Blood Safety TranscriptsDEPARTMENT OF HEALTH AND HUMAN SERVICES
ADVISORY COMMITTEE ON BLOOD SAFETY AND AVAILABILITY Twelfth Meeting THE ROLE OF VARIOUS CONSIDERATIONS IN DECISION
MAKING RELATED TO NEW AND EXISTING
BLOOD SAFETY MEASURES 8:10 a.m. Thursday, August 24, 2000 Hyatt Regency Capitol Hill Hotel
400 New Jersey Avenue, N.W.
Washington, D.C. 20001 P A R T I C I P A N T S Arthur Caplan, Ph.D., Chairman Stephen D. Nightingale, M.D., Executive Secretary Larry Allen James P. AuBuchon, M.D. Michael P. Busch, M.D., Ph.D. Mary E. Chamberland, M.D. Richard J. Davey, M.D. Jay Epstein, M.D. Colonel Fitzpatrick Ronald Gilcher, M.D. Fernando Guerra, M.D. Paul F. Haas, Ph.D. William Hoots, M.D. Dana Kuhn, Ph.D. Karen Shoos Lipton, J.D. Paul R. McCurdy, M.D. CAPT McMurtry Gargi Pahuja John Penner, M.D. Jane A. Piliavin, Ph.D. David Satcher, M.D., Ph.D. John Walsh Jerry Winkelstein, M.D. C O N T E N T S AGENDA ITEM PAGE Welcome, Roll Call, Conflict of Interest Announcement 4 Comments by the Assistant Secretary for Health and Surgeon General David Satcher, M.D., Ph.D., Department of Health and Human Services 7 Centers for Disease Control and Prevention Hepatitis C Initiatives, Harold Margolis, M.D., Chief, Hepatitis Branch, CDC 37 Statement of Issue, Stephen Nightingale, M.D., Executive Secretary, Advisory Committee on Blood Safety and Availability 91 Comments by Chairman and Members 99 Comments by Public -- Lunch 191 Committee Discussion and Recommendations -- Adjournment -- P R O C E E D I N G S DR. NIGHTINGALE: Good morning. My name is Dr. Stephen Nightingale, and this is the 12th meeting of the Advisory Committee on Blood Safety and Availability. Could I begin by calling the roll? Dr. Caplan? CHAIRMAN CAPLAN: I'm here. DR. NIGHTINGALE: Mr. Allen is in transit. Dr. AuBuchon DR. AuBUCHON: Present. DR. NIGHTINGALE: Dr. Busch? DR. BUSCH: Present. DR. NIGHTINGALE: Dr. Chamberland? DR. CHAMBERLAND: Present. DR. NIGHTINGALE: Dr. Davey? DR. DAVEY: Present. DR. NIGHTINGALE: Dr. Epstein? DR. EPSTEIN: Here. DR. NIGHTINGALE: Colonel Fitzpatrick? COL. FITZPATRICK: Present. DR. NIGHTINGALE: Dr. Gilcher? DR. GILCHER: Here. DR. NIGHTINGALE: Dr. Gomperts is unable to attend today. Dr. Goosby I believe is in transit. Dr. Guerra? DR. GUERRA: Here. DR. NIGHTINGALE: Dr. Haas? DR. HAAS: Here. DR. NIGHTINGALE: Dr. Hoots? DR. HOOTS: Here. DR. NIGHTINGALE: Dr. Kuhn? DR. KUHN: Present. DR. NIGHTINGALE: Ms. Lipton? MS. LIPTON: Present. DR. NIGHTINGALE: Dr. McCurdy? DR. McCURDY: Here. DR. NIGHTINGALE: Ms. Pahuja? MS. PAHUJA: Here. DR. NIGHTINGALE: Dr. Penner? DR. PENNER: Here. DR. NIGHTINGALE: Dr. Piliavin? DR. PILIAVIN: Here. DR. NIGHTINGALE: Dr. Secundy is unable to attend. CAPT Snyder? [No response.] DR. NIGHTINGALE: CAPT Snyder would be in transit. Mr. Walsh? MR. WALSH: Here. DR. NIGHTINGALE: And Dr. Winkelstein? DR. WINKELSTEIN: Here. DR. NIGHTINGALE: The public service notice regarding conflict of interest that has been read at the beginning of all prior meetings of this Committee is included here by reference and will be read in full after Dr. Satcher's and Dr. Margolis' comments. Dr. Caplan will introduce Dr. Satcher. CHAIRMAN CAPLAN: I'm very pleased that the Surgeon General is here with us again. We have been wrestling for some time with a variety of issues, and as I think he knows, today's meeting has more of an open agenda than we've had in the past in terms of trying to respond to requests by him and the Department. We're going to touch upon a number of topics that this group has wrestled with in the past, and I suspect members of the Committee may bring up a few others maybe that are brewing as we go along. But I know he's going to comment to us about a few of the issues that we have been wrestling with and bring us up to date. So let me turn the floor over to the doctor. DR. SATCHER: Thank you very much. I'm again delighted to be able to join you at least briefly--I'm sorry. Thank you. I'm delighted again to be able to join you, if only briefly, to again express our appreciation for the outstanding work that you continue to do and also to help try to put in perspective how we see the challenges and certainly the significance of today's meeting. This summer, in response to your request, our office prepared summaries of both the origin of this Advisory Committee and your accomplishments to date, and I think all of you have now received the formal summary as of June 12th, probably, and the latter summary you should have received by now. I think it was sent out on August 4th. There are six broad areas which you have addressed in a very productive fashion: hepatitis C lookback, the issue of the transmissible spongiform encephalopathies, the shortage of plasma derivatives, the shortage of blood products, reimbursement for blood products and plasma derivatives, and the management of error in transfusion medicine. In each of these areas, I think we've made substantial progress, and we want to thank you for your contributions. But as you know, there are many challenges which remain, and now is certainly not a time to relax our vigilance or lessen our efforts when it comes to assuring the safety and availability of the blood supply. Let me take a minute to review our progress with the hepatitis C lookback, which was the first major issue. A guidance to the industry that incorporated your January 1999 recommendation was published by FDA on June 17, 1999. A proposed rule based on this guidance has been prepared by the Department, and it is presently awaiting final review by the Office of Management and Budget. And I think you're probably familiar with that process. The target date for completion of direct notification is September 30, 2001. We've received assurances from the blood industry that direct notification will be completed within that time frame, and we have reviewed assurances from the Commissioner--we have received and reviewed assurances from the Commissioner of FDA that her agency is prepared to monitor compliance with this process. Our general notification program for hepatitis C is also underway, and Dr. Alter provided you with an update on this program last January, and today I understand Dr. Margolis will provide you with an additional program update, in fact, in just a few minutes, and this is very important. But I do want to mention something else. In January of 1998, when the Secretary announced the initiation of the hepatitis C lookback efforts, she acknowledged your first set of recommendations on this subject, but she also said something else which I want to remind you of. She said, "I intend to go even beyond your recommendations. I consider these steps to be only the first phase of a comprehensive plan to address this significant public health problem. So it is my intention to reach effectively as many people at risk as we can. Today's decision," she said, "will allow us to move immediately to address concerns among transfusion recipients at greatest risk. At the same time we will educate the public at large, evaluate our efforts, and take even more steps to address unmet needs as we identify them." And this is what we have tried to do with the hepatitis C lookback. This is the same approach we've taken to the other challenges, I think, to blood safety and availability that we've encountered, and we hope to continue to do so. But I do want to mention the latest effort in this regard because we have had discussions about sending a letter from the Surgeon General to every household in America about hepatitis C because of the magnitude of this silent epidemic affecting four million people. And the struggle, of course, has been that there's only one model for doing that, I guess, in the past and that was when Surgeon General C. Everett Koop sent a letter about the HIV/AIDS epidemic. There have been some major changes since that time. At that time the Surgeon General's office had what we call franking privileges, and there was no problem in sending mail to all of the families in America. Congress has long since withdrawn that, and now only Congress has such privileges, so it would cost us between $30 and $40 million to send such a letter. However, in discussions with leaders in Congress, especially Congressmen Bliley and Coburn and Brown and some others, we agreed that we would take advantage of the franking privilege of the Congress to send the letter. So on July 27th, we held a press conference with members of Congress and announced that, in fact, a letter from the Surgeon General would be sent to all the constituents through congressional mail. And so we have moved forward with that in terms of putting together a letter, and the Congressmen have sent letters to all of their colleagues urging them to transmit this letter. There are a couple of things that we have to deal with. One has to do with the separation of the different branches of government and to make sure that the letter is written in such a way that it doesn't imply any breach of that separation. So we'll be changing a sentence here or there from what you received, especially the one that says, "We have joined with the Congress." We're going to say that differently. [Laughter.] DR. SATCHER: So nobody will misunderstand what we're saying. The other issue, which I think is a very important one, is we are sending letters to all of the households, hopefully, and we hope that it will get the desired response. Now, if you ask me if we're prepared to deal with the desired response, that raises another issue that we should be aware of, and that is that there are not adequate federal funds to support the state and local level programs to respond if people will, in fact, as we would like for them to do, if everybody would come seeking testing and treatment as indicated. But I think that's a good problem to have in the sense that--the good problem, of course, is that we have put the problem in perspective by sending this letter, and hopefully it will lead us to move forward to make the resources available to deal with this issue. We want to deal with it. So that's sort of where we are there. Today I understand that one of the things you're going to be discussing is the role of various considerations in decision making related to new and existing blood safety measures, or I guess to answer the question: What are the principles on which a policy to assure a safe, available, and affordable blood supply should be based? So we certainly look forward to the outcomes of this meeting, but I also want, before in conclude, to express our appreciation to those members of the Committee whose terms are expiring. I want to thank Mr. Allen, Dr. AuBuchon, Dr. Gomperts, Dr. Penner, and Dr. Secundy for your contributions to the Advisory Committee during your three-year term, which ends, I guess, on September 30th of this year. But we certainly want to assure you and to assure those who are not here that they have not seen the last request for public service, and we hope that they will be as generous with their talents in the future as certainly they have been as members of this Committee. Now, one final comment. In addition to advising us on blood safety, I want you to know where all of this fits into the bigger picture of Healthy People 2010, the nation's health plan for the next ten years. And I think we released that plan on the day when the government was closed down, and we were having this national meeting, and you met and I remember coming here to meet with you. But we did something for Healthy People 2010 that we've never done before in Healthy People. We have now over 400 objectives. We felt that there needed to be a national strategy based on easily definable and a set of indicators that we could easily communicate to the American people. So we came up, with the help of the Institute of Medicine, with leading health indicators, and that's what you have at your desk. You have a bookmark of the leading health indicators. It's interesting. Five of them we say are lifestyle and five are health system indicators. And what we hope to do over the next ten years is use them as we use leading economic indicators. We want to monitor the progress, and we have measurable objectives on each one of these indicators. And we hope to monitor the progress of the nation toward reaching these measurable objectives. Now, I won't go any further than that except to say you might want to take any problem that you're concerned with and ask yourself how these indicators would impact upon that. I did that last week with cancer, and you might want to just go through and say if your concern is reducing mortality from cancer in this country, how would each one of these indicators relate to that? I think you'll be surprised to find that virtually every one of them has an impact on the risk for cancer. I want you to know that because I want you to help us also with the whole issue of Healthy People 2010 and moving this nation forward to meet those goals and objectives. Thank you very much. CHAIRMAN CAPLAN: Do you have a minute for some questions? DR. SATCHER: Sure. CHAIRMAN CAPLAN: Okay. Why don't I open the floor for questions, comments. Dana? DR. KUHN: Dr. Satcher, I want to just thank you and the CDC for the efforts you put through in putting--in this "Dear Citizen" letter. I think it is much timely and much needed, given the fact of how long we've been dealing with the issue of hepatitis C. But two questions I wanted to ask you, because I think what I'm hearing you say is there's a little concern about how Congress has withdrawn the franking privileges of the Surgeon General. Is anything being done to reinstate the franking privileges? And then, second, is anything being done to request funding perhaps in this next budget so that this letter can go out to the citizenship of the United States? DR. SATCHER: Well, the letter is going out. It's going out through the good graces or the support of Congress. So that part is taken care of. They have made a commitment to send this letter to their constituents. So it does raise the next question that you raise. What will be the impact of this letter and will we be prepared to deal with it? If we receive the maximum impact, it would stress, severely stress the system as it now exists and really bring into sort of bold perspective the fact that perhaps there's not adequate support for the state programs in this area. We know that already. However, we don't know how many people will need--how many people will have insurance coverage and things like that as they seek to respond, how many people will go to the public system. We could envision a situation where the "public system" was, if not overwhelmed, severely stressed. And we're aware of that, and we hope that Congress will continue to increase funding in this area. But certainly I can tell you that the Association of State and Territorial Health Offices are concerned about being able to respond properly. CHAIRMAN CAPLAN: Jane? DR. PILIAVIN: Your talking about how the letter is actually going out to all the households makes me think in terms of our unhoused people. Is there going to be any way of trying to reach them? Clearly, many of those people have substance abuse problems, and almost none of them have access to medical care. DR. SATCHER: That's a general problem that we have with all of our programs, and I can only say there are different levels of programs in different communities throughout the country now dealing with that. You know, one of the best examples of that has been, I have to recall, dealing with tuberculosis, when we had the dramatic rise in tuberculosis from '85 to '92, almost a 7 to 10 percent increase a year. What we discovered was that much of that problem was in the population of homeless people in this country, so we had to develop strategies, including directives of therapy, to reach them. So there are strategies that can deal with this issue, and CDC certainly is always looking for new strategies, and maybe Dr. Margolis will comment on that. But, yes, we are concerned about that population, and jails and prisons, homeless, those are major challenges for our public health system. And it really raises the bigger issue: To what extent is our public health system now relevant to a population in which so many people are in our jails and prisons? For example, I believe the rate of HIV infection in jails and prisons is like eight times what it is in the rest of the population. So any public health system that does not respond to that and which people are--the jails and prisons are part of the community. People go in and out, in and out. So whatever goes on there is actually a part of the general community, whether we like it or not. And, therefore, increasingly our public health system must include how we deal with the jails and prisons. We're trying to deal with that. As you know, my Deputy Surgeon General, Dr. Ken Moritsugu, before he became Deputy Surgeon General, was Medical Director of the Bureau of Prisons. So we have improved our working relationship. CDC has some targeted programs both for the homeless and for people in jails and prisons, working very closely with the correctional institutions. So we are going to be sending a letter. I didn't respond to your point about franking, and I can't. You know, it's a tough issue. Congress made this decision, and I guess there has even been a ban on using the franking privileges now for a period of time. DR. NIGHTINGALE: We discovered that you cannot send franked mail within 90 days of an election. When we had the press conference on the 27th, it was the impression of both the executive and the legislative staffs that that ban was 60 days. A lot of work has gone into this so far, and obviously a lot of work remains to go into it. The commitment is to do the work. DR. SATCHER: But there are a lot of things--to get back to your basic question, there were a lot of things that happened to the Office of the Surgeon General during the last four years, between '94 and '98, in terms of reduction in budget and things like that that have been a problem for us. We have found ways to compensate for them in many cases to get reports done and to get them out. But it's not because of the resources in that office. It's because we have managed to use the agency resources, and they have been great in providing them and responding to requests to get things like the mental health report and the oral health report and the tobacco report done, not because of money in our office but because we have been able to work with other people, and now working with Congress directly in getting this letter out. I took a deep breath on that one. DR. GUERRA: Dr. Satcher, again, thank you very much for making the time to join this Committee at our meetings. You commented about the public health responsibility and certainly the increasing demands on a system that has not always had in place the kind of structure and support that is very much needed. And certainly one of the very important considerations relates to the identification of individuals that have infection with hepatitis C virus and that are progressing with their illness and that obviously need a variety of interventions for more clearly defining the status of their disease and hopefully connecting them to some treatment. But on the public health side of that, we certainly need to make sure that they are protected against hepatitis A and hepatitis B in the instance where they're at risk for those diseases, and also that they have access to detox programs when they're substance users or alcohol-dependent, which obviously is a comorbidity that puts them at even greater risk. The resources are not in place to do that. In the instance of my own community, where in a relatively short period of time we presently have over 5,000 individuals in our registry for hepatitis C that we have identified just with some minimal efforts that we have been able to support through our own department for screening and counseling, doing the testing. But we don't always have enough vaccine for the adult population because they're not eligible for the Vaccines for Children Program to protect them against hepatitis A or B, and then also to try to get them into some system of care. Unfortunately, many of these, as you well know, are within some of the minority communities, for instance, within the Mexican-American or Hispanic and Latino community that has many who are uninsured and/or marginally employed and not eligible for any benefits. In the instance where they do have some coverage, you know, managed care organizations will not often cover the preventive measures and/or the work-up that needs to be done. Is there something taking place at the federal level to try to at least put some of that responsibility on those systems that are in place for serving uninsured or in the instance of managed care organizations that they do have an obligation to their patient populations? What is your sense also of the availability of additional vaccine program support for these populations? DR. SATCHER: Well, let me just say I think we continue to review our relationship certainly with managed care organizations who contract for the care of Medicaid populations, and I think that is going to continue. It is a very serious problem, because we have had cutbacks in several areas in terms of the budget, and as we look at our budget situation today, it is really critical that we look at the areas of need in public health. Those have been documented very well by, again, the Institute of Medicine's report in 1988 talked about a public health system that is in disarray, and documented the loss of infrastructure, especially at the State and local level. We have been trying very hard to rebuild that infrastructure. We have made some progress, in terms of the State public health laboratories, for example. Most of this progress has come about in response to emerging infectious diseases and the threat of bioterrorism. We have a long ways to go, as you point out, so we are looking for strategies of public-private partnerships to reach the populations in greatest need. You know, ultimately, obviously, we keep dealing with a system that is, in some ways, well-funded, but not well-organized, in terms of the need for universal access and dealing with the lack of universal access in this country, which is one of the things that led the World Health Organization to rank us so low among the nations of the world. I think we're ranked number 37 in terms of health systems efficiency. So, part of what we're trying to do is figure out a way to adequately fund the system and then organize it in such a way that it operates most efficiently for everybody. So, the gulf between here and there is still pretty wide. You know that better than I do, because you have been on the front line a long time, and, obviously, our relationship, federal, state, and local, putting together a public health system that is well-coordinated, is one of the real challenges that we face. CHAIRMAN CAPLAN: Mike? DR. BUSCH: Yes, Dr. Satcher, I would also like to commend both you and the Public Health Service for the enormous focus and contribution in the area of blood safety. I think today the risk of blood is extraordinarily low, and the progress is really a tribute to the system and to the incredible accomplishments of technology, in applying it to blood safety. I think the discussion over the next day will be how much additional resource can we afford to put into closing that last bit of the window period or adding safety measures, such as leukodepletion, which have marginal safety benefit. So, we're struggling with the enormous resources that are required to further reduce risk in blood safety. I think there are two related areas, though, where a modest amount of resources could have a high impact. One of the other charges of this committee is the availability of blood, and there remains a serious problem with blood donations. About half the blood centers in the country now are struggling to collect enough blood, and I know that about a year ago, there was discussion about a public health sort of campaign where yourself and others were going to do television commercials, et cetera. I have not heard much about that. We have seen in Canada an enormous impact through an orchestrated public health campaign to increase blood donations, and I think that is an area where I could imagine Give Blood being added to this list, because I think that giving blood is a process that encourages safe health. The process of going through that interview, understanding risk behaviors, et cetera, could ramify out in terms of broader public health safety implications for individuals as a whole, as well as, obviously, it is a good, you know, general sort of ethical behavior. So, that is one area I would like you to comment on; the other is the issue of blood safety around the world. We heard, at our last meeting, the reality of developing countries, where I think it is estimated that, in developing countries, perhaps 20-to-30 percent of the blood that is collected is not even screened for basic antibody tests, and that translates into more units of blood than are collected in this country altogether every year, are being transfused without even basic screening. I will show later that basic screening with simple, inexpensive tests would interdict probably 98 percent of the infectious units. So, I am wondering, I know there was the major focus by yourself and the world on Africa recently. I am wondering if there's any potential that significant U.S. research or resources safety could be put towards bringing forward basic blood measures in developing countries. DR. SATCHER: Well, let me start at the end, and forgive me if I forget some of the things you have raised, but I think the World Health Organization meeting in November is certainly an opportunity for us to engage in a discussion about the global implications of blood safety, and to also put into perspective how we and the United Nations World Health Organization can best contribute to blood safety worldwide. So, I think that is what this is all about. That discussion is underway. I believe we had--at the World Health Day, I believe we had a discussion about blood safety. So, we are trying to put that into perspective. Let me just say to you that is a very difficult issue. I have visited the hospitals in Africa. I remember going to a hospital in Kissimu, western Kenya, where the choice between transfusing blood that is not, as we would define it, safe, and saving the life of a child with cerebral malaria is such that, are you going to take the time to go through the process when you know that you have got to give the child the blood? You have got to choose between safety right now and a child that will die within the next week or so, but a child that might well be infected with HIV because of that unit of blood that you have to give anyway because of the situation. So, we have got to deal with all of the things at the same time, but I believe we can get to the point where we can make the technology available to developing countries. When I led the team to Kenya and Tanzania after the bombing of our embassies, and the whole issue of blood safety was another issue we dealt with there, where again the systems were just not in place. So, hopefully through the United Nations, through the World Health Organization and our participation, that we can begin to bring to bear our technology on blood safety in developing countries. As far as--Damon, do you want to comment? MR. THOMPSON: On the PSAs. DR. SATCHER: Yes. The next issue is what are we doing about getting people to contribute more blood in this country. It is a very important point, because we have had an evolving strategy in which we have made several recommendations, some of them we have implemented, but, also, we have had a public campaign. Damon, who is the Director of Public Affairs, do you want to comment? MR. THOMPSON: Sure. Hi, I'm Damon Thompson. I am Dr. Satcher's communications director. I'm pleased to announce that just a couple of months ago, we teamed up with the AABB, America's Blood Centers and the Red Cross. We provided the HHS studios at their disposal, as well as the personnel. They brought some people in who had benefited from blood products from around the nation, and we spent the morning cutting several public service announcements, and the AABB and the ABC and the Red Cross have all committed to working on the distribution of those PSAs. If you like, I can get you some information. They sent us a storyboard with some of the photos involved. If you like, I can see that Steve transmits to you the storyboards for those, so you can see just what we have done. DR. SATCHER: When do we expect those? I remember spending the whole morning doing the taping of those PSAs. MR. THOMPSON: Right. You know, I'll have to check. I'm under the impression that they have already gone out. Sometimes it takes awhile to get into the pipeline. DR. SATCHER: But we agree with you. It's something we need to really do. It's too late to add it to the indicators, but-- [Laughter.] CHAIRMAN CAPLAN: Karen? MS. LIPTON: I can just comment on the distribution. We do try to get them out. I think one of the things that we find is that we compete with so many other--when you are going into a public service announcement. And we have talked a lot about different ways to get around that. Some suggestion is that if you plan earlier and ask them to place them in December, you get a better result than asking them for next week. But I do think there is also a contrary view that you get what you pay for. And if we are not willing to put money into purchasing advertising time that will get us at Super Bowl or something like that, that we will be always placed in the slots that the stations have allocated for public service announcements. I also want to mention that there is an NHLBI, a committee to try to increase blood donation, and they have been looking at the Canadian campaign and trying to look at different ways, and I think they will come up with some very productive recommendations for all of us, in terms of trying to put together both the national campaign, which I would call an awareness campaign, and then coordinating that at a local level with recruitment, which really has to occur in the communities. DR. SATCHER: I know I have gone over my time. Damon knows a lot about the franking issue, because I think he was working in Congress during the time when the situation was different, and the decision about not allowing franking privileges for the Surgeon General was not limited to the Surgeon General. Basically, except for Congress, they were done away with. But, will you say something about this, Damon? MR. THOMPSON: Yes. It was part of the budget agreement, and it had to do with the Postal Service budget and getting more efficiency out of the Postal Service. The Postal Service agreed to be able to achieve a certain amount of savings, but, in return, they wanted to be relieved of the responsibility of providing free postage and expense for all of the agencies of government. So, no agency was particularly singled out or anything. It was part of an overall budget agreement. I should also note that as far as the 90-day ban on mass-mailing for Congress, that does not mean that Congress has to sit on its hands on this message until after the election. There are many things that are available to them, many resources available. There are radio and TV shows, which they do, newspaper columns, town hall meetings. There are still many avenues available to them to be able to disseminate this message, and it will simply be any mass-mailings, and that is just to duplicate the verbatim letter and send it out to each doorstep. That will probably have to wait until after the election, but that doesn't stop them from communicating the message from now to the election in many other ways. CHAIRMAN CAPLAN: Well, I want to thank Dr. Satcher for coming, and you should know that the committee is more than willing to try and push forward some of our recommendations in tandem with you when the letter goes. You should feel free to tie into our interest in making sure that the system is available to respond, as well as to notify. DR. SATCHER: Thank you very much. CHAIRMAN CAPLAN: Thank you. We're going to hear next from Hal Margolis about basically where we are with the notification and hepatitis C information programs that we've been trying to push forward and track. At the last meeting there were members of the committee who expressed interest in having an update on this important area, so--in terms of CDC activity, so Hal has agreed to present to us on the latest situation. While I've got the floor here, by the way, I always was interested in doing an empirical study to see if there was a correlation between insomnia and organ and tissue donation, looking at PSA targeting. Blood could be added to that. DR. MARGOLIS: Thank you. What I'm going to do this morning, was asked to do, is to try and focus on--is this thing on? Can you hear me? Is to focus on some of the issues in terms of look-back, and I kind of phrase it in--realizing that most of the effort and most of the concerns have been around the issues of targeted look-back, but I think as we recognize, it's not the total answer to the issue and the problems. And then I'll also touch on some of the things that Dr. Satcher mentioned in terms of CDC's efforts in terms of hepatitis C education and identification of infected individuals. I think one of the things we've all learned, is that while we have initially focused on identifying persons who are infected by transfusion, that as soon as you start talking about hepatitis C, you actually start talking about all this group, and you really can't wall these things off. I have given everybody a copy of these overheads, so you shouldn't have to take too many notes in terms of the direct data. This kind of gives the summary. We've used the denominator of an estimated 300,000 individuals who have been infected among the 4 million estimated by blood transfusion. The data that Miriam Alter presented the last time, which until the next survey, but based on the power of that last survey, gives us an estimate that about 1,600 individuals have been identified through the targeted look-back, which, unfortunately, only represents about a half of one percent of all the infected individuals. What you all want to know is this last part, is that, okay, and so how well has our general look-back effort done in terms of identifying everybody else? I think you got some glimpse of that in the targeted look-back data, which indicated that about one-third of these 1,600 individuals already knew their hepatitis C status. And so, again, I think we have to at least presume that, as defined, general look-back has been having some effect. I put this up here just to remind everybody that there are a number of reasons why targeted look-back is not going to identify everyone. The single donor, even the donor with multiple donations who didn't come back after HCV testing came in place. And then a number of issues about the recipient, including, you know, the obvious, you can't find them, they changed their name. And the last one, which I think we never discussed here, but which is a very real issue, is that many people in the United States in fact have been transfused outside of the United States and they're among our American citizens, and in fact, as we look at this from a public health perspective, that's also an issue, and again, targeted look-back was not going to identify those people. This one's the sound bite. You know what the recommendation is. And now what our challenge has been is how do you put this into the context of what we at CDC have been calling now our national strategy for prevention of hepatitis C, which has four components, very simple: prevent new infections; identify those individuals who are infected, and make sure that they are evaluated for liver disease and treatment; surveillance and research in terms of the issues that we don't know about. Now, what we have done from a CDC perspective is, okay, how do you get this out there? How do you deal with both the public and private sector in terms of implementation of any strategy? And we've really focused in four areas, and you know, you've heard from me and others on my staff and other in the PHS that in fact communication of information about hepatitis C has been our number one priority, and I'll show you some data that says, "Boy, we're sure not there, but we've made a lot of strides." The other big issue, which Dr. Satcher brought up and which we're just beginning to do some things on are what we call state-based prevention activity, and when I talk about state-based, it's not all just public sector, it is in fact public and private, and I'll give you some glimpses of where we are at this point. Obviously, surveillance to figure out how well we're doing is key to this, and again, I think everybody on this committee knows the issues about hepatitis C and the difficulty of surveillance, but I'll show you again some glimpses of things that may help us. And then, lastly, you know, we don't know everything, and so there is a research agenda to this, which I will not discuss at all today. In terms of the communication issues, as I've said, we've primarily focused on education of health care professionals. The other big issue has been public service advertising or general public education, and then education of persons at risk, in the risk groups, and as I said, we have started at CDC. All of our effort over the last two years has really essentially been focused on the transfusion recipient. But as we have seen, as we put out just general information about hepatitis C, other risk group issues come up, and very quickly you're dealing with the whole universe of risk of HCV infection. We've only now begun to target some activities at injection drug users, and most recently, there was a joint agency symposium on hepatitis C or hepatitis and HIV in the injecting drug use community. It was held in Baltimore and co-sponsored by CDC, NIDA, CSAT, which is the Center for Substance Abuse and Treatment, and really realizing that the issue now in this last population is one that everybody said, "Oh, gee, it's HIV that's the problem." In fact, now drug users or people who had previously injected, are now dying from their chronic liver disease because their HIV disease can in fact be managed in terms of long-term treatment. Put at the bottom here are the array of things that we are doing which have gone--and which we are funding at CDC, which include cooperative agreements with a number of NGOs, and in fact, there's a new round of funding that has just begun that is going to expand out. I can't tell you who everybody is because the awards aren't officially out yet. Starting with the recommendations for hepatitis C control in 1998, which really gave the blueprint and the framework for how we're going to PSAs, to distance learning issues on the Web--and I'll give you some of that data later--to the STD and an HCV hotline that is in fact available to a group that you probably aren't aware of, called the STD Prevention Centers, which exist--there are 10 of them around the country, and in fact, train both practitioners on the medical direct physicians as well as others dealing with STDs and prevention of these diseases, with counseling messages. You know, again, one of the strenghts of HIV prevention is in fact formal counseling scripts. How do you do it? How do you do client center counseling? Well, that's not there for hepatitis, and in fact, we're developing those now, and those will be in the PT centers within the next six months or so, and again, this available to both, and heavily used by both the public and the private sector. DR. EPSTEIN: Hal, I think that this very broad-ranging effort on targeted look-back related to blood transfusion is commendable. But what troubles me is that it's been estimated that only somewhere between 4 and 7 percent of all of the living people with HCV got it from transfusion. And the question is what percent of that larger majority, around--round figures--95 percent, do we think are reachable through general look-back strategies and where are we on those? DR. MARGOLIS: Well, as I'm saying, we don't have any idea. The fact is we don't, and we don't have any reasonable mechanism to look at that. We're currently, as I say, I think some