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SECURING THE HEALTH OF THE AMERICAN

PEOPLE

HEARING

BEFORE THE

SUBCOMMITTEE ON

HEALTH AND ENVIRONMENT

OF THE

COMMITTEE ON COMMERCE

HOUSE OF REPRESENTATIVES

ONE HUNDRED SIXTH CONGRESS

SECOND SESSION

SEPTEMBER 13, 2000

Serial No. 106–163

Printed for the use of the Committee on Commerce

(

COMMITTEE ON COMMERCE

TOM BLILEY, Virginia, Chairman

W.J. ‘‘BILLY’’ TAUZIN, Louisiana

MICHAEL G. OXLEY, Ohio

MICHAEL BILIRAKIS, Florida

JOE BARTON, Texas

FRED UPTON, Michigan

CLIFF STEARNS, Florida

PAUL E. GILLMOR, Ohio

Vice Chairman

JAMES C. GREENWOOD, Pennsylvania

CHRISTOPHER COX, California

NATHAN DEAL, Georgia

STEVE LARGENT, Oklahoma

RICHARD BURR, North Carolina

BRIAN P. BILBRAY, California

ED WHITFIELD, Kentucky

GREG GANSKE, Iowa

CHARLIE NORWOOD, Georgia

TOM A. COBURN, Oklahoma

RICK LAZIO, New York

BARBARA CUBIN, Wyoming

JAMES E. ROGAN, California

JOHN SHIMKUS, Illinois

HEATHER WILSON, New Mexico

JOHN B. SHADEGG, Arizona

CHARLES W. ‘‘CHIP’’ PICKERING,

Mississippi

VITO FOSSELLA, New York

ROY BLUNT, Missouri

ED BRYANT, Tennessee

ROBERT L. EHRLICH, Jr., Maryland

JOHN D. DINGELL, Michigan

HENRY A. WAXMAN, California

EDWARD J. MARKEY, Massachusetts

RALPH M. HALL, Texas

RICK BOUCHER, Virginia

EDOLPHUS TOWNS, New York

FRANK PALLONE, Jr., New Jersey

SHERROD BROWN, Ohio

BART GORDON, Tennessee

PETER DEUTSCH, Florida

BOBBY L. RUSH, Illinois

ANNA G. ESHOO, California

RON KLINK, Pennsylvania

BART STUPAK, Michigan

ELIOT L. ENGEL, New York

TOM SAWYER, Ohio

ALBERT R. WYNN, Maryland

GENE GREEN, Texas

KAREN MCCARTHY, Missouri

TED STRICKLAND, Ohio

DIANA DEGETTE, Colorado

THOMAS M. BARRETT, Wisconsin

BILL LUTHER, Minnesota

LOIS CAPPS, California

JAMES E. DERDERIAN, Chief of Staff

JAMES D. BARNETTE, General Counsel

REID P.F. STUNTZ, Minority Staff Director and Chief Counsel

SUBCOMMITTEE ON HEALTH AND ENVIRONMENT

MICHAEL BILIRAKIS, Florida, Chairman

FRED UPTON, Michigan

CLIFF STEARNS, Florida

JAMES C. GREENWOOD, Pennsylvania

NATHAN DEAL, Georgia

RICHARD BURR, North Carolina

BRIAN P. BILBRAY, California

ED WHITFIELD, Kentucky

GREG GANSKE, Iowa

CHARLIE NORWOOD, Georgia

TOM A. COBURN, Oklahoma

Vice Chairman

RICK LAZIO, New York

BARBARA CUBIN, Wyoming

JOHN B. SHADEGG, Arizona

CHARLES W. ‘‘CHIP’’ PICKERING,

Mississippi

ED BRYANT, Tennessee

TOM BLILEY, Virginia,

(Ex Officio)

SHERROD BROWN, Ohio

HENRY A. WAXMAN, California

FRANK PALLONE, Jr., New Jersey

PETER DEUTSCH, Florida

BART STUPAK, Michigan

GENE GREEN, Texas

TED STRICKLAND, Ohio

DIANA DEGETTE, Colorado

THOMAS M. BARRETT, Wisconsin

LOIS CAPPS, California

RALPH M. HALL, Texas

EDOLPHUS TOWNS, New York

ANNA G. ESHOO, California

JOHN D. DINGELL, Michigan,

(Ex Officio)

(II)

2

C O N T E N T S

Page

Testimony of:

Bennett, Catherine P., Chair, Board of Directors, Cancer Research Foundation of America .......................................................................................... 117

Brady, Robert, Partner, Hogan & Hartson, on behalf of Biogen, Inc ........... 106

Bryan, R. Nick, Professor and Chairman of Radiology, Hospital of University of Pennsylvania ...................................................................................... 87

Burton, Hon. Dan, a Representative in Congress from the State of Indiana .................................................................................................................. 101

Dunnick, N. Reed, Professor and Chair, Department of Radiology, University of Michigan Health System .................................................................. 77

Fraser, Tomiko, National Spokesperson, Lupus Foundation of America,

Inc .................................................................................................................. 84

Gekas, Hon. George W., a Representative in Congress from the State

of Pennsylvania ............................................................................................. 70

Hillman, Bruce J., Professor and Chair, Department of Radiology, University of Virginia .............................................................................................. 80

Lang, Thomas A., Senior Vice President, Strategic Product Development,

Serono Laboratories, Inc .............................................................................. 112

Meek, Hon. Carrie P., a Representative in Congress from the State of

Florida ............................................................................................................ 72

Meyers, Abbey, President, National Organization for Rare Disorders ........ 110

Navarro, James, father of Thomas Navarro ................................................... 103

Wirth, Dyann, Professor, Department of Immunology and Infectious Diseases, Harvard School of Public Health ...................................................... 73

Material submitted for the record by:

Brady, Robert, Partner, Hogan & Hartson, Counsel to Biogen, Inc., letter

dated September 21, 2000, enclosing material for the record ................... 138

Bryan, R. Nick, Professor and Chairman of Radiology, Hospital of University of Pennsylvania, letter dated November 20, 2000, enclosing response for the record ..................................................................................... 136

Department of Health and Human Services, additional testimony for

the record ....................................................................................................... 125

Fraser, Tomiko, National Spokesperson, Lupus Foundation of America,

Inc., responses for the record ....................................................................... 127

Hillman, Bruce J., Professor and Chair, Department of Radiology, University of Virginia, responses for the record .................................................... 134

Meyers, Abbey, President, National Organization for Rare Disorders, responses for the record ................................................................................... 131

Navarro, James, responses for the record ...................................................... 128

(III)

(1)

SECURING THE HEALTH OF THE AMERICAN

PEOPLE

WEDNESDAY, SEPTEMBER 13, 2000

HOUSE OF REPRESENTATIVES,

COMMITTEE ON COMMERCE,

SUBCOMMITTEE ON HEALTH AND ENVIRONMENT,

Washington, DC.

The subcommittee met, pursuant to notice, at 10:10 a.m., in room

2123, Rayburn House Office Building, Hon. Michael Bilirakis

(chairman) presiding.

Members present: Representatives Bilirakis, Upton, Stearns,

Burr, Ganske, Cubin, Bryant, Brown, Waxman, Pallone, Stupak,

Green, Barrett and Capps.

Staff present: Marc Wheat, majority counsel; Nandan

Kenkeremath, majority counsel; Kristi Gillis, legislative clerk; and

John Ford, minority counsel.

Mr. BILIRAKIS. The hearing will come to order. My thanks to all

of the witnesses who have taken the time to testify before this subcommittee. This hearing will address, as you know, several pieces

of legislation designed to improve the quality of health care.

Today we will hear about H.R. 2399, the National Commission

for the New National Goal: The Advancement of Global Health Act.

This legislation introduced by my friend, Representative George

Gekas of Pennsylvania, would establish a commission to recommend a national strategy to coordinate public and private sector

efforts toward the global eradication of disease. The Commission

would specifically address how the United States may assist in the

global control of infectious diseases through the development of

vaccines and the sharing of health research information on the

Internet.

Also on the first panel we will hear testimony on H.R. 1795, the

National Institute of Biomedical Imaging and Engineering Establishment Act. This legislation introduced by Representatives Richard Burr and Anna Eshoo, members of this panel, would establish

a National Institute of Biomedical Imaging and Engineering at the

National Institutes of Health.

Finally, our first panel will address legislation introduced my

Representative Carrie Meek, H.R. 762, the lupus research and care

amendments of 1999, which expands immediate lupus research activities and authorizes the Secretary of Health and Human Services to make grants for the delivery of essential services to individuals with lupus and their families. Congresswoman Meek has been

a tireless proponent of this legislation, and I would also be remiss

2

if I failed to mention the advocacy efforts of Sandy Freer from my

area of Florida.

I discussed this legislation at the full committee markup of the

minority health disparities bill, and I look forward not only to the

testimony today, but to advancing this very important legislation.

Our second panel will include testimony on H.R. 4242, the Orphan Drug Innovation Act. This bill amends the Federal Food,

Drug and Cosmetic Act to allow sponsors for a drug for a rare disease or condition, so-called orphan drugs, to ask the Secretary of

Health and Human Services to provide written recommendations

for the nonclinical and clinical investigations which must be conducted with a drug before it may be approved as a new drug or licensed as a biological product. It also authorizes the Secretary to

provide recommendations on whether such a drug is for a disease

or condition which is rare in the United States.

I would also like to welcome Mr. Jim Navarro, a concerned parent, to our second panel. He will be discussing H.R. 3677, the

Thomas Navarro FDA Patient Rights Act. This bill is named after

his son, who was 4 years old when he was diagnosed with a form

of cancer known as medulloblastoma. After researching their options, the family decided that the best course of action was through

a nontoxic FDA-approved clinical trial. The FDA denied Thomas

access to this clinical trial because he had not first undergone and

failed treatment by chemotherapy and radiation, which can have,

as we all realize, I think, serious side effects for children of that

age.

H.R. 3677 precludes the FDA from establishing a clinical hold on

the basis that there is a comparable or satisfactory alternative

therapy available if a patient is aware of the other therapy and

aware of the risk associated with the investigational drug, yet still

chooses to receive the treatment.

Finally, in honor of Childhood Cancer Month, we will hear testimony in support of a resolution sponsored by Representative Deborah Pryce on the importance of researching childhood cancer. I

think all of us remember that Representative Pryce lost their little

daughter a few months ago. The testimony and the resolution focus

on the importance of promoting awareness of and expanding research on childhood cancers. The resolution would encourage medical trainees to enter the field of pediatric oncology, encourage the

development of drugs and biologicals to treat pediatric cancers, and

promote medical curricula to improve pain management. The resolution would also support policies that reduce barriers to participation in clinical trials.

I welcome all of our witnesses, including our colleagues, to this

hearing. And to cover as much ground as possible, I would ask

members to limit their opening statements. Under the rules, I can

limit opening statements other than chairman and ranking member to 3 minutes, and I would appreciate it if you would hold them

to within that period of time.

And I would also note that some Members of Congress who are

not members of the subcommittee will also give brief introductory

remarks regarding their legislation and introduce their witnesses.

And I just hope that this hearing will shed light on a number of

3

important public health issues and that we can devote most of the

time to our witnesses.

With that I yield to the ranking member, Mr. Brown.

Mr. BROWN. Thank you, Mr. Chairman. I would like to welcome

our witnesses also. Thank you for joining us. We have an ambitious

agenda this morning. Among the six bills, we will consider two that

would affect access to medications, H.R. 4242 and H.R. 3677.

In the case of both bills, it is likely that today’s hearing will not

produce definitive answers. The issues involved are simply too complex and the implications of any actions we take too significant.

However the questions these bills seek to answer, the concerns

they seek to address are important, and it is valuable for the subcommittee to learn about them.

I am also glad we will have an opportunity to review legislation

focussing on lupus and childhood cancers. Both types of illnesses

devastate and too often take young lives, and neither has received

the attention that they both deserve.

But in the interest of time, I want to focus my comments on two

of the other bills we will consider this morning, H.R. 2399 and H.R.

1795. I fully support the efforts of my colleague Mr. Gekas to establish the improvement of global health as a national priority, because global health should be a national priority for several reasons.

Global health and the health of Americans are linked. Americans

travel abroad, the world travels here. Lethal infectious diseases

cross borders. The reemergence of tuberculosis in the United States

now in drug-resistant strains that are difficult to treat is a grim

reminder that when a disease affects other nations, it is bound to

affect us. Tuberculosis last year killed more people than in any

year in history; 1,100 Indians die every day from tuberculosis.

A second reason that global health should be a national priority

is because the United States is a world leader. We are the wealthiest Nation in the world, we are the most influential force in the

world. Our action sets a precedent; our inaction sets a precedent.

The United States is in a unique position to save lives, to save families, to save children all over the world.

An investment that is modest by U.S. standards literally can

save millions of lives, prevent millions of children from being orphaned, prevent the social, economic and political turmoil these

killer diseases too often engender. It is an opportunity and it is a

privilege that our Nation should embrace.

The other bill I want to mention briefly is H.R. 1795, which

would establish an Institute for Biomedical Imaging and Engineering within the National Institutes of Health. Unfortunately, my colleague Mrs. Eshoo couldn’t be here this morning, but I wanted to

acknowledge her outstanding leadership and the leadership of Mr.

Burr on this measure. I extend a special welcome to Dr. Dunnick

from the University of Michigan who is joining us to discuss 1794

at Mrs. Eshoo’s request. Adding an institute to NIH is a major

step, but Mrs. Eshoo and Mr. Burr make a compelling case for it.

Advancements in medical imaging technology have led to stunning breakthroughs in the early detection and the treatment of

many diseases. By identifying these diseases early, and without

invasive procedures, patients are often able to receive less painful,

4

more therapeutic treatments that greatly improve the likelihood

that they will live longer and healthier lives. Additionally, when

treatment is initiated at the early stage of a disease, doctors are

able to rely on less expensive treatment options that reduce overall

health care costs.

I am glad we are taking time to access the benefit of establishing

an institute dedicated to equipment and techniques that are indispensable to modern health care. I thank the chairman.

Mr. BILIRAKIS. I thank the gentleman.

Mr. Upton.

Mr. UPTON. Thank you, Mr. Chairman. I ask unanimous consent

to put my full statement in the record.

Mr. BILIRAKIS. Without objection, the opening statement of all

members of the subcommittee will be made a part of the record.

Mr. UPTON. I would just like to say one thing verbally here. I am

very glad that we are having these hearings, and I am particularly

happy that we are focusing on H.R. 672, the Lupus Research and

Care Amendments Act. Sadly, my sister-in-law suffered from this

disease and died last year from this illness, so I know how important that it is to commit ourselves to finding a cure for this devastating disease.

I commend my colleague from Florida for offering her bill, and

I am delighted to be a cosponsor, and I yield back.

Mr. BILIRAKIS. Mr. Waxman for an opening statement.

Mr. WAXMAN. Thank you, Mr. Chairman.

Let me begin by saying how pleased I am that H.R. 762, the

Lupus Research and Care Act, is receiving our attention. It is an

excellent bill and deserves our support. Lupus is also one of the

dozens of autoimmune diseases which are the subject of my own

bill to establish an Office of Autoimmune Diseases at NIH, which

has already passed this committee and the House.

But today I am principally concerned about H.R. 4242, the Orphan Drug Innovation Act. As the author with Senator Metzenbaum of the Orphan Drug Act, I care deeply about the issues

raised by this legislation.

For many years I have been very gratified by the success of the

Orphan Drug Act in stimulating the development of new treatments for rare diseases. I am pleased that we will have Abbey

Meyers testify again before our subcommittee on this, and that she

is willing to come.

Market exclusivity is the foundation of the Orphan Drug Act. But

we created exceptions to that exclusivity in the law. The bill before

us would limit the scope of exclusivity granted to drugs proven,

‘‘clinically superior,’’ to an existing orphan drug; that is, drugs

which are safer, more effective or provide a major contribution to

patient care. It has been alleged that the bill is intended to anoint

a winner in a commercial dispute, but the bill raises an important

and legitimate question: What is the right balance between preserving exclusivity, encouraging competition, and encouraging affordable access to these lifesaving drugs?

As a first step to the best answer, I was looking forward with

great interest to the FDA’s public clarification of its policy toward

clinical superiority. There are questions about its consistency and

its relationship to a generic approval process for biotech drugs.

5

This subcommittee requires some clear answers. They have significant implications for patient health and for access to reasonably

priced breakthrough drugs. But this morning I learned that the

FDA has withdrawn its witness and testimony. While this may be

the result of late notice to the administration, it nevertheless ensures today’s hearing will be of less assistance in guiding our deliberations.

I would add that orphan drug policy deserves a hearing on its

own. There are 25 million Americans suffering from over 6,000 rare

diseases. There is a great deal of unfinished business for Congress.

There is the question of how high a bar clinical superiority should

be. There are some multimillion-dollar orphan drugs, drugs for

which 7 years of exclusivity is unjustified and serves only to boost

prices and profits, putting those lifesaving therapies out of the

reach of many patients. And just as important, there is the urgent

need for more orphan disease research at NIH and FDA.

I sincerely hope that we will have an opportunity early next year

to examine these issues in greater detail than will be possible

today.

Finally, Mr. Chairman, I would like to submit for the record a

series of articles and scientific reviews relating to the alternative

cancer treatment offered by Dr. Stanislav Burzynski, the intended

beneficiary of H.R. 3677, the Thomas Navarro Patient Rights Act.

Mr. BILIRAKIS. Without objection, that will be the case.

[The information referred to follows:]

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Mr. WAXMAN. As ranking member of the Committee on Government Reform, I have attended that committee’s many hearings to

defend and endorse alternative medicine and dietary supplements.

But I am pleased that this subcommittee, which has jurisdiction

over these issues, has finally turned its attention to them.

Developing new forms of cancer prevention, detection, and treatment never ends. Ensuring patients have access and accurate information about their treatments is also vital. So we must keep an

open mind about innovative or unconventional approaches to cancer treatment and prevention.

But our first priority must be ensuring access to treatments

which are proven to be the best chances of curing patients. And

second, our priority must be rigorous testing of new therapies, including complementary and alternative therapies, to determine

their safety and efficacy.

The problem with H.R. 3677 is that it undercuts these goals. If

research is under a clinical hold, you can be sure that there are unresolved questions about the conduct of that research. But this bill

would shield such research from scrutiny, discourage practitioners

from cooperating in rigorous research, and lessen our chances of

ever knowing for sure whether an alternative treatment actually

works or not.

And at a time when research and patients alike complain that

IRBs are overburdened and informed consent is not always truly

informed, this bill would increase the chances that patients are put

at inappropriate risk, not lessen them.

I join my colleagues in welcoming our witnesses, and I look forward to their testimony.

Mr. BILIRAKIS. I thank the gentleman.

Mr. Burr to give an opening statement.

Mr. BURR. I thank the chairman, and I thank the chairman for

this hearing. Mr. Chairman, we have a lot on our plate this morning, and it is all extremely important. I will focus just briefly on

the NIBIEE bill which Ms. Eshoo and I have introduced, which

currently has 169 cosponsors. It is unfortunate today as we meet

this morning that Ms. Eshoo is in California under the weather,

but I am sure if she were here, she would speak out very loudly

in support of this legislation that she and I and others on the Hill

and throughout the country have worked on.

I don’t think I can sum it up any better than the committee brief

for this hearing. In their description of the NIBIEE bill it said:

Breakthroughs in imaging such as magnetic resonance imaging

and computer tomography have revolutionized the practice of medicine in the past quarter century. But those technologies are inadequate in diagnosing some diseases.

What that statement says is that we have made tremendous

progress, despite a lack of a focused effort, on our ability to detect

at the early possible point. What we have heard, Mr. Chairman,

from people around the country is that we can do better. If you give

us the type of focus that it takes in resources, we can come through

with an earlier detection of disease, and we can give physicians

who are treating disease many more options because of that early

detection.

65

What NIBIEE does is create an institute of health for biomedical

imaging at the NIH, the same NIH that every member of this

panel and most Members of this Congress are committed to putting

new resources into. What we want to make sure when we make

that commitment to the American people for additional resources

to chase the disease that affects every family in this country, is

that biomedical imaging is one of the concentrated focuses of the

NIH because we know that early detection will give us more options and will give patients more options.

Mr. Chairman, I would urge my colleagues today to ask as many

questions of the witnesses that are here to testify on this bill, but,

in the end, to also be supportive of this legislation. This is extremely important that we get it done and we get it done now. We

spend a lot of time talking about health care policy. This is a place

where we can, in fact, make sure that our options are greater down

the road. And I applaud the chairman. And I yield back.

Mr. BILIRAKIS. I thank the gentleman.

Mr. Pallone for an opening statement, going on basis of seniority.

Mr. PALLONE. Thank you, Mr. Chairman. I will limit my comments to the two bills which have I cosponsored, H.R. 3677, the

Thomas Navarro FDA Patient Rights Act, and the H.R. 1795, National Institute of Biomedical Imaging and Engineering Establishment Act.

The first of these, the Thomas Navarro FDA Patient Rights Act,

deals with the rights of patients and parents to make informed

choices about medical treatment. The bill’s namesake, young Thomas Navarro, has unfortunately been suffering from the effects of a

brain tumor. As any parent with a child in Thomas’s situation

would, the Navarros researched the treatment options available

and found the treatment of radiation and chemotherapy would

have extremely debilitating side effects which they did not want to

risk. Rather, the Navarros preferred to have Thomas treated with

antineoplaston therapy, a therapy surrounded by some controversy

that is under clinical trial. The Food and Drug Administration has,

however, refused to allow this to happen on the basis that his parents have not yet tried the radiation and chemotherapy path.

I cosponsored the bill because Thomas Navarro’s parents should

be allowed to decide for themselves whether or not the

antineoplaston treatment for Thomas in the setting of a clinical

trial is an appropriate path to follow. They researched the issue,

and they understand the issue, and I do not believe in light of the

circumstances surrounding the case that the Navarros should be

denied their right to choose.

The issue is important not just for Thomas, t for other patients

in similar circumstances. We shouldn’t be restricting the rational

choices and measured choices of individuals who choose to pursue

alternative medical treatments whose possible outcomes they fully

comprehend.

The second bill I want to mention, the National Institute of Biomedical Imaging and Engineering Establishment Act, is an excellent piece of legislation that I hope all of my colleagues on this subcommittee will support. I have discussed the importance of this legislation on a number of occasions over the last 2 years with medical

professionals from the radiology department of the University of

66

Medicine and Dentistry of New Jersey and other medical professionals from my home State. All of them have stressed the importance an institute for imaging research within NIH can play in promoting further breakthroughs in a field that has already vastly

changed the practice of medicine for the better.

And I want to thank the chairman for having the hearing on

these two bills and the other that we have today. I yield back.

Mr. BILIRAKIS. Mr. Stupak for an opening statement. I am going

to try to continue on rather than break, as long as someone gets

back in time to spell me.

Mr. STUPAK. Mr. Chairman, I thank you for holding this hearing,

and I thank the witnesses for being here. I look forward to their

testimony.

I am a cosponsor of H.R. 762 and H.R. 1795, and for the sake

of time, and I want to hear the witnesses, I yield back the balance

of my time.

Mr. BILIRAKIS. I thank the gentleman so very much.

Mrs. Capps for an opening statement.

Mrs. CAPPS. Mr. Chairman, I thank you for holding this hearing,

and I want to thank—extend a welcome to our witnesses. Today we

are going to be discussing several worthy pieces of legislation all

focused on securing the health of the American people.

Because of the nature of our hearing today, I want to remind you

and other members of the bill H.R. 353, the ALS Treatment and

Assistance Act. This is a bill that I am offering, enjoying bipartisan

support; currently has 280 cosponsors, many of whom serve on this

committee. I am so glad that we are having a hearing today on so

many important pieces of legislation. I commend you for making

that happen, and my hope is that this committee can address H.R.

353 before the 106th Congress is over.

I want to state my strong support in this setting for H.R. 762,

the lupus research and care amendments of 1999. I am so pleased

that our colleague Carrie Meek is here, the author of this bill,

which would authorize the Secretary of Health and Human Services to make grants for the delivery of essential services to individuals with lupus and their families. As a nurse, I know what an insidious disease this is. For many people lupus is a mild disease affecting only a few organs; for others can cause serious, even lifethreatening problems.

My district is home to the Scleroderma Research Foundation.

Scleroderma is a condition that is closely linked to lupus, and I

have seen the work of women like Sharon Monsky in Santa Barbara in my district, who has fought so long to raise awareness of

scleroderma and lupus, diseases which disproportionately affect

women and can have life-and-death consequences. So I applaud the

subcommittee for recognizing this legislation.

I also want to acknowledge the legislation sponsored by my colleague Anna Eshoo which was described by our colleague Richard

Burr, H.R. 1795. This legislation will fill a critical void at the NIH

by creating an independent institute on this topic of bioengineering. These disciplines have made such contributions to the

improvement, as our colleague has said, and have no research

home in the current structure of NIH. And I support this legislaVerDate 11-MAY-2000 09:33 Oct 24, 2001 Jkt 010199 PO 00000 Frm 00070 Fmt 6633 Sfmt 6633 E:\HEARINGS\67114 txed01 PsN: txed01
67

tion, again commending our colleagues for their leadership in this

area.

Finally, I know my statement submitted will be longer than this,

but I want to say one word about my good friend and colleague

Deborah Pryce and offer my strongest words of support for her resolution. Her resolution focuses on the importance of promoting

awareness and expanding research on childhood cancer. This is

Childhood Cancer Month, September. It is the second leading cause

of death in children past infancy. Many childhood cancers can be

cured, but, sadly, dozens still cannot. And I applaud Congresswoman Pryce’s efforts in this difficult area and pledge any support

that I can give to help get this legislation passed into law.

Mr. Chairman, this is an important topic. Thank you for holding

this hearing, and I yield back.

Mr. BILIRAKIS. I thank the gentlewoman.

[Additional statements submitted for the record follow:]

PREPARED STATEMENT OF HON. BARBARA CUBIN, A REPRESENTATIVE IN CONGRESS

FROM THE STATE OF WYOMING

Our individual health care needs have changed over the years, but the bottom line

is we all need care—and we want it to be the best.

That’s all the reason we need to make sure we keep moving forward with innovative technologies, new drug therapies, and better standards of care.

We must continue to protect and nurture the different fields of research and development in health care because we live in an unpredictable and sometimes hostile

bacterial environment that is constantly reinventing itself.

That means that clinical trials will take on an even greater role in the future as

we try to develop new drugs to counteract new diseases.

Giving patients the proper access to these trials is therefore paramount to our success. Of course, these trials are not possible without the new drug therapies and

biologicals that sustain them so supporting drug research and innovation is critical.

By the same token, we’re making technological advances that we never thought

possible—such as MRIs, Cat Scans, laser devices, telemedicine, and the like.

We must continue to push the envelope in the field of health care technology because it has already proven to enhance the quality of patient care.

There are, no doubt, countless things we have yet to discover about biomedical

imaging and we should continue to explore its capabilities.

Today we’re discussing specific legislative proposals that are designed to secure

the future health of this country. I look forward to the discussion and stand ready

to work with all of you.

PREPARED STATEMENT OF HON. TOM BLILEY, CHAIRMAN, COMMITTEE ON COMMERCE

Thank you Mr. Chairman.

I am pleased that you are having this hearing today which continues the extraordinary public health work that Members of the Commerce Committee have done

over the past six years.

I would like to take a moment of personal privilege to state how proud the Members of the Committee should be. In the prior two Congresses, this Committee has

empowered states and localities to meet the health care and nutritional needs of

low-income residents; and provided relief to those hardest hit by the AIDS epidemic.

The Health Insurance Portability and Accountability Act allows working Americans to change jobs without risking the loss of their health care insurance due to

a preexisting condition. The law also attacked health care fraud and eliminated tax

code discrimination against millions of small businesses and the self-employed. It

also provided tax relief for long-term health care needs and terminally ill patients

and their families.

The Food Quality Protection Act and the Safe Drinking Water Act Amendments

of 1996 modernized programs and enhanced Americans’ access to safe, abundant,

and affordable food and water.

We established Medicare+Choice and the State Children’s Health Insurance Program. Among other bills, we enacted the Food and Drug Administration ModernizaVerDate 11-MAY-2000 09:33 Oct 24, 2001 Jkt 010199 PO 00000 Frm 00071 Fmt 6633 Sfmt 6621 E:\HEARINGS\67114 txed01 PsN: txed01
68

tion Act; the Birth Defects Prevention Act; the National Bone Marrow Registry Reauthorization Act; the Mammography Quality Standards Reauthorization Act; the

Women’s Health Research and Prevention Amendments.

This Congress, we have passed prescription drug legislation and HMO reform. We

reauthorized funding to help those suffering from AIDS and moved forward on a

major children’s health initiative. We also have moved on the Breast and Cervical

Cancer Treatment Act, the Health Care Fairness Act, the Cardiac Arrest Survival

Act, the Developmental Disabilities Amendments, The Drug Addiction Treatment

Act, the Date-Rape Prevention Drug Act, the Health Research and Quality Act, the

Pain Relief Promotion Act, the Organ Procurement and Transplantation Network

Amendments, and the Nursing Home Resident Protection Amendments. We have

also provided new options under Social Security for the disabled.

It is a spectacular record.

Now for the work before us today. I look forward to hearing from today’s witnesses and to making even further progress on public health with the Members of

this Committee. Today we will discuss global health concerns, new medical technologies, drug approval systems, expanding access to clinical trials, Lupus, and

childhood cancers. Some of these efforts may go forward this Congress and others

may not. I only ask the Members of the Committee to maintain their workman-like

commitment to bipartisan improvements to our public health programs.

PREPARED STATEMENT OF HON. GENE GREEN, A REPRESENTATIVE IN CONGRESS FROM

THE STATE OF TEXAS

Mr. Chairman, thank you for calling this hearing today. I appreciate the opportunity to examine legislation that has been introduced to improve America’s health

care programs.

There are several bills being discussed today, two of which I am a cosponsor of,

the Lupus Research and Care Amendments of 1999 and the National Institute of

Biomedical Imaging and Engineering Establishment Act.

