12 DR. ALPERT: I mean, again just 13 for the full discussion, the device site 14 already does a lot of required post- market 15 additional collection of data as part of 16 approval. HDE is still a little bit 17 different. So I don't know. I mean, that's 18 a real question for them. 19 MS. LESS: Is this additional 20 follow-ups with the same patients or another 21 cohort? 22 DR. LUMPKIN: It's both. It's to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 284 1 try to -- the data that you need to validate 2 the invalidated surrogate. It's based on 3 the fact that the invalidated surrogate is 4 thought to be reasonably predictive of 5 clinical benefit. If, at the end of the 6 day, no clinical benefit is shown, then 7 it's, you know, a discredit to the surrogate 8 and the product will be approved. 9 Blessedly, we've not had to do that so far. 10 The data has thus far, in all the ones we've 11 done, validated the surrogate and then that 12 becomes the surrogate that one can use 13 subsequently. 14 I mean, it's used for serious and 15 life-threatening illnesses, but again, this 16 is what you might want to think about as a 17 way to make the argument with the HDEs. 18 That's all. 19 DR. ABRAMSON: Okay. It's 2:30. 20 We'll take a 15-minute break, until quarter 21 to 3:00 and we'll finish up by 4 o'clock. 22 If I understood -- but I may not have BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 285 1 understood correctly -- can the FDA 2 combine -- two companies have essentially 3 the same device; okay -- can the FDA combine 4 the data on those two devices? 5 MS. LESS: It depends on the 6 market. With the 510(k), we were building 7 on one 510(s). If it's a 510(k) though, a 8 PMA, but they didn't 컴컴 belongs to that 9 company. 10 DR. ABRAMSON: Right. This is not 11 building on one. 12 MS. LESS: Right. 13 DR. ABRAMSON: This is two 14 difference companies. 15 SPEAKER: Joanne, could you speak 16 up just a little, please? 17 DR. ABRAMSON: Yes. Because 18 there's no patent -- 19 DR. ALPERT: There are patents. 20 DR. ABRAMSON: There are patents. 21 SPEAKER: There's no exclusivity. 22 DR. ALPERT: There's just no BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 286 1 exclusivity. 2 DR. ABRAMSON: Right. Well, let 3 me rephrase it. Because two devices may 4 come to the market at essentially the same 5 time, okay, can the FDA combine -- use data 6 from essentially the same devices? Can the 7 FDA combine those data? 8 MS. LESS: No. 9 DR. ABRAMSON: They have to look 10 at them separately? 11 MS. LESS: In the PMA, we have to 12 look at the data from that company. You 13 can't use somebody else's data. 14 DR. ALPERT: Unless the companies 15 agree. 16 MR. CONNAUGHTON: I'd like to 17 throw something out for discussion on this. 18 DR. ABRAMSON: Yes. 19 MR. CONNAUGHTON: Susan mentioned 20 this morning the importance of the materials 21 for kids; bio-compatibility information. 22 Can't we find a way that that information BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 287 1 can be made available? You guys don't have 2 to make everybody approve the same thing 3 over and over again and we could lose 컴컴 4 quicker? 5 MS. LESS: There are companies 6 that send a master file and we allow you to 7 refer to their master files that we don't -- 8 like with silicon; we don't have to keep 9 reviewing that same information over and 10 over. We just get access to that master 11 file. 12 MR. CONNAUGHTON: Can't we make it 13 more universal 컴컴 where we could shortcut 14 this situation to be done administratively 15 or before the law changes? 16 SPEAKER: Can you speak up? 17 MR. CONNAUGHTON: Can this be done 18 more widely, the use of this 19 bio-compatibility information so that we can 20 save a lot of time, whether it can be done 21 administratively or does there have to be a 22 change in the law? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 288 1 MS. LESS: We already have a lot 2 of master files in house. 3 MR. CONNAUGHTON: Yes. 4 MS. LESS: I mean, we can 5 encourage the use of them or encourage 6 sharing of them, but there would be a cost 7 associated with that. 8 DR. ALPERT: Because they are not 9 publicly available. 10 MS. LESS: Right. 11 DR. LUMPKIN: I think that's the 12 fundamental point he's asking. I mean, it's 13 one thing to have a master file that a 14 company gives another company permission to 15 look at -- 16 MR. CONNAUGHTON: To use, yes. 17 DR. LUMPKIN: -- and that's a 18 business relationship. I think he's looking 19 at basically saying once we have determined 20 that material is safe, is there a way we can 21 make that determination public so that other 22 people don't have to do it? Now, the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 289 1 question I would come back to you is if that 2 were the -- yes; there's a way to do it. 3 Congress can pass a law and give us 4 permission to it. The question I would come 5 back to you is if that were the system, what 6 would be the incentive for you to be the 7 first one to do it and spend the money and, 8 you know, find the safety and then everybody 9 else kind of piggyback on your expense? 10 MR. CONNAUGHTON: To get the 11 marketplace, and indeed we do have patent 12 laws. If someone infringes on our patents, 13 we can sue them for that, but it seems to me 14 these laws are to promote and protect the 15 public health. Let's just think about that. 16 Let's not worry about us fighting each 17 other. 18 DR. LUMPKIN: No, no, no. I'm not 19 saying that. I mean, I'm just saying, you 20 know, you have to think about the 21 consequences of this. 22 MR. CONNAUGHTON: I understand the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 290 1 consequences. 2 DR. LUMPKIN: The public health 3 question is if no company is willing to be 4 the first one, then how is the public health 5 served if nobody does it because they say 6 why should I spend the money and then all my 7 competitors get the benefit from the money I 8 spent to show that this material was 9 whatever? 10 That's an issue for you guys. 11 MR. CONNAUGHTON: Yes. 12 DR. LUMPKIN: I mean, we can 13 enforce whatever law Congress gives us to 14 do, but -- I mean, I would that would be 15 interesting to hear from your industry 16 colleague why he believes that might be a 17 good idea. 18 MR. CONNAUGHTON: I think many 19 would disagree, but I would submit to you it 20 wouldn't change our behavior one bit. 21 Getting first to market is terribly 22 important to all of us and I think that we BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 291 1 will continue to do that. 2 DR. LUMPKIN: Well, that's an 3 interesting idea. 4 DR. ALPERT: Only if the incentive 5 is large enough and then again you're back 6 to the -- 7 DR. ABRAMSON: We can't hear you, 8 Susan. I'm sorry. 9 DR. ALPERT: If the incentive is 10 large enough, I think the issue then comes 11 down to the same thing you've been talking 12 about. If someone's going to invest a 13 couple of million dollars in testing and 14 proving that a bio-material is appropriate 15 for neonates, aren't they going to want to, 16 in some way, recoup their research expenses? 17 DR. LUMPKIN: Right. 18 DR. ALPERT: That's what we've 19 been talking about in HDE and worrying about 20 the cost. You've got to at least recoup, 21 and Liz pointed out that there's a whole 22 industry that does just materials; BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 292 1 bio-materials, for the medical device 2 industry. Where's the incentive for them? 3 You know, how do they recoup if all of their 4 work is public and it's publicly available? 