of these state-based surveillance systems, once states can look at who these people are and figure out how individuals acquired their infection, will be able to help answer part of that question; in other words, in New Mexico, what proportion of those 17,000, in fact, had transfusion as their risk factor? And from that I think we can then begin to estimate. Basically, we have to get some population-based approaches to looking at general look-back. And we are sitting right now trying to figure out how best to do that in a way we can afford it, and that's really our next step. We put our major effort into looking at the effectiveness of targeted look-back, and now we feel we need to do, as we have done with the targeted look-back, is look at the general look-back kind of in interval or, you know, looks. So we need a baseline right now to see where we are because everybody says hardly anybody knows they're positive, yet you and I know there's a lot of HCV testing that goes on each year, and I know there are a lot of positive people in state health department records. So we just need to figure out who they are and what their risk factors are. So as I said initially, we don't know, and I think that's the difficult part. DR. KUHN: Dr. Margolis, there was a question I had, and I was thinking about as you were talking about methods and modes of communicating this to the public, and the question that came to my mind, and I think it kind of follows along with what Jay was speaking, is if I'm an average American working person, I'm busy in my job and perhaps I, I mean, I received either a blood transfusion before 1992 or I had it through another mode, and I have Hepatitis C, but I don't know it because I hadn't had any need to go to a doctor because the disease is not presenting in any way, shape or form, what is the best method or mode of communicating or informing me that I may be at risk? And I'm concerned because there are people out there, and they have busy lives, and how are we communicating to them that they are at risk? DR. MARGOLIS: Well, again, I think we've taken a lot of different approaches, from the surgeon general's letter to those PSAs to what we have heard, and we've done over a dozen focus groups in different parts of the country with lots of different people of different races and ethnicity. And they all say to us, "I'm not going to go, most likely, if I'm--" and these were people who have had transfusions, but they all essentially are saying, "I'm probably not going to go to my physician just because I had a transfusion. I expect my physician to ask that question when I go there." And that we have heard over, and over and over again. I mean, that was the very first data. And that's why we think that, and people do go to physicians for other reasons and as part of a standard health history. Now, for instance, the American College of OB-GYN has now put this in their health practices, their latest health history. So they've been moving forward with this. So what I'm saying is, and it's what this group told us, is that the message has to be on both sides. We have to get it to the public and get it to the public as close to their health care setting as possible is what, again, the educated approach was. And the other is that physicians have to ask the question because if they don't ask it, it's not going to happen. I mean, that we've heard both from the patient side and from the physician side. So that's where we're trying to go. I mean, I don't--it's difficult. DR. KUHN: Yeah, and I understand it's a dilemma right there. But, again, I kind of look back to where most public citizens are all of the time is they are on the road, they're driving. And I think one of the most effective, that I saw, ways of a PSA were the yellow eyes, that poster. That was a very effective way of getting people's attention and maybe that needs to be looked at again, done on a broader scale across the United States. I don't know how, but there are people in marketing who have a way of being able to reach the mass public on how to inform them that they are at risk if they meet one of these entities. DR. MARGOLIS: And just to assure you that we/CDC aren't doing this alone. We're doing this with the big marketing people. So that's why there's a lot of different approaches out there. But, no, I agree, and again the yellow eyes, which was done by the American Liver Foundation I think is still running. The big issue, though, is does it get somebody into the physician to get the test? And that's where the link has to occur. But you need both, and we agree. CHAIRMAN CAPLAN: Keith? DR. HOOTS: I'd like to congratulate you, at least, from a couple of anecdotes that I've observed. At least two patients over the last 2 months who clearly had been told long ago they were HIV infected because they were in an at-risk group and had been presumably educated, at least we think we've educated them, but as you indicated, sometimes it takes reinforcement over and over again. These were two individuals who hadn't been seen in the health care system for several years because they had done pretty well, but came in not only asking about their Hep C and commenting about, well, you know, it's been in the news a lot, and I wanted to know, and they came with specific questions, which indicated to me that some of this message is getting out even to people whom you would think would be the ones who wouldn't need it the most. But the fact that they translated what they--just some peripheral knowledge that had probably been long since forgotten into specific questions suggests to me that, at least in that broad way, and clearly what they said to me was that it was in the news and that they had been looking, and it raised questions in their mind. CHAIRMAN CAPLAN: I have a question, actually, three quick ones. I had occasion to be talking recently to a group of infertility clinics, and when they manipulate sperm, and eggs and embryos, it turned out that not all of them, but many, were routinely testing for Hepatitis C, among other things. So in addition to the scripts, one question I have is how is CDC working with the professional organizations and societies to make them have, as part of their standards, testing for risk behavior in the good standards and practices area? DR. MARGOLIS: We go to a lot of meetings. In fact, I was just at the Infectious Disease Society of OB-GYN and working also with, again, OB-GYN's Practices Committee. Miriam, and I and others in my group spend a lot of time working because the reality is the tough part of this is getting this uniformly into medical practice. And that comes from several ways, getting professional organizations to say we agree or we're going to rewrite the CDC recommendations for our own organizations, and, again, that was part of in that February meeting, and some groups are doing that. And then the subspecialty groups within an organization has to do it. And let me tell you, you have to knock them down one at a time. I mean, there is no other way. We actually now have a list, and we went back after that February meeting to find out of the 150 groups that were invited and for whom we even gave dummy--dummy--but, you know, dummied up articles for their newsletter. How many of them have done something with it? Well, 25 have. So they've actually put it out in their monthly newsletter or magazine, and then a much smaller group are actually putting it into a committee to write recommendations. And that's what we're tracking and working with them. And there is really no other way to do it because that's our current medical system. But what it really all starts with were the CDC recommendations and recommendations from this committee and others that begin to say now we need to move this forward. CHAIRMAN CAPLAN: The second question I had for you is at some--we spent a lot of time, and we'll probably spend a lot of time today starting to or revisiting issues of cost benefit, trying to achieve improvements in safety. And in one sense, as Jay points out, Hepatitis C is not primarily a blood transfusion issue. On the other hand, I think the committee has always understood that there are special obligations to notify, and look back and maybe spend more because of the nature of the blood system. In order to cement trust in the system, you may want to do that. And also, to be blunt, it may be easier to carry some of the public health factors about Hepatitis C on the back of the blood issue. So there it is, and that's what it's going to do. At some point, however, in the expenditures, cost-benefit expenditures, there comes a time, I suspect, at which we start to say you ought to get a test if you're older than 20 or older than 30--I mean, forgetting about the individual risk factor thing. Do you envision a time, has CDC been thinking about simply saying, look, anyone over the age of "X," risk factors or not, we really should make that part of routine testing, as part of what gets done? Cost and so on I understand with the-- DR. MARGOLIS: We've not done cost analyses. We've done it on kind of an identification effectiveness analysis. And that, again, is the reason, for instance, that while HCV is sexually transmitted, the number of people who have the types of sexual practices that would put them at risk of HCV is so incredibly large that the effectiveness of identifying people, such as doing routine testing in an STD clinic. Now, we're looking at this in a number of the demo projects, and there are data coming in. And, again, the effectiveness of routinely testing, even in an age group, turns out to have an incredibly low yield. And so we've not done it as a formal cost analysis where, actually, it will happen, but we've done it as an identification effectiveness type analysis, and that's why we haven't used those approaches because they just don't come close to any of the things that we do in terms of other public health activities. CHAIRMAN CAPLAN: Last quick question. I see that this letter probably, sounds like, is going out under some disguise or stealth mechanism. So if the letter is going, and there are PSA announcements in somebody's basement waiting to be shown at 2:00 in the morning to various people, and you have activities underway, can the committee know or can we be assured that we could get an integrated push? This is a wonderful opportunity, it seems to me, to really get the attention of our political candidates, congressional candidates, all kinds of people, if we could get a coordinated push around the appearance of the letter. So is CDC thinking now about what to do when this letter goes? DR. MARGOLIS: Our problem has been we get the sense this letter is not all going at one time. And, again, I'm just talking about some of our--what little bit of forecasting we can get. The other part is some of these things which I've told you, such as the next piece to the physicians, is in the pipeline. When that's going to happen may not quite come together with the letter, to be honest, in terms of just the lag time of the funding, and what the contractor produces and what we all think we want. So we are ready to be receptive; in other words, the hotline has been geared up. There are more people. We have tried to do some forecasting as to what may happen, and if this upward trend puts another set point in there, we can do that. In terms of other pushes, you know, we can reissue some of what we have. Whether we'll have a new rollout like we did at that May thing almost a year-and-a-half ago, I honestly don't know. But it's a good idea, and we'll sit down and strategize. CHAIRMAN CAPLAN: Steve? DR. NIGHTINGALE: If I can make one additional comment in response to Dr. Caplan. There is not necessarily a conflict, but there should be a balance between an integrated approach and a sustained approach. One of the things that I have taken from Dr. L'Enfant and his very successful management of the National Cholesterol Education Program is his very firm belief, which I think is backed up by very extensive data, that the duration of a public education campaign is of comparable importance, if not more than comparable importance, to its intensity. The primary purpose of the Department's efforts is not to achieve a campaign that gains intensity at a single point in time. In fact, there is probably less enthusiasm for an intensity-driven campaign within the Department than there is without. I think there is more enthusiasm within the Department, and I believe I am speaking for the agencies as well, of the duration of the campaign. What we're both looking for is effectiveness of the campaign, whether or not intensity or duration is the most important, perhaps will be debated. There is room for both. But from within the Department, duration is what we're looking for. DR. PENNER: Two quick comments and a question. The learning curve for the health professionals is directly related to Board examination questions, and it would be a strong suggestion, if it gets on the Board, it'll be picked up very quickly. Secondly, the PSA letters, as they come out, require I think some attention on emphasis. When we get letters that start out with substance abuse up top, for example, the stigma of that suddenly turns off the rest of the message. You say, well, if these are drug users, that's fine, and forget about it. So if you emphasize that, and I think this will bring back the question that was already brought up, is it can be carried as a message and part of the transfusion and blood which I think most of the physicians, health care workers and the public respect. So they'll look at it a little bit more carefully than if it just comes, oh, another drug abuse situation and then just discard it. The question I have is that 3 years ago we dealt with a look-back situation and made some recommendations. And at this point, what percentage of the blood banks do you believe have completed the look-back? DR. MARGOLIS: The data that Dr. Alter presented was that in April it was about 85--again, the estimates were based on 85 percent. It was around 85 percent. And the next survey, which will be done early in 2001, I mean, we projected essentially it's, you know, it's done. That was on 85 percent of the data reported back. Now, many of them had already done all of their work, but didn't have the data in terms of being able to report the numbers. DR. PENNER: To 1990 or to 1992? DR. MARGOLIS: Oh, excuse me. That was, actually, that was back through '90, again, that was the-- DR. PENNER: The first-generation testing. DR. MARGOLIS: No, that was not first--this was only second-generation testing or second-version testing. DR. PENNER: So what's happened on the first-generation testing that we have asked for the look-back to be reviewed with the specifications that we had made with regard to cutoff period? What's happened on that end? DR. MARGOLIS: That we have done because at the time when the survey was done, again, essentially last January or February/March at that time, that wasn't in that survey. That would then be put in the next survey. And so we realize we're now going to have to look at version one effectiveness data, which will probably carry us into 2002, in terms of getting that data. Do you see what I'm saying? DR. PENNER: Yes. DR. MARGOLIS: In other words, all of the data I've shown you so far is for version two, for the second generation. And so for us, for the evaluation, it has to be added to the questionnaire that will go out in 2001. DR. PENNER: So you're really not sure what that part of the look-back is-- DR. MARGOLIS: Don't have any data on that. DR. PENNER: Mike, do you have any idea what that might be, just offhand? DR. BUSCH: Well, just I remember when we looked at this there was data from Stanford that indicated that their actual incremental pick-up with the version one-driven look-back was quite low just because of the tracing issues, the lack of records, the number of patients alive. In terms of the first-gen look back, I think most programs have implemented it. There's actually not a formal final FDA recommendation, in terms of exactly how to conduct it. But sort of verbally, I think BPAC meetings, et cetera, FDA has indicated their position. So most programs have initiated it and I think probably completed it. DR. PENNER: With the first part, but the other part-- DR. BUSCH: No, I'm talking about the first-generation-driven, BIA-driven look-back programs have, to my knowledge, been implemented and are probably well on the way to completion. MS. LIPTON: If I can just, the difficulty we don't know. I mean, we're pretty confident about what the blood centers have done. When you get into more problems is trying to ascertain whether the hospitals have actually been able to make the contact. I think most blood banks got on it right away because if you were going to go through the records once, you just wanted to accomplish it. But as to how, you know, finding patients who were back much further I think was a very different issue. And there are time lines. I think everyone is working diligently. But, Kay, you don't know, do you? I just don't think we know right now. And we periodically send out surveys, but we don't have one on the--and it's really the hospitals we need to hear from. DR. GUERRA: Harold, a couple of public health questions and concerns. Most states now are doing universal screening for HIV and Hepatitis B in their populations of women that are being taken care of in labor and delivery room suites or during their prenatal care, and it must be documented. It is a requirement, at least prior to dismissal of the infant from the hospital because of certain therapeutic decisions perhaps that have to be made. Are we anywhere close to considering that as a universal recommendation for prenatal populations, given what obviously is a tremendous increase or at least the suspected increase in serum prevalence rates is one question. And the other is within some of the efforts that are taking place, are we also doing something to try to dispel the myths and misperceptions about Hepatitis C? We often get questions about household members being in contact with somebody that is identified as being Hepatitis C. And it's almost a real stigmatization that occurs in infants or children in day care settings, where a parent has declared themselves to be Hepatitis C, and it becomes a matter of public concern. CHAIRMAN CAPLAN: I just wanted to piggyback something that I forgot to ask onto that question. We had a big battle, which you're aware of, Hal, in Philadelphia about firemen getting infected with Hepatitis C. And I got a lot of calls about this casual contact transmission, bleeding contact, that sort of thing. DR. MARGOLIS: I would venture to say we spend 50 percent of our time, professional time, both public inquiries and actual time "doing the studies," to dispel some of the myths, actually maybe working from the fire fighters back. Again, unfortunately, there are a lot of things that go wrong out there, so incorrectly reported data, which turns into somebody's political agenda, which doesn't serve anybody. And as you saw, we moved pretty quickly to test old data sets, analyze data, get an MMWR out and try and answer and at least hopefully set the information platform straight. The same goes on with the question of transmission. I think there are, again, good data, and those get handled both through hotline and a lot of calls, and, no, we don't have a pamphlet that says what do you do in a day care center. That's on the list that needs to be written. And so that's where, and again, we try and clearly work with our partners to identify certain groups or information areas in some of these cooperative agreements that we do. I mean, that's frankly how we work is to let them put that information together and get it out. And so some of that type of, you know, those areas where we're getting a lot of inquiries, we then try and generate, you know, some written information or put something on the website and go that way with it. So it's kind of both, if we need the data--you know, tatoos is, again, still one of the big issues. So there are RFAs out there, there are awards that have been made for looking at tattooing in various settings to, again, look at risks. So sometimes we need to generate the data, which is the research side. Other times it's just communicating it that we try and deal with. The question about perinatal transmission and screening pregnant women, there is a CDC study that's being presented now and is in the process of being written up for publication that showed, again, that the rate of perinatal transmission is low. It's about 3-3.5 percent. Transmission only occurred in an HCV RNA-positive woman. But, in fact, since this was actually a prospective multicenter study, it showed two additional things: One, it showed that there was an increased risk for internal fetal monitoring--somewhat, you know, that's kind of a logical thing, but it's never been looked at before; and the other that there was increased risk with prolonged rupture of membranes greater than 6 hours. And actually those in the multi-variant analysis part of it actually became the only dominant risk factors, in fact, over HCV RNA titer in the mother. It raises the question of, given that kind of information, is there something we ought to be doing differently in terms of identifying HCV-positive pregnant women because in the past there wasn't anything you could actually do as an intervention. And, again, going back to how you make things happen in practice, we're currently working with ACOG, and their Fetal Medicine Committee, and their Infectious Disease Committee to review those data and see if it warrants such a recommendation for screening because that gets back into that issue of, you know, identification of all of the issues and what one might do. So those are new data that, as I say, have been presented, and several meetings now are being put together for publication and are being worked on by the groups that would be most affected by it. So we are trying to move in that direction. DR. GUERRA: But beyond, obviously, the port of transmissions or just they're serving the purpose of identifying the Hepatitis C women in child-bearing years, that obviously could then be put into a registry for tracking and for doing the other kinds of preventive measures. DR. MARGOLIS: Again, it goes back to a bit of the question that Dr. Caplan asked, which turns out that actually in that age group, if you just did it uniformly, you're identification rate is actually very low because that's actually one of the lower-prevalence areas. We do have recommendations that if women have risk factors, they should be screened. And, again, if you go around and talk, especially to large inner-city OB-GYN and delivery services, many of them are screening, some of them now to the point of routine. They're definitely asking questions. And, again, ACOG has put that in one of their, you know, in their newest screening questionnaire. So, again, it's this issue of, you know, should you do everybody or should you do some, and some of the new data on possible intervention for the infant may change the equation in terms of should we do all. And that's where are right now. And as I say, this is just in the last couple of months. So we're trying to deal with it with various advisory committees. DR. GILCHER: A couple of comments from a large regional blood center that might be helpful. With respect to first-time donors, it's 95 percent of our HCV hits are in first-time donors. It's actually 95.4 percent at our blood center. We've gone back and queried these individuals. There are not a lot, but we've queried them. And what we have found is that, number one, they were not seeking tests. They really did not know they were infected. What we did find, though, was that about 50 percent of them did admit, even though they had denied this at the time of the donor screening, they did admit that they had tried IV drugs even one time. We then added another question, and this is really a comment that I'd like you to comment on. We said, "Do you have any friends that are Hepatitis C positive?" And almost every instance, they have friends. And, in fact, when we query, it's those friends with whom they tried IV drugs even one time. The other interesting finding that we have now from our NAP data, and I can only speak for my own center, is that roughly--and this is a donor population, not a general population, is that about 25 percent of the donors who are RIBA-positive appear to have cleared the infection. That's higher than what has been found in the general population. But of that group, interestingly, about 30 percent of the women have cleared, but only about 17 or 18 percent of the men appeared to have cleared the infection. I'd appreciate your comments. DR. MARGOLIS: Starting with the last one, when we looked at the NHANES data, 25 percent were, in fact, RNA negative, realizing that's a one-time RNA test. But only 75 percent were positive. The younger you were, the more likely you were to be RNA negative. And, again, that gave us some pretty wide confidence intervals, but there are other data that kind of keep coming out that way. And, again, in that data set, as you recall that African Americans had the highest chronic infection rate, at about almost 90 percent. And, again, those data and other studies have been seen that way. So that when you put that together, I think that's probably what we're seeing, what you're seeing, and it's part of, I guess, better knowing the biology and the natural history of the infection. The issue that an HCV-positive individual may have another positive individual either in their family or close to them, we're now seeing again, in a number of data sets that we're analyzing, and where again I can just give you from the NHANES that we're looking at, for instance, in families actually close to 30 percent of the families had more than one HCV-positive person in it. But when you actually look genetically, these aren't the same viruses. So it wasn't that they were transmitting to each other because, unfortunately, NHANES didn't have all of the risk factor data we would have liked in NHANES 3, but from what we have, it seems they had similar risk factors. And, again, I think that is beginning to be noticed, and we just need to get a little more precise with how common that is and how we can use it to identify individuals. It's not that this is, you know, intrafamilial transmission, but it's shared risk factors. And I think, frankly, we need to figure out better how to use that information so we can identify people. But, yes, we've seen that in the NHANES, we've seen it now in a couple of other data sets, and we're trying to, again, figure out ways I guess really to best understand it so we can use it for identifying people. DR. DAVEY: Dr. Margolis, I think we can all agree, and the comments have reflected this, that the toughest group to approach is the IV drug-abusing community. Probably over 50 percent, I believe, of infections are thought to be by that route, as Ron and others have pointed out. Could you comment on the CDC's efforts to link their control measures on Hepatitis C with other government agencies that have responsibility for managing drug abuse. And secondly, specifically, what's the CDC policy on clean needles and providing clean needles for a prospective management of this infection in that community? DR. MARGOLIS: I think probably the best indicator of what the Public Health Service--how we view this was this meeting in May in Baltimore called Drug Use, Hepatitis, and HIV--or I can't remember which way they had it--bringing it all together, in fact, sponsored by the agencies who have responsibility both for prevention, treatment, and control of substance abuse. When you then really start talking to drug treatment center directors as well as the research investigators and trying to--how do we figure this out, I think everybody's well aware and I think now is beginning to believe that the paradigm for prevention of infections among injection drug users, while HIV has been the focus, it's really HCV because it's there immediately, and, in fact, I think it's made us all--and, again, based on data that was done in syringe and needle exchange programs, actually sponsored by CDC, show that it's probably things other--I mean, the syringe and needle are extremely important, but transmission also goes from the rest of the activity, and to put it kind of quite bluntly and frankly, you need universal precautions in a drug use setting, then reflect on that and realize how difficult that is. But that's, in fact, what the issue becomes. It's everything else that's transmitting, and, in fact, we've done studies to ferret out those other things, including blood on the hands and all those things that go on with drug use. So you still got to get at the prevention side. You have to figure out how to interdict in terms of those who are using. And let me tell you, one of the things that I've seen--and I'm kind of new to this--is that in the states where we have now seen hepatitis C coalitions from a state perspective put together, it has heavily driven the issue of drug treatment. So that, again, several states now have moved drug treatment actually into clinical public health settings instead of that "over there" kind of situation. And these people are now talking to each other. And, you know, there's been real changes in total philosophy. Yes, CDC recommends that syringe and needle exchange should be carried out. The Federal Government doesn't fund it. So that's, you know, where there's some divergence. But, in fact, it's very effective, and most recently some involvement we've had with vaccinating drug users in exchange programs shows that it's highly effective, can be done, and you can access people. So I think things are changing, and the people who are supposed to be dealing with this are talking to each other a lot. Is there money? That's what Fernando asked earlier. Unfortunately, no, there's not a lot of money that's coming together with this. But I think at least we're finally talking about it and realizing what the issues are. So, you know, that's kind of--this is new and this is evolving, and evolving pretty rapidly. CHAIRMAN CAPLAN: Maybe what we will do is take one more question from the Committee. I might look to see if there's one question out in the audience. Then I will finally relieve Hal from standing up here so long. Paul? DR. HAAS: It's impressive the amount of work that you have done, and I have to believe it's also very frustrating in terms of how slow the information comes out. And this part might be the wild part, but I'm listening to this and thinking of watching these ads now showing up on TV for different types of pharmaceutical drugs and the awareness it has, I suppose, given the patient showing up at the doctor's, probably asking for the drugs for the wrong purpose, but at least they're aware that it's out there. I'm just wondering, now that we do have treatment for hepatitis C, whether some of those drug companies might be willing to start funneling dollars in to help the continued promotion that you're doing. DR. MARGOLIS: In fact, the PSAs, you know, the TV PSAs, which are very expensive, were funded through the CDC Foundation and a drug company consortium. We just didn't have the resources directly from what we had. And so we haven't gone to the subliminal advertising yet, but we're clearly partnering. And I think it's been working well. And it's also including immunizations. So when I talk about, you know--because again, as Dr. Guerra said, this is the whole thing. I mean, I don't know if you've heard me say it here, but our buzz word around CDC now--and this is with the AIDS groups and others--is one-stop shopping. I mean, the reality is you've got to think of these all together, and all the bloodborne infections are together, and we've got to start talking about it that way. And so we've been trying to do that with industry. CHAIRMAN CAPLAN: Could I just ask you to identify yourself for the record? MS. JACOBS: Yes, Mary Beth Jacobs from FDA. I have a follow-up question to the last one. About a year ago, I saw an ad in the Washington Post directed toward women from a company saying: The next time you go to your gynecologist, why not ask if you should be tested for hepatitis C? Has CDC evaluated the effectiveness of that type of direct ad to consumer, not the approaching of having companies fund the PSAs, but the comparison between that kind of approach in someone who has not yet been diagnosed? DR. MARGOLIS: No, we haven't. MR. CAVANAUGH: Dave Cavanaugh, Committee of 10,000. The occasion for this presentation is the letter, which is stopped. There are several barricades to the letter going out. We understood kind of elliptically from Dr. Satcher that a sentence is being changed, and I don't know if that means the letter's been pulled back or never went to other Congressmen. And even with the ban, is there any kind of assurance that something will happen that any number of the 435 members will be sending it when they come back in January? Thank you. DR. NIGHTINGALE: Just for the record, I spoke to Mr. Slobodan of the House Commerce Committee yesterday. We do have a plan, and we'll be in touch with you. There are separation--because of the separation of powers, I'm not going to say anything else right now, but I will say for the record that we continue to work actively with the Congress and fully respectful of their prerogatives. CHAIRMAN CAPLAN: We will come back, undoubtedly, to the letter with, I'm sure, other illuminating responses. But let's stick with Hal for now. I'm going to take one more question, if that's to Hal, and then we'll take--we're getting ready for a break, although Steve has one comment to make before we do. DR. SAYERS: Merlyn Sayers from Carta (ph) Blood Care, which is the community blood program for Dallas-Fort Worth. Heaven forbid I should delay getting into the break, but some comments that relate to remarks by Dr. Satcher, Dr. Busch, Dr. Gilcher, and Dr. Margolis. It's not all that long ago that community blood banking was a lot simpler. All we really needed to do was recruit donors, collect blood, test the blood, make components, and distribute it. But whether we like it or not, the role for community blood programs to become centers of community and public health is increasing dramatically, and that's understandable. Something like 40,000 volunteer donors a day are scrutinized by an extensive health history and extensive serological testing. So our role in community and public health then immediately relates to counseling those individuals that have been identified as potentially worthy of counseling. That community and public health role then gets extended with targeted lookback, and I have no doubt that that role is going to be extended even further when this letter comes out announcing to the nation at large what the risks are of hepatitis C, the silent epidemic. And whether we like this or not, I have no doubt that even though individuals will be cautioned against going to their blood program to donate to get tested, I would not be at all surprised if we do not see a small surge in individuals who are found to be reactive in HCV because simply they're one of the many millions that do not have health care coverage. So at every point, the cost of doing business at blood programs is increasing, and a significant element of that increased cost has to do with the fact that we now have a community and public health role. Now, we cannot exactly pass those costs, understandably, on to the individuals that we sell blood to. Goodness knows they can't get reimbursed for the additional testing that we're doing. So, Dr. Margolis, you posed the question just a couple of minutes ago, is there the money? And what I'm wondering is, if there is the money which is going to recognize that community blood programs are now a very valuable and very important source of community and public health, could there be creative ways to fund these public health programs which are centered at the blood centers? End of sermon. DR. MARGOLIS: Well, let me just tell the group, the Committee, because it's public record, you know, our budget through this year, the end of this fiscal year, is about $13 million. So that pays for all these things you're hearing about and some things you're not hearing about, like the sentinel counties, the NHANES, all of those things, and also pays for some staff. Congress, in the current President's budget for 2001, the estimate mark is an additional $5 million, and that's kind of where we are, and that's how we put it together. There's been testimony in a number of hearings as to what the estimates might be for a program that would fund counseling and testing and support of the various community activities that you're describing, and that's in the range of $40 to $60 million per year. So we're a long way and, you know, we're trying to be as creative as we can. Yes, we think it ought to be a part of the mix, and if you look at HIV, you know, some of those types of things do occur. But we don't have that for hepatitis C. DR. GILCHER: Merlyn, in response to your statement, something that we have done for over 12 to 15 years is offered what is called non-donor testing. We clearly found out that there is a segment of the population who wants anonymous testing not at a doctor's office but are willing to pay for it. And we believe that that has actually enhanced the safety of our blood supply and has removed test seekers from donating blood because we now offer this kind of program through our system, which is really in a sense a public health maneuver. CHAIRMAN CAPLAN: Okay. Thank you, Hal. Steve, you wanted to say a word about the WHO issue that the Secretary brought up, I think. DR. NIGHTINGALE: A word or two, and about several subjects. I am taking over Dr. Snyder's obligation to be brief before the break. I'm not sure that I will succeed. Hal said that you had to hear a message seven times before you really understand it. This will be the tenth time that the Committee will have heard either in full or slightly abbreviated fashion the conflict of interest statement. Relative to what we're up to, I would ask you to listen to it at least as carefully as you have on the previous occasions because there are some very important things in it, and it reads as follows: The following statement is made as part of the public record to preclude even the appearance of a conflict of interest at this meeting. General applicability has been approved for all Committee members. This means that unless a particular matter is brought before this Committee that deals with a specific product or firm, it has been determined that all interests reported by Committee members present no conflict--potential conflict of interest when evaluated against this agenda. In particular, specified in Title 18 of the United States Code at 208(b)(2), a special government employee, which all Advisory Committee members are, may participate in a matter of general applicability, for example, advising the government about its policies on the hepatitis C epidemic, even if they are presently employed or have the prospect of being employed by an entity, including themselves if they are self-employed, that might be affected by the decision of the Committee--and here is the key point--provided that the matter will not have a specific or distinct effect on the employer or the employee other than as a member of that class. The example give in 5 C.F.R. 2640.203 is as follows: A chemist employed by a major pharmaceutical company has been appointed to serve on an Advisory Committee established to develop new standards for AIDS vaccine trials involving human subjects. Even though the chemist's employer is in the process of developing an experimental AIDS vaccine and, therefore, will be affected by the new standards, the chemist may participate in formulating the Advisory Committee's recommendations. The chemist's employer will be affected by the new standards only as part of a class of all pharmaceutical companies and other research entities that are attempting to develop an AIDS vaccine. In the event the discussions involve a specific product or a specific firm in which a member has a financial interest, that member should exclude him- or herself from the discussion, and that exclusion should be noted for the public