H.R. 762 by Rep. Carrie Meek is a bill that would expand and intensify research

at the NIH to diagnose, treat, and eventually cure lupus. It also increases the funding for lupus research and education and establishes a grant program to expand

availability of lupus services.

I commend my colleague for introducing this bill and look forward to the testimony on this piece of legislation.

I am also a cosponsor of H.R. 1795 by Rep. Richard Burr. This legislation would

create an independent institute to support basic research in medical imaging and

bioengineering. These disciplines have made great contributions to the improvement

of medical care in the past two decades, yet they have no research home in the current NIH structure. The creation of the National Institute of Biomedical Imaging

and Engineering would create a research environment in which new imaging and

bioengineering technologies techniques and devices can be developed for clinical use

more rapidly than under the present system. This would allow for continued rapid

progress in fields such as genetics and molecular biology, which utilize advanced imaging techniques.

I represent the medical center area and I can tell you that this piece of legislation

would help advance the technology that can be used for clinical use more rapidly

than under the present system.

I look forward from hearing from our witnesses today.

PREPARED STATEMENT OF HON. ANNA G. ESHOO, A REPRESENTATIVE IN CONGRESS

FROM THE STATE OF CALIFORNIA

Thank you, Mr. Chairman, for holding today’s hearing. With six bills before us

today, we have a lot on our plates. However, I’d like to focus my comments on the

bill that my colleague Mr. Burr and I have introduced, H.R. 1795 to establish a National Institute of Biomedical Imaging and Engineering at the National Institutes

of Health (NIH).

Mr. Chairman, dramatic advances in imaging and bioengineering have revolutionized medical practice in recent years. Development of new, noninvasive imaging

techniques, such as Magnetic Resonance Imaging (MRI) and Computed Tomography

(CT), has allowed for earlier detection and diagnosis of disease, dramatically improving the quality of healthcare. But, the next generation of breakthroughs will be

longer in coming, or in some fields, may not come at all unless we modernize the

structure at NIH.

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Today, these disciplines, which have made unmatched contributions to the improvement of medical care in the past two decades, have no research home in the

current NIH structure. Research at the current institutes at NIH is based on molecular biology, which is fundamentally different from research in imaging and bioengineering. If we are to ensure the continued development of new techniques and

technologies, these disciplines require an identity and research home at the NIH

that is independent of the existing institute structure.

H.R. 1795 would fill a critical void at the NIH by creating an independent institute to support basic research in medical imaging and bioengineering. It would create a research environment in which new imaging and bioengineering technologies,

techniques, and devices can be developed for clinical use much more rapidly than

under the present system. By doing so, H.R. 1795 replaces disorganization with efficiency, effective management, accountability, and an improved scientific focus.

At a time when Congress has committed to doubling the NIH budget, we must

ensure that research dollars are expended more effectively and efficiently and that

the fields of medical science that have contributed the most to the detection, diagnosis, and treatment of disease in recent years receive appropriate emphasis. Establishment of a National Institute of Biomedical Imaging and Engineering at the NIH

would accelerate the development of new technologies, improve coordination and efficiency throughout the Federal government, reduce duplication, lay the foundation

for a new medical information age, and provide a structure to train the young researchers who will make the pathbreaking discoveries of the next century.

I’m proud to join Representative Burr in sponsoring H.R. 1795 and I’m pleased

that the Committee has finally turned its attention to it. I encourage my colleagues’

support at tomorrow’s full committee markup and I look forward to passage by the

full House.

PREPARED STATEMENT OF HON. JOHN D. DINGELL, A REPRESENTATIVE IN CONGRESS

FROM THE STATE OF MICHIGAN

Mr. Chairman, we have six bills and resolutions before us today, so I will be brief.

H.R. 2399 would establish a national commission to examine how the United

States can most effectively use our scientific and technical expertise to tackle disease on a global basis. This is an ambitious undertaking. A panoply of public and

private sector organizations spend considerable time and resources on projects that

collectively span virtually all global health issues. Nevertheless, the commission

could generate useful information, which in turn could optimize the use of scarce

resources and which could lead to improvements in global health.

H.R. 762, the Lupus Research and Care Amendments, is an excellent piece of legislation that has been developed by my good friend and colleague, Representative

Carrie Meek. As we will learn, lupus is a debilitating and sometimes fatal autoimmune disease that disproportionately afflicts women, particularly women of color.

H.Res. 576 by Representative Pryce is another measure worthy of our support.

Children are not simply ‘‘little adults.’’ I note that our colleague, Representative

Forbes, has a similar bill, H. Con. Res. 115.

H.R. 1795 would create the Institute of Biomedical Engineering at the National

Institutes of Health (NIH). I note the fine work that our colleagues, Representatives

Eshoo and Burr, have done on this bill and believe that it deserves our careful consideration, although NIH has some concerns with the bill.

H.R. 3677 causes me great concern, and I can not support it as drafted. This bill

would dramatically alter the basic role of the Food and Drug Administration (FDA)

in the supervision of human subject protection in the development of experimental

drugs. FDA must play a fundamental role in protecting the public in both the development and approval of drugs. The FDA Modernization Act, which has provisions

on this matter, is less than three years old, but we should examine the investigational drug process to ensure that it is serving the public in the best possible manner. The moral, ethical, and safety issues presented in the informed consent process

are particularly important in the case of experimental drugs and their use on persons with serious and life threatening diseases.

Finally, I oppose H.R. 4242, the Orphan Drug Innovation Act. We will hear testimony opposing this bill from the National Organization for Rare Disorders (NORD).

NORD represents approximately 25 million Americans with more than 6,000 ‘‘or- phan’’ diseases. The orphan drug law has been a success. Anyone wishing to enact

significant changes in this important health statute bears a heavy burden. I do not

believe the proponents of this bill have met that test.

Thank you, Mr. Chairman.

70

Mr. BILIRAKIS. Mr. Gekas and Mrs. Meek are here to testify on

behalf of their legislation briefly and also introduce the witnesses.

What is your pleasure? Should we go to you now, or would you like

to return? I don’t want to really rush you, but we do want to make

this vote. Would like to return? I will be here.

Mrs. MEEK. With your pleasure and Mr. Gekas’s, I would rather

go forward, if I may.

Mr. BILIRAKIS. What would you prefer to do?

Mr. GEKAS. I do not mind proceeding.

Mr. BILIRAKIS. Well, then, proceed. The only thing is I am liable

to cut you off.

You are recognized, the gentleman from Pennsylvania.

STATEMENT OF HON. GEORGE W. GEKAS, A REPRESENTATIVE

IN CONGRESS FROM THE STATE OF PENNSYLVANIA

Mr. GEKAS. Thank you. The opening remarks made by the chairman and the ranking member in describing the bill which I have

placed before you were more than adequate in describing the purport of the legislation.

I simply want to add to that the fact that the national goal for

the 20th century is well-known to everybody. The one that we just

completed, that goal was thrust upon us. It was the repulsion of

totalitarianism and the reestablishment and preservation of democracy across the globe. That was the national gole thrust upon us.

Now we have an opportunity in the next century to assume leadership in what I envision to be, and others do, the national goal

for the 21st century, namely the eradication of disease worldwide.

Why is that important? Not only for the humanitarian and altruistic rationale that are the foundation for such a project, but also

in the enlightened self-interest of our country, which is the leader

in all of these disciplines that are so vital to the health of the

world, that enlightened self-interest we not only protect our people

in the future from these diseases and other catastrophes that

might occur, but at the same time we create jobs, we create interests, we develop new technologies, new pharmaceuticals and all the

other necessaries to further envision a world without disease with

our country in the forefront.

That is what the purpose of it is. That is why our witness is so

important. She has testified before our Biomedical Research Caucus as one of the leading lecturers in her field, and you will see

from her testimony that she will be a vital force if we implement

the legislation which I have offered.

She is Professor Dyann Wirth, of the Department of Immunology

and Infectious Diseases, Harvard School of Public Health, and has

a slew of publications which she is the author. She is renowned in

her field. She impressed the Members of the Hill, the Capitol, who

engaged in the Biomedical Research Caucus series, and I am sure

she will impress you. Unfortunately she has impressed me so much

that I am leaving right now to go vote, but I know what she will

testify and commend her to you.

[The prepared statement of Hon. George W. Gekas follows:]

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PREPARED STATEMENT OF HON. GEORGE W. GEKAS, A REPRESENTATIVE IN CONGRESS

FROM THE STATE OF PENNSYLVANIA

Mr. Chairman, and Members of the Committee, I would like to thank you for giving me the opportunity to testify at this hearing on such an important matter.

The latter part of the twentieth century saw the dismantling of the U.S.S.R., the

fall of the Berlin Wall, and a worldwide blossoming of democracy. To many this

seemed an impossibility at the time. Most of the world rightly places the credit for

these events in the hands of our United States. Our leaders and our government

put forth endless efforts to achieve these ends successfully. While these accomplishments are extraordinary, it is time to turn our attention to another seemingly impossible goal.

With the dawning of the new millennium, the time has come to focus our national

energy and resources on efforts to eradicate all disease across the globe. This is indeed an awesome goal that may not be attainable in itself, but its purpose could

lead to new treatments of diseases, and new approaches to controlling them.

Beyond the humanitarian reasons for promoting this idea, the U.S. has enlightened domestic goals as well. Eradicating global disease would protect American citizens, improve the quality of life worldwide, enhance our economy, and advance

American interests across the globe. Achieving this goal would impact every aspect

of our society, not just the field of health care.

In order to reach the objective of eradicating disease globally, I have introduced

H.R. 2399, the Advancement of Global Health Act, which would establish a commission, the National Commission for the New National Goal: The Advancement of

Global Health. The commission’s task would be to recommend a strategy for the

global eradication of disease. The United States has the resources, through the National Institutes of Health (NIH) and the National Science Foundation, to take the

lead in expanding health research information globally, especially with the recent

explosion of Internet technology. Additionally, the commission would assist the Center for Vaccine Development at the NIH to achieve global control over infectious disease. A one-time $1 million allocation would be granted to the commission to coordinate and attract other sources of funding both domestically and abroad for the purpose of achieving these objectives.

The fifteen-member commission would be charged with coordinating governmental, academic, and public and private health care entities for the purpose of

global disease eradication. The commission would then be required to submit a final

report to Congress within one year of its establishment, with its recommendations

for legislative, administrative, and other appropriate actions. The wide-sweeping

goals of this legislation could encompass ideas like the simple act of teaching a

youngster how to properly wash his or her hands, reaching across to the more complex, such as medical advances learned from space exploration.

It gives me great pleasure to have Dr. Dyann F. Wirth here today to further discuss the idea of eradicating global disease. Dr. Wirth earned a Ph.D. in Cell Biology

and Biochemistry from the Massachusetts Institute of Technology. She currently

serves as a professor at the Harvard School of Public Health in its Department of

Immunology and Infectious Diseases. Dr. Wirth is a widely published author in numerous esteemed scientific and medical journals. She also worked for ten years as

an NIH Study Section Member on Tropical Medicine and Parasitology, which is Dr.

Wirth’s particular area of expertise. Again, I am glad to have her with us today.

The intelligence and imagination of American researchers and scientists did not

fail us in our attempts to preserve and promote freedom and democracy across the

globe. It is now time for us to unleash these same great minds towards the goal

of improving the quality of life for everyone. We must summon all of the resources

at our command in our efforts to eradicate disease from the face of the Earth.

Again, Mr. Chairman, I thank you for this hearing on this very important matter

that can change the lives of countless individuals.

Mr. UPTON [presiding]. I thank the gentleman from Pennsylvania. Now I recognize Mrs. Meek, and I didn’t know that you were

here when I gave my opening statement, but I commended you for

your good bill, and I am delighted to be a cosponsor and delighted

to recognize you now.

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STATEMENT OF HON. CARRIE P. MEEK, A REPRESENTATIVE IN

CONGRESS FROM THE STATE OF FLORIDA

Mrs. MEEK. Thank you, Mr. Chairman. I am pleased to be before

the committee again, and I want to thank you for bringing this

hearing up again. 762 is an extremely important piece of legislation. It is time that it be passed, Mr. Chairman, and of course I

am hoping that this committee will see fit to pass it out and send

it to the floor as quickly as possible so that no one else will have

to wait for the kind of assistance that this Lupus Research and

Care Act will bring.

The Lupus Foundation has really stuck with the Congress

through this, Mr. Chairman. They have assiduously watched this

bill for many, many years, and I do hope we can get it passed.

What it will do is add additional services for lupus victims.

But I am here this morning because I am pleased and privileged

and blessed to have a young lady who is sitting at the table, the

testimony table, to testify for lupus, a very beautiful, lovely lady,

Tomiko Fraser. She is the spokesperson for the Lupus Foundation,

and I do not have to take your time to tell you all of the demerits,

I would say, or all of the real terrible effects of lupus. I lost a sister

to it. I have lost so many friends to lupus. It is a young woman’s

disease, and as a result of that, I think as this committee you have

243 cosponsors behind this bill.

And I want to have my statement placed in the record, Mr.

Chairman, and with your permission.

Mr. UPTON. Without objection, your entire statement will be put

in the record, and, again, we thank you for your leadership on this

very important issue that touches so many American families in

every State.

[The prepared statement of Hon. Carrie P. Meek follows:]

PREPARED STATEMENT OF HON. CARRIE P. MEEK, A REPRESENTATIVE IN CONGRESS

FROM THE STATE OF FLORIDA

Good morning, Chairman Bilirakis, Ranking Member Brown and my other colleagues. It’s a pleasure to be with you. Thank you for holding this hearing and inviting me to appear before your Subcommittee to discuss my lupus bill, H.R. 762. My

bill would authorize additional funding for lupus research and treatment programs.

Providing such additional help for lupus victims is not a Democratic issue or a Republican issue. It’s an American issue. My bill has broad bipartisan support (243

cosponsors from both sides of the aisle).

I won’t take the Subcommittee’s time to lay out all of the details of H.R. 762. In

a nutshell, this bill would authorize spending of up to $75 million for lupus research

and $75 million for lupus care and treatment programs.

I want to recognize and introduce to the Subcommittee the beautiful young

women sitting next to me, Tomiko Fraser. Tomiko is a nationally recognized

spokesmodel and actress. She is the first African-American women to be a

spokesmodel for Maybelline. Tomiko’s sister has lupus. Tomiko has seen firsthand

the devastation that lupus has caused for her sister and she speaks eloquently

about what it is like for her sister to live with lupus. She makes a powerful case

for why we need the additional funding for lupus research and treatment that my

lupus bill authorizes.

Tomiko, I salute you and your sister for your courage and thank you for your commitment to obtaining additional relief for lupus victims and their families.

As many of you know, I know firsthand the heartache that lupus causes, I lost

a sister to lupus and have seen many others suffer from this disease. We all know

the debilitating pain and fatigue that lupus often causes, pain and fatigue that

makes it difficult for persons with lupus to maintain employment and lead normal

lives. We also know the profound impact that this disease has on family members

of those with lupus.

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Mr. Chairman, lupus victims and their families need more help and they need it

now. Congress and the President can provide it by passing and signing H.R. 762.

We can do it, and we must do it this year, but, to make this happen, I need your

help to persuade the leadership to bring this bill to the floor immediately. I won’t

be satisfied, and none of us should be, until we get this bill to the House floor, pass

it overwhelmingly, pass it in the Senate and have it signed by the President.

I urge the Subcommittee and the full Commerce Committee to mark this bill up

immediately and implore the Leadership to bring this bill to the floor on the Suspension Calendar at once so that it can pass the House this Session. Thank you,

Mr. Chairman.

Mrs. MEEK. Thank you, Mr. Chairman. And I would love to hear

Tomiko, but I must go and vote.

Mr. UPTON. Well, you can come back.

Mrs. MEEK. All right.

Mr. UPTON. At this point, as no members are coming back from

the vote that is currently ongoing, I would like to invite the first

panel to come to the table. They include Dr. Nick Bryan, professor

and chairman of radiology at the Hospital of the University of

Pennsylvania; Dr. Reed Dunnick, professor and Chair of the Department of Radiology, University of Michigan. Go blue. Beat

UCLA this weekend. Dr. Bruce Hillman, professor and Chair, Department of Radiology, University of Virginia; Ms. Tomiko Fraser,

who is, of course, at the table already, and obviously the national

spokesperson for the National Lupus Association; and Dr. Dyann

Wirth, professor at the Department of Immunology and Infectious

Diseases at Harvard.

I just want to say before we start that there are a number of

things ongoing this morning, and a number of committees and subcommittees that are meeting. We have a very important issue on

the House floor, that being the marriage penalty tax as well, where

I am going to have to return to engage myself in that debate a little bit later this morning.

Your statements are made part of the record in their entirety.

We would like to keep this to 5 minutes each or less. And Dr.

Wirth, we will start with you. Thank you for being here with us

this morning.

STATEMENTS OF DYANN WIRTH, PROFESSOR, DEPARTMENT

OF IMMUNOLOGY AND INFECTIOUS DISEASES, HARVARD

SCHOOL OF PUBLIC HEALTH; N. REED DUNNICK, PROFESSOR AND CHAIR, DEPARTMENT OF RADIOLOGY, UNIVERSITY OF MICHIGAN HEALTH SYSTEM; BRUCE J. HILLMAN,

PROFESSOR AND CHAIR, DEPARTMENT OF RADIOLOGY, UNIVERSITY OF VIRGINIA; TOMIKO FRASER, NATIONAL SPOKESPERSON, LUPUS FOUNDATION OF AMERICA, INC.; AND R.

NICK BRYAN, PROFESSOR AND CHAIRMAN OF RADIOLOGY,

HOSPITAL OF UNIVERSITY OF PENNSYLVANIA

Ms. WIRTH. Mr. Chairman and members of the subcommittee,

thank you for the opportunity to testify today. My name, as you already know, is Dyann Wirth. I am a professor at Harvard University School of Public Health and the Department of Immunology

and Infectious Diseases, and I am here today on behalf of the Joint

Steering Committee for Public Policy, which has worked closely

with Representative Gekas in his outstanding efforts in support of

biomedical research.

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The Joint Steering Committee for Public Policy is a coalition of

four life sciences societies representing more than 25,000 researchers. I am here today to support—to express the support of the joint

steering committee for Congressman Gekas’s bill which we have

just heard about on the advancement of global health, H.R. 2399.

This bill, if enacted into law, would create a Presidential/congressional commission to investigate how we as a Nation can most effectively seize the scientific opportunities presented by modern advances in research to eradicate many of the diseases that are

plaguing millions of the world’s people.

We support this bill because we believe that in this next millennium it is within the grasp of human capacity to accelerate the role

of basic biomedical research and the translation of that research to

the benefit of the world’s least fortunate people.

Now is the time. This is an attempt to focus all of the tremendous scientific energy in the United States on fighting diseases

throughout the world. This is a noble endeavor for the United

States. We have the means to do this, and I believe we should

make it a priority.

My particular experience is in malaria, but as devastating as malaria is, it is just one of the several infectious diseases that are not

only killing millions, but costing billions. According to the World

Health Organization, infectious diseases account for more than 13

million deaths a year. That is 35 percent of the deaths in the world

today. That means during the duration of this hearing, 1,500 people will die from infectious disease. Malaria alone kills 2.7 million

people each year. Tragically, every 30 seconds a child somewhere

in the world, probably in Africa, dies of malaria.

The enormous volume of travel and trade have made infectious

diseases blind to national borders, and this has been recognized.

The January 2000 unclassified report from the CIA’s National Intelligence Council entitled ‘‘The Global Infectious Disease Threat

and Its Implications for the United States’’ suggests that in modern

warfare infectious diseases are likely to account for more military

hospital admissions than battlefield injuries. The report claims,

and I concur, New and reemerging infectious diseases will pose a

rising global health threat and will complicate U.S. and global security over the next two decades. These diseases will endanger U.S.

citizens at home and abroad, threaten U.S. Armed Forces deployed

overseas, and exacerbate social and political instability in key countries and regions where the United States has an interest.

Research into prevention, treatment and control of tropical and

infectious diseases is now more important than ever. I will talk just

briefly about malaria because that is where my interest and passion is. Among adults living in high-transmission areas, malaria is

considered a chronic disease. A single bout can incapacitate someone for weeks, and despite massive efforts to eradicate this disease

in the 1950’s, there is more malaria in the world today than there

ever has been in history. One-fourth of the world’s population is at

risk of infection.

Clearly, we need better implementation of the tools that we have

in the short term, but our tools are not adequate. New research

interventions are desperately needed. Cutting-edge technology has

led to the development of new paradigms. The genome of the most

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important parasite is being sequenced. We have DNA vaccines, new

technologies. And it is important to seize the opportunities of these

scientific advances to accelerate and defeat malaria worldwide.

But equally important as progress in research and public support

and awareness of these major health threats, in order to conquer

malaria, AIDS, malaria, other infectious diseases, we need a global

strategy that includes American leadership and resources to invest

in continued research into prevention and treatment.

As we begin the 21st century, we are blessed with unimaginable

opportunities to build on breakthrough research to control and prevent global infectious diseases. This is not just altruism to reduce

suffering of the world’s most needy; this is also a question of national security and health for the United States and its citizens.

Renewed investment in the treatment and prevention of global infectious diseases is a win-win for the country. By helping others

across the world, we are launching the best defense to protect the

health of our Nation’s people.

We hope that you will seriously consider passage of H.R. 2399

and thank you very much for the opportunity to present.

[The prepared statement of Dyann Wirth follows:]

PREPARED STATEMENT OF DYANN WIRTH, PROFESSOR, HARVARD UNIVERSITY SCHOOL

OF PUBLIC HEALTH

Mr. Chairman and members of the Subcommittee, thank you for the opportunity

to testify today. My name is Dyann Wirth. I am a Professor at the Harvard University School of Public Health Department of Immunology and Infectious Disease. I

am here today on behalf of the Joint Steering Committee for Public Policy, which

has worked closely with Representative Gekas in his outstanding efforts in support

of biomedical research.

The Joint Steering Committee for Public Policy (JSC) is a coalition of four lifescience societies representing more than 25,000 researchers in the fields of genetics,

cell biology, biophysics, biochemistry and molecular biology. The JSC was formed in

late 1980s to bring scientists together to advocate for federal funding for basic biomedical research. Eric Lander of MIT chairs JSC, and among its 20 board members

are Nobelists J. Michael Bishop, Paul Berg and Harold Varmus.

Founders of the JSC realized that there was a great need for the United States

to invest in biomedical research and called for the doubling of the NIH budget. Since

that time, Mr. Chairman, the Congress’ visionary support of the NIH has lead us

to the dawn of a new age in science. I have no doubt that the coming decade will

be remembered for major discoveries enabled by the mapping of the human genome

which will lead to the prevention and cure of diseases. The JSC also worked with

Congressman Gekas to introduce the Congressional Biomedical Research Caucus to

the Halls of Congress. Today, the Biomedical Research Caucus has been called by

Chairman John Porter and former Speaker New Gingrich among others, ‘‘the most

influential Caucus in Congress.’’

I am here today to express the support of the Joint Steering Committee for Congressman Gekas’ bill the National Commission for the New National Goal: The Advancement of Global Health Act, H.R. 2399. this bill, if enacted into law would create a Presidential/Congressional commission to investigate how we as a Nation can

most effectively seize the myriad scientific opportunities presented by modern advances in genomic to eradicate many of the diseases that are plaguing millions of

the world’s people. We support this bill because we believe that in this third

Millenium it is within the grasp of human capability to accelerate the role of basic

biomedical research and the translation of that research to the benefit of the world’s

least fortunate people. Now is the time: scientific potential is there; it requires only

political will to make it reality.

My particular experience is malaria, but as devastating as malaria is, it is just

one of several infectious diseases that are not only killing millions but costing billions. According to the World Health Organization, infectious diseases account for

more than 13 million deaths a year. That means that over the duration of this hearing 1,500 people will die from an infectious disease—over half of them children

under five.

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According to the WHO the seven infectious diseases that caused the highest number of deaths in 1998 are AIDS, TB, malaria, hepatitis B and hepatitis C, diarrheal

diseases, and measles. Of these, TB and hepatitis are renewed threats because they

are becoming increasingly resistant drug resistant. But, malaria alone is estimated

to cause up to 500 million clinical cases and 2.7 million deaths each year, representing 4 percent to 5 percent of all fatalities globally. Tragically, every 30 seconds a child somewhere in the world dies of malaria. As you know, most of these

deaths occur in developing countries where extreme poverty and lack of access to

basic health care, adequate sanitary and essential drugs can seal the fate of children before they’re born. However, the enormous volume of travel and trade today

have made, infectious diseases blind to national borders.

A January, 2000, unclassified report from the CIA’s National Intelligence Council,

entitled ‘‘The Global Infectious Disease Threat and Its Implications for the United

States,’’ suggests that in modern warfare infectious diseases are likely to account

for more military hospital admissions than battlefield injuries. The report assesses

claims, and I concur, that ‘‘New and reemerging infectious diseases will pose a rising global health threat and will complicate US and global security over the next

20 years. These diseases will endanger US citizens at home and abroad, threaten

US armed forces deployed overseas, and exacerbate social and political instability

in key countries and regions in which the United States has significant interests.’’

Research into the prevention, treatment and control of tropical and infectious disease are now more important than ever to the US and the world. I will address malaria as an example because I know more about malaria than about other global

health threats.

Among adults living in areas of high transmission, malaria is best thought of as

a chronic, debilitating illness that robs its victims of years of productivity. A single

mosquito bite can transmit one of the four parasites that cause malaria, setting in

motion bouts of fever, chills, and nausea that can recur for weeks. According to a

1993 World Bank Report, malaria represents a global public health burden second

only to tuberculosis among infectious diseases of the 2-3 million children who die

of malaria each year, most of them live in Africa, continent already overwhelmed

by poverty and internal conflict. Those who survive can suffer chronic anemia and/

or immune suppression that leave victims vulnerable to other fetal diseases.

Despite massive efforts to eradicate in the 1950s, today than at any other time

in history. More than 500 million people are infected with malaria worldwide; onefourth of the world’s population is at risk for infection. Better implementation of

currently available control measures, including the use of insecticide, and better and

more rational use of existing drugs, should be the goal in the short term; in the

long-term, new research interventions are desperately needed. Cutting-edge technology has led to the development of new paradigms—the genome of the most important malaria parasites is being sequenced, DNA vaccines are being developed

and tests of methods to prevent transmission by the mosquito are being explored.

We must seize the opportunity presented by these scientific adversities to accelerate

the defeat of malaria worldwide. But equally important as progress in research is

public support and awareness of this major health threat. In order to conquer malaria, we need a global strategy that includes American leadership and resources to

invest into continued research into prevention and treatment. I must also point out

the great need for action with regard to HIV/AIDS in Africa. Africa remains the epicenter of the pandemic, bearing the largest disease burden, with 70 percent of people living with AIDS worldwide, 83 percent of global AIDS deaths, and 95 percent

of the world’s AIDS orphans. AIDS is reversing decades of progress from important

public health efforts, lowering life expectancy, and significantly affecting daily life

form millions of Africans. This situation cries out for leadership.

The JSC supports efforts to encourage research and development on vaccines to

combat malaria, tuberculosis, AIDS and other infectious diseases causing and to ensure that existing vaccines are accessible to populations in developing countries

most impacted by these diseases. These efforts will require partnerships among federal agencies, industry, non-profit foundations and other NGOs, the World Bank,

and international organizations to combat the scourge of infectious diseases. This

Commission could vastly accelerate the pace of these efforts.

Specific mechanisms might include, enhanced R&D tax credits and new tax credits for sales of vaccines, contributions to international organizations such as the

Global Alliance for Vaccines and Immunizations (GAVI) for the purchase and distribution of vaccines in developing countries, and measures that will improve the

public health infrastructure in developing countries in order to expand immunizations, prevent and treat infectious diseases, and build effective delivery systems for

basic health services.

77

As we begin the 21st century, we are blessed with unimaginable opportunities to

build on breakthrough research to control and prevent global infectious disease.

This is not just altruism to reduce the suffering of the world’s most needy: this is

also a question of national security and health for the United States and its citizens.

Renewed investment in the treatment and prevention of global infectious disease is

a win-win for the country: by helping others across the world we are also launching

the best defense to protect the health of our Nation’s people. We hope you will seriously consider passage of H.R. 2399.

Thank you for the opportunity to present the views of the Joint Steering Committee for Public Policy. I would be happy to answer your questions.

Mr. UPTON. Thank you, Dr. Wirth.

Dr. Dunnick, welcome to Washington’s version of the ‘‘Big

House.’’

STATEMENT OF N. REED DUNNICK

Mr. DUNNICK. Thank you. Good morning. Thank you for this opportunity to share my support for H.R. 1795 with you. I also appreciate the leadership shown by Mr. Burr and Ms. Eshoo in support

of this legislation.

I am Reed Dunnick. I currently serve as the Chair of the Department of Radiology at the University of Michigan. Prior to coming

to Michigan in 1992, I served on the faculties at Stanford and at

Duke. In addition, I spent 4 years as a staff radiologist in diagnostic radiology at the National Institutes of Health.

The Congress has recognized the structural impediments to imaging research that exist at the NIH in the conference report on

H.R. 3194, the Consolidated Appropriations Act for Fiscal Year

2000. The language in that conference report is a good summary

of the current situation at the NIH.

Continued advances in biomedical imaging and engineering, including the development of new techniques and technologies for

both clinical applications and medical research, and the transfer of

new technologies from research projects to the public health sector

are important. The disciplines of biomedical imaging and engineering have broad applications to a range of disease processes and

organ systems, and research in these fields does not fit into the

current disease and organ system organizational structure of the

NIH.

The present organization of the NIH does not accommodate basic

scientific research in these fields and encourages unproductive diffusion of imaging and engineering research. Several efforts have

been made in the past to fit imaging into the NIH structure, but

these have proved to be inadequate.

This congressional report is correct. The current structure of the

NIH does not promote basic research in medical imaging and bioengineering, two disciplines that have become critical to improving

health care. The next logical step suggested by this congressional

finding is the creation of a National Institute of Biomedical Imaging and Bioengineering as proposed in H.R. 1795.