5 So I don't -- you know, we don't 6 develop our own materials, by and large. We 7 turn to materials developers who develop 8 materials and do a lot of the testing and 9 then we have to test it in our own uses 10 because when we process products -- and 11 depending on what else we put in them, and 12 sterilization and things -- we have to do 13 additional testing, but the basic bio- 14 materials are developed by bio-materials 15 companies and I think that's getting to 16 their issue; that's not us. 17 We already have trouble with some 18 of the big bio- materials people, like Dow, 19 who don't want their products used in 20 medical devices because they're not 21 protected. 22 MR. O'HOLLA: We're not even 컴컴 BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 293 1 of their production. 2 SPEAKER: Or a rounding 컴컴. 3 DR. ALPERT: We're rounding area 4 and they don't want to take the liability. 5 So if that then became also -- not only 6 that, but they couldn't charge us even to 7 utilize -- you know, they could only charge 8 us for, you know -- 9 MR. CONNAUGHTON: Well, we'd still 10 be buying their materials, Susan. 11 DR. ABRAMSON: Yes. Yes. 12 DR. ALPERT: But I think that 13 there's -- 14 MR. CONNAUGHTON: We all know 15 something's bio- compatible. We all just 16 have to go prove it again and waste 17 everybody's time. 18 DR. ALPERT: But I think that's -- 19 I think there's some real issues, as Nat 20 points out, on incentives and I think that's 21 a real problem and we don't even make 컴컴. 22 I'm not worried about us. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 294 1 DR. ABRAMSON: Okay. I want to 2 hear other issues that we haven't brought 3 up; barriers, other concerns, then I'm going 4 to try to summarize and get some response to 5 my summary and some response to proposed 6 feedback mechanisms because we're not -- 7 this is not -- obviously we're not solving 8 the problem today. 9 MR. O'HOLLA: But we're taking 10 good steps. 11 (Laughter) 12 DR. ALPERT: I'd just put on the 13 table I think a lot of -- as a barrier 14 challenge, not only for what we were working 15 on, you know, the focus here for pediatric 16 devices, but as we move forward, a barrier 17 and a challenge is going to be the right 18 kinds of communication and the right venues 19 for communication and I just want to put 20 down that that's an aspect of development. 21 Whatever we're going to develop, we need to 22 figure out how do we do this communicating? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 295 1 You know, it shouldn't take five or ten 2 years to get everybody in the room like 3 this. 4 So we need to really think about 5 how do we do this ongoing communication and 6 what are additional models to widen the 7 group that comes to the table? More 8 academics, more of the small companies; get 9 some of the bio-materials people. We need 10 to figure out what are the right 11 communications and coordination vehicles for 12 whatever we're developing? 13 I just want to, you know, keep 14 that as an aspect of this and an aspect of 15 the report; that that's one of the issues. 16 DR. ABRAMSON: Okay. Other 17 barriers, other issues that people want to 18 talk about that have not been discussed? 19 Yes? 20 DR. HAFFNER: Just one thing that 21 was touched on, but not really talked about 22 and that is if one takes as an assumption BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 296 1 many of these are orphan-type devices, then 2 what we've seen in the drugs arena is that, 3 at least for the most part, it's not the big 4 guys that were developing these products and 5 an entire industry has grown up around the 6 Orphan Drug Act. 7 Now, how one plugs that in to 8 devices, I don't pretend to have an answer 9 except that whatever those -- except that 10 with the incentives that were developed, 11 they appealed to companies that did not need 12 to, did not feel they need to make the same 13 degree of profit. Now, that's not entirely 14 correct. 15 At other times, we've also taken 16 credit for developing a large part of the 17 biotech industry where patenting was very 18 different, a whole different situation than 19 here, but those are just two things that 20 figured into the equation, for better or 21 worse, or non-information. 22 DR. ABRAMSON: We've spent some BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 297 1 time on the orphan issue, but do other 2 people want to talk about that issue? It 3 exists on the drug side. We have to deal 4 with it on my side probably more frequently 5 than the drug side. 6 Do other people want to bring up 7 any other issue that hasn't been raised that 8 we need to consider? 9 All right. Let me see if I can 10 summarize some points here. Number one is I 11 think there's general agreement, not about 12 my specific proposal -- but I want feedback 13 if I'm wrong -- but about a central 14 repository where the various groups that 15 have stakeholders that have issues or 16 concerns or create devices, would like to 17 create a central repository for storing? 18 Now, this central repository, in 19 one sense, could be just a place where ideas 20 come, in one area, and distributed out, sort 21 of a free idea, that could include a study 22 to especially non- orphan devices, where BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 298 1 there are substantial numbers that exist; 2 could be a place where studies are done. It 3 could be a place where education is done on 4 issues surrounding devices. It could be a 5 place where further discussion is done 6 surrounding patent laws and things like 7 that. 8 Let me hear anybody who doesn't 9 feel that a central repository, for lack of 10 a better word -- and again, I'm not stuck on 11 the idea that this has to be the equivalent 12 of a pharmaceutical academic center. 13 Anybody who feels that that's not a good 14 idea? 15 MS. JACOBSON: I guess personally 16 I still have a lot of problems with that 17 concept because I'm not exactly sure what it 18 means. I'm willing to go along with the 19 idea that we ought to be thinking about it, 20 but it's still a little too loosey-goosey 21 for me. 22 I mean, a central repository for BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 299 1 an industry that's so incredibly diverse, to 2 me -- I'm not sure it's workable. If you 3 mean by a central repository, you know, some 4 kind of a continuing, ongoing effort of 5 people coming together, I'd be willing to do 6 that, but not if you're thinking of a 7 physical place or a group of people that are 8 credentialed to take on the issue. That to 9 me is -- I don't think we're there yet, you 10 know. 11 DR. LUMPKIN: Just to ask for a 12 clarification. I mean, one idea that came 13 into discussion -- I don't know whether this 14 is No. 2 on your list or if this is part of 15 No. 1 -- people had talked about the 16 possibility of the AAP forming a committee 17 on devices like they have for drugs as a 18 center for the academicians. 19 Now, is that what you're talking 20 here or is that the second thing? A lot of 21 people thought that was a very, very good 22 idea. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 300 1 DR. ABRAMSON: Well, that is a 2 central repository. I'm trying to loosen up 3 the original 컴컴, which was an equivalent 4 for devices of the pharmaceutical. I'm 5 loosening that up to be a central repository 6 where ideas about needs for devices come in, 7 shared with industry, shared with the FDA, 8 just so that we're -- there are a 9 thousand -- one of the problems with drug 10 companies is you're talking about a dozen 11 that really create drugs. Here you're 12 talking about a lot of different companies 13 that might create a specific device that 14 somebody thinks about. 