<DOC>
[108th Congress House Hearings]
[From the U.S. Government Printing Office via GPO Access]
[DOCID: f:95598.wais]
HARNESSING SCIENCE: ADVANCING CARE BY ACCELERATING THE RATE OF CANCER
CLINICAL TRIAL PARTICIPATION
=======================================================================
HEARING
before the
COMMITTEE ON
GOVERNMENT REFORM
HOUSE OF REPRESENTATIVES
ONE HUNDRED EIGHTH CONGRESS
SECOND SESSION
__________
MAY 13, 2004
__________
Serial No. 108-189
__________
Printed for the use of the Committee on Government Reform
Available via the World Wide Web: http://www.gpo.gov/congress/house
http://www.house.gov/reform
______
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COMMITTEE ON GOVERNMENT REFORM
TOM DAVIS, Virginia, Chairman
DAN BURTON, Indiana HENRY A. WAXMAN, California
CHRISTOPHER SHAYS, Connecticut TOM LANTOS, California
ILEANA ROS-LEHTINEN, Florida MAJOR R. OWENS, New York
JOHN M. McHUGH, New York EDOLPHUS TOWNS, New York
JOHN L. MICA, Florida PAUL E. KANJORSKI, Pennsylvania
MARK E. SOUDER, Indiana CAROLYN B. MALONEY, New York
STEVEN C. LaTOURETTE, Ohio ELIJAH E. CUMMINGS, Maryland
DOUG OSE, California DENNIS J. KUCINICH, Ohio
RON LEWIS, Kentucky DANNY K. DAVIS, Illinois
JO ANN DAVIS, Virginia JOHN F. TIERNEY, Massachusetts
TODD RUSSELL PLATTS, Pennsylvania WM. LACY CLAY, Missouri
CHRIS CANNON, Utah DIANE E. WATSON, California
ADAM H. PUTNAM, Florida STEPHEN F. LYNCH, Massachusetts
EDWARD L. SCHROCK, Virginia CHRIS VAN HOLLEN, Maryland
JOHN J. DUNCAN, Jr., Tennessee LINDA T. SANCHEZ, California
NATHAN DEAL, Georgia C.A. ``DUTCH'' RUPPERSBERGER,
CANDICE S. MILLER, Michigan Maryland
TIM MURPHY, Pennsylvania ELEANOR HOLMES NORTON, District of
MICHAEL R. TURNER, Ohio Columbia
JOHN R. CARTER, Texas JIM COOPER, Tennessee
MARSHA BLACKBURN, Tennessee ------ ------
PATRICK J. TIBERI, Ohio ------
KATHERINE HARRIS, Florida BERNARD SANDERS, Vermont
(Independent)
Melissa Wojciak, Staff Director
David Marin, Deputy Staff Director/Communications Director
Rob Borden, Parliamentarian
Teresa Austin, Chief Clerk
Phil Barnett, Minority Chief of Staff/Chief Counsel
C O N T E N T S
----------
Page
Hearing held on May 13, 2004..................................... 1
Statement of:
Christian, Dr. Michaele, Associate Director, Division of
Cancer Treatment and Diagnosis, Cancer Therapy Evaluation
Program, National Cancer Institute; and Dr. Richard Pazdur,
Director, Division of Oncology Drug Products, Center for
Drug Evaluation and Research, U.S. Food and Drug
Administration, accompanied by Dr. Patricia Keegan,
Director of the Division of Therapeutic Biological Products 12
Pecora, Dr. Andrew, chairman and director, the Cancer Center,
Hackensack University Medical Center; Dr. Robert Comis,
president and Chair, Coalition of National Cancer
Cooperative Groups; and Ellen Stovall, president and chief
executive officer, National Coalition for Cancer
Survivorship............................................... 74
Letters, statements, etc., submitted for the record by:
Christian, Dr. Michaele, Associate Director, Division of
Cancer Treatment and Diagnosis, Cancer Therapy Evaluation
Program, National Cancer Institute, prepared statement of.. 15
Comis, Dr. Robert, president and Chair, Coalition of National
Cancer Cooperative Groups, prepared statement of........... 82
Davis, Chairman Tom, a Representative in Congress from the
State of Virginia, prepared statement of................... 4
Murphy, Hon. Tim, a Representative in Congress from the State
of Pennsylvania, prepared statement of..................... 11
Pazdur, Dr. Richard, Director, Division of Oncology Drug
Products, Center for Drug Evaluation and Research, U.S.
Food and Drug Administration, prepared statement of........ 44
Pecora, Dr. Andrew, chairman and director, the Cancer Center,
Hackensack University Medical Center, prepared statement of 77
Stovall, Ellen, president and chief executive officer,
National Coalition for Cancer Survivorship, prepared
statement of............................................... 100
Waxman, Hon. Henry A., a Representative in Congress from the
State of California, prepared statement of................. 8
HARNESSING SCIENCE: ADVANCING CARE BY ACCELERATING THE RATE OF CANCER
CLINICAL TRIAL PARTICIPATION
----------
THURSDAY, MAY 13, 2004
House of Representatives,
Committee on Government Reform,
Washington, DC.
The committee met, pursuant to notice, at 10:03 a.m., in
room 2154, Rayburn House Office Building, Hon. Tom Davis of
Virginia (chairman of the committee) presiding.
Present: Representatives Tom Davis of Virginia, Duncan,
Murphy, Carter, Waxman, Cummings, Kucinich, Watson, Van Hollen,
and Norton.
Also present: Representative Garrett.
Staff present: David Marin, deputy staff director/director
of communications; Drew Crockett, deputy director of
communications; Teresa Austin, chief clerk; Brien Beattie,
deputy clerk; Susie Schulte, professional staff member; Corinne
Zaccagnini, chief information officer; Robert White, press
secretary; Kristin Amerling, minority deputy chief counsel;
Josh Sharfstein, minority professional staff member; Earley
Green, minority chief clerk; Jean Gosa, minority assistant
clerk; and Naomi Seiler, minority staff assistant.
Chairman Tom Davis. Good morning. A quorum being present,
the committee will come to order.
I want to welcome everybody to today's oversight hearing on
cancer clinical trials. This hearing will examine the status of
efforts to bring innovative cancer treatments to patients and
discuss how to change the face of cancer into a less terminal
and more treatable disease.
The two panels of witnesses today will present testimony on
the various factors contributing to low accrual of adult
patients in cancer clinical trials and what efforts are being
taken to obtain reasonable participation levels to better
provide more treatment options for cancer patients.
Cancer is the second leading cause of death in the United
States, taking the lives of over a half million Americans each
year, more than 1,500 people each day. Roughly 1.3 million new
cancer cases are diagnosed in this country each year. These
statistics are sobering. All of us here today know a relative
or friend who has been diagnosed with some type of cancer.
Anyone who has been affected by cancer understands the needs
for more and better treatment options for patients.
In order for new drugs and therapies to be approved by the
Food and Drug Administration, several cancer clinical trials
must be conducted. Clinical trials are essential for
determining safe and effective therapies in modern medicine.
Early detection of cancer and the application of new treatments
available through clinical research are responsible for
significant improvements in cancer survival rates. Clinical
trials are designed to answer scientific questions which
translate into better and less toxic therapies for patients.
Trials allow doctors and researchers to gain information about
the benefits, side effects, possible applications, and doses of
new and existing drugs.
In order for scientists and oncologists to make accurate
conclusions about an experimental new drug's effect, clinical
trials require the participation of numerous cancer patients.
Further, research has shown that trial participants nearly
always receive equivalent or better care than those receiving
standard treatments, despite the experimental nature of these
investigational treatments.
Clinical trials can offer patients advanced treatments that
would be otherwise unattainable. Thousands of people are helped
each year by joining cancer clinical trials, and millions of
people have ultimately benefited from others' participation in
trials.
So we pose the question to our panel of witnesses today:
why do only 3 percent of adults nationwide enroll in centers
when up to 20 percent are eligible? And what efforts are being
taken to resolve the barriers to better clinical trials and
adequate adult enrollment?
We want to examine the different scientific, logistical,
and financial realities that interact and impede reasonable
participation in adult trials. The lack of patient and
physician education about clinical trials, problems traveling
to the trial sites, strict eligibility criteria, and third
party payer reimbursement policies prevent a large number of
patients from participating. As a result of these contributing
factors, a vast majority of cancer patients fail to even
consider clinical trials when reviewing their treatment
options.
We will hear today from the cancer community the urgency to
reverse this situation and resolve the barriers to adequate
adult enrollment in clinical trials. Clinical trials are
essential for improving outcomes in cancer patients. By
improving participation levels and creating more trials to new
test therapies, we can transform cancer into a more treatable
and less fatal disease.
The equation is simple: clinical research leads to
discovery of new and better therapies for cancer patients,
helping them live longer and improving their quality of life.
I know all of our witnesses this morning will agree that we
need to boost participation in clinical trials. Along with
improving accrual rates, we may need to consider improving
other ways our health community approaches cancer. Clinical
trials are just a single component of the cancer spectrum. I
understand the complexity of the disease and the intricacies
surrounding the discovery, development, and delivery of
treatments. I look forward to a constructive dialog on this
topic.
The committee welcomes our witnesses for this important
testimony today.
I would now yield to my colleague, Henry Waxman, for an
opening statement.
[The prepared statement of Chairman Tom Davis follows:]
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Mr. Waxman. Thank you, Mr. Chairman. I am pleased to
participate in this hearing on how to accelerate progress
against cancer. This is a topic that I've worked on for many
years. When I was the chair of the Health Subcommittee of the
Energy and Commerce Committee, I was responsible for
legislation reauthorizing the National Cancer Institute. We
worked with experts inside and outside of the Government to
improve rehabilitation services, expand research on
reproductive cancers, and strengthen education and grantmaking
decisions.
It has also been my priority to make sure that all
Americans have access to benefits of medical progress against
cancer, and I'm particularly proud of legislation that expanded
access to screening for breast and cervical cancer and of
legislation that provided Medicaid coverage for those who are
found on screening to have these tumors.
Today's hearing highlights how much more needs to be done.
Over the last several decades, while rates of heart disease
have dropped dramatically, rates of cancer have largely
remained stable. Despite progress against a few specific
tumors, cancer will kill an estimated 500,000 Americans in
2004.
The simplest and quickest way to make a dramatic reduction
in cancer in the United States is to prevent it. Every Member
of Congress knows that the No. 1 preventable cause of cancer in
the United States is the cigarette. Last year a committee
advising the Department of Health and Human Services
recommended a simple evidence-based plan to help 5 million
people quit smoking and save 3 million lives. The plan was
endorsed by former Surgeons General Dr. Julius Richmond, Dr.
David Satcher, and Dr. C. Everett Koop. Unfortunately, the Bush
administration has shelved this report, and this Congress has
not held a single hearing to discuss or review its
recommendations.
This week, New York City announced its smoking rates have
dropped 11 percent in just 1 year as a result of Mayor
Bloomberg's aggressive anti-tobacco policies, saving an
estimated 30,000 lives. The response to this news should be
obvious. The President and congressional leaders should pursue
how to replicate these achievements across the country. But
don't hold your breath. The National Republican Party is so
closely aligned with the tobacco industry that the only
hearings we have had on tobacco in the House recently have
highlighted the alleged health benefits of smokeless tobacco,
unbelievable as that is. That's the only hearing that has been
held on the topic of tobacco.
Today's hearing will focus on the challenges facing
clinical research in cancer. Let me mention two issues at the
outset. First, to find cures for cancer we must adequately
support a clinical research infrastructure that can prove that
cures work. I'm very concerned that Dr. Robert Comis, a senior
oncologist who represents the Cooperative Groups program, will
testify today that current finding stifles innovation;
destabilizes key functions such as our tissue banks, data
management, and informatics platforms; and acts as a
disincentive to both academic and community physician
participation in research. That's because of these current
funding levels. Now that reductions in reimbursement for
oncologists mandated by Congress are due to take effect, it is
critical that NCI and Congress assure adequate funding for
research.