record. With regard to the other meeting participants, we ask in the interest of fairness that they disclose any current or previous financial arrangements with any specific product or any specific firm on which they plan to comment. The point here, the tenth time, is that conflict of interest is an extremely important issue in a democracy. The process of regulation--it's very important that we do this right on several different levels. We have and will continue to talk about issues where the advice--we cannot get the advice we need as a government unless we get it from people who will have a conflict of interest. This Committee is intentionally much more inclusive than some of the other Advisory Committees, and I think that has been one of its strengths. And one of the things that--perhaps my personal agenda is to try to make other committees stronger by being more inclusive. I believe that we have in the statement that I just read, and, as you can see, I deeply respect, a principle analogous to the principles that we will be trying to elucidate--to gather from you today on the broader issue of blood safety that goes part of the way but not all of the way. And that's why I wanted you to focus on it. The principle for conflict of interest works extremely well, I think, for individuals. Does it work as well for aggregate committees? That's where we fall short. I saw the lawyer to my left give a knowing smile. I think there are a few others. For example, it is perhaps not quite in our technical capacity yet to clone the chemist that I mentioned earlier and several times previously, but clearly a committee that was made up of 10, 18, or 24 clones of the chemist would not be an ideal committee. We really don't have the principles quite yet for aggregates as we do for individuals in regard to conflict of interest. How we develop a committee that is not collectively biased is something we haven't figured out yet. We have some standards, though, and I think you should look--when we make our disclaimers or our proactive statements that we encourage members of minorities, women to apply, that geographic diversity is indeed a criteria for membership on the committee, these are perhaps sentinels that we would use to see whether--as a first pass, but they're clearly not sufficient. So as you are thinking today about either the certain matters or the principles, however we formulate the statement, I would encourage you to consider that we've come part of the way towards that but not all of the way. Now, in that context, one other thing that I think we have that we don't use perfectly but I think use well is the charter that we have for this committee identifies people--the class from which we wish to draw nominees, and, in fact, this is my segue to the comments on our request for nominations for membership in the committee. Our charter does not identify specific people who have chairs on the Committee other than that there are six non-voting governmental representatives. There is somewhat of a split between people on the left, people on the right, and people in the center. That is not cast in stone. That's something we're still working on, and comments on that either now or sometime in the future from the Committee would be helpful. But as we actively solicit nominations for membership in the Advisory Committee, we would be interested in nominations that make the whole Committee stronger rather than individuals. One final point, of course, is that the Committee, while it might be the people around the table, we have made and will continue to make a deliberate attempt to act as much as we can as a Committee of the Whole. Dr. Caplan has been superb--and I would like to make that compliment for the record right now--in including members of the audience. The audience has been equally superb in their contribution, and for the record, thank you for your continued support. With that, then, on May 31st, notice was published in the Federal Register, Volume 65, No. 105, page 34705, soliciting nominations of individuals to serve on the Advisory Committee in accordance with its charter. As Dr. Satcher noted, the terms of five members will expire on September 30, 2000. Appointments will be made for a term of four years, and it is now necessary to renominate individuals previously nominated. In accordance with the Committee's charter, persons nominated for membership should be from among authorities knowledgeable in blood banking, transfusion medicine, bioethics and/or related disciplines. Members shall be selected from state and local organizations, blood and blood products industry including manufacturers and distributors, advocacy groups, consumer advocates, provider organizations, academic researchers, ethicists, private physicians, scientists, consumer advocates, legal organizations, and from among communities of persons who are frequent recipients of blood and blood products. Membership is by secretarial appointment, and I can assure you that it is by secretarial and not by staff appointment. A copy of the announcement is available at the back of the room. We have attempted to make the nomination process as simple as possible. We need to know who the nominee is, how to reach her or him, which of the very broad categories I just mentioned the nominee fits into, and that is only because of the requirement of the Committee charter, and a written statement of the nominee that, if appointed, he or she will serve. We need a copy of the nominee's C.V. Additional supporting materials are welcome but not necessary. Individuals may and are encouraged to nominate themselves. In accordance with well-known Department policies regarding nondiscrimination and diversity, women and members of minority groups are encouraged to apply. If someone other than the nominee is the nominator, we need that person's name and address. If the nominator is a corporation, we need a human contact in that organization. Finally, we need to receive the materials by 4:00 p.m. on August 31, 2000, which will be the 92nd day since the notice was published on May 31, 2000. If anyone has any questions, please contact CAPT McMurtry. His direct telephone line is 202-260-1351, and it will not be changed until after the close of business on August the 31st. [Laughter.] DR. NIGHTINGALE: Now, to the statement of issue for the meeting, at your request you are meeting to discuss the role of various considerations in decision making related to new and additional safety measures. Dr. Satcher suggested the alternative but not contradictory title of what are the principles on which a blood policy to assure a safe, available, and affordable supply should be based. This is meant to encourage rather than to limit comment. I think one of the uses, perhaps the immediate use of the comments will be as the Department considers how best to support the efforts of Dr. Emmanuel, who you met at the last meeting, and certainly Dr. Epstein, who has made huge contributions to this process, to the meeting in Geneva on November 13-17 by WHO, the first Global Collaboration for Blood Safety. A copy of the announcement was distributed with your briefing memoranda. We approach this with an open mind, with, as you heard from Dr. Satcher, a desire to participate in a constructive manner both in regard to the needs and the policies and the political conflicts of developed countries as well as developing countries. Finally, having made that comment about the immediate purpose, that is, of course, not the only purpose of the meeting. The Department is aware, in part because of its response to your previous recommendations, of the issue of reimbursement for blood products and reimbursement for the services that are incorporated into the provision of blood products, many of which economists would call externalities. The issue of what the market recognizes and what it doesn't is one of which we are aware, but do not mind being reminded once again at this meeting. The agenda for today's meeting is much less structured than it has been in the past and much less structured than I anticipate it will be in the future. The reason we have done this is to provide the members of the Advisory Committee and the members of the public in attendance an opportunity to say whatever they want to say on this issue and to do so in an unbiased context as possible. The one request I have, although I may not have honored it myself, is to keep it short. CHAIRMAN CAPLAN: Steve, just for the record, some members of the Committee have asked me, having perhaps not been as intimately acquainted with the charter of this Committee as you are, with a new election how does that affect if there's a turnover at HHS, with the Secretary, how does that affect our business, our charter, what goes on? DR. NIGHTINGALE: On November 9th, all bets are off. At the same time--I've actually--I've never gone through a government transition, particularly not being kind of in the--I don't want to call it "the bunker," but in the Secretary's office. What I do anticipate, however, is that there would not be a complete change of administration. I am aware of very broad bipartisan support for this Committee. It's been incorporated into report language in the past. It's been expressed to me privately, and I communicated it to you because, folks, it's your work that has been recognized. Where are we going? The speech that Dr. Satcher said was this Committee, I believe very successfully, has addressed six very complex issues. The burden of Dr. Satcher's--at least the text of his message was that these problems, while addressed, remain, have not gone away, and if we let them drop, they could become problems again very soon. To give a little bit of my political feel for this, it is that the establishment of this Committee and the maturation of this Committee was a very labor and emotionally intensive process. I know of no one in the government or I think in the private sector who wants to start all over from scratch. DR. DAVEY: Steve, one quick question about membership. Assuming the Committee continues, I would recommend--and I think we've discussed this--that we include a representative from the Health Care Financing Administration as a representative on the Committee joining our other government representative colleagues. DR. NIGHTINGALE: Noted. Also, I think membership on the Committee by a nongovernmental individual who may have expertise in that area would also merit consideration and will be considered. Dr. Davey did remind me to say one of the many things that I wanted to say and didn't say when I was reading my text real fast: Membership on this Committee is a membership of individuals in accordance with the charter. We nominate, the Secretary approves individuals for membership in the Committee. Having said that, I would say something else. The Committee needs new blood. You get tired of listening to me read that conflict of interest after a while, and you get tired of listening to some of the other things. At the same time the Committee needs continuity. These are issues for which we don't have good guidelines. We make it up as we go along. But I think in a government, the more, first of all, that the public participates in the process and the more--the better the road map, the easier it is to govern with the consent of all who are being governed. That's what we're looking for. CHAIRMAN CAPLAN: Okay. Unless there are any other questions about our membership and what to do to put people forward, why don't we take a 15-minute break? Then what I would propose is we come back and follow up on the issues raised by Dr. Satcher and Dr. Margolis in terms of hepatitis C lookback, notification, that area. Then I think we have some public comment to do, which I suspect is going to take us toward the values and principles issue about increasing efforts at safety relative to cost and practicality, which I know members of the Committee want to talk about, and that should get us up through lunch. So let's plan on thinking about what we heard this morning, going to the lookback issue and notification and public awareness, and spend some time with that and then move on to the public testimony as a way to move us toward the consideration of continued efforts to push for safety. DR. NIGHTINGALE: Could I have a show of hands about how many members of the Committee wish to make statements? One, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen. CHAIRMAN CAPLAN: Well, forget it. [Laughter.] CHAIRMAN CAPLAN: Okay. DR. NIGHTINGALE: On that note... CHAIRMAN CAPLAN: We have time, so we will go there. Did you want to do that sort of pre-public testimony? You want to go around that way? DR. NIGHTINGALE: Yes. CHAIRMAN CAPLAN: All right. We'll do it that way. Maybe we'll get us into that and then move into the public testimony side after lunch, if that's how that's going to work. Okay. [Recess.] CHAIRMAN CAPLAN: Could we take our seats back here, please? What I'd like to do is have the members of the committee spend whatever amount of time they want, but just a few minutes on the presentations we heard this morning on hepatitis C on the look-back. I know we've had discussions about, and requests about this matter of sending the letter. I understand that this is a subject under discussion, and has legal and even constitutional issues in play, but you may want to say a bit more about that in terms of advice to the Secretary. One idea that I had which I can toss up in front of the committee is that we might want to say if something hasn't happened by a certain date, than we would hope that monies would be appropriated to make sure that something happens by another date, but that's just my particular thinking about letters. But let me open the floor and see if, based upon the presentations, we have any discussion, comment that you want to make about the hepatitis C, the look-back, the notification issue. One thing I think we might want to urge, if not recommend, is that there be, with acknowledgement to Dr. Nightingale's comment about intensity versus duration, some effort to coordinate the letter with CDC efforts, patient and foundation activities in private sector activities. It seems to me, whether you want to commit to an intense effort or make sure that something is there that's going to go on over time, it's just important to get the ducks lined up so that you get a maximum impact of sending the letter. Plus, if the Secretary--if you remember what he said, he said in part, we're not sure we're ready for a response that might be large, to sending out a letter. Other organizations and other groups need to be on board here in terms of knowing what's going on, being ready to both field questions, but also perhaps to bring pressure to bear to make sure that the infrastructure for an adequate response, if not right after the letter goes back, that at some point in the future is there. So that is of concern to me, that we try to push that they coordinate on this kind of thing, and that we urge everybody to try and work together, all the interested parties here. Jim? DR. AuBUCHON: I certainly agree with you that coordination would appear to be helpful, although we have no data to know exactly what is going to work, and that is an unfortunate impediment, as Dr. Margolis identified, but even beyond coordination, I would urge the federal government to identify resources to put toward this problem. If I could make a--what will probably be perceived as a cynical observation--when this committee began its existence several years ago, there was a great push on from the Congress that we had to address this hepatitis C problem immediately, and we have addressed it from a transfusion point of view, but as Dr. Epstein pointed out, that is a very small piece of the puzzle. The larger piece of the puzzles is not getting the attention and the resources it deserves. One might suggest that some in the federal government--and I do not mean those around this table--directed attention to hepatitis C through transfusion as a cheap means of addressing what they thought was the hepatitis C problem, because the federal government didn't have to pay for hepatitis C look-back, primarily. They foisted it off on someone else. I think it's time, and the situation deserves additional resources from the federal government to address the larger part of the problem. CHAIRMAN CAPLAN: Fernando? DR. GUERRA: I think as we continue to take the hepatitis C national effort to the scale, we need to somehow--and I'd be interested in Dr. Margolis's response--we need to build that onto the efforts that have been in place for HIV/AIDS, the national campaign, and not take away from that, because that continues to pose a very significant threat in communities. CHAIRMAN CAPLAN: Well, perhaps we can come back after we listen to committee presentations up until the lunch period, to what we want to say, if anything, about both budget resource commitment and coordination in general. Since we've been around for the three years, I continue to find it somewhat surprising that the total budget to send out the letter is bigger than the CDC Hepatitis Office budget, but all right. Okay. I guess the way to go on this, we have a lot of people who took the request for comment very seriously, and that's great, and I am now in the unfortunate position of trying to steer a group, in terms of time, that I have learned to be unruly about these matters. But I think we have a 5-minute aspiration on presentations and statements, and what I'd like to do, is instead of organizing us by height or alphabet or something, I'm going to start down with John over there. I tend to--these people have accused me of looking to the left first, so let me go over there, and then we'll just move right around the room for committee members to make their presentations. I didn't watch all the hands, so not everybody has one, but if you do have one, let's start there and just come down. So, John, I give you the first 5-minute opportunity. MR. WALSH: Thank you. I'm used to being at the end of the alphabet. First of all, I'd like to express the appreciation on behalf of the alpha one community to this committee for taking the shortage situation with respect to A1PI products as seriously as we have. The Alpha One Foundation is dedicated to providing the leadership and resources that will result in increased research, improved health, and worldwide detection, and ultimately a cure for alpha one. AAT is a single-gene defect leading to loss of one serum protein, and there is currently only one product available, manufactured by one manufacturer, naturally, to provide augmentation therapy for patients with alpha one. The resolutions that I would like to report on in the form of an update that helped us through a crisis that lasted some 24 months with supplies decreasing for allocation between 40 and 80 percent throughout our population. On April 28, 1998, resolution: "The Department of Health and Human Services should explore, in collaboration with industry, health care providers and appropriate consumer groups, methods to optimize and standardize allocation of available products in an equitable manner, including management of emergency supplies and programs that distribute products directly from manufacturers to registered consumers." This distribution issue was addressed by the Alpha One Association, the alpha one community, in conjunction with the foundation and the medical and scientific advisory panel. We did address it, and a direct distribution strategy was developed to respond to the request for direct consumer allocation, and deliver prolastin directly to the consumer. Prolastin is no longer sold to distributors. It is allocated directly from the manufacturer to the consumer, ensuring that the fully-prescribed dosage is available to each alpha as long as there's product available, which includes issues related to lot releases and ultimate supply issues. Everyone enrolled in the program has received their full prescription at 28-day intervals, resolving the need for reduced dosages or increased intervals at this time. In addition, over 200 consumers that did not have access prior to November '99, are currently on augmentation therapy. So a controlled direct distribution in the case of a one-product-one-manufacturer community like ours has definitely resolved the inequities and directly related to decrease and severe shortages. April 28, 1998, the committee made a recommendation that industry should explore with the FDA strategies for reallocating partially processed plasma materials from one manufacturer to another, you know, to optimize production of alpha1-antitrypsin deficiency and other plasma derivatives. We are able to work very closely with industry, and again, on behalf of the Alpha One community, I'd like to thank the American Red Cross and Baxter for working very closely with Bayer in a cooperative relationship that ultimately provided enough 401 paste to optimize production capacity at both of Bayer's manufacturing facilities. So for now we have enough raw paste to produce at maximum capacity. That does not mean we're going to have enough end product or throughput to be able to satisfy demand. April 28, 1998, again the NIH and industry should immediately evaluate alternative dosing schedules and alternative delivery systems for alpha one therapy, including prophylactics strategies and strategies for treatment during acute exacerbations of disease, and accelerate the development of gene-based products and gene-directed therapies for alpha one. This definitely supported the evaluation of new delivery technologies. The advisory committee recommendations for expedited development of new and non-plasma derived options helped break the logjam for aerosol or inhaled development of A1PI, and we currently have three manufacturers that are in various processes of development for an aerosol product, including one transgenic product, will be the first recombinant product available to our community, potentially available to the community, obviously, pending trials and licensure, but it's already gone through a Phase I. The current situation, with only one manufacturer and one product, with limited production capacity, it is inevitable that demand will exceed supply. In fact, I believe we're there right now, where we're going to see, within the next two months, the inability to be able to dispense 100 percent of prescribed dosages to patients, so we've already hit the wall in optimizing the distribution. We need another product. This will ultimately affect every consumer. The product will continue to be shipped in sequence with no prioritization given to reimbursement issues, which was one of the problems in our distribution that's corrected by this, effectively, or clinical triage. There's been no determination by medical and scientific advisory committee that clinical triage is possible, let alone appropriate in relationship to augmentation therapy for alpha one. It failed in Europe. The European Respiratory Society tried to implement one in 1999. The future IV products--there are two IV products currently under different stages of development. One is finished the Phase III and delayed in PLA application for numerous reasons. The other is in Phase III now. It's fully recruited for enrollment in the trial and should be completed, and once their data is analyzed, will obviously get to the FDA for expedited licensure. There are three initiatives, as I said, with respect to the aerosol delivery, which would--we hope, would make a more efficacious process to deliver the drug directly to the lung. It's hoped that aerosolized products will provide increased access to more consumers, being able to take care of up to five times as many consumers with the same raw material, and also be more cost effective. The Alpha One Foundation will continue to work closely with industry and the FDA to promote the development of new therapies. Alpha One has a meeting scheduled with the FDA and CBER, which has been very cooperative in addressing the issues related to clinical trial design and the IND issues. One of the issues we're discussing is a recommendation to form a working group between the FDA, the NIH and the Alpha One Foundation Medical and Scientific Advisory Group, to be able to actually look at some of the surrogate marker endpoint issues and other impediments to design of clinical trials and approval of products. And the foundation is organizing and HR CT scan, using high resolution CT scanning to look at the progression of lung disease as a potential surrogate marker, and also an animal model study workshop, which will be conducted in Sienna in Italy. There's just a couple other comments that I would like to make to the committee. Regards HCFA, the committee's action, I think HCFA had more response to the outpatient prospective payment issues. The APC code change, where there would be a direct path to plasma derivatives, definitely made it possible so that all of our HCFA consumers would not be cut off from product and create a real problem for access. So we thank the committee for the support in that. We've taken the responsibility to communicate directly with all of the distributors, all of the providers for HCFA treating alpha one patients, and let them know how to actually do the billing, and we're working closely with HCFA to accommodate that. The transition to recombinant is a result of this committee's strong recommendation, although I notice that the--in the final recommendation that was published, it only mentioned hemophilia factor products. I believe the committee discussed that in the broader context of plasma derivatives, and I'd like to state for the record that I think that very much helped the PPL Therapeutics out of Scotland to focus their attention on alpha one, and not just cystic fibrosis. Finally, I'd like to thank the members of this committee for their support for the Five Points of Life, speaking of donor awareness, and the Surgeon General's remarks earlier, the Five Points of Life event is to raise donor awareness for organ tissue, DNA, plasma pheresis, obviously, donations country-wide. Dr. Gilcher, his group has a rider involved with that program that raises a lot of awareness, and I think it's just a ripple and we need to do more, as much as possible, we're committed to. ARC, AABB, ABC and ABRA have all contributed to sponsor the event, and there will be an activity here in Washington, a reception for congress people. And even the insurance industry is involved. State Farm, I think, is the only one I'm aware of so far that's embraced this, but I think it's important for us all to take on the responsibility to get involved with creating more donor awareness. I would also like to thank the organizer of the ride, Life South, for all their efforts, and to thank our committee's Executive Secretary, Dr. Steve Nightingale, for his ongoing participation and support throughout the process. Dr. Nightingale is actually riding the first week, from Bar Harbor, Maine to Boston, Massachusetts. So again I thank the committee on behalf of our community, and look forward to making more progress in the future. CHAIRMAN CAPLAN: Thank you. Unless it seems--I mean if someone--I'll take a minute to see if there's a question or a comment after each speaker, but you don't have to feel compelled to do so, comment or--that's a polite way of-- [Laughter.] CHAIRMAN CAPLAN: All right. Jerry? DR. WINKELSTEIN: Well, I was unprepared. I'm usually last alphabetically, so thank you very much. Well, I wanted to make two comments. The first is in the form of a thank you, which is heartfelt, and the second is in the form of a proposal for a future agenda item. Now, the first is a thank you, and if you will remember, one and two years ago I presented information to this committee when I was not on the committee, but a member of the audience, about the shortage of IV gamma globulin and the many patients with primary immune deficiency diseases. I'll remind you that well over 10,000 patients receive IV gamma globulin, and it is the only thing for primary immune deficient patients which is therapeutically beneficial. There's no substitute for the IV gamma globulin. But during the past few years there had been a very significant shortage of IVIG for these patients, which was impacting very significantly on their health status. Now, the part of the thank you is that through the efforts of this committee, a similar committee advising the FDA, the Immune Deficiency Foundation, and under the leadership of Dr. Epstein, the FDA itself, all of these groups developed a realistic and achievable clinical protocols which will speed the licensing of new IV gamma globulin preparations from a number of old manufacturers and new manufacturers. One such protocol, my understanding is, nearing completion, if not been completed, from the patients' point of view at least. Another clinical protocol has begun to enter patients over this summer, and two other manufacturers are developing clinical protocols as we speak. I believe that the availability of these new preparations will help very significant in alleviating the shortage. So my thank you is that I would like to publicly thank both this committee and the FDA for their efforts to alleviate the shortage. I do believe it made a difference, and I think we're seeing the results of that even as I speak. So if you ask yourself if the committee has done anything worthwhile, which I had to ask myself before I joined the committee, rather than sit around, I can give you evidence that you made a significant difference for these patients. Now, my second point relates to asking your advice as to whether or not there should be consideration for a new agenda item over the next number of months or year, and I'd like you to consider whether this is an appropriate agenda item. Now, as you know, patients with primary immune deficiency diseases are the only long-term users of IV gamma globulin, one of the plasma products. Many of the patients have been on for decades. In fact, there are patients entering their third decade of use of licensed IV gamma globulin in this country, and most of them will remain on IV gamma globulin for a period of four, five or six decades if the therapy is as good as we think it is. From that point of view they're quite unique, and represent, if you will, a canary population for patients receiving IV gamma globulin and many other disease states in the short term. These long-term patients receive it for decades, as I said. Now, in recent years, there's been a growing suspicion that long-term consequences have not been well documented. There are at least two articles of anecdotal case reports of patients with primary immune deficiency disease, who have received IV gamma globulin, presenting with unexplained central nervous system diseases. In addition, there are some other problems associated with the use of this material, as there would be with any pharmacologic or biologic material. Renal disease, immediate adverse events, and the consequence of long-term use have been looked at, but not in a formal way. And so what I'm wondering is whether or not this committee should consider adding a future agenda item which would include presentations on the value of a formal assessment or prospective study of the long-term and short-term adverse effects of IVIG. Obviously, I would hope then that they would endorse such studies because these studies are not being done currently. Whether that's a role for this committee or not, I'm young on the committee, and so I'm not sure, but I did want to bring it to your attention. CHAIRMAN CAPLAN: Thank you. DR. NIGHTINGALE: I would comment briefly that there are many ways to view the role of the committee and many readings that you can make of the charter, but one that I think that would encompass not only your statement but the statements that I anticipate from the other side of the room here, would be that this committee very fundamentally addresses what economists call externalities. For those of you who are not either economists or children of same--and I am in category B--and externality is a cost of producing a good or product that the market for one reason or another does not recognize. So I think I've answered your question constructively. DR. WINKELSTEIN: Then my impression would be that this would be an appropriate agenda item, depending on priorities of the committee. CHAIRMAN CAPLAN: Jane. DR. PILIAVIN: I was under the impression that our remarks were supposed to be addressed to the precautionary principle. So of course, as soon as I start to talk, my voice acts up. And I guess I'd like to start by referring to the article that you included in our voluminous materials for this meeting, entitled, "Will Blood Transfusion Ever Be Safe Enough?" And that's the point that I guess my remarks are all oriented around that. Whether that puts me on the left or on the right, I don't know, because I don't know where that dimension goes from to. I also want to note that we were just handed out a bunch of new stuff, one of which is a memo from Merlyn Sayers about leuko-reduction, which just ties in with this same issue. First I want to say that I read everything you gave us about the precautionary principle and I still don't know what it is. That's because very early on in the material it says that it's not going to give a definition of it, and then as you read the examples, clearly, the precautionary principle goes everywhere from saying if something has any kind of potential harm to the environment, to human health, you shouldn't do it, to a very basic kind of risk cost benefit analysis on the other hand, that says when it comes to new technological things, you should be really, really careful and think about the concerns for human health. So I don't know what the precautionary principle is. I think we all have been trying to be careful, and if the precautionary principle says "Be careful", then we've been following it. I get the sense that because of the examples they use about the European community, there's more attention in regard to this principle to new developments than to long-standing situations, and I'm wondering whether that's appropriate. Is it only about new technological things or is it about any kind of dangers? And I'm going to deal with it more as if it's any kind of dangers. Okay. I kind of liked one of the things I read in here which said that when dealing with data under the precautionary principle, you need less than a preponderance but more than a scintilla of evidence of harm. I just love the word "scintilla" anyway. And I'm wondering to what extent we in the past and other committees have been dealing with scintillas or less rather than with preponderances, and that we should take that into account. I'm specifically referring to the NBCJD issue, which strikes me as having less than a scintilla of evidence. As you all know, I have been opposed to that regulation regarding people who have been in Great Britain. Also in the materials on the precautionary principle, one of the things that they said--and this was clear--is that you should deal comparably with things, that you should not have one sort of reaction to one problem and a different kind of reaction to another problem, that things should be dealt with in some equitable kind of way. And again, referring to the response to NBCJD, I would like to ask why did we respond that way to that issue and have not responded to what struck me as more evidence about Chagas Disease, and certainly lots more evidence about problems with errors, simply blood matching and other kinds of errors. Now, these--I mean, the latter is of course not technological in the usual sense and it's not new, but if we're going to apply this principle to concerns about risk, I think we have to look at having comparable responses to issues, and certainly there are far more people who die from errors of the sort we talked about last time than have, obviously, NBCJD--nobody's died--and Chagas Disease, I don't think anybody's died from transmission, and certainly there's all sorts of things that could come down the pike. In terms of equity issues of a different sort--no, I think I'm going to skip over that because I know I don't have that much time here. I want to get back on my usual hobby horse of safety equals availability. At the level of infectivity that we now have in the blood supply, the idea of adding leukocyte depletion and individual NAT testing strike me as inappropriate use of money for a variety of reasons. Of course it's going to drive the price up, which will lead to both a decrease in the number of people who can afford the product, and a decrease in money that's available for other things. Certainly it will lead to an increase in medical premiums. It will put an excessive drain on the public funding, Medicare, Medicaid, and from what I saw in terms of the estimated dollars per year of quality adjusted life that will be added by the individual NAT testing, this struck me as really inappropriate use of money. I want to think, in terms of other uses of money and how much life could be saved, things of the sort of child immunization, sex education and HIV prevention, prenatal care, visiting nurse programs and even cancer research, and certainly putting in funds for getting more information to more people about Hepatitis C would come under better uses of money. In regard to availability then, these things also have the impact of further decreasing the availability of blood, but also the possibility of bankrupting the blood centers. Because it's more or less guaranteed, I think we all know, that reimbursement for the Medicare/Medicaid patients won't be sufficient. As a social scientist, I was thinking about this as I was reading the materials, I would love to get a survey of all of the blood centers in the United States to see where they are financially. I mean, it's conceivable to me that all of a sudden a good proportion of these organizations, which are mainly nonprofit, are just going to go belly up, and they're not going to do it one at a time so we can see a trend going. There's going to be a bunch of them who are going to say, "This is the straw that breaks the camel's back. We can't do it. We have to quit." And that can be a disaster. It would be very nice to know where they are, how close to that point these organizations are. Because if anything like this disaster scenario were to happen, we would be in deep trouble. It's clear, also, from the materials that this message we've been trying to send, that we want a no-fault coverage for people who do, indeed, get injured by these very, very, very few people who get injured by infectivity in blood, that nobody is paying any attention to this. The secretary says they can't do it, and I'm sure that they can't. And the Congress, who mandated this committee, seems uninclined to do anything. I think the best precaution against the very small known risk would be accepting that risk at this point and providing that kind of relief for people who are, indeed, harmed, as we do for people, the very few people who are harmed by vaccines. I'm trying to think of a comparison that would be apt in terms of the number of people who are injured in this arena, as compared to other arenas. Unfortunately, I was late reading my material, and therefore did not have access to even the Internet to check anything. But I know that we lose many more people on the highway in one day than from transfusion-transmitted diseases in the last 15 years. And so that struck me as apt. Why aren't we putting a lot more money into educating people about safe driving and so on? Undoubtedly, we lose more mothers and babies from inadequate prenatal care, to put it in the same arena, but the people that we're losing are probably, for the most part, from groups that aren't powerful enough to lobby Congress for their needs. Why aren't we doing cost-benefit analyses comparing the things that we spend our money on? Now, obviously, this committee as a committee can't do that. But you asked us to give you our opinions, and this is my opinion. I think that the next HHS secretary should ask Congress to appoint a committee to assess how our medical dollars are spent across the spectrum of things that endanger the health of our populations--how much bang for our buck are we, indeed, getting? I want to end with sort of the old simile about, in terms of where we're spending money, are we like