15 It is true that the academy could 16 have thought of that -- forming a group; I'm 17 not saying it would -- but it could form a 18 group that says all right. Here are 15 19 subspecialties represented. Think about 20 devices that you need. That's a part of 21 what a central repository could be. 22 MR. MUELENAER: I could see how BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 301 1 this would work for industries, too, so far 2 as in others. The repository, there's the 3 practicing clinician who just basically says 4 I have a need; find the solution. There's 5 also the practicing health care provider, 6 whoever, who says I've identified the need 7 and I have a somewhat immature solution and 8 I just can't do it on my own. I'd love to 9 partner with the smart guy in one of these 10 little companies and that's where you get 11 into a business agreement or an intellectual 12 property agreement where it's my idea, but 13 you've got the ability to take my idea and 14 do something with it. 15 So it's a win-win for both of them 16 and that's where having a repository where 17 the resources are all you know, you can 18 subscribe to be a part of that repository. 19 It could be little companies. It 20 could be big companies; little companies who 21 develop it to a point where then they 22 license it up to the big guys and then just BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 302 1 education. 2 Al and I were talking about that 3 earlier. A lot of us as pediatricians, 4 academic physicians, we don't understand 5 this whole industry. We just know we want 6 to take care of our patients and we don't 7 know how to talk to J&J or Medtronic. We 8 don't know you just don't show up with your 9 idea written on a napkin and they just let 10 you in the front door. 11 (Laughter) 12 MR. MUELENAER: But folks do that 13 all the time and they just get -- they get 14 frustrated, but there are mechanisms, that I 15 think could be put into place -- especially 16 for the orphan medical devices. You know, I 17 was thinking about -- you know, I mentioned 18 stents. There's definitely a need, in our 19 subspecialty, for airway stents. 20 The existing stents for adults 21 were developed to 컴컴 care for cancer, and 22 we want to put stents in babies that either BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 303 1 have to grow with that baby or it has to be 2 such that you can get it out without tearing 3 up the airway, and it just does not exist 4 right now. That's an orphan medical device. 5 There aren't enough babies out 6 there that are going to need these things 7 that J&J or whoever is going to invest the 8 millions to develop that product, but as 9 part of this whole process, if they were 10 given the incentive or a small company were 11 given the incentive to develop this and they 12 could get it through the approval process in 13 a reasonable way, there are definitely those 14 of us out there that will be users and our 15 alternative right now is to do operations on 16 kids and put them on ventilators for months, 17 if not years where, you know, a spring in 18 the airway could fix a lot of these 19 problems. 20 DR. HAFFNER: But is that a 21 science issue or a money issue or a 22 materials issue? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 304 1 MR. MUELENAER: It's a -- yes, 2 yes, and yes. 3 DR. ABRAMSON: Yes. 4 DR. ALPERT: That's exactly where 5 I was going to go. I think, Jon, rather 6 than saying a repository, why don't we 7 identify what are the things that we want to 8 accomplish and then figure out what the tool 9 is to accomplish it? So I think that that's 10 what we seem to be hearing, the goal being 11 an access place for the academic to put a -- 12 to raise issues and ideas; a resource place 13 for small companies to look at areas of 14 need. 15 I mean, if we identify what some 16 of those are, then maybe we can capture what 17 this thing looks like because I think the 18 idea of calling it a repository -- well, 19 it's not really. Is it a clearinghouse? 20 Well, not exactly. We're trying to deal 21 with all these different issues. 22 So why don't we just capture -- BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 305 1 let's capture what do we want to accomplish 2 because we've had enough discussion around 3 it, see if we can bullet point what we want 4 to accomplish and then figure out what 5 things lend themselves to one model; what 6 things lend themselves to another model, and 7 probably come up with two or three 8 difference things that need to go on maybe 9 simultaneously in order to move this process 10 forward a bit. 11 DR. ABRAMSON: It's perfect from 12 my standpoint because I see a set of 13 meetings coming out here dealing with some 14 fairly separate issues that eventually have 15 to come back together again, but I think, 16 just like today, we cannot try to cure all 17 of it at once and I think it's going to take 18 subgroups, and I don't mean to eliminate 19 who's here, but it's going to take subgroups 20 of people taking on these kinds of issues to 21 then come back at some point and figure out 22 where we are. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 306 1 I'm sorry. Somebody raised their 2 hand. 3 DR. HAFFNER: No. I was 4 stitching. 5 (Laughter) 6 DR. HAFFNER: But one of the 7 things that was not brought up today is 8 that, from an academic perspective, the FDA 9 does have a grants program in orphan 10 products. We fund promising devices in 11 drugs and then we help find companies to 12 further develop them. So, you know, if the 13 science exist, then there are admittedly 14 limited but mechanisms and Sarah is the 15 chief of that, to allow it to go forward, 16 and a few -- Bob Campbell's sitting there; 17 knows about our grants program firsthand -- 18 but we have developed other devices and I 19 don't think any of the ones that are 20 approved, that came through our grants 21 program, are for kids, but that certainly is 22 an avenue when the science already exists. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 307 1 DR. ABRAMSON: Orphans are very 2 important, but this is not limited to orphan 3 devices, is it? 4 DR. HAFFNER: No, no; of course. 5 I'm just saying that that's something that 6 wasn't raised today and does exist, albeit 7 the funding is extraordinary. 8 DR. ABRAMSON: Yes. 9 DR. JENKINS: Just the other 10 models are put on the table that already 11 exist, but service programs funded through 12 the AHRQ, that's the Centers for Excellence 13 and Research and Therapeutics, that has a 14 mandate to develop public-private 15 partnerships around the appropriate use of 16 therapeutics and does cover devices, 17 although it's heavily weighted towards drugs 18 right now, just as it exists. 19 There is a pediatric cert which 20 has very little device component right now, 21 but does have central repositories, 22 collections of experts, and an ability to be BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 308 1 very open door about who's in and who's out 2 and for what purposes people are a part of 3 some projects and not others. 4 So as a Federal model for some of 5 what we're talking about, it might be worth 6 thinking about a pediatric device service or 7 something along this line. 8 DR. ABRAMSON: I've talked to some 9 of them and I think they'd be extremely 10 important to bring to the table because they 11 feel things are missing also out of their 12 mechanisms that need to be dealt with and I 13 think they'd be 컴컴. 14 DR. JENKINS: You mean the peds? 15 DR. ABRAMSON: Yes, yes; 16 pediatrics. Other comments? 