Second, to provide access to clinical trials, it is
important that Government resources such as
www.clinicaltrials.gov work well. This is a Web site created by
the Congress in 1997 that is supposed to contain information
for patients about ongoing trials for serious and life-
threatening disease such as cancer. A 2003 study by the FDA
staff found that fewer than half of the cancer studies that are
legally required to be listed on this Web site were actually
listed by the companies. This lack of participation by the drug
industry in an important resource for patients is inexcusable,
and I'm disappointed that the PHRMAceutical Research and
Manufacturers Association, PHRMA, which was invited to testify,
has been unable to send a witness to this hearing.
Today we will hear from leading health officials at the
National Cancer Institute and the Food and Drug Administration,
from senior cancer researchers, and from a leading
representative of cancer patients. I thank these distinguished
witnesses for coming today. I look forward to their testimony.
[The prepared statement of Hon. Henry A. Waxman follows:]
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Chairman Tom Davis. Thank you very much. Do any other
Members wish to make statements? If not, any statements can be
put in the record.
Mr. Murphy.
Mr. Murphy. Sure.
Chairman Tom Davis. The gentleman is recognized.
Mr. Murphy. Mr. Chairman, thank you for holding this
hearing on cancer screening trials. We all know few issues have
as negative an impact upon so many as cancer. Though all of us
have not been diagnosed, we certainly all hold the roots of
this disease and we all know someone close to us who has or has
had some impact of cancer.
While modern medicine has brought us a long way toward
winning this battle, anyone who has a parent or child or friend
diagnosed with cancer knows all too well we have not come
anywhere near far enough. Increased participation in cancer
clinical trials would significantly increase the discovery of
newer cancer treatments with the ability to keep cancer
patients feeling better while undergoing treatment, add years
to their lives, and even cure them of the disease altogether;
however, we will never have enough adult volunteers if patients
continue to be misinformed or not encouraged to participate.
It is certainly sad to me to read the survey cited that the
National Cancer Institute revealed that 85 percent of cancer
patients are either unaware or unsure of participation in
clinical trials is an option, and of the few who are aware of
the trials, most of these individuals believe clinical trial
treatment would be less effective than standard care, or that
their insurance would not cover the cost, so something has to
be done to change the public's perception of these trials.
I know in southwestern Pennsylvania the University of
Pittsburgh Medical Center has received two grants to study
these barriers and improve minority participation in clinical
trials. This grant money is being used to essentially bring the
trials to the patient through the utilization of
teleconferencing, video equipment in outlying hospitals,
providing modes of transportation to bring patients to trials
and treatment, and working with other cancer centers and
hospitals outside of the University of Pittsburgh Medical
Center system.
Improving access and public perception of cancer clinical
trials may seem to be an overwhelming task, but the doctors in
my District are committed and excited about the cause.
I'm looking forward to the witnesses' testimony on the
various steps groups are voluntarily taking to achieve higher
rates of participation, as well as some of the problems they
are confronting in their efforts.
In addition, I appreciate the committee's efforts to raise
national awareness of this issue crucial to the future of
medical innovation.
Thank you, Mr. Chairman.
[The prepared statement of Hon. Tim Murphy follows:]
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Chairman Tom Davis. Thank you very much.
The gentlelady from California, Ms. Watson?
Ms. Watson. I, too, want to add my thanks to you, Mr.
Chair, for bringing this issue up. I'm sure that Congressman
Waxman will remember that way back in the 1980's a group of us
got together in the California Legislature, a group of females,
when we found that the only cancer testing was done on males,
and breast cancer was coming more into high profile.
My statement ends up this way: when you are making good
public policy, it takes years because you have to educate. So I
thank you for gathering the witnesses here that will educate us
to let us know that clinical trials are a must if we are going
to make a dent in cancer.
Thank you, Mr. Chairman.
Chairman Tom Davis. Thank you very much.
We have a great selection of witnesses today. In our first
panel we have Dr. Michaele Christian of the National Cancer
Institute, along with Dr. Richard Pazdur from the Food and Drug
Administration. They are going to provide the committee with an
overview of the Federal Government's role in cancer clinical
trials and highlight efforts the Government is taking to
increase participation in clinical trials.
It is the policy of the committee that we swear all
witnesses, so just rise with me and raise your right hands.
[Witnesses sworn.]
Chairman Tom Davis. Thank you very much. We are very
privileged to have both of you here today. Your entire
testimony is a part of the record and has been read, and what
I'd like to do is we have some lights that will be in front of
you. The green light goes on for 4 minutes, then you get an
orange light for a minute, and then red is the end of 5. Try to
sum up, and then we can move right to questions. Your entire
statement is in the record.
Dr. Christian, we will start with you and then to Dr.
Pazdur. Thanks for being with us.
STATEMENTS OF DR. MICHAELE CHRISTIAN, ASSOCIATE DIRECTOR,
DIVISION OF CANCER TREATMENT AND DIAGNOSIS, CANCER THERAPY
EVALUATION PROGRAM, NATIONAL CANCER INSTITUTE; AND DR. RICHARD
PAZDUR, DIRECTOR, DIVISION OF ONCOLOGY DRUG PRODUCTS, CENTER
FOR DRUG EVALUATION AND RESEARCH, U.S. FOOD AND DRUG
ADMINISTRATION, ACCOMPANIED BY DR. PATRICIA KEEGAN, DIRECTOR OF
THE DIVISION OF THERAPEUTIC BIOLOGICAL PRODUCTS
Dr. Christian. Good morning. Thank you Mr. Chairman,
Representative Waxman, and Members for the opportunity to
discuss NCI's efforts to deliver innovative and effective
cancer treatments to the public.
I am Michaele Chamblee Christian, a medical oncologist and
associate director of the Division of Cancer Treatment of the
National Cancer Institute.
I have slides which are going to be hard to see, I think,
on these screens, but you have hard copies. Cancer is actually
more than 100 complex diseases and as depicted on this first
slide, cancer cells have many potential targets and pathways
and processes that have been subverted by the malignant
process. These differ in different patients and different tumor
types, yet, because of our investment in basic research and
advances in our understanding of biology, we now have a growing
list of new agents and chemical entities in clinical trials and
unprecedented opportunities to make significant progress in the
treatment and prevention of cancer.
NCI funds an extensive clinical trial system, including
over 3,000 clinical trial sites, more than 13,000 clinical
investigators that accrue over 30,000 patients each year to
trials. We study 138 investigational or experimental drugs. And
this system has been very effective at developing the
treatments and defining the standards of care for patients we
treat today, and contributing to the fact that more patients
with a diagnosis of cancer are living longer today.
We also have 88 formal clinical trials agreements within
companies the biopharmaceutical industry, which is the source
of most of the promising new agents in clinical development
today.
Because of these extensive relationships, NCI is in a
unique position to sponsor clinical trials of combinations of
investigational agents owned by different companies. NCI has
worked with over a dozen industry collaborators to arrange more
than 20 trials of novel investigational combinations to date,
and more are in development. Many of these regimens would not
have been evaluated until one or more of the agents had
received FDA marketing approval, potentially resulting in years
of delay.
Why is this important? You have copies of the slides. We
are going to try to do this without the slides. The cartoon
that I was going to show you depicts one of the common problems
and challenges with the targeted therapy of cancer, and that is
that there are multiple branching and redundant signal pathways
that control the behavior of cancer cells, and it is widely
believed that many of the most promising new molecularly
targeted agents will demonstrate their optimal utility in
combinations that inhibit or modulate multiple targets in these
critical pathways blocking progression of cancer, so we need to
be able to give these simultaneously, and that's why these
combinations are important.
I wanted to tell you about the components of the clinical
trials program. There is an extensive early clinical trials
program which is comprised of phase one and phase two clinical
trials done via contracts and grants at academic centers. There
are numerous translational research components that conduct the
correlative of laboratory studies on blood and tumor specimens
from patients so that in clinical trials we may learn not only
whether a treatment works but how it works, so that we can
select future patients better for treatment.
The map that you saw up there at one point represents the
distribution of these clinical trial sites around the country
and shows a very broad and I think good distribution of these
sites.
The next slide should have been on Cooperative Groups
funding, since funding for clinical trials is an issue, and
points out that during the period from fiscal year 1998 to 2003
funding to the Cooperative Groups program increased by 62
percent.
NCI was asked to comment on why Cooperative Groups are not
fully funded at the levels recommended by peer review, and I
wanted to point out that the Cooperative Groups grants are
amongst the largest in NCI's portfolio. In addition, each phase
three trial that we sponsor costs anywhere from $2 million to
$10 million, depending on its size. Our groups undergo peer
review once every 6 years, where plans for the next 6 years are
reviewed, along with the requested budget. However, this is a
projected plan and a provisional budget because it is not
possible to predict which clinical trials will actually be
conducted 4 or 5 years in the future. So peer review
recommendations are one component of effective coordination and
stewardship that NCI staff consider in arriving at a funding
plan.
In the next slide I wanted to show you that during this
same period accrual to clinical trials also rose dramatically,
by 24 percent in the phase three program and, importantly, by
58 percent, as shown in the light blue bars, in the early
clinical trials program. That's important because that's where
many of these promising new agents and combinations that will
be evaluated in phase three trials are initially studied.
So my final slide just points out that there are a number
of ongoing initiatives at NCI to broaden access to clinical
trials for patients and to facilitate physician participation.
The slide lists a number of them.
I wanted to just comment also in closing, that NCI is
committed to effectively integrating its clinical trials
mechanisms in order to make smarter use of the available
resources and to ensure that we are optimally positioned to
take advantage of emerging scientific and medical
opportunities, speed accrual to the highest priority clinical
trials, and accelerate the delivery of promising new approaches
to cancer prevention and treatment to the American public.
I thank you for the opportunity to testify, and I will be
happy to answer any questions.
Chairman Tom Davis. Thank you, Doctor.
[The prepared statement of Dr. Christian follows:]
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Chairman Tom Davis. Dr. Pazdur, thanks for being with us.
Dr. Pazdur. Mr. Chairman and members of the committee, I am
Richard Pazdur, M.D., the Director of the Division of Oncology
Drug Products at the Center for Drug Evaluation and Research at
the Food and Drug Administration. Dr. Patricia Keegan, the
Director of the Division of Therapeutic Biological Oncology
Products at CDER, is accompanying me today to answer any
questions on biological products.
I am pleased to be with you today to discuss what our
agency is doing to accelerate the delivery of innovative cancer
treatments to meet the needs of cancer patients and their
families. FDA's mission is to ensure that new cancer drugs are
safe and effective. We also facilitate access to promising
therapies for seriously ill and dying patients when no other
treatment is available.
Since the FDA last testified before this committee in June
2000, a number of important cancer drugs have been approved and
are helping cancer patients. Of particular note are the number
of innovative drugs that are targeted to specific parts of the
cancer cells. These new therapies are a glimpse of the future
of cancer therapy and should be a source of encouragement to
the American public and to cancer patients and their families.
FDA has numerous programs in place to help speed the
development and approval of promising drugs to cancer patients.
Let me briefly mention some of these programs.
Under the accelerated approval route, FDA can approve drugs
for serious or life-threatening conditions. These drugs
demonstrate the potential to address unmet medical needs based
on a surrogate end point that is ``reasonably likely'' to
predict clinical benefit.
Second, priority review is intended to direct overall FDA
review attention and resources to the evaluation of
applications for products that have the potential for providing
significant therapeutic advances.