The imaging science community has worked with the NIH leadership for three decades to fit imaging into the existing NIH organizational structure of individual institutes dedicated to specific

disease processes and organ systems. However, nothing short of an

institute will be effective in stimulating and coordinating biomedical research to the extent that it is needed.

78

The imaging community has not proposed the establishment of

a new institute lightly. We recognize and agree that the bar for

structural change should be set high. For that reason we looked to

the National Academy of Science’s Institute of Medicine in their

1984 report titled Responding to Health Care Needs and Scientific

Opportunity: The Organizational Structure of the National Institutes of Health.

They recommend a new institute when each of the following five

criteria are met: One, the activity is compatible with the mission

of the NIH; two, the research area in question is not receiving adequate attention; three, there are reasonable prospects for scientific

growth; four, there are reasonable prospects of sufficient funding;

and five, the proposed structural change will improve communication, management, priority setting and accountability.

The proposed National Institute of Biomedical Imaging and Bioengineering is consistent with these criteria. In identifying imaging

as one of its top research priorities, the NCI has stated that this

field is compatible with the mission of the NIH. The NCI has indeed increased its level of support for biomedical imaging in recent

years. However, even with this increase in resources, the amount

of moneys carried out by radiology departments throughout the

country account for less than 1 percent of the NIH budget.

Finally, the proposed institute, which would include a division to

coordinate imaging research throughout the Federal Government,

would certainly improve communication and management in a field

in which these qualities are sorely lacking.

Mr. Chairman, breakthroughs in medical imaging have revolutionized the way in which physicians detect, diagnose and treat disease. Imaging holds the promise of further advances that will move

us into an era of noninvasive medicine. To reach that goal, however, we need to create a climate that promotes discovery and innovation in imaging just as the NIH provides such a climate for other

fields.

For that reason I urge the committee to support the establishment of the National Institute of Biomedical Imaging and Engineering. Thank you.

[The prepared statement of N. Reed Dunnick follows:]

PREPARED STATEMENT OF N. REED DUNNICK, PROFESSOR AND CHAIR, DEPARTMENT

OF RADIOLOGY, UNIVERSITY OF MICHIGAN HOSPITALS

Good morning. Thank you for this opportunity to share my support for H.R. 1795

with you. My name is Reed Dunnick, and I chair the Radiology Department at the

University of Michigan. Prior to coming to Michigan in 1992, I served on the faculties at Stanford and Duke. In addition, I spent four years as a staff radiologist

in the Diagnostic Radiology Department at the National Institutes of Health.

Like everyone in my discipline and throughout the imaging sciences, I was extremely pleased that the Congress recognized the structural impediments to imaging research that exist at the NIH in the Conference Report on H.R. 3194, the Consolidated Appropriations Act for Fiscal Year 2000. The language in that Conference

Report is a good summary of the current situation at the NIH:

‘‘Continued advances in biomedical imaging and engineering, including the development of new techniques and technologies for both clinical applications and medical research and the transfer of new technologies from research projects to the public health sector are important. The disciplines of biomedical imaging and engineering have broad applications to a range of disease processes and organ systems and

research in these fields does not fit into the current disease and organ system organizational structure of the NIH. The present organization of the NIH does not accommodate basic scientific research in these fields and encourages unproductive difVerDate 11-MAY-2000 09:33 Oct 24, 2001 Jkt 010199 PO 00000 Frm 00082 Fmt 6633 Sfmt 6621 E:\HEARINGS\67114 txed01 PsN: txed01
79

fusion of imaging and engineering research. Several efforts have been made in the

past to fit imaging into the NIH structure, but these have proved to be inadequate.’’ This Congressional report is correct. The current structure of the NIH does not

promote basic research in medical imaging and bioengineering, two disciplines that

have become critical to improving health care. The logical next step suggested by

this Congressional finding is the creation of a National Institute of Biomedical Imaging and Bioengineering as proposed in H.R. 1795. Like my colleagues Dr. Hillman

and Dr. Bryan, I have been involved in imaging research at the NIH for many

years. The imaging science community has worked with the NIH leadership for

three decades to fit imaging into the existing NIH organizational structure of individual institutes dedicated to specific disease processes and organ systems.

During that period, numerous plans have been tried. In 1982, for example, most

extramural research in imaging was transferred from the National Institute of General Medical Sciences to the National Cancer Institute with the understanding that

NCI would support imaging research beyond that related to cancer. However, the

NCI has focused almost exclusively on cancer imaging.

On the intramural side, the Laboratory of Diagnostic Radiology Research (LDRR)

was transferred from the Office of the Director of the NIH to the Clinical Center

a couple of years ago. This move was an improvement but far from a solution because the Clinical Center lacks the research mandate and resources to allow LDRR

to achieve its full promise.

Despite good will on both sides, these initiatives did not solve the problems faced

by either extramural or intramural imaging investigators. Only after such repeated

efforts failed did the imaging community conclude that the NIH structure is not

compatible with an effective imaging research program and that creation of a new

institute is justified and necessary. Nothing short of an Institute will be effective

in stimulating and coordinating biomedical research to the extent that is needed.

The imaging community has not proposed the establishment of a new institute

lightly. We recognize and agree that the bar to structural change at the NIH should

be set high. For that reason, we looked to neutral, expert guidance, which we found

in the National Academy of Sciences’ Institute of Medicine. In a 1984 report titled

Responding to Health Needs and Scientific Opportunity: The Organizational Structure of the National Institutes of Health, issued in response to a Congressional directive, the IOM concluded that new institutes should be created only in unique circumstances when the following five criteria are met:

(1) the activity is compatible with the mission of the NIH;

(2) it can be demonstrated that the research area in question (defined either as a

disease or health problem or as a biomedical or behavioral process related to

a health problem) is not receiving adequate attention;

(3) there are reasonable prospects for scientific growth in the research area;

(4) there are reasonable prospects of sufficient funding for the new organization;

(5) the proposed structural change will improve communication, management, priority setting, and accountability.

The proposed National Institute of Biomedical Imaging and Bioengineering is consistent with these criteria. In identifying imaging as one of its top research priorities, the NCI has stated clearly that this field is compatible with the mission of

the NIH and that there are reasonable, even extraordinary, prospects for scientific

growth. The NCI has increased its level of support for the Biomedical Imaging Program in recent years. Even with this increased commitment of resources, however,

extramural support for imaging research carried out by Radiology Departments continues to account for substantially less than one percent of the NIH budget—a level

that is inadequate for an ‘‘Extraordinary Opportunity for Investment.’’ Finally, the

proposed institute, which would include a division to coordinate imaging research

throughout the federal government, would certainly improve communication and

management in a field in which these qualities are sorely lacking.

Two years ago, again in response to a Congressional mandate, the IOM issued another report that addressed the question of structural change. In its 1998 report titled Scientific Opportunities and Public Needs: Improving Priority Setting and Public Input at NIH, the IOM recommended that ‘‘The U.S. Congress should use its authority to mandate specific research programs, establish levels of funding for them,

and implement new organizational entities only when other approaches have proven

inadequate.’’ The imaging community agrees with this recommended limitation on

Congressional action and believes firmly that the proposed National Institute of Biomedical Imaging and Bioengineering is consistent with it.

In addition, and just as important, the proposed institute is also completely consistent with the NIH’s own rationale for the elevation of the National Center for

Human Genome Research to institute status in 1997. According to the statement

issued by the NIH to announce the creation of the National Human Genome ReVerDate 11-MAY-2000 09:33 Oct 24, 2001 Jkt 010199 PO 00000 Frm 00083 Fmt 6633 Sfmt 6621 E:\HEARINGS\67114 txed01 PsN: txed01
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search Institute, ‘‘As an institute, NHGRI can more appropriately interact with

other Federal agencies, and develop collaborations with industry, academia, and

international organizations.’’ The same is true for imaging. The proposed institute would coordinate imaging

research throughout the federal government, a mission that cannot be accomplished

successfully by a lower level office or organization lacking sufficient institutional

stature and authority to deal effectively with cabinet-level departments. Similarly,

industry-government collaborations are essential to the development of new imaging

technologies. The proposed institute would assist industry in setting research priorities and assessing potential fields for development. The National Electrical Manufacturers Association, which represents the companies that produce imaging devices,

supports this proposal.

This matter of coordinating imaging outside the NIH is important. Other federal

agencies such as NSF, NASA, the intelligence agencies, and the Departments of Defense, Commerce, and Energy all support imaging research. There is little or no coordination of these efforts. In one key area, telemedicine, the General Accounting

Office found a couple of years ago that more than 35 separate federal organizations

in nine different departments have sponsored telemedicine initiatives. Despite a

major federal investment of $646 million over three years, the GAO found that ‘‘no formal mechanism or overall strategy exists to ensure that telemedicine development is fully coordinated among federal agencies to serve a common purpose.’’ According to the GAO, the Joint Working Group on Telemedicine, created in response

to a directive from the Vice President, encountered serious difficulties even in developing a federal inventory of telemedicine programs.

This lack of coordination not only encourages duplication and inefficiency, it impedes the transfer of imaging technologies from research projects to the public

health care sector. The proposed institute could do much to ensure that federal research dollars are expended more efficiently and productively.

The National Institute of Biomedical Imaging and Bioengineering would also provide a focused effort to meet the medical needs of the information age. It has been

estimated that computerization requirements in the coming decade will double just

to keep pace with developments in all segments of society. The largest component

of that need will be in the area of medical imaging information. In addition to the

enormous amount of imaging-related, unprocessed information generated, there will

be a need to process and analyze the huge date sets produced by medical imaging

to improve the medical value of those data to the referring physicians who will access the network. An imaging institute would support research focused on the acquisition, transmission, processing, and optimal display of images.

Mr. Chairman, breakthroughs in medical imaging have revolutionized the way in

which physicians detect, diagnose, and treat disease in the past two decades. Imaging holds the promise of further advances that will move us into an era of noninvasive medicine. To reach that goal, however, we need to create a climate that

promotes discovery and innovation in imaging just as the NIH provides such a climate for other fields. For that reason, I urge the Committee to support the National

Institute of Biomedical Imaging and Engineering Establishment Act.

Mr. UPTON. Thank you very much.

Dr. Hillman.

STATEMENT OF BRUCE J. HILLMAN

Mr. HILLMAN. Good morning. I am Dr. Bruce Hillman, Chair of

the Department of Radiology at the University of Virginia, and I

am also a Chancellor of the American College of Radiology. I am

grateful to the committee, especially to the bill’s sponsors Mr. Burr

and Ms. Eshoo and my own Congressman Chairman Bliley, for the

invitation to testify in support of H.R. 1795, the National Institute

of Biomedical Imaging and Engineering Establishment Act.

Medicine now stands at the threshold of a new and exciting revolution in how we think about disease. It is the molecular revolution

wherein we will develop the tools needed to diagnose and treat disease at its earliest stages when the chances of success are likely

to be much greater than currently.

Medical imaging must be a critical element in this new paradigm. Medical imaging is the noninvasive biopsy that will detect alVerDate 11-MAY-2000 09:33 Oct 24, 2001 Jkt 010199 PO 00000 Frm 00084 Fmt 6633 Sfmt 6602 E:\HEARINGS\67114 txed01 PsN: txed01
81

terations in the genetic or molecular makeup of cells that have the

potential to progress to disease. Imaging technologies will precisely

determine what faction of cells are affected. Finally, medical imaging technologies will be integrated with new therapeutic methods

to either guide or monitor treatment so that only diseased cells are

treated while preserving normal tissue.

The basic knowledge exists to begin to implement this vision;

however, the current means by which the NIH institutes address

imaging research is as a stepchild, a part of the research portfolio

of nearly all of the institutes, but the principal focus of none. As

a result, basic research into the development of new imaging technologies has been subject to overlap and duplication, inefficient use

of resources and lost opportunities.

The initial invention of and basic research into new technologies

that have emerged in recent times such as CAT scanning, MRI,

and image-guided interventional methods have most frequently occurred outside the U.S. where the logistics and funding of basic research into medical imaging can be handled in a more straightforward and integrated fashion.

The establishment of a new Institute of Biomedical Imaging and

Bioengineering would correct many of these structural problems.

The institute would address the needs of imaging research directly

and comprehensively. It would provide a home and focus for the

fundamental disciplines of computer sciences, physics and engineering that are so inextricably connected to progress in imaging

research. It would foster basic imaging research lacking in the current NIH structure that would lead to the more efficient development of the new broad-ranging technologies applicable to my vision

of molecular medicine.

Through relationships the new institute will develop with regulatory agencies and industry, it would facilitate technology transfer, allowing important innovations to more rapidly be employed in

medical care. And very significantly the new institute would foster

the more rapid assessment of new technologies as they enter practice to ensure that their use is appropriate and cost-effective.

This last aspect of the institute’s proposed functions is critical

and is yet another example of how the current institutional structure insufficiently addresses the needs of the American public.

Among my other responsibilities, I am Chair of the American

College of Radiology Imaging Network, or ACRIN. ACRIN is a National Cancer Institute-funded cooperative group that through clinical trials gathers information to extend and improve the quality of

lives of cancer patients.

ACRIN is a remarkable endeavor that evaluates the effectiveness

of imaging technologies in improving health outcomes for individual patients and measures the balance of benefit and costs the

American public receives for its expenditure on cancer imaging.

The results of major definitive ACRIN trials of such technologies

as digital mammography, a screen for breast cancer, and CAT scan

for the detection of early lung cancer will guide medical practice

and reimbursement in the years to come.

The National Cancer Institute should be applauded for its vision

in establishing ACRIN less than 2 years ago. Yet again, these same

technologies that ACRIN will study and many other current and

82

future technologies are broadly applicable to diseases other than

cancer.

There is no counterpart to ACRIN at any of the other institutes.

Even if there were, the fragmentation of imaging technology assessment on such arbitrary grounds would be wasteful, inefficient

and leave important gaps.

The structural inadequacies that hinder imaging research can be

rectified only through an institute. Institutes are the standard NIH

administrative units for areas of such significant scientific research. Any entity devoted to biomedical imaging, bioengineering,

and related fields will necessarily be of the size that will make any

organizational unit short of an institute inappropriate.

Related research occurs in numerous Federal agencies such as

the Departments of Defense and Energy, and the National Science

Foundation. A subordinate administrative unit would lack the stature necessary to coordinate research involving imaging outside of

NIH. For these reasons and for those I have detailed in this testimony, I hope you will vote favorably on H.R. 1795 and pass it on

to the full House of Representatives for its consideration. Thank

you.

[The prepared statement of Bruce J. Hillman follows:]

PREPARED STATEMENT OF BRUCE J. HILLMAN, CHAIR, DEPARTMENT OF RADIOLOGY, UNIVERSITY OF VIRGINIA SCHOOL OF MEDICINE

Good morning. I am Dr. Bruce Hillman, Chair of the Department of Radiology at

the University of Virginia School of Medicine and a Chancellor of the American College of Radiology. I greatly appreciate your invitation so that I may testify in support of H.R. 1795, the National Institute of Biomedical Imaging and Engineering Establishment Act.

During the past thirty years, no specialty of medicine has advanced technologically so much as medical imaging. And no specialty of medicine has so drastically and positively changed the way we detect, diagnose, stage, and treat disease.

The introduction during that time period of such computer-based technologies as

CAT scanning and MRI, and the use of imaging to guide a host of interventional

procedures has revolutionized medicine. As a result, the preferred diagnosis and

treatment methods for a broad range of diseases—cancer, heart disease, orthopedic

injuries, and infectious diseases, to name just a few—has become less invasive, less

expensive, and less risky for patients.

Medicine now stands at the threshold of a new and exciting revolution in how we

think about disease. It is the molecular revolution, wherein we will develop the tools

needed to diagnose and treat disease at its earliest stages, when the chances of success are likely to be much greater than currently. Virtually everyone agrees that

medical imaging must be a critical element in this new paradigm.

Medical imaging is the ‘‘non-invasive biopsy’’, the method of disease quantitation,

the guidance for new treatments still to be developed that will form the

underpinnings of molecular medicine. Under this scenario, new medical imaging

technologies will detect alterations in the genetic or molecular makeup of cells that

have the potential to progress to disease. We then will employ imaging technologies

to precisely determine what fraction of cells are so affected. Finally, medical imaging technologies will be integrated with new therapeutic methods to either guide or

monitor treatment, so that we can much more precisely than ever before ensure that

only diseased cells are treated while preserving normal tissue.

The basic knowledge exists to begin to implement this vision. However, for this

optimistic and exciting prophecy to come to fruition, we will need to invest in the

development and assessment of new imaging technologies. We are ill-equipped to do

so under the current NIH organizational structure that focuses the work of existing

institutes on specific organ systems and diseases.

Imaging technologies, with few exceptions, are multi-potential. They are applicable to many organ systems and diseases. Their value in detection, diagnosis, staging, and treatment of disease cuts across traditional institute lines. The leadership

of existing institutes do not generally have training or expertise in imaging. The requests for applications and the public announcements that are the principal instruVerDate 11-MAY-2000 09:33 Oct 24, 2001 Jkt 010199 PO 00000 Frm 00086 Fmt 6633 Sfmt 6621 E:\HEARINGS\67114 txed01 PsN: txed01
83

ments used by institutes to guide research in their respective fields view imaging

more as a tool to address disease-specific questions than as a focus for research in

its own right. The critical research training of new young imaging investigators,

when it is supported at all, is forced into unnatural pathways that address imaging

technology research obliquely rather than head-on.

Thus, the current means by which the NIH institutes address imaging research

is as a ‘‘stepchild’’—a part of the research portfolio of nearly all of the institutes but

the principal focus of none. As a result, basic research into the development of new

imaging technologies has been subject to overlap and duplication, inefficient use of

resources, and lost opportunities. The initial invention and basic research into new

technologies that have emerged in recent times—such as CAT scanning, MRI, and

image-guided interventional methods—have most frequently occurred outside the

U.S. where the logistics and funding of basic research into medical imaging can be

handled in a more straightforward fashion.

The establishment of a new Institute of Biomedical Imaging and Bioengineering

would correct many of these structural problems. The Institute would:

• address the needs of imaging research directly and comprehensively; • provide a home and focus for the fundamental disciplines of computer sciences,

physics, and engineering that are so inextricably related to progress in imaging

research; • provide a home for basic imaging research—lacking in the current NIH structure—that would lead to the more efficient development of the new, broad-ranging technologies applicable to the vision of molecular medicine that I have detailed earlier; • through relationships the new institute will develop with regulatory agencies and

industry, facilitate technology transfer, allowing important innovations to more

rapidly be employed in medical care; • and very significantly, foster the more rapid assessment of new technologies as

they enter practice, to ensure that their use is appropriate and cost-effective.

This last aspect of the Institute’s proposed functions is critical and is yet another

example of how the current institutional structure insufficiently addresses the needs

of the American public.

Among my other responsibilities, I am the chair of the American College of Radiology Imaging Network, or ACRIN. ACRIN is a National Cancer Institute-funded cooperative group that conducts clinical trials of medical imaging technologies at community practices and academic health centers across the country. The overriding

goal of ACRIN is, through clinical trials, to gather information that will extend and

improve the quality of the lives of cancer patients.

ACRIN is a remarkable endeavor that evaluates the effectiveness of imaging technologies in improving health outcomes for individual patients and measures the balance of benefit and costs the American public receives for its expenditures on medical imaging. The results of major, definitive, ACRIN trials of such technologies as

digital mammography for screening for breast cancer, CAT scanning for the detection of early lung cancer, and the use of PET scanning for patients’ response to

chemotherapy will guide medical practice and reimbursement in the years to come.

The National Cancer Institute should be applauded for its vision in establishing

ACRIN less than two years ago. Yet again, these same technologies that ACRIN will

study, and many other current and future technologies, are broadly applicable to

diseases other than cancer. There is no counterpart to ACRIN at the National

Heart, Lung, and Blood Institute, or the National Institute for Neural Diseases and

Stroke—institutes whose purview includes organ systems and diseases where imaging plays a large and critical role—nor, for that matter, at any of the other institutes. Even if there were, the fragmentation of imaging technology assessment on

such arbitrary grounds would be wasteful, inefficient, and leave important gaps.

The unification of imaging technology assessment activities under the aegis of the

proposed Institute obviates these concerns. It ensures that assessment activities

critical to both the health and financial well-being of the American public will be

orderly, strategic, coherent, and efficient and that they will best advise us on how

to most wisely expend our resources on imaging technologies as they are employed

in medical practice.

The structural inadequacies that hinder imaging research can be rectified only

through an institute. Institutes are the standard NIH administrative units for areas

of such significant scientific research. An entity devoted to biomedical imaging, bioengineering, and related fields would necessarily be of a size that would make any

organizational unit short of an institute inappropriate. Related research occurs in

numerous federal agencies, such as the Departments of Defense and Energy and the

National Science Foundation. A subordinate administrative unit would lack the stature necessary to coordinate research involving imaging outside of NIH.

84

For these reasons and those I have detailed in this testimony, I hope that you

will vote favorably on HR 1795 and pass it on to the full House of Representatives

for its consideration.

Mr. BILIRAKIS. Thank you, Dr. Hillman.

Ms. Tomiko Fraser is the national spokesperson for the Lupus

Foundation of America.

Thank you very much for being here today.

STATEMENT OF TOMIKO FRASER

Ms. FRASER. Good morning, Mr. Chairman and members of the

subcommittee. I appear before you today representing the Lupus

Foundation of America on behalf of the 1.4 million Americans who

have lupus erythematosus, a devastating disease that causes the

immune system to attack the body’s own cells and organs. Unfortunately, one of the victims of lupus is my younger sister Shneequa,

who has a very serious case of lupus that affects her brain. The disease has been so devastating to Shneequa that she must receive

around-the-clock care at a skilled nursing facility.

That is why I have agreed to serve as the national spokesperson

for the Lupus Foundation of America. I want to help educate all

Americans about the devastating impact lupus has on its victims.

I urge Congress to pass H.R. 762, the Lupus Research and Care

Amendments Act of 1999. Congresswoman Carrie Meek, who lost

a sister to lupus, introduced this legislation. Two hundred fortythree Members of the U.S. House of Representatives are cosponsors

of H.R. 762.

The legislation authorizes a $23 million increase to the current

funding level for lupus medical research supported through the National Institutes of Health. It also authorizes $75 million to fund

a grant program. This program would provide local governments,

community hospitals, and other nonprofit health care facilities with

a pool of funds so they could offer lifesaving medical care to the

poor or uninsured people with lupus.

This grant program will help local communities hardest hit by

lupus, especially in medically underserved areas including rural

and urban communities where often there is a shortage of medical

facilities to treat people with lupus.

Lupus deserves special funding consideration. Lupus is the

prototypical autoimmune disease. Research on lupus benefits all

autoimmune diseases that disproportionately affect women. Autoimmune diseases are the fourth leading cause of disability among

women.

Lupus is an expensive disease to treat. The cost to provide medical care for a person with lupus averages between 6- and $10,000

annually. The Lupus Foundation of America estimates the economic impact of lupus on the Federal Treasury to be several billion

dollars every year. These costs include disability income payments

to the tens of thousands of lupus victims disabled every year by the

disease. They also include the cost of government-sponsored medical care provided through the Medicare and Medicaid programs

and uncollected tax revenue due to lost wages when individuals

with lupus are unable to work.

The Lupus Research and Care Amendments Act of 1999 is a bipartisan effort to address an urgent national health care crisis that

85

inflicts an enormous burden on individuals, families, the business

community, the Federal Government and society. Many scientific

opportunities exist, but current funding levels can support only one

in four of the promising studies submitted for funding that eventually lead to a cure for lupus. By accelerating medical research for

lupus now, Congress will reduce future health care costs and save

billions of dollars for the Social Security and Medicare Trust Funds

in future years.

Lupus is a complicated and mysterious disease that needs extensive study. Presently there is no cure for lupus, nor do researchers

fully understand what causes the disease. We do not know why

lupus alternates between periods of remission and periods of disease activity called flares. We do not know why the disease can remain mild in some individuals and become life-threatening in others. What we do know, Mr. Chairman, is that lupus has a devastating impact on its victims and their families. We know that

lupus causes debilitating health effects including extreme joint

pain and swelling, constant fevers, overwhelming fatigue, horrible

skin rashes, organ failure and a host of other devastating symptoms.

Lupus destroys the quality of life for many of its victims. The disease can severely damage the kidneys, heart, lungs and other vital

organs. Lupus disables one in five of its victims, often at a very

young age, and tragically every year thousands of lupus victims die

from complications of the disease.

Lupus is not an equal opportunity disease. Ninety percent of the

victims of lupus are women. Also, lupus is more common among

women of color. Lupus is two to three times more likely to affect

African Americans, Hispanics, Asians and Native Americans than

Caucasian women. Lupus also appears to be more serious among

African American women.

Approximately 20 percent of lupus cases begin in childhood. Unfortunately, lupus is more severe in children. Nearly 70 percent of

children with lupus have kidney disease as opposed to 30 percent

of adults who develop lupus. Whereas half of those with adult onset

lupus have organ-threatening disease, nearly 80 percent of those

with childhood onset lupus go on to develop organ-threatening conditions.

Lupus strikes women in the their childbearing years between the

ages of 15 and 44. This is one of the most devastating realities of

lupus. It destroys the quality of life during a time when young

women should be enjoying their best health.

Many people with lupus suffer 3 to 5 years, visiting 5 or more

doctors before they receive a correct diagnosis. Many medical

schools do not provide family physicians with sufficient training to

diagnose lupus. By the time some lupus patients are diagnosed, especially in poor or rural communities, irreversible damage to vital

organs may have already occurred. This increases the need for expensive treatments such as kidney dialysis or transplantation.

Medical researchers have made progress, and there is great hope

for new discoveries. Still, most lupus patients are frustrated that

the disease remains incurable.

As you can imagine, Mr. Chairman, lupus is not an easy disease

to live with. Over a million American families are struggling to

86

cope with lupus every day of their lives. I know this personally

from watching my sister suffer from the devastating effects of the

disease.

It is time for action. A majority of Members of the U.S. House

of Representatives, a total of 243, are cosponsor of H.R. 762. I urge

that this legislation be brought to the floor of the House for a vote

as soon as possible.

Thank you for the opportunity to represent the victims of lupus

at today’s hearing, and I will be happy to answer any of your questions. And thank you for the extra time.

[The prepared statement of Tomiko Fraser follows:]

PREPARED STATEMENT OF TOMIKO FRASER, NATIONAL SPOKESPERSON, LUPUS

FOUNDATION OF AMERICA

Good Morning Mr. Chairman, and Members of the Subcommittee. I appear before

you today representing the Lupus Foundation of America on behalf of 1.4 million

Americans who have lupus erythematosus, a devastating disease that causes the immune system to attack the body’s own cells and organs.

Unfortunately, one of the victims of lupus is my younger sister, Shneequa, who

has a very serious case of lupus that affects her brain. The disease has been so devastating to Shneequa that she must receive around-the-clock care at a skilled-nursing facility.

That is why I have agreed to serve as a National Spokesperson for the Lupus

Foundation of America. I want to help educate all Americans about the devastating

impact lupus has on its victims.

I urge Congress to pass H.R. 762, the Lupus Research & Care Amendments Act

of 1999. Congresswoman Carrie Meek, who lost a sister to lupus, introduced this

legislation. 243 members of the U.S. House of Representatives are cosponsors of H.R.

762. The legislation authorizes a $23 million increase to the current funding level

for lupus medical research supported through the National Institutes of Health. It

also authorizes $75 million to fund a grant program. This program would provide

local governments, community hospitals, and other non-profit health care facilities

with a pool of funds so they could offer life-saving medical care to poor or uninsured

people with lupus.

This grant program will help local communities hardest hit by lupus, especially

in medically under-served areas, including rural and urban communities where

often there is a shortage of medical facilities to treat people with lupus.

Lupus deserves special funding consideration. Lupus is the prototypical autoimmune disease. Research on lupus benefits all autoimmune diseases that disproportionately affect women. Autoimmune diseases are the fourth leading cause of

disability among women.

Lupus is an expensive disease to treat. The cost to provide medical care for a person with lupus averages between six and ten thousand dollars annually. The Lupus

Foundation of America estimates the economic impact of lupus on the federal treasury to be several billion dollars every year. These costs include disability income payments to the tens of thousands of lupus victims disabled every year by the disease.

They also include the cost of government-sponsored medical care provided through

the Medicare and Medicaid programs, and uncollected tax revenue due to lost wages

when individuals with lupus are unable to work.

The Lupus Research and Care Amendments Act of 1999 is a bipartisan effort to

address an urgent national health care crisis that inflicts an enormous burden on

individuals, families, the business community, the federal government, and society.

Many scientific opportunities exist, but current funding levels can support only one

in four of the promising studies submitted for funding that eventually will lead to

a cure for lupus. By accelerating medical research for lupus now, Congress will reduce future health care costs and save billions of dollars for the Social Security and

Medicare trust funds in future years.

Lupus is a complicated and mysterious disease that needs extensive study. Presently there is no cure for lupus, nor do researchers fully understand what causes

the disease.

We do not know why lupus alternates between periods of remission and periods

of disease activity, called flares. We do not know why the disease can remain mild

in some individuals and become life-threatening in others.

87

What we do know, Mr. Chairman, is that lupus has a devastating impact on its

victims and their families. We know that lupus causes debilitating health effects including extreme joint pain and swelling, constant fevers, overwhelming fatigue, horrible skin rashes, organ failure, and a host of other devastating symptoms. Lupus

destroys the quality of life for many of its victims. The disease can severely damage

the kidneys, heart, lungs, and other vital organs. Lupus disables one in five of its

victims, often at a very young age. And tragically, every year thousands of lupus

victims die from complications of the disease.

Lupus is not an equal opportunity disease. Ninety percent of the victims of lupus

are women. Also, lupus is more common among women of color. Lupus is two to

three times more likely to affect African-Americans, Hispanics, Asians and NativeAmericans than Caucasian women. Lupus also appears to be more serious among

African-American women.

Approximately 20% of lupus cases begin in childhood. Unfortunately, lupus is

more severe in children. Nearly 70% of children with lupus have kidney disease, as

opposed to 30% of adults who develop lupus. Whereas half of those with adult-onset

lupus have organ-threatening disease, nearly 80% of those with childhood-onset

lupus go on to develop organ-threatening conditions.