17 MR. GREINWALD: Jon? 18 DR. ABRAMSON: Yes? 19 MR. GREINWALD: One thing that 20 kind of comes to mind is that our overall 21 goal is to identify needs and bring 22 potentially beneficial devices for pediatric BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 309 1 use in the clinical practice. Everybody 2 that's -- there's a general assembly of kind 3 of why we're here. 4 What role does the AAP want to 5 have in this because somebody's got to drive 6 the train and is the AAP the organization 7 that can all encompassing look at not only 8 surgical subspecialties, medical 9 subspecialties, medical practitioners? Can 10 that, as a -- whether this is part of a 11 working group that starts or a formal 12 committee that is here to deal with the 13 issues that we're talking about? 14 Information clearinghouse, resource 15 clearinghouse, and then eventually beginning 16 of trial centers and those kinds of things 17 and I think that -- one of the first things 18 they need to decide is is the AAP, as an 19 organization that has an outreach, bigger 20 than all of us put together? Is that the 21 organization that needs to drive this as the 22 organization that's there to look at the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 310 1 pediatric health more than anybody? 2 DR. ABRAMSON: I don't know. 3 Marilyn, you might want to speak to this. I 4 think that the Institute of Medicine is 5 simultaneously thinking about this issue and 6 is going to issue a report at some point. 7 Is that correct? 8 MS. FIELD: Yes. 9 DR. ABRAMSON: Yes. 10 MS. FIELD: About a year from now. 11 DR. ABRAMSON: Yes. 12 MS. FIELD: But that's post-market 13 surveillance and we have to look at this in 14 the context of the whole innovation 15 trajectory to see how it fits, partly to 16 deal with the question that's been raised so 17 often here is that you don't want to do 18 something at Stage X that creates a 19 disincentive upstream for the thing you want 20 to accomplish, but I don't think that will 21 necessarily -- I mean, I've been thinking 22 about some priority- setting issues in that BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 311 1 context, but it's a -- the focus is a little 2 further down the line and although we're 3 trying to think of the whole process, it's 4 still -- you know, our focus is on the FDA 5 post-market surveillance system. So that 6 limits -- I mean, you have to answer those 7 questions so that limits some of what we're 8 doing. 9 DR. ABRAMSON: I guess my answer 10 to this is the following: In my mind, 11 having watched this, I think the AAP drove 12 the pharmaceutical regs and laws and stuff 13 like that and I don't see a better group to 14 do it, but I'd be interested in anybody's 15 opinion. 16 I'm not through yet, by the way, 17 with other things, other subcommittees, I 18 think that have to be created, so don't 19 think this is the end of it, but can anybody 20 else think of any other groups that could 21 drive this process? 22 MR. QUATRANO: I was going to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 312 1 comment on a group. I was just going to say 2 that there's a couple of other models we 3 might want to look at from experience and 4 one is, of course, the small business 5 program at NIH, which people mentioned, 6 hasn't, quote unquote, partnering or 7 matching or trying to identify areas that we 8 can get companies that are interested in 9 sort of doing that. It would be interesting 10 to look at that to see what the success rate 11 is. 12 On another level, for example, 13 there was, to a large extent, which is 14 called the BCON, which is bioengineering 15 consortium at NIH, which was all the 16 participating institutes in terms of looking 17 at sort of this trans-NIH types of 18 initiatives and probably most of you are 19 most familiar with those in terms of the 20 roadmap activities of the recent 21 directorate. So that's another level that 22 we may look at. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 313 1 The third level, which I haven't 2 seen a lot of here would be, for example, 3 out of the Office of the Secretary for all 4 HHS agencies or across them relative to -- 5 so, for example, CMS has a lot to do with 6 reimbursement and look at that level in 7 terms of your 컴컴 device, seeing the 8 devices go all the way from initiation right 9 through -- into development and also 10 technology transfer, which is getting 컴컴, 11 which is a problem. 12 So those are just three 13 suggestions. 14 DR. ABRAMSON: Very good. Anybody 15 else want to add into the idea about how 16 we'll process this whole sets of issues? 17 Not one? Okay. Let me take on the second 18 issue, and that is -- I think it's fairly 19 clear that we are going to need to 20 prioritize -- whatever we do -- we're going 21 to need a system to prioritize what we 22 studied and I guess maybe the NIH and the BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 314 1 FDA already feel like they have a system 2 that encompasses people feeding in 3 information about priorities and then making 4 a decision on how to prioritize all these 5 expert groups, and the question is are you 6 comfortable that that's -- is anybody 7 comfortable that that will work or do you 8 need to rethink that whole issue for 9 devices? 10 DR. LUMPKIN: I think, Jon, when 11 you start thinking of prioritizing for what? 12 I think people need to be clear. You know, 13 what the group is doing right now is to try 14 to prioritize those off-patent 15 pharmaceuticals that cannot benefit form the 16 exclusivity provisions in order for FDA and 17 NIH to issue written requests for the 18 publicly funded studies. 19 You know, the prioritization of 20 what companies do is their business. I 21 mean, the companies are going to decide, 22 rightly or wrongly, what is in their best BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 315 1 business interest and prioritize from that 2 perspective what they do. So I just don't 3 want anybody to think that, you know, we 4 have this way of prioritizing what is done 5 in pharmaceutical research on pediatrics. 6 It's not; it's driven clearly looking at the 7 publicly funded aspect of it. 8 It is an interesting mechanism, 9 nonetheless, of trying to go through that 10 exercise to try to prioritize those products 11 for which we might want to spend public 12 dollars. 13 MS. IRELAND: I was just going to 14 say I see it the same way. I see this kind 15 of coming in three tiers. I can't see what 16 Elaine wrote up there, but I see the first 17 tier as stimulating the market by providing, 18 you know, conversations between the 19 manufacturers and the physicians. So the 20 first 컴컴 is going to be where can the 21 market actually work with a little bit of a 22 push to have people talking more? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 316 1 The second one would be where the 2 market as it is, is it going to work that 3 well, but perhaps you can provide incentives 4 to manufacturers to again stimulate the 5 market. 6 The third would be all those not 7 met by one or two or really the government 8 needs to step in. In that case because 9 you've got public funds going, you do have 10 to say what the priorities are. 11 DR. LUMPKIN: Right. 12 MS. IRELAND: The other two 13 priorities will fall out because they're are 14 going to be market-driven solutions. 