Third, a drug sponsor may request fast track status. This
designation facilitates the investigational development and the
approval of drugs that provide significant advancements in the
treatment of serious or life threatening diseases. These
programs have been instrumental in shortening the time to
approval for many promising cancer treatment drugs; however,
the FDA is aware that there is growing concern that many of the
new basic science discoveries made in recent years may not
quickly yield more effective, affordable, and safe medical
products for patients. This is because the current medical
product development path is becoming increasingly challenging.
During the last several years, the number of new drugs and
biological applications submitted to the FDA has declined
significantly. The number of innovative device applications has
also decreased.
In response, on March 16, 2004, the FDA released a report
entitled, ``Advancing America's Health: Advancing Medical
Breakthroughs.'' We refer to this FDA report as a critical
path. This timely paper calls for academic researchers, product
developers, and patient groups to work with the FDA to identify
ways to modernize tools for speeding approval, innovative
products to the market to improve public health.
The report provides FDA's analysis of the current pipeline
problem, the recent slow down instead of the expected
acceleration in innovative medical therapies reaching patients.
FDA is planning an initiative that will identify and prioritize
the most pressing development problems, and, second, the areas
that provide the greatest opportunities for rapid development
and public health benefits. This will be done for all three
dimensions along the critical pathways, namely: safety
assessment, evaluation of Maryland utility, and product
industrialization. We will work together with stakeholders to
identify the most important challenges.
Concurrently, FDA will refocus its internal efforts to
ensure that we are working on the most important problems and
intensify our support of key projects.
Thank you for the opportunity to discuss these important
issues with you. I would be happy to answer any questions.
[The prepared statement of Dr. Pazdur follows:]
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Chairman Tom Davis. Thank you both. Let me start. We'll
take 5 minutes.
Dr. Christian, the witnesses on our second panel today are
going to cite lack of physician education as a barrier to
adequate accrual in clinical trials. You talked briefly, but I
wonder if you could elaborate on what efforts the National
Cancer Institute has taken to inform physicians about the
cancer trial support unit program. I mean, it seems to me
that's where the word needs to get out. People go see their
doctor, they get the diagnosis, they want a list of options. I
think you'd just be teaming with people who want to get in on
the latest and be a part of this, but it really starts and ends
with the physician that they're treating who really gives them
their menu of options.
Dr. Christian. Well, I think that is absolutely correct.
The NCI and the Cancer Trial Support Unit have worked with a
number of organizations, the Coalition for Cooperative Groups
being one, since they are intimately involved in that, but also
with the American Society for Clinical Oncology and others, to
make physicians aware of the opportunities to participate in
trials through the Cancer Trials Support Unit. They also use
electronic systems----
Chairman Tom Davis. Let me ask this. In continuing medical
education, do you have requirements of that? I don't know if
you have it in every State, but in most States is this part of
it?
Dr. Christian. To my knowledge it is not part of continuing
medical education requirements. We do offer sessions, however,
at national meetings so that there are educational
opportunities there, but it is not a requirement, per se.
Chairman Tom Davis. I mean, it just seems to me when you're
going in every year to get updated, that menu option, it's
pretty easy to include it. If I were a physician, I'd sure want
to know it and be able to give my patients that option,
particularly some of those that don't have a lot of good
options, as you're working on.
Dr. Christian. Can I just elaborate also?
Chairman Tom Davis. Yes, please.
Dr. Christian. We have also, working with the Cooperative
Groups and others, invested quite heavily in patient education,
because having patients be aware of clinical trials and
requesting those opportunities of their physicians, I think is
another way to approach this problem, and so we have, I think,
all made major efforts to improve the education of patients
about these opportunities.
Chairman Tom Davis. I think you touched briefly, but Dr.
Comis of our next panel is going to testify that the National
Cancer Institute only reimburses physicians about $2,000 per
case to perform research in community-based physician
practices, while studies suggest the cost is closer to $4,000.
Is it possible, working with NCI's budget, to increase the
allocation to offset these costs? Physician reimbursements are
low on everything. This is an area where you really don't want
to do it on the cheap.
Dr. Christian. Well, the cost at a site for conducting
clinical trials has been a subject of great interest and
concern to us. During the 5-year period that I showed on my
slide, there was a 62 percent increase in funding to the group
system overall. But importantly, I think, funding to the sites
actually doubled during that period. So while $2,000 remains
perhaps meager, it represented a substantial increase in what
we had been able to fund previously. So we are continuing to
seek ways to increase funding and to think about how best to
allocate the clinical trials resources that we have overall so
that we get the work done.
There are a number of groups--Dr. Comis and I work on
several of them--that are actually trying to nail down much
more precisely what the real components of cost are so that we
can make, I think, more effective judgments in terms of how we
are able to fund.
Chairman Tom Davis. I don't mean to single you out. Our
reimbursements that we allocate to physicians under Medicare
and Medicaid are pitiful, so I hear you.
Dr. Pazdur.
Dr. Pazdur. I just wanted to jump in. Having done clinical
trials for almost 20 years, there is a difference between
knowing if they exist and actually doing them. OK? And I think
people have to understand that the enrollment of a patient when
one is conducting a busy practice is a very time consuming
activity. It requires infrastructure to be present. It requires
data managers. It requires research nurses. So there has to be
an infrastructure within a clinician's practice that will allow
him to do the clinical trials that he views to be of
importance.
It is an issue, and I think when we take a look at the
whole issue of why patients do not participate in clinical
trials, to leave out the physician component is one that would
not be appropriate. It is, as you pointed out, the physician
that ultimately will be prescribing the therapy that the
patient will be getting, and he has to have the appropriate
incentives and also the infrastructure that will allow him to
place patients on trial.
Chairman Tom Davis. Let me ask you, just so I know,
understand, how many investigational products fail in clinical
trials? I mean, the ratio compared to products approved, any
idea? Ball park?
Dr. Pazdur. I could--the vast majority of them. It's a
small--probably our critical pathway states that one--if you
take five drugs that are being developed in their very earliest
stages, probably one will make it to the market.
Chairman Tom Davis. OK. Thank you very much.
Mr. Waxman.
Mr. Waxman. Dr. Christian, the Clinical Trials Cooperative
Groups Program at NCI, they play a key role in clinical
research against cancer. I know you're familiar with that.
Studies by these networks of researchers have led to major
advances in survival, particularly in the pediatric cancers,
but we have a chart showing that the funding for this program
has not increased in the last several years. And Dr. Comis, who
is chair of the Coalition of National Cancer Cooperative Groups
is going to testify that current funding stifles innovation,
destabilizes key functions such as our tissue banks, data
management, and informatics platforms, and acts as a
disincentive to both academic and community physician
participation. You can see from that chart there is a decrease
for leukemia, gynecologic oncology, breast, and bowel cancer.
How do you respond to the view that this important research
program is threatened?
Dr. Christian. Well, I can't see the details there, but my
slide also covered, I think, some of those years, and, as I
point out, we actually substantially increased funding over a
significant portion of that time. Now, with that said, I think
that there is no doubt that the costs for enrolling a patient
at a site still are not being reimbursed at the proper rate. I
think that is something that we continue to need to address.
You know, I think that there are many components of the
clinical trials program. There is the Cooperative Groups
Program, which is extremely important, as you point out, but
there are many other critical elements, too, and I think that,
given all of the new targeted agents that are coming into the
clinic, the early clinical trials are extremely important, too,
in advancing regimens to the point that they can go to phase
three trials, and, indeed, many of those have been funded at
much higher rates and, in fact, new resources have been created
to try to get those new novel agents into a point where they
can go to phase three trials, so----
Mr. Waxman. Do you agree that with less money and rising
expenses the Cooperative Groups will have a harder time
recruiting patients and doctors to their clinical trials?
Dr. Christian. I think that with less money at each site
that would be true, and our approach to that actually is to
look at the entire clinical trials program and find ways to
better integrate, to make the cost of putting patients on
clinical trials lower by having consistent and standard
approaches to data collection and other things that cost time
and money. Data managers, as Dr. Pazdur pointed out, are one
important component.
So we are trying to look across the system and find places
where we can better integrate, conserve resources, and then
allocate them to the places that need them the most so that we
can, indeed, raise the funding at the sites where the research
is actually being done.
Mr. Waxman. Given the NCI's emphasis on the genetics of
cancer and the importance of tissue banks, what is NCI doing to
enhance the role of the tissue banks run by the Cooperative
Groups?
Dr. Christian. Well, NCI actually has put forward a request
recently for proposals for funding for tissue banks. We are
planning not only to increase the funding for tissue banks
because we agree that it is a really critical component of this
research, but to actually stabilize that funding by awarding
grants specifically to that purpose. So, rather than just
general Cooperative Groups funding, we are going to provide
additional funds specifically targeted to tumor banks in our
Cooperative Groups.
Mr. Waxman. As NCI reorganizes itself to deal with the
challenges of the future, I think it is important not to
undermine those resources such as the Cooperative Groups that
are the bedrock of our clinical research efforts, and I'm sure
you agree with that, as well.
Dr. Christian. I agree absolutely.
Mr. Waxman. Dr. Pazdur, clinical trials are a key tool in
our fight against cancer, but they also can provide one of the
few sources of hope for those people who have failed standard
treatment options. The Web site, www.clinicaltrials.gov, is a
searchable, online registry of clinical trials that patients
with serious or life-threatening disease and illness and their
providers can use to see if they are eligible for
participation. I'm sure you're familiar with this Web site.
Now, Federal law requires that the sponsor of any
effectiveness study conducted under an investigational new drug
proposal register with the data base within 21 days of the
start of the patient enrollment. In April 2003, FDA reported
that many sponsors of clinical studies of cancer treatments had
not submitted the information to the registry. While 91 percent
of NIH- and NCI-sponsored studies had been posted, only 47
percent of industry-sponsored studies had been posted, even
though FDA had released a detailed guidance for industry in
March 2002. Do you think increased industry compliance would
benefit patients?
Dr. Pazdur. The answer to your question is emphatically
yes. We also are greatly concerned about the low participation
of industry in listing their trials on www.cancertrials.gov. We
have taken a concerted effort to try to find why, what is the
reason, and I really don't have a good reason at that time if I
could say, you know, this is the reason why industry is not
placing studies on the Web site. One would think they would
have every reason to place their trials on. If we're talking
about poor accrual to clinical trials, industry can't cry about
poor accruals to clinical trials if they are not putting it on
the Web site.
In our own division and at the FDA, in general, after every
phase two meeting and industry meeting we have a written bullet
that is part of the minutes to that meeting that specifically
informs the sponsor of the existence and their obligation to
list the Web site. That is a written part of the minutes of
every end of phase two meeting.
We've taken concerted efforts to talk to patient groups, to
encourage patient advocates to advocate for participation of
commercial sponsors to list their trials. In addition to that,
we've taken a concerted effort of talking to industry about
this.
There may be some concerns of confidentiality in listing
clinical trials on www.clinicaltrials.com. I really don't buy
that, Mr. Waxman.
Mr. Waxman. Well, I'm disappointed we couldn't get a PHRMA
representative come in and testify today. It's ironic that,
while they're refusing to comply fully with the Government Web
site, PHRMA has a Web site, and on that PHRMA Web site there
are--it's called, ``New medicines and development,'' and on the
PHRMA Web site they'll often list clinical trials that they're
not listing on the Government Web site, but on their Web site
they frequently don't include eligibility details on clinical
trials or provide contact information for the trials. I don't
know why companies may list information about studies in a form
that's not useful to the patients, because if you read about
it, you want to find out more about it, there's no contact
information.
What is FDA going to do to enforce participation in the Web
site?
Dr. Pazdur. At this point we obviously have a process where
we are communicating with the sponsors. We are trying to find
out reasons why they are not putting the trials on this. We
have begun an education program, as I pointed out, where at
every meeting we are asking them and informing them of their
obligation to do so.