Lupus strikes women in their child-bearing years, between the ages of 15 and 44.

This is one of the most devastating realities of lupus—it destroys the quality of life

during a time when young women should be enjoying their best health.

Many people with lupus suffer three to five years, visiting five or more doctors,

before they receive a correct diagnosis. Many medical schools do not provide family

physicians with sufficient training to diagnose lupus. By the time some lupus patients are diagnosed, especially in poor or rural communities, irreversible damage

to vital organs may already have occurred. This increases the need for expensive

treatments, such as kidney dialysis or transplantation.

Medical researchers have made progress; and there is great hope for new discoveries. Still, most lupus patients are frustrated that the disease remains incurable.

As you can imagine, Mr. Chairman, lupus is not an easy disease to live with. Over

a million American families are struggling to cope with lupus every day of their

lives. I know this personally from watching my sister suffer from the devastating

effects of this disease.

It’s time for action. A majority of members of the United States House of Representatives—a total of 243—are cosponsors of H.R. 762. I urge that this legislation

be brought to the floor of the House for a vote as soon as possible. Thank you for

the opportunity to represent the victims of lupus at today’s hearing. Now I will be

happy to answer your questions.

Mr. BILIRAKIS. Thank you very much, Ms. Fraser.

Dr. Bryan.

STATEMENT OF R. NICK BRYAN

Mr. BRYAN. Good morning. My name is Nick Bryan. I currently

serve as professor and Chairman of the Department of Radiology

at the University of Pennsylvania. I really appreciate this opportunity to share some of my experiences as an imaging researcher

and a former NIH staff member with you and to express my support for H.R. 1795.

I would like to thank you, Mr. Chairman, and the committee

leadership for holding this hearing, and I would like to thank the

sponsors of the bill, Mr. Burr and Mrs. Eshoo, for their leadership

and efforts on this issue.

You have already heard about the importance and uniqueness of

biomedical imaging and engineering, and I will not belabor the

point. I will instead focus on what I view as current structural inadequacies to support this field in NIH.

Prior to coming to Penn, I served for 2 years as Director of Diagnostic Radiology and Associate Director, Imaging Sciences Program, at the Warren G. Magnuson Clinical Center at the NIH.

During my tenure, and with superb support from Dr. John Gallen,

director of the clinical center, we were able to consolidate several

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disparate imaging departments into a unified imaging sciences program, which elevated the status of imaging research on the NIH

campus and began to lay a foundation for an advanced research

program.

In the final analysis, though, I felt the imaging sciences program

could not be wholly successful mainly because the very structure

of the NIH makes such an endeavor problematic. Research authority and resources reside in the institutes, not in programs at the

clinical center. As a result, the success of our imaging research was

ultimately dependent on the ability of me and my colleagues to convince one or more of the institutes, institutes whose primary missions and priorities are in areas other than imaging, to divert

funds from their main activities and commit those funds to imaging

research.

I accepted the position at the clinical center knowing that it involved a significant challenge, but in the hope and in the belief

that an effective imaging research program could be developed

within the parameters of the NIH structure. In fact, at that time

I was skeptical about the need for a new institute. My experience,

however, gradually changed my opinion and convinced me that the

existing NIH organization will not work optimally for imaging in

bioengineering.

Ultimately, my decision to leave the NIH owed much to the inherent obstacles to imaging research that are built into its structure. It should be recognized that the NIH does acknowledge the

importance of imaging and has taken steps to make imaging research a more visible part of its portfolio, as you heard. And, for

instance, the National Cancer Institute has authorized significant

expansion of the extramural biomedical imaging program.

The NIH Biomedical Engineering Consortium, known as

BECON, sponsored a conference in 1999 entitled Biomedical Imaging Symposium: Visualizing the Future of Biology in Medicine. This

year the NIH, in response to a congressional mandate, has begun

to organize a new Office of Bioimaging, Bioengineering and

Bioimformatics in the Office of the Director of the NIH. The new

office is to provide focus for and facilitate work in our fields.

Unfortunately, all of these initiatives suffer from major flaws.

First, the NCI program applies real resources to imaging, but the

research is limited to cancer imaging. Cancer imaging is clearly important and should be extremely high priority, but imaging, as I

have said, is not disease- or organ-system-specific. It has applications far beyond cancer, applications that are neglected when the

research focus is on cancer or any other individual disease.

Initiatives such as BECON and OB3, as it is called, the new office, constitute a useful effort to identify research opportunities and

focus attention on imaging, but they bring little in the way of actual research dollars to imaging research. They represent a strong

commitment by the NIH to identify potentially fruitful areas of research, but no commitment at all to supporting that research.

The Director of the OBBB will have to do what I did. He or she

will have to pass the hat by the current institutes for contributions,

and I am certain that the donations will be insufficient to support

a robust imaging research program.

89

In fact, it is unrealistic and perhaps even inappropriate to expect

existing disease and organ system institutes to divert resources

from their primary missions in order to support basic research to

advance the science of imaging. For these reasons I believe that the

creation of a National Institute of Biomedical Imaging and Bioengineering is essential to promote the development of new imaging techniques and technologies.

In order to flourish and grow consistently at the NIH, a scientific

field requires organizations with the mandate, the responsibility,

the authority, and the resources to direct and drive investigation

in that field. In the NIH structure, institutes possess those attributes.

I would like to conclude by noting that my opinions are not

alone. Nearly all of radiology and bioengineering supports this is

initiative. During the current year, I am also privileged to serve as

Chairman of the Board of Directors of the Radiological Society of

North America. The RSNA is the largest radiological organization

in the world, with a membership of more than 30,000 radiologists,

physicists, and allied scientists. The RSNA and more than 40 other

professional organizations representing physicians, radiologic technologists, bioengineers and imaging scientists have joined coalitions

that support H.R. 1795. The total individual membership of these

organizations is well over 100,000.

All of us believe that this is the time to create a National Institute of Biomedical Imaging and Bioengineering to support a field

of inquiry that is central to continued progress in advanced research in biomedicine as well as the development of better systems

for delivery of health care. This institute would be good for patients, physicians, and the NIH itself.

I urge the subcommittee to approve this bill. I would be pleased

to answer any questions.

[The prepared statement of R. Nick Bryan follows:]

PREPARED STATEMENT OF R. NICK BRYAN, CHAIRMAN, DEPARTMENT OF RADIOLOGY,

UNIVERSITY OF PENNSYLVANIA HEALTH SYSTEMS

Good morning. My name is Nick Bryan. I have been a radiologist specializing in

neuroradiology for more than 25 years. I currently serve as Chairman of the Department of Radiology and Eugene P. Pendergrass Professor of Radiology at the University of Pennsylvania. Prior to coming to Penn, I served for two years as Director

of Diagnostic Radiology and Associate Director, Radiologic and Imaging Sciences

Program, at the Warren G. Magnuson Clinical Center at the National Institutes of

Health.

During the current year I am also privileged to serve as Chairman of the Board

of Directors of the Radiological Society of North America. The RSNA is the largest

radiological organization in the world, with a membership of more than 30,000 radiologists, physicists, and allied scientists.

I appreciate this opportunity to share some of my experiences as an imaging researcher and NIH staff member with you and to express my support for H.R. 1795,

the National Institute of Biomedical Imaging and Engineering Establishment Act.

I would like to thank you, Mr. Chairman, and the Committee leadership for holding

this hearing and the sponsors of the bill, Representatives Burr and Eshoo, for their

leadership and efforts on this issue.

It is important to note that all of radiology and imaging supports this initiative.

More than 40 separate professional organizations representing physicians, radiologic

technologists, bioengineers, and imaging scientists have joined coalitions that support H.R. 1795. The total individual membership of these organizations is well over

100,000.

This is perhaps the most exciting time in the history of medical imaging and, indeed, all of medicine. Breakthroughs in imaging have allowed physicians to elimiVerDate 11-MAY-2000 09:33 Oct 24, 2001 Jkt 010199 PO 00000 Frm 00093 Fmt 6633 Sfmt 6621 E:\HEARINGS\67114 txed01 PsN: txed01
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nate much surgery, including virtually all exploratory surgery, and to diagnose disease at earlier and earlier stages of development, when treatment is most effective.

Because of advances in imaging, patients receive more effective treatment, avoid

painful, expensive, and often dangerous surgical procedures, and live longer.

The National Institutes of Health is the premier medical research institution in

the world and has been at the center of pathbreaking research in most areas of

medicine. In imaging, however, the NIH is not—and under its present structure

cannot be—the catalyst of imaging innovation. The various institutes are focused on

specific disease processes or organ systems, but imaging cuts across those lines and

is broadly applicable to virtually all diseases and organ systems. Consequently, imaging is used as a tool in all the institutes, but there is no home at the NIH for

the basic research that is essential to develop new imaging techniques and technologies for the 21st century.

The basic science of imaging and bioengineering, it must be remembered, is fundamentally different from that of the existing institutes at the NIH. Imaging is

based on mathematics and physics, not the biological sciences that underly most of

the research in the current institutes. Imaging and bioengineering are unique scientific fields at the NIH and are also critical to future advances in the delivery of

high quality health care.

While at the NIH, I directed intramural research efforts in imaging in the Clinical

Center. During my tenure, we were able to consolidate several disparate imaging

departments into the unified Imaging Sciences Program (ISP), which elevated the

status of imaging research on the NIH campus and began to lay a foundation for

an advanced research program.

In the final analysis, though, the ISP could not be wholly successful, mainly because the very structure of the NIH makes such an endeavor problematic. Research

authority and resources reside in the institutes, not in programs at the Clinical Center. As a result, the success of imaging research proposals was ultimately dependent

on the ability of ISP researchers to convince one or more of the institutes—institutes

whose primary missions and priorities are in areas other than imaging—to divert

funds from their main activities and commit those funds to imaging research. Even

when imaging researchers are successful, which sometimes requires artificially tailoring proposals to create the appearance of disease- or organ-specific research, the

institutes are likely to assume practical control of projects and, in all probability,

recast the research to fit their own missions.

I accepted the position at the Clinical Center knowing that it involved a significant challenge but in the hope, and in the belief, that an effective imaging research

program could be developed within the parameters of the NIH structure. In fact,

at that time I was skeptical about the need for a new institute. My experience, however, gradually changed my opinion and convinced me that the existing NIH organization will not work for imaging. Ultimately, my decision to leave the NIH owed

much to the inherent obstacles to imaging research that are built into its structure.

It should be recognized that the NIH has taken steps to make imaging research

a more visible part of its portfolio. The National Cancer Institute, for example, has

designated imaging as one of only a few ‘‘Extraordinary Opportunities for Investment’’ and has authorized significant expansion of the extramural Biomedical Imaging Program. The Biomedical Imaging Program at the NCI, under the extremely

able leadership of Dr. Dan Sullivan, has benefited from growing staff resources and

new research initiatives.

In addition, the Bioengineering Consortium, known as BECON, sponsored a conference in June 1999 titled ‘‘Biomedical Imaging Symposium: Visualizing the Future

of Biology and Medicine.’’ Participants produced an ambitious research agenda for

imaging science that calls for focused efforts in a number of fields:

—multidisciplinary research;

—imaging technology, probes, and contrast agents;

—education and training;

—clinical trials and informatics

—greater cooperation among the NIH, the Food and Drug Administration, the

Health Care Financing Administration, and private industry to improve the

speed with which new imaging technologies, probes, and contrast agents are

transferred to clinical practice.

The 1999 BECON symposium was actually the second NIH-sponsored conference

in recent years devoted to imaging research. In 1994, the NIH brought together

more than 40 top researchers from inside and outside government at a Conference

on Developing a Long-term Plan for Imaging Research. Conference participants developed a set of recommended research goals in 33 separate areas of basic science,

basic and applied technology, and organ-based clinical research.

91

Finally, this year the NIH, in response to a Congressional mandate, has begun

to organize a new Office of Bioengineering, Bioimaging, and Bioinformatics in the

Office of the Director, NIH. According to the Vacancy Announcement seeking candidates to direct the OBBB, the Director of the new Office ‘‘will provide a focus for

stimulating and coordinating the development of biomedical engineering, bioimaging

and bioinformatics activities among the 25 Institutes and Centers (ICs) at the NIH;

and will facilitate the overall planning, development, and implementation of NIH

biomedical engineering, bioimaging and bioinformatics research programs and activities.’’ Unfortunately, all of these initiatives suffer from one of two fatal flaws. First, the

NCI efforts apply real resources to imaging, but all of the research is on cancer imaging. Cancer imaging clearly should be an extremely high priority, but imaging,

as I have said, is not disease- or organ-system specific. It has applications far beyond cancer—applications that are neglected when the research focus is on cancer

or any other individual disease.

ACRIN, the cooperative clinical trials group chaired by Dr. Hillman, offers a clear

example of the shortcomings of this approach. ACRIN represents a significant and

wise investment, but this application of resources could produce so much more if imaging technologies beyond cancer were included.

The ACRIN approach, valuable as it is, actually shortchanges cancer research as

well as the broader field of imaging. Evaluating the use of existing techniques and

technologies for the diagnosis and treatment of breast, prostate, and other cancers

will produce important knowledge that will result in incremental improvements in

patient care. But the real breakthroughs that will produce quantum leaps forward

are likely to occur through the development of wholly new imaging modalities that

do not result from disease-specific research.

The second group of NIH initiatives—the 1994 conference, the BECON symposium, and the creation of the OBBB—represents the second fatal flaw. These initiatives constitute a useful effort to identify research opportunities and focus attention

on imaging, but they bring little in the way of actual research dollars to imaging.

They represent a strong commitment by the NIH to identify potentially fruitful

areas of research but no commitment at all to supporting that research.

The Director of the OBBB will be, as I was as Director of the Imaging Sciences

Program, dependent on the goodwill and interest of the other institutes. Again,

these are institutes that do not have imaging as primary missions and which are

faced continually with competing claims for scarce resources from within their primary research constituencies.

The disciplines represented in the existing institutes use imaging, but they cannot

accommodate the basic science of imaging itself. It is unrealistic, and perhaps even

inappropriate, to expect the existing disease and organ system institutes to divert

resources from their primary missions in order to support basic research to advance

the science of imaging.

Without grant-making and decision-making authority, these NIH efforts to improve coordination can be marginally successful at best. No one would suggest that

the search for better treatments for cancer, diabetes, or other diseases should be undertaken by organizations that lack the capability to make research grants—or that

progress in these vital areas should be dependent on the ability of researchers to

convince other institutes to divert a portion of their resources away from their chief

responsibilities. Yet that is precisely the approach the NIH has taken to imaging.

In consequence, while the NIH might consider the recommendations from the 1994

and 1999 imaging conferences to be priorities, there is not much evidence that significant action has been taken on this research agenda. The present organization

of the NIH makes such action unlikely.

For these reasons, I believe that the creation of a National Institute of Biomedical

Imaging and Bioengineering is essential to promote the development of new imaging

techniques and technologies. In order to flourish and grow consistently at the NIH,

a scientific field requires an organization with the mandate, the responsibility, the

authority, and the resources to direct and drive investigation in that field. In the

NIH structure, only institutes possess those attributes.

Institutes, for example, can issue Requests for Applications (RFAs) and Program

Announcements (PAs) to initiate research projects and direct resources toward investigations on specific subjects that offer particular opportunities for scientific advances. Such institute-initiated research projects represent a substantial portion of

the institutes’ extramural research portfolios. Even smaller and mid-sized institutes

can exert considerable influence on the direction of research. A recent analysis

showed that the National Institute on Aging (NIA), with only the 10th largest budget among the institutes and major centers at the NIH, issued seven RFAs covering

a wide variety of topics with a total price tag of more than $16 million in Fiscal

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Year 1999. In the same year, the NIA collaborated on 16 additional RFAs in which

other institutes were the primary sponsors. Without an institute, imaging lacks this

fundamental capability to guide and support the research in this field.

Research training is another key issue. Training grants ensure the continuity of

a pool of trained researchers in the institutes’ fields of research. Under the current

structure, training opportunities in imaging are generally limited to grants that

focus on the use of imaging in connection with specific diseases and organ systems

rather than on training imaging scientists to conduct the basic research that will

produce new modalities. An analysis of NIH data on T32 grants, the most common

NIH training awards, found only three imaging awards of the 148 active T32 grants

in the National Heart, Lung, and Blood Institute. Moreover, the National Institute

of Neurological Disorders and Stroke (NINDS), which is the institute most closely

related to my work in neuroradiology, had no active imaging grants among its 44

T32 awards.

The National Institute of Biomedical Imaging and Bioengineering would help to

ensure that the brightest young radiologists and imaging scientists have opportunities to obtain research training. Such opportunities are largely non-existent under

the present system.

For all of these reasons, I believe that this is the time to create a National Institute of Biomedical Imaging and Bioengineering to support a field of inquiry that is

central to continued progress in advanced research in molecular biology as well as

to the development of a better system for the delivery of health care. The proposed

would be good for patients, physicians, and the NIH itself. I urge the Subcommittee

to approve H.R. 1795, and I would be pleased to answer questions.

Mr. BILIRAKIS. Thank you so much, Dr. Bryan.

I will start off the questioning.

Ms. Fraser, why does lupus seem to affect women of color more

often than Caucasian women?

Ms. FRASER. Well, this is a subject of a research project currently

under way by the NIH Lupus and Minority Studies, or LUMINA.

We believe lupus has a genetic basis, and it appears that the gene

suspected of causing lupus may be more prevalent among women

of color.

Mr. BILIRAKIS. So we sort of know that or have come to that conclusion on the basis of studies that are taking place?

Ms. FRASER. Yes. That is correct.

Mr. BILIRAKIS. We do not know of any other reason, though,

other than the fact?

Ms. FRASER. Not yet, we are still checking.

Mr. BILIRAKIS. In terms of the administration’s support or nonsupport of the legislation, my understanding—and I may be wrong,

and if I am, I wish to be corrected, but I think it is significant—

that they have problems with title 2. The administration has problems with title 2. Are you aware of that?

Ms. FRASER. I would be happy to answer that, but I would like

to submit a written response to that question, if that is okay with

the chairman.

Mr. BILIRAKIS. Okay. Yes, we would like to have that from you,

by all means, because it would be very helpful in terms of not only

moving the legislation through, but we also try to work with the

Minority in most cases to work things out ahead of time, and that

would be very significant.

Dr. Wirth, can you tell us the organizations, or at least some of

the organizations, you are familiar with that are working on the

issue of global disease eradication?

Ms. WIRTH. Well, there are several organizations in the world.

The World Health Organization is very active in this area, but the

World Health Organization is more of an implementation organizaVerDate 11-MAY-2000 09:33 Oct 24, 2001 Jkt 010199 PO 00000 Frm 00096 Fmt 6633 Sfmt 6602 E:\HEARINGS\67114 txed01 PsN: txed01
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tion rather than a research organization. They have a very small

research arm.

Really the United States is really the only—the United States

National Institutes of Health and to a certain extent the NSF are

really the only organizations that have the knowledge base and the

research base to bring that to bear on these important tropical diseases. There is some work in Europe funded by the European

Union, but, again, I think the United States really has the leadership role, and we need to maintain that.

Mr. BILIRAKIS. I know—I am a Rotarian. Do not attend very

many meetings these days for business reasons, but in any case

they have worked on eradicating polio around the world, as you

know.

Ms. WIRTH. That is correct.

Mr. BILIRAKIS. And that is working and has worked very well;

has not it?

Ms. WIRTH. Uh-huh. Polio actually will be eradicated in this

hemisphere this year. And there have been many groups involved

in that, and certainly the Rotary has been involved particularly in

the last several years.

And, again, I think that is implementing a very important step,

implementing the sort of research in discoveries that have been

made over the years primarily here in the United States. So I think

there are many steps to eradicating global disease. We have to get

those vaccines and drugs that we have to the people who need

them, and that is very important. But we also need for many of

these diseases to develop new interventions. The tools we have just

aren’t working.

Mr. BILIRAKIS. Okay. So the World Health Organization is just

not doing the job, and you feel that the national commission that

Mr. Gekas is a proponent of would do the job?

Ms. WIRTH. I think so. And it would particularly establish the

United States in its natural leadership role in this area. I think

that we need political leadership at this point to bring to bear on

this problem. We have the skill set in the United States to develop

these interventions and to implement them, but we need to take

that leadership role in the world.

Mr. BILIRAKIS. Do we have now—and if not, is that the reason

maybe for the national commission—do we have the proper coordination? For instance, I don’t know, how has Rotary gone about it

all to know exactly where to go? Have they coordinated?

Ms. WIRTH. That is right. I think one of the things that the National Commission could do is to have a focus point for this kind

of work in the United States. I think in the case of Rotary and

other nongovernmental organizations, they have sort of gone about

it themselves, having to go to different agencies, to different interest groups to begin to find out about it, and then to become involved with the implementation.

Mr. BILIRAKIS. Well, let me ask you this. If this commission is

formed, the administration feels that CDC and NVPO, the National

Vaccine Program Office, should be included in the composition of

the commission’s membership. And also that the FDA, as the agency overseeing vaccine safety and approval of new vaccines, should

also have a role in it if the bill is enacted. Your opinion?

94

Ms. WIRTH. I think that those, particularly the CDC and the

FDA, would be appropriate to become involved in this. They have

implementation roles. And I think the national vaccine program is

also one that certainly could be involved. They are dealing very

specifically with vaccine issues. As you know, there are broader

issues of implementation including drug development and development of other controlled, measured environmental and insecticides

at some point.

Mr. BILIRAKIS. Any other opinions regarding that particular legislation that you all may want to offer?

All right. That being the case, the Chair yields to Mr. Brown.

Mr. BROWN. Thank you, Mr. Chairman.

Dr. Wirth, I am sorry I missed your testimony. I was voting. But

I read your testimony, and you said, as we begin the 21st century,

we are blessed with unimaginable opportunities to build on breakthrough research to control and prevent world disease.

Dr. Gro Brundtland of the World Health Organization—I would

argue that the World Health Organization has done phenomenal

work over the last 20 years. Nonetheless, she said talking about tuberculosis—and I know your expertise is more malaria, and I want

to get to that in a second, but she said it is not medical eradication—dealing with tuberculosis is not a medical problem, it is a

political problem. But—and I think back just less than a year ago

in December 1999, the Government of India, working with nongovernment organizations around the world, including the World

Health Organization, including all kinds of groups from this country, had a national immunization day and immunized 134 million

children in 1 day, which tells me that Mr. Gekas’s bill goes in the

right direction in this country. Our country should show a great

deal more leadership in dealing with issues that surely we can.

Tuberculosis and malaria both do not get the attention from the

big drug manufacturers in their research arms that they should.

The drug companies seem much too interested, in my mind, in ‘‘me

too’’ drugs, in drugs that are more cure for baldness than for tuberculosis, malaria, lupus, a whole host of diseases where there simply

is not the moneys, potential profit available. There is not a lot of

profit in malaria or TB especially, diseases that hit this country not

very hard and hit the poorest countries with the poorest citizens

especially hard.

Shift gears to Walter—Walter Reed has done especially and the

Defense Department has done especially good research in malaria.

We underfund Walter Reed. We fund organizations like NIH, a

wonderful government agency. We want to double its budget in the

next 5 years, yet we do not fund CDC very well, which its budget

is about one-sixth of the NIH. And we do not fund the Walter Reed

research arm of the Defense Department particularly well, putting

it mildly.

Is the only real hope for a malaria vaccine, TB vaccine, better

treatment of those diseases—TB, as you know, you need to take a

pill every day for 6 months, which in countries with military occupation, in places like Chiapas in southern Mexico, people are afraid

to go by the military checkpoint to get their TB pills every day.

And even though we can cure it, it is difficult because of that. Is

the only hope for a TB vaccine or malaria vaccine better medicines

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to treat those two diseases? Must there be government funding because the drug companies won’t do it? And what do we need to do?

Talk about malaria. What do we do with Walter Reed in the Defense Department, and what do we do with NIH and CDC on malaria? Even though it is not a great issue for me to go back to my

district in Ohio and say, I am working on malaria and TB, it does

not matter much directly today to citizens of this country, it will

down the road, and that is a whole other issue. But what do we

do with places like Walter Reed?

Ms. WIRTH. I share your respect for Walter Reed and the work

they have done over the last several years in developing antimalarial drugs. They really are the only group that has consistently maintained a research program, even in spite of very limited

funding.

And, in fact, I think that the solution to these diseases is going

to require a very large governmental component because the pharmaceutical industry, as you say, is driven by developing drugs that

are important for this country. These are important drugs for this

country, but the diseases of tuberculosis and malaria and many

other diseases found in tropical countries just will never have profits like drugs for diseases in this country. The drug companies will

not develop them. And I think we are going to have to—it is going

to require governmental intervention and governmental funding.

I recommend that Walter Reed certainly receive funding, that

the NIH receive funding for basic research and for translational research, something I think that the NIH has become very interested

and very active in.

And in terms of CDC, CDC is our implementation arm; once we

have these tools, we have to get them out. And, in fact, for many

diseases we could certainly improve the situation today just by better implementation of the tool we have. We still face the challenges, but certainly better implementation through CDC is important. So I recommend support for all of these organizations, and let

me correct myself if I misspoke. I certainly have a great deal of respect for the World Health Organization, but I think they need

help and they need leadership from the United States. Their budget is very small compared to the budget of the NIH, for example,

and I think they provide a forum, but I think they need help from

us, and I think we can assume the leadership role in these diseases.

Mr. BROWN. Thank you.

One last brief question. Should Walter Reed and the CDC be included in this bill, both?

Ms. WIRTH. Yes. I think that is an excellent idea.

Mr. BROWN. Okay. Thanks.

Mr. BILIRAKIS. Mr. Burr to inquire.

Mr. BURR. Thank you, Mr. Chairman.

Dr. Wirth, I don’t know that you misspoke, I don’t think you

need to apologize. Sherrod and I participated in the same hearing

in International Relations on the threat of global infections, a debate over whether it was a public health issue or whether it is a

national security issue, and I think we can all agree it is probably

(d) All of the above.

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Clearly the World Health Organization and other international

organizations that are targeted toward health issues have been effective on some things. Clearly there are other things where health

care professionals have pointed out the deficiencies that exist; and

with deficiencies in place, we cannot be assured of successful immunization or successful eradication of diseases that ultimately we

see as a threat, not only here but spreading throughout the globe.

And your reference to AIDS in Africa is a very good one. It is important that we recognize that that spread, as it begins to happen

in Asia, is of a magnitude that we have never seen before, potentially; and that every effort that we can make, not relying on any

one entity, is in fact the policy that we should adopt.

And I appreciate your allowing me to editorialize just a little bit.

Let me move to some of the other witnesses if I can because I

do have some real interest in another piece of legislation. Let me

turn to you, Dr. Bryan.

Who benefits? Who benefits from the creation of an institute for

biomedical imaging?

Mr. BRYAN. Well, the people who benefit the most will be the patients.

Mr. BURR. Isn’t that who it is all supposed to be about?

Mr. BRYAN. That is exactly right.

Mr. BURR. For any person who is on the fence about this issue

as to whether we should create this, if they stopped for a minute

and thought, who is this about; if their answer was, the patients,

then the answer is, vote for this bill.

Mr. BRYAN. I would agree.

Mr. BURR. Is it safe to say—and I open this up to anyone—as we

identify breakthroughs in technology, that we can also expect

health care costs to possibly decline because if we detect earlier,

our treatments may be less intensive as it relates to a period of

time; and if you looked at the patient from that standpoint, the

quality of the care we deliver might in fact be better because we

have put them through less?

Mr. HILLMAN. That has been the history of the development of

imaging technologies: that, in fact, they do detect disease earlier,

they do replace more morbidity-inducing, more illness-inducing

technologies. And over time I believe that imaging technologies

have been cost-saving and also improve patient outcomes.

Mr. DUNNICK. I would like to make two comments in response

to that. First, when the DRGs were established a number of years

ago, my assumption was that the medical centers would try to reduce the number of ancillary tests being performed. In fact, just

the opposite occurred. We went to more ancillary testing in an effort to get to the answer faster, which in the long run will reduce

the cost of medical care.

My second comment is a reflection of my own experience. When

I was a medical student, my first research project was with influenza, and we tried to use immunization to protect against that disease.

We use death as the end point. Fortunately, we were using mice

as an animal model to test that. As we move along, radiology has

become very good at identifying disease processes being able to

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quantify them in many cases. And so we can use changes in imaging assessment as the end point for testing this.

We are now in what we call the era of molecular imaging or functional imaging, where we can actually detect changes before they

become manifest with routine testing. This allows us to see the

changes, see whether treatment is effective before the disease has

gotten out of control. I think these will make dramatic changes in

decreasing the cost of health care.

Mr. BURR. Can any of you address a specific disease where, say,

in the last decade the imaging improvements have changed in—— Mr. DUNNICK. Absolutely. Trauma would be the first response to

that. The patient comes into the emergency room, and in fact it

does not even have to be a traumatic injury. It can be a patient

with abdominal pain and the conventional way to treat that would

be first to do an operation to open the abdomen and find where the

pathology is.

We can do that noninvasively. In the trauma setting specifically,

we can now identify not only the problem, but in many cases, quantify it, which enables more conservative therapy.

So it has resulted in a dramatic decrease in the number of patients that have to go to the operating room.

Mr. BURR. Let me ask one last question with the chairman’s indulgence.

One of the fears that I have is that we are successful and that

not only in imaging, but in other areas of medical breakthroughs,

we are successful. Technological improvements have not necessarily

been rewarded through the reimbursement process in this country,

specifically Medicare.

If, in fact our reimbursement system does not recognize the cost

of technology and the cost of this research, what will that do to further development of new innovations, new treatments, new imaging that might detect disease earlier?

Mr. BILIRAKIS. Important question, but brief answers, please.

Mr. HILLMAN. Yes, there are two things that this new institute

will be able to do better than we are currently: One, as I indicated,

that it will have an assessment component that will run clinical

trials in a timely fashion to provide the information to guide reimbursement. In fact that has been problematic under the current

NIH structure.

The other is that we will develop relationships directly with the

regulatory agency and payers to quickly move these technologies

into practice.