15 DR. ABRAMSON: You missed one. 16 The idea is there are lots of things on the 17 market right now that may or may not be 18 safe; may or may not work and industry will 19 pick new things to study or not study, based 20 on possibilities, but it's unlikely, I 21 think, that they'll come back for the old 22 stuff to do those studies that are necessary BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 317 1 just in case, from our standpoint, and so 2 that's the question and it sounds to me like 3 there's not an established mechanism that 4 the NIH or the FDA would feel comfortable 5 about right now that would work. So we have 6 to give that some more thought. 7 DR. LUMPKIN: The players who are 8 in the pharmaceutical prioritization group 9 would not be the right players for the 10 device 컴컴. 11 DR. ABRAMSON: Right. Oh; 12 absolutely. 13 DR. LUMPKIN: I mean, we clearly 14 have to get the right players to do it. 15 DR. ABRAMSON: I will put out a 16 point of view and let industry react to it. 17 I think industry has to come back to us and 18 propose things that might work for them to 19 incentivize them to study not only orphan 20 devices, but other devices, whether they're 21 often or not, that we see as a need that 22 industry right now doesn't think it can BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 318 1 handle for whatever reasons. 2 What are the things that industry 3 needs to get those pediatric devices for 4 children made and made safely and 5 efficaciously? What are those? 6 I don't think personally we're in 7 a position to make those proposals. I think 8 you guys are and we can look at them and 9 comment on it. 10 DR. ALPERT: You're talking about 11 identifying the right incentives? 12 DR. LUMPKIN: Yes. 13 DR. ABRAMSON: Yes, yes. 14 DR. LUMPKIN: For big companies, 15 small companies, and then the industry as a 16 whole. 17 DR. ALPERT: They will be 18 different? 19 DR. LUMPKIN: They will be 20 different, yes. 21 DR. ABRAMSON: So comments on 22 that? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 319 1 MR. O'HOLLA: I think that's 2 absolutely right. I already had it down 3 before you even said it. 4 DR. ABRAMSON: So there are at 5 least tow and maybe three subcommittees 6 here; prioritization of things that are 7 already on the market -- I actually think 8 it's a separate issue from the central -- 9 the first issue. Let me hear from others 10 about other things that people think need to 11 be up there, need to be thought about, need 12 to be considered as we move along. 13 DR. LUMPKIN: I thought I heard 14 there was also a group of things that people 15 thought were kind of corrections that needed 16 to be made to presently existing ways of 17 doing things. One of them is looking at the 18 HDE program of whether to take away the 19 requirement for the IRB and the prohibition 20 on the profit. One was looking at the 21 IRB -- inconsistencies in the IRB 22 requirements -- between NIH and FDA as a BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 320 1 disincentive. 2 One was looking at the laws that 3 prevent us from declaring a bio-material as 4 generally regarded as safe so that people 5 could use it and that that's a redundancy 6 and a disincentive. So I mean, it might be 7 a group that looks at some of these very 8 specific things that might need to be 9 tweaked to the way that we're doing the 10 present system. 11 DR. ABRAMSON: I don't know what 12 patents -- patents seem to fall under the 13 issue of -- 14 DR. LUMPKIN: Incentives. 15 DR. ABRAMSON: -- incentives or 16 the issues that you raise, but I think 17 patents have to be up there. I don't think 18 we can avoid that issue and come out with a 19 better set of circumstances. 20 MR. O'HOLLA: I would add to the 21 HDE thing. We're looking at the number? 22 DR. LUMPKIN: Yes, the number. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 321 1 MR. O'HOLLA: Okay. 2 DR. LUMPKIN: Good point. 3 MR. O'HOLLA: The patient numbers. 4 DR. ABRAMSON: Now, one of you had 5 proposed a survey, and I think there's lots 6 of interesting data. I'm not sure we can do 7 this survey, but we might chat about what a 8 survey would look at if we did one and we 9 could fund it and what you'd want to know. 10 Obviously, one thing a survey 11 would want to know is what device is needed, 12 what devices are out there that -- those 13 컴컴? I mean, there are a number of things, 14 but does anybody want to talk about a survey 15 or do we want that to come out of the 16 groups' discussion, thinking about what is 17 needed? 18 DR. CAMPBELL: Yes. I don't think 19 it's a big 컴컴. I think each president of 20 each subspecialty group could poll the 21 membership in an e-mail and get feedback. 22 Then there'd be help on probably BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 322 1 standardizing questionnaires, so we'd get, 2 you know, uniform data, but I don't think it 3 would be a huge task. I don't know about 4 surveying industry and their feedback, but I 5 think from the medical end, that would be 6 one way to do it. 7 DR. ABRAMSON: I want to make 8 clear one thing because they actually did 9 try to do a little bit of this. The 10 understanding of pediatricians -- I'd 11 probably say the same thing for family 12 practitioners about devices -- is nowhere 13 what it is for drugs; nowhere near, and I 14 don't think a lot of pediatricians actually 15 understand. Now, the subspecialists may 16 have a better understanding, but I'm not 17 even clear on that. 18 Elaine, you may want to talk a 19 little bit about when you initially 20 contacted subspecialty groups about the 21 issue of devices. 22 MS. VINING: They had not given it BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 323 1 a great deal of thought. I think there's 2 not a great deal of understanding about that 3 and actually I think that some of the 4 discussion today is about trying to 5 understand what the unmet needs are and the 6 reality of the pediatric world is that you 7 makes things happen when there isn't a lot 8 of choice, and so I don't know that a lot of 9 people are looking at things as unmet needs. 10 They just get it done and they are using 11 feeding tubes to be part of child care and 12 whether they view that as an unmet need or 13 not, they know that it is a need and they're 14 going to get it done. 15 So I'm not sure -- I mean, the 16 challenge or the survey is going to be how 17 to ask the questions to get the kinds of 18 helpful information that will lead us to the 19 pathways that we need to start taking, but I 20 think people have not given this a lot of 21 thought and a lot of time because they're 22 getting it done and they don't even know BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 324 1 what they don't know. 2 We had a little bit of a different 3 baseline when it came to drugs, but I think 4 we're starting -- you know, further back the 5 device is going to come, thinking about 6 kids. 7 DR. ABRAMSON: Okay. Going 8 forward. Oh; I'm sorry. Go ahead. 9 MR. O'HOLLA: Just one thing that 10 was on my list that we didn't get up there 11 was we had a discussion this morning about 12 looking at the approval criteria, what valid 13 scientific evidence is, and how to apply 14 that to some of the pediatric uses in a 15 creative way, much along the lines that 16 Dr. Lumpkin pointed out earlier. In fact, I 17 see it almost as some of the critical path 18 document leading into new ways of looking at 19 things for smaller pediatric groups, that 20 kind of thing. 21 DR. ABRAMSON: All right. Any 22 other comments, thoughts? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 325 1 MR. O'HOLLA: The comment about 2 the survey, I just wanted to make one 3 comment. It seems to me that if we're going 4 to do a survey, you probably need a group to 5 decide what is it? What do we want to find 6 out from this survey and develop a question 7 컴컴. I have a general idea that we've -- a 8 survey would provide sort of grace, but I 9 don't know what that information is. 10 DR. ABRAMSON: All right. Elaine, 11 I guess we need your help now in that -- I 12 think we delayed one 컴컴. Oh; I'm sorry. 13 MR. QUATRANO: No. I just have a 14 point of clarification. Going to the 15 practitioners and having a survey at some 16 point is useful. Are you going to match 17 that against any databases of the agencies 18 that are currently supporting the device at 19 all? 20 DR. ABRAMSON: I mean, these are 21 all things that absolutely need to be 22 thought about it before we make out a survey BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 326 1 and try to get the maximum information out 2 of it. So we are not proposing any 3 specifics here. I really want to finish up 4 in the next half an hour. 5 I'm sorry. 6 MS. IRELAND: Just to follow up on 7 the last point: That might be interesting 8 information to get from FDA if you're moving 9 forward with changing your ability to 10 collect 컴컴 pediatric devices. If you can 11 give us some thoughts on how whatever we 12 might collect in the survey might link with 13 what information you're gathering as you 14 move forward. That would be useful, I 15 think. 16 DR. ABRAMSON: I think it cleanly 17 lays one of the issues on the industry's 18 table, and so I don't know what you want to 19 do and I guess we'll act as the central 20 repository for feedback -- the academy 21 will -- just for the moment of, you know, 22 what you want to do. How does industry -- BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 327 1 and I'm not asking for an answer today -- 2 how does industry want to get together and 3 propose back to us things that would be 4 helpful from their standpoint in the 5 development of devices? 6 MR. O'HOLLA: In the development 7 of devices or in the incentives 컴컴? 8 DR. ABRAMSON: The incentives are 9 what I'm asking. The incentives to develop 10 devices; how about that? 11 MR. O'HOLLA: Question: How do we 12 want to get back to this group? How do we 13 want to communicate after we get answers to 14 what would be appropriate incentives to 15 develop these kinds of devices for industry? 16 MS. JACOBSON: I don't know. I 17 mean, I think we have to go out and ask -- 18 poll our members and how do you find this 19 컴컴? 20 DR. ABRAMSON: Well, I guess the 21 question I asked of you is are you just 22 going to feed us back everything your BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 328 1 members say or are you going to go through 2 it with some thought about it? I'm not 3 trying to answer that question for you. I'm 4 just simply saying that someone's going to 5 have to do a survey or a set up a 6 conference. 7 MS. JACOBSON: I think we need to 8 go back and talk about how we're going to do 9 it and how 컴컴. 10 DR. ALPERT: What kind of a time 11 frame are we talking about here, too? 12 DMS. JACOBSON: Yes. 13 DR. ABRAMSON: Well, you'll have 14 to tell us when you think you can get it 15 done. 16 DR. ALPERT: No, not just for 17 this, but for the -- you know, are we trying 18 to -- 19 DR. ABRAMSON: We'll come back to 20 that. 21 DR. ALPERT: -- come back with a 22 couple of things in a two months? Three BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 329 1 months? 2 MS. JACOBSON: I mean, you're 3 basically asking us to go back to our ideas 4 and what we incentivize in terms of 컴컴 5 products; right? 6 DR. ABRAMSON: Yes. 7 DR. ALPERT: That's right. 8 MS. JACOBSON: We probably have 9 to -- we may want to take this to our board 10 and talk to them as well. 11 DR. ALPERT: We have lots of other 12 players that need to speak. 13 MS. IRELAND: Well, I guess one 14 thing we have hanging over us, of course, is 15 the legislation that's moving forward, with 16 or without the information, but I mean, it 17 certainly isn't the only course of play 18 here, but there is legislation that's being 19 considered by Congress. 20 MS. LESS: There's the report on 21 barriers that we need to do. 22 MS. IRELAND: There's the report BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 330 1 to the FDA, too. 2 MS. JACOBSON: The comment period 3 for the FR notice closes at the end of 4 August. 5 DR. LUMPKIN: But realistically, 6 though, do you think anything's going to 7 happen prior to the election and prior to 8 the new Congress being seated? 9 MS. JACOBSON: Jeannie, you can't 10 hear anything you're saying back here. 11 DR. LUMPKIN: Yes. 12 MS. IRELAND: Oh; I didn't know. 13 MS. JACOBSON: I'm sorry. I 14 wasn't speaking at that time. It was 15 actually Mac asking a question. 16 MS. IRELAND: No, but I mean 17 before. What is it that -- I don't know 18 what you said. 19 MS. JACOBSON: Oh; I'm simply 20 saying when we're thinking about the time 21 frame for this, there's two things that are 22 going on: There is the FDA's requirement on BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 331 1 FDA to issue a report. The Federal Register 2 notice says they have to get comments by 3 August -- 4 DR. LUMPKIN: 20th. 5 MS. VINING: End of August. 6 MS. JACOBSON: -- end of August. 7 There is also legislation moving forth. 8 There are a number of people in the room 9 that have been involved in this. We have 10 this, you know, with every bill, there's no 11 guarantee when something might or might not 12 happen. It could move very quickly. It 13 could move next year. 14 DR. LUMPKIN: Yes. 15 MS. JACOBSON: But there are 16 several bipartisan interests in the issue, 17 which gives it more legs than -- 18 DR. LUMPKIN: Than most. 19 MS. JACOBSON: -- I think one 20 thing that would be -- 21 DR. JACOBSON: So you're say8ing 22 sooner rather than later? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 332 1 DR. LUMPKIN: Yes. 2 MS. JACOBSON: So you're saying 3 sooner rather than later with that? 4 DR. LUMPKIN: Yes. 5 DR. ALPERT: I would agree with 6 that. 7 MS. IRELAND: Yes; but the thing 8 is that it may be very well that we can't 9 move fast enough to inform them. If we 10 could, we'd 컴컴 legislation, move forward 11 with information rather than without it. 12 MS. VINING: Well, one of the 13 things that this group may want to -- 14 MS. IRELAND: Not that they've 15 ever held anybody back. 16 DR. ABRAMSON: Exactly. 17 MS. VINING: One of the thing that 18 this group will want to think about is 19 whether we are at a point where we think 20 that there is something reasonable to offer 21 the Congress or do we think that we want to 22 suggest to the folks on the Hill that we BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 333 1 need more time to think about this in a 2 thoughtful, thorough manner. I mean, if 3 that's the case, that's a message that I 4 think would be powerful to take back to 5 folks. 6 MS. LANGLEY: The other thing is 7 there is -- you know, if you do have a 컴컴 8 for 컴컴, I mean, the comment is the logical 9 deadline. Quite frankly, I've done 컴컴 10 happens in the next three weeks and then 11 it's going to happen until, you know -- 12 after September, it's probably annoying, the 13 session, so we're in some -- we have 14 immediately like a big 컴컴 and a 컴컴 when 15 Elaine's not here to 컴컴; relevant, you 16 know, to say maybe not now. We have an 17 obvious deadline and we 컴컴. So maybe the 18 focus was on that, but if you're familiar 19 with that of (?) 