In addition to that, we have a massive process during
professional education to encourage physicians and to encourage
patients to utilize this resource. We are somewhat limited on
what we can do. We can educate, we can talk.
Mr. Waxman. Well, thank you very much.
Chairman Tom Davis. Thank you very much, Mr. Waxman.
Judge Carter.
Mr. Carter. Thank you, Mr. Chairman.
Richard Nixon was President of the United States in 1970
and he declared war on cancer. He said our goal was to cure
cancer in our lifetime. Well, he's dead. We haven't even come
close. We spent $52.5 billion under the theory the Government
could come up with a solution, and it is my understanding--and
please correct me if I am wrong--that if you view the overall
war on cancer, it has been a pretty bad failure. If you compare
it to other wars in health areas, like heart disease, for
instance, there has been much more success. Are we doing
something wrong in our direction on the war on cancer as you
see it? That's the question that's really concerning me,
because where I come from there's a lot of folks dying of
cancer. They don't see a whole lot of hope and they don't see a
whole lot of success.
Do either one of you want to comment on why this--$52
billion and 35 years--hasn't succeeded in any way?
Dr. Pazdur. I hear you. OK. I sympathize wholeheartedly,
having had patients and family members with this disease. I
think it is important for us to understand that cancer is not
one disease. As Michaele pointed out, at this time we can say
it is 100 diseases, but probably it is even many more diseases
on a molecular basis.
The riddle of cancer I feel is far, far more complicated
than, for example, the problems that we face with HIV
infections where we know the ideology, we know the virus that
is causing the problems. For most cancers we have very limited
or rudimentary knowledge of what causes the cancer, and even
sometimes the natural history and the variations.
For example, even what we call breast cancer probably is
hundreds and hundreds of different diseases. The problem is the
science. We have to make scientific advances, and that is on
the basic level. We are beginning to do so, I feel, by
understanding the genetic causes of cancer. We have seen some
drugs that have dramatically changed the face of some diseases.
While you are entirely right, if you took at look at the entire
scope of cancer, one would have to look at it somewhat
pessimistically. However, there are some diseases--for example,
CML, a disease that when I began my medical career that was
uniformly fatal with drugs that we used from the 1950's to
treat it, which now we have a drug called Glevic, which
transformed that disease into probably a chronic disease. One
can't use the word ``cure'' at this time with many of these
diseases, but clearly was an important medical development.
Why did we develop this drug? What gave us the
capabilities? It was the basic understanding of the genetics of
the disease, the molecular pathogenesis of the disease, and
marrying that basic understanding of the disease with a therapy
that interacted here. I think that is going to be the
overriding principle as we take a look at newer drugs,
understanding the disease on a molecular basis and then drugs
that are targeted toward molecular abnormalities or molecular
deficiencies.
This is an area that I think is evolving, and I am somewhat
pessimistic with the past, but on the future I am very
optimistic that we are exactly--or we are now beginning to have
the tools that will enable us to move forward.
Mr. Carter. About 3 weeks ago Lance Armstrong has a cancer
survivor group in Austin, TX, and I went to that, and it was
very uplifting about all these cancer survivors, but when you
cut through it the definition of a cancer survivor is they
survived the first round, really. There's an awful lot of
people there that, although they are in remission right now,
they face the distinct possibility of seeing the cancer again,
and it ultimately killing them. Where I stand from, cure of
cancer means you go in, you get treated, and you're not going
to have cancer, that cancer at least, again.
So we haven't reached that point, I understand, on almost
anything but maybe childhood leukemia maybe where we've got a
handle on it to some extent, so I'm just concerned about that
much money and that much time and that little success, and I'm
wondering, is there something innovative we can look at that
would stimulate the challenge of the market go to out to win
cancer? I firmly believe that if I could invent something to
cure cancer I could be, you know, richer than Microsoft, and I
think we ought to be able--somebody ought to be able to come up
with some incentive to do that.
A question I want to raise--and I realize my time is gone,
Mr. Chairman, a few more minutes--the question I want to raise
is the issue on the development of drugs. Is that becoming a
stumbling block to giving incentive to private enterprise to
take on full-fledged the challenge of cancer treatment. It
takes you 9 or 10 years to approve a cancer drug, gives you
another 9 years to recover your cost if you're in the business
of inventing or creating that cancer drug. Could we change our
intellectual property laws to give a longer time after approval
where you still have the assurance of a trademark, a patent
which might enhance the ability of private industry to invest
the kind of money they are going to invest to go into fighting
cancer? How do you feel about that?
Dr. Christian. I'd like to comment on that, and then I'd
like to comment also on your previous question.
You know, I think that intellectual property issues are
certainly a problem, particularly for combination treatments,
particularly when we want to look at a much broader range of
cancers than the more narrowly focused FDA approval pathway,
for example. And, you know, I think it is possible that
incentives might encourage industry to work more broadly with
NCI, with each other, etc., so that we can do the combinations
and do the broader development that will speed up this whole
process, so I think that there are issues there that are
probably worth looking at.
I mean, we, for example, have been following the Best
PHRMAceuticals for Children Act to see what the impact of that
might be on drug development, and I think that will give us
some notion, so I think intellectual property is probably an
issue that warrants further thought.
With regard to where we are with cancer, though, you know,
I do want to point out that there are, you know, a growing list
of tumors where we actually do cure patients and do prolong
survival by adding treatment to surgery. You know, I think 20
years ago the list was negligible and now there is a growing
list of situations where we actually do cure patients, and many
more where we prolong their lives. So your pessimism I
understand, but we have made progress, and I think, like Rick,
that, given the array of new entities that we have to use and
to develop at this moment, molecularly targeted entities, I am
more optimistic than I have been in 20 years of therapeutics
development that we actually may make fundamental molecular
strides.
Of course, the case that he gave with Glevic and chronic
myelogenous leukemia is one example. The reason that the
numbers remain so daunting is that the major solid tumors--lung
cancer, colon cancer--are much more complex molecularly, and so
we are going to take a little bit longer, I think, to sort out
what the relevant targets there are.
But it is very interesting--in two major medical journals
this past month, ``The New England Journal of Medicine'' and
``Science,'' there were articles about a mutation found in
patients with lung cancer which may help explain how we should
better use some of these new targeted agents that we are
investigating. It was the first such article, so we are really
very optimistic, again, that we are entering a period where we
really are going to understand the molecular nature of these
tumors and how to treat them.
Chairman Tom Davis. Thank you very much.
Mr. Carter. Thank you, Mr. Chairman.
Chairman Tom Davis. Yes, sir, Mr. Murphy.
Mr. Murphy. Thank you, Mr. Chairman. I have a lot of
questions. Let's see what I can get through here.
First of all, there has been some frustration in the
Hillman Cancer Center in Pittsburgh trying to recruit minority
members for these studies--these are more than just racial
minorities. These are also socioeconomic minorities--getting
them to sites. Statistically speaking, do you believe there are
significantly fewer minorities in studies on cancer trials
nationwide? Is that a concern? Are there other things we need
to be doing to recruit people of various income levels, a wide
range of income levels, etc.?
Dr. Christian. There are some situations with NCI-sponsored
clinical trials where minorities are not accrued in proportion
to the numbers that one would expect based on the prevalence of
the cancer, for example. That's particularly true of African
American men. It's true of Asian men and women. It's true of
Hispanic men and women. And there are a lot of efforts ongoing,
both in NCI-sponsored trials and at the cancer centers,
University of Pittsburgh being one that has a funded grant
actually to look at what some of the barriers are to accrual
for racial and ethnic minorities and for people of lower
socioeconomic status and for the elderly, which are also under-
represented on clinical trials. So this is an issue that is
important to us, and we are approaching it from a variety of
different perspectives.
In our cancer centers I think, for reasons that are not
altogether clear to me, there are some even greater
disparities, so they have an even harder time than we do to our
national trials accruing what would seem to be a representative
and reasonable number of minorities.
I chair actually the Task Force for the American Society of
Clinical Oncology on Health Disparities and Workforce
Diversity, and there are many issues that have to do with trust
in communities, which have to do with the very, very low
representation of minority medical professionals who might be
able to reach these communities in more effective ways, so
there are many issues. I think it is an important problem and
one that we need to continue aggressively to try to address.
Mr. Murphy. Let me move on to another area here that is
important, and that has to do with the issue of people who may
have insurance. Some States like California require insurance
companies to cover clinical trials, and many other insurance
companies will simply say they're not going to cover anything
experimental. I'm not sure whether other States in addition to
California have these laws. My question is this: has there been
a cost/benefit analysis on these things, because there are
times when people feel they are desperate and they want to try
anything and the insurance company may say, ``No, we're not
going to cover that. There's simply no efficacy to support this
and it appears to be very expensive.'' Have we done any sort of
analysis overall? Is that ongoing?
Dr. Christian. There have been a couple of studies looking
at the incremental cost of care on clinical trials which have
shown that they are not significantly higher than care
delivered outside of clinical trials.
Mr. Murphy. What does ``significantly higher'' mean?
Dr. Christian. I don't remember what the actual dollar
amounts were. Do you remember that?
Mr. Murphy. Rough idea? Percentage?
Dr. Christian. Yes, I can certainly provide those precise
details, but the estimate is around 5 percent.
We have attempted to look at those incremental costs, but I
think in addition there are other important things to consider
here. Patients are going to be treated, and the treatments in
the community may or may not be as well developed, as well
based in evidence, and so there are costs associated with
delivering----
Mr. Murphy. Plus, you have differences in communities that
may have a university medical center versus what might be in a
community that might not be near some of those more advanced
research.
Dr. Christian. I mean, there are community participants in
clinical trials, but there are also the vast majority of
patients who are treated outside of clinical trials who are
just treated in private practice settings. There, the evidence
on which the treatments are based may or may not be as sound as
that in the clinical trials. So I think there are a lot of
things you have to take in account, but the cost concern, I
think there is growing evidence that it should not be an
impediment to providing those opportunities for patients
through their health insurance coverage.
Mr. Murphy. Thank you. That's all I have at this point.
Thank you.
Chairman Tom Davis. Thank you.
Mr. Cummings.
Mr. Cummings. Thank you very much, Mr. Chairman. I want to
also thank you for holding this hearing. It is a subject I am
very much interested in.
Dr. Christian, in my District I have Johns Hopkins, and I
also have the University of Maryland Hospital, and one of the
things that, in trying to get people involved in trials, not
just for cancer, but trials, period, African Americans, is that
there is a tremendous--and I think you mentioned it a moment
ago in response to a question--a tremendous distrust. People
cite the Tuskegee experiment. My mother, for example, says at
one of those hospitals, if she is in dire straits on her death
bed, don't stop there. And that's because they have seen and
had rumors at least of African Americans who were experimented
upon, and it causes them not to want--many people not to want
to be a part of any kind of experiment. And so even when the
argument is made that some of what they may have heard in the
past isn't absolutely true, what seems to happen, just when we
get to a point like, for example, with AIDS, for people to
finally get right there at the doorstep to participate,
something happens.
We have a situation we will be having a hearing here on the
18th where another hospital in my District tested some 2,500
patients and, come to find out, for AIDS and Hepatitis C, and
come to find out the results, the machinery was malfunctioning.
People knew it was malfunctioning and nobody did anything about
it. So then when they hear that kind of information it makes it
even worse, so they say, ``Wait a minute. You're talking about
AIDS and Hepatitis C, things that could be life threatening,
and you mean to tell me I went to--'' people have gone to the
hospital, gotten results that may not be accurate, and nobody
even waved a red flag.
