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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

(II)

COMMITTEE ON GOVERNMENT REFORM

TOM DAVIS, Virginia, Chairman

DAN BURTON, Indiana

CHRISTOPHER SHAYS, Connecticut

ILEANA ROS-LEHTINEN, Florida

JOHN M. MCHUGH, New York

JOHN L. MICA, Florida

MARK E. SOUDER, Indiana

STEVEN C. LATOURETTE, Ohio

DOUG OSE, California

RON LEWIS, Kentucky

JO ANN DAVIS, Virginia

TODD RUSSELL PLATTS, Pennsylvania

CHRIS CANNON, Utah

ADAM H. PUTNAM, Florida

EDWARD L. SCHROCK, Virginia

JOHN J. DUNCAN, JR., Tennessee

NATHAN DEAL, Georgia

CANDICE S. MILLER, Michigan

TIM MURPHY, Pennsylvania

MICHAEL R. TURNER, Ohio

JOHN R. CARTER, Texas

MARSHA BLACKBURN, Tennessee

PATRICK J. TIBERI, Ohio

KATHERINE HARRIS, Florida

HENRY A. WAXMAN, California

TOM LANTOS, California

MAJOR R. OWENS, New York

EDOLPHUS TOWNS, New York

PAUL E. KANJORSKI, Pennsylvania

CAROLYN B. MALONEY, New York

ELIJAH E. CUMMINGS, Maryland

DENNIS J. KUCINICH, Ohio

DANNY K. DAVIS, Illinois

JOHN F. TIERNEY, Massachusetts

WM. LACY CLAY, Missouri

DIANE E. WATSON, California

STEPHEN F. LYNCH, Massachusetts

CHRIS VAN HOLLEN, Maryland

LINDA T. SANCHEZ, California

C.A. ‘‘DUTCH’’ RUPPERSBERGER, Maryland

ELEANOR HOLMES NORTON, District of

Columbia

JIM COOPER, Tennessee

——— ———

———

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

(III)

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

(1)

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.

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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.

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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 manVerDate 11-MAY-2000 11:34 Sep 21, 2004 Jkt 000000 PO 00000 Frm 00010 Fmt 6633 Sfmt 6633 D:\DOCS\95598.TXT HGOVREF1 PsN: HGOVREF1
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dated 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

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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 wantVerDate 11-MAY-2000 11:34 Sep 21, 2004 Jkt 000000 PO 00000 Frm 00017 Fmt 6633 Sfmt 6633 D:\DOCS\95598.TXT HGOVREF1 PsN: HGOVREF1
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ed 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.

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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.

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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?

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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 lifethreatening disease and illness and their providers can use to see

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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.

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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

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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 fullfledged 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.

69

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

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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.

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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

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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 developVerDate 11-MAY-2000 11:34 Sep 21, 2004 Jkt 000000 PO 00000 Frm 00076 Fmt 6633 Sfmt 6633 D:\DOCS\95598.TXT HGOVREF1 PsN: HGOVREF1
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ment, 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.

74

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 distinVerDate 11-MAY-2000 11:34 Sep 21, 2004 Jkt 000000 PO 00000 Frm 00078 Fmt 6633 Sfmt 6633 D:\DOCS\95598.TXT HGOVREF1 PsN: HGOVREF1
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guished 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

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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

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conceptions, 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 com- munity-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

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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, trials, and

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multiple myeloma advocates’ involvement more recently with trials

for Velcade. 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 highquality 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

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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

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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 manVerDate 11-MAY-2000 11:34 Sep 21, 2004 Jkt 000000 PO 00000 Frm 00109 Fmt 6633 Sfmt 6633 D:\DOCS\95598.TXT HGOVREF1 PsN: HGOVREF1
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agers, 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 nonlegislative 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

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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.

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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.

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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?

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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.

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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

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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:]

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