the drunk who drops his keys while trying to open his front door, but looks for them under the streetlight because he can see better over there? Are we pursuing technological and bureaucratic fixes for smaller and smaller risks very expensively simply because we can, while ignoring much more critical problems because we can't? CHAIRMAN CAPLAN: Comments? DR. NIGHTINGALE: I need to make a couple of brief procedural comments. First of all, Jane asked, very legitimately, what is the precautionary principle. It was included in your packet because it is one of the many approaches to the answer of the question not because it was a preferred approach. If it has any primacy, it is because it is, in fact, the law of a very large chunk of land with which we have trade, in which we have biologic trade, and it is not something that I think that we are free to ignore, although we are, by no means, required to accede to it. And if my own personal take on it snuck in, in that last comment, so be it. I realize, also a comment to Jane's why was the precautionary principle put in, in something this big, it was put in because this is a very complex question. And I think one of the things that the government can do wrong when it runs a committee like this is to try to dumb it down so you can get an answer. And one of the things we have not done here is to try to dumb this committee down. And along those comments, when Jane finally asked are we getting our bang for our buck, this meeting costs about $25,000 to put on. Most of it goes to plane tickets and most of the rest goes to the Hyatt. Not much goes to food, as you tell. [Laughter.] DR. NIGHTINGALE: But I would say, so far, we are getting advice at about a thousand bucks a pop, and so far it is the judgment of the government that we are very much getting our money's worth, and I thank you. DR. PILIAVIN: Steve, I wasn't talking about this committee. I was talking about the medical budget of the United States. DR. NIGHTINGALE: No, no. But I was trying to say thank you. [Laughter.] DR. NIGHTINGALE: It's easier to say that to some people than others. [Laughter.] CHAIRMAN CAPLAN: I do think the precautionary principle is used by some outside the United States, and their policy is for new things, so it doesn't really set itself up for comparative risk assessment. John? DR. PENNER: It seems to me that the recurring theme of our deliberations is what price safety. And I'd like to reemphasize the fact that I don't believe blood is an industrial product. I don't think it's comparable to a drug or a medication. I think it's unique, it has no alternative, and you do not have a dose ratio of efficacy to safety. In other words, exposure and the occurrence of any viral effects to that exposure are not reversible. It's all or none. You can't just reduce the dose and reduce the side effects or complications associated with this item, which we call blood. If we had a situation whereby a medication I think was put up for approval and would produce a death rate of, say, 1 percent or 1/2 percent or so on in every recipient that received it, I don't think that drug would be expected to be approved. And we do have that situation with blood, that it does, once it's administered, produce an effect that is not going to be reversed in those individuals who are exposed to whatever the contaminants are. And since there is no alternative, I think we're put into a very unique situation that is not comparable to what we find with other manufactured medications. And then lastly, I think the public expects safety with this product. The donor population is particularly sensitive to this issue and always will respect the fact that if the blood is not considered to be safe, we will probably continue to have problems on recruitment of donors. It will have an impact. So it would seem, therefore, to me that cost will have to respond to these requirements. And despite the fact that the cost effect may be considerable, I don't think we really have a lot of choices if we want the public to respect the fact that we are providing them with something that they don't have to fear. CHAIRMAN CAPLAN: Good. Karen? MS. LIPTON: I just had a few short comments. And we're going to have more of an opportunity later on the precautionary principle, so I was going to leave that aside for now. I wanted to let you all know, some of you knew, I actually had an opportunity to participate as a blood safety and availability committee member in the fourth annual meeting of GAIN. And GAIN is the Global Aviation Information Network. It's a very interesting organization. It sort of takes off from where we talk domestically about air and accident reduction. And the whole purpose of GAIN is to really improve aviation safety worldwide by promoting the exchange of information by and among members of the aviation community. When you get into the details of what GAIN is, it's truly a remarkable partnership between government, FAA in particular, but other government regulatory agencies around the world, and the airline industry globally. And the whole purpose is really to share information about near misses, and deviations and problems that come up--I mean, to share it in a way that really is a no-fault exchange and really does improve safety. The FAA provides technical support, but the aviation industry is truly in partnership with the FAA because, together, they have constructed a data base that everyone has access to. Now, interestingly, they have the same barriers that we identified in our last meeting, the principle barrier, of course, being legal obstacles. There's fear of discovery of the information that's in the database, and there's also fear of the punitive action that might be taken as a result of the information in the database. It's interesting that they've been able to solve those problems. They've been able to solve it both through international treaty and through an international organization that's very interested in promoting this and has gotten different countries to sign on to their principles. FAA itself I think we saw by the regulations has agreed that they will not use the information that's reported through the system to take punitive action. Some of the other obstacles they reported will sound familiar--lack of support from people within their own profession, that cultural shift that needs to be made, and also from the CEOs' perspective in the airlines, demonstrating cost-effectiveness. But they are making some headway there. I wanted to comment about this conference and tell you about it because, at the end, the conference came up with five guiding principles. They were consensus statements. And I only want to talk about the first two because they do relate to our discussions later today, whether it's on precautionary principle or blood safety issues. One is that the first guiding principle is that the safety of passengers and workers is of paramount concern to this industry. My guess, as they stated, it's because generally the airline pilot is first at the scene of an accident. But that being said, I think there are some things that we can take into our own community from that. But the second was very, very intriguing to me, and that is that the public perception of safety, of airline travel, is as important to them as absolute safety. And this is a principle that, excuse the pun, they live and die by. They don't have a problem incorporating that into the actions that they take to improve safety, even when they think that airline travel, if you look at it, is safer than it's ever been. We've heard that before. You know, your chances of really dying in an airline accident are quite small. But they don't care, they are continually trying to drive down the number of accidents. So I just wanted to bring that up, and perhaps we could get back to that again when we talk about our own decision making. The second issue is to talk about reimbursement, and again to thank this committee for its support, and HHS in particular. We did achieve some beneficial changes to outpatient reimbursement. We're now really working diligently and very hard on trying to change reimbursement for inpatients for people who will require transfusions in the hospital. We've been greatly encouraged by the interest of congressional members in this issue. They clearly appreciate that both safety and availability, as Jane pointed out, are really tied to reimbursement issues. I think, at the same time, we've frankly been I guess challenged and maybe somewhat disheartened by the lack of uniform appreciation and support within the health care community itself for the need to fix reimbursement for blood and blood products. There's a general need to say we need to fix hospital issues. But getting the attention focused on blood and blood products continues to be a dilemma. After all, we compete with a lot of other issues that hospitals are concerned about, and we're critical, but we're small. But, again, we are critical, and I think that we lose a real opportunity if we don't keep this committee's attention on the reimbursement issue and if we don't keep pushing. I guess we're going to hear a little bit later from Paul on some adequacy data. But, again, related to reimbursement, adequacy remains a critical issue in this country. But to my mind, adequacy, again, it's not related to a lack of good ideas, it's not related to the fact that we don't have good professionals or very motivated people. The real issue is it all comes down to costs. It costs money to recruit donors, and we have not been paying enough attention to putting money into that side, and that will raise the cost of blood. I think, frankly, as a government and as a society, we've been kind of content with supplying just about enough blood--80 to 95 percent. We could easily get to 100 percent, where there aren't shortages, where there aren't surgeries that are postponed. But it all comes down to reimbursement and comes down to the cost of what that last unit will be. And it really isn't, in most cases, to the individual patient, it's what we as a society and we as government or, you know, part of the government today are willing to pay for. CHAIRMAN CAPLAN: Jim? DR. Au BUCHON: If I could just second Karen's note about the importance of public perception of safety and commend to the committee's attention an article that appears in this month's issue of Transfusion, entitled, "Public Perception of the Risk of Blood Transfusion." And in that article they note that about two-thirds of individuals in a national telephone poll noted that blood transfusion was associated with images of safety or high levels of safety, but one-third did not. And they regarded blood transfusion as risky or very risky. And the authors went on to note that the perception of an individual about the degree of safety in transfusion today was closely correlated with their perception of safety of other technologic matters and that even for those individuals who did not regard blood as being unsafe today, it wouldn't take a whole lot to sway them in the other direction should something pop up. And in their conclusion they note that it is better to spend resources prophylactically on this issue because the consequences of not averting potential concerns about real or imagined risks, and thus losing public confidence, can be extremely costly. We've seen that in blood banking many times over. CHAIRMAN CAPLAN: Dana? DR. KUHN: Mr. Chairman, I really don't have a comment unless we're not going to revisit the "Dear Citizen" letter. I still had some questions that have been left unresolved, and hopefully, I'm not sure if we're going to come back to address that issue. CHAIRMAN CAPLAN: You can do it now. We can come back. We should say something more about it. DR. KUHN: I think that I understand that there is a dilemma about allocating resources to inform the public versus the resources to handle the requests for testing, once that letter is out. And that brings me to the question has that letter gone out. I seem to have, maybe I'm interpreting things wrong, but it seems to me what I have been hearing is there's kind of some elusive answers to whether or not it has officially gone out, the letter. Has it gone out? In what capacity has it gone out to the public? Has it been funded? And to what extent has it been funded to go out? Did the House Administration Committee request the funding for it? Has it in this budget year? Is it there? And the other question I have, has it perhaps not gone out because of the 90-day rule, and will it go out after the 90-day rule is complete? The question I have, I was hearing that it had gone out, is that I happen to be a constituent of Congressman Bliley, and I have not seen a letter come to me notifying me of anything of the kind. The time I saw it, the first time, was when it was sent to us in a packet. So there are a lot of questions I think are still unresolved that I would like to hopefully have answered to know more about whether or not or what this committee may be able to do. If the funding is not there, does the committee have the power to request the secretary somehow, some way, maybe--as we all know, the elusive budget or member of the budget is usually the HHS bill. And I'm not sure if it could be attached onto there, the funding to do it adequately in getting out this letter. I'm still, there are a lot of questions that I would like to see if there are ways, perhaps in the time we have today, these could be answered. DR. NIGHTINGALE: Let me try to do a better job than I did the last time. The letter had been the subject within the Department long before I arrived. When I arrived, it got a formal hearing. In fact, after Dr. Kuhn asked Dr. Margolis a question in February of 1999, is this still on the table, and Hal said, yeah, it's still on the table. And following that meeting, I made a second investigation of the cost. I had made one actually in August of 1999, and the cost that I had gotten some bids from private manufacturers was far in excess of $30 million. What I found was that the post office charges 13.5 cents to send a letter. And if you're going to send $100 million letters, that's going to be $13.5 million. The printing of a letter--if it was going to be on official stationery, something that would make you look at it, would probably be two-color with the surgeon general's letterhead, it's blue, it says, "Public Health Services," it's the letterhead we use--would probably be in the range of 11 cents. And one of the issues, of course, is you put it one side English and one side Spanish, where do you stop, where do you start? Probably low end will be about 11.5 cents for English only, two color. In addition to that, there are costs for sorting the letters. You've got to put 100 million labels on there. That's going to be about 4 cents a letter. And you've also got to deliver it. So while I might, until right now, privately peg the thing at about 26.5 cents per letter sent out, I don't know if we could do it for 26.5 cents. A hundred million is a round number, but that's the number I've gotten from a couple commercial suppliers. So there is real money involved in that. This is 20th century technology. There are other ways of delivering letters right now. They may be in the process of development, but the Internet is not necessarily the best way to deliver mail to the targets of this--to many of the targets of the letter. But a third way that came up in private conversations that went on for several months between the Department and the House was inclusion of this into a congressional mailing. The idea was not to have a separate letter, you know, a separate envelope on with Bliley's frank on it, but Congressman Bliley or anybody else in the House who had a teenager who knew how to use Adobe Pagemaster--I do, that's presently unemployed--and I think there are others in that group that what we thought we could do is get the same message out at less than $30 million. I think that there are the problems, the objection to the separation of powers, was not one that was anticipated by either side at the time that we had the press conference. We weren't going to do the press conference. The thing came up. Hey, I was in Ely, Minnesota, when I got word of it, came back and have this being dealt with. Max has been dealing with it, and we'll be dealing with the issue next week. We did review this with Dr. Satcher on Monday morning. Max had the conversation with Al, and I've had a conversation with Mr. Slobodan. And we're going to proceed as quickly as we can to resolve the issues. The one thing that I have to emphasize, and this is a very direct order from the surgeon general of the United States to his employee, is respect the Constitution, the autonomy of the House. And that is the sole limitation on what I have to say right here. I think I've probably said as much as I can. But if you want to try to pry some more out of me, go right ahead, and I'll try to open up. CHAIRMAN CAPLAN: The issue still, however, remains, and we can get back to it later, of whether we want to say anything about how to proceed with the letter in terms of should things not go well, in terms of the autonomy and privileges of the Congress looming larger than the surgeon general's mail opportunities. Do we want to say something about what should happen then or, as I said, put a date forward and say if it doesn't happen by X, then let's ask for Y, appropriate monies, et cetera, et cetera. DR. KUHN: Yeah, I think we need to be specific in asking for a date. I guess what I'm hearing you say, Steve, is that the letter is not going to go out. DR. NIGHTINGALE: Did I say that? DR. KUHN: Has it? Well, I guess the question I'm asking, has it gone out? DR. NIGHTINGALE: If you go to www.surgeongeneral.gov, you will find the letter. It's one of the four little blue lines up at the top. It's on the CDC's website. Before we received the concern of the House Management Office, a photo-ready copy of the letter that was underneath, not on top of, but underneath the press release by Congressman Bliley was hand-delivered to every office of the House of Representatives. I believe that the American Liver Foundation was provided with some copies of the letter, as well, these being at taxpayer expense. This was what I was doing between the time the letter went out and between the time I mailed it to you guys. So it was something being done, yeah. It's being done. DR. KUHN: And I understand it can go out on the Net, but then there's not a whole lot of access to the American public to the Net and then even finding where it is on the Net. I guess, and I'm understanding also that it probably went to each member in Congress, this letter? DR. NIGHTINGALE: It was a copy in a white manila--well, in a manila-colored manila folder--was, in fact, delivered by--we hired a temp, a really good guy. CAPT. McMurtry: It went to every member of Congress, every voting member of Congress, every nonvoting member of Congress, the representatives from the trust territories and the District of Columbia. If there was an office in any House building, it got a copy. DR. NIGHTINGALE: And it got a copy the day after. And that copy--actually, it was 2 days after, because we spent a day having the temp run the letter through the autopen, so it would have the same signature--the original legal signature and not just a rubber stamp. CHAIRMAN CAPLAN: I'm going to go over to Larry in a second. But so far we know that the Congress has been notified about Hepatitis C. So anybody else besides them? MR. ALLEN: I guess a couple of things that I wanted to know about. First of all, it's been passed on to members of Congress. Do they have an obligation, from that point on, to send a letter out? DR. NIGHTINGALE: No. MR. ALLEN: Beyond the fact that the surgeon general has written this letter, who is actually in charge now? Who do we go to to find out where the next steps are going to be taken for this? DR. NIGHTINGALE: Well, I think it was suggested earlier that the Advisory Committee might wish to make some statement on the subject. I have not been told by my boss, the surgeon general, to discourage such a statement. Did you see me wink? [Laughter.] CHAIRMAN CAPLAN: Mike? DR. BUSCH: I think this is an interesting discussion because all of us, at the initial discussion, the idea of sending out a letter to notify the public, said it sounds like a reasonable thing to do. But then hearing the costs to me, $100 million, in the context-- DR. NIGHTINGALE: Thirty. DR. BUSCH: In the context--or $30, depending on, you know, how it's structured, et cetera--is extraordinary. And I really would question whether the concept of a letter to the public, particularly one focused, in part, on transfusion recipients or even on HCV is an appropriate--this is an appropriate mechanism to raise this issue. I think you've done the correct thing in putting the brakes on this and asking is this the mechanism. And I'm not so sure it is. And certainly if there is going to be a letter, I think it perhaps should be framed with much broader implications than certainly transfusion recipients or Hepatitis C specifically. I think 99 percent of these are going to end up in the trash can. DR. NIGHTINGALE: Dr. Busch raises--we didn't come to the 99-percent in the trash can letter--but if I could quote, without hopefully misquoting Dr. AuBuchon in another context, I think I heard him once at a public meeting say, "If this cost five bucks, we wouldn't be talking about it." That was in September of 1998. Jim recognizes the allusion and doesn't fight me too bad. There are a lot of things that we could do with $30 million. Dr. Margolis just talked about a couple of them. If time was not an issue, I could go on for a number. There is a--yes, I'm saying it--a finite amount of money here, and what we're trying to do is to make the best use of the available money that we have. In that context, however, I would say one thing that gives me an opportunity to respond to Jane and perhaps anticipate a response that I might want to make to some of the other members of the committee, there is a very common assumption among noneconomists that many economic issues are zero sum gains. We spend so much money on a letter, we don't have the money to spend on something else. That assumption is not, in many economic domains, true. For example, those of you who got through EC 1 heard of the multiplier effect. Hopefully, you remembered it when it came to the final exam. The recruitment of funds from a government source to a nongovernmental source is another. In a simple world, we do simple things. At the risk of dumbing down to the committee, this ain't a simple world. CHAIRMAN CAPLAN: Does anybody care to comment on the impact/effectiveness of the previous Koop letter? I mean, we did have an experiment on letter writing from the surgeon general about something. DR. PENNER: I think that issue that Koop proceeded with on the tobacco? No. On the HIV? Or the HIV--yeah, both had surfaced very effectively I think in the media. So I don't think it would be as startling as the Hepatitis C. maybe we should send this out with the income tax forms. That would be cheap. DR. MARGOLIS: There were several formal studies done of the America Responds to AIDS letter. Basically, about half of the households recalled getting the letter. Those who recalled getting the letter, and this was again with some pretty wide sampling, of those who recalled getting the letter, it was probably around half of those individuals used it to discuss issues about HIV. Now that letter was focused on transmission issues, not a call-to-action to do anything. And, in fact, it was quite variable of what was looked at as to whether anything happened. Now, you have to realize that what was in place at that time were hotlines not only at the CDC or the national hotline, but also essentially every state was funded for an HIV hotline. And some states saw increases, some didn't see any change. So it was kind of inconclusive as to whether it changed anybody's behavior, but it was clear that it did change or had people discussing it. I mean, that was kind of the focus group or the context of it. But, again, it was a very different at least thought-to-be-purpose. That was clearly to talk about transmission issues. And I know much of the issue for this letter is to, again, get people to do something; namely, to get tested. And so, again, we have no experience with whether these types of things do that. MR. ALLEN: I hear a couple of things. I hear Dr. Busch say something about it might have been right to put the brakes on. I know I missed the morning session here, but have we put the brakes or has someone put the brakes on this letter? That's the first part. DR. NIGHTINGALE: No. MR. ALLEN: Okay. Secondly, in my opinion, I see this committee having an obligation to at least continue what we've done, you know, up until now, which is continue to push for some form of notification. I don't see how we can get around that being on this committee, that we go ahead with that beyond things like the Internet or PSAs. I think we need to continue to push for some type of a letter to go out and find a means of doing it, so that if it is $30 million, maybe there's a way of getting it out cheaper than $30 million. But I just see that that is an obligation of this committee to make sure that as many people as possible are notified in the proper manner. CHAIRMAN CAPLAN: Well, one thing we could do, if we're amenable, is ponder this a bit more and return to it this afternoon. It's somewhat disquieting to me that we may get the letter rolling without coordination, and the involvement of other things that might want to accompany the mailing of the letter. I know the Surgeon General would like to probably put his health indicators thing into any mailings that he does so you can find out you should get tested and you're fat, too. [Laughter.] CHAIRMAN CAPLAN: But that's my personal animus about this thing. The fact is, without coordination, I worry about impact here. It is expensive, although one thing we can also ponder if we're going to return to what we want to do on the letter business is: Has Congress really taken hepatitis C seriously, the challenge of it in terms of budgeting and so forth? I remind you, again, we're spending more on the letter than the CDC office budget, so that's an issue. And maybe we should spend a lot more on both, but we may want to say something about rising to the challenge here in terms of adequate funding for this public health problem. That was a way of saying why don't we table the discussion, but come back to it, and go to Keith. DR. HOOTS: Well, even though it's the heat of the summer, this is kind of, as I understood it, our January meeting and the fact that we were looking backwards where we've come from and perhaps forward where we ought to go. And so I thought it might be an appropriate time both in reality and philosophically to look at a couple microcosms. John has already looked at one. I thought I'd look back at the hemophilia issue, particularly in the context of what Jane alluded to, which we've been over many times, which is that safety is intrinsically linked to adequate supply, and also alluding to what Karen was talking about with regards to the precautionary principle. Perhaps implicit in that is being ever vigilant to not only do what we perceive to be the precautionary way, with all the precautionary pattern, but, in fact, to continue to monitor the fact. And that, of course, leads into the principles of aviation safety, error management, which we spent the last two meetings talking about. So I thought I would give you just a little bit of an example of how I think some things have worked in this Committee related to one microcosm, supply of clotting factor concentrates, but also to point out the fact that it is an ever present danger and it's always hanging on the precipice, and give you some examples in real time of things that could actually influence that availability versus the demand for that product. I should start by saying that if--I'm putting myself in the ever present proverbial pharmaceutical chemist role, that some of the things I will say, which I won't--first of all, time won't permit, but I won't offer opinions about what the solution should be. But were I to do that, I would have to change my lab coat about five different times for conflict of interest reasons. But I want to point out some of the things that have been going on behind the scenes, and before I do that, I would be remiss if I didn't acknowledge really a lot of people who worked very hard on all the elements we talked about today, but particularly this microcosm: the FDA, the pharmaceutical industry, the consumer groups and interests, this Committee, and particularly its Executive Secretary and its staff, all of whom have been involved on all these issues on both very high-level, superior sort of policy roles, but also at the very grassroots level. If I could have the first--I have two slides just because these issues are so complex that I thought if I tried to even remember them all, I'd probably use up all my time. And I'm not going to go into great details, but what I want to tell you is that right now, as you all know, as a direct outgrowth of the discussions that took place on May 8, 1988, and August of 1988, we have had consecutive reports from PPTA on clotting factor concentrate availability. We, all members of this Committee, plus all the consumer and governmental agencies, get these data. We've been following them very closely, and I think it's fair to say that we made it through some stormy times in late 1988, but now in early--or mid-2000, entering late 2000, we're probably back very close to where we may have been in 1988. And that's the reason I thought we should visit some issues. So what could--I should tell you the data shows that at the very best of times between those two periods, we've had about 9 weeks' worth of inventory, up to 9 to 11 weeks. We're now back down to 4 weeks of inventory for clotting factor concentrates overall. Why is that? Well, these are the issues, at least as I can identify them, having spent some time about it. First is production. There have been, as you know, as we've talked about, new production capacities that are coming online, new bioreactors by certain pharmaceutical companies that are scheduled to come on. Overly optimistic projections on the time line in terms of FDA approval in some cases have compressed our more optimistic projections and put us a little bit more precarious than we thought we might be if everything had gone according to the best projections. But, again, those are moving along. As recently as yesterday, we got notification that one of the newest products is now FDA licensed, and, again, to be applauded is the FDA for having moved this along very quickly. But because of some of the last issues I'll talk about, which are international relationships and the companies' inability to really meet their own projected time lines, we won't have this product available next month as we had originally hoped. And, in fact, it's now projected to be available in 2001. So all these things are part of what go into making a projection model in terms of supply. Reimbursement issues are continuously, as with all the issues this Committee has taken up, are howling around us all the time. Most recently, one that has particular imminent import is actions related to reimbursement of HCFA programs, particularly--specifically Medicaid and Medicare, and the reaction by states' attorneys general to average wholesale pricing, a collective impression on their part that these AWPs on which reimbursement was based were too high and, therefore, categorical decisions but not--many times they were unilateral, those categorical decisions, to modify those adjustments. What has been the outcome of that is that certain of the private sector distributors, like home care companies, have been put in tenuous binds about being able to get adequate reimbursement for their services, and in cases of patients that they supply who are HCFA-supported, Medicaid or Medicare, have at least to my knowledge on a few cases actually said they could no longer do it because they were losing money. So, clearly, even though that's not a direct supply issue on a national basis, it has localized geographical significant import. Similarly, there have been--to say discussions is probably to be euphemistic. There have been discussions going on about a prime vendor program which we discussed once upon a time, and I don't expect anybody around this table to remember that discussion unless they're in hemophilia. But essentially HRSA was charged by the original act that created lower federal pricing for factor concentrates to look for a way to make sure that all this pricing could be accessed by all hemophilia treatment providers and patients around the country. Well, that also has created discussions about whether that really is anti-trade and all kinds of issues. If that were to be--if that were to really go at this particular point in time to a confrontation between, say, PPTA and HRSA, to where both threw down the gauntlet and said we're going to fight this out, whether legally or otherwise, that could have an imminent impact on supply. It's particular important, I think, to draw from the analogy of the aviation industry where we learned very quickly that when weird things happen in multiples, things that shouldn't happen, that's when they happen. I mean, that's when you are most vulnerable, and that's the reason I decided to point out these issues, because at this point in time I think we're vulnerable to each of these issues. The next slide, please? Distribution. There have been proposals. Some of the newest technologies that are coming on, recombinant technologies, are just--one of which has been delayed, as I just told you, but another one that's coming online imminently, there have been proposals that it be provided on an allocation basis based on certain individuals who opted that they wanted to just go that route and put their names in, it would be a first-come, first-served basis. A number of us have argued strongly that that takes the flexibility out of the system in terms of the end-user level, if I've allocated Product A for little Johnny and little Sammy has a bleed that's acute and little Sammy is not part of that allocation system, if they do that, I can't borrow from little Johnny to help little Sammy. So it takes our flexibility as treaters out of play. So those are all issues, I think, that in a time where a shortage is imminent or where supply is marginally adequate, where we have to continue to argue all the facts, because keep in mind that these decisions in many cases are made irrespective of issues of supply. They're made for economic reasons. They're made for political reasons or any other kind of reasons. And so it's our job collectively, both as, you know, members of this constituency but also as broader--this whole Committee, I think, to have people around who are continually--and we do have them--continually monitoring along with the federal agencies like the FDA. The other thing about it, as everyone knows, we recommended on this Committee that clotting factor concentrate use in the United States moved to an all recombinant supply. Well, clearly, the biggest impediment to that is the supply itself, and the less available recombinant there is, the more likely that people who would otherwise move are not going to be able to. Which leads me into the last point, and I think I'm probably right at the end of my five minutes, to say that as we've talked about before, that's not just a U.S. issue. That's an international issue because these are multinational producers, and they're also chains of suppliers that are multinational as well, along with supply routes. And so I'll take the example of the most recent product that got delayed until January 2001. In that case, that product was licensed in Europe first, and right now the demand in Europe is so great that there has been a reluctance, not to divert because there was never any intention to divert from that supply, but I'm sure it's influencing the availability, how quickly they can come online to provide a North American supply to this, which would help ameliorate the recombinant shortage, which then finally kicks down to the plasma-derived supply piece, which I want to end up with by saying--to remind ourselves--and it's already been alluded to multiple times--that this is a domino effect. So that if we don't have the recombinant supply in the developed countries, we're going to draw on the plasma-derived supply that is intrinsic to providing the care for the developing world. So all of these issues are exceedingly complex, as you all know or you wouldn't be here, but I think they're things that indicate why we need to be ever mindful as we go along not only what we should recommend for our government and our policymakers to do, but to kind of stay on the case to make sure that, as we go along, as new contingencies occur, which they inevitably will, that we're there ready. Because the one thing I, as a member, personally--as a member of this Committee, I would want to think that when someone says, well, why didn't somebody think of this, we can say we did think of it and we tried. Even if we fail, we at least thought of it and we tried. CHAIRMAN CAPLAN: Comment? [No response.] CHAIRMAN CAPLAN: Thanks, Keith. Let's go to Paul. DR. HAAS: I guess I'm going to ask you to indulge me as an academic for five minutes. And as I was putting these thoughts together, I had several titles running through my head, but I guess I ended up with "Economics and Blood Products: Do They Mix?" The two most common economic terms, supply and demand, are probably the most commonly misused terms. Supply and demand reflect dimensions of both price and quantity. Supply and demand flow from the concepts of competition, which is built on the assumption that there are a large number of sellers of a homogeneous product, that buyers and sellers are well aware of the properties of that product, and that the entry into a market is free and easy. Furthermore, it is assumed that products are manufactured in a single plant producing a single product. Right away we should understand or see the complications with these assumptions related to the so-called market for blood products. While there's a significant homogeneity within various blood products, there are multiple products included in the blood product category. Depending on the product and the timing, there may or may not be many sellers. And we heard from John that there's one seller of his product. And the concept of a single plant producing a single product doesn't exist. Entry is not free and easy. While some of the general forces of competition might exist, the distinction of real conditions from those in the competitive market cause alterations, often significant alterations, in the expressed outcome. In addition, the so-called market for blood products is complicated by the role played by government. Also, the term demand depends upon a large set of assumptions that rarely are met in medical economics. For example, the demand concept is compromised by the existence of third-party payers, which themselves are compromised by the existence of privately purchased insurance, fee-for-service and managed care, government-provided, insurance and charity. When demand for blood products is considered, are we really talking about, one, the willingness and ability of patients to pay for the product? I don't think so. Two, the decision to provide blood products with or without the payment by individuals or insurance? Or, three, simply a measure of quantity devoid of any concern about price? The first option is the definition of demand under conditions of a free market, which, of course, do not exist in the market for blood products. The last view doesn't make any economic sense because the cost to provide the products always exists. Even if the society were to supply the blood products free of charge, there are still the taxes and the opportunity costs associated with using the resources to supply that blood and not something else. Obviously I could become very pedantic, but the fundamental point is that economics is very much a discipline that's concerned about choices, but its models must be used carefully or the choices offered by the model will not be equitable or efficient. Economic reasoning applied to the public sector must use supply and demand reasoning very cautiously. Since society has determined that one's income should not determine one's access to health, then health care and blood products move out of the private domain of demand and supply and into the public sector. Yet this movement doesn't avoid the problems associated with cost or rationing, as those of us on the Committee read that article about rationing. Rationing is there because there's a trade-off. Every economic decision is a rationing decision. The controversy isn't about rationing but how the rationing should be accomplished, and Jane and Karen were really saying similar type things. Economics has given us cost/benefit analysis and cost-effectiveness analysis to approximate the forces of demand and supply. Cost/benefit analysis attempts to determine the most efficient way of accomplishing a given activity. Cost-effectiveness analysis attempts to broaden the scope of the analysis by including other dimensions such as pain, suffering, and disability, that is, value judgments, again referencing another article we have in the packet. Cost-effectiveness is the more appropriate analysis because value judgments are an essential part of the process. If we could rely upon the existence of a competitive market, then we could rely more heavily on the concepts of demand and supply or cost/benefit analysis, which under conditions of competition provide results that are both efficient and equitable. Since the competitive market for blood products does not exist, use of cost/benefit analysis is likely to provide deceiving results. As the article "Cost-Effectiveness Analysis in a Setting of Budget Constraints--Is It Equitable?" points out, lack of measures of demand and supply leads to a form of cost-effectiveness, equity does matter, equity matters in competition. But the competitive assumptions are unrealistic in the blood market. If we are not careful, then efficiency concerns dominate equity concerns in economic decision making. The supply problem associated with the blood supply are complicated by the desire to provide only the best--and I think that means safest--blood product. If we truly believe in market forces, then blood products with many different degrees of safety would exist at a variety of prices. The safest blood products--and that includes getting the blood product safely to the bedside--would have the highest price. Because of equity concerns, society would want blood to be as safe as possible, but often forgetting the costs associated with that desire. Yet we don't know what safe really means. Is a blood product safe if the probability of transmitting the disease to a typical blood product recipient is one in a million? What if that same product is given to a heavy user of the product, such as hemophilia, alpha 1, immune deficient patients, would the probability of transmission of one in a thousand or one in ten thousand be considered safe? Is it possible to provide a variety of varying qualities of blood to different groups? I don't think so. Yet, as an economist, I'm supposed to present options. I'm supposed to--but as soon as we move away from the conditions necessary to permit an effective use of the concepts of demand and supply, economists are subject to concerns other than efficiency and profitability. In a perfectly competitive market, efficiency, profitability, and equity happen naturally. No human interference is necessary or even desired. Unfortunately, no one has ever seen that competitive market, certainly not in the health and blood areas. Unless we or society are willing to define what is meant by safe blood and what is meant by the demand for and supply of blood products, then this Committee will always be facing the impossible task of deciding what error we are willing to accept: error one, very safe blood but inadequate supply and high cost of production; or error two, less safe blood, more supply, and lower cost. And, yes, I know there are many other options, but I'm not going too far over my five minutes. In the article "Cost-Effectiveness Analysis in a Setting of Budget Constraints--Is It Equitable?", the options are clear. Of course, with a little bit of creative thinking, there are additional options, such as increasing the budget. And, again, a couple of other people have mentioned that. This approach is harder to achieve, but failure to think outside of the so-called box limits our ability to assess all options. If we and society want an adequate supply of the safest blood products, then more resources need to be devoted to this area, and some other area--who knows what?