So I was wondering, and I think that this is a situation
that probably exists all over the country. And then, of course,
with the whole issue of health care disparities, in the
Congressional Black Caucus one of our No. 1 issues is health
care disparities. African American people, as you well know,
are dying early, suffering needlessly, and, as a matter of
fact, just recently I was in an audience of about--I'd say
about 400 African Americans in my District, and I asked how
many of them believed in the last 5 years--within the last 5
years that they had a relative to die earlier than they should
have because of some medical foul-up or to suffer serious
injury because of something like that, and three-fifths of them
raised their hand. I can cite situations in my own family, at
least four or five, that I know things like that have happened.
So the question becomes: how do you deal with--how does--
and we in the Congress, we not only have these hats that we
wear here sitting on these panels, but we also take up the
bully pulpit trying to get our constituents to do the right
thing. Even when we pass legislation, we still want them to get
out there and take the colon test and to do all those things to
stay healthy. How do you say and how do you guarantee--not
guarantee, but how do you assure people it's OK, particularly
when they have these thoughts embedded in the DNA of every cell
of their brain?
Dr. Christian. Well, I appreciate the opportunity to talk
about this a little bit. I grew up in a medical family and
Tuskegee was very real to us, too, and it was a real
phenomenon. But I think that there have been many years since
Tuskegee and there are many new protections for patients. I can
assure you for NCI-sponsored trials, for example, that they are
reviewed exhaustively by experts in the management of the
cancer that we're talking about, by people at the National
Cancer Institute, and by institutional review boards and others
to ensure that the nature of the research is reasonable and
ethical. That said, there clearly are health disparities across
the entire spectrum of medical care.
I actually tell patients that on a clinical trial patients
get the same treatment as everybody else. It is prescribed. It
is written in a protocol. Exactly what needs to be done is
written there and patients are treated according to that
protocol. And we audit those sites. We go to the place and we
look at the records and we make sure patients were treated the
way they were supposed to be treated on the protocol, so there
are even additional protections.
So there are many protections in place that I think make
participation in an NCI-sponsored clinical trial a safe and
reasonable thing. I think it is important for minority
communities to benefit from the opportunity to participate and
from the knowledge that is gained. There are concerns about
whether there may be differences in the way various racial
groups handle drugs, for example. We won't know that if we
don't study them. We won't know that if we don't participate in
trials. And so when the new drug is then approved for the
treatment of some cancer, we won't know whether that actually
benefits us as it does the rest of the population. I think it
is important for us to be a part of that and to have the
opportunity to have those treatments and to, you know,
aggressively pursue those opportunities so that we are sure at
least in that venue that we are getting comparable care.
So that's what I tell patients. I don't think patients
should feel coerced to do it, but I think the opportunity
should be made available to them.
Mr. Cummings. Thank you.
Chairman Tom Davis. Thank you very much.
Let me just ask one final question, Dr. Pazdur. You raised
concern in your testimony that the development of new cancer
treatments will make clinical trials more costly and
complicated. How do we address the concern if the criteria for
enrollment in trials becomes based more on a patient's
biological characteristics than clinical ones?
Dr. Pazdur. Well, I think the eligibility criteria of the
protocol will say patients must over express a particular
enzyme, for example, and then patients will be enrolled that
have that particular expression of the target that is aimed at.
I look at this as a benefit to patients, to drug development,
and to drug regulation because one of the problems obviously
that we have in oncology today is even or most effective drugs
are relatively modest in their response rate or in their
clinical efficacy, so if we can predefine an enriched
population that is more likely to benefit from the drug, that
efficacy will be greater expressed, we'll have higher response
rates, we'll have higher timed progression and better survival.
Therefore, I look at it as a positive aspect for the whole area
of drug development, and I don't really look at it as an
obstacle at all. I look at it as a positive thing.
Chairman Tom Davis. OK. Thank you both. Dr. Christian,
thank you, as well. You have been very helpful, and I will
allow you to go now and we'll go to our second panel. Thank you
very much.
Before we do that, I want to welcome my colleague from New
Jersey, Representative Scott Garrett, to our hearing. We'll
take a 10-minute break because we just switched, and then, Dr.
Garrett, I'll allow you to introduce one of our panel members.
[Break.]
Chairman Tom Davis. The committee will come back into
order.
We are pleased to have our colleague from New Jersey here
with us today. Mr. Garrett, you are recognized.
Mr. Garrett. Thank you, Mr. Chairman. I appreciate the
opportunity to introduce Dr. Andy Pecora, who is a 20-year
veteran of the war on cancer. When I first met him, I knew a
little bit about his background, now I know a whole lot more
about his background and I would like to share that with the
panel.
He is a graduate of Seton Hall back in 1979. He went on to
receive his medical degree from the University of Medicine and
Dentistry in New Jersey, the Great State of New Jersey, in
1983. He completed his residency over at New York Hospital,
Cornell Hospital Systems, and then moved on to the Memorial
Sloan Kettering Cancer Center and completed a fellowship in
hematology and oncology in 1989, after which he moved on to
Hackensack University Medical Center to serve as director of
hematology and oncology in the adult blood and marrow
transplant program, and now has recently been promoted to
chairman and director of the Cancer Center at Hackensack
University Medical Center.
He is a diplomat of the American Board of Internal Medicine
with subspecialties in hematology and subspecialties in
oncology, and he has received numerous awards and honors, some
of which include the Women's Guild Premedical Academic
Achievement Scholarship back in 1978. In 1979 the Academic
Excellence Award in Biology. In 1983 the Doctors Milton and
Rose Petrokowski Award for Overall Excellence in Patient Care.
And then the Outstanding Teacher Award from the Department of
Internal Medicine at Hackensack University Medical Center in
1989. And for all doctors I think this is important--he was
selected as one of the best doctors in America in 1997, 1998,
and 2003, and then received the American Cancer Society
Physicians in the Forefront Award and the Susan G. Komen Breast
Cancer Foundation Award as a hero in the fight against breast
cancer. He received the EBMTESMO Award at the International
Conference on High Dose Chemotherapy in Breast and Ovarian
Cancer.
His professional positions include such things as the
scientific advisor for the companies ProNeuron and ProVirus. In
addition, he has co-founded and served as chairman and chief
executive officer of Progenitor Cell Therapy and now serves on
the Board of Directors of the American Society of Bone Marrow
Transplant, and previously on the International Society of
Hemotherapy and Graft Engineering, the Hackensack University
Medical Center IPA, and served as chairman of the medical board
and board members of the Affiliated Physician Network.
In addition to these things, he has served as chairman of
the Transplantation Committee on the International Society of
Hemotherapy and Graft Engineering and served as a member of the
Cancer Institute of New Jersey Protocol Advisory Committee.
Recently, he was appointed to the Steering Committee on the
Transplant Treatment Trials Group, and he is a fellow of the
Academic Academy of Medicine of New Jersey and a fellow of the
American College of Physicians and American Society of Clinical
Oncology and American Society of Oncology.
Finally, the doctor has been involved in numerous research
projects in an effort to improve the outcome of patients with
cancer. His recent work includes the production of stem cell
products that are free of contaminating malignant cells using
technology including CD-34 selection and ex vivo expansion. He
has led several national trials in the field of transplantation
and has published numerous peer reviewed articles and abstracts
and has presented the results of his research at many national
and international scientific meetings.
Probably most importantly, he is married and has three
great children and resides in the fair State of New Jersey in
the beautiful town of Ridgewood.
We welcome you to the panel.
Chairman Tom Davis. Thank you very much, Dr. Pecora. Thank
you very much. We are joined here today with Dr. Robert Comis,
who is president of the Coalition of National Cancer
Cooperative Groups and is a professor of medicine and director
at the MCP Honoman University Clinical Trials Research Center
in Philadelphia; and Ms. Ellen Stovall, who is a 28-year
survivor of two bouts with cancer and president and CEO of the
National Coalition for Cancer Survivorship.
This panel of witnesses is going to provide the committee
with their perspective on the seriousness of low accrual levels
in cancer clinical trials and what efforts are being taken to
improve outcomes in cancer patients. They are obviously a very
distinguished panel. We appreciate all of you being with us.
It is our policy to swear everyone in, so if you would rise
with me and raise your right hands.
[Witnesses sworn.]
Chairman Tom Davis. Thank you.
What we will do is your entire statement is already part of
the record. Dr. Pecora, I'll start with you. Try to do it
within 5 minutes. You have your lights there that turn orange
after 4 minutes, red after 5, and then we'll go straight down
the line and then we'll move to questions. Thank you all very
much for being with us.
STATEMENTS OF DR. ANDREW PECORA, CHAIRMAN AND DIRECTOR, THE
CANCER CENTER, HACKENSACK UNIVERSITY MEDICAL CENTER; DR. ROBERT
COMIS, PRESIDENT AND CHAIR, COALITION OF NATIONAL CANCER
COOPERATIVE GROUPS; AND ELLEN STOVALL, PRESIDENT AND CHIEF
EXECUTIVE OFFICER, NATIONAL COALITION FOR CANCER SURVIVORSHIP
Dr. Pecora. Thank you. Thank you, Mr. Garrett, for your
kind words. First and foremost, thank you, Chairman Davis and
distinguished committee members, for providing me the
opportunity to participate in this important hearing that
hopefully will result in actions leading to improve outcomes
for people afflicted with cancer. I have been active in the war
on cancer for over 20 years, participating in basic science,
clinical trials, and now cancer care administration. I welcome
the opportunity to share my ideas on why and how increasing
participation in clinical trials, regardless of the status of
innovation, will improve outcomes for people suffering with
cancer.
We all well know that over the past 35 years Government,
industry, and the public have spent billions of dollars to
create and operate the agencies that oversee and fund efforts
in basic and clinical discovery aimed to improve outcomes for
people battling cancer. As a result, substantial advances have
been made in the understanding of the biology of cancer and, as
a consequence, new and more effective treatments have emerged.
Unfortunately, even with this focus and extensively funded
effort, cancer remains a serious problem. This year in the
United States, alone, cancer is expected to claim more than
500,000 lives; thus, criticism of our current system exists. In
a recent article in ``Fortune'' magazine authored by Clifton
Leaf, significant criticism is levied at the cancer research
community claiming the culture is dysfunctional and that the
search for knowledge has supplanted the search for cures, they
lead to discoveries of marginal benefit regardless of a great
expense of time and money. I believe, however, that these
claims are only partially correct, and that, as a consequence
of our national effort, it is now within our reach to turn
cancer in most cases into a chronic disease much like diabetes,
while searches for prevention and cures continue.
As Mr. Leaf eloquently points out in his article, we must
make the entire system of discovery and application of new
agents more efficient. Clearly, continued improvements in our
understanding of the underlying root causes of cancer and
methods of detection, of efficacy, and safety are essential. Of
equal importance however is active and robust participation by
people with cancer in clinical trials. No matter how promising
a therapy appears in laboratory testing, it is only through
clinical trials that safety and effectiveness can be
established in people. Simply stated, no person or computer
program is capable of predicting whether a new treatment will
work and be safe in people. In my current experience, it is not
the lack of good ideas that is slowing progress in our quest to
cure cancer, but it is much more a result of the slow pace of
completing active clinical trials.
In 2003, there were approximately 1,700 ongoing clinical
trials, of which the NCI sponsored 1,200. Despite this large
number of trials, only 3 percent of adult patients
participated, while 20 percent were eligible. Low participation
in clinical trials slows the continuum of drug development from
initial concept to FDA approved products, and as a consequence
impedes improvements of outcomes for people with cancer.
In addition, poor participation at clinical trials
lengthens the new drug approval process, estimated now at 10 to
12 years, and has the cascade effect of increasing new drug
development cost, now estimated at $800 million, inflating the
cost of drugs to consumers once approved, and, worst of all,
limiting the number of new agents that make it through the
process of the discovery pipeline.