Mr. BURR. I thank the witnesses. I thank the chairman. I yield

back.

Mr. BILIRAKIS. Dr. Ganske.

Mr. GANSKE. Thank you, Mr. Chairman, for having this hearing.

I think there are several bills that we are talking about that have

merit, and while they may not be the biggest health care issues

that Congress is facing, such as prescription drugs or patient protection legislation or even, for that matter, a bill that this committee will be doing shortly on providing relief for Medicare, in particular, I hope, relief for rural hospitals.

I just completed my series of town hall meetings back in the district, and I get asked a lot about the high cost of prescription

98

drugs, and I find that there is one of these bills that I think relates

to that and that is the Orphan Drug Act which created incentives

for drug companies to develop therapies for rare diseases by awarding a period of 7 years of market exclusivity to a product approved

for an orphan indication.

I find the testimony of Mr. Thomas Lang to be convincing. He

says in his testimony, recently FDA has adopted a policy position

related to the scope of a clinically superior orphan drug’s exclusivity that actually undermines the incentives for companies to continue to innovate for additional improvements in these areas. As

noted earlier, FDA’s policy also raises questions of fairness, alternate product availability and patient and physician choice of therapy.

Now, after approval an original orphan drug, whenever a subsequent orphan drug with a clinically superior improvement has also

been approved and awarded exclusivity, FDA totally restarts the 7-

year exclusivity clock for the drug as a whole, and in this way the

improved drug shields the original drug from competition, even

when—after the original drug’s exclusivity period is over. In these

instances, companies that have developed new competing versions

of the same drug to treat the disease in anticipation of the expiration of the original 7-year exclusivity are unfairly denied access to

the market for an additional 7-year period.

I think this has pertinence to the high cost of prescription drugs.

And Congress, even in the short time period that we have left,

should significantly look at the Thornberry bill, H.R. 4242, because

I think that additional extensions of exclusivity will surely keep

prices higher. That is why I and others have been fighting an extension of—patent extension for the drug Claritin.

And so, Mr. Chairman, I again thank you for holding this hearing. I thank the people for testifying. I have another hearing that

is ongoing at this moment that I will be going to and I will yield

back.

Mr. BILIRAKIS. And I thank the gentleman. If he would yield to

me maybe 30 seconds of his time before me yields——

Mr. GANSKE. I will.

Mr. BILIRAKIS. You know we have a dilemma here in terms of,

let’s say, NIH funding. Let’s just talk NIH funding, and the dilemma is, should we in this so-called ivory tower determine the

amount of money for research that ought to go to specific diseases?

I mean, the experience that we have had on this committee has

been just amazing, the number of diseases that I am sure most of

us, if any of us, although some are medical doctors, were not even

aware of.

Just some terribly sad stories that we are going to hear, and we

are going to hear certainly even on the next panel, and the plea

for more funding for Parkinson’s, more funding for lupus. We can

just go on and on. Mohammad Ali was here pleading for more funding for Parkinson’s.

So the thought has been that we just do not know enough of actually what is taking place up there in terms of research and how

close they may be to a breakthrough and that sort of thing; and

should we be telling them, rather than just giving the money or

doubling the money as Mr. Brown has indicated?

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Any opinions in that regard, because I consider that quite a dilemma. We have come to maybe a conclusion.

I have not talked with Mr. Brown on his feelings on that subject.

I don’t remember that we have in any case. But any feelings in

that regard? Just very quickly, please.

Mr. BRYAN. Mr. Chairman, I think you do have indeed a major

challenge, and that is the responsibility you all accept as our public

representatives. I think that your directive is to provide broad

strokes of direction to institutes such as the NIH. And I do think

you have to leave some of the details to them.

Mr. BILIRAKIS. Yes, sir?

Mr. DUNNICK. I think in terms of H.R. 1795, what we are really

talking about is not necessarily more funding, but reorganization

to establish focus and priority setting.

Mr. BILIRAKIS. Which is basically what Ms. Fraser has testified

to and what Mrs. Meek’s bill does, right?

Ms. FRASER. Yes. I just want to say that we just want to level

the playing field pretty much. Lupus, I did not really know a lot

about it before my sister was infected with the disease. And as I

learned more about it and I learned that there are so many Americans, 1.4 million infected with it, I think it is a disease that should

be on the forefront right now.

Not putting anybody else’s cause down or their testimony, but we

just want to level the playing field is why we are here.

Mr. BILIRAKIS. I just wanted to sort of share with you the dilemma that we have and the difficulty sometimes. Did you want to

add something quickly?

Ms. WIRTH. Yes. Very quickly, I come from the sort of training

where I feel getting basic training and understanding fundamental

mechanisms is very important to understanding disease. So, in

general, I think it is very important that NIH be given as much

free rein to follow the advances as they come.

But I also think it is important that the interests of individuals,

who perhaps cannot sit at a table like this, are represented in the

area of biomedical research. And I think without influence from the

public to help direct the NIH to areas of importance—I mean, the

area of importance I clearly consider very important is global

health; and rarely is there anyone sitting at this table with direct

experience in it.

So I think it is very important that that be heard at NIH at least

in an advisory and perhaps not absolutely directive way.

Mr. BILIRAKIS. Thank you. I see that Mr. Bryant, who was here

earlier and had to leave, has returned. Did you have any questions

of this panel, Ed?

Mr. BRYANT. Mr. Chairman, thank you. Just some very brief

statements and perhaps a question of Dr. Bryan. I think I am

thinking more of the medical research at Pittsburgh, and you are

down the road a little bit I guess in the other direction. But perhaps you know something about this.

I agree with Dr. Wirth in terms of that NIH ought to be given

a broad rein—range, I guess, in which to make their decisions and

less input from those of us who come into contact with a lot of

these difficult situations and have to—can’t really pick and choose.

We are not knowledgeable either to make those determinations.

100

But on the other hand, I think there is some need for input from

outside, as you point out, some representation, and I guess to a degree we do that.

It seems to me—and maybe I am not using the setup of NIH correctly, but I have heard the representation on their board or perhaps the doctors’ panels that help set these priorities. Perhaps

maybe we could have a better play in what groups are represented

there—what specialties, what doctors, what diseases are represented there. And that would be a way of again giving them

broad powers, but yet we in Congress being able to make sure that

one disease is not given priority over another one for the wrong

reasons.

Second—and my last comment in this area, and I am going toward something that I just mentioned earlier—I have been working

really closely with a group in Memphis in terms of a disease that

again does not address a large part of our population, but a lot of

our—a percent of our young children. It is Duchenne’s muscular

dystrophy; I was at a fund-raiser for them about a week ago in

Memphis, and I am told that that is a disease in which there have

been great advancements made, and I think a lot of that has come

out of the University of Pittsburgh or the Pittsburgh area.

I think our priorities also ought to be, in addition to all the other

priorities, trying to find cures for those diseases regardless of the

size of the population affected; those diseases that are getting close

to being solved, cured. That, to me as a layperson, a nonmedical

person, makes some sense, that if we are getting close—because

that can open the doors to other related diseases, I would think.

I would think Duchenne’s muscular dystrophy would have some

very close cousins in terms of diseases that could be affected in a

positive sense.

So, Dr. Bryan, I am asking you cold, do you know anything about

that particular disease in terms of are we making progress there?

Mr. BRYAN. I am familiar; I am not an authority on that disease.

But you are correct, it is a disease that affects a relatively small

population, but in a devastating fashion. And remarkable advances

have been made, mostly in understanding the genetics and etiology

of the disease.

I think the dilemma is one that is difficult. Your committee has

to face the public needs, define areas where you think emphasis

should be placed. But then I think, to be honest, one has to defer

to our peer review system which—the NIH has a superb peer review system, where the experts have to adjudicate whether, in fact,

it is time, whether the knowledge is there, the technology is there,

the feasibility is there, to actually, at that time, fund the additional

research in that area.

So I think you all have to define priority from a public perspective, but then I think you have to take into account the experts and

the peer review system to help decide when you actually support

a particular research project area.

Mr. BRYANT. Quickly, does anyone have an additional comment?

Thank you for being here and thank you, Mr. Chairman.

Mr. BILIRAKIS. And I thank the gentleman.

We will excuse this panel at this time. We customarily furnish

written questions, and we request written responses. We would apVerDate 11-MAY-2000 09:33 Oct 24, 2001 Jkt 010199 PO 00000 Frm 00104 Fmt 6633 Sfmt 6602 E:\HEARINGS\67114 txed01 PsN: txed01
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preciate your assistance if you are all willing, to do that in a timely

fashion, Ms. Fraser, sooner rather than later, particularly on the

question that I raised—— Ms. FRASER. That will not be a problem.

Mr. BILIRAKIS. Thank you very much.

The second panel consists of—was scheduled at least—Mr. Jack

McCormick, Deputy Director of the Office of Orphan Drugs for the

Food and Drug Administration. Is Mr. McCormick here? No? Is

someone else going to be here to represent FDA on this matter?

Mr. DOLESKI. I work for the FDA.

Mr. BILIRAKIS. Well, you do not want to testify at all? Technical

responses?

In any case, you will be here for the testimony and the questions

so that you can take those back too? I appreciate that.

Why don’t you give us your name, sir, for the record?

Mr. DOLESKI. Dave Doleski, D-O-L-E-S-K-I, Legislative Analyst

with the FDA.

Mr. BILIRAKIS. I am going to introduce Mr. Robert Brady, a partner with Hogan & Hartson. They are here on behalf of Biogen; Ms.

Abbey Meyers, President of the National Organization of Rare Disorders; Mr. Thomas A. Lang, Senior Vice President, Strategic Product Development, Serono Laboratories, Rockville, Maryland, and he

is accompanied by Nick Ruggieri, Vice President of Governmental

Affairs; Ms. Catherine Bennett, Chair, Board of Directors, Cancer

Research Foundation of America.

And I would now yield with the committee’s indulgence to Mr.

Dan Burton, who is not on this committee, but who chairs of course

another very significant committee, who will introduce Mr. Navarro

and at the same time take 2 to 3 minutes to talk about his legislation. You are recognized.

STATEMENT OF THE HON. DAN BURTON, A REPRESENTATIVE

IN CONGRESS FROM THE STATE OF INDIANA

Mr. BURTON. Thank you, Mr. Chairman. And I hope you will

grant me just a minute or 2 latitude because I think some of the

things that I would like to say are very important.

To my classmate and chairman of this committee, Chairman Bilirakis, it is nice to be with you. I think it is the first time in the

18 years that we have been here that I have appeared before your

committee.

Mr. BILIRAKIS. I am sure that is true. And, Dan, I am sure the

thought has crossed your mind, there are not too many of us left.

Mr. BURTON. No, and unfortunately we just lost one of our classmates.

Mr. BILIRAKIS. Yes, we just lost one of ours.

Mr. BURTON. Anyhow, I appreciate your holding this hearing and

allowing us to testify on H.R. 3677, the Thomas Navarro FDA Patient Rights Act.

The United States of America is a country based on freedoms,

and among the freedoms guaranteed through our Constitution are

freedom of speech, freedom to practice the religion of our choice

and a free press. However, we are not, as individuals, guaranteed

the freedom to make a life-and-death decision in the area of medicine.

102

Imagine our own government forbidding your child access to a

nontoxic treatment, a nontoxic treatment with full human subject

protection through clinical trials that has already saved the lives

of other children. Imagine being told that you must subject your

child to treatments that may cause him to be blind, to be deaf, to

make him sterile, to stunt his growth, to give him hormonal deficiencies, to lower his IQ and to give him secondary cancers.

Imagine having your choices reduced to chancing no treatment

and possibly death or toxic treatment and possibly creating a special-needs child with no guarantee of success, all at a time when

another treatment is available.

Imagine learning that the treatment that the FDA wants your

child to receive, that two of the three drugs in the, quote, ‘‘standard

protocol’’ of approval drugs, clearly state on their package inserts, ‘‘Not proven safe or effective in the pediatric population.’’ Now, that is exactly what Donna and Jim Navarro have been

faced with. Imagine being a doctor who has treated cancer patients

successfully for over 20 years. Imagine being repeatedly attacked

by the FDA in an attempt to stop your work. Attacked by the very

agency that is supposed to encourage and promote research.

Imagine submitting the BT-29 protocol so that a 4-year-old boy

can be treated with a nontoxic cancer therapy whose safety has

been established. A treatment which has saved the lives of other

children with the same type of cancer. Imagine this government

agency putting that protocol on hold because of other existing

treatments. That is exactly what has happened to Dr. Burzynski

down in Texas.

Many have heard the story of little Thomas Navarro. You may

have seen his story in ‘‘People’’ magazine, in the New York Post or

on CNN. His father, Jim Navarro, is here today to testify, and I

will leave the full story of Thomas’ specific condition for Mr.

Navarro to talk about.

Two years ago the parents of another little boy, Dustin Kunnari,

testified before our committee, the Government Reform Committee,

about FDA’s gatekeeping on clinical trials. Dustin had the same

form of cancer as little Thomas Navarro. Dustin was the last person the FDA allowed to receive antineoplastons without having

first failed chemotherapy and radiation. He is healthy and cancerfree today and without the devastation of chemotherapy and radiation side effects.

Over the last 3 years, the Committee on Government Reform has

conducted five hearings looking at cancer treatments and access to

care. Unfortunately, Thomas Navarro is just one of thousands of

Americans who have been excluded from clinical research because

of the FDA. He is just one of the thousands of children who are

denied access to the parents’ treatment of choice because the government’s agency has made a life-or-death decision for the family

and not allowed them the freedom to choose.

The heart of this whole issue, Mr. Chairman, is, who decides? Is

it the role of the U.S. Government to make a treatment decision?

Or is it the right of the patient and the family to make an informed

treatment choice?

H.R. 3677, the Thomas Navarro FDA Patient Rights Act is the

first step in restoring medical freedom. It is the first step in taking

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the decisionmaking out of the hands of the government and putting

it back in the hands of the individual where it belongs, an informed

decision.

Mr. Chairman and members of the committee, H.R. 3677 has 43

cosponsors from both sides of the aisle, Democrat and Republican.

I respectfully request your help in getting this bill passed during

this Congress.

I am now pleased to introduce Jim Navarro, Mr. Chairman. And

once again I want to thank you very much, my colleague, for holding this hearing.

Jim testified at our June hearing and shared with us the challenges that they faced as a family dealing with a cancer diagnosis

and the Federal agency that has forced them into a corner. They

have spent almost all of their money—I think they sold their

house. They completely depleted all of their resources—in trying to

solve the problem of their boy. And it is a heart-rending story and

I know Jim is going to go into it in detail. He is here to testify

about this bill.

Jim and Donna Navarro are intelligent, conscientious parents.

They love their son. They stood firm in the battle to find the best

and safest treatment for their child. And Jim is a brave man fighting a battle on two fronts. While he is in the battle for his son’s

life, he is in a battle for his own life. Several months ago Jim was

diagnosed with prostate cancer. So, Jim, we wish you the best. And

we pray for you and your boy.

And with that, Mr. Chairman, I would like to yield, if you do not

mind, to Mr. Navarro.

Mr. BILIRAKIS. Thank you, Dan. Thanks for your interest in this

subject, all issues in America.

The Chair will now yield to Mr. Navarro, who uses as his address: Ronald McDonald House, Room 1101, 405 East 73rd Street,

New York, New York.

Mr. Navarro, please proceed, sir.

STATEMENTS OF JAMES NAVARRO, FATHER OF THOMAS

NAVARRO; ROBERT BRADY, PARTNER, HOGAN & HARTSON,

ON BEHALF OF BIOGEN, INC.; ABBEY MEYERS, PRESIDENT,

NATIONAL ORGANIZATION FOR RARE DISORDERS; THOMAS

A. LANG, SENIOR VICE PRESIDENT, STRATEGIC PRODUCT

DEVELOPMENT, SERONO LABORATORIES, INC.; AND CATHERINE P. BENNETT, CHAIR, BOARD OF DIRECTORS, CANCER

RESEARCH FOUNDATION OF AMERICA

Mr. NAVARRO. That is home, as you stated because as the chairman stated, there is no longer a home for us.

Good morning, Mr. Chairman, my name is Jim Navarro and I am

the father of 5-year-old Thomas Navarro for whom this bill is

named.

I have been asked to speak on the benefits of this bill, and I

would like to first go on record saying that my son’s health has not

stood still while the slow wheels of government move, and thus this

bill will not help my son. It is too late to bring hope to our family,

hope that the FDA would stand down and allow my son access to

our first choice of treatment.

104

We were forced to begin the FDA’s preferred treatment this summer. This bill will, however, help thousands of others. This bill was

conceived as a result of the FDA’s unwillingness to allow Thomas

access to a treatment which had a higher rate of success than the

treatment offered through conventional means.

This bill will, however, bring hope to others, others who, like us,

have been denied access to treatments that show promise and give

a chance of survival, treatments which are good or greater than

those treatments currently available for treating pediatric cancer.

We were faced with a decision almost a year ago, which changed

our lives forever, when our son Thomas was diagnosed with medulloblastoma, which is a nonsurvivable type of cancer. Thomas was

rushed to surgery within hours to remove a 4 by 6 centimeter

tumor from his cerebellum.

After surgery, we were faced with the decision of follow-up therapy. We discovered in short order that the standard follow-up

therapies, radiation and chemotherapy, both had severe and irreversible side effects. These included the possibility that he would

become blind, deaf, and sterile; that Thomas would develop hormonal deficiencies that would have stunted growth; that he would

have had an immediate and progressive loss of IQ; and that he

would develop secondary cancers as a result of the treatment itself.

We immediately began our search for a safer, nontoxic means of

treating our son. We found a treatment that showed a great promise for treating medulloblastoma only to discover that our son

would be denied access to the treatment by the FDA.

The doctor was not allowed to treat my son because the FDA did

not approve his access to the treatment. Yet the FDA has never approved radiation and chemotherapy for treating pediatric cancers.

In fact, if you read the manufacturer’s information that the drug

companies put in the box, they state, ‘‘Safety and effectiveness in

pediatric patients has not been established.’’ This sentence, in and of itself, should cause concern. The FDA

has no problem forcing this therapy on my son and thousands of

others, even though the safety and efficacy has not been established in children. In fact, if you are the parent of a terminally ill

child, your child can be taken away from you for experimentation

and, as parents, if you do not cooperate with this madness, you can

be thrown into jail for being bad parents.

Based on your experience, Mr. Chairman, what actions must I

take today to get you and your committee to take the required actions to save the Thomas Navarros of tomorrow? During the course

of this last year, my family has lost everything—our home, our

business, even our State of residency, which although it is hot, it

is a dry heat. It has been because of the kindness and generosity

of others, especially the support of Citizens for Health, that Thomas has been able to receive medical care.

H.R. 3677 introduced by Congressman Dan Burton now has 43

cosponsors, and I implore to you take this issue up and get H.R.

3677 passed into law.

Thomas is very hard to recognize now as a result of conventional

therapy. And I would like to encourage Mr. Waxman and others

that would stand in opposition to this bill to come see him, what

he looked like before and what he looks like now.

105

Thomas’s fight for his life now includes fighting against the very

treatment that he has been forced to take. And I can only tell you

it has been a very long and hard year.

Thank you for letting me speak.

[The prepared statement of James Navarro follows:]

PREPARED STATEMENT OF JAMES NAVARRO

Good morning Mr. Chairman, my name is Jim Navarro. I am the father of 5 year

old, Thomas Navarro, for whom this Bill is named. I have been asked to speak of

the benefits this Bill would present. I would first like to go on record saying that

my son’s health has not stood still for the slow wheels of Government to move, and

thus this Bill may not help my son. It is too late to bring hope to our family. Hope

that the FDA would stand down and allow my son access to our first choice in treatment. We were forced to begin the FDA’s preferred treatment this summer. This Bill

will, however; help thousands of others.

This Bill was conceived as a result of the FDA’s unwillingness to allow Thomas

access to a treatment which had a higher rate of success than the treatment offered

through conventional means. This Bill will however bring hope to others. Others,

who like us, have been denied access to treatments that show promise and give a

chance of survival. Treatments which are as good or greater than those treatments

currently available for treating pediatric cancers.

We were faced with a decision almost one year ago, which changed our lives forever. When our son, Thomas, was diagnosed with Medulloblastoma, Thomas was

rushed to surgery within hours to remove a 4 X 6-cm tumor on his cerebellum. After

the surgery we were faced with the decision of follow up therapy. We discovered in

short order that the standard follow up therapies, radiation and chemotherapy, both

had severe and irreversible side effects. These side effects included the possibility

that he would become blind, deaf, and sterile. That Thomas would develop hormonal

deficiencies would have stunted growth, that he would have an immediate and progressive loss of IQ. And that he could develop secondary cancers as a result of the

treatment.

We immediately began our search for a safer, non-toxic means for treating our

son. We found a treatment that showed great promise for treating Medulloblastoma.

Only to discover that our son would be denied access to the treatment by the FDA.

The doctor was not allowed to treat my son because the FDA did not approve his

access to the treatment. Yet, the FDA has never approved radiation and chemotherapy for treating pediatric cancers. In fact, if you read the manufacture’s information that the drug companies put in the boxes, they state, ‘‘safety and effectiveness in pediatric patients have not been established.’’ This sentence in and of itself

should cause concern. The FDA has no problem forcing this therapy on my son and

thousands of others—even though the safety and efficacy has not been established

in children. In fact, if you are the parent of a terminally ill child, your child can

be taken away from you for experimentation. And as parents, if you do not cooperate with this madness, you can be thrown in jail for being ‘‘bad parents.’’

Based on your own experience Mr. Chairman, what actions must I take today to

get you and your committee to take the required actions to save the Thomas

Navarros of tomorrow?

During the course of the last year, my family has lost everything—our home and

business in Arizona. It has been because of the kindness and generosity of others,

especially the support of Citizen’s For Health, that Thomas has been able to receive

medical care. HR 3677 introduced by Congressman Dan Burton, now has 43 cosponsors. I implore you take this issue up and get HR 3677 passed into law.

I would be pleased to entertain any questions from the Committee.

Mr. BILIRAKIS. Thank you very much, Mr. Navarro. I do—well,

what can one say? We want to be able to accomplish something

here. We want to be able to pass Dan’s bill, or essentially Dan’s

bill, but it has got to be done on a bipartisan basis. That is your

reason for imploring Mr. Waxman, who frankly has just been very

much interested in health care all through the years. I know I have

worked with him on this committee for many, many years. And I

do not really know personally what his position is on the legislation. I guess staff here does, but we are going to do everything we

possibly can.

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Mr. NAVARRO. Mr. Chairman, if I might add real quick: It is interesting, when I testified last time in Chairman Burton’s hearings

and spoke to a number of the directors of the FDA outside in the

halls, they kept trying to reiterate the great successes of conventional therapy in Thomas’s case. Yet the irony is, here before me

are the consent forms to the treatment Thomas is going through

now, which state, ‘‘Permission to for participation of child in research.’’

He is not in a protocol because they do not have a protocol. They

really do not know quite what they are going to do with him. It

is a hit and miss, and as they would say, a crapshoot. In fact, one

of the things that is sad that disturbed me, especially after hearing

Dr. Pazdur testify that the rate of success was 70 and 80 percent—

and this is coming out of the horse’s mouth—however, with standard therapy, there is less than a 30 percent chance of curing these

malignant brain tumors in young children. Furthermore, young

children treated with radiation therapy for brain tumors may experience serious and irreversible, long-term side effects from the radiation.

And yet yesterday, the doctors announced to us that because

Thomas has fared the toxic side effects better than the other children in the ward, they are anxious to start using high, high-dose

radiation and chemotherapy five to six times greater than they

have used on him so far.

And to be honest sir, he is tired of fighting the drugs. We need

to have the freedom to seek out a treatment that is nontoxic and

nonlethal. It is our right as Americans to have that freedom.

Mr. BILIRAKIS. Thank you, Mr. Navarro.

Mr. Brady. Mr. Brady? Obviously, the written statement that you

all submitted is made a part of the record, and we would prefer

that you might sort of supplement it.

STATEMENT OF ROBERT BRADY

Mr. BRADY. Thank you, Mr. Chairman. I will be quite brief and

just summarize my comments.

I am Bob Brady. I am here appearing this morning on behalf of

Biogen, Inc., a biotechnology company from Massachusetts. I am a

partner in the law firm of Hogan & Hartson where I have been

practicing food and drug law, focusing on pharmaceutical matters

for 25 years, including the implementation of the Orphan Drug Act.

Let me summarize my points, and then I am just going to focus

on two or three of them.

If enacted, H.R. 4242, the Orphan Drug Innovation Act would actually undercut the carefully crafted incentives of the Orphan Drug

Act without providing any real benefit to patients or promoting innovation. The Orphan Drug Act has been an unparalleled success.

Any changes to the act should be made only after careful analysis

and consideration by fully informed Members of the Congress in

the context of the entire law.

The FDA and its Office of Orphan Products Development, which

has done a conscientious and successful job in implementing the

law to date, should be consulted and its views taken into account.

Moreover, Biogen knows of no patient advocacy groups supporting

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this law nor do we know of any other organization, other than one

here at the table, supporting this provision.

The Orphan Drug Act shouldn’t be amended piecemeal by an

amendment hastily packaged together with noncontroversial measures at the end of a legislative session. It would undermine the

foundation of the Orphan Drug Act so a single company can market a product that has not been shown to be clinically superior to

orphan drug products already on the market.

Let me speak one moment about the Biogen product, which is a

product to treat multiple sclerosis, which was approved and is the

only multiple sclerosis drug approved for two indications to treat

this terrible disease. And it has been approved by the judgment of

FDA that it is clinically superior for safety reasons to the prior

drug approved in this marketplace. That is important, because that

will be a point of discussion here during the rest of this morning’s

testimony.

The Orphan Drug Act is one of the most effective laws enacted

by Congress with full bipartisan support in the last 20 years, especially in terms of the lives it has enhanced, the pain and suffering

it has diminished, and the hope it represents to Americans with

rare diseases.

I might also add parenthetically, after 25 years it has been the

least controversial piece of FDA law ever enacted in terms of subsequent debate and litigation, suggesting that it was well done to

begin with and remains properly implemented.

However, H.R. 4242 would undercut the overwhelming success of

this act. The key incentive of the act is a 7-year period of marketing exclusivity for the first product to be approved as an orphan

drug. H.R. 4242 would significantly narrow the scope of this exclusivity by limiting it to particular aspects of the orphan product subsequently approved.

Narrowing this key incentive, especially for a product which has

not shown any clinical superiority, would not only hurt companies

that make orphan drugs, but would also undercut Congress’ intent

that there be new and innovative treatments developed for millions

of Americans who suffer from rare diseases.

Orphan drug policies first passed by Congress and implemented

by FDA have been fair. Companies are rewarded when they

produce a clinically superior drug that represents an innovation

among the current marketplace.

Biogen, in fact, satisfied this standard in the law in the mid1990’s when it was found to be clinically superior to the existing

multiple sclerosis product. Serono Laboratories is testifying here

today on behalf of this bill. They manufacture a drug for multiple

sclerosis that is the same as Biogen’s multiple sclerosis product.

Serono would like to get their drug into the American market, but

they are blocked by the market exclusivity of Biogen’s product,

which does not expire until May of 2003.

The Orphan Drug Act and the FDA Act implementing regulations currently provide a way for Serono’s product to get to market

precisely the same way that Biogen’s product got to market in

1996, which is to prove clinical superiority to the two existing products that are already available to multiple sclerosis patients today.

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This is not a situation where there are not products available to

patients. There are two Interferon products already approved by

FDA in this area. Serono or any other company should not be held

to a lesser standard than the products that are already on the market.

Thank you very much, Mr. Chairman, for allowing me this brief

statement, and I am prepared to answer any questions you may

have.

[The prepared statement of Robert Brady follows:]

PREPARED STATEMENT OF ROBERT P. BRADY ON BEHALF OF BIOGEN, INC.

I am Robert P. Brady, and I appear here this morning on behalf of Biogen, Inc.

(Biogen). I am a partner in the law firm of Hogan & Hartson L.L.P., in Washington,

D.C. I have practiced law for 25 years, and spend almost all my time on matters

involving pharmaceutical and biotechnology laws including the Orphan Drug Act. I

would like to thank you for the invitation to Biogen to testify before this Committee.

At the outset I would like to summarize the key points of my testimony. If enacted H.R. 4242, the ‘‘Orphan Drug Innovation Act,’’ would actually undercut the

carefully crafted incentives of the Orphan Drug Act without providing any real benefit to patients or promoting innovation. The Orphan Drug Act has been an unparalleled success. Any changes to the Act should only be made after careful analysis and

consideration by fully informed members of Congress in the context of the whole Orphan Drug Act. The FDA office of Orphan Products Development, which has done

such a conscientious and successful job in implementing the Orphan Drug Act,

should be consulted and its views taken into account. Moreover, Biogen knows of

no patient advocacy groups supporting H.R. 4242, including the National Organization of Rare Disorders (NORD) which is the chief consumer advocacy organization

for orphan drug research and development and was instrumental in the development of the Act. The Orphan Drug Act should not be amended piece meal, by an

amendment hastily packaged together with non-controversial measures at the end

of a legislative session. It would undermine the foundation of the Orphan Drug Act,

so a single company can market a product that has not been shown to be clinically

superior to orphan drug products already on the market.

Biogen is a biotechnology company based in Cambridge, MA and manufacturer of

a product for the treatment of relapsing forms of remitting multiple sclerosis (MS)

that was approved in 1996. Biogen’s product (Avonex) was approved as an orphan

drug and thereby received a grant of seven years of marketing exclusivity. Two important medical facts about Avonex must be kept in mind. It is the only MS drug

approved for both reducing the number of exacerbations and slowing disease progression. Also, the FDA concluded that it was clinically superior to the existing MS

product due to greater safety. As a result patients have benefited greatly from this

approval.