--education, defense, environment--again, Jane mentioned some of these--will lose resources. The economic refrain of Tans Stoffel (ph), "There ain't no such thing as a free lunch," never goes away. With this thought in mind, I personally prefer to push the envelope on safety and search for resources to accomplish this goal. I take this stand in spite of Dr. Klein's editorial in JAMA pointing out the trade-offs between safety and equity. I argue that we need to set the safety standard according to the needs of those who use the product on a regular and continuing basis. I do not argue that blood products need to be 100 percent safe. I know that goal is unrealistic. But I do, however, argue that until the blood industry restores its reputation, safety has to be the dominant concern. CHAIRMAN CAPLAN: Okay. Thank you. Let's go to Fernando. Then we'll get to me, and then I guess we'll get to lunch and then we'll pick up with Ron and go around. I'm sort of hopping over our ex officio and non-formal members in the presentations, and I thought we could hear them, open that up for discussion, and then swing back around to reconsideration of anything that others who are observers or ex officio members might want to say, and then come back to the letter issue and whatever else is on the table. So that's my rough tactic here. DR. GUERRA: I think Ron had a comment to make. I saw his hand up. No? Okay. Thank you for the opportunity, and certainly being privileged to serve on this Committee has given me a real-time opportunity to see for the first time what I consider some interfaces of public health and the blood industry and blood banking and those enterprises, especially as that interface plays out in large urban centers. But I think that in the first instance there are clearly some overlapping obligations, responsibilities, and opportunities, and those are certainly for surveillance, for prevention, for screening, for testing, for communicating, for tracking, for doing a lot of things that maybe we have not always thought about in the context of that interface, and where I think the collaboration certainly in the future could open up some incredible opportunities for how we convey to the general public those issues, those concerns related to the transmission of disease beyond hepatitis C, HIV/AIDS, but any number of other conditions that perhaps in one way or another, directly or indirectly, come very close to the nation's blood supply. I think that there is a real need for being able to better communicate what is real versus perceived risk, which, again, is very much a part of what public health does on a regular and ongoing basis because of so many conditions that we're faced with and that we have to somehow communicate to communities that today are very diverse and that at times their grasp of information is limited, and so one has to develop some very creative types of strategies, especially for dealing with populations at risk, as some of the targeted populations, the populations that are homeless or those that engage on a regular basis in a variety of risk-taking behaviors. I think that an area where there is a real strength in trying to more clearly define that interface--and I hope that it is an opportunity for the future in terms of some of the agenda items--that public health probably has a much greater access to population data, linking data sets, looking at vital records, what birth and death rates are, what the number of C-sections are, how or what the utilization of blood is, what inventory is. I mean, some of that is tracked because of other public health responsibilities that one has. But there is an emerging natl information system called the Health Alert Networks, where I would think that it is possible to link into some of those information technology networks, some of the issues, concerns, and opportunities related to the blood banking industry and the populations that are served. Public health in the instance of accessing the political arena, in particular elected public officials, especially in local communities and at the state level, where that access could perhaps be a very powerful one for the blood banking enterprise in both the public and the private sectors. On a regular basis one is faced with having to access that arena for either allocation of resources, for concerns for development of legislation, for ordinances, et cetera. There is hopefully--even though I think we heard from Dr. Satcher on any number of occasions, and certainly we've heard it in some of our discussions, we don't always have the capacity and/or the support for that capacity for tracking populations. But there is some expertise that could be expanded, and I think that there perhaps could be some additional support brought into it for such things as outreach and case management. The DIS staff, for example, in public health departments that track--that does the contact investigation when there are a number of infectious diseases could certainly be called into play for some of these other efforts. I think the interface would allow really for the expansion on both sides of the leadership role in first responder type of activities. There's no question but that the nation's blood supply faces the same threat that especially large population centers face related to weapons of mass destruction, bioterrorism. Contamination of the nation's blood supply could be a tremendously serious situation that I think all of us would be concerned about. I think public health has at times had some special initiatives, some that are just emerging related to environmental concerns. This is an area that really needs to be linked very closely to both the supply of blood, the donor supply, et cetera, related to environmental pathway exposures. We don't always understand, for example, the exposures to potentially toxic chemicals, insecticides, pesticides, or dietary substances or heavy metal exposures--any number of things, radiation, et cetera, that I think perhaps could pose some additional threats that certainly have to be looked at and addressed. I think if there is an opportunity to deal with some of the issues of disparity and social justice, it is in the interface of public health with the blood banking industry. We've learned in public health, in keeping with some of the finest traditions--and I think we've seen it certainly in the list that Dr. Satcher handed us. But there's an even longer list that deals with disparities across population groups and communities by race, ethnicity, and socioeconomic status, and I think we see that play out every day within the blood banking industry and the populations that are served or not served or those that have particular conditions that have to be recognized as part of a greater social justice discussion. Then, finally, in the instance where there is potential harm to large numbers of people, it is public health in keeping with, again, the authority that is placed within that system, and in particular those individuals that carry the designation of local health authority that have to sometimes issue quarantines and/or shut down operations if they pose a threat to groups of individuals. And so I think that it is very clear, as I have been on this Committee now over several years, that somehow we need to better define and forge the relationship at the interface between public health and the blood banking industry. Thank you. CHAIRMAN CAPLAN: Thank you, Fernando. I think I'm last up and headed for lunch, so I will keep to my five minutes, although somebody can yell at me if I start to lurch over. I tried to think hard at the beginning of this summer about values and principles. I got asked to write something about leukocyte reduction and some of the issues that came up there, and I never got it done because I got caught up in brokering this peace treaty between the private sector and the public sector on who is going to figure out what to do with the human genome. But I still have been thinking about it, and I hope to write about it, and it led me to reflect on a couple of things which, I guess, in the spirit of Paul's remarks, I could call it bloody ethics. Sometimes ethics looks like a nuisance here. I think overall when I try to think about competing social goods that we have to wrestle with, spending money on blood versus other things, what I find myself thinking about this Committee is that our mandate is blood safety and availability, and the advice we should give, as I see it, is to figure out how to get a safe and available supply of blood, but it is not always to weigh other things that are important to do or good to do. If I had more confidence in the political system, I'd feel better about that. But, nonetheless, I find myself thinking the job is to figure out, given many choices and options and expenses and opportunities, what do you do to get a safe and available blood supply? I have always found it interesting that our Committee is called Blood Safety and Availability. It's not Blood Availability and Safety, and a lot of our debates go have we gone too far down the safety road and jeopardized the availability part. So we sort of took safety as our starting point. Safety in some ways triggered our existence. Safety has been the driving force behind a lot of what I think the congressional or the public concerns are. And, ironically, availability often takes second place. I'm not sure that is true. But I don't worry as much overall in a sense of justice about trying to weigh childhood vaccination or a better highway system or more seat belts or better tires. I think it is our mandate to think about blood safety and availability, and then Congress and the politicians will think about all the rest of the things. So that's how I sort of think about the large picture of competing goods when we ask questions about $30 million letters or is it worth doing that testing or leukocyte reduction. It may be that we shouldn't even have a Blood Committee. We should have the Surgeon General send out a letter saying: Do you know you don't have health insurance? And that would be the most politically adept thing we could with mailings, but, all right, it's not about blood so there we are. Within that context, then, I always find myself thinking not so much about principles as about values. And one thing I know--and Jane's knows this better, but I have read her book and I've talked to her about it off and on--is that this is a wacky area because it is not about economics since the provision of the substance that is at issue is a gift, and it always is rooted in this ethics problem of how do you cement public altruism to give this substance, blood, that then gets a cost put on it and then gets into distribution. I do know for sure that if the public perceives that the distribution is not fair and that the cost or price that's being charged is too high, then altruism as the basis of collecting the substance is in jeopardy. It just becomes tremendously put at risk. I know that because I've studied for a long time the organ and tissue worlds, and nothing dries up altruism faster than a perception of inequity in the distribution of a gifted item. I also know that this is a weird area, as Paul was hinting at, because in terms of values, if we are going to commit to altruism, we have certain obligations to watch distribution that aren't market-driven because we are trying to get everybody to give, in theory, and that makes for a problem as opposed to those who could pay. The second thing I know is that the use of the substance is involuntary. So it's not something that you go and get; it's something that you have to--very few people have said to me, Boy, I hope I get to use blood anytime soon. Most people, the majority of users, I would venture, don't want to. They have to for various reasons. That, of course, puts them in a position then of feeling exposed to risks or dangers that might be different if somebody said I'm going to drive real fast and have many deaths on the highway every day, but I chose to do that, as opposed to here's the safety that I have to face if I must use this thing, which I don't want to, but it's foisted upon me. I think sort of the first value that's out there that we have to be alert to is altruism. The second is the involuntary nature of the use and what that means in thinking about safety. I think it means something different than when you voluntarily assume risk or voluntarily do certain things vis-a-vis behavior that can be pretty risky. Another factor that plays a role here is what I would call privacy and stigma. If you look at blood and blood transfusion, blood product use over the years, we can't even talk about hepatitis in this country without a lot of people worrying that they're going to be typed as a particular lifestyle or having a particular background. And HIV certainly has plenty of that, and most of the infectivity in the blood supply carries stigma. It also carries the very real prospect of discrimination. So that values about privacy and confidentiality loom large because of the connection to stigma and discrimination. So here we have to not only account for what's efficient, we have to make sure we're building privacy and confidentiality protections in as we think about safety and availability at all points, just because of the nature, the controversial nature of the substance. I have to say, too, even though it makes me sound almost like Martin Boober (ph) for a second, that blood is symbolic. There are a fair number of people who still say that the way they define kinship with one another is through blood. And I could go on about the symbolism here, but when you have an entity that is not seen as an oxygen-carrying fluid but a mystic substance of life or other types of things that different cultural and ethnic groups have, then it imposes even more limits on what you can do vis-a-vis safety and purity. I once mentioned to someone in the biotech industry that were I to start making genetically modified foods, my first one would not have been milk. Blood has this problem, too. It's just fraught with symbol, and, therefore, people have expectations about purity and safety not consistent with what they might expect from other arenas of their lives. That's a reality that we have to struggle with. I'd say one other thing. As I watch this group function and listen to different voices, I come to understand that blood is one of the few ways Americans can seem to be a community. There's almost nothing that makes them seem to be a community. We don't even have baseball anymore. But we do have blood collection and blood drives, and not-for-profit voluntary organizations that pull the community together, and we make appeals to one another to pull society together. This may be a funny social glue, but there it is. And we could shift the ideology of it. We could be less concerned about gifting. We could be less concerned about altruism. We could be less concerned about community. But if you look at the blood organizations, the blood banks, the kinds of things that they talk about, it is very clear that the value of community is trying to be exemplified at all points in what takes place with respect to blood. We get disappointed when we hear about blood donation rates dropping, not just because it means that we're at risk, it's because it says something about society. I've had that said to me as I've left this room, whenever we see that little curve, somewhat in dispute about how bad the dip is. But when you put up a curve that looks like it might be a dip in supply, people sort of say, Boy, this country's going to hell. They don't say I'm at risk. They say this is bad. This is a bad thing about America. So the value of community is there, and I might add it's reflected in another two special areas: the liability on the product is different from what happens in the market normally, so it's got special status and protection because of this altruism community set of values; and you've got in play something about the modulation of the cost since a good deal of the blood industry moves under the banner of not-for-profit. We can dispute whether that's true. There are certainly segments that are for-profit, I understand, but generally speaking, I think the American people have said a gifting, altruistically driven, community-based system should try to reflect a not-for-profit ethos in terms of what makes it tick and function. So what I would say by way of my pre-luncheon reflection is I don't know how yet--I still don't understand exactly how issues of fairness, compensation, precaution, and risk avoidance play out. But I would say this: It becomes very tough, I would agree with Paul, to just take cost/benefit or cost-effectiveness analyses or efficiency as the sole value here because you've got this other set of values that you're constantly trying to mix with this notion of efficiency. I think it's also true that even though it irritates us all the time about trying to say how important is it to get marginal safety or marginal increases on risk avoidance, to some extent the symbolism, the history, the sort of moral status that blood donation plays for us, is reflected in what people are willing to pay to get that marginal utility. It doesn't make sense. If you just toted up the numbers, there's no sense at all. But it's probably playing roles other than that, and to change that--I'm not saying that's the correct ethical outlook, but if you want to change it, you've at least got to say you want to modify these other value dimensions I've been talking about, you want to shift them, they don't make sense, or they're not worth preserving. They cost too much, literally, if you want to put it that way. But I think that's why we're not so efficient in what we do. That's because we're doing a lot of other things with blood that have nothing to do with who's going to get a safe unit transfused to them, or at least a reasonably safe unit, and it's why people I think are so concerned and maybe even why Jim's article comes out the way it does that you've got one of the safest things going, and yet a third of the people who hear about it are still not sure that it's safe enough, and a lot of others could shift their attitudes about it. It probably tells you what they think about their neighbors, what they think about stigma, what they think about symbol, as much as it does what they think about somebody's safety analysis. So there are some big thoughts to launch us off to lunch. I will take no questions on these truths, and-- [Laughter.] CHAIRMAN CAPLAN: And then the game plan is, however, to swing back around over to this side, stop, talk about what we've heard from the members add other people in who are here, who may want to say something, observers in the ex officio role, and then revisit what we need to revisit. I think the dream today--I mean, I'm amenable to hanging around as long as people want to hang around, but the target goal might be to maybe get us out by 4:30, but I mean, if we go longer, I'm here. However, if we're going to do that, you really have to get back from lunch in an hour or less, so one hour. It's now about 12:30, so I'm going to try to kick this off at 1:25, and that should give us enough time to keep moving here. Okay. DR. HOOTS: Can I have a autographed copy of the stone tablets? [Laughter.] [Whereupon, at 12:30 p.m., there was a luncheon recess.] A F T E R N O O N S E S S I O N CHAIRMAN CAPLAN: Can we reconvene? You will recall the moving final statement by the Chair before lunch left us in a position to now move to a more concrete insight. Ron, I think you're up next if you want to, for comment. DR. GILCHER: Thank you. It is interesting that the comments about--which I will make in a moment from a prepared statement that I prepared before coming to the meeting--are very similar to comments that have been made already by Dr. Penner, by Karen, supporting those views, but in somewhat of a contradistinction to what Jane Piliavin said. And the statement relates to blood safety, blood supply and cost, and it is from my perspective as the director of a large regional blood center and the impact that the initiatives that we have put in place have had in our system. So I'll read this statement and try to stay below 5 minutes, Mr. Chairman. The safety of blood products is regarded by the recipient patient as being of such critical importance that the inherent and perceived risks should approximate zero risk as closely as possible. The receipt of a blood transfusion is analogous to flying as a passenger in an airplane, which we've heard from you, Karen. Specifically, zero risk or zero defects, even though realistically not possible, remain the goal. In transfusion medicine we have approached the safety of blood products in three general ways, and these are not the only ways. Number one is pathogen detection. Number two is pathogen removal, and number three is pathogen inactivation. Very briefly, pathogen detection, that is, testing, now uses the state-of-the-art testing, nucleic acid testing, to approach zero risk for specific pathogens, again, HCV and HIV. In a low-risk system for HIV, such as in our system in Oklahoma, the estimated cost to detect and prevent a window transmission for HIV will probably be around $7 million, with one detection estimated to occur over and above our current systems, using that about once every nine years. For HCV this cost is about $1 million per detection in our system. Theoretically, these are the costs to detect one HIV or one HCV positive unit, yet nobody knows which unit that is until it happens. Number two, pathogen removal, which includes macro and micro-filtered blood for removal of clots, aggregates and other debris, has been used for decades to prevent theoretical embolic risks and other risks, and now we are using leukocyte reduction, which has the ability to remove cell-associated pathogens for which we do not, cannot, or will not test. At the Oklahoma Blood Institute we adopted universal leuko-reduction as of July 1st, 2000 for all red cells and platelet transfusions. We had had that in place for platelets already for over five years. From hospital surveys which we did, we estimated that approximately 40 percent of all red cell transfusions in our system went through a micro-aggregate filter, for which the cost of that was about $380,000 per year, and average cost of $9.85 per filter. Universal leuko-reduction has removed the need for micro-aggregate filters, but has added about 1.9 million or a net increase, if you look at that in our system, of about 1.54 million in 96,000 red cell transfusions, and interestingly, that comes out to about $16 per red cell unit, and that is applied to every single blood product that goes through the system, in contradistinction to NAT, which is only picking up the two. Longer term cost effective studies are now in progress at two of our major hospitals, and the preliminary data is very interesting because one of the hospitals was a nay-sayer, and in fact, they have the data that supports leuko-reduction even more so than the hospital that was in favor. Number three, pathogen inactivation is the newest safety initiative for blood products with much of it being research based, although it has been used for plasma derivatives, and now a pool form of fresh frozen plasma, where it has doubled the cost, with some questions regarding safety enhancement in the face of the advanced pathogen detection technology, that is, NAT. These three approaches, pathogen detection, pathogen removal, and pathogen inactivation, at times clearly overlap, and there's a significant cost to that overlap. Identification and subsequent removal of the unnecessary overlap can result in cost savings so that the goal of zero risk and the approaches toward zero risk, can be economically, ethically and medically justified. The perception and reality or working towards zero risk or zero defects for blood products is--and this is in my experience and opinion--also very important to blood donors, and ultimately influences the donation rates and availability of the blood supply. We have clearly focused on that in our system, and as you know, it is one of the systems that generally always has enough blood. In summary, zero risk, although not achievable, should remain the goal in transfusion medicine. To do less will continue to fuel the fears of patients and the distrust, mistrust of both donors and patients. The end result is then an inadequate blood supply and ultimately a less safe blood supply. Thank you. CHAIRMAN CAPLAN: Questions, comment? Thanks, Ron. Rick? DR. DAVEY: Well, Steve, I took you at your word fairly concretely when you suggested that we as a committee identify a set of intellectually consistent and politically acceptable principles on which a coherent and durable policy to assure safety, availability and affordability of blood and blood products can be established. And so I did look over some of the readings, do some thinking about this, and thought that I might just have a condensation of some of the principles that were in the precautionary principle paper, as well as some of the thoughts on papers by Ubel and others, and maybe suggest a template that might have been useful for us to use in the past on some of our deliberations, that might be also useful for us to consider when further actions of this committee might be considered, and again, just putting this in the context of some of the comments that Art made about our special gift relationship, the altruism, that we have to consider the confidentiality, the privacy, also the political, scientific and financial environment that we specifically have to deal with in blood and transfusion medicine. But with those--in that context, I'd like to suggest seven evaluation parameters from the readings and some elaboration that I've had on them that we might want to consider. I guess I would consider them evaluation parameters, and maybe think of these seven things almost as a template. Whenever a new action is considered, are we going to think about each of these seven items and consider them before we decide on what to do. Again--and this is in some of the readings--but the seven are as follows. Number one: Whenever we want to consider an action that affects the blood and blood supply, is it proportional to the chosen level of the protection that we want to have? For instance, we knew we were going to need to tailor measures to be appropriate for the level of protection that we're looking at, and again, we might want to think of the appropriateness of the UK ban here. Is that proportional to the level of protection? That's number one. Number two: Is the action equitable? Is it something like in consideration of what Jane was saying earlier and in consideration of the paper by Ubel, is it something that can be equally applied to all people that the action affects? I think the paper by Ubel is very interesting, if you read it, where there was a evaluation of two different ways to screen for colon cancer. One was more cost effective and one was more equitable, if you will, and it was the equity that carried the day in terms of when ethicists and medical professionals reviewed the two opportunities. So proportional to the chosen level of protection, equitable. And three--I think this is what Jane was looking at--is it comparable? Can comparable situations be looked at comparably? Can we look at Chagas Disease and New Variant CJD and say, "Look, are we dealing with these two issues in a comparable fashion or not?" So is our action--is the consideration of the action comparable? Fourthly: Is it consistent with other similar measures that have already been taken? The actions we might want to consider should be of the scope and nature of those that have already been done, that we're not going off on some kind of tangent. Fifth: The actions should be based on cost benefit analysis. There should be a evaluation, not only maybe of the economic cost benefit analysis of a particular action, but maybe some of the non-economic considerations also. Is this an acceptable action for the public to consider? So cost benefit analysis for sure. That's five. Six: Is the action really subject to review? Is it something that can be periodically reevaluated, and if necessary, reviewed in the light of new scientific progress, amended if necessary? Can it be reviewed? And lastly, and maybe related to the subject of the review, can responsibility be assigned for getting the scientific evidence so that it can be reevaluated and amended? Can we assign responsibility to follow up on these issues? And I think when we think of 100 percent leukocyte reduction and HCV look-back, many of these, I think, principles, could have been perhaps better utilized in our deliberations. So, again, I would very briefly suggest that we have a template, that we think of these seven things when we review our actions, that they might have been good in some cases in the past. Again, let me quick review them again. Number one: Is the action proportional to the level of protection? Is it equitable? Is it comparable to other situations that have occurred in the past? Is it consistent with similar measures we've already taken? Is it based on cost benefit analysis? Is it subject to review? And can we assign responsibility for producing that evidence? Simple, but it might be seven little principles that would be useful as a template whenever we think of something new. Those are my comments. DR. BUSCH: Just a follow up. I know both Steve and Jay and I were involved in a WHO program that I guess is going to play out in the next meeting as well, but similarly attempted to define a process, you know, a really on-paper consensus process of issues that needed to be addressed in terms of making decisions. I know Jay has been much more involved than I, but I think what you've done in terms of trying to lay out concrete elements of decision making is what I hope we end up talking a lot about and working a lot on. DR. HOOTS: I just wanted to make a comment in terms of one of the articles. I think one of the--where the rubber meets the road and where the complexities comes in, as is pointed out in the cost efficacy versus equity discussion. And perhaps what we need to do in addition to--and I applaud your effort to organize the thought process--but to look at really where the conflicting components almost inevitably come into play, and then also then further sub-stratify or sub-strategize, perhaps is a better word, how you deal with those issues, because that's really where we always kind of end up. DR. PENNER: Maybe one other comment, and that is a question. Is it relevant with respect to other costs that are involved in therapeutic and medical care? As I'm recalling, we were paying, I think, something like about $45 20 years ago for a pint of blood at that point, and now it's something like about, what 92? So it's--over 20 years it's increased, doubled. And what's happened to the antibiotics and the other therapeutic agents that we're using cost-wise? I think I'd still make the point that we are probably under selling or under costing our blood products in comparison to many of the other products that are being used as therapeutics, and that kind of mindset has been hard to dislodge, that we should just maintain that level of pricing for those products just because they're, supposedly, initially, voluntary. I think we have to really look at it in terms of market, and market value on everything else has gone sky high. If we're paying $1,000 a day for some antibiotic regimens in our intensive care unit, and we're still giving two units of blood at maybe $140. It sounds like there's a discrepancy there in relationship to the significance of the product that we're giving that is being overlooked. DR. BUSCH: Yeah. I presented about two months ago a talk that Steve was at at CDC that he thought maybe some of this would be useful, and a lot of this is stuff we kind of know, but I think could make some points sort of relevant to the decision process, particularly as it's evolved in my area of focus, which is in the testing side of blood safety. If you could turn on the first slide, please. Yeah, this is just sort of a strong backdrop of how much safety we've achieved, and I think there were earlier comments about sort of the perception of the public. And I remember a colleague from CDC, who worked in blood safety only for a few years, Lyle Peterson, five or six years ago made the comment that, "You guys are completely missing the aim. You should be out there emphasizing what an incredible success story the elimination of transfusion-transmitted infections is to the public." Instead, all the focus is down on the incredibly minute residual risk, and we're not adequately educating the public about the extraordinary safety of blood. Next slide. One of the other things that I think we've struggled to do, and it's kind of bit us, is we've spent a lot of time and a lot of energy trying to estimate risk, the residual risk. And it's required--you know, we've moved away from simple ways to measure the risk to recipients, following recipients and measuring sero-conversion rates or doing special testing of donor units to find rare residual infections. We've moved away from those because you just can't do studies big enough to quantify the extremely low levels of residual risk. So what we've done in the last, you know, five to ten years is develop model strategies that estimate the rate of window-pair period donations, the potential sources from variant viruses, unusual people who don't sero-convert, and testing errors, and this has been a sort of building process over the last, you know, ten years, that have come down with numbers that are extremely low and essentially unmeasurable in the range, for example, of HIV of, you know, 1 per million anticipated transmission event. And the problem again is how do people weigh, in a risk analysis sense, these extremely low numbers? In general, my sense is that people take any quantifiable number as a problem, instead of having some way to balance the risk of these remote transfusion events compared to other risks that are faced. But in any event, we have put numbers on risks and have developed strategies that we thought were pretty reasonable to estimate risk. These model projections of risk and value of new tests have been criticized in the past. For example, after the debate over antigen testing, where we presented estimates of the yield of antigen screening, Congress came back and criticized those as gross underestimates of the yield without a lot of data. So I think one of the questions that is important is, as suggested a few minutes ago by Rick, is coming back to our estimates and trying to benchmark and confirm that those were reasonable. And we'll come back to that in a minute, because I think the introduction of nucleic acid testing has really very adequately confirmed these estimates that are laid out here. Next slide. Because the window period, as you saw on the prior slide, has been the major theoretical source of residual risk, there's been a lot of work that's gone on to estimate, understand the dynamics of virus during the window period, and estimate the ability of various new tests, be it antigen, NAT, either applied to small pools or single donations, to further close the window period. We don't have time to go into that, but I think there's an enormous amount of strong data that allows us to estimate how many additional days of closure could be achieved by adding this test or that test, and that's both for HIV, and on the next slide, for hepatitis C there's a similar large body of data that's over the last few years been generated to understand the duration of the viremic