Advances in knowledge which will lead to better questions
should continue to be supported, but at the same time we need
to improve participation in clinical trials. So what can we do
about it? Lack of participation is due to several factors that
can and should be addressed. A lack of public knowledge of
availability of clinical trials and a growing public bias
against participation due to poor outcome high profile cases is
a key factor. Government should do everything it can to educate
the public on the value and importance of participating in
clinical trials.
In an era of shrinking reimbursement for clinical care,
funding needs to be established for clinical programs, both
hospital and office based, to support the required
infrastructure, including research staff and informatics, to
participate in clinical trials. Reductions in their growing
regulatory burden, including centralization of institutional
review boards, streamlining adverse event reporting, and
minimizing regulation resulting in increased cost and
complexity without compromising patient safety or privacy must
also be accomplished.
Finally, insurance reimbursement for clinical trial cost
needs to be addressed nationally. In my home State of New
Jersey, I was a member of the New Jersey working group to
improve outcomes in cancer patients. Our group was successful
in convincing the insurance companies covering New Jersey
residents to voluntarily reimburse for approved clinical trial
related expenses. This could serve as a model for a national
effort.
Another important aspect to improve outcomes for people
with cancer is to have more clinical trials available. This can
be accomplished by increasing the efficiency of moving clinical
trial concepts through the approval process before they become
available to the public. The current system should be more
efficient and held to more businesslike timelines for results.
Specifically, the Cooperative Groups in the national cancer
review process takes too long, at times years, and should have
efficiencies mandated by Government, since it is Government
that supports these efforts. Moreover, encouraging and
rewarding the national Cooperative Groups to work together on
questions that require large number of patients to answer is
essential.
Finally, the issues of creating an environment--
intellectual property protection, FDA approval support, etc.--
for multiple agents to be tested together for effectiveness
prior to the FDA approval process needs to be addressed.
In summary, I believe this is an exciting time for those
engaged in the battle against cancer. The fruits of our efforts
over the past 35 years are just beginning to be realized. It is
clearly no time to retreat or claim defeat, but instead refocus
our energies to make the entire system more efficient, less
expensive, and more user friendly. Our family and friends
afflicted with cancer deserve our collective best effort. In
doing so, participation in clinical trials should increase,
resulting in meaningful answers and better answers sooner for
those battling this dreaded disease.
Thank you. I am happy to answer any of your questions.
[The prepared statement of Dr. Pecora follows:]
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Chairman Tom Davis. Thank you very much.
Dr. Comis.
Dr. Comis. Congressmen Davis, Waxman, and members of the
committee, I want to thank you for this opportunity to testify
on behalf of 8,000 Cooperative Groups members from cancer
centers, community practices, and patient advocacy groups
across the country. Most importantly, we should all thank the
courageous patients who enter our clinical trials. They are the
real pioneers who move the frontiers of cancer treatment
forward.
There are two distinct forces in cancer clinical trials--
those studies directly supported by industry and overseen by
the FDA, and those studies supported by the NCI which are
conceived, designed, and executed in academic and community
practices throughout the Nation. Typical industry supported
trials are directed toward drug approval; Cooperative Groups
trials are designed to evaluate new approaches and establish
new evidence-based standards of care. We estimate that
approximately 50,000 patients participate in clinical trials
yearly. The NCI-funded Cooperative Groups account for about
half, or 25,000 of those patients. The Cooperative Groups have
always played a key role in the Nation's cancer research
system. We develop curative therapies for childhood cancers,
improve the post-surgical survival for patients with breast and
colorectal cancer by 25 to 30 percent, and show that cancer
can, indeed, be prevented in high-risk patients.
As importantly, though, the publicly funded system allows
us to ask and answer questions that challenge the mainstream.
Our studies evaluating high-dose chemotherapy for breast cancer
showed that this extraordinarily expensive and toxic treatment
was of no clear benefit, saving the country hundreds of
millions of dollars and patients unquestionable toxicity.
Much has changed since President Nixon declared the war on
cancer. The understanding of the biology of cancer has
increased tremendously. The public and private sector has
invested huge resources in the development of biologically
directed therapies, and new targeted agents are entering the
oncology practice in our phase two and three trials.
The Cooperative Groups have adjusted to the opportunities
and challenges created by these changes. We are investigating
the newest molecules and approaches. Virtually all of our
studies now include laboratory correlative studies which
attempted to find why something does or does not work. In order
to do this, we've established excellent tissue banks and
laboratory programs in cancer centers throughout the country
which collect, store, and analyze tissue specimens and
correlate biology with clinical events occurring in our
controlled clinical trials. But we must do more to ensure that
patients have the opportunity to benefit from our work.
First, let me address the issue of accrual of adults onto
cancer clinical trials. We estimate that only about 3 to 5
percent of adult cancer patients participate in clinical
trials. This number was confirmed prospectively in our survey,
which we did along with Ellen's group, which also revealed that
only 15 percent of patients were aware that participation was
even an option. That survey also reinforced the critical role
of the oncologist in informing and educating patients about
this option. Increasing awareness, dispelling misconceptions,
engaging physicians are key elements of the solution to the
accrual problem.
These considerations led the Coalition of National Cancer
Cooperative Groups to launch a national awareness campaign
along with ``Newsweek,'' which is in its 4th year, develop Web-
based tools to facilitate trial searches, and work with the
American Society of Clinical Oncology in developing both
recognition and educational programs for physicians.
Indeed, the efforts of the Coalition and others have born
some fruit. There has been a 30 percent increase in overall
accrual onto cooperative group studies from 1997 to 2002, from
about 20,000 patients a year to about 26,000 patients, but more
needs to be done. However, the system is stressed even at this
level of accrual. The Cooperative Groups have been and remain
chronically under-funded. Two extensive reviews of the system
in the mid 1990's recommended that the Cooperative Groups be
funded at the full peer recommended level. We continue to be
funded at approximately 60 percent of that level, and funding
has been flat for the last 3 years. This stifles innovation,
destabilizes key functions such as our tissue banks, data
management platforms, and acts as a disincentive to both
academic and community physician participation.
Keep in mind that about 60 percent of accrual comes from
community-based practices. The NCI reimburses $2,000 per case
to perform the research at the site. It is estimated in the
ASCO survey that the actual cost is more like $4,000 to $6,000
per case. The ability for both academic and community sites to
continue in Government-sponsored work will be increasingly
challenged, particularly when the full effect of the Medicare
Modernization Act of 2003 takes place in 2005.
The entire system is being buried under a regulatory
mountain. It is estimated that about 30 percent of clinical
trials research dollars goes toward ensuring regulatory
compliance.
Our studies are overseen by about 1,600 separate IRBs. HIPA
compliance complicates our laboratory work. The current
discussions about off-label drug use in oncology could have a
huge impact on our studies, which try to explore new
indications and uses for targeted agents as they become
available.
We all believe that there is an important balance between
the need for innovation and the critical societal concerns, but
the balance must ultimately be struck for the advantage of all
who suffer from cancer.
The Cooperative Groups remain totally committed to
providing high-quality care and new opportunities for cancer
patients, but rest assured the development of the newer cancer
treatments will make clinical trials more complicated and more
costly and accrual will remain a major concern.
The Cooperative Groups chairs have developed a white paper
entitled, ``Harnessing the Science: A Proposal to Improve the
Publicly Funded Cancer Clinical Research System,'' which I have
submitted
for the record, which outlines our thoughts on what can be done
to ensure the continued vitality and importance of the
Cooperative Groups in the publicly funded system, which is so
critical to our cancer patients in the Nation.
Thank you.
[The prepared statement of Dr. Comis follows:]
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Chairman Tom Davis. Thank you very much.
Ms. Stovall, thanks for being with us.
Ms. Stovall. Thank you, Mr. Chairman. Good morning. I am
Ellen Stovall, president and CEO of the National Coalition for
Cancer Survivorship, and I am a 32-year, two-time survivor of
cancer.
NCCS is the Nation's oldest survivor-led organization for
people with all type of cancer. Our mission is to advocate for
quality cancer care for all Americans, including the 10 million
cancer survivors alive today in this country.
I'd like to thank you for the opportunity to testify to the
important work of this committee.
I have a very direct and personal experience with cancer
clinical trials. When I was first diagnosed in 1971, I actually
started treatment on the day that President Nixon signed the
National Cancer Act. My father literally thought I would be
cured in 7 years, as the whole world would be, of cancer.
Unfortunately, I was unable to participate in a cancer clinical
trial promising a new therapy for the type of Hodgkin's Disease
that I had because I was deemed ineligible for the trial, as I
had just had a baby. Today, that therapy has become the
standard of care for Hodgkin's Disease, and when I was re-
diagnosed with the same disease 12 years later I was able to
take the drugs that had been in that clinical trial some 12
years earlier, so I really do understand the progress that is
made through clinical research.
I cite this experience to draw your attention to two key
issues: first, restrictive standards for trial enrollment
unnecessarily prohibit many patients from entering a trial;
and, second, clinical trials do serve as the means of testing
new therapies and moving the standard of care forward step by
step, extending or even saving many lives that would have been
lost to cancer.
There are many reasons why the rate of participation in
trials is low. Both physicians who enroll their patients in
trials and those individuals who agree to receive their care in
a trial encounter several barriers to participation. All of
those obstacles must be addressed if we are to improve the
clinical trial system.
The community has made great strides in increasing the
awareness that care in a clinical trial may, indeed, be the
best treatment option for a cancer patient, but our educational
mission is incomplete. We still have to address the fears of
some regarding the risks associated with trials, as well as the
reservation of others about the value of trials. This is
perhaps most acutely felt in under-served communities where
socioeconomic, cultural, ethnic, and language disparities
present even more barriers. Cancer patients may have to make
sacrifices to enroll in a trial, and they want to believe that
their time and energy are well spent in a valuable research
endeavor.
Over the last several years, some researchers and companies
have taken the step of involving advocates early in the
clinical trial design process. The FDA has also made great
progress, particularly in the last few years, of involving
advocates at earlier and earlier stages of drug development.
Those efforts have generally been rewarded because advocates
have embraced those trials and encouraged participation in
them. Examples of this are breast cancer advocates' involvement
with the design of the hterceptin<SUP>'</SUP>, trials, and
multiple myeloma advocates' involvement more recently with
trials for Velcade<SUP>'</SUP>. For more than a decade, NCCS
and a number of other patient advocacy organizations and
professional societies like ASCO collaborated in a legislative
effort to address the failure by third party payers to pay for
the routine patient cost in trials. After many years of
unsuccessful legislative effort, we were able to persuade the
Clinton administration to issue an Executive memorandum
instructing Medicare to allow all beneficiaries, those with
cancer as well as other life-threatening diseases, to
participate in high-quality clinical trials such as those
sponsored by Federal programs or under the oversight of FDA.
With this change in the leadership role of Medicare in health
policy, reimbursement has seemingly become less of an obstacle.
While cost is a primary concern, of no less concern is the
fact that so few doctors recommend a clinical trial for their
patients as a viable treatment option. Clinical research is
expensive, requiring an extensive infrastructure both at the
central point of control that is the research centers providing
overall management of the trial and at the level of the
individual provider. Research requires sophisticated, dedicated
personnel such as research nurses, as well as the means for
data collection and management, not to mention additional time
commitment from physicians involved.
For many years, cancer clinical researchers have made clear
that the rate of payment from NCI for their participation is
inadequate, despite some modest increases over the last few
years. Privately funded research has overtaken that sponsored
by NIH and other Federal sources because industry is willing
and able to pay the full cost of research, whereas the
Government's funding lags behind.