Biogen is strongly opposed to H.R. 4242 for the following reasons:

The Orphan Drug Act is one of the most effective laws enacted by Congress with

full bipartisan support in the last twenty years, especially in terms of the lives it

has enhanced, the pain and suffering it has diminished, and the hope it represents

to Americans with rare diseases. The Orphan Drug Act has been an unqualified success. In particular, it spurred the development of breakthrough drugs for Multiple

Sclerosis, Cystic Fibrosis, Hemophilia, Leukemia, as well as over 100 other rare diseases. During the ten years before the law, only ten drugs were approved by the

Food and Drug Administration (FDA) for the treatment of rare diseases. Since the

law was enacted, however, about 200 orphan drugs have been approved and about

1,000 are in the pipeline. Clearly, any modification of the Act must be the end result

of a deliberative process that increases incentives to develop breakthrough treatments and, most importantly, benefits patients.

This is not the case with H.R. 4242—it would undercut the overwhelming success

of the Orphan Drug Act with no real benefit to patients. The key incentive of the

Act is a seven-year period of marketing exclusivity for the first product to be approved as an orphan drug. H.R. 4242 would significantly narrow the scope of this

exclusivity incentive by limiting it to particular aspects of the orphan product. Narrowing this key incentive would not only hurt companies that make orphan drugs

but would also undercut Congress’s intent that there be new and innovative treatments developed for the 20 million Americans who suffer from rare diseases.

The FDA has skillfully implemented the Congressional intent of the Orphan Drug

Act in a manner that balances the seven year marketing exclusivity incentive with

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the need to foster the public health goals. One way in which FDA has balanced this

issue is through the development of a regulation defining scientific/medical criteria

under which an orphan drug which is the same as an orphan drug already approved

for marketing can be determined to be ‘‘clinically superior’’ and, therefore, allowed

to come to market in spite of any remaining marketing exclusivity granted to the

original approved product. (See 21 C.F.R. § 316). FDA, the scientific and medical expert in this area, has defined three such criteria to determine clinical superiority.

These criteria were thoughtfully and deliberately developed through notice and comment rulemaking by the FDA. All interested parties had an opportunity to present

their views. Ultimately, the FDA crafted a well reasoned definition of clinical superiority.

Critically important since the finalization of this rule almost a decade ago, FDA

has carefully exercised its scientific and medical judgment in implementing this rule

in a manner that is truly in the best interests of patients. When another orphan

drug truly is clinically superior, FDA has allowed it to go to market so that particular patients will benefit. It has done so sparingly, however, because the FDA has

correctly concluded, based on its extensive experience, that, absent a real showing

of clinical superiority, preserving the seven year marketing exclusivity incentive is

vitally important to the development of new orphan drugs and that will help even

more patients suffering from orphan diseases.

These regulations are sound and fair. Companies are rewarded when they produce

a clinically superior drug that represents an innovation above the current marketplace. Biogen satisfied these regulations when the FDA found that its product

Avonex was ‘‘clinically superior’’ to another existing beta interferon product in 1996.

Serono Laboratories (Serono) is testifying on behalf of H.R. 4242 today. They manufacture a drug for multiple sclerosis that is the same as Biogen’s MS drug. Serono

would like to get their drug onto the American market, but they are blocked by the

market exclusivity of Biogen’s multiple sclerosis product, which does not expire until

May 17, 2003. The Orphan Drug Act and the FDA implementing regulations currently provide a way for Serono’s product to get to market: a showing of ‘‘clinical

superiority’’ based on appropriate scientific data.

Serono, or any other company, should not be held to a lesser standard than its

competitors in the marketplace. To date Serono has not demonstrated in head to

head comparative trials that its product is safer or more effective than the other

beta interferon products on the market for relapsing remitting multiple sclerosis. In

1999, the FDA found, based on data submitted to the FDA by Serono, that Serono’s product was not clinically superior to the other similar multiple sclerosis products

on the market. Therefore, it is barred from the U.S. market until the Biogen marketing exclusivity expires in May 2003. Because Serono does not represent an innovation, patients are not being denied a new or improved therapy. Serono is seeking

to change these requirements because Serono has not been able to satisfy them.

Serono’s situation highlights one of the key problems with H.R. 4242. Under the

bill, Biogen’s market exclusivity for its multiple sclerosis drug would be limited to

blocking from the market only those products that cause fewer injection site reactions and less skin necrosis. However, a product which is less safe than Biogen’s by

causing more site reactions and skin necrosis—such as Serono’s product—would be,

under this bill, eligible for approval by the FDA. Biogen does not understand how

it benefits patients to allow a drug on to the market during the exclusivity period

that is neither safer nor more effective.

The Orphan Drug Act’s market exclusivity is not a barrier to approval of a subsequent product that is not the same drug. A subsequent drug for the same indication

may be found to be not the same drug if it is either chemically different or clinically

superior. Serono’s Rebif product meets the statutory and regulatory standards for

‘‘same drug’’ because chemically it is the same drug for the same disease as both

Avonex and Betaseron. Because Rebif chemically is the same drug as Avonex, in

order for Serono to receive marketing approval prior to 2003, Serono must demonstrate that it is clinically superior to Avonex. The FDA’s clinically superior criteria protects the drug development incentive, while permitting the introduction of

better products to treat serious illness.

Aside from the serious policy concerns with H.R. 4242, another fundamental flaw

is that it is, in part, unconstitutional. As presently introduced, the bill would apply

to any drug designated on or after January 1, 1990. By going back and retroactively

narrowing the scope of the market exclusivity, this would constitute an unconstitutional taking under the Fifth Amendment. This legislation would not only effect the

property rights of Biogen but property rights of many other companies with orphan

drug designations that have made significant economic investments based on an expectation of market exclusivity. Biogen has attached a legal opinion on the unconstitutionality of the bill that was previously sent to the Committee.

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For Congress to make a change to a law as successful and important to the health

of the American people, as the Orphan Drug Act, one would expect that there would

be strong support from the biotechnology and pharmaceutical industries and patient

advocacy groups. Biogen knows of no outside parties that favor the H.R. 4242. There

are no patient advocacy groups supporting this bill. The National Organization of

Rare Disorders (NORD), which is the chief consumer advocacy organization for orphan drug research and development and was instrumental in the development of

the law, is opposed to the bill. The views of NORD and other patient groups should

not be ignored.

The stated purpose of this hearing today is to consider legislation that would secure the health of the American people. The Orphan Drug Act has already fostered

the development of numerous breakthrough treatments for rare disorders and

helped countless persons. H.R. 4242 will threaten this continued development and

risk the security of the health of the American people with rare disorders.

Mr. BILIRAKIS. Thank you, Mr. Brady.

Ms. Meyers, please proceed, ma’am.

STATEMENT OF ABBEY MEYERS

Ms. MEYERS. Thank you, Mr. Chairman.

For those of you who do not know us, the National Organization

for Rare Disorders is the consumer organization that advocated for

passage of the Orphan Drug Act, and we continue to monitor its

implementation.

We do not support H.R. 4242. And let me say at the outset, we

have no relationship with Biogen. Biogen has never donated to

NORD. This is totally independent.

Most orphan drugs have only one sponsor, and that is very important to understand, because this situation comes up very rarely

when more than one sponsor is interested in the same drug. And

so we caution you not to change the Orphan Drug Act in any way

based on something that happens so rarely.

You can get the same drug, orphan drug, on the market to compete against the innovator drug. You can do that in several ways.

You can get an orphan drug approved for a different disease.

For example, if beta Interferon was approved for cancer or something else, they could get it on the market and it could compete in

the marketplace. Or you could prove that it is chemically or structurally different than the first drug to get on the market. Or you

can show that it has clinical superiority.

Clinical superiority means that you have to prove that it is safer

or more effective or a major contribution to patient care. In the

case of Avonex and Betaseron, for example, Avonex showed that

you need less injections every week, it had fewer side effects and

did not cause one particular side effect. And so it was a major contribution to patient care and you needed only one injection a week.

So the current law protects the major incentive of the Orphan

Drug Act, which is 7 years of exclusive marketing rights; and it is

only through regulations that the current definitions of ‘‘same’’ and

‘‘different’’ was created. And I want to tell you that the Orphan

Drug Act passed in 1983, but those regulations weren’t written and

published until 1992. So we waited many years and there was a

lot of public input on the development of those regulations.

The Thornberry amendment, we feel, would destroy the backbone

of the law because it would undermine the major incentive of the

Orphan Drug Act. And also be aware that the Orphan Drug Act’s

success has been replicated all over the world. The European Union

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just passed an orphan drug law; Japan has one, Singapore, every

country in the world admires what we have been able to do here.

So we need to keep the incentive in place that would spur other

manufacturers to develop clinically superior orphan drugs.

In the case of multiple sclerosis, for example, people have very

poor muscular control. Giving themselves an injection is climbing

Mount Everest every day. And then they lose their eyesight, so

they can’t see to fill up their syringe. It is a major improvement

to patient care when you only need one shot a week and a nurse

can come to your house to do it.

So what do we see in this situation here with this argument over

beta Interferon? If Serono—and we have the greatest respect for

Serono, but if Serono believes that its drug is either safer or more

effective or that it is clinically superior, or even if they want to say

that their drug is the same as the original orphan drug so it would

be able to get on the market today if it could prove it is the same

as Betaseron, they should take their proof to the courts. They

should not be hiring lobbyists to come down here and ask you to

change the law. It is wrong for company after company, year after

year to come to you and ask for an amendment to the Orphan Drug

Act. It works; and if it ain’t broke, don’t fix it.

I will be glad to answer any of your questions that you may have

about the law. And we say again, we do not support this amendment.

[The prepared statement of Abbey Meyers follows:]

PREPARED STATEMENT OF ABBEY MEYERS, PRESIDENT, NATIONAL ORGANIZATION FOR

RARE DISORDERS

Mr. Chairman and members of the Committee, the National Organization for

Rare Disorders (NORD) is the consumer organization that worked for passage of the

Orphan Drug Act (ODA) of 1983, and we continue to closely monitor its implementation today. NORD represents approximately 25 million Americans with more than

6,000 rare ‘‘orphan diseases’’, and we are very pleased to be here today. Thank you.

As you know, the Orphan Drug Act is one of the most successful pieces of health

legislation ever enacted by Congress. Today, approximately 1,000 orphan drugs have

been designated by the FDA, and over 200 of them have been approved for marketing in the United States. Recognizing the public health impact of the American

law, other nations have implemented orphan drug statutes including Japan, Singapore, Australia and the entire European Union.

It is extremely important that Congress not undermine the intent of the law,

which is to encourage the commercial development of treatments for small populations of patients. We do not support H.R. 4242, the Orphan Drug Innovation Act,

for many reasons, and we urge the committee not to approve the legislation for further consideration by Congress. Let me explain why we do not support H.R. 4242.

Early in the evolution of the American Orphan Drug Act, it became necessary to

define the words ‘‘same’’ and ‘‘different’’. In other words, as defined by FDAs carefully crafted regulations, if a manufacturer of a similar orphan drug can prove that

their drug is chemically different or clinically superior, even though it contains the

same active ingredients as the original orphan drug, the FDA will approve it for

marketing.

There are several ways to prove that a drug is ‘‘clinically superior’’: either by providing FDA with scientific data proving that it is either safer or more effective, or

that it represents a ‘‘major contribution to patient care’’. The latter is usually an

obvious improvement, such as developing an oral version of an injectable drug—so

that patients no longer have to suffer painful injections—or developing a long-acting

version of a drug that must otherwise be taken several times each day, for example.

Thus, the orphan drug regulation defining ‘‘same’’ and ‘‘different’’ not only promotes,

but encourages development of new improved versions of marketed orphan drugs

while PRESERVING the chief incentive of the ODA.

Since most orphan drugs have no competition because companies are generally

not interested in investing the huge sums necessary for research and development

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of a drug that will have a very small market, the ODA offers an important incentive

to encourage orphan drug innovation.

Companies can receive seven years of exclusive marketing rights for both the innovator drug and the clinically superior follow-on drug.

Mr. Chairman, from time to time there are orphan drug ‘‘races’’ when more than

one company is developing the same orphan drug for the same disease, and the law

purposely creates a winner-take-all contest. This is the very core of the success of

the ODA because it prevents competition for seven years, and ensures that a manufacturer of an FDA-approved orphan drug will recoup its investment and make a

profit. But losers of the race sometimes ask Congress to change the law because

they want an exception for their drug. Thankfully Congress has been wise enough

not to allow this, knowing that tinkering with the Act could destroy it.

In this case, Congressman Thornberry’s bill aims to redefine FDA’s definition of ‘‘same’’ and ‘‘different’’, and to codify it into law, based on the mistaken belief that

people with rare diseases do not already have access to clinically superior orphan

drugs. However, H.R. 4242 will NOT enhance patient choice because current regulations not only permit, but encourage competition when a therapeutic advantage can

be scientifically proven.

We believe that H.R. 4242 would disincentivize companies to develop clinically superior orphan drugs and biologics, and it would allow companies to seek approval

for clinically inferior products. Moreover, H.R. 4242 would reduce the exclusivity of

orphan drugs and biologics that have demonstrated they are clinically superior, because it would limit exclusivity to the innovation that enabled a clinically superior

product to reach the market.

There are no benefits to patients if H.R. 4242 becomes law. There are only benefits to companies that want to break the innovators exclusivity, but that exclusivity

is the very backbone of the Orphan Drug Act which has since 1983 saved the lives

of millions, and improved the quality of life for countless others.

The current regulations, which are based on sound scientific knowledge and common sense, were written to promote innovation and to allow consumers access to

clinically superior orphan drugs. They are fair to consumers and fair to companies.

The ODA is good public health policy and continues to be one of the most successful

pieces of health legislation ever written.

We are profoundly grateful to Congress for enacting the Orphan Drug Act, and

for preserving its integrity since 1983. If you write the Thornberry bill into stone,

it will require an act of Congress to change it when new medical technologies

emerge in the future. If you leave the orphan drug regulations alone, the FDA can

easily fine tune the rules, if and when that becomes necessary.

Mr. Chairman and members of the Committee, ‘‘if it ain’t broke, don’t fix it.’’ We

urge you NOT to enact H.R.4242.

Mr. BILIRAKIS. Thank you, Ms. Meyers.

Mr. Lang.

STATEMENT OF THOMAS A. LANG

Mr. LANG. Good morning. My name is Tom Lang. I am Senior

Vice President for Strategic Product Development at Serono, Inc. I

want to thank the committee for the opportunity to testify on the

issue of orphan drug evergreening, which is addressed by H.R.

4242.

Serono believes this issue needs to be addressed irrespective of

the impact on our products. FDA’s current evergreening policy affects all drugs governed by the Orphan Drug Act. We fully support

the remedy posed by H.R. 4242, whether or not it would apply to

any of our products.

Furthermore, Serono believes orphan drug evergreening is not a

single-product issue.

Serono is a strong supporter of the Orphan Drug Act. However,

we have recently encouraged an anomalous and confusing interpretation of the FDA orphan drug regulations which results in orphan

drug exclusivity evergreening. ‘‘evergreening’’ refers to FDA’s

granting of a new 7-year orphan drug exclusivity period for the entire drug substance upon the approval of a clinically superior

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version of the same drug, rather than protecting only the innovative feature exhibited by the second drug.

The results are to close the market to competition beyond the initial 7 years of exclusivity intended by Congress. This raises troubling policy issues of fairness, impediments to price competition

that would benefit consumers, and delays in availability of alternative therapies for patients.

Mr. Chairman, Congress needs to decide exactly what the scope

of exclusivity should be for improved versions of originator orphan

drugs. We note that other areas of food and drug law limit the

scope of exclusivity for new versions of previously approved products in a manner consistent with H.R. 4242. Like the Orphan Drug

Act, the Waxman-Hatch Act seeks to create incentives for continued research on improved drugs and product improvements. The

Waxman-Hatch Act, as one would expect, rewards only innovative

features with exclusivity, rather than shielding the entire drug

substance from competition when its original exclusivity period has

run. This serves as evidence of Congress’ intent and provides a

basis for supporting the principle in H.R. 4242.

FDA’s handling of one particular product has resulted in several

very strained policy positions on the part of FDA. In a letter to

Serono, dated November 1999, FDA indicated that while it would

not allow an NDA or a BLA product to be marketed in competition

with the original drug, it would allow a generic version of the original product to come on the market if it were eligible for an abbreviated new application.

Mr. Chairman, there is no rationale whatsoever for preventing

competition from products that are supported by full NDAs and

BLAs. Subsequently, Serono became aware of an instance where

FDA has taken what appears to be a different position than that

previously described, a position which actually is consistent with

H.R. 4242, in a letter to Genentech.

Serono believes orphan drug exclusivity evergreening can be resolved by FDA or Congress by simply limiting the second clinically

superior drug’s scope of orphan drug exclusivity to the superior

characteristic that distinguished it as clinically superior. This solution would probably reward the improvement found in the clinically

superior drug while still allowing competition with the expired

drug as intended by the law.

This would be consistent with other exclusivity-related legislative

initiatives, such as the Waxman-Hatch amendments and patent

law as well.

Limiting the scope of exclusivity of a clinically superior orphan

drug to its clinically superior feature still leaves the drug sponsor

with adequate incentives. A clinically superior drug would gain

three significant rewards as follows: .

First, it would achieve the benefit of being allowed on the market

immediately despite the originator drug’s exclusivity; Second, it

would obtain 7 years exclusivity for the improved feature; and

Third, the company would be able to market its product as a clinically superior product.

These are substantial awards and incentives. These incentives

make it unnecessary to keep the market closed to other products

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wishing to compete with previous versions whose exclusivity have

expired.

In summary, the current evergreening policy actually inhibits innovation, deters competition, and creates an anomalous windfall

extension of drug exclusivity.

We have attempted to work with the FDA to resolve this issue

for 2 years. Nevertheless, in Serono’s opinion, FDA continues to administer the exclusivity principle in an inconsistent and unclear

manner. The evergreening policy is now riddled with ad hoc exceptions not found anywhere in the statute or in the regulations. We,

therefore, believe that clarifying legislation is warranted.

Again, I would like to thank the committee for the opportunity

to testify on this important matter affecting the incentive to develop improved drugs for rare diseases. We appreciate the committee’s attention and consideration, and I would like to thank Dr.

Ganske for his earlier comments.

[The prepared statement of Thomas A. Lang follows:]

PREPARED STATEMENT OF THOMAS A. LANG, SENIOR VICE PRESIDENT, STRATEGIC

PRODUCT DEVELOPMENT, SERONO, INC.

INTRODUCTION.

Good morning, my name is Tom Lang. I am Senior Vice President for Strategic

Product Development at Serono, Inc. I would like to thank the Chairman, and other

members of the Committee, for the opportunity to testify on the issue of orphan

drug exclusivity ‘‘evergreening,’’ which is addressed by H.R. 4242. At this time, I

want to make it clear to the Committee that Serono believes this issue needs to be

addressed irrespective of the impact on our products. FDA’s current evergreening

policy affects all drugs governed by the Orphan Drug Act (ODA) and represents a

policy issue that demands your attention. We fully support the remedy posed by

H.R. 4242; however, we would be equally supportive of an administrative remedy

accomplishing the same goal.

As a global leader in biotechnology with a number of drugs and biologic products

already approved in the U.S. and many more in our research pipeline, Serono is a

strong supporter of the Orphan Drug Act. We recognize the need to provide strong

incentives to develop drugs for rare diseases, and indeed, many of our drugs have

orphan drug designations as well as orphan drug exclusivity. However, we have recently encountered a problem with FDA’s anomalous and confusing interpretation

of the Orphan Drug regulations, which results in orphan drug exclusivity

‘‘evergreening.’’ In this context, ‘‘evergreening’’ refers to FDA’s granting of a new

seven year orphan drug exclusivity period for the entire drug substance upon the

approval of a second, clinically superior, version of the same drug, rather than protecting only the innovation exhibited by the second drug. This results in closing the

market to competition beyond the initial seven years of exclusivity intended by Congress.

This is an unwarranted extension of orphan drug exclusivity. It presents troubling

policy issues of fairness, impediments to price competition that would benefit consumers, and the delay in availability of alternative therapies for patients.

BACKGROUND.

The phenomenon of orphan drug exclusivity ‘‘evergreening’’ is a result of FDA’s

interpretation of its regulations giving effect to the ODA, and not a result contemplated or intended by Congress. The ODA itself created incentives for drug companies to develop therapies for rare diseases by awarding a period of seven years

of market exclusivity to a product approved for an orphan indication. During these

seven years, FDA may not approve other applications which are for the ‘‘same drug’’

and the same disease or condition. Congress intended that after this period of exclusivity, the public would benefit from increased treatment options as well as price

competition among various products in these areas. The ODA overall has been a significant success in driving research for rare diseases.

However, the statute is silent as to improved versions of previously approved orphan drugs. In the regulations adopted by FDA to implement the ODA, the agency

created a mechanism by which a second product could also be approved during the

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period of market exclusivity awarded to the first drug. Such exceptions are made

where a second drug is deemed to be clinically superior to the first orphan drug.

FDA’s intention in creating this mechanism was to maintain incentives for companies to continue research on orphan drugs, and to reward additional advancements

by allowing them earlier access to an otherwise closed market. While this objective

is laudable, FDA has recently chosen to implement it in a very problematic fashion.

FDA’S EXCLUSIVITY POLICY.

Recently, FDA has adopted a policy position related to the scope of a clinically

superior orphan drug’s exclusivity that actually undermines the incentives for companies to continue to innovate for additional improvements in these areas. As noted

earlier, FDA’s policy also raises questions of fairness, alternate product availability,

and patient and physician choice of therapy.

Now, after approval of an original orphan drug, whenever a subsequent orphan

drug with a clinically superior improvement has also been approved and awarded

exclusivity, FDA totally restarts the seven-year exclusivity clock for the drug as a

whole. In this way, the improved drug shields the original drug from competition,

even after the original drug’s exclusivity period is over. In these instances, companies that have developed new competing versions of the same drug to treat the disease in anticipation of the expiration of the original seven-year exclusivity are unfairly denied access to the market for an additional seven-year period. Under FDA’s

current policy, this total period of exclusivity barring the entry into the market of

competing product versions could theoretically be as long as fourteen years if two

drugs were approved; as long as twenty-one years if three drugs were approved, and

so on. This possible extension, or ‘‘evergreening’’ of the original drug’s exclusivity

period by restarting the clock for the entire drug substance when a second or third

clinically superior version is approved is the problem sought to be addressed by the

Thornberry Bill (H.R. 4242).

ORPHAN DRUG EVERGREENING IS NOT A SINGLE PRODUCT ISSUE.

FDA has designated at least five drugs as orphans, based solely on their demonstration of superiority over a previous version.

• Avonex (recombinant beta interferon la for relapsing remitting multiple sclerosis), exclusivity based on clinical superiority to Betaseron.

• Sandostatin LAR Depot (generic name octreotide for several orphan indications,

primarily transplant rejection)—long acting formulation, exclusivity based on

superiority in dosing to original drug.

• Nutropin Depot (recombinant human growth hormone for pediatric growth hormone deficiency) dosing superiority, long acting formulation.

• Benefix TM (Coagulation Factor IX for hemophilia) - Recombinant version judged

safer than two previous versions.

• Prolastin (Alpha 1 proteinase inhibitor for emphysema), long acting formulation

superior in dosing convenience to original orphan drug.

All five were considered to have presented a safety or dosing improvement over

the original version of the drug. The active chemical entity in all five cases is the

same as the original drug. The older versions were all approved as safe and effective

products and are still being marketed. Thus, a new competitor in these other disease areas would also be expected to face an evergreening problem, based on FDA’s

policy.

OTHER AREAS OF FOOD AND DRUG LAW LIMIT THE SCOPE OF EXCLUSIVITY FOR NEW

VERSIONS OF PREVIOUSLY APPROVED PRODUCTS.

As with the Orphan Drug Act, the Waxman-Hatch Act seeks to create incentives

for continued research on approved drugs and product improvements. The WaxmanHatch Act, as one would expect, rewards only the innovative feature with exclusivity, rather than shielding the drug substance from generic competition when its

original exclusivity period has run. This serves as evidence of Congress’ intent, and

provides a basis for supporting the principle in H.R. 4242.

FDA’S POSITION OF ONLY ALLOWING ABBREVIATED APPLICATIONS TO COMPETE WITH AN

EXPIRED ORPHAN LACKS A RATIONALE.

FDA’s handling of our product has resulted in several very strained policy positions on the part of the agency. For example, in a letter to Serono dated November

8, 1999 (copy attached), FDA indicated that while it would not allow our product

to be marketed in competition with the original drug approved for this orphan drug

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indication, it would approve a generic version of the original product to come on the

market if it were eligible for an abbreviated new drug application (ANDA.)

In Serono’s opinion, this position indicates that FDA in fact agrees in principle

that the exclusivity that was awarded to the second clinically superior drug should

not prevent competition with the original product whose exclusivity has lapsed.

However, FDA makes an arbitrary determination that only ANDA drugs can compete, but not drugs that are supported by full new drug applications (NDAs and

BLAs). There is no rationale whatsoever for preventing competition from products

that are supported by full NDAs and BLAs.

FDA’S ACTION IN A SUBSEQUENT CASE IS ACTUALLY CONSISTENT WITH H.R. 4242.

Recently, Serono became aware of an instance where FDA has taken what appears to be a different position than with our product, and one which appears to

be consistent with H.R. 4242. In a letter to Genentech dated October 28, 1999 (copy

attached), FDA advised the company that new long acting formulation of recombinant growth hormone (Nutropin Depot) has been designated as an orphan, but

that the orphan designation ‘‘applies only to the long acting formulation,’’ rather

than to the entire drug substance. This means that the Nutropin Depot improved

formulation, once approved, would achieve orphan protection for seven years, but its

exclusivity only would cover the improvement, and manufacturers wishing to introduce additional versions of the conventional dosage form would not be blocked.

Thus, in this instance, FDA’s position appears to be totally consistent with H.R.

4242.

SOLUTION TO ‘‘EVERGREENING’’ PROBLEM.

Fortunately, the ‘‘evergreening’’ problem is one that has an extremely simple solution. Orphan drug exclusivity evergreening can be resolved by FDA or Congress by

simply limiting the second, ‘‘clinically superior’’ drug’s scope of orphan drug exclusivity to the superior innovation, feature, or characteristic that distinguished it as

clinically superior. This solution would properly reward the innovation found in the

clinically superior drug, while still allowing competition with an expired original

drug, as intended by the law. Again, FDA could remedy this problem itself, without

legislation, by simply modifying its current policy as to the scope of exclusivity associated with a ‘‘clinically superior’’ orphan. This would be consistent with other exclusivity-related legislative initiatives, such as the Waxman-Hatch Amendments, and

patent law as well.

THE SOLUTION PROPOSED IN H.R. 4242 WOULD RETAIN INCENTIVES FOR INNOVATION IN

ORPHAN DRUG RESEARCH.

Limiting the scope of exclusivity of a clinically superior orphan drug to its clinically superior feature still leaves the drug sponsor with an adequate incentive. A

clinically superior drug would gain three significant rewards. First, it achieves the

benefit of being allowed onto the market immediately despite the originator drug’s

exclusivity. Second, it obtains seven years’ exclusivity for the improved feature.

Third, it will be able to market its product as clinically superior. These are substantial rewards and incentives. These substantial incentives make it unnecessary to

keep the market closed to other products wishing to compete with previous versions

whose exclusivity may have expired.

CONCLUSION

In summary, the current evergreening policy unnecessarily denies patients and

physicians alternative therapeutic options. In our view, given the way it is being administered, it actually inhibits innovation and deters competition, and creates

anomalous windfall extensions of drug exclusivity. We have attempted to work with

FDA to resolve this issue for two years. Nonetheless, in Serono’s opinion FDA continues to administer the exclusivity principle in an inconsistent and unclear manner. The evergreen policy is now riddled with ad hoc exceptions not found anywhere

in the statute or in the regulations. This has caused significant confusion for industry. We therefore believe that clarifying legislation is warranted to avoid policy that

we believe was never intended by Congress. That is why we support H.R. 4242.

Again, I would like to thank the Committee for the opportunity to testify on this

important matter affecting the incentive to develop improved drugs for rare diseases. We appreciate the Committee’s attention and consideration.

Mr. BILIRAKIS. Ms. Bennett, please.

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STATEMENT OF CATHERINE P. BENNETT

Ms. BENNETT. Thank you, Mr. Chairman and members of the

subcommittee. I appreciate this opportunity to testify on an issue

of great personal importance to me, cancer awareness treatment

and research.

I am here representing the Cancer Research Foundation of

America as chairman of its board of directors. We are a national

nonprofit health organization whose mission is cancer prevention

through scientific research and education.

Since its founding in 1985, the Foundation has funded research

by more than 200 scientists at more than 100 leading universities

and medical centers. And it is one of the only 10 non-Federal agencies whose grant review process is approved by the National Institutes of Health.

Within the last year, CRFA has increased its focus on childhood

cancers with the establishment of Hope Street Kids, a foundation

created under the umbrella of CRFA following the loss of Caroline

Pryce Walker. The mission of Hope Street Kids is to eliminate

childhood cancer through advocacy education and cutting-edge research and to help sustain and support children with cancer and

their families during and after treatment.

Unfortunately, most us have had a personal experience with cancer. We have seen it attack a family member, a friend, a coworker,

or we have been diagnosed ourselves. I was diagnosed with breast

cancer in 1993. It is a dreaded and pervasive disease that claims

the lives of more than 500,000 Americans each year, and it is a disease that knows no racial, ethnic, economic or gender boundaries.

Perhaps what is even more disturbing is that cancer also does not

discriminate based on age. Many of us think of it as a disease of

the elderly or middle aged, but we must also recognize that cancer

is the No. 1 cause of death by disease for children.

Each year, more than 12,000 children are diagnosed with cancer

and some 2,300 children will die from the disease. That is about

100 classrooms filled with children who won’t start school next September. September is significant in that it is recognized as National Childhood Cancer Awareness Month.

So it is appropriate that the committee has House Resolution 576

sponsored by Congresswoman Deborah Pryce on its agenda.

I am pleased to testify in support of in resolution which seeks to

raise awareness about the realities of childhood cancer and make

suggestions or recommendation about where Congress could help

ensure that more children live to start a new school year. The statistics in the resolution demonstrate the challenges we face. The incidence of cancer among children is rising by 1 percent each year.