period prior to antibody, and the ability of various test strategies to interdict these window period donations. And using that--next slide--we've been able to estimate how much these nucleic acid tests, which are now in place, have been able to reduce the window period, and one of the big issues that I'm focused on is what the potential additional benefit that we would achieve in terms of window closure or yield, and at what cost would the transition from mini-pool screening to individual donation NAT achieve? And you can see here that the mini-pool screening, because of the dynamics of the window period for each virus, detects the vast majority of the overall window period for HCV, and a less proportion of the window period for HIV and HBV. But it's--what I'm trying to emphasize is I think the scientific efforts to get empiric data to help make these decisions is a first step in the decision process. Next slide. And the other point that I wanted to emphasize is, again, that I think we have to always ask whether our prior predictions, be they in this arena for NAT yield, or risk, or issues like in HCV look-back, where there was all the controversy over how effective would it be, how many infections would we actually identify? And I think it's very valuable and important that CDC undertook the effort to try to quantify what the real impact was, so that we can then use the knowledge, and I think in HCV, as with HIV--I'm sorry--in HCV look-back as with NAT, what we've discovered is that our estimates were really very accurate. The yield of HCV look-back was a very small fraction of the total proportion of infected recipients, let alone infected people. And it's important to go back to that, because I think that question of whether those estimates were accurate was a major driver in the decision to do something that some of us argued would not be very effective. Here again we say--if you just look at the yield of nucleic acid testing over the first year of screening, we picked up 42 HCV and 4 HIV window-phase infections. Some of these actually would have been detected by other screening measures like ALT, but these were all antibody-negative yield cases. And if we then estimate--derive from this yield the observed rate of detection, we can actually then compare the yield that was observed with the predicted yield from those model estimates I presented earlier. And again, the big message here really is that our predictions were really pretty close. We actually slightly over estimated the yield, implying that we probably over estimated the risk. In addition, for HCV, we can look at what kind of yield we picked up in terms of window-period versus error versus these silent carriers, and again, it's really quite comparable to our predictions. So, to me, I think we have in place now a strong surveillance program and strategy for making these projections, and I think it's very important that we use that to reassure the public that we know what we're talking about and use these data to frame future questions. Next slide. Just in terms specifically about moving to individual donation testing, we can then use these window-period closure estimates, the further closure that could be achieved by taking this next step of testing every unit individually, and given the incidence in the donor pool, we can estimate the yield, and these are per 10 million donations. So these are the projected number of additional infected donations that we will detect essentially per year in the United States. So we're talking really about two or three additional HCV and HIV infections, and with HBV, the incremental yield of individual donation NAT would be greater, but HBV is much less important in terms of most patients who are exposed clear the infection, resolve it completely. And the next slide is coming to a conclusion, just puts this into the cost effectiveness, and these are numbers that were generated with Jim, and for important comparison purposes--and I'll come back to this at the end--what I've done here is to juxtapose the cost effectiveness, kind of the cost, the number of infections detected, and then the cost effectiveness in the formal dollars per quality calculation, of the basic antibody assays with these, you know, sort of next-generation high-tech window closure detection methods. And what you can see is the basic antibody test for HIV and HCV, that because they detect the vast majority of infected donors, the prevalent infections, and are relatively inexpensive, they're actually extremely cost effective. In fact, for HCV, it's actually a negative dollars per quality, which means that we save a lot more health care cost by screening the donor units and preventing the transmission than it costs to screen. So these are very--you know, these are sort of "gimmes." And one of the things I'll close with is the big problem is that these tests are not being done in many parts of the world. In strong contrast to that, we can see that these window closure assays, because the yield of additional infections that are being detected, are so low, and the costs are relatively higher, you know, the cost per quality is just--from a cost effectiveness, economic perspective, you know, out of control. Whether these still justify, in terms of safeguarding the US blood supply and public trust, et cetera, is, I think, perhaps being defined. Next slide, just final. This is just a compilation again with Jim of the cost effectiveness of various blood safety initiatives. These are the mini-pool and individual donation NAT testing. You have some of the viral inactivation methods over here, and you know, basic antibody testing and other generally accepted medical practices come in under 50,000 per quality. We're talking about measures in blood safety in the millions of dollars per quality, which there's nothing comparable, I think, perhaps, except for airplane safety in terms of public health initiatives. And finally, next slide. Just a point that although, you know, you can argue negatively that these direct virus detection methods like NAT are perhaps inappropriate or cost ineffective. I think they are important for one reason, which is that the perpetual discovery of new viruses that are coming now every year, one of these is eventually going to prove to be clinically important, I suspect, and having a direct virus detection platform like NAT in place is going to be a very important safeguard at some point in the future, and should cause us to revisit the whole paradigm of screening in terms of, you know, perhaps getting rid of some of the older antibody tests, antigen tests, obviously P-24, but probably surface antigen, and relying more on the high-sensitivity direct virus assays. Certainly as we look at new agents, I think our first decision or first choice will often be to add a system to the NAT screening program. Next slide. Just wanted to make one comment about international safety and close. I mentioned this earlier. These are slides from Luke Noel at WHO, but what we sort of ignore is the fact that a large proportion of the world, and nearly, you know, a third of the global blood supply, is collected and transfused in developing countries, and in these settings, almost half of the blood is untested. Next slide, again from WHO. They estimate that in the range of 10 million units that are transfused annually that are not tested for HIV, 15 or so million for HBV, and probably in the range of 25 million not tested for HCV. And much of this is in regions of the world where the prevalence of these viruses are extraordinary compared to here. So, finally, the last slide is sort of a new slide that we built as part of a group that I'm involved with, which is called the International Consortium for Blood Safety, which is trying to get resources toward the international safety arena. And what this just illustrates is the point that that sort of cost effectiveness slide also emphasized, which is that the basic first generation--or relatively standard antibody tests, are able to interdict, you know, probably at least 95, and probably closer to 99 percent of all potential infectious donations, and that these technologies are really relatively inexpensive on a per donation basis and very cost effective, because they do detect such a high proportion of the transmitting units, and you know, what's sort of our of equilibrium on a global level is the extraordinary expenditure that's being applied to these sort of asymptotic residual risk infections in the US and other developed countries. And although, clearly there's a mandate to this committee and to us to try to do what we can to maximize safety, I think we also should consider our responsibility globally to make sure that basic screening tests are brought into play throughout the world. That's it. CHAIRMAN CAPLAN: Questions? Comments MS. LIPTON: Just one comment. Mike, when you were talking about risk perception, you were really focusing on, well, you know, we have a good story, and we do, and so we should try to change the public's perception. And that's really not my point, and I just want to make that clear. From my dealings with the FAA, they accept what people's perceptions are, and they're not trying to change them. You don't hear the FAA talk about how safe airline travel is. What they say is any accident is bad, and our goal is to get rid of those. And so I think that we think that if we just educate the public enough they're going to get the point. And I think what we have to do is say to ourselves, if we educate ourselves enough, we will get their point. And so I would turn it a little bit on its head. I absolutely agree with you, too, about the international issue. And you know at AABB we've been working a lot in the international field. I think testing is critically important and technologies. But the other thing that we've found in working in countries is it's not just the testing technology. You must work to build infrastructures there and systems that can actually use the tests appropriately, maintain them on an ongoing basis and training. And I think there are a lot of initiatives going on right now that are very good and I think are coordinated more and more. And I know, again, our obligation is here, and I don't bemoan what we spend in this country, but I do think we could look outside of our borders more often. DR. HAAS: Mike, were you using cost benefit or cost effectiveness? Because at least as I was hearing you, I was hearing cost, and I was hearing prevention of disease. And that would put, in my mind, more the cost benefit rather than cost effectiveness. DR. BUSCH: Well, these are numbers that, in terms of those specific numbers that Jim derived, and he's saying cost effectiveness. DR. HAAS: I'd like to see some background on--not today. DR. Au BUCHON: The process by which societies, their governments and skilled technocrats make decisions about safety have fascinated me for many years. I'd like to make a few preliminary comments on the issue in general and then proceed to discuss a specific illustrative example. This committee has considered many issues of pressing medical, social and political importance over the first 3 years of its existence. Although a more rational approach might have been to first lay out the framework by which decisions related to blood safety should be made, I can readily understand that action was first required on the issues of the day before we could take a collective step backwards, draw in a deep breath and develop a plan by which future issues should be addressed. I'm glad that we're now at that point. In considering how this committee should address the often conflicting issues of safety and availability, I believe it would be prudent to recognize that health care resources are limited. It was the federal government that first created a prospective payment system for senior citizens in our country, and it is that same largest of all health care payers that has, on multiple occasions over the last 10 years, reduced payments to hospitals for care that is increasingly more complex, sophisticated, costly and successful. This committee was specifically charged to consider the cost of its recommendations, along with other important implications. While efforts through and beside this committee to obtain additional resources for hemotherapy are of course welcomed and encouraged, we cannot kid ourselves into thinking that the pot of gold from which these resources come is boundless. I believe it is the task of this committee to identify the risks, benefits, costs and alternatives in critical blood safety decisions. We should highlight what can be done with the resources available and highlight where the commitment of additional resources will lead to further improvements in hemotherapy. Where the people indicate a desire to pursue efforts beyond a point that may make sense from a health benefit point of view, implementation of these strategies should be pursued if, one, the commitment of the public is reflected in the commitment of additional resources to the effort so that, two, no net detriment to health will rise through the implementation. This committee will, hopefully, continue to provide insights into how we can improve transfusion in this country. However, I believe the decision-makers should be made well aware of the facts about yields and costs of proposed programs and that such considerations are an important part of our deliberations. When resources are limited and choices have to be made, this committee may be of invaluable assistance by saying to society or its elected or appointed representatives that certain issues deserve attention first and that more resources are necessary to accomplish all that could be done to make transfusions safer or to improve availability. Now I would like to turn my attention to the issue of universal leuko reduction as an example of the kinds of situations that we will find ourselves in in the future, an example of the dilemmas that our intentions and our limitations lead us. I do not do this to speak for or against universal leukocyte reduction, but merely to use it as an illustrative case. As a former medical officer at the national headquarters of the American Red Cross and as a physician dedicated to providing the best hemotherapy to the patients I serve, I'm always on the lookout for new means to achieve safer transfusion. For example, my institution uses only apheresis platelets and donor retested plasma in an attempt to reduce the inherent risks of allogeneic transfusion. And to my knowledge, we are the only hospital in the country that routinely cultures all platelet units to detect bacterial contamination and one of the few to employ a mechanical barrier system to prevent mistransfusion. What is best for our patient should always be paramount in the minds of health care providers, and our institution has an admirable record of directing its resources to that end. I would hope that those around this table and in this audience can accept that my intentions are those supposed by Hippocrates and not Adam Smith. [Laughter.] DR. Au BUCHON: Some would apply the precautionary principle to require that something be done just in case leukocytes are harmful to transfusion recipients. I do not believe the data are yet available to conclude from an academic point of view that the safety of transfusion will be advanced by universal leukocyte reduction. In fact, there's a reasonable possibility that diversion of resources, including our attention, toward universal leuko reduction will prevent transfusion services from addressing issues that have already been documented as causing more facilities than the presence of leukocytes in allogeneic blood components; namely, mistransfusion and bacterial contamination. That would be a mistake. I have been told by more than one blood center official in confidence that the push by many blood centers toward universal leukocyte reduction is driven by the economics of their finances and the inability of many facilities to maintain operations with their current red cell pricing structures. If this is the case, it should be addressed directly and not through diversion of additional funds, amounting to approximately half a billion dollars per year, to an effort of unproven consequence. We need, as a society, to pay for the safety improvements already implemented. And the push toward universal leukocyte reduction, at least by some blood centers, may be derived really from a perverse approach to the problem of economics and is a sad commentary on how we have attempted to pay for past improvements in blood safety. Is it wise to force hospitals to spend precious limited resources on an unproven technology? When the potential for harm is great, the trigger for action should be easier to squeeze. However, in my medical opinion, there does not appear to be the horrendous threat to transfusion recipient safety, about which some are raising the alarm with respect to allogeneic leukocytes. If clinical harm were indeed evident, then it should be prevented. If the public wishes to spend additional resources on an unproven technology, I will be happy to implement it, providing it does no harm. But to ask me to direct limited resources to an arena where I can predict no benefit and in doing so deplete the resources needed to address more well-documented and larger problems, is to ask me not to deliver the best health care I can to my patients. As a physician, I have difficulty accepting that directive. A federal directive to implement universal leuko reduction takes the decision how to treat patients out of my hands. We have an opportunity today to gather the technical resources of those trained in the field with the representatives of society charged with overseeing them and the associations of those who are the beneficiaries of the efforts of the first two groups to define how this society should make decisions about blood safety in the future. Although a substantial part of my academic career has been based on cost-effectiveness analyses, I would be the first to acknowledge that there is more to decision making than determining the cost-per-quality-adjusted-life-year saved. At the same time, we as a society cannot continue to demand a risk-free blood supply at Wal-Mart prices. This committee is the perfect forum for considering options and opportunities, and I hope that we will explore them honestly and openly. Much has been accomplished over the last 15 years to make transfusions safer. We have many significant and important opportunities open to us to improve further the safety of a transfusion. To the extent that existing or new resources are available to advance toward the mutual goal of safer transfusion, let's direct them towards the biggest problems. Although universal leuko reduction has garnered the limelight recently, this is not the biggest problem we face. The patients that I treat every day expect me to do my best to make their transfusion an event they will not regret. To meet their expectation, I need to direct the resources available to me toward the largest risks that they face. Although emotion and rhetoric can be powerful, helping patients should be our goal. And directing resources, time and money toward the largest problems is the way to improve the health of patients. We do need more resources to make transfusion as safe as it could be, and we need to direct these to the problems that cause the greatest morbidity and mortality. CHAIRMAN CAPLAN: Comments? Keith? DR. HOOTS: In light of what you said and what Karen said earlier, it seems to me that one of the things we don't have that might be useful here is cost utility because one of the things that's critical for this whole decision process is what are people willing to pay if they're given all the facts. And that's what cost utility is supposed to measure. And I wonder, maybe you can--I mean, you would know, I'm sure, if anybody is doing cost utility related to transfusion events and are they doing general population or are they starting--if they are doing it, are they starting with more people--people who are more sophisticated in terms of risk analysis? But it seems to me that that's part of the equation that we've always been missing. But as Karen was saying in terms of aviation safety, the perceptions are incredibly important. And if people, I mean, it's obviously a major undertaking just to educate this committee to all of the subtleties of the data that might just show, much less the whole population, but it seems like, at some point in time, we have to at least try to get some data on that side of the equation that's collected in a scientifically appropriate fashion and also probably could be put side-by-side with cost benefit and cost efficacy. DR. Au BUCHON: A willingness to pay I think is a problem in health care analyses often because the patient usually does not see the bill for what their health care really is. And when their health is on the line or when they're about to step into an airplane, they want an absolute assurance of safety. But yet when taken out of that immediate threat context and put in the framework of do you want to pay more income tax in order to make sure that there's enough resources in the system to provide the very safest blood, well, then people say, well, what am I really getting for this? And that question is answered differently when they're about to be transfused versus some unknown person at the other end of the country is about to be transfused. DR. HOOTS: Yes, and I understand that. And maybe the targeted population initially then should be people who are getting ready to undergo the transfusion and also have an experiential base for other risks that they're undertaking related to their medical care as well. So at least they'd have some basis of comparison to what risks on other medical-related issues compared to transfusion-related issues and relative costs of each. DR. HAAS: If I may just jump in very quickly, I agree with the concept that the ability to measure that is almost nonexistent because you are playing with two different fields of information. You're asking someone to say what would I do if, and there have been some economic studies on uncertainty, and it comes out saying people have to make decisions. And I think that's why these discussions around here become very important. Where we have slight differences, one of our jobs I think is to say, as a committee, what do we recommend here because we're not going to get the data. DR. EPSTEIN: Jim, although you discussed universal leuko reduction, for example, you kind of took a position on the issue. And I would just ask you, just at a technical level, do you feel that there has been an adequate assessment of cost effectiveness or cost benefit for universal leuko reduction? And if so, where do you put it on a scale on the kind of graph that Mike displayed? Because I think that a lot of the underlying debate, even if we can put aside the reimbursement problem, which is, of course, real, it really focuses on the difference between immediate benefit to patients without known indications versus long-term benefit to the population as a whole. And one of my concerns is that that issue has not been framed adequately scientifically, and it tends to confound the debate and is the underlying reason why opinion is so polarized on this. So could you just comment on whether there has been an adequate cost-effectiveness or cost-benefit assessment and what did it yield. MR. ALLEN: I don't feel we have seen that yet in the literature. There have been several economic analyses of the effects of providing leukocyte reduction, in terms of potentially reducing length of stay or antibiotic usage or other such benefits. The studies to which those analyses have been attached have had some difficulties in terms of their structure and in their interpretation, although some adherence of the concept of universal leukocyte reduction I firmly believe that it will be cost saving. It's very difficult to document that because most of the studies have been retrospective. And with the rapid change in health care and the pressures to reduce length of stay, it's hard to construct a longitudinal study to answer the question. Like many others, I'm anxiously awaiting the results of the study that has recently been concluded at Massachusetts General Hospital, where for the first time in a U.S. hospital situation patients were prospectively randomized between receiving leukocyte-reduced blood, when they had no specific indications, versus receiving nonleukocyte-reduced blood. And specifically the end points that are being sought in that study are economic or have economic implications, such as length of stay. So I'm hoping that that study will provide some very useful information to try to guide decisions as to exactly what economic benefit we will see. In order to really conduct a cost-effectiveness analysis, one would need to determine what the effectiveness is, and I have great difficulties projecting what the yield of universal leukocyte reduction will be. MS. LIPTON: I think, and then to add, you know, if you look at this from a different viewpoint, and some people are struggling with another concept, and that is that if you accept that there are certain subsets of patients who would benefit from this, we are unfortunately in a situation in our society where I don't believe we can effectively identify accurately, in every situation, those patients who do need them. And the way the DRGs are structured, and the way you go into a hospital, and the limited medical history you get, and you go in on a specific service, and it's their job to get you off of that service as fast as possible, really doesn't have us treating patients, you know, from birth to death. We treat events. And I think that there is some anxiety on the part of people who think if we accept this principle of selective, you know, doing selective leukocyte reduction, that really, in the long run, as Jay said, when you look at a lifetime of these issues, that you don't have a way of measuring that, but you've totally discounted that as a potential good effect. DR. NIGHTINGALE: Jim, I'd like to follow up on Karen's question with the following one. One of the things that skilled technocrats do, and I think there's several people around the table who would self-identify themselves as skilled technocrats do when confronted with a problem and having the resources, is to throw money at the problem. And I said that not just--I wanted to get a laugh out of it to diffuse the situation, but to ask you a very, very serious question. One of the frustrations of us technocrats--skilled or otherwise--when dealing with issues of blood, is whether or not money that we would throw at a problem would actually reach it. Do you have any suggestions as to how any such money that we might throw at this problem, which is the problem of limited resources for blood establishments, broadly, limited reimbursement at the level of the blood establishment, how would you suggest rectifying that problem? If you, in fact, feel it is one. DR. Au BUCHON: I could think of a number of approaches, not all of them, probably none of which, actually, are politically viable, at least in this country. But, for example-- DR. NIGHTINGALE: Yeah, but don't stop trying. DR. Au BUCHON: Okay. No. For example, the blood collection and delivery service could be directly funded by the government. And, in fact, in most countries, most developed countries, that is indeed what is done. So if the society then decides that they want a new test, society would couple that decision with putting more money into the blood supply system. It would directly go to those who are expending the money to buy the test kits and do the test. That would be one way to do it. Another way that has been discussed recently, as we've been considering how best to try to get society to reflect their interest in increased safety with a willingness to pay for it, would be to have a separate payment category for blood transfusion. Right now blood transfusion is rolled into the diagnosis-related groups through which federal government pays for Medicare patients and that there is, indeed, no guarantee that increasing reimbursement through the Medicare system as a whole will be identified by hospitals as due to increased costs of blood. If one were charging out blood directly, then it would be easier to have that recognized. It would at least be hoped that with the amount of attention, amount of press at least within the health care community that the cost of blood is currently getting, that any increased reimbursement through Medicare to hospitals would be able to be used by hospital transfusion service directors when internally negotiating with their administrators to say this additional money should be allocated to our budget in order to bring about additional blood safety initiatives in the hospital. DR. NIGHTINGALE: If I could have a follow-up question then, one of the problems that we have in this country in dealing simplistically with this issue is that we don't have a national blood supply, we don't have a nationalized payer. I think it's 22 percent of health care expenditures, last I checked, and it's in the packet that I prepared for you, are Medicare. So simply if the government were to set a price for blood, it would only account for 22 percent of the benefits. I guess the question I would ask you to consider is, is there a way that the government could set a price for blood without nationalizing the blood business? We've tried, as you know, with the outpatient--APCs. MR. ALLEN: I do not have a direct answer to your question. Maybe I could defer to the economist among us, but I would say that the federal government, while obviously not having control over all health care expenditures or paying for all health care, has incredible power to cause things to happen in the marketplace and particularly in health care reimbursement. So if the federal government were to, for example, indicate that a particular avenue was appropriate and the federal government were willing to put more resources into that to pay for that, I believe that private insurers would probably follow suit. DR. HAAS: Steve, can I just add on to that? I agree with what Jim has said, but I don't think there's any reason to assume the federal government would put more money. They could put less, as Jim already indicated in his comments, so that's a pretty dangerous route. DR. NIGHTINGALE: The federal government has stated on April 7th that the price it is willing to pay for a unit of leuko-reduced blood, when used in an outpatient hospital setting, is $137.21. That's a provocative statement by the government. It's a policy that's in place right now. It's clearly not an adequate policy by itself. It can be viewed, at least as I view it, as a noble experiment, but it is one of the potential responses to the very legitimate issues that you just raised. MR. ALLEN: My understanding is we will get back to the "Dear Citizen" letter, so I basically just have a comment. As was mentioned earlier about the blood industry and the issue of safety insofar as the perception goes, basically what I wanted to say was that we do have a long way to go in terms of educating consumers about how low the risk is now through transfusion, as far as contamination. However, when consumers, such as some of us here at the table, go out into our communities, we don't talk about the numbers like we do here. We talk about the individuals and the effect that these issues have on their families and these people. So I'd just, because of some of the things I hear and we're talking about numbers, I just think it's important that we remember that we are talking about people here and that these issues have a great impact on not only their lives, but their families' lives. And we also heard earlier about the possibility of blood banks going under. I mean, I just want to emphasize that we have families that go under as well. So we just need to, I think, keep all of that in mind when we have these discussions. CHAIRMAN CAPLAN: What I hear or take away from the committee comments might be lumped into four categories. There's an interest in talking about correspondence that people might send around. That's come up. There's interest in talking about do we want to have a template of principles or considerations that we might agree are relevant, even if we don't agree on their application or how to interpret any one of them, but just factors to consider when you're looking at an issue and sort of leave saying, yep, that's a rough outline of what we'd like to have. We were reminded by a number of people that there are groups who rely heavily on blood who are still concerned about supply and equitable access, whether it was IVIG or alpha or hemophilia and asking whether we could put that on the agenda or keep maintenance going on those areas to make sure that they get done. And then there's a discussion out there about what we want to say and do on issues of safety, continued safety, both here--I'll call it the marginal safety issue--and then overseas, the sort of impact on global safety. I may have not lumped them up completely. But, anyway, those are areas that I heard kind of presented to us. I was going to suggest to sort of not illuminate it, but I think it is our responsibility to keep an eye on the supply and access issues for the populations heavily dependent. So on that one I suspect we can just direct ourselves to return to these issues. We may want to go to IVIG and hear about that in terms of a sentinel study or something, but to devote parts of future meetings to that topic. So I don't think there shouldn't be too much controversy about that I would imagine. And then I'm open to going in whichever direction you all want to go to. Are people--well, let me throw open the floor and see. Do people want--what they would like to pursue, if I've got those categories straight, is there an interest in discussing the letter a bit further and trying to do that or-- DR. EPSTEIN: Art, were you going to entertain 5-minute presentations from-- CHAIRMAN CAPLAN: What I was going to do is let them comment a bit on this and then go to the 5 minutes. But it sounds to me like you think your 5 minutes is germane. DR. EPSTEIN: I think before we, you know, cone down on one of the four topics, it might be helpful. At least it speaks to one of them. It speaks to one of them. CHAIRMAN CAPLAN: All right. We'll do your 5 minutes because it may be relevant to one of them. All right. DR. EPSTEIN: Okay. Well, as a hopefully skilled technocrat, I took literally Steve's charge for this meeting, that we hope to identify a set of intellectually consistent, politically acceptable principles on which a coherent and durable policy to assure the safety, availability and affordability of blood and blood products can be established. And so what I sought to do in my 5 minutes was to look at the different paradigms of decision making that have been in use as a framework for trying to think about underlying principles. And my first observation is that I think that there are two large categories that tend to get confounded. You need to go backwards to the first slide. One is how we deal with known threats, and the other is how we deal with potential threats. So with respect to known safety threats, some of the paradigms that have been in operation, and we could talk about which cases were addressed when and how, have dealt, particularly in the post-AIDS era, with a zero risk concept, which is intervene at any cost. And what I've tried to do is rank these in some order of what one might call stringency, and I would say that that's the least stringent because it requires the least reflection about benefits and costs or tradeoffs. Another principle, which I think is a little bit less more stringent than zero risk is looking at whether there's a favorable benefit-to-risk ratio. However, that's also a limited framework because it implicitly is at any cost. As long as sort of the gains outweigh the losses, then it's good and you should do it. But that's independent of whether it costs too much. I think that a larger framework which begins to encompass cost has been the concept of cost-effectiveness is favorable and that that should drive decision. But there's been criticism that at least the FDA shouldn't look at the world that way. We should be cost neutral from our purview. Another principle that has been utilized in other domains, not particularly in the blood area, but has been a successful paradigm, is the notion of trying to have risk as low as reasonably achievable, so-called ALARA, and that's yet another way that one can look at the problem integrating all of the different ways of framing benefits. And then lastly I think the most global point of view is something that's been called public health or wellness, which is to try to look at a possible intervention and rate its value for wellness amongst all alternatives, including things that aren't of a like kind; in other words, tradeoffs for, say, different parts of public health--money into the vaccine versus marginal blood safety, for example. Now, as hard as these decisions obviously are dealing with known risks, they usually are made in the face of unknown risk and/or unknown benefits of particular interventions. And yet once again I think it's possible to recognize that there have been a range of strategies with, again, varying stringency as to how much scrutiny is applied as the basis for decision. And so in the approach for potential safety risks, I think that the most stringent framework, and here I'm going in reverse, has been to withhold all action pending scientific certainty. And I think that that's the paradigm that we had in place approximately 20 years ago, where we waited until the data were conclusive and essentially all fair-minded scientists were convinced. Short of that was the idea that we would withhold action pending a scientific consensus, which basically meant that the decision-makers, whoever they happened to be, tried to figure out if there was sort of a dominant scientific view and then they would go with it. Less stringent than that is what has been called the precautionary principle. And here I'm pretty much describing it as it has been explained in the recent document from the European Commission, which is to adopt precautionary measures based on a consideration of options considering the underlying factors of proportionality, nondiscrimination, consistency, and cost benefit. And I think we need to recognize that we have also had operating in some situations a precautionary principle, but one which has been even less stringent than as articulated by the European Commission, which is to adopt precautionary measures, but in the absence of a full consideration of impacts and alternatives, and that part of the problem has been that some of our decisions have been on that paradigm. Now, I guess I had hoped that at this meeting or perhaps as possible topics for future meetings, we might try to examine some of the upcoming decisions in blood safety and availability or, alternatively, I suppose we could adopt the retrospective model, look at cases where we've already made decisions and ask what paradigm were we on and did it have value or didn't it have value. But I thought it useful to at least note some of the pending decisions. And these fall also into two bins: potential added safeguards and potential relaxations of existing standards. In the area of potential added safeguards, we have, you know in the near horizon, things such as implementation of the minipool nucleic acid test for Hepatitis C, for HIV, which of course are well along in development. But then a big question mark about Hepatitis B, which is a subject of current debate. Shortly over the horizon, lies the question of whether there should further be single-unit nucleic acid testing. And there's a question of whether that should supersede minipool NAT or whether it should be seen as following minipool NAT as an additional incremental safety benefit. And Mike showed us what that would mean in terms of yield and cost and likewise for the same agents. Again, echoing Ron Gilcher, we look forward to an era where there will be infectious agent and activation technologies for cellular components. And the current paradigm would layer them onto existing testing, and I think that the