20 MR. O'HOLLA: In answer to your 21 question, when you said it, I kind of 22 breathed a sigh of release for one reason? BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 334 1 I've seen pediatric proposed legislation 2 floating several times and the last time we 3 got some, you know, language, that you know, 4 well, study this. We'll do this. If we 5 move forward now -- I mean, I would bet 6 today, I think we've accomplished more today 7 than we have in two years in talking about 8 this in separate groups, and if we move 9 forward with, for example, let's fix the 10 IVE -- the HD provision and let the 11 companies make a profit. 12 You know why? They're going to 13 think they vexed it. So if we think we're 14 going to have a better solution, we don't 15 get a lot of bites at that apple on the 16 Hill. Once they think they've fixed 17 something and they think they're done and 18 they're moving onto something else, I would 19 urge that we seriously consider looking at 20 what are the things we should be asking for 21 so we don't have to go back and convince 22 them that we just took a mid-step the last BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 335 1 time. 2 DR. ABRAMSON: Other comments on 3 that? All right. Who would the NIH and the 4 FDA, like at the table -- I think they'll 5 want more than just themselves at the table 6 to correct some of those systemic issues. 7 Some of those systemic issues in the 8 existing regulatory issues. 9 In a subcommittee, again, so 10 that 3-D -- I've got to process all of this 11 and I will see the potential of moving 12 forwards with what recommendations we can 13 sit and think about as our whole group or 14 maybe others at the table, but who else 15 would you like at the table? 16 DR. LUMPKIN: I mean, I can't 17 imagine any of the groups not being here. I 18 mean, the industry clearly needs to be 19 there. The academics clearly needs to be 20 there. We just look at issues -- I really 21 do think the patents ought toot be under the 22 incentive. That was not something we're BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 336 1 particularly good at and it probably 2 shouldn't be within this group. It's 3 systemic, it really is, an incentive group. 4 Yes; okay. Jeannie and people, do 5 you see a role in these particular issues 6 for the advocacy group? 7 MS. IRELAND: In the systemic 8 issue? 9 DR. LUMPKIN: In fixing the 10 regulatory pieces over there on the other 11 side is kind of dated -- 12 MS. IRELAND: I think so, yes. 13 DR. LUMPKIN: Okay. All right. 14 Yes. I think, you know, it's all 15 stakeholders. I can't imagine not having 16 any of them. 17 DR. ABRAMSON: All right, then I 18 would propose that the Academy and again, 19 Marilyn, and I think we'll have to think to 20 think about whether you got one role and, 21 you know -- but the Academy 컴컴 in picking 22 out this issue of 컴컴 various proposed BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 337 1 models to the table to be discussed in the 2 subcommittee. 3 It then brings back to this big 4 room about what the pros and cons are and 5 that orphan law is very well and you just 6 simply whisked her in time -- the various 7 models -- a lot of things naturally fall off 8 the table or got 컴컴 on the table or get 9 컴컴 on the table. I've watched it many 10 times. So we could 컴컴 in a group to 11 consider just the pros and cons without a 12 specific recommendation, in going back. 13 When you say this group, think 14 about whether it's the model by which we get 15 better exchange of information and ideas. 16 Any thoughts about that? 17 MS. VINING: When you're talking 18 about the 컴컴, you're talking about how to 19 bring this group together and exchange ideas 20 and come up with an evaluation of some 21 things? 22 DR. ABRAMSON: Well, there have BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 338 1 been various models proposed for 2 evaluating -- for exchanging information 3 about what's needed in devices, for 4 potentially doing studies with devices for 5 educational issues around devices. I think 6 it's time we put together a group that would 7 consider these various models. We could 8 bring in, for instance, the group in North 9 Carolina and hear what things work and don't 10 work from them. 11 It's one multiple model that has 12 been proposed here and it's not necessarily 13 mutually exclusive. It may be a combination 14 of two or three. 15 DR. ALPERT: I'm not sure what 16 models we're talking about. Are you talking 17 about things like the CERTS model and the 18 small business model? 19 DR. ABRAMSON: Exactly. 20 DR. ALPERT: The network model? 21 DR. ABRAMSON: Exactly. 22 DR. ALPERT: I'm just trying to BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 339 1 figure out what models would they be that 2 you would be doing pros and cons on? 3 DR. ABRAMSON: Those models. 4 DR. ALPERT: So the things on 5 existing programs -- 6 DR. ABRAMSON: Yes; existing 7 programs are newly created programs that we 8 have. You know, if you want to call the 9 pharmacy group an existing model which we 10 would then -- yes, but those would be the 11 models to discuss the pros and cons. If I'm 12 hearing you right, I think it's going to be 13 either a combination of a couple of models 14 or two or three models, you know, or two or 15 three things together. 16 DR. ALPERT: Okay. It just seems 17 to me that we need to be clearer about what 18 models we want the 컴컴 to talk about. 19 Otherwise, it's 컴컴 we're going to need. 20 Are there specific things that we 21 want to capture here today to give to 22 somebody to start talking about pros and BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 340 1 cons? 2 DR. ABRAMSON: Yes; we will. 3 DR. ALPERT: I think you need to 4 be exclusive. 5 DR. ABRAMSON: We will talk about 6 the fact that industry doesn't feel or a lot 7 of the small companies don't feel like they 8 have access to the ideas. A lot of 9 individual physicians don't feel like their 10 ideas -- they have nowhere to go with them. 11 Those are the kind of issues that this group 12 would then think about; what model might 13 work to make this easier. 14 DR. ALPERT: So it's to identify 15 the models as opposed to just 컴컴? 16 MS. VINING: I think what you're 17 suggesting is take some of the elements that 18 we came up with today, in terms of 19 identification barriers, some of the 20 concerns raised, put those down at the 21 starting point and then figuring out if 22 models that exist already either to the 컴컴 BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 341 1 to the PPO, either the small business 2 program or the orphan drug have elements 3 that are going to be able to address that. 4 Is that it? 5 DR. ALPERT: So it's sort of 6 matrixing and then seeing where it goes. 7 MS. VINING: Okay. I mean, let's 8 see what the problems are and let's see if 9 there are existing solutions. If not, where 10 are the gaps and if the gaps are a set of 11 issues or if the gaps are just some 12 regulatory issues how to try and modify 13 things and propose solutions. 14 MR. QUATRANO: I might encourage 15 the group that's going to be thinking about 16 this to look at -- and I think what was 17 suggested earlier which was this issue about 18 new licenses and so forth and existing ones 19 and applying maybe the models to them versus 20 sort of nesting it within because I think 21 that there will be some characteristic and 22 there may be a priority relative to what BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 342 1 this group would like to do in terms of some 2 areas; to think about it at least that way 3 or possibly cutting it that way. 4 DR. JENKINS: As a follow-up to 5 that or a subset, too, I think, for example, 6 for a new production, there's a distinction 7 between products which could also test the 8 use for kids versus the development of new 9 products that really don't have an adult 10 adaptation. 