One in every 330 Americans develops cancer before age 20. It constitutes about 8 percent of deaths between the ages of 1 and 19.

And as I mentioned, it is the leading cause of death by disease in

children.

It is clear to me that we cannot dismiss this disease as rare or

ignore the substantial loss of life for which childhood cancer is responsible. In my mind, even one child lost to cancer is unacceptable. The good news is that progress has been made. Four years

ago a diagnosis of childhood cancer was a death sentence. Today,

almost 70 percent of children diagnosed will survive. Nonetheless,

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that means 30 percent do, in fact, succumb. The success rate can

be attributed in part through research through clinical trials. They

have become the standard of care for pediatric oncology patients

with approximately 70 percent of the children who are diagnosed

participating. This makes sense to build on these efforts by making

sure that opportunities for childhood cancer research are funded

and that we attract the best and brightest to pediatric oncology and

that we make sure that as many children as possible have access

to the centers of excellence and clinical trials.

The resolution suggests that Congress support such policies. Additionally, H. Res. 576 encourages support for policies that encourage the development of new drugs in biologics. As members of this

committee know, the Food and Drug Administration Modernization

Act provides additional incentives to encourage greater private investments and research by providing some additional 6 months of

market exclusivity to sponsors of new or approved drugs if they

conduct pediatric studies. Despite the good intentions of this law,

the policy has not proven as effective in stimulating research or

providing additional information about drugs that may prove useful

in pediatric oncology. I believe it is worth reevaluating the policies

reflected in that statute.

While we look to the future with hope that we will see the day

when no child becomes the innocent victim of cancer, we must also

face the reality that children today are suffering and are dying. We

must focus our attention on improving the quality of life for these

patients. The horrors of cancer are many, but it is hard to imagine

anything more tortuous than a parent witnessing their child in

pain. Yet many will tell you that they have been forced to stand

helplessly by while their children are enduring invasive and painful treatments.

The resolution points out a recent study which revealed that 89

percent of children with cancer experienced substantial suffering in

the last month of life. Why, in this day of modern medicine and

technology, is this necessary or acceptable? In my view it is not.

The reason for inadequate pain relief for children in cancer patients may be many, but one can be found in the lack of training

for pain management received by physicians in their medical training.

We can begin to address this issue by expanding knowledge

among medical personnel to help them recognize the signs of pain

and treat them effectively. The resolution is supportive of such curriculum as part of medical training.

The battle against childhood cancer is being hard fought, but

those that know the horrors of this disease, and many of them will

be in Washington this week to do what they can to raise awareness

and recruit Congress and others, whoever will listen, in fact, to

their cause. I believe Mrs. Pryce’s resolution is a good first step

that indicates a congressional understanding of the issues at hand

and provides an outline for what a successful policy aimed at defeating childhood cancer should entail. I encourage the subcommittee to lend its support to this legislation and again, appreciate the opportunity to participate today.

[The prepared statement of Catherine P. Bennett follows:]

119

PREPARED STATEMENT OF CATHERINE P. BENNETT, CHAIRMAN, BOARD OF DIRECTORS, CANCER RESEARCH FOUNDATION OF AMERICA

Thank you, Mr. Chairman and members of the Subcommittee. I appreciate this

opportunity to testify on an issue that is of great personal importance to me—cancer awareness, treatment, and research.

I am here representing the Cancer Research Foundation of America, as Chairman

of their Board of Directors. For those of you not familiar with CRFA, we are a national, non-profit health organization whose mission is the prevention of cancer

through scientific research and education. Founded in 1985 by Carolyn Aldige ́, the

Foundation has funded research by more than 200 scientists at more than 100 leading universities and medical centers, and is one of only ten non-federal agencies

whose grant review process is approved by the National Institutes of Health. And,

I am pleased that within the last year, CRFA has increased its focus on childhood

cancers with the establishment of Hope Street Kids, a foundation created under the

umbrella of CRFA. The mission of Hope Street Kids is to eliminate childhood cancer

through advocacy, education and cutting-edge research, and to help sustain and support children with cancer and their families during and after treatment

Unfortunately, most of us have had a personal experience with cancer. We have

seen it attack a family member, a friend, a coworker, or we have been diagnosed

ourselves. This dreaded and pervasive disease claims the lives of more than 500,000

Americans each year. And, it is a disease that knows no racial, ethnic, economic,

or gender boundaries. Perhaps what is even more disturbing is that cancer also does

not discriminate based on age. Many of us think of cancer as a disease of the elderly

or middle-aged. But, we must also recognize that cancer is the number one cause

of death by disease for children. Each year, more than 12,000 children are diagnosed

with cancer and each year, some 2,300 children will die from the disease. That’s about 100 classrooms filled with children, who won’t start school next September.

September is also significant in that it is recognized as National Childhood Cancer Awareness Month. So it is appropriate that the Committee has house resolution

lll, sponsored by Congresswoman Deborah Pryce, on its agenda. I am pleased

to testify in support of this resolution, which seeks to raise awareness about the realities of childhood cancer and make suggestions about where Congress can help ensure that more children live to start a new school year.

The statistics in the resolution demonstrate the challenge we face:

• The incidence of cancer among children is rising by one percent each year.

• One in every 330 Americans develops cancer before age 20.

• Cancer constitutes about 8% of deaths between ages 1 and 19.

• And, as I mentioned earlier, it is the leading cause of death by disease in children.

• It is clear to me that we cannot dismiss this disease as ‘‘rare’’ or ignore the substantial loss of life for which childhood cancer is responsible. In my mind, even

one child lost to cancer is unacceptable.

• The good news is that progress has been made. Forty years ago, a diagnosis of

childhood cancer was a death sentence, but today almost 70 percent of children

diagnosed with the disease will survive. This success rate can be attributed to

research through clinical trials. In fact, clinical trials have become the standard

of care for pediatric oncology patients, and about 60 percent of children that are

diagnosed with cancer participate. That compares with only 3% of adult cancer

patients and 1.5 % of Medicare patients.

It makes sense to build on these efforts by making sure that opportunities for

childhood cancer research are funded, that we attract the best and brightest scientists to pediatric oncology, and that as many children as possible participate in

and benefit from the discoveries made through clinical trials. H. Res. lll suggests that Congress support policies consistent with these goals.

Additionally, H.Res. lll encourages support for policies that encourage the development of new drugs and biologics. As the Members of this Committee know, the

Food and Drug Administration Modernization Act of 1997 provided an incentive to

encourage greater private investment in research on the use of drugs to treat pediatric diseases. Specifically, the Act provides an additional six months of market exclusivity to sponsors of new or approved drugs if they conduct pediatric studies that

may produce benefits for children. Despite the good intentions of this law, the policy

has not proven effective in stimulating research or providing additional information

about drugs that may prove useful in treating pediatric cancer. It is worth re-evaluating this policy and its implementation by the FDA so that we can ensure that children are not left out of the tremendous advances in the treatment of disease that

new drugs and biologics can provide.

While we look to the future with hope that we will see the day when no child

becomes the innocent victim of cancer, we must face the reality that children today

120

are suffering and dying. We must also focus our attention on improving the quality

of care and of life for these patients. The horrors of cancer are many, but it is hard

to imagine anything more torturous for a parent than witnessing their child in pain.

Yet, many parents will tell you that they have been forced to stand by helplessly

while their child endured invasive and painful treatments. As H.Res. lll points

out, a recent study revealed that 89 percent of children with cancer experienced substantial suffering in the last month of life. Why, in this day of modern medicine and

technology, is this necessary or acceptable? In my view, it is not. The reasons for

inadequate pain relief for children and cancer patients may be many, but one can

be found in the lack of training for pain management received by physicians in their

medical training. We can begin to address this issue by expanding knowledge among

medical personnel to help them recognize the signs of pain and treat them effectively. H.Res. lll is supportive of such curriculum as part of medical training.

The battle against childhood cancer is being hard fought by those that know the

horrors of this disease, and many of them will be in Washington this week to do

what they can to raise awareness and recruit Congress and others—whoever will

listen—to their cause. I believe H.Res. lll is a good first step that indicates a

congressional understanding of the issues at hand and provides an outline for what

a successful policy aimed at defeating childhood cancer should entail. I encourage

this subcommittee to lend its support to this legislation.

Again, I appreciate the opportunity to participate in today’s hearing and to speak

to this issue during Childhood Cancer Awareness Month.

Thank you, Mr. Chairman.

Mr. BURR [presiding]. Thank you, Cathy, and welcome. The

Chair would take this opportunity to recognize himself, as soon as

he gets his thoughts. And we apologize that there are members trying to get back. And it is the intent of the committee to continue

with the hearing rather than take a break for lunch because of the

afternoon schedule. Here we think it is not only more beneficial to

us, but also to you to go ahead and allow those members to make

it back to ask questions.

Ms. Meyers, let me ask you some specific questions. Things have

changed significantly since we originally put together the orphan

drug legislation, haven’t they?

Ms. MEYERS. Yes.

Mr. BURR. Can you be a visionary for us just a minute and look

out once the human genome project is complete, once we have

mapped the genetic outlay of the human structure, how many of

what we classify as rare diseases today do you think that researchers will be out there trying to find the key to the cure for in the

future?

Ms. MEYERS. Well, it is very complicated because it is not just

a matter of everybody, for example, with muscular dystrophy having the same genetic defect. There are many different genetic defects that may result in Duchenne’s muscular dystrophy. And down

the road in about 20 years, the way I foresee it, the way the scientists do, is that they will be able to personalize drugs for the particular genetic defect that has occurred in individuals. So we will

have custom-made bio technology drugs to address the specific defect in that gene.

Mr. BURR. Which means the population, that because they are

going to be subsets of disease, the population that they are going

to target is going to be tremendously small.

Ms. MEYERS. Minuscule.

Mr. BURR. So is it safe for the members of this committee to assume that a large share of the pharmaceutical applications that

will go in are going to be under the orphan drug legislation, because the population is defined at 200,000 people, if I remember

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correctly, we will clearly be chasing a multitude of things under

that population.

Ms. MEYERS. It will be a growing number of treatments for the

small populations, most of which will come from biotechnology.

Mr. BURR. Is there any reason that we as a committee and as

an institution should, in any way, shape or form, look out at that

200,000 person number, knowing the changes that are going to

take place through the genetic mapping, and at least debate or possibly change that number to be more reflective of where we think

exclusivity should be in the future? I am not talking about the debate that we are at at this table, I am trying to think out a number

of years.

Ms. MEYERS. Well, looking back over the 17-year history of the

Orphan Drug Act, the problems that have arisen have not arisen

around the size of the population. The problems that have arisen

are pricing problems. And even drugs for very tiny numbers of people, if you are going to charge $100- or $200,000 a year for that

treatment, you are going to make a lot of profit. And so, if there

are any changes to the Orphan Drug Act and one of them was introduced and actually passed the House and Senate by Mr. Waxman in 1990, and it was vetoed by President Bush and that was

aimed at shortening the period of exclusivity for blockbuster drugs.

So I would not lower the size of the population because 200,000 is

not a huge number and believe me, it is even hard to find companies that are willing to make drugs for 3- or 400,000 Americans.

Mr. BURR. In today’s research environment?

Ms. MEYERS. Yes.

Mr. BURR. Ten years from now, in tomorrow’s research environment where you have got a map that leads to you a point that it

took you 5 years now to hopefully do research to find, my question

was not should we, it was should we at least have a debate on it?

Should we bring in individuals out of biotechnology and pharmacological research to discuss what do you see down the road? Are

you going to be chasing diseases because of the information you

have that there is a population of 5,000 and 7,000 and 12,000,

which means that the majority of the stuff that we do will be classified as under the Orphan Drug.

Ms. MEYERS. It is true, but, you know, the bigger these companies are getting with their mergers and their acquisitions, I mean,

they are interested in Viagra, they are not even going to be looking

at these types of diseases. The latest one is something about removing facial hair. I mean these kinds of markets are so huge, the

big companies don’t want to look at a drug with an estimated sales

under a billion a year.

Mr. BURR. Clearly you make a point that is probably an accurate

one today, if through these advances it is much easier for them to

design that drug of the future, as you said, a custom-designed drug,

it may be a whole different situation.

Ms. MEYERS. I think it will be, yes.

Mr. BURR. Did you ever envision under the Orphan Drug law

that—let me ask it a different way: Do you think it is right under

the Orphan Drug law that a company could have an approval,

could have their exclusivity, at some point during that period of exclusivity they made an enhancement to the product, they reapplied,

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and were approved for whatever reason at FDA and got a new

year—7-year exclusivity?

Ms. MEYERS. Yes.

Mr. BURR. Did you envision when the Orphan Drug law came

about, that that was something that would happen?

Ms. MEYERS. First of all biotechnology was in its infancy. We

couldn’t imagine what would happen with biotechnology. But we

saw early on in 1985, Genentech got approval for human growth

hormone, and a few months later Eli Lilly came on with a different

version of human growth hormone. And it created exactly this situation. FDA approved Eli Lilly’s second version of human growth

hormone saying it was economically or structurally different.

Mr. BURR. Two different companies.

Ms. MEYERS. Two different companies.

Mr. BURR. Should the same company have the ability to reapply

for whatever changes, get a new 7-year exclusivity agreement?

Ms. MEYERS. Yes. And that also happened with Genzyme’s drug

for genetic disease for Gaucher’s disease where they did improve it.

It had been made out of a natural blood substance or something,

and then they made a biotechnology version and they got another

7 years. Yes, they should, because the main incentive is to develop

a better drug. And it worked.

Mr. BURR. Do you see any problem with the fact that the company who has the current exclusivity certainly has a tremendous

advantage because they have the data? That is not—that is not

data that is shared within the community of researchers that are

out there. And if, in fact, nobody wants to invest the money to create that data base to chase that small population drug, you really

do have an inherent ability of one company to continue to restart

the clock. I am not saying that it happens today. I think that to

some degree, in health care we have to start getting visionary in

this institution.

We do a poor job at crisis management, but that seems to be the

only thing that we try to address now is the crisis management of

today’s problem. And I think that we have got to focus out on the

future and ask ourself what do we need to do in preparation for

the changes. I would only suggest to you that I see a potential

problem there as a Member of Congress. I see the ability for one

company to continue to restart the clock almost like FDA used to

do in their application process when they changed investigators

and when they wanted to slow down the process, they asked for a

new piece of information and the new 180 days started. And that

became more the norm than the exception. But it is a question that

I raise.

Ms. MEYERS. I agree with you. It could be a potential problem,

but the fact is when the exclusivity on the first drug expires, any

other company can get on the market and make that first drug.

Like a generic drug, except for one thing. Congress has never

passed a law that allows the FDA to approve generic biologics. And

so they have to do all of the research, all of the clinical research

and prove all the safety and effectiveness of a brand new drug, and

then they are allowed on the market to compete with the drugs

whose exclusivity has expired. That is what could happen here.

Betaseron, the first beta interferon, their exclusivity has expired.

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If any company can prove that their beta interferon is the same as

Betaseron, they would get on the market.

Mr. BURR. We have clearly got some work that we know we need

to do.

I want to turn to Mr. Navarro. Mr. Navarro, I don’t want you to

think in any way, shape or form that members of this committee

and Members of Congress haven’t struggled not just this year, but

for a number of years to try to find the right balance of the goals

standard of the FDA, their process, and the innovative treatments

that Dr. Brezinski and others have in the marketplace today, and

certainly I have been involved for 4 years in Dr. Brezinski’s treatments. And hopefully we have—this committee has contributed

greatly to the process forward of the current clinical trials that he

has, the expansion of those trials as a liaison between FDA and Dr.

Brezinski on the data that was needed for us to get expansions.

But I don’t want to address Dr. Brezinski’s treatment specifically,

because one thing I want you to understand is that Members of

Congress are not here to practice medicine. But we are here to try

to address the structure that is needed for everybody to receive the

quality of care that they deserve. In doing that, I have found it to

be very difficult. Because quite honestly, many of the patients that

visit me with the personal stories of their fight don’t come back the

next year. That makes a very, very big impact on every Member

of Congress I can assure you, as it does the families, of which many

of us have affected in our families.

My hope is that we can be visionary, we can look at some of the

treatments that exist out there. And that we can form a partnership between medicine and FDA and medicine and NIH and medicine and HCFA, and that we can get patients back to the forefront

of the health care delivery system in this country. We spent a lot

of time arguing whether it is reimbursements or whether it is doctors or whether it is hospitals or whether it is insurers, and really

more time about the process than we do about the outcome. I understand you are only concerned with the outcome. That is all you

should be concerned with. We have got to deal with everything

else.

But let me ask you specifically as it relates to your son, is it your

understanding from the health care professionals that treated your

son, that there was no conventional treatment that was FDA approved, be it chemotherapy or anything else that they had suggested that was specifically FDA approved for pediatrics?

Mr. NAVARRO. You have to understand that radiation and chemotherapy, and I am going to pick just on Thomas’s disease for a

minute, has not been approved for the very reason that it doesn’t

produce successful results. I have had the opportunity in the last

year to speak to more parents than I care to remember that are

the parents of dead children who presented to me their medical

records, the results of the chemotherapy the results of the radiation. And it became very clear very early on that this was a very,

very dangerous option that I did not want to take with Thomas. In

the case of chemotherapy you have to understand that chemotherapy is a cytotoxic poison and Thomas’ oncologist made it very

clear that we are going to basically stretch you to your limits because it is unnatural for a parent to voluntarily poison their child

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in the hopes that it will create a cure. And we have had to go

through this process with Thomas and watch him endure the poisoning with great frustration and anxiety realizing that there was

a non toxic chemotherapy available that other children had been

allowed to use and yet Thomas had been denied access to that.

That particular therapy has been with us for almost 30 years,

and for the last 18 years there have been efforts made to bring it

to the forefront where it can be approved but again, it has been

continually blocked. And the point that I have been trying to make

for the last year is if I have to choose between two unapproved

therapies, which both are, why as a parents do I not have the right

to go with the therapy that will do the least amount of damage to

my son and then if it doesn’t work, step up to a more aggressive

therapy. I have spoken to parents of children that have been destroyed by radiation and chemo. And I am thinking in particular

of the young man from Houston, Texas who today, at 19 years old,

is deaf, dumb, blind, strapped to a wheelchair, has an arm’s length

list of side effects, and yet now that his parents need help in his

maintenance and care, are denied access to that. Because this

child, who is—picture him strapped to a chair, he can’t see, speak

or hear, can’t move, can’t function, is deemed a danger to the other

patients, therefore he can’t go into a group home. I am still, after

almost a year, trying to figure out how he becomes dangerous if he

can’t operate under his own power.

And again, my frustration with the FDA is we have even applied

for a compassionate use exemption. Now the doctor that we chose

to go to in Houston has a protocol for medulloblastoma. He has

treated with the blessings of the FDA children with medulloblastoma. But I found it odd that as more and more children came

through the process well, that all of a sudden there was a new step

put in place saying we can no longer allow you to treat these children until they first go through radiation and chemotherapy and

fail and have recurrent measurable tumor.

If this is a pure glass of water, and my agency is in charge of

making sure that water is available that is healthy to all and I

allow someone to come over here and pour a substance into it and

say, well, Mr. Brady, we want you to have clean water, but before

you can drink this clean water, someone is going to be allowed to

taint it. I think he would be reluctant to drink the water.

And in Thomas’ case, how can we know if the FDA is truly and

sincerely interested in progress and medical and scientific breakthroughs? How can we ever know if the treatment we wanted for

him is successful, if we taint the baseline about other therapies

that take, to be honest, a lifetime to recover from?

Mr. BURR. I hope you will accept my answer which is, I don’t

have one. I can’t explain it to you. But I will assure you that this

committee has not quit, the members on this committee have not

quit to try to one, wade through the modernization of the Food and

Drug Administration, which we completed in 1997, which people

gave us no hope could be done and had passed with unanimous bipartisan support from this House and from the Senate and was

signed into law by the President. We are still waiting to see the

full changes as they are implemented from that legislation. It is

not always a fast process. But much of that is by design in this sysVerDate 11-MAY-2000 09:33 Oct 24, 2001 Jkt 010199 PO 00000 Frm 00128 Fmt 6633 Sfmt 6602 E:\HEARINGS\67114 txed01 PsN: txed01
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tem. I hope you understand that we will continue to strive to make

sure that we have the answer for you and for the other parents

that I know will be here in the future, whether it is on this treatment or another treatment, because we will never build a system

that is perfect. But we will never be content with what we have.

We will always strive for something better.

The unfortunate thing is I have been notified that we have a series of votes. And because I know that that will throw further the

end of the turmoil of members’ schedules this afternoon because of

the knowledge of their schedules, I am going to take this opportunity to apologize to all of you, because I know that we will have

a lack of participation if we take 45 minutes off and try to reconvene.

I am going to leave the record open for written questions to come

to each of you from any members of the subcommittee. And I hope

you will respond to those written questions with answers for the

purposes of the record. Let me, once again, on behalf of the chairman, thank you for your participation in this hearing. This hearing

is now adjourned.

[Whereupon, at 12:45 p.m., the subcommittee was adjourned.]

[Additional material submitted for the record follows:]

ADDITIONAL TESTIMONY FOR THE RECORD OF THE DEPARTMENT OF HEALTH AND

HUMAN SERVICES

The Food and Drug Administration (FDA or Agency) has serious concerns about

H.R. 3677, Thomas Navarro Patients Rights Act because this bill will seriously

weaken the Agency’s ability to protect individuals who volunteer to participate in

clinical trials, one of its primary statutory missions. The Agency would be precluded

from protecting a segment of the population from insufficient information, misinformation and, at worst, fraud. The Federal Food, Drug and Cosmetic (FD&C) Act

created a process that carefully balances the need for scientific support for new

products with the overriding need to protect human subjects. H.R. 3677 upsets this

balance and could lead to harm or possibly death for some patients.

Under the FD&C Act, FDA has been provided the authority to regulate the use

of investigational (unapproved) drugs. As an element of this authority, FDA regulates clinical human investigation conducted by a sponsor. Under statutory and regulatory authority, sponsors wishing to use investigational, unapproved drugs in

human patients must file an Investigational New Drug application (IND) with FDA.

This IND is either an IND that is designed to involve a number of patients or can

be filed as a single patient IND to treat one patient.

The Food and Drug Administration Modernization Act of 1997 (FDAMA) codified

and expanded FDA’s programs to provide access to unapproved products in section

561 of the FD&C Act. This was done after extensive review and consideration of the

needs of patients. The intent was to provide access to therapies for which there was

no effective, approved therapy and particularly for patients who had failed existing

approved therapy. The provisions are clear in requiring the individual physician,

FDA and the sponsor of the investigational drug to go through a series of steps before allowing the drug to be made available to the patient. These ultimately require

a balancing of the risks and benefits of the proposed administration of the investigational drug. As part of the access program, the sponsor is still required to file either

a single patient IND or an IND to treat a small number of patients.

FDA is obligated to evaluate an IND submission within 30 days and make a determination if the clinical investigation should proceed or the investigation should

be put on clinical hold. The primary focus of this decision is the safety of the patients who may receive the unapproved drug. The evaluation includes a determination of the nature and level of risk to the patients who may be the subject of the

clinical investigation, design of the clinical investigation, various qualifications of

the investigators, the disease being investigated and other information about the

drug. The same evaluation is done for submissions that may be considered single

patient INDs or emergency INDs, although FDA makes the decision in a considerably shorter time period than 30 days and in the case of an emergency IND usually

within 24 hours or less.

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FDA has, in rare instances, placed on clinical hold a proposal to administer an

investigational drug about which little was known to treat a serious or life threatening disease when there was known effective, or life saving, therapy for that condition. We did so because those subjects would have been exposed to an unreasonable

and significant risk of illness or injury. This is also required under FDA regulations

governing clinical holds. (Title 21, Code of Federal Regulations § 312.42). The risk

in these cases was not simply the possible untoward effects of the investigational

agent but also the risk of substituting a known effective therapy with something

that might have no effect. Although these circumstances occur rarely and are

dwarfed in numbers by those clinical trials allowed to proceed, the ramifications of

being unable to put a particular investigation on hold would be dramatic.

FDA understands the seriousness of placing any investigation on clinical hold and

does so only after following a careful process that includes deliberation with internal

experts and, if necessary, consultation with external experts about the particulars

of the disease state and potential for available therapies.

The ability to put an investigation on clinical hold is the primary mechanism FDA

has to protect human subjects who are being asked to participate in a clinical investigation and asked to be part of an experiment with unapproved investigational

drugs. H.R. 3677 contains several provisions that could impair the ability of FDA

to put clinical investigations on hold even if a patient’s safety is being compromised

and could prevent FDA from taking action specifically for an individual patient who

may be at a high level of risk.

Section 2 (a) of H.R. 3677 amends section 505(i)(3) of the FD&C Act by limiting

the ability of FDA to impose a clinical hold on an investigation. The new provision

would prohibit a clinical hold even if another therapy is determined to be safer because it is a known curative therapy. The entire basis for this prohibition on FDA

is that the patient has, in effect, waived their right to informed consent. The patient, by declaring in writing that s/he is ‘‘aware of the comparable or satisfactory

alternative therapy... aware of the risk involved in receiving the drug in the investigation, and chooses to receive the drug notwithstanding such risk and notwithstanding the comparable or satisfactory alternative therapy’’ could prevent the imposition of a clinical hold even for safety reasons which may be directly related to

the individual patient’s safety.

The bill creates a situation in which research subjects may be presented with incomplete and/or biased information by investigators who often have substantial personal, financial or professional interests at stake in the research. FDA is concerned

that the consent obtained under these circumstances will not be truly informed consent because it will not be based on a thorough and objective explanation of the

risks and benefits of both the unapproved investigational product and the proven

treatment that is being foregone.

H.R. 3677 does not even require that the sponsor administering the unapproved

investigational drug provide all the information to the patient typically contained

in an informed consent. The idea that a patient could essentially sign away their

rights to adequate health care to anyone who is able to convince them to do so, without oversight and without any assurance of proper information, is offensive and unethical. Even absent mal-intent, the most well intentioned investigator is unlikely

to have access to all that is known about an unapproved investigational drug very

early in its development.

Furthermore, since FDA has been provided the authority to oversee the use of unapproved investigational drugs, the Agency is the one central location that collects

data on those unapproved investigational drugs. FDA is often the only party in possession of information from different sponsors that could impact the decision as to

whether an unapproved drug should be used in a clinical investigation. There is no

means of ensuring that the patient actually knows all of the risks involved. Reliance

on the sponsor of the investigational drug to provide all the known risks is misplaced since that particular sponsor may not have access to all of the information

known about a drug. Thus, through no fault of the sponsor, complete information

on risk may not be provided to the patient considering the use of the unapproved

investigational drug.

The importance of clinical hold as an Agency tool to help ensure the protection

of human subjects in clinical trials is illustrated by the recent example of the Jesse

Gelsinger case. At age 18, Mr. Gelsinger volunteered to participate in a clinical trial

of a gene therapy product and died shortly after the administration of the product.

The investigator who recruited Mr. Gelsinger to the trial did not follow the terms

of his protocol and did not reveal important safety information during the informed

consent process, so that Mr. Gelsinger’s consent was not fully informed. When FDA

learned of this subject’s death, the Agency put this trial on clinical hold so that no

other patients would be subjected to the dangers inherent in this trial.

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Under H.R. 3677, FDA would have no ability to protect subjects even if the Agency had information that practitioners were using dishonest means to coerce patients

into participating in trials in lieu of taking proven therapy. If H.R. 3677 is enacted

and such ethically suspect practices are allowed to proliferate, it also could seriously

undermine the public’s confidence in the process of conducting biomedical research

in this country with dangerous consequences to the public health.

There are other technical drafting problems with H.R. 3677 which are not included in this submission. Even if technical changes were made, however, FDA

would still have concerns with the impact of the proposed legislation.

FDA has a long, and successful, history of expediting access to investigational

agents for those who patients with serious and life threatening illnesses who have

no satisfactory therapy available to them. We also have a long and successful history of protecting patients who are most vulnerable, including those with life threatening illnesses who are desperately seeking help and hope.

LUPUS FOUNDATION OF AMERICA

November 9, 2000

The Honorable MICHAEL BILIRAKIS

Chairman, Subcommittee on Health & Environment

U.S. House of Representatives

Committee on Commerce

2125 Rayburn House Office Building

Washington, DC 20515

DEAR MR. CHAIRMAN: In response to your letter of November 2, 2000, I am

pleased to submit the attached answers to the questions prepared by members of

the Subcommittee on Health & Environment. Please contact me if I can provide additional information.

It was a pleasure to appear before your Subcommittee on behalf of the 1.4 million

Americans with lupus. I want to express my sincere gratitude to you and the Members and staff of the Subcommittee for your support of the Lupus Research & Care

Amendments of 2000 Act.

Sincerely,

TOMIKO FRASER

National Spokesperson

ANSWERS TO QUESTIONS SUBMITTED BY SUBCOMMITTEE MEMBERS.

Question 1. Why does lupus seem to affect women of color more often than Caucasian women?

Response. This is the subject of a research project currently underway by NIH.

(Lupus in Minorities Study, or LUMINA) We believe lupus has a genetic basis and

it appears that the genes suspected of causing lupus might be more prevalent

among women of color.

Question 2. Are manifestations of lupus more serious among African-Americans

than among Caucasians?

Response. African Americans have more kidney involvement than Caucasians. Researchers may have located a gene believed to cause kidney disease in African

American lupus patients.

Question 3. Can lupus be prevented, or the health impact minimized in any way?

Response. Unfortunately, you can’t prevent lupus. However, you can take steps

to minimize health effects of lupus, such as adopting a healthy lifestyle, such as

avoiding stress, getting plenty of rest, eating well, light exercise, and following your

doctor’s advice. Diagnosing lupus early, and seeing a doctor regularly can minimize

damage to vital organs. The earlier lupus is diagnosed and treated, the more likelihood of preventing the need for more expensive treatment.

Question 4. Do we know why lupus strikes mostly young women?

Response. The exact cause of lupus is unknown, but researchers believe lupus has

a genetic basis. Hormonal influences may explain why lupus affects mostly women

in their childbearing years. But we don’t know if there is something about women

that makes them more vulnerable to developing lupus, or if there is something

about men that protects them from lupus.