challenge is whether we can deal with the overlap and perhaps not do both always. Likewise, we have the challenge of dealing with emerging infectious agents, and Chagas disease has been mentioned, as well as perhaps the inconsistency of how we've been approaching Chagas versus other things. But the list doesn't stop. It goes on: Human herpes virus type 8, human parvovirus B19, Hepatitis A virus, and other things which are less-well characterized. Then, of course, we have the question of whether to expand the exclusions for TSE risk not only related to Mad Cow disease, but potentially related to other TSEs of mammals that may also be consumed in the food supply, and as has been already mentioned, the questions of routine use of leuko reduction. So under the heading of "Relaxation of Standards," again, I would echo Jane Piliavin's comment that we shouldn't only be looking at the new technology and the new safety threat. We should concurrently and perhaps always be reexamining existing policies and standards and reassessing their benefit in a current scientific light. And I would put on this list such considerations as the voluntary discontinuation of ALT, the movement toward relaxing the restriction on donation by persons with hereditary hemochromatosis as to the current requirements for unit labeling and restricted donor frequency, and we've already discussed the fact that FDA has moved toward permitting exceptions, whether to discontinue HIV 1P24 antigen testing in the era when we can approve minipool NAT and perhaps single-unit NAT, relaxing potentially the current exclusion criteria based on behavioral risk of males who have sex with males, whether there is continued utility of the serologic test for syphilis and what is the continued utility of the test for antibodies to the core antigen of Hepatitis B. These are just ones that are already under consideration, not even getting into the question of things that may come down the road. So what are the key issues then in terms of the decision-making process? My concept is that the issue of the day is to talk about a process by which blood safety availability and affordable cost decisions can be made in the post-AIDS era based on some appropriate set of underlying principles that should govern that process. My own notion of those principles is shown on the next two slides, and fundamentally they conform with the recent statement of the European Commission regarding application of the precautionary principle. However, again, I would point out that the underlying principles really are not limited to the situation of threats of unknown risk or unquantified risk; that the same principles really should underlie consideration in the case of known or quantifiable risk, as well as reconsideration of existing measures. So what are these principles? Well, I would put way to the top of the list that I think acceptance of risk is a political decision. And what I mean by political is that ultimately it's a matter of social choice, however the society goes about that. Related to that, I would agree with what was stated, at least by Dr. Gilcher, that zero risk should remain a goal, but it cannot be viewed as a mandate. Regarding it as a mandate in any given situation may lead to irrational actions, even if we continue to embrace as a reality public fear and the public goal of zero risk. Secondly, I would say that just as acceptance of risk requires political decision, acceptance of cost is a political decision. Why? Because in the end there are finite resources, and it is up to the society where to place its resources and for whatever gains or perceived gains. Thirdly, in a democracy, I think it's inevitable that decision making must be transparent. But I think that this is also a necessary feature to obtain a public endorsement, both of the process and its outcome. Fourth, I concur with the EC statement that any effective decision-making process in this domain must be structured and must include the elements of risk assessment or risk management; that is to say, well-defined strategies of known or presumed effectiveness, and additionally, risk communication, however effective or ineffective that might be. Further, I believe that there has to be ongoing scientific input; that this has to be both prospective and retrospective in any situation. And I would add two dimensions that are part of the WHO thinking, but are not really echoed in the EC document, which are that in this global village, blood safety decisions need to be considered in an international framework because they have international repercussions bi-directionally from the U.S. point of view, and that additionally it's my personal view that wherever possible, the decision makers nationally should attempt to independently articulate the scientific basis, economic basis and political basis of blood safety decisions because I think that that effort contributes to clarity and creates increased freedom for national governments and societies to make different decisions in the face of the same available scientific data. And so that's my stab at trying to frame what I think are the underlying problems in examining decisional paradigms, as well as my view of the basic principles we might wish to discuss. CHAIRMAN CAPLAN: All right. We can move toward principles and a matrix discussion or we can move toward some discussion of the correspondence issue. Anybody want to take us in a direction? I'm going to see which way the comments go here. DR. KUHN: I'd like to give a stab at the correspondence issue, and hopefully it can be addressed pretty quickly. After listening to much of the discussion this morning, it seems like we do have a correspondence that was sent out to congressional members. They did get it in some kind of a packet, but they are not under any obligation to mail it to their constituents. And it seems like there probably is--funding is probably not available in the 2000 budget for trying to address the correspondent issues. But I believe that in the spirit of what the committee accepted and their recommendations of August 13, 1997 and November, 24, 1998, regarding Hepatitis C look-back notification and education, and also seeing that the surgeon general deemed the "Dear Citizen" letter most important, I would offer a recommendation, hopefully, that could be considered, and that would be that the committee actively supports the surgeon general's effort to inform the American public of the risks that Hepatitis C or HCV infection and transmission. Moreover, the committee strongly urges the secretary to seek adequate supplemental fiscal year 2001 funding in order to provide the CDC with the most efficacious and widespread means of informing the American public, including the consideration of sending a "Dear Citizen" letter to the American public by March 31st, 2001. CHAIRMAN CAPLAN: That sounds like a proposal. Why don't we have a little discussion. MR. ALLEN: Would it make sense to consider possibly asking HHS to allocate the funds directly to the surgeon general? No? Why not? DR. NIGHTINGALE: I think--we don't--not that much money passes through us, and there's a reason for it. I don't think that where the money goes is essential the perf--is material to the performance. MR. ALLEN: I guess what I'm concerned about is obviously I'm one of the people that would like for this letter to go out. But my concern, one, is if it comes from a congressperson who may feel obligated to send it out, but really doesn't want to send it out, and then once the constituents get this letter, they're more than likely going to call that congressperson's office, and they may or may not have the right information to give them. So I'm a little concerned about doing it that way. So that's one of the issues. If this is a letter that the surgeon general feels strongly about, I want to back him in getting this letter out. DR. NIGHTINGALE: I apologize. Larry, while you were talking, I was looking over my shoulder to see if the window that was blocking the text of the statement had been obliterated. So I misunderstood what you said. Could you repeat it once more for me. I know it's already in the record. MR. ALLEN: I just wanted to know whether or not we could ask that funds be given directly to the surgeon general for the purpose of sending out this letter directly. DR. NIGHTINGALE: Oh, here, I just have to speak personally, and this is from the heart. The administrative staff of the surgeon general is limited. You are looking at them. [Laughter.] DR. NIGHTINGALE: I think, given that reality, there are more administrative staffs in agencies where such programs are usually based, and there is a reason for that. MR. ALLEN: Okay. Well, then besides letting Congress do this is what I guess I'm getting to here. I'm just concerned about the letter coming from congresspeople that might, you know-- DR. NIGHTINGALE: If the money were to be allocated, I cannot anticipate problems spending allocated money. But if I could anticipate a problem, it is one person, contrary to public belief, in the government can only spend so much money so fast. It takes more of us to spend all of that tax money. CHAIRMAN CAPLAN: Paul? DR. HAAS: I guess, listening to some of the discussion before lunch, I guess before the discussion I wanted a letter out. Listening to the discussion, I'm not so convinced. I just don't know. And the way the proposal is written, it doesn't say, "Send a letter." It says, "Let's get appropriate information out there." And in the spirit of some of the discussion we have just had, I guess I'm a little reluctant this afternoon to say the letter is the absolute most important thing to do or the best way to do it. So I guess I'd prefer to keep it the way it is, and then figure out a way to put the nice gentle pressure and say, "This is extremely important", and the intent of that letter's got to go out there whether it's the letter or not. So, again, I guess my fundamental point is I'm not right now in favor of tying anybody's hands. DR. NIGHTINGALE: Again, I'm just speaking as a grammarian here, not as an official of the government, if that is possible--and it probably isn't. But I don't see anything up on the board that would tie our hands. DR. HAAS: I agree. That's what I'm saying, I like it the way it is. MR. WALSH: Mr. Chairman, on the contrary, I think our hands are shackled right now without this. And Larry, maybe that you weren't here earlier this morning for the discussion of--the entire discussion, but the letter is a letter signed by the Surgeon General on his original letterhead. It's not as if it's coming from a member of Congress, advising a constituent of a potential health problem, so I think that hopefully they would look at the Surgeon General's letterhead and not the Congress person. DR. GUERRA: I certainly agree with trying to get information to the greatest number of people in the shortest period of time, but I think incumbent in the process is also the need to have some capacity in place to serve the general public that is going to have the questions, and that is going to need to be counseled and screened and tested, and then connected to resources, and I think that that is a moral and ethical obligation that we will have, but I think it's part of this process. DR. NIGHTINGALE: Again, I have to phrase this more carefully than perhaps I phrased some of the things that I've put into this microphone. But there are several proposals currently before Congress, of which I am aware, that address the point that Dr. Guerra just raised. What are they? DR. GUERRA: Yeah. What are they and how far along are they in the process, because there are very few resources out in the field right now. DR. NIGHTINGALE: I understand. Rather than just telling everybody to go to Thomas dot LOC and search for hepatitis, that's one way to do them. To answer your question--and I haven't done that search recently--I am aware of one proposal that is an authorization rather than a dollar amount to spend money for this purpose--a children's health insurance plan. Just kind of a for instance, because that's the one that I looked at yesterday. CHAIRMAN CAPLAN: Mary? DR. CHAMBERLAND: Just for the record, I haven't really had any involvement with the development of the letter at CDC. That's something that Hal Margolis and others, as you heard this morning, have been working on. I guess before we vote on anything, my sense from the comments that I heard this morning, Steve, is that the letter is not a dead end, and that as I understand it, there has been a very public announcement by the Surgeon General and Congressman Bliley to put out a letter using Congress and its mailing capacity to do so, to its individual constituents. And, yes, there is no obligation for each individual congressman or woman to do that. And it has hit a snag, a couple of snags, in terms of the separation of powers issue and this 90-day moratorium on mail-outs prior to an election. But what I heard this morning is that what is under way is--actively under way, is to try and work through those two implementation issues, and-- DR. NIGHTINGALE: And furthermore, if you--excuse me--to search for alternative means of distribution that would not subvert the purpose of the message, changing the letterhead, say, to a commercial entity signed by the Surgeon General is not on the table, but-- DR. CHAMBERLAND: Exactly. DR. NIGHTINGALE: We could discuss it, I suppose. DR. CHAMBERLAND: Right. So--and I understand there's this whole other discussion that's been going on this morning about the merits of a letter and how effective, whatever it could be. And I guess I'm just wondering if such a vote is a little premature. Perhaps we should--you know, if the committee wants to make some statement, recommendation about their support for such a letter and that it be sent out, and that Congress, individual members of Congress, support this effort, because I guess I'm believing that this is eventually going to be worked out, that there will be a way for Congress and the Surgeon General to work together to get a letter out, but it can't be until after this 90-day period that has to be paid attention to. And that, really, we should maybe be supporting efforts to see that that does happen once these sort of implementation issues can be worked through. DR. NIGHTINGALE: This is Steve Nightingale. I agree with Dr. Chamberland. Let me restate that while I can't predict the future, I can state my own intentions, and I can state the result of a conversation that we had on Monday with the Surgeon General, was to proceed on the basis of our private discussions with congressional staffers that the issues were prudentially resolvable, and also to proceed with other avenues for distribution of the letter. Also in the context of support for the overall CDC program report. I think it is important here for me to state that it is not our view--this is not the only component of the CDC's or the government's effort in this area. It is not our intent to get into a discussion of the relative importance of this or other initiatives, because, frankly, we don't care. We want to get the job done, and successful as possible, with the--and make--I should find a better word--the minimum amount of mess in the process of doing so. This is a messy issue. At the same time, since we are certainly open to alternatives to distribution, we are certainly open to getting the maximum amount of effect for the money that we spend. I think it's fair for me to say that I don't--I didn't see anything up here, as I said earlier, tied our hands on this issue, but that's because I'm not looking at it right now. I'm looking at the committee, and if somebody else sees something that would tie our hands, please let me know. CHAIRMAN CAPLAN: I see something that will tie our hands. If anybody thinks--this is my opinion--that they're going to sneak a $30 million expense under the franking privilege around the lawyers that are now paying attention to this, forget it. So my hunch is that unfunded, this may not fly. You betting me? All right. I'll bet the lawyers. I'll take it. So if you want to be risk averse and follow the zero risk principle, you might want to look at something like that as a ace in the hole of the letter, finding a way to send out a efficacious letter. I'm assuming here, that as we deliberate about this, it might turn out that putting it all on TV was better than sending a letter, but that's my outlook on things. But whatever, some way to get that message out. That may be our safest course, it would seem to me. DR. EPSTEIN: I just wanted to propose some rewording that might be a little bit better received by the Secretary. What I'm suggesting is that the part directing the Secretary what to do simply be omitted, and that the date certain be omitted because that would increase flexibility. So if we do that, it would read, "The Committee actively supports the Surgeon General's efforts to inform the American public of the risk of the HCV infection and transmission", and then jump down, "including the consideration of sending a "Dear Citizen" letter to the American public as soon as feasible." I think the virtue of that is that you have the committee endorsement, but you really have not dictated how the message should be conveyed. You've suggested the sense of urgency, but you've not, you know, put a burden on the Secretary should it not be feasible by that particular date. So it's a little bit softer, but I think it gets our message across. Let me just reread what I'm saying. Basically what it would be, deletion from the word "moreover" through "American public." So it would say--yes. And then I would strike "by March 31st", and substitute "as soon as feasible." So this version would read: "The Committee actively supports the Surgeon General's efforts to inform the American public of the risk of HCV infection and transmission, including the consideration of sending a "Dear Citizen" letter to the American public as soon as feasible." And that way we're not telling the Congress what to do, we're not telling the Surgeon General what to do. We're just saying that something should be done and as soon as feasible. DR. KUHN: I thought about the wording very carefully, and I think it--and that the logic or rationale I had behind that was, number one, I think it fulfills Congress's concern that they have had on this issue for quite some time. I think it addresses that, number one. Number two, I think it also addresses the urgency of many of the decisions that this committee has made, and also the encouraging ways that the CDC is trying to get this information out to persons. I think, number three, it supports the Surgeon General's--I believe his wishes of trying to get the communication out as quickly as possible in a widespread manner. And also when you're dealing with Congress, I think we all know, you have to have money. And I think it has to be mentioned in there in order for this to fly. And I also thought about putting--when I put this together, that we needed to make it flexible enough--a directive, but a soft directive, and flexible enough so that there is latitude to be able to accomplish the objective. It doesn't mean that it has to be a "Dear Citizens" letter. That is the direction that the Surgeon General proceeded in in having that letter written, but it doesn't necessarily mean that is going to be the most effective way to accomplish it. I think the goal is accomplishing it. How do we make the American public aware in a widespread way? And it's going to take funding, and I don't think--I think if we ignore mentioning the funding, I think this will get lost someplace in the budget process that's going to be taking place in the next month here. MR. ALLEN: I agree with what Dana's saying. My concern is leaving it open-ended like that. I think maybe if we could ask that they get--give us some response back by the next meeting in terms of where we're at with--where they're at with this letter, the timeline that they feel maybe that will give them enough time to have some answers, because right now, you know, if we leave it the way it is now, look at how long it's taken us to get to this point. By the time they finally get a letter out, it might not mean anything. So I'm concerned about that. I would like some kind of language in there that at least ask someone within HHS to get back to this committee by the next meeting with a timeline on what's happening with this issue here. CHAIRMAN CAPLAN: Being somewhat befuddled about my parliamentary procedure here, we have two proposed statements with nothing moved yet, so somebody could move one or the other, or we can have a little more discussion. DR. KUHN: Mr. Chairman, I move that the first proposal or recommendation that I had submitted by put on the floor. CHAIRMAN CAPLAN: Did you save that one, Mac, in your-- DR. AuBUCHON: Second. CHAIRMAN CAPLAN: Discussion? About amendments to this short of Jay's amendment. We could do it that way. Any other language clarification as soon as it reappears? DR. BUSCH: Just that the "infection and transmission", I'm trying to understand what those--how they're different. One thought would be to, instead, have "infection and disease" instead of "transmission." DR. EPSTEIN: I thought the point of that was to deal with the issue of secondary transmission. In other words, your own infection and the risk to transmit to others. Your modification would be correct, of course, but would lose that conflict. That's how I read it. CHAIRMAN CAPLAN: Jim? DR. AuBUCHON: From time to time the Executive Secretary of this Committee offers us valuable insights into the workings of the government. Might he offer some comments as to which two versions that have been discussed would provide the intended outcome? And I do not perceive that there is really any difference around the table in terms of what we would like to see happen, but how best to make it happen is not entirely clear. DR. NIGHTINGALE: I can obviously live with either one, because it's my job to live with each other one, appearances sometimes to the contrary. I--this is a gut feeling, something that comes from the committee, particularly if it is very strongly endorsed by the committee, will have more force, because believe me, if they want to get a hold of me or Jay, they have our phone numbers and they can get our advice--well, not for free, but at a relatively discounted price to the market. So for that reason, I suspect that the more potent one would be the one from the committee. Did I walk the fine line? DR. AuBUCHON: Very ably. MR. ALLEN: Steve, what would be your opinion then on how long of a time before we got a response from the Secretary? DR. HAAS: Maybe we could ask Steve to turn off his mike. [Laughter.] DR. NIGHTINGALE: I think that the--obviously, the Secretary's FY 2001 budget is in. At the moment, what happens with the budget that begins on October 1st is in the hands of Congress. Yes, there is a lot of discussion going back and forth, but really, most of that discussion at this point is White House, sort of is White House coordinated. I'm not speaking in absolute terms. I'm trying to give the committee information based on what I know general processes are, but specifically, what I know the processes for the health budget are. The Secretary has not had problems in the past saying, "Thanks, but no thanks" or "Thanks, but reconsider." And if she or the senior staff were to disagree, we're not in a confrontational mode here because we're all trying to do the same thing. That's why I made the suggestion that I did. I wouldn't sweat the small stuff here right now, because it's not going to offend anybody, I think, or put anything off track. I think you've heard from me what our consensus within this administration is, which is we consider that a component of what we're trying to do, we're trying to make it happen. We've also--there's a lot of other things that we would like to do with 30 million bucks, and if we can do this for less than 30 million or get somebody else to pick up the tab, we'll be--we could still use the money. So I mean, given that bias, if yours is not--if yours, the committee, is not identical to that--and I think to some members of the committee, it is not identical to the one that i just articulated--then if you wish to articulate your own position very clearly, this would do it. Again, I'm really--and not just for the record. I think people understand, I'm not trying to talk you into one position or another. These are easy sells for me one way or another because the distinctions--I mean, these are tactics rather than strategy. Everybody wants to get to the same place here. CHAIRMAN CAPLAN: Jane? DR. PILIAVIN: There is some discussion. I just heard in fact one mention of there being lots better ways to spend $30 million. Speaking now as a social scientist, which I don't get to do specifically very often here, I think we should think about the response that was made by the gentleman who's no longer here, to how effective the last Surgeon General's letter was, and it didn't sound as though it was very effective. You mentioned the use of television. I think you mentioned it, perhaps not seriously, but you could get a lot of spots in very high-profile places. John mentioned the Super Bowl. It only costs $500,000 for a spot in the Super Bowl, which in comparison to--I always used to think that was a lot of money, but in comparison to $30 million, it's a drop in the bucket. In terms of the persuasive power that we know different media have, television has a whole hell of a lot more than a letter that comes in the mail, that if it has got a congressional stamp on it, is most likely to end up in the waste basket, because a lot of people don't think very highly of the Congress, and a communication from them is unlikely to be seen as terribly valuable, whereas a communication-- CHAIRMAN CAPLAN: I hope you have the data to back that up. [Laughter.] DR. PILIAVIN: I don't, but I could probably find it. But seriously, it's clear that this is what the Surgeon General would like to do. I think a spot with him saying this on television, that could be put on 15 times for a third of this money, even in extremely high-profile places, would reach more people with more effect, and I would suggest that maybe it would be good to have some social scientists who are more expert in persuasion than I am--and I could give you a list of people--speak to him about alternative ways of doing the very same thing. CHAIRMAN CAPLAN: Well, just two quick comments. One, there will be many television marketing people available after November 9th who might want to work on this, and there are also--I think the language that I like about this is to try and figure out the most efficacious and widespread means of informing, including the letter, because it does make a window there to have it taped, read, broadcast, and, as I was trying to indicate, my concern is coordinated. There are a lot of other things going on, and I hope that the way that language reads would get a coordinated effort going with the letter. I too am not so sanguine about the fate of the letter actually, even though I was joking about it, but I'm not impressed that a letter alone is going to get us where we want to be, and I think that was the lesson of the Koop thing. So now, how about a call for vote? Yes, I see some sentiment for that. All in favor of the Kuhn proposal on encouraging correspondence? [Show of hands.] DR. NIGHTINGALE: Eleven votes in favor. CHAIRMAN CAPLAN: All opposed? DR. NIGHTINGALE: I see no votes. CHAIRMAN CAPLAN: Abstain? [A show of hands.] DR. NIGHTINGALE: I see-- CHAIRMAN CAPLAN: I got two abstain. DR. NIGHTINGALE: We have two abstentions? The motion has 11 votes in favor and no votes against, two abstentions. Motion carries. CHAIRMAN CAPLAN: All right. Now, I'm in a mild dilemma here. I want to leave some time for public comment, and I want to leave some time for consideration or talk about further comment about the matrix principles, whether there's something we can do. I know we don't have to settle that one, but I'd like to at least--since we had people kind of turn in homework assignments that covered some of this, it would be useful to give some opportunity for a little bit more comment on that. So my proposal is this: How many people do we have who want to make public comment? If I could get hands way up. Okay. What I'd like to do then is ask you, as I often do, to limit it to two minutes, come to the mike. We're going to do it in the order in which you arrive at the microphone. There's someone going first. I like that. Yet again, let me ask you to identify who you are, and give me your last name and that will give me the clue about who's coming next. MS. HAMILTON: Okay. My name is Jan Hamilton. I'm Executive Director of Hemophilia Federation of America. When the IOM gave its report on crisis and decision making in July of 1995, it considered the nation's blood supply a unique, life-giving resource. They said the safety of the blood supply is a shared responsibility of many organizations, including the plasma fractionation industry, community blood banks, the Federal Government, and others. The precipitating event for the findings of the IOM was contamination of our nation's blood supply by the HIV virus and all that it entailed. In the ensuing years, we've heard much rhetoric about who failed to do what and when and what should be done about it. We've also discussed the same things today. Thousands of lives have been lost, and even more families' lives turned upside down because of the lack of a systematic process in the past. The charge from the IOM was that we learn from the past and prepare for the future, and that's what I hope I hear coming out of this Committee. We would like to urge that we continue the charge from the IOM. Several of the charges have been addressed by Dr. Satcher as he mentioned them this morning. There are still some areas that need to be visited and some that need to be revisited. Please continue to monitor foreign bodies in the blood supply: CJD, HIV, hepatitis C, hepatitis XYZ, whatever, and even such things as bacteria and/or mold in the manufacturing process. We appreciate the proactive stands in these areas, including, but not limited to, NAT testing and leukocyte reduction. Continue to monitor problems of supply. Dr. Hoots mentioned it earlier today, and we have been very concerned about the decline in the recombinant supply and are speaking with industry directly. But we could use a little help from our friends. Continue to address errors and accidents. Some of these have proven to be disastrous and cost dear lives. We've been pleased about the Committee's stand on the prospective payment system issues, and now we would request some assistance in addressing looming inequities on AWP for coagulation products, and especially recombinant products for Medicaid and Medicare patients. There should not be a double standard for these patients, or for anyone. The establishment of this Committee has been a bright light on the horizon, and we're very pleased to be able to attend, learn, and put in our two cents' worth of comments on issues heavily impacting the coagulation disorder population. We hope you will continue to be vigilant in the areas of blood and blood product safety and continue your strides towards excellence. Thank you for allowing us a few minutes to comment. CHAIRMAN CAPLAN: Thank you. Questions? No? Okay. Again, I'll ask you to state your name for the record. MS. FOSS: Thank you. I'm Mary Foss from Mayo Clinic, Rochester. Dr. Brendan Moore and I would just like a few minutes to talk about costs and benefits related to leuk reduction. I would like to start with just a little bit of data to give you an idea of the scope of our practice in Rochester so that you can kind of compare our costs with our size. In 1999, we transfused about 39,000 red cells, about 46,000 platelet unit equivalents, close to 14,000 fresh frozen, and about 6,000 cryoprecipitate. If I could have the next slide, please? Our blood inventory comes from the blood we collect at Mayo Clinic, Rochester. We collect, test, process, as well as transfuse, and we also receive supplemental blood supplies from the St. Paul Red Cross. So about 56 percent of the red cells that we transfuse at Mayo Clinic, Rochester, are collected at Mayo. And the other 44 percent come to us from St. Paul Red Cross. Red Cross provides 29 percent of our platelet unit equivalents, and about 71 percent are collected by us at Mayo. Of those 71 percent platelet unit equivalents that we provide, about half of them, a little more than half come from apheresis donations and the other half are random donor platelets made from whole blood donations. So you can see we rely heavily on the random donor platelets made from whole blood donations. So, consequently, we feel that if and when we go to 100 percent leuko reduction, leuko-reduced blood supply, we will need to continue to manufacture random donor platelets from whole blood donations. If I could have the next slide? You can see that when we calculate what that's going to mean to us when we switch from our current situation, which was that we were at 17 percent of our red cells being leuko-reduced and 70 percent of our platelets. If we go to 100 percent, we will go from a supply cost of $15.50, approximately, to a supply cost of $40. This is exclusively due to the need to switch than to a new collection set with the in-line filter. If I can have the last slide, please? I wanted to just show you the incremental cost for us to switch from our current situation to 100 percent leuko reduction at Mayo Clinic, Rochester. When we look at the increased cost for us for the blood we collect as well as the increased charges from the St. Paul Red Cross for all of their blood to be leuko-reduced, for us at Mayo Clinic, Rochester, the incremental cost is $1.2 million. And when we saw those big costs, we knew we needed to step back and better define the benefits before we made the final decision. We thought we wanted to go to 100 percent leuko reduction. We saw a lot of reasons why we probably should. But $1.2 million in our institution is a lot of money, and we needed to be able to justify that decision. So now I'd like to turn it over to Dr. Moore to have him give you some of his thoughts and ideas about those benefits and this conundrum that we find ourselves in in making the decision. DR. MOORE: I'm Dr. Brendan Moore. I'm the Chairman of the Division of Transfusion Medicine at Mayo Clinic. Next slide, please? Next? This is a figure that's been shown recently looking at the total number of blood collections in the United States, and it's available to anyone to look at, but there's clearly a down trend, which is a national problem. Next, please? If you just look at the question of benefits and concentrate on certain areas of benefits for leuko reduction, one of the areas that stands out in my mind as being potentially where the money is is post-operative infections. If you look at the number of surgical procedures annually in the United States, there are 18 million, and post-op infections are either surgical site, catheter-related, pulmonary, or general sepsis. Now, if you just look at surgical site infections alone, by the best estimate about 2.7 percent, or 486,000, surgical site infections per year. Approximately 50 percent of the transfused blood in the United States goes to surgical patients, and there are data to support this. You'll see where I'm going with this in a moment. Next, please? These are the data from the Vamvakas' study of surgical versus medical use, and they're approximately the same in Olmstead County. So we think it's probably the same nationally, about 50 percent. And, of course, if you're going to use surgical site infections, then you're only looking at the benefit from half of the blood that you leuko-reduce. Next, please? Here's a study by Kirkland, et al., from Duke, I believe. They did a matched cohort study of surgical site infections on 255 pairs in inpatient surgery. Now, the main point of this slide is to show that mortality was different. Those requiring ICU admission was different. The median hospitalization, translate that to dollars, and median direct costs were different if they got a surgical site infection or they didn't. And we've all known this for years. Next, please? If you then looked at the survivors requiring readmission, you now look at 41 percent of those with surgical site infection versus 7 percent, excess hospitalization of 12 days, and in this one study alone of just 255 matched pairs, the incremental cost attributable to surgical site infections alone was $1.9 million--255 patients, $1.9 million, surgical site infection alone. Next, please? So if you extrapolate from that--and I know that economists and maybe epidemiologists would shudder if they saw how I did this, but if you just take those figures and extrapolate them to the national data, one is potentially looking at a cost of surgical site infection alone in this country annually of $3,764.1 million. Now, that's real dollars. However, the proportion of inpatient surgery which is associated with transfusion is not known, so it's not clear that all inpatient surgery, even major surgery, is indeed now associated with transfusions. You can see where this leads. Next, please? Multiple studies have demonstrated that there are various risk factors for surgical site infection, depending on the type of surgery, the age of the patient, whether it's spinal surgery, whether they have a high admission hematocrit, and whether they're allogeneic transfusions, and those contain white cells. This is non-leuko-reduced. So transfusions are only one of the factors that may well have affected the surgical site infection or other infections. But it probably is one. Next, please? The relative contribution of allogeneic transfusion to the risk of SSI is actually unknown for most surgical operations, and this is clear--and I'll come back to this point. We don't know enough yet. If you look at the study of post-op infections, localized or systemic, in 120 patients--this is from Heiss' study--having colorectal cancer surgery, those getting allogeneic transfusions had an odds ratio of 2.84 by a multivariate regression analysis. So, in other words, in that study it appeared to make a difference. Next, please? If you look at Vamvakas' study, retrospective analysis of nearly 1,000 colorectal cancer patients at MDH, allogeneic transfusions were associated with a relative risk of 1.07 for post-op infections. In other words, there was a 7 percent increase in those transfused with allogeneic blood. And another study from Vamvakas in the same institution, this time looking at just CABG and pneumonia, which is a common occurrence after CABG, the allo-exposed versus the unexposed had a clear difference, and the risk was related to the length of storage of the blood. None of these were prospective, randomized studies. Next, please? If we weren't looking at this unfortunate situation, none of us, as was mentioned earlier, would even bother discussing this question. We'd all have universal leuko reduction a long time ago. But, unfortunately, we are dealing with large dollars. Next, please? So, in summary, what I would like to say is that allogeneic transfusion exposure appears to be one of many significant factors in post-op infections. The result of multiple studies, in fact, appear to implicate the white cells in that blood, hence, leuko reduction. The potential savings to society are enormous if the post-op infection rate can be significantly reduced. And, remember, transfusions may only be one factor, but it may be an important one. The final comment I would make is really a plea that before we make significant decisions--and this Committee makes significant decisions relative to blood safety in the United States--that there be more data obtained so that the decisions that are made are based on some sort of analysis that gives you a balance. And I think most experts would agree that there really is a need for large, multi-center, prospective, randomized clinical trials to assess the role of white cells, red cells, and even plasma, free hemoglobin, and maybe even iron content in post-op infections, because there are data supporting the role of each one of these, but we don't know the full answer yet. So before we spend the money, let's figure out what it's likely to--what the