As you probably know, over the last two decades cancer care
has truly moved into the community. As much as 80 percent of
cancer care is provided by community oncologists around the
country. This system has been welcomed by cancer patients who
prefer to record their care near their homes, thereby avoiding
the dislocation that occurs if they must travel. Obtaining care
in the community does not eliminate a patient's ability to
receive care in a trial. As we just heard from Dr. Comis, as
many as 60 percent of clinical trial enrollees are referred to
trials by community doctors.
The fact remains that only a small percentage of adults are
enrolled. We are hearing disturbing reports from community
oncologists that, as a result of changes in Medicare
reimbursement for cancer care that were included in the MMA,
they may be forced to reassess their participation in clinical
trials altogether. The MMA reformed the system of payment that
was over-paying for chemotherapy drugs, a reform that we all
agree was necessary. The bill also made a temporary adjustment
in the payment for expenses associated with delivering
chemotherapy, but the concern of all of us who care about
quality cancer care is that in 2005 this new law will reduce
total payments to cancer care that such an extent that services
offered by the community oncologists will have to be reduced,
and clinical trial participation may be among the first things
to go.
We often describe the system of cancer care in the United
States as the best in the world, and yet a series of reports
from the Institute of Medicine's National Cancer Policy Board
proclaimed great inconsistencies in the quality of care and the
lack of any systematized way of assuring access to it. We do
know that a good deal of this disparity could be corrected if
more people were involved in clinical research and were assured
access to a high quality clinical trial as a matter of first
course rather than last resort.
Our country is unusual in our ability to provide high-
quality care, including care in a trial in a community, but the
system is suffering from so many strains that I fear all these
factors will create such a stress that it may be impossible to
carry on clinical research in the future that people could have
access to.
NCCS and others have been engaged for more than a decade in
efforts that will ensure that clinical trials are an integral
part of cancer care in this country. We are dedicated to that
outcome, and we look forward to cooperating with this committee
and others in ensuring that it continues in the future.
Thank you.
[The prepared statement of Ms. Stovall follows:]
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Chairman Tom Davis. Thank you all very much. I think the
committee has some questions, so I'll start with Judge Carter.
Mr. Carter. Thank you, Mr. Chairman. And I thank all of you
for being here. Ms. Stovall, please don't be mad at me for what
I said about Lance Armstrong, but it was a shock to me to
realize that the definition of a survivor was survive each
time, and as you pointed out in your testimony, you said, ``I'm
a two-time survivor.'' To me a survivor is it's all over and it
won't happen again.
Ms. Stovall. It would be nice if that were true.
Mr. Carter. Yes, and I think that's the goal we are looking
for. And a question I also have, I question what's going on,
and maybe you can give me an answer. It seems to me that the
research that we're doing in the areas of cancer is how to
fight the tumor. Do you know, in these clinical research
experiments that are being done, are we doing anything to
inoculate for cancer, to come up with a genetic engineering to
fight cancer? Are we still in the same direction we were in
1970, how to fight a tumor? Does anybody know the answer to
that?
Dr. Pecora. I'm happy to comment on that. I think it is
two-fold. I think, one, and sort of a generic way of speaking,
is there is a focus to make the tumor go away, and that's a lot
of giving medicines, doing surgery, radiation, but I think
there is a growing and equal emphasis of keeping it from coming
back and understanding how and what you need to do.
You're right. I mean, there are strategies now aimed at
using certain approaches to make tumors go away and then using
cancer vaccines as an example to prevent it from coming back.
When you have therapies that are only of modest benefit, you do
the best you can. There are a whole new class of agents now--
you heard about them this morning--that's changing the whole
cancer paradigm that I'm not even sure how to answer that
question, because it may be you don't need to make the tumor go
away and the person could have a happy and healthy life, like
Glevic that you heard about. It doesn't cure CML, but it makes
that clonive cell go away for a very long period of time, maybe
forever.
So the answer to that question is changing, but I do think
your concern about keeping it from coming back is on the minds
of people who do this sort of thing.
Mr. Carter. You know, one of the things, just human
nature--and I have no expertise in this at all, just human
nature and comments--in Texas MD Anderson has a great
reputation in Texas. Anybody that has cancer in Texas will try
to go to MD Anderson Hospital. I'm sure there are people at
Brackovitch Hospital in Austin, oncologists that can do a great
job in treating. That's the publicly perceived--it is perceived
all the way--it's really a private hospital now--it is
perceived by the people in Austin to be a public hospital
because it was at one time our public hospital. If given the
choice, they will go to MD Anderson, which is funded heavily by
public funds, and it is perceived to be a great scientific
research center, a private hospital, if you will. It is
perceived that way and everybody would want to go to MD
Anderson because they think they have success.
I think that's part of what your clinical trial situation
is. People perceive this as another Government program rather
than--do you get my drift? When you're talking about the
National Cancer Institute, well, they've been at it for 50
years with $52 billion worth of money spent. They're just
another Government program. And if I can go to MD Anderson and
participate, that's fine. In fact, I think MD Anderson actually
runs some of your programs. But do you understand? It's the
public perception.
I would be willing to bet we have a better turnout at MD
Anderson in Texas than you would some place else. I'd be
willing to bet the farm on that. So a whole lot of what you
have is the public perception that Government is failing in the
war on cancer and that it is going to take private involvement
to succeed in the war on cancer.
Dr. Pecora. Well, I did make a statement that I will stand
on. I think that the Government side of the equation can be
more efficient, and I think that it takes too long to get
things through the process, and I think we have created a
bureaucracy that you heard about that is impeding discovery and
making it harder to do.
I've learned more in the last 2 years as a cancer
administrator than I ever learned as a cancer investigator
about why we're not getting more people into clinical trials,
and many of them are business issues. They're not science
issues. These are the things that--one of the reasons I wanted
to come here today was to address this with Congress, because
you fund these efforts. So I think if you--the money for you is
to look at these things and to try to drive efficiencies into
the system.
Mr. Carter. Absolutely, and that's one of the reasons I
mentioned it to the last panel about the intellectual
properties issues. The incentives--and let's face it, we live
in a world where we're all trying to make a living, and the
incentives to go out and meet these challenges and advance
private capital in meeting these challenges, in my opinion,
needs to be encouraged. The Government can't fight this war
forever. We fought it and we can use some help, I guess is what
I'm saying.
Dr. Pecora. There's one other thing I want to say before--I
don't want to monopolize the microphone, but another misnomer,
this concept of clinical research, people hear ``research'' and
it has all these connotations that we heard one of the
Congressmen speak to before. In cancer care, when the outcome
is dismal, clinical trials should be the standard of care, not
that there's something better and they're trying this out. I
mean, that's a bad way of looking at it, particularly when the
likelihood, as we get smarter about the mechanisms of the
disease, how to read if something is effective or not are
improving at light speed. The likelihood of you having a better
outcome by participating in trial is going to go up
proportionately.
So what we need to do as a Nation is to push cancer trials
out into the community offices, into the hospitals that aren't
the MD Anderson's of the world, because that's not where all
patients are treated. That's where the minority of patients are
treated.
Mr. Carter. That's right.
Dr. Pecora. We have to get this in the doctors' offices,
and in order to do that we're going to have to support them.
We're going to have to provide them funding for research
nurses, data managers, and we're going to have to simplify the
process or it is not going to happen.
Mr. Carter. We're going to have to convince the public's
perception that they'll get that equal treatment in that
doctor's office that they would get in this famous--supposedly
famous cancer center. And that's the perception you've got to
overcome on these clinical trials, in my opinion.
My time is up. Thank you, Mr. Chairman.
Chairman Tom Davis. Thank you very much.
Mr. Garrett, would you like to ask any questions?
Mr. Garrett. Thank you. I appreciate the testimony of
everyone.
A couple of quick questions. First of all, with respect to
New Jersey and on the insurance side of the issue, you
indicated how you were able to convince the insurance industry
to provide coverage for the expenses of clinical trials. How
did you do that? What is the status nationally, if you know?
And what is the recommendation as far as facilitating that on a
national basis?
Dr. Pecora. Well, how we did it in the State is we got the
major cancer program directors and people involved in various
aspects of clinical trials to come together in a forum and we
brought in the CEOs and other representatives of the insurance
industry and showed them the data. We made the claim, ``Look,
you know, you're paying for things that are marginally
effective. Wouldn't you want to pay for something that could be
better for your subscriber?'' And they got it. And they got it
to the point where they did it voluntarily.
I can't speak to the rest of the Nation. I know there's
efforts around the country, but I'm not privy to that
information.
Dr. Comis. Maybe I can help clarify. This is a very
complicated issue. In the Harris Survey that I mentioned before
we asked several questions about personal barriers to
participation--travel, taking time off from work, insurance
coverage, etc.--and the thing that was on the very top of the
list, 60 percent of the 6,000 cancer patients that we surveyed
said that they were afraid their insurance companies wouldn't
pay.
Then we went to the 4 percent of patients who did actually
participate and asked a final question which was: in the end,
did your insurance company pay? And 86 percent said yes.
Now, how hard it was to get there we didn't ask, or how
difficult it was to navigate the system, but this insurance
barrier issue is a major perception barrier, at least, and
there are now--Ellen may know the exact number. I think there
are 19 States now that have legislative solutions, there are
about three States that have non-legislative solutions.
Medicare said they would pay. I think it is incumbent on us,
and this is what we try to do in a lot of our materials is to
get the word out that, in fact, your insurance companies have
said that they would pay, that States are backing you, and if
you are having trouble you have to use that information to make
sure that you have access to clinical trials.
Mr. Garrett. And, following upon this, then, if I may, Dr.
Comis, you made the comment--and you did, too, Andy--as far as
the responsibility of greater education, but to me isn't the
education responsibility on the part of the doctor, the
oncologist? Isn't he supposed to know this, and isn't he the
one that's supposed to convince the patient that clinical
trials are necessary and, if he has been in the practice for a
while, that he should know the statistics that he can rattle
off that he can put his patient at ease?
Dr. Pecora. Right. Well Mr. Carter I think hit the nail on
the head. It is very hard to battle public perception. I am a
practicing physician. I see cancer patients. I still put people
on clinical trials. I do it every day, and it is hard. And the
reason it is hard is because people come in with preconceived
notions, and the minute you start talking about a clinical
trial all of the sudden warning bells go off.
You know, we have high-profile cases in our country, the
Jesse Geisinger case, going back historically to the Tuskegee
experiment, the whole concept of what IRBs are doing now. It
is, I think, pushing people in the general direction of being
suspicious and having a bias against clinical trial, and I
don't think at the individual physician level that's going to
be reversed very readily. I think it has to be a societal
issue.
Dr. Comis. Maybe I can followup on that, because we've
studied this a lot. I agree totally. In the end, it's the
interaction between the doctor and the patient that decides
when somebody goes on. And, in fact, I mentioned in my remarks
that only 15 percent of the patients in the survey were aware
that they could participate, 85 percent weren't.
If you look at the people who were aware, a quarter went
on. And if you look at the difference between the quarter that
went on study and the three-quarters that didn't, it was all
the doctor. The doctor helped educate them about trials, helped
find a trial for them. The doctor and the staff worked on this
together.
I agree. There are two components on how we have to
approach this. One is to increase awareness and decrease
misconceptions on the part of the patients and the public, but
the other thing is to facilitate the involvement of the doctor
in the process.
You know, it's not just reimbursement. It takes time. It
takes staff time, patient time to do this, and we have to get
the resources out to the sites, particularly the community
sites that are really committed to do this, and the resources
are not there and the challenges are great.
Ms. Stovall. And I just want to add that, you know, I put a
lot in my testimony, my submitted testimony, about physician
reimbursement issues which, Mr. Chairman, you touched on, and
it is not about the income of doctors or what doctors make,
it's about how we value the time they spend with their patients
and their families. When we have been over-paying for the
chemotherapy that they provide and grossly under-paying for the
time that they spend counseling families and patients about
treatment decisions which are more and more complex as time
goes on with the new science, I think that we really have to
look at our reimbursement system and put the dollars where we
value the doctors' time.