11 So if both of the subsets I think 12 could break that out, that would be very 13 helpful to us. 14 DR. ABRAMSON: Okay. 15 DR. LUMPIN: Can I just make one 16 comment, and I know this is something that 17 Elaine is very, very aware of and sensitive 18 to, but since those of us who are from the 19 Executive Branch are all career members of 20 the Executive Branch and not political 21 members, you know, I think it's important 22 how the work of this committee is portrayed. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 343 1 Obviously, it's extremely inappropriate for 2 us to make recommendations to Congress. 3 Our job is to execute the laws 4 that Congress passes and we always get into 5 trouble if we are seen to be recommending 6 things to Congress. Congress asks us for 7 our technical assistance when they want it 8 and so I think as we go forward, you know, 9 the way FDA and NIH and any of the other 10 Executive Branches are portrayed as part of 11 this effort will be something that we need 12 to look at and I know you're sensitive to 13 that, but let's just kind of keep it in mind 14 as we go forward, because we all want to 15 stay employed. 16 (Laughter) 17 DR. LUMPIN: Thank you very much. 18 MS. LANGLEY: In keeping with that 19 sensitivity, I notice that there is a 20 Republican Majority staff -- in my packet 21 anyway -- there's something that is 22 descriptive of what they've been 컴컴. If BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 344 1 there is the same thing in the packet as to 2 컴컴. 3 MS. VINING: 컴컴. 4 MS. LANGLEY: It would be useful, 5 you know, in that they talk to a myriad of 6 people, too, to have that as background for 7 these groups as they go forward, just for 8 the -- to look at those -- 9 MS. VINING: If they create one, 10 we will happily provide it. 11 MS. LANGLEY: Thanks. 12 DR. ABRAMSON: Other comments or 13 questions? Do you have some sort of 14 deadline in mind for these three groups to 15 report back; work on that? 16 MS. VINING: Something that's 17 realistic and 컴컴. What's the timing on 18 this? I mean, would it be valuable to 19 have -- I'm trying to think of how to help 20 the FDA out in their response to Congress. 21 SPEAKER: Well, we have to -- 22 SPEAKER: But we're going to have BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 345 1 to end up having this broken into subgroups 2 with people who are going to actually give a 3 little bit more thought to this and that's 4 going to take time. I mean, we're already 5 at June 28th, with vacations and everything 6 else fast approaching, and a deadline of 7 August 20th, is it? 8 DR. LUMPIN: But, Joanne, isn't 9 this part of what we can write in our -- 10 that, you know, we've heard in response to 11 the government register notice, we've had 12 this kind of a public meeting. The issues 13 that have been brought up are X, Y and Z. 14 You know, the solutions to those means the 15 barriers have been identified, but the 16 solutions are yet to come kind of thing. 17 You know, it's still early in the process. 18 I mean, there's no expectation 19 that this paper is going to say here are all 20 the barriers and here are all of the 21 solutions. I can't imagine that. 22 MS. LESS: Right. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 346 1 DR. LUMPIN: I mean, that might be 2 the expectation, but that can't be the 3 reality. 4 MS. LESS: Right. There's 5 supposed to be a presentation on the 6 barriers and the recommendations, but I 7 don't think that there would be anything 8 wrong with us saying that, you know, we've 9 had some preliminary meetings, but we still 10 need to explore it some more. 11 DR. LUMPIN: People say there are 12 a lot of potential areas that need to be 13 looked into and developed further and people 14 are doing this and, you know, stay tuned, 15 kind of thing. 16 DR. ALPERT: You're saying that's 17 the recommendation 컴컴 the area as work; 18 that need to be done? 19 DR. LUMPIN: That need to be done; 20 yes. These are areas that needed to be 21 further explored; that kind of thing, that 22 people are -- BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 347 1 MS. VINING: I think we have an 2 ongoing commitment by groups around this 3 table to continue the discussions and 4 explore the solutions. 5 DR. ABRAMSON: Yes. 6 MS. VINING: I'm uncomfortable 7 giving it a timeline. 8 DR. ABRAMSON: Yes. Correct me if 9 I'm wrong, but having moved in the academy 10 structure for a while now, you do actually 11 have to take this idea back to the board and 12 make sure that they're willing to 컴컴 this 13 like they were willing to 컴컴 the drug 14 issue. 15 (Laughter) 16 MS. VINING: You think Congress is 17 tough. 18 (Laughter) 19 MS. IRELAND: Yes. I can't 20 remember when we -- it's not going to be 21 until mid-fall, so for us to bring this back 22 and get a response, and that doesn't mean BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 348 1 that we can't continue to work along the 2 way, but some of the recommendations about 3 establishing new committee structures within 4 the academy and a variety of other things 5 need to be 컴컴. 6 Let me ask you if you have the 7 time frame we're expected to meet? I guess 8 컴컴 deadlines; right? 9 컴컴 release that before August 10 컴컴. 11 MS. VINING: Do they? What are 12 peoples' availability? Is this the right 13 group? I mean, do you think, from your own 14 group perspective that the right people are 15 at this table right now? 16 I mean, I thought -- no; I thought 17 that we were missing some of the small 18 companies and their input. I thought that 19 perhaps we needed some other biochemists 20 and -- we've got bioengineers -- but a 21 variety of other people are sort of missing 22 in the -- BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 349 1 MS. DORMAN: Why don't the three 2 of us and Ann -- all four of us -- kind of 3 sit down and kind of flush that out in the 4 next couple of days and then get that 5 information to this entire group that way 6 and think it out just a little bit more? I 7 think that will probably be more comfortable 8 for everybody. We could do that by next 9 week; by the end of this week? 10 MS. VINING: That seems 11 reasonable. 컴컴. So we'll summarize his 12 slide and make it a little clearer and then 13 circulate that. 14 MS. DORMAN: Yes. I think that's 15 a good idea. 16 MS. VINING: I think a lot of 17 ideas are up here and we're not really -- 18 MS. DORMAN: Yes. 19 DR. ABRAMSON: All right. 20 DR. JENKINS: It does seem 21 categorically though that you've brought the 22 right groups together. BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382 350 1 MS. DORMAN: Yes. 2 DR. JENKINS: We have the 3 regulatory bodies -- representatives of 4 industry, academic and pediatric concerns. 5 MS. VINING: We might have to work 6 with NIH also. 7 DR. JENKINS: NIH, yes. 8 MS. VINING: Thank you. 9 DR. ABRAMSON: I appreciate 10 everybody coming, taking the time. 11 Hopefully, you've found this helpful. I 12 have and we'll proud of working with you. 13 Thank you. 14 (Whereupon, at 3:45 p.m., the 15 PROCEEDINGS were adjourned.) 16 * * * * * 17 18 19 20 21 22 BETA REPORTING (202) 638-2400 1-800-522-2382 (703) 684-2382