Question 5. Why is lupus so expensive to treat?

Response. Lupus requires constant medical attention by a number of specialists,

requiring many tests to monitor the status of the immune system. Because the disease usually presents multiple symptoms, people with lupus must take many medications. It is common for people with lupus to take over a dozen medications. In

addition, monitoring lupus activity requires many expensive tests to determine the

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functioning of the immune system and many vital organs, such as the kidneys,

lungs, heart, and brain.

Question 6. What impact does lupus have on the work force or corporate community?

Response. One in five people with lupus is disabled. Many victims of lupus must

cut back their work hours, or change jobs to reduce stress. This results in lost productivity for corporations, and costs millions of dollars. In addition, disability costs

rise to cover people with lupus.

Question 7. What is The financial impact of lupus on the rest of the family?

Response. It’s difficult to measure, but it has to be significant. On average lupus

costs $6,000 to $10,000 annually to treat, but some victims incur costs of several

thousand dollars a month. This level of expense can have an enormous impact on

the family budget.

Question 8. Does the environment play a role in causing lupus?

Response. Yes, while lupus has a genetic basis, we know that certain environmental factors trigger disease activity, including UV light, infections, certain chemicals and drugs, and stress. There is much interest in this area of research, particularly in regard with the role breast implants may have in causing an autoimmune

reaction.

Question 9. Are we seeing more cases of lupus today than in the past?

Response. It’s hard to determine the exact number of lupus cases. We don’t know

if lupus is on the rise, but doctors are getting better at diagnosing the disease,

which may be the reason we are seeing more cases of the disease. However, some

researchers do believe that lupus is increasing among young women.

Question 10. Can lupus be treated with less expensive herbal or complementary

therapies?

Response. There is considerable interest in this area. Some therapies, when used

in combination with a doctor’s care, can help reduce symptoms, but they are no substitute for traditional medicine. Lupus is a dangerous disease that needs constant

monitoring by a trained doctor. The FDA has given fast track designation to a new

therapy for lupus using the hormone, DHEA.

Question 11. Are there new treatments in the pipeline?

Response. Yes, there are several therapies undergoing clinical trials that will address various manifestations of lupus, but the disease is so complicated, no magic

pill will ever cure lupus. It will take much more research. Some therapies include

biologics that can block the immune system from producing autoantibodies.

Question 12. What is the outlook for a cure for lupus?

Response. While there has been progress, a cure is not on the horizon. We are

getting better at treating symptoms of the diseases and patients are living longer,

but there is no cure for the foreseeable future.

RESPONSE OF JAMES NAVARRO TO QUESTIONS OF THE SUBCOMMITTEE ON HEALTH

AND ENVIRONMENT

Question 1. Mr. Navarro, in your opinion, who should decide the course of medical

treatment for your son: you, or the FDA?

Response. This answer requires very little thought. The Food and Drug Administration (FDA) is an agency made up of many different people from many schools of

thought. These people many times as we have discovered, get caught up in defending a position, or a particular discipline of medicine and often forget the ‘‘PATIENT’S RIGHT TO CHOOSE’’. Often, the patient is ignored entirely. We as parents of a terminally ill child, have only one agenda, and that is to see our son survive, with dignity and quality of life. Agencies and doctors are often driven by egos

and money, as we have tragically experienced during our journey with Thomas. Nobody and I mean nobody, will ever have his best interest at heart, more so than

his mother, Donna, and I do.

Question 2. My understanding is that the FDA denied Thomas access to a clinical

trial because he had not first gone through and failed chemotherapy and radiation.

Why did you decide to forgo this treatment?

Response. Before I can answer this question, we must first clarify a very important fact which is quite often ignored, that fact is that, ‘‘RADIATION AND CHEMOTHERAPY HAVE EVER BEEN APPROVED BY THE FDA FOR USE IN TREATING PEDIATRIC CANCERS’’, it has merely become the unopposed standard of care

for treatment, because anyone who stands in opposition to its use is either crushed

as far as career advancement goes, or is dismissed as a charlatan as history has

bore out. Chemotherapy alone represents a $107,000,000,000.00 ($107 Billion) a

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year industry. Our history unfortunately has always born out that profit always

comes before people.

It is important to remember that ‘‘STANDARDS OF CARE’’ does not mean that

a treatment has been thoroughly tested and adequate evidence reviewed by the FDA

or other Federal Agency to assure safety and efficacy. A ‘‘STANDARD OF CARE’’ is not and should not be an endorsement by a Federal agency that has never evaluated the data. ‘‘STANDARDS OF CARE’’ are protocols that doctors in cancer research centers have developed according to their own research as the best treatment

option according to their perspective in how to treat cancer.

Now, to be more specific, our reasons for not wanting to use these ‘‘STANDARDS

OF CARE’’, on our son were much simpler. The simple fact is these treatments are

extremely dangerous to use, and more often than not, end in permanently damaging

or even killing the patient. Quite simply, if it is all a ‘‘crap shoot’’, we as parents

are compelled to start with a treatment which will do the least amount of harm

first. The following is a list of just some of what Thomas would suffer as a result

of being treated by Radiation and Chemotherapy: FATIGUE, NAUSEA, VOMITING,

ABDOMINAL CRAMPING, HAIR LOSS, LOSS OF IQ, LOSS OF HEARING, LOSS

OF MEMORY, FLUID IN THE MIDDLE EAR, HYPOTHYROIDISM, SPINAL

GROWTH DEFICIT, HYPOPITUITARISM, SECONDARY TUMORS, LOW LEVEL

HORMONES (For the rest of his life), RADIATION NECROSIS, KIDNEY NECROSIS, AND DEATH FROM EITHER RADIATION POISIONNG OR CYTOTOXIC

POISIONING. These are just some of the possibilities we faced with Thomas. You

must also understand that every child we have met during Thomas’s journey that

was treated using the ‘‘STANDARD OF CARE’’, is now dead, the most recent we

buried just two weeks ago. The choice we made was not a difficult one. We chose

life. We knew through careful research that there were other possibilities for Thomas, we never thought our government would stand against us in making those

choices.

Question 3. According to the administration’s written testimony, the intent of current law is to protect ‘‘our most valuable citizens, those who are desperately ill’’ and

that the FDA believes this bill would undermine FDA’s ability to help assure reasonable safety and effectiveness of subjects in clinical trails and informed consent

for patients given access to experimental therapies.’’ In that Administration statement, with what do you agree or disagree?

Response. The opening statement of this question reminds me of the old axiom; ‘‘THE ROAD TO HELL IS PAVED WITH GOOD INTENTIONS.’’ First, all citizens

of this great country should be considered valuable, not just the sick, and in keeping

with that thought, it is we the people who should be allowed to decide what is best

for us. Second of all, the Agency’s roll is to monitor safety and effectiveness, not to

sit in judgment, deciding who can and can’t introduce new promising therapies: as

is the case with the treatment we choose for Thomas. For almost twenty years, the

FDA has stood as a roadblock to progress, instead of helping to advance a therapy

which shows great promise in treating the specific cancer that Thomas suffers from.

Third, as far as informed consent goes, this is a process that we personally have

seen abused and the FDA and HHS does nothing to correct it. There needs to be

better accountability at the FDA and amongst the Doctors. Until or unless that happens, no expanded authority in the decision making process should be considered.

The role of both the doctor and the FDA should be to assist us in making decisions

by providing us with all of our treatment options and offering their best advice. It

is not the role of the FDA or the doctor to take control of our lives and forcing us

to submit to their will.

Question 4. H.R.3677 precludes the FDA from establishing a clinical hold on the

basis that there is a comparable or satisfactory alternative therapy if the patient

is 1) aware of the other therapy; 2) aware of the risk associated with the investigational drug; and 3) chooses to receive the drug. How would this bill affect you and

others you may have met during the ordeal you have faced in getting your son the

treatment you have decided to be best? Do you see ways in which this bill might

be abused by charlatans pushing treatments that do not work?

Response. Again we see in the opening statement, the FDA, usurping a patient’s

right to choose. Understand that ALL CANCER THERAPIES ARE EXPERIMENTAL AT THIS TIME IN OUR SEARCH FOR THE CURE, and to deny a patient access to their personal choice of treatment based on a personal bias is IMMORAL. The bill does not open the door for charlatans to abuse the law anymore

than current laws do. This bill would have allowed us access to the therapy of our

choice, a therapy that would not have destroyed our son as conventional treatment

would. Also understand that if we had been allowed access to it and it had not

worked, we would have stepped our mode of treatment to a more aggressive treatment like chemotherapy or radiation. But to be FORCED into a treatment from the

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onset is wrong. The FDA will still be allowed to put clinical trials on hold that have

safety concerns. It is the role of the FDA to advance science monitoring the safety

of trials involving human subjects. It is not the role of the FDA to pick one trial

over another, or to stand in the way of advancing science by excluding access to a

clinical trial for a ‘‘STANDARD OF CARE’’ that has never been through an FDA

approval process for the specific condition or age group in question.

Question 5. In a news account entitled ‘‘PARENTS FIGHT TO SAVE SON’’, published by Wired News, the article stated that ‘‘When the Navarro’s decided they

wanted their son to be treated by Burzynski, the FDA denied them permission, ruling that the treatment could only be used as a last resort. FDA officials threatened

to take Thomas into protective custody if the Navarro’s denied him traditional treatment.’’ Do you have any documentation you can provide the Committee that the

FDA, or any other government agency, was going to place your son in protective custody?

Response. First of all, I would like to state for the record that I was unaware of

this article until I read of it in your questions from the subcommittee. With that

said, I found a copy of the article and read it. Now in answer to your question:

It is true that the FDA denied Thomas access to treatment at the Burzynski Clinic, citing that there was no scientific, ethical, or moral basis for allowing Thomas

access to treatment when an existing ‘‘STANDARD OF CARE’’ was already available. It didn’t matter to them that the ‘‘STANDARD OF CARE’’ had such devastating and deadly results. It didn’t matter to them that in the ‘‘STANDARD OF

CARE’’ two of the three recommended chemotherapy drugs stated on the package

insert, ‘‘this product not proven safe or effective in the pediatric population.’’ It was

their way of doing business, and to that end their word was final.

In following their logic for a moment, if you have used the most damaging and

deadly treatment first, what is left of the patient to treat if the patient has been

rendered permanently damaged, or worse, if the patient has died? At this point,

treatments that would offer as great or greater a hope have been rendered useless

by the FDA’s decision making process. In effect, ‘‘THEY HAVE THROWN THE

BABY OUT, WITH THE BATH WATER’’.

It is incorrect that the FDA threatened to take Thomas into protective custody.

In actuality, When my wife and I made the decision not to subject Thomas to the

standard of care, Thomas’s oncologist back in Arizona swore out a complaint, alleging CHILD ABUSE, CHILD ENDANGERMENT, AND MEDICAL NEGLECT for refusing a treatment which had discovered would leave our son retarded, deaf, sterile,

blind, with stunted growth, and even dead. WHAT IS WRONG WITH THIS PICTURE? It is our undaunted opinion, that the current ‘‘STANDARD OF CARE’’ is

LEGALIZED CHILD ABUSE. What loving parent would knowingly and willing subject their child to this type of torture with no guarantee of success, knowing that

there were other treatments available, that didn’t do this type of damage that

hadn’t been tried first.

Question 6. Critics at the FDA state that by pursuing alternative therapies that

are ‘‘not FDA approved’’, you are placing your ‘‘son at greater risk of death’’ than

if he first pursued FDA approved therapies that include radiation and chemotherapy, that may render your son to be retarded. How would you respond to your

critics at the agency?

Response. First, I would like to remind my critics at the FDA of an oath they took

many years ago. And I quote, ‘‘FIRST, DO NO HARM’’, it is the beginning of the

Hippocratic Oath. With that said, let me start by saying, I agree, unapproved therapies can present risks. Some are great and some are small. The risk is no greater

than the risks taken by using Radiation and Chemotherapy, which again I will remind you are, ‘‘ NOT FDA APPROVED FOR TREATING PEDIATRIC CANCERS’’.

They are standard treatments used, which ‘‘IMPLIES APPROVAL’’, it does not

mean that have been approved going through the ‘‘NORMAL APPROVAL PROCESS’’. LET US NOT CONFUSE THE TWO! If under any other means, if I were to

go out with forethought and blind my son, or deafen my son or by some means,

cause him to become retarded I would be arrested, tried, and thrown into jail, and

rightfully so, but it is done everyday in the treating of childhood cancer with NO

ACCOUNTABILITY . And not allowing my son to be subjected to these medieval

treatments, makes me a bad parent in the eyes of the ‘‘STANDARD OF CARE

COMMUNITY’’. There is nothing in my life that I love greater than my children,

and they will be no doctor’s ‘‘LAB RAT’’, not while I breath.

I hope this has clarified any questions you might have. Please feel free to contact

me if you have any further questions.

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NATIONAL ORGANIZATION FOR RARE DISORDERS, INC.

November 15, 2000

The Honorable MICHAEL BILIRAKIS

Chairman

Subcommittee on Health and the Environment

US House of Representatives

2369 Rayburn House Office Bldg.

Washington, DC 20515

DEAR CHAIRMAN BILIRAKIS: Thank you for your letter of November 2, containing

additional questions from the September 13, 2000 hearing on H.R. 4242, the Orphan

Drug Innovation Act. My answers to the questions follow:

Question 1. Do you believe that shielding the original orphan drug from competition for longer than 7 years is good policy?

Response. No. The Orphan Drug Act of 1993 provides seven years of exclusive

marketing rights to the sponsor of an orphan drug, and no manufacturer should

have more than seven years without competition. However, there are many orphan

drugs that have had no competition after seven years on the market simply because

no other companies have made an effort to compete after the innovator’s exclusivity

expired.

On the other hand, the European Union enacted the Orphan Medical Products

Regulation in December 1999, providing ten years of exclusivity to orphan drug

manufacturers. Since this is a new law, we do not yet know how successful it will

be in comparison to the U.S. law. In other words, is ten years of exclusivity a better

incentive than seven years? Will more companies develop orphan drugs in Europe

than the United States because American incentives are not as strong? We believe

it is premature for Congress to consider revising (either contracting or expanding)

orphan drug exclusivity in the United States at this time.

Question 2. Do you believe that this policy needs clarification?

Response. Under very limited circumstances the FDA may allow the manufacturer

of a ‘‘similar’’ orphan drug to reach the American market before an innovator’s orphan drug exclusivity expires IF it can prove that the follow-on drug is ‘‘different’’

from the original orphan drug. A manufacturer must prove that its drug is chemically or structurally different from the first orphan drug, or that it is superior because it is more effective or safer, or represents a ‘‘major contribution to patient

care.’’ FDA’s regulations defining these requirements were established in 1992. We

believe the regulations have worked very well for many years, and they do not need

to be revised at the current time.

Please note that the orphan drug regulations were printed nine years after the

Orphan Drug Act became law, they went through extensive public comment periods,

and they have been time tested since 1992. Mr. Chairman we believe these regulations effectively carry out the spirit and intent of the law, and they should NOT

be written into law because minor changes would subsequently require an act of

Congress. Regulations are easier to change when the need arises, and the public is

encouraged to comment and provide input into revised regulations.

Question 3. On February 7, 2000, you sent a letter to FDA Commissioner Henney

stating, ‘‘As you probably know, we have been concerned about the blockage of a

new version of beta interferon form multiple sclerosis. FDA seems to believe that

the product is the same as both Avonex and Betaseron, even though those two products have already been determined by both FDA and a federal court to be ‘different.’

This puts Serono in a no-win situation, even with its full BLA and having been initially determined to be ‘the same’ as Betaseron under the Orphan Drug Act.’’ Why

did you write that the FDA implementation of the Orphan Drug Act puts Serono

in a no-win situation?

Response. If you read my entire letter of February 7, 2000 to FDA Commissioner

Henney, you will clearly see that the question I raised involved FDA’s refusal at

the beginning of this year, to decide whether Avonex was the ‘‘same’’ as Betaseron

or the ‘‘same’’ as Avonex, but I asserted it could not be the same as BOTH. The

letter was an effort to force the agency to decide which ONE of those two drugs

Rebif is the same as.

Let me explain. At the beginning of this year, FDA determined that Rebif is the

same as the two competing versions of the multiple sclerosis treatments, Betaseron

and Avonex. Betaseron was the first version of beta interferon to reach the market,

but FDA subsequently decided that Avonex was a ‘‘clinically superior’’ orphan drug,

and therefore should be made available to multiple sclerosis patients before

Betaseron’s exclusivity expired. The manufacturer of Betaseron went to court to stop

Avonex from reaching the market, claiming that its orphan drug exclusivity would

be violated. The court decided that FDA’s decision was correct and that Avonex is

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a ‘‘different’’ drug because it was ‘‘clearly superior,’’ and thus could be approved by

the agency despite Betaseron’s exclusivity.

Late last year, FDA told Serono that it could not approve its multiple sclerosis

treatment, Rebif, because it was the ‘‘same’’ as both Betaseron and Avonex. I wrote

to Commissioner Henney in February explaining that FDA cannot claim Rebif is the

‘‘same’’ as both of these drugs because the FDA had already determined, and a federal court had agreed, that Betaseron and Avonex are not the same drug. Serono

was in a no-win situation because the company would have to prove that Rebif was

‘‘different’’ than two different drugs, not one. I urged the Commissioner to determine which of those two Multiple Sclerosis treatments Rebif was the ‘‘same’’ as. I

did not urge the Commissioner to cast a vote toward one drug or the other; we simply wanted a decision to be made. Later this year FDA did make the decision that

NORD was asking the FDA to make, and the agency decided that Rebif is the

‘‘same’’ as Avonex. Apparently Serono disagrees with that decision.

Note. The answer to the following three questions is written below:

Question 4. Can you reconcile your written testimony today with your February

7 letter to FDA Commissioner Henney where you state, in reference to 7-year market exclusivity enjoyed by Biogen, ‘‘However, after seven years expire, competitors

should be allowed on the market without undue delay, and the beta interferon scenario, as a precedent, very troubling.’’ Question 5. Would you consider your February 7, 2000 letter to FDA Commissioner Henney to be at variance with your testimony today?

Question 6. What caused you to change your mind?

Response. My testimony on September 13 conforms to the statements made in the

February 7 letter to Commissioner Henney. The beta interferon scenario was very

troubling because there was no way that Rebif could be the ‘‘same’’ as both Avonex

and Betaseron! It could only be the same as ONE of those drugs.

I believe that FDA was wrong for not making a decision on this matter much

sooner, and for keeping their decision confidential when it was made. Unfortunately,

FDA is required under law to keep all information confidential unless a drug sponsor agrees to make it public. It was only after Serono gave written permission to

FDA to talk to me about Rebif that I was told the agency’s scientific analysis concluded that Rebif is the ‘‘same’’ as Avonex, and not the same as Betaseron. This

means FDA cannot approve Rebif for sale in the United States until the exclusivity

of Avonex expires. If Serono disagrees with this decision, the onus is on the company to scientifically prove their drug is not chemically the ‘‘same’’ as Avonex, or

to prove their drug is ‘‘clinically superior’’ to Avonex. I understand that Serono is

conducting clinical trials now in an effort to prove clinical authority.

Question 7. The testimony of your organization was requested by Biogen, the company that has been trying to thwart Serono’s legislative activities in this area. Have

you had any contacts with Biogen or its agents on this matter?

Response. I have had no contact with Biogen on this or any matter. I am not surprised that Biogen recommended that we testify at the hearing because we are usually invited to testify at all hearings concerning the Orphan Drug Act. In fact, I was

quite surprised when I learned there would be a hearing about orphan drugs, and

we were not invited to testify. I finally received a telephone request from your staff

a few days before the hearing and was delighted to change my plans and go to

Washington, DC. I had no idea that Biogen made this recommendation, and let me

assure you NORD is not conspiring with anyone to keep Serono off the market.

Since Biogen had no way to know what I would say in NORD’s testimony, it was

certainly considerate of them to suggest that NORD be included. However, people

in Washington generally know that NORD is always fair and unbiased, it is the

quintessential patient advocacy organization, it does not favor one drug over another, one company over another, and NORD can always be relied on to defend the

Orphan Drug Act and its regulations.

Question 8. Do you believe that co-marketing during the original orphan’s exclusivity period, protection for that innovation, and the opportunity to market that advantage are enough of an incentive to foster research and development investment

to improve orphan drugs? If not why not?

Response. This is a very complicated question, but the basic answer is: Exclusivity

is the most important incentive of the Orphan Drug Act, and any weakening of exclusive marketing rights would greatly undermine development of future treatments

for rare diseases. If you allow orphan drug exclusivity to be violated because a manufacturer makes a minor change to a drug that has no substantial benefit to patients, then you will have diluted the ODA’s chief incentive, and fatally weakened

the law.

Mr. Chairman, when a pharmaceutical company decides which drugs to invest in,

they prefer to focus R&D on the least risky products. This is why so many drug

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companies invest billions of dollars in research and development of ‘‘me-too’’ drugs,

compounds that are very similar and vary only slightly from other marketed drugs

that are very successful and profitable. They practically copy the original compound

and make some minor chemical or structural changes so that they do not violate

the innovator’s patent, and then they get the drug on the market to compete with

the original drug. Historically this is why we have so many beta blockers on the

market for hypertension, so many anti-inflammatories for arthritis, and soon there

will be many drugs for erectile dysfunction.

This is the way the marketplace works so well for drugs that are used by large

numbers of people. But orphan drugs affect few people, manufacturers know there

is a limited potential market to buy their drug, and they want assurance that a

competitor will not take part of their market away. The industry did not manufacture orphan drugs before the Orphan Drug Act was enacted (e.g., only ten orphan

drugs were brought to market in the 10 years before the Orphan Drug Act became

law); but since 1983, over 200 orphan drugs have reached the American market.

These companies will tell you they would not have invested in development of

their orphan drug if they were not guaranteed seven years of exclusivity.

In the very few instances when FDA has approved a ‘‘similar’’ orphan drug before

the exclusivity of the first drug expired, it has only occurred when manufacturers

AGREED to SHARE exclusivity, or the follow-on company PROVED SCIENTIFICALLY that their drug is clinically superior.

In the case of the three versions of beta interferon the first version (Betaseron)

caused a very serious injection site reaction necessitating surgery. The second

version (Avonex) does not cause this very serious adverse reaction, so it was allowed

on the market. This is a safety advantage, and it would have been unjust to prevent

Avonex from reaching Multiple sclerosis patients. Rebif on the other hand has not

yet proven that it is clinically superior to Avonex, FDA has determined that Rebif

is scientifically the ‘‘same’’ as Avonex, but it also causes the same serious injection

site reactions as Betaseron.

The onus is now on Serono to prove that their drug is clinically superior to

Avonex. The company is conducting a clinical trial right now, comparing Avonex to

Rebif. We believe that the scientists at FDA will then be able to determine whether

Rebif is clinically superior to Avonex. Thus Congress should await the results of

that trial and allow FDA to make that determination. We believe that tinkering

with the law now, and diluting the exclusivity incentive of the Orphan Drug Act,

will weaken the law and remove any incentive for manufacturers to develop clinically superior orphan drugs that patients need.

Question 9. Do you believe FDA’s policy should distinguish between drugs that are

clinically superior based on improved safety or efficacy from those based on being

a major contribution to patient care?

Response. We believe FDA’s current regulations defining clinical superiority are

right on target, and they should be left as they are. If and when FDA decides to

change the regulations, the agency is required to publish the proposed revisions in

the Federal Register, and patients will then have an opportunity to express their

point of view. Today the agency will only approve a competing orphan drug if it can

prove that it is safer, more effective, or is a major contribution to patient care. Patients want and need these therapeutic improvements. The current regulations act

as an important incentive to companies to develop better orphan drugs.

Question 10. Do you object to Congress providing FDA with guidance on handling

clinically superior drugs, an issue not currently covered in the statute?

Response. We do not believe it is necessary or warranted for Congress to provide

guidance to FDA on handling ‘‘superior’’ orphan drugs. Firstly, we recommend that

Congress ought to leave these decisions up to the physicians and dentists at FDA.

Secondly, although ‘‘clinical superiority’’ is not specifically mentioned in the statute,

it was absolutely proper and necessary for the agency to develop this regulation because the terms ‘‘same’’ and ‘‘different’’ in the statute had to be defined in regulations.

The FDA’s orphan drug regulations define the terms ‘‘same drug’’ and ‘‘different

drug’’ because recombinant DNA technology made this necessary. Seventeen years

ago when the law was written we were dealing solely with chemical compounds that

could easily be differentiated. Today, however, many new treatments are developed

through biotechnology engineering and the differences between biologics is very difficult to discern. One simply cannot define the chemical structure of a biologic and

determine if it is the same or different from a ‘‘similar’’ biologic. Most of these products are copies of proteins or enzymes that human bodies naturally make. Moreover,

Congress cannot develop a formula that fits every clinically significant difference,

and which factors should be considered. For example, is a three-hour intravenous

infusion clinically superior to a six-hour infusion? Does a lower price for a followVerDate 11-MAY-2000 09:33 Oct 24, 2001 Jkt 010199 PO 00000 Frm 00137 Fmt 6633 Sfmt 6621 E:\HEARINGS\67114 txed01 PsN: txed01
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on orphan drug represent clinical superiority? Once you ask questions like these,

you open a very big can of worms.

In conclusion Mr. Chairman, the patient community is indebted to Congress for

enacting the Orphan Drug Act in 1983. We advise that if ‘‘it ain’t broke, don’t fix

it,’’ nor its regulations. Serono is doing the right thing now; they are conducting

clinical trials to try to prove scientifically that its drug is superior to other competing drugs. This process is available to them under the current Act and its regulations. NORD’s concern is not which company is right or wrong, nor, how much profit

they may lose when FDA denies them early marketing approval, but whether patients are suffering because of lack of access. There are three good FDA approved

treatments for multiple sclerosis available to American patients today, and at best

any clinical superiority that Serono will claim will not indicate that Rebif is a cure

for multiple sclerosis. If it were, FDA would approve it! Rebif may be a treatment

that is superior in some ways, but inferior in others. Only science can tell us, and

we await results of its clinical trials comparing it directly to Avonex.

Please do not hesitate to contact me if you have any other questions.

Very truly yours,

ABBEY S. MEYERS

President

UNIVERSITY OF VIRGINIA

DEPARTMENT OF RADIOLOGY

November 10, 2000

Congressman MICHAEL BILIRAKIS

Chair, Subcommittee on Health and Environment

U.S. House of Representatives

Rayburn House Office Building, Room 2125

Washington, DC 20515-6115

DEAR MR. BILIRAKIS: The following are my responses to the questions in your letter of November 2, concerning my testimony on HR 1795.

Question 1a. Why is an institute necessary to solve the problems associated with

biomedical imaging research at the NIH?

Response. That imaging research is spread over 16 institutes and centers means

that there is no single institute charged with responsibility for support of basic research to develop new imaging techniques and technologies with broad applications

to the diseases and organ systems that are the focus of the existing institutes. Consequently, such research, which is critical to advances in imaging, receives little or

no support from the NIH. There is also no coordination of imaging research at NIH.

Major opportunities are lost, as they are not apparent in the content of the institutes’ disease focus. There is duplication, as there is little coordination of imaging

opportunities. Given the declining ability of both academic departments and industry to finance imaging research, an institute directed specifically at imaging, with

a comprehensive plan, able to prioritize and pursue opportunities is essential.

Question 1b. Could the Bioengineering Consortium (BECON) that the NIH has established, or a coordinating committee of some type be an alternative?

Response. Such alternatives fall short of what is needed in both scope and authority. An institute has the capability of addressing the diverse needs that are essential

to successfully addressing the nation’s needs with respect to medical imaging, including the authority to fund grants, set a research priorities through the request

for applications process, and enable research training. This level of comprehensiveness does not exist through any other mechanism.

Question 2. The National Cancer Institute has made imaging a top research priority and has put much more money into this field. Can’t we solve the problem by

further increasing the amount of money that NCI commits to imaging?

Response. While more NCI money certainly can increase imaging research in cancer, it does not address the need to advance imaging research more broadly in support of the nation’s health. Indeed, it is this ‘‘silo’’ approach to imaging that is so

ineffective. Imaging is applicable across a broad range of organ systems and diseases and needs, as such, to be addressed more directly.

Question 3. Other groups have come to the Congress requesting that new institutes be created. How can Congress distinguish among these proposals?

Response. The Institute of Medicine has advised Congress in a 1984 report titled

Responding to Health Needs and Scientific Opportunity: The Organizational Structure of the National Institutes of Health—on when it should consider establishing

a new institute. The proposed Institute for Biomedical Imaging and Bioengineering

fulfills all of these criteria and is also consistent with a second IOM report, which

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was written in 1998 and titled Scientific Opportunities and Public Needs: Improving

Priority Setting and Public Input at NIH. Establishment of the proposed institute

will advance research that will have a positive impact on the public health while,

at the same time, reducing inefficiencies and duplication. Dr. Reed Dunnick discussed both IOM reports at greater length in his testimony.

Question 4. What role can new imaging technologies play in the advanced research in molecular biology and genetics that is conducted by the other institutes

at the NIH?

Response. Both advances in established imaging technologies and the emergence

of a host of new technologies promise spectacular contributions to our understanding

of the early phases of such important disease processes as cancer and heart disease.

Medical imaging is, in essence, the ‘‘noninvasive biopsy’’ that can provide insight

into how subcellular structures are altered by disease in both their morphology and

function. Imaging technologies already are being used for these purposes. Their importance in investigation, diagnosis, and treatment will grow over the near term.

Question 5. What makes the basic scientific research involved in imaging and bioengineering different from the scientific research at the disease and organ-system

institutes?

Response. The most fundamental difference is in the nature of the training and

expertise of the individuals involved. Medical imaging technology development requires the skills of physicians, computer scientists, physicists, mathematicians, information technology specialists, and engineers. The research is interdisciplinary

and cuts across disease and organ system lines.

I appreciate the opportunity to further comment on the need for an Institute for

Biomedical Imaging and Bioengineering. Please let me know if you wish me to address these or other issues further.

Sincerely,

BRUCE J. HILLMAN, MD

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