Mr. Garrett. Thank you.
Chairman Tom Davis. Thank you. Thank you very much.
Mr. Duncan, do you have any questions?
Mr. Duncan. Well thank you, Mr. Chairman. Thank you for
calling this hearing.
One thing I'm curious about, I have read in the ``Wall
Street Journal'' and other places sometimes that it takes--I've
seen figures of $650 to $850 million to get a typical drug
approved in this country, and it sometimes takes 10 or 12
years, and I've also read that in no other developed nation
does it take anywhere close to as long. I remember the ``Wall
Street Journal'' had on its front page several years ago this
small company in Illinois had a breast cancer detection pad
that had been approved in every other country where they had
asked for approval, most of them within days or weeks, but they
had been--I think it was 9 years, and they still weren't
approved in this country, and they had some quotes from cancer
specialists saying that thousands of lives have been lost
because that had happened.
I'm just wondering. I assume that none of you can say
anything critical about the FDA or maybe they'd get back at you
later, but are we doing any better on any of that stuff? Why is
it that it takes so much longer and so much more money to get
approved here as compared to any other developed nation? I
mean, you can go overboard on anything, and I'm just wondering
about all that.
Can any of you say anything----
Dr. Pecora. I'd like to comment on that.
Mr. Duncan [continuing]. Without getting in trouble?
Dr. Pecora. Well, you always get in trouble.
Mr. Duncan. OK.
Dr. Pecora. But I do think that the FDA talked a little bit
about this critical path document that they put out, and
personally, as someone involved both on the academic side and
on the corporate side, I find them getting more and more user
friendly, and I do think that some of the initiatives will
decrease time to discovery and cost to discovery, particularly
as we get better at screening for toxicities and putting the
right kind of people on trials, i.e., people who have the
potential for benefit.
But I see the major stumbling block becoming this issue
about clinical trials. This is not going to go away. This is
going to get worse. People in the community, people who are
doing this, you're not going to answer a question of whether or
not something is safe or effective until you test it on a
person, period. And until we fix this system, which is going in
the wrong direction, that's going to maintain that high cost of
discovery, the 10- to 12-year timeline. You heard plenty of
testimony today to attest to that, and I think that's where the
emphasis should be now.
Ms. Stovall. I just want to add on to that. I mean, I
remember Dr. Pazdur, who was on your first panel, remarking at
several meetings over the last few years that we've attended
that when a really good drug, a really novel therapy comes to
the FDA, you see it move very, very fast. I don't know what
that means if they're not exciting therapies that are coming to
the FDA what the countervailing point would be. But I do know
that the FDA--the burden on the FDA in terms of peer review
capabilities, well-trained specialists to review oncology
products is just not what it needs to be in terms of capacity
building. I think that's another area for this committee
perhaps to examine in its future deliberations. I think that
would be a very interesting thing to pursue.
Mr. Duncan. Well, what happens? If it takes, you know,
hundreds of millions or years to get a drug approved, then
obviously what you do--this is one of the main reasons why the
drug industry has ended up in the hands of a few big giants,
because a small company can't handle that. And then also the
small companies don't have the connections within the FDA.
Chairman Burton said in here one time that 9 out of the last 14
FDA commissioners work for the big drug companies now. I don't
know if that's true or not, but, boy, there just is a lot of
things going on apparently that--I mean, people wonder why
drugs cost so much, and that's--this seems to me to be why. It
is our own--we've let the Government get too big and too
bureaucratic, and if we don't cut this down a little bit and
speed this process up and make it where a small company has a
chance again, these drug prices are just going to go up even
more, it seems to me.
Thank you, Mr. Chairman.
Chairman Tom Davis. Thank you very much.
Let me just try to wrap a few questions up. First of all,
let me just pick up on where Mr. Duncan left off. If there's
one or two things Government could do to really help this
process along, would it be the funding dollars, would it be
speeding up the regulatory process, would it be reducing the
paperwork and the bureaucracy that you have to go through and
patients have to go through, would it be information
dissemination? Let me start, Ms. Stovall. You've taken a
leadership role on this from the patients' perspective. From
your perspective, what do you see? And then let me ask
everybody what they see from their perspective. We're talking
about Government's role. So much of this is private.
Ms. Stovall. Well, I think as patient advocates we do look
to Government and the very, very important role of both the FDA
and the NIH and CMS, frankly, play in this whole, you know,
landscape of both developing new drugs, the research approval,
and then finally paying for them and getting them to people.
I would like to see better coordination among these
agencies, working more collaboratively, having some of the
regulatory barriers removed, having a bit of a more
transparency to the FDA processes that I believe could truly
make things work better, better training of reviewers, more
attention paid to that whole process, including I think
something that has been mentioned but largely not examined very
closely, and that is institutional review board reforms,
because I think the regulatory burdens on the system, as Dr.
Comis and others have mentioned, are at this point very
onerous, and really helping lawyers more than they are helping
patients succeed in getting these new therapies.
Chairman Tom Davis. I like that one. That's not even, I
mean, that's something that is within this committees
jurisdiction and is not even big dollars. It's just trying to
be efficient with what we do.
Ms. Stovall. It's just making more efficient the things
that we already have in place, because I do think that the
protections that Government offers are very important to
patient care but shouldn't be burdensome.
Chairman Tom Davis. Thank you.
Dr. Comis, do you have any thoughts on that?
Dr. Comis. Yes. I would followup with three areas. One is I
think the Government--the NCI has to recognize that it needs to
fund these things at an acceptable level, at a level it can be
done. For the group system, $150 million out off a $4.3 or $4.4
billion budget, I mean, that's like chump change. So, I mean,
people have to decide whether they want the Government to be
involved in this. And they have to be, because we can ask
questions that a company can't.
The second thing is we have to be able to interact and
develop relationships between the public side and the private
side. The private side has developed all the drugs, and we have
to be able to work with them very, very effectively, and there
are a lot of barriers to that need to be broken down.
As well, I think that the layering of the Government
bureaucracies have to be harmonized between FDA, NCI, etc.
And, last, I'd followup with one other huge thing that
could happen, and it does relate to the OHRP, the regulatory
office. If that office wrote a letter to the 1,600 IRBs that we
deal with tomorrow and said, ``We will accept the
recommendation of the central IRB that has been sponsored by
the NCI,'' that would open up the whole deal.
Those three things could really make a huge difference.
Chairman Tom Davis. Thank you very much.
Dr. Pecora, any thoughts?
Dr. Pecora. Yes. It's somewhat repetitious, but for the
Government which funds all of these efforts to take a product
development, like you want to make a product mindset, and look
at all of the issues that we've discussed and see where
Government can intervene in a way that continues to protect
patient safety, continues to protect patient privacy but gets
rid of the bureaucracy and the inefficiencies, centralizing
IRBs, getting rid of the craziness we have with the way we do
adverse event reporting, and there's a list of things that I
don't want to repeat in the interest of time that can and
should be done.
Chairman Tom Davis. Well, let me ask you this. Do you think
that the central IRB that has been developed by the National
Cancer Institute has proven to be effective in eliminating
duplicative applications in the review process?
Dr. Pecora. I think it will. I think it has been and I
think it will, and I think centralization of IRBs in the
country would be wonderful.
Chairman Tom Davis. Well, let me just ask this. In terms of
getting the doctors involved in this, because that's really
your pressure point here--people get diagnosed by their
doctors. What are my options? What's the best way to get that?
Is continuing medical education an option here for oncology?
You do an hour talking about what is involved here, what are
the options, how they can counsel patients? Or is there a
better way to get that word out? Because it seems to me if we
do a better job of that, we're going to have plenty of people
lining up to be part of these trials.
Dr. Pecora. It will only happen if you match that with the
resources they need to do it, and they don't have it right now.
Chairman Tom Davis. OK.
Dr. Comis. But I also think that--you know, I mentioned in
the body of my talk that the Coalition or the Cancer
Cooperative Groups are working closely with ASCO, the American
Society of Clinical Oncology, in education. You know, I think
that we have to--you know, ASCO is perfectly positioned to try
to take the lead in this educational process along with us,
and, in fact, there have been some innovative approaches with
regards to recognition awards at the annual meeting, and also
with we're developing a series of meetings to try to have the
25 or 30 percent of the practices that are really great at this
educate the people who are really interested but can't see a
way how to do it. And over the course of the next 3 years we
hope to have several meetings and a syllabus that arises from
that.
I think we have to focus on the doctors who are interested
in doing this but don't seem to have the wherewithal to do it,
but it can't be done without resources.
Chairman Tom Davis. Ms. Stovall, let me ask you--you
answered that, but also, as you look around and you network
with patients and so on, are we seeing any geographical issues
on this, as well, or any demographic issues in terms of who is
getting notified, who sees the options, and who is lining up?
Ms. Stovall. Well, to answer your last question first, I
really think that if you looked at the map that Michaele
Christian put up originally with all the dots on it about where
places are funded to do the work, there's a big gap right in
the middle of the country where there aren't too many dots, and
this represents a lot of farmland, it represents a lot of rural
America and a lot of poor people.
I want to add on to that the disparity again is created
both in the inconsistency in the way treatment is provided and
offered to patients, but also the health care disparities. The
uninsured and under-insured are terribly disadvantaged by not
having access.
I really think that the point again, building on what Bob
just said about physicians, physician education, training, all
of that is wonderful. If we do not fix the reimbursement system
that's being dismantled with the current MMA, we really are
going to see even more disparity in care than we are seeing
now. And that's not just with clinical research, that's with
all kinds of treatment, because doctors are just going to go
out of business, and it is just a pure and simple fact.
Chairman Tom Davis. And that's a problem----
Ms. Stovall. It's a serious problem.
Chairman Tom Davis [continuing]. Across the medical field.
It's not just here, it's everywhere.
Ms. Stovall. Right.
Chairman Tom Davis. You get the Government buying so much
health care, and that's how we think we save money.
Let me ask you this, too. Has the FDA's accelerated
approval, their expanded access, priority reviews, and fast
track policies--do you think they've approved and shortened the
length of the approval process as a whole? And do patients
receive drugs and therapies more quickly under these policies?
Or do you think it is just a lot of rhetoric?
Ms. Stovall. I have seen improvement, and I think it is
because I know that patient advocates are actually in there and
they are involved and they are constantly putting pressure on,
as well. They have the most to gain or lose from what happens
with new therapies that come through the FDA. So I would say
yes, there has been improvement, and I think particularly under
Dr. McClellan when he was there and Dr. Pazdur specifically we
saw tremendous improvement.
Dr. Comis. I agree with that, and I think that the drugs
that appear active are getting in the hands of the physicians
and patients quicker, and I think that most as importantly, you
know, we're regulated by two bureaucracies, the NCI bureaucracy
and the FDA bureaucracy, and we need to harmonize those things
and, in fact, Rick Pazdur and Michaele and those of us from the
extramural environment are working on trying to do those
things. So it will be very, very important to facilitate this
interaction between the public side and the private side of the
system.
Chairman Tom Davis. Well, let me say to all of you thank
you for, first of all, your testimony. I think it has been
very, very helpful to us. I hope it has been helpful to the
previous panel, as well, as they take notes on this and try to
improve and see what we can do about it. But I also thank you
for what you're doing in the fight against cancer. You are in
the front lines, all of you. You have a little bit different
roles, but what you're doing is very, very important and I want
to thank you for that.
We now adjourn the hearing.
[Whereupon, at 12 noon, the committee was adjourned, to
reconvene at the call of the Chair.]
[Additional information submitted for the hearing record
follows:]
[GRAPHIC] [TIFF OMITTED] T5598.054
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