bang is likely to be. Thank you. CHAIRMAN CAPLAN: Questions? Larry? Dr. Moore, do you want to stay up there? MR. ALLEN: I was just curious. In the best of both worlds for you, what would you prefer to have? What would you like to see happen? DR. MOORE: Well, to make life very simple, I would like the FDA to mandate leuko reduction. Number two, I would like the government to then recognize this is going to cost an enormous amount of money, and before the mandate is done, more data are obtained, and they're obtained in decent studies with large numbers in a fashion similar to what the TRAP study attempted to do and did very well some years ago for a totally different issue. So that everybody would arrive at the same point and say we have a consensus, we don't need a mandate that people fight over, it's very obvious that we have cost-effectiveness, let's do it. Because there are multiple medical reasons for giving leuko-reduced blood, but not necessarily to everyone. That's the problem. COL. FITZPATRICK: Dr. Moore, on your cost estimates, do you use a micro-aggregate filter at the ward? And did you eliminate that as part of your cost estimate? DR. MOORE: No, we don't use micro-aggregate filtration, and, in fact, if you look at the data on micro-aggregate filtration over the years, it really hasn't been effective in taking out the numbers of white cells that one needs to get to. And, in fact, recent data from Europe particularly would indicate that the level that we should be aiming at is not 5 by 106 per unit, it's really 1 by 5 by 10--1 times 106 per unit. And that is achievable with modern filters, but not at the bedside and not micro-aggregate. They'd have to be done in the lab with proper QC. COL. FITZPATRICK: I'm not sure--the question was more pointed to how you're currently using them, and would you eliminate them with ULR? DR. MOORE: Oh, no, we don't--we have never used them. For those patients who need leuko-reduced products in our practice--and you saw the figures for the numbers--we use third and fourth generation filters. They're not micro-aggregate filters. CHAIRMAN CAPLAN: Last one to Jerry. DR. WINKELSTEIN: I noticed that the increment between pre- and post-leuko reduction cost estimates was incrementally in terms of percent greater for the Mayo Clinic than the American Red Cross. I think the Mayo Clinic went from 400,000 to 900,000, and the American Red Cross from 1.6 million to 2.1. Is that a real difference? Are there cost savings that differ from provider to provider, or what? DR. MOORE: Mrs. Foss might want to make a comment about this since she pulled the data together and put it together. But it seems to me that what we did was a fairly rough and ready estimate as to what our own cost difference was going to be based upon the materials--not the blood itself, the materials that we would have to buy, the filters, for example, the bags, the new bag systems, in order to do it in our establishment. We really can't compare that to anybody else's cost where scale may be different, for example, at Red Cross, et cetera. The contracts that we have with the manufacturers of blood bags and filter systems might be quite different from the contract that the Red Cross would have. So it's apples and oranges, and I wouldn't like to compare more than that. Mary, do you want to say anything? [No response.] DR. WINKELSTEIN: Thanks. CHAIRMAN CAPLAN: Thank you. I'm going to move us along here. Please tell me who you are for the record. DR. FANG: Thank you, Mr. Chairman and members of the Committee. My name is Chyang Fang, and I am Director of Scientific Affairs of Chiron Corporation's Blood Testing Division. The purpose of my comments today is to update you on the impact of Chiron's genomic Nucleic Acid Testing (NAT) capabilities. Since March of 1999, Chiron and its strategic partner Gen-Probe, Inc., has been supply NAT reagents, instrumentation, training, and technical support to U.S. blood centers performing NAT under FDA-approved Investigational New Drug (IND) protocols. The Chiron HIV-1/HCV assay is currently utilized to screen approximately 75 percent of all volunteer blood donations in the U.S. under IND. Blood banks from the civilian blood collection sector and, most recently, the Armed Services Blood Program are now routinely screening blood donations using this highly sensitive and new technology. Scientific studies estimate that NAT may reduce the window periods of potential HCV infection by 70 percent and by nearly 50 percent for HIV. Working with all blood centers in the United States, by June of this year NAT assays have identified 62 HCV-positive donors and four HIV-positive volunteer donors whose infectious units would have been transfused but for NAT testing. In addition, NAT assays are responsible for identifying three HCV-positive donors that were initially HCV EIA negative due to laboratory errors. In addition to interception of infected donors, NAT has demonstrated other public health benefits. NAT can identify infected persons at the early stage of infection for more effective antiviral treatment. In addition, NAT results are an important tool for counseling of volunteer blood donors and also paid plasma donors. NAT can enhance diagnosis and treatment and prevent secondary infections. Outside of the U.S., the Chiron NAT assay has been specifically approved for blood screening in France, Germany, Spain, Australia, and Singapore. The Australian Red Cross began routine screening in May 2000. Various European countries are finalizing plans for full implementation of nucleic acid testing. Blood is a national resource that must be preserved and maintained. Each person in the U.S. shares equally in the potential need for blood and the resulting potential for contracting transfusion-associated illness, such as hepatitis and AIDS. Therefore, we must strive to protect and maintain both the safety and availability of the nation's blood supply. There are still cases of transfusion-transmitted HIV and hepatitis in the United States and other countries. We can substantially reduce these infections by adopting new technologies, such as NAT, in order to improve detection of these infectious agents. NAT testing ensures that our nation's blood supply is truly as safe as it can be. Thank you. DR. NIGHTINGALE: Do we have any questions? Are there any questions from the committee members? [No response.] DR. NIGHTINGALE: If not, thank you very much, doctor. Merlyn? I'm sorry, Merlyn, could you identify yourself in the microphone? DR. SAYERS: I still am Merlyn Sayers. I'm going to be speaking on behalf of America's Blood Centers, and we really do appreciate this opportunity to address the committee. America's Blood Centers is an association of some 75 diverse community blood programs that are responsible for about half of the nation's volunteer donor blood supply. ABC has many concerns that really reflect the division of opinion, both within the organization and nationally, regarding the justification for universal leuko-reduction. While some ABC blood programs have embraced universal leuko-reduction as appropriate, those who point to the lack of medical consensus on the topic also consider that the selection of such components is an expression of the practice of medicine. ABC members are, however, in agreement that if FDA does go forward with a recommendation for universal leuko-reduction, the agency must proceed with formal rule making, rather than allowing implementation to proceed until a standard of care has been established, followed by regulation under CGMP. Only through formal rule making will there be consistent quality control and licensure requirements. Furthermore, with regard to licensing, this ponderous process must be streamlined before the expected surge of universal leuko-reduction linked applications, and to these ends we ask this committee to urge the FDA to continue considering creative, effective and efficient methods, as the agency outlined in a June concept paper, to assure the quality of leuko-reduced components and the pace of their licensing. We're concerned that as we move towards universal leuko-reduction some other unforeseen issues are going to arise, such as the problems currently being seen with leuko-reduction of red cells from donors with sickle cell trait. And finally, we ask this committee to exhort the FDA, even as that agency proceeds with rule making, to cooperate with PHS, health care agencies and hospital organizations to help remedy reimbursement deficiencies. And while we recognize that FDA is not charged with solving reimbursement problems, it no longer is acceptable for regulation to be divorced from reimbursement. And in this context, America's Blood Centers applauds members of this committee for their resolution of April the 26th, which recommended legislation to provide funding for blood-related costs, and we respectfully solicit this committee to persist in encouraging steps that put an end to unfunded mandates. Thanks. DR. NIGHTINGALE: Thank you. Before Ms. Gregory approaches the microphone, are there any questions from the committee for Dr. Sayers? [No response.] DR. NIGHTINGALE: If not, Kay. MS. GREGORY: Some disadvantage to being short. My name is Kay Gregory, and I'm here with two separate statements. First of all, I want to speak--when I get the microphone fixed--on behalf of the new multiple organizational task force that the AABB has developed, to evaluate and develop recommendations to simplify the uniform donor history questionnaire, including consideration of an abbreviated version for repeat donors. The task force appreciates the opportunity to make this advisory committee aware of its activities. We hope that this meeting will also provide an opportunity to let the public and those with a special interest in donor screening know of our activities. So we're here to tell you about a concern, but a way in which we're going to address the concern, instead of just letting somebody do something. The task force was formed in response to information from the FDA that the agency would like to see a simplified questionnaire developed, perhaps sometime in 2001, and would prefer to have a single initiative supported by the entire blood banking community. The task force, chaired by Dr. Joy Friday, is composed of representatives from the AABB, ABC, ABRA, ARC, CDC, and the FDA, and we will shortly be joined by representatives from NHLIB and the Armed Services Blood Program Office as well. The task force is intending to be the core group guiding the effort, but each organization will be active participants, assisting the task force with things such as identifying member centers to pilot questions and generate additional information or data as needed. It is vital that we include everyone in this effort including donors. The task force charges are to reevaluate the scientific validity of all FDA required infectious disease questions in view of the most recent scientific data, including current testing technology, to identify and reword questions for which the wording may represent comprehension difficulties for average individuals, to identify questions that can logically be grouped together and simplified, and to reorder questions as appropriate, and finally, to evaluate methods and develop recommendations for administering the questionnaire. These would be things like oral, written, computer-based questioning methods, how to handle recurring questions, et cetera. And then lastly, when we complete our task, submit it to FDA to be sure that it meets their approval. It's an active task force. It was only organized in June. We've already had three conference calls where the entire task force and numerous conference calls for the subcommittees that are working. I just want to list for you some of the activities that are currently under way. First, we're working with the FDA, planning a joint workshop, which will be held October the 16th, and information about that will be posted on both the AABB and the FDA web page and will be announced in the Federal Register shortly. Secondly, we've distributed a survey to obtain information about questions currently in use to selected blood centers, hospital blood banks and plasma collection facilities. Third, the AABB members have specifically begun to review which of the AABB added questions need to remain and which we might do something about. We're not going to blame it all on the FDA. The AABB has made this questionnaire somewhat complicated as well. And then, finally, the FDA is busy compiling information about questions that are most frequently cited in error and accident reports, and they're also looking to give us some direction about those questions or those errors where they're non-negotiable, that is, they're going to need to stay on the questionnaire in some format, maybe not the exact wording we use now, but at least so we're not spinning our wheels on things that we can't do anything about. I thank you for the opportunity to speak today. The task force is excited about the opportunity to accomplish meaningful change, and we plan to keep giving you regular, progress reports. DR. NIGHTINGALE: Thank you, Ms. Gregory. Are there any questions? Dr. Penner? DR. PENNER: Just a quick question. Will there be a first-time donor questionnaire as opposed to those repeated donors, or is all going to be strictly a global thing? MS. GREGORY: We really haven't gotten quite that far into it yet. That is one of the things we're considering, is, you know, can the first-time donor be different from the repeat donors? Are there local issues that need to be addressed? So I can't really give you an answer yet. DR. PENNER: Yeah, because I'm sure it's a nuisance to continue to answer the same-- MS. GREGORY: That's one of the things that we hear is, "I've already answered this, and if I said I never did it, why do you keep asking me?" DR. NIGHTINGALE: Are there any other questions from the committee for Ms. Gregory? Is there anybody else in--I'm sorry. Kay, you've got another one. You don't have to identify yourself again. MS. GREGORY: This time I'm speaking on behalf of the American Association of Blood Banks, and we would like to take this opportunity to recognize the activities of the advisory committee on blood safety and availability. We note, however, that the committee charter indicates that the committee would cease to exist on October 9th unless renewed by appropriate action prior to its expiration date. Even though we've not always agreed with all of the committee recommendations and conclusions, we believe the committee has served, and should continue to serve, a vital function. Although there are other public forums for discussing scientific matters, this committee is the only public forum for addressing other important issues such as availability, cost, other economic issues, reimbursement. Further, the committee has been remarkably successful in obtaining action in response to its recommendations. Clearly, your voice is being heard in the right places. In keeping with the general approach of the committee to enunciate positions in the form of a resolution, the AABB makes the following recommendation: Whereas, the Advisory Committee on Blood Safety and Availability provides a public forum for discussing issues of concern to the blood banking community and the public, and whereas the committee has successfully formulated recommendations presenting potential solutions to the issues it has discussed, the AABB recommends that the committee charter be renewed and that the committee continue to provide this valuable service to the blood banking community and the public. In short, we urge the Secretary to take appropriate steps to allow for the committee's ongoing work to provide patients with a safe and available blood supply. Thank you. DR. NIGHTINGALE: Thank you, Ms. Gregory. Would you state for the record that my mother did not write that statement? [Laughter.] MS. GREGORY: I will state that I wrote the statement. DR. NIGHTINGALE: Then I would state more formally for the record, that we have completed the process of applying for a two-year continuance of our charter, and that we anticipate a favorable response from the Secretary. The process is such that she does not sign the reauthorization, I believe, until after the conclusion of the current committee, but CAPT McMurtry is the administrator who understands this far better than I. Comment, Mac? CAPT. McMURTRY: We expect the Secretary's signature right around the end of September. DR. NIGHTINGALE: We, nevertheless, appreciate the kind words very much. CHAIRMAN CAPLAN: We have approximately, I would say, 30 minutes before we start losing airplane travelers. My suggestion would be that we take advantage of that time to think about--and this is just a suggestion; I'm open to other suggestions--but my suggestion is that we take advantage of that time to think about not resolving the issue of what matrix or dimensions to use, but perhaps to direct the staff to take under advisement what Dr. Epstein presented, what Rick presented, some other comments, in the formulation of a matrix of points and factors to consider. The reason this becomes important, that we give some direction to a matrix, if you will, is that with this international meeting coming up, the Secretary, I suspect, could use some advice about what framework to bear into that meeting in Geneva. What's that, November? DR. NIGHTINGALE: November 13th--14th, 15th, 16th and 17th, I believe. CHAIRMAN CAPLAN: I mean, I may be wrong, but I think we're going to today, arrive at the framework, but I think we probably have enough material here to assemble what starts to look like a series of points to consider or principles to consider, and sort of use that as the outcome of our trying to struggle to do this on a case-by-case basis, but saying that it jumped out of there. So anyway, that's my thinking about where we might go with principles, but the floor is open for other business and other approaches. DR. AuBUCHON: I am pleased to see that we're not going to try to come up with that framework in the next 28 minutes. I was very impressed with Dr. Epstein's enumeration of the different approaches, and I think Dr. Davey's distillation of similar concepts to a template format could indeed be useful. I would like to suggest that we consider hearing from Dr. Salmi [ph], who produced the template that was utilized at the WHO meeting in March, which now has had some practical application, at least within that meeting, to see another approach from another country, but one that has had some international application, and it may help move us toward understanding the factors that really push us to make certain decisions. COL. FITZPATRICK: In light of Dr. Caplan's comments, I'd like to add some input for the staff when we start formulating that or they start working on that. We have the advantage of being one of the largest organizations in the nation that collects, manufactures, processes, and transfuses blood products, and so we get to see the global perspective. We now have more U.S military deployed throughout the world than ever before. In every instance of that deployment during this time of peace, we have had to collect blood, fresh whole blood, and transfuse it untested to treat either U.S. casualties or local national casualties or accident victims. This presents us a unique problem in safety and availability challenges because the charter of our office is to continue to maintain and supply safe, compliant blood to all U.S. forces deployed throughout the world. Each additional test makes it more difficult to do this. We now have multinational forces supported by multinational medical forces and a multinational hospital being built in Kosovo. Adhering to the policy of the United States that U.S. deployed forces will receive FDA-licensed or equivalent blood becomes much more difficult in these situations. Timing is everything, and it appears we have actually timed something appropriately. November 9th and 10th we will have the NATO Civil-Military Blood Committee meeting here in Washington, D.C., immediately after the American Association of Blood Banks meeting and immediately prior to the meeting in Geneva. The topic and focus of the NATO meeting is interoperability and harmonization of international blood supplies. In order to achieve those goals, we need our federal regulatory agencies of each nation and our blood committees and blood bank organizations of each nation to work together in Geneva to try and harmonize the requirements and the donor selection criteria and infectious disease testing criteria in order to make support for these multinational forces more possible, because as each nation draws its military down, we will have more multinational events. Costs continue to be a major factor, and as I have mentioned before at this Committee, every time a new test is required, it takes us two years to accomplish budgeting to do that test. Because of that, reallocation of resources is required, and in the military medical health care system we do have to take from some other pot to put into the infectious disease testing pot, and some factor of health care suffers for those two years. So I would just ask the Committee to continue to keep in mind the aspect of funding for the Department of Defense blood program when a new test is required, and that we feel the development of a template or cost/risk/benefit model which will provide a framework for making these decisions and discussions extremely important in our strategic planning and the world's strategic planning in keeping a safe and available blood supply. I want to thank HHS for allowing DOD to be a part of this Committee, and we hope that we can continue to contribute. Thank you. DR. DAVEY: I have a couple of comments, first about the international meeting coming up, Mr. Chairman. I spent a year with WHO working with their blood program and spent a lot of time in Africa, and I can only second I think what Karen was saying earlier for those who are going to be at the meeting that the testing techniques have been there and have been available for 10, 15 years, mini-pool testing, cartridge tests. The technology has been there, and the funds, almost, to provide the testing has been there. What is lacking, again, which Karen pointed out, is the training and infrastructure and also the importance--and, again, this was brought out--of each country developing their own blood program based on their own needs and their own culture and their own customs. There have been a lot of mistakes about moving technology in in a Western fashion with Western technology and Western thinking, and it hasn't worked. So there's been a lot of experience. We're at another threshold, I think, of consciousness raising, and perhaps we can move this forward now with the experience, and I think the program at WHO has really gotten funded with some good people, so there's a good opportunity now to move it forward. On another topic, I fully support the Chairman's recommendation that staff go ahead and work on a matrix and see what we can come up. I think Jay has had some good ideas. Perhaps my seven points might be considered. Also, I think it would be useful as maybe a preamble, since this is a turning point for the Committee, we're looking backward, looking forward, that a listing of some of the pending issues and actions--again, Jay had a good one, I think Mike and others have pointed out some very key issues--that that be kind of a preamble. These are things that are facing this Committee and the country, and this is a template that we can use to address them in the future. It would be a useful piece to put in the minutes. CHAIRMAN CAPLAN: We did mention that one of the things that might be useful to add to our agenda was a consideration of changes of unnecessary or out-of-date safety measures, and we haven't sort of gone at that systematically, and that might be an important agenda item to flag for the future, too, using the matrix approach to help us think about that. DR. NIGHTINGALE: Yes, I appreciate Dr. Davey's comments. In response to the anticipation of future agenda items, while the process might appear somewhat undirected, I hope it's appeared to be transparent. We have tried to use the Committee to identify problems that, bluntly, we thought might be resolvable. This is a very useful instrument of government, but it's by no means the perfect--better still, it's not the only instrument of government. You saw that, for example, when the TSE scientific debate went to the TSE Advisory Committee rather than to this Committee, not something that everybody agreed with but, nevertheless, if I'm a little reticent to commit to the next year or even to the next meeting's agenda, it is because blood is a complicated business. And it's also because blood is a high-level business. I think there were some kind words spoken about what happens after resolutions are made here, but that's really only possible when there is consensus within the Department about the topics and the expected outcomes before the decisions are made. I mean, we can perhaps--an analogy I've used elsewhere--keep the river from flooding the village, but we can't make the water go back uphill here. And I think that that's been one of the strengths of the Committee. So while I take it under advisement, there is a clearance procedure that I would have to go through, and I'll at least try to keep that clearance as transparent as possible to the members. MS. LIPTON: My only comment, I absolutely support looking at what we could do to reduce or eliminate some of these things, but I think there is a process here, and the process begins with FDA. And if they have that on their agenda--I mean, I don't think--I certainly don't feel qualified to sit here and evaluate scientific data. So anytime something comes up to this Committee, I would hope that we have, you know, some kind of deliberation before BPAC or some other body that we can then add those other factors. I would hate to see us bypass that route before it got here. DR. NIGHTINGALE: And if I may second that, I believe I'm on the record repeatedly as supporting that, and possibly to simplify what Ms. Lipton just said, you know, if there's science on which to base a decision, it shouldn't be here. We don't get the hanging curves. So far we haven't got them, and if a hanging curve shows up here, it probably should have been somebody else who had a chance to hit it out. CHAIRMAN CAPLAN: Jim? DR. AuBUCHON: I understand what you're saying, Steve, but at least today in blood safety I don't see many issues where the scientific conclusion or the scientific consensus alone creates a slam-dunk situation. And there are clearly other factors, particularly economic, that need to be factored in. Furthermore, Blood Products Advisory Committee or other Advisory Committees may not be in a position to take into account all of the availability discussions, which are part of an ultimate conclusion of an issue. So I would like to, as we look at how decisions are made, discuss not only the factors that should be considered in making a decision but which arms of the Federal Government in its Advisory Committee structure can be utilized and how they should interact with one another. CHAIRMAN CAPLAN: It's fair to say that the Chair occasionally gets from the people that--even though we sometimes think of ourselves as advising the Secretary, occasionally e-mails arrive at my desk asking about things that the public wants to know about. Some I pass to Steve. Some which are more acerbic I don't. But one thing that comes up a lot is the issue of male sex and the rule about donation. I've heard a lot of communication about that. People are interested in that. My point in getting us to some issues that might be considered by us was not so much to jump ahead of where the science might be but to act as a prod to make sure that the science gets done if it doesn't seem to be getting done because we've grandfathered in a lot of things that may make no sense or may be sort of up for reconsideration. Jay's list is pretty good. I didn't get the sense that the FDA was asleep about these things, but it's sort of pushing more than it is saying, oh, okay, well, we can set the standards here about all those things. DR. EPSTEIN: Yes, I think--I presented a list of things that are in the hopper. I mean, these are happening now. We are considering them. But I resonate very strongly to both what Karen Lipton said and what Jim AuBuchon said, which is, you know, we start with an FDA process, but we have an underlying problem of divided responsibilities. And the reason for that is that the lines have been drawn in a certain way over areas of responsibility. I mean, FDA is not supposed to look at cost. We're supposed to look at, you know, safety, effectiveness. We can go as far as to look at, you know, public health, risk/benefit, but not the C word. You know, that creates a problem in an era of limited resources and very difficult trade-offs. And on the one hand, I think that we have evolved to a system where we do have fora to vet related issues, global concerns. But the process by which we decide which issues surface, how they surface, where they go, when the decision should get made, what is linked to what, that's the part that's ill-defined. I mean, we recognize, for example, that the issue of safety advances and how to pay for them is linked to the reimbursement system. But, on the other hand, it's been pointed out many times, and correctly, that that isn't really FDA's charge. But then whose charge is it, and what system do we have to ensure the integration? And I think that's really where the challenges lie. I think we do have a pretty good idea what the particular concerns are, but we don't have a system that decides which is the correct paradigm to address that issue. You know, I guess we aren't going to do it at this meeting, but my notion was that we might want to go through that list and ask ourselves what paradigm are we applying now and is it the right one, kind of issue by issue. Now, that doesn't mean that we want to take on all issues in this forum, but I think thinking along those lines is what's needed. You know, there are some people who would say, well, you know, you're doing the right thing about HHVA wanting to have proof of transmission before you attempt to intervene. And there would be other people who say, But that's not following the precautionary principle. You know, you've already got enough reason to be concerned because it's leukocyte-associated. So, you know, the whole problem is where should you be and how do you decide where to be. How do you measure the relative importance of the different issues? I think part of the problem is that at least to the FDA, they each present as an entity in their own right, because we're really not charged with trading them off against each other. We're charged with dealing with them all at once. And so, again, my feeling is, yes, it starts at FDA and, yes, we don't bypass FDA. But there is a dilemma related to divided responsibilities. DR. NIGHTINGALE: To follow up that, I think that the issues we've had over the last three years, the six that I enumerated--hepatitis--or the Surgeon General did, I'm sorry--hepatitis C, CJD, plasma shortages, blood shortages, reimbursement, and error management--were issues that came to us. We're at a nice time right now, as the Surgeon General said this morning. We may not have put them to bed, but we've made constructive progress on them. It may very well signal a transition not only for the Committee but for the blood community as a whole that we are in a position to start acting proactively rather than reactively. And if that, in fact, is the case, that's a good thing. I also think if that is the case, we've made a really good start this afternoon. We do not give door prizes out at the meeting for the best talk, and that's good because, not to offend anybody, but the last two speakers would have had to fight over the door prize, not because they happened to have the right words, I think, but because I think both of them--and if you'll forgive me, particularly Dr. Epstein--captured where the Department is right now. Dr. Epstein's is not exhaustive--it was not an exhaustive analysis. It was a useful framework, and what he said there very much reflects what we were--the internal discussions of the Department over the last month after we set on this agenda. This is a process, a discussion--what we wanted to do was find a place to start where hopefully there was some consensus outside not only of the Humphrey Building but outside of the FDA, CDC, Humphrey, NIH axis. And that's the reason why I brought up the analogy of the door prize because that was a tricky thing to do. It is my impression from reading the body language, if you will, that Dr. Epstein's formulation of the position has fairly wide support. And if it does--for what it was intended to be, a formulation of talking points, a set of principles that we realize are not the final answer to a very complex question, but a point of departure. And if that is--if my perception is shared, it would be of some assistance, I think, to Dr. Epstein and the others involved in planning for, say, the Geneva meeting to have some expression of that support, if, in fact, that's there. CHAIRMAN CAPLAN: John? DR. PENNER: Jay brought up the "C" word, which I presume is cost. And at this point I'm getting a little confused inasmuch as I pay something like a thousand dollars a day for antibiotics on a patient in the intensive care unit, and $3- or $400 worth of blood may be life saving. And I don't quite understand how the price of blood is being set by HCFA, at this point, which then sets the pace for the rest of the reimbursement situation. Our movement from some $48, as I mentioned, 20 years ago to the 90-some-dollars now seems to be rather negligible in comparison to other drugs that are being used and employed very effectively at very, very high levels of cost. Does this need more attention or have we spent as much as we can on our energies in getting that area taken care of? DR. NIGHTINGALE: No. I think the one last point that I would want the committee to recall is something I said earlier, on November 9th it's a new ball game. The issue of reimbursement for blood products I suspect we have taken it as far as we can take it in the isolated context of blood alone. And while I'm not suggesting that we have failed because I don't think we have, I think that to get beyond where we have gone with our recommendations and actions resulting from them, we're going to have to look more carefully not only as to how blood fits into the current reimbursement framework, but perhaps into limitations of the current reimbursement framework. And a new administration is a convenient place for that to happen. I said far more right there than I perhaps should have. DR. PENNER: Blood is cheap in comparison, and I think we all fail to look at that because we are left over with the years of getting blood, and it's donated, and therefore it should be free concept in our minds, and that I think has got to be altered. CHAIRMAN CAPLAN: Just to respond to Steve's point and see if we can get agreement perhaps on a recommendation or suggestion to the staff on this one. Jay's framework I don't think is a basis for consensus about decision making. It's a good matrix, however, of points and approaches to consider. I'm not a particular fan of the precautionary principle, for example. So I know it's on the list, it's a way to go. It wouldn't be my way to go. I can't imagine capitalist-mad America deciding that it's going to be risk averse in the way that the precautionary principle suggests, but maybe--I doubt it. That's why we'll be eating GMO and everybody else won't. However, there is enough there to set out a matrix of points to consider ways to approach, and that's what I would like us perhaps to recommend that the staff develop for us. Can we perhaps even take a vote so I can get a formal or a second or a motion or something? A motion. I'm making a motion that we direct the staff to develop a matrix out of the presentations we have of points to consider. We then might move on with that matrix to some weighting or what we in the trade would call a prescriptive position about which is better or which is worse or which we want to go with. But first we need to get the whole thing in front of us. DR. NIGHTINGALE: Since I would--Mac and I would have to be the people to do what you're directing us to do, are you directing the staff to develop a matrix from the presentations--plural--made at the committee as a basis for further discussion about principles-- CHAIRMAN CAPLAN: Right. DR. NIGHTINGALE: --that would underlie safe, effective and portable blood supply? CHAIRMAN CAPLAN: That's my idea. DR. NIGHTINGALE: That's eminently doable, and thank you for the opportunity if that's what you choose to do. DR. HOOTS: Kind of implicit in that, but would you consider, as a friendly amendment, that essentially this draft would then--we would kind of commit ourselves to applying it, as it's already been implied, that we apply it to certain models, whichever ones we prioritize in the next few meetings, to see how it works; in other words, we actually commit ourselves to seeing if we can use this paradigm to develop policy? DR. NIGHTINGALE: While my own enthusiasm for Dr. Epstein's and Dr. Davey's presentation is there, I think that the presentations require further public discussion before there is a commitment to them. And I think not because of any inherent weakness in them, but because these are new ideas to get into the public-- DR. HOOTS: I didn't mean to imply that we would do it for all times. I mean just experiment with trying to use that thought process as we go through a problem and learn as we go. That's what I meant, not that it would be the end all and be all. DR. NIGHTINGALE: Beta testing, in other words. DR. HOOTS: Correct. DR. DAVEY: So moved. DR. GUERRA: Second. CHAIRMAN CAPLAN: All in favor? [Show of hands.] CHAIRMAN CAPLAN: Opposed? [Show of hands.] CHAIRMAN CAPLAN: Abstained? [No response.] CHAIRMAN CAPLAN: That's a fairly innocuous recommendation I suspect. I'm going to take the last few minutes here to thank the people who have served on the committee whose service is now over. When is our next meeting? January what? DR. NIGHTINGALE: I was afraid you'd ask. Mac? The next meeting of the committee? The last Thursday and Friday in January. We've had a mix-up with days before. But if anybody has a 2001 calendar, it's the last Thursday and Friday. CHAIRMAN CAPLAN: Of January. DR. NIGHTINGALE: Of January 2001, right. CHAIRMAN CAPLAN: January 25 and 26; is that the last? January 25-26? DR. NIGHTINGALE: Let me state for the record that you will be informed through the Federal Register, and personally and on the committee's website of the next meeting of the Advisory Committee. We do have a contract with this hotel, but to the extent that we can minimize conflicts with our I don't know if I want to say sister organization, we will certainly strive to do so. CHAIRMAN CAPLAN: So still hang onto the last Thursday and Friday date until you're told otherwise. The other thing that obviously is going to happen is elections come, Steve has used the word "new ball game" a couple times. There could be changes, not by the time we meet next, but changes could come in the administration, and the people that we talk to at HHS and so on, and the secretary's office. So it'll be an interesting time for us to transit. My hope is, however, that our work has been such that we will sail on, despite new winds in the air, potentially, or for certain--actually, there will be no winds for certain no matter what goes on--and that whoever is in Congress, whoever is in the White House, whoever winds up at HHS is going to see the value of having this group here. Remember, please, that the floor is open for nominations to membership. And I think you have to get it in by the end of the month, and Mac will accept by phone or e-mail or letter names and ideas, and so that is very important that we get the right people to replace the good people that we're losing. Unless there's new business, I'm going to suggest that we now adjourn. [No response.] CHAIRMAN CAPLAN: Okay. We stand adjourned. [Whereupon, at 4:19 p.m., the proceedings were adjourned.]
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