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COMPASSIONATE USE OF INVESTIGATIONAL NEW

DRUGS: IS THE CURRENT PROCESS EFFECTIVE?

HEARING

BEFORE THE

COMMITTEE ON

GOVERNMENT REFORM

HOUSE OF REPRESENTATIVES

ONE HUNDRED SEVENTH CONGRESS

FIRST SESSION

JUNE 20, 2001

Serial No. 107–34

Printed for the use of the Committee on Government Reform

(

Available via the World Wide Web: http://www.gpo.gov/congress/house

http://www.house.gov/reform

(II)

COMMITTEE ON GOVERNMENT REFORM

DAN BURTON, Indiana, Chairman

BENJAMIN A. GILMAN, New York

CONSTANCE A. MORELLA, Maryland

CHRISTOPHER SHAYS, Connecticut

ILEANA ROS-LEHTINEN, Florida

JOHN M. MCHUGH, New York

STEPHEN HORN, California

JOHN L. MICA, Florida

THOMAS M. DAVIS, Virginia

MARK E. SOUDER, Indiana

JOE SCARBOROUGH, Florida

STEVEN C. LATOURETTE, Ohio

BOB BARR, Georgia

DAN MILLER, Florida

DOUG OSE, California

RON LEWIS, Kentucky

JO ANN DAVIS, Virginia

TODD RUSSELL PLATTS, Pennsylvania

DAVE WELDON, Florida

CHRIS CANNON, Utah

ADAM H. PUTNAM, Florida

C.L. ‘‘BUTCH’’ OTTER, Idaho

EDWARD L. SCHROCK, Virginia

JOHN J. DUNCAN, Tennessee

HENRY A. WAXMAN, California

TOM LANTOS, California

MAJOR R. OWENS, New York

EDOLPHUS TOWNS, New York

PAUL E. KANJORSKI, Pennsylvania

PATSY T. MINK, Hawaii

CAROLYN B. MALONEY, New York

ELEANOR HOLMES NORTON, Washington,

DC

ELIJAH E. CUMMINGS, Maryland

DENNIS J. KUCINICH, Ohio

ROD R. BLAGOJEVICH, Illinois

DANNY K. DAVIS, Illinois

JOHN F. TIERNEY, Massachusetts

JIM TURNER, Texas

THOMAS H. ALLEN, Maine

JANICE D. SCHAKOWSKY, Illinois

WM. LACY CLAY, Missouri

DIANE E. WATSON, California

——— ———

———

BERNARD SANDERS, Vermont

(Independent)

KEVIN BINGER, Staff Director

DANIEL R. MOLL, Deputy Staff Director

JAMES C. WILSON, Chief Counsel

ROBERT A. BRIGGS, Chief Clerk

PHIL SCHILIRO, Minority Staff Director

(III)

C O N T E N T S

Page

Hearing held on June 20, 2001 ............................................................................... 1

Statement of:

Santino, Fred, Arlington, MA; Frank Burroughs, Arlington, VA; Doug

Baxter, Woodland, CA; Shannon Kellum, Ft. Myers, FL; and David

Barr, New York, NY ..................................................................................... 30

Temple, Robert J., M.D., Associate Director for Medical Policy, Center

for Drug Evaluation and Research, Food and Drug Administration,

Department of Health and Human Services; Patricia C. Delaney, Public

Health Specialist, Office of Special Health Issues, Office of International and Constituent Relations, Office of the Commissioner, Food

and Drug Administration; and Samuel D. Waksal, Ph.D., president

and chief executive officer, ImClone Systems, Inc. .................................... 92

Letters, statements, etc., submitted for the record by:

Barr, David, New York, NY, prepared statement of ..................................... 62

Baxter, Doug, Woodland, CA, prepared statement of .................................... 52

Burroughs, Frank, Arlington, VA, prepared statement of ............................ 39

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

Article from the Boston Globe .................................................................. 83

Information concerning David Baxter ..................................................... 88

Letter dated June 19, 2001 ...................................................................... 19

Prepared statement of ............................................................................... 22

Prognostic disclosure article ..................................................................... 3

Kellum, Shannon, Ft. Myers, FL, prepared statement of ............................. 58

Santino, Fred, Arlington, MA, prepared statement of ................................... 33

Temple, Robert J., M.D., Associate Director for Medical Policy, Center

for Drug Evaluation and Research, Food and Drug Administration,

Department of Health and Human Services, prepared statement of ....... 97

Waksal, Samuel D., Ph.D., president and chief executive officer, ImClone

Systems, Inc., prepared statement of .......................................................... 116

(1)

COMPASSIONATE USE OF INVESTIGATIONAL

NEW DRUGS: IS THE CURRENT PROCESS

EFFECTIVE?

WEDNESDAY, JUNE 20, 2001

HOUSE OF REPRESENTATIVES,

COMMITTEE ON GOVERNMENT REFORM,

Washington, DC.

The committee met, pursuant to notice, at 1:14 p.m., in room

2154, Rayburn House Office Building, Hon. Dan Burton (chairman

of the committee) presiding.

Present: Representatives Burton, Morella, Horn, Ose, Lewis,

Mrs. Jo Ann Davis of Virginia, Platts, Weldon, Duncan, Waxman,

Cummings, Kucinich, and Clay.

Staff present: Daniel R. Moll, deputy staff director; James C. Wilson, chief counsel; David A. Kass, deputy counsel and parliamentarian; Mark Corallo, director of communications; S. Elizabeth

Clay, Michael Canty, and John Rowe, professional staff members;

Robin Butler, office manager; Toni Lightle, legislative assistant;

John Sare, deputy chief clerk; Corinne Zaccagnini, systems administrator; Elizabeth Crane, staff assistant; Phil Barnett, minority

chief counsel; Kate Anderson and Sarah Despres, minority counsels; Ellen Rayner, minority chief clerk; and Earley Green, minority

assistant clerk.

Mr. BURTON. Good afternoon. We will have Members coming and

going throughout the hearing, but I want to go ahead and get started because we’re already a little behind schedule, so you are going

to have to look at my pretty face alone for just a few minutes, but

all of this will be on the record for all of the Members.

A quorum being present, the Committee on Government Reform

will come to order, and I ask unanimous consent that all 11 Members’ and witnesses’ written and opening statements be included in

the record. And without objection, so ordered.

And I ask unanimous consent that all articles, exhibits, and extraneous or tabular material referred to be included in the record.

And without objection, so ordered.

To be told that you or someone that you love has a life-threatening illness, shakes you and your family to the very core. The life

that you have known is changed forever. Suddenly you are thrown

into a maze of medical tests, doctors’ appointments, and tough decisionmaking. You and your family become experts in interpreting

complex medical jargon and searching the Internet for treatment

options. At times you think that the bureaucracy of government

pales in comparison to the medical bureaucracy.

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This week, a survey published in the ‘‘Annals of Internal Medicine’’ reports that doctors are many times not candid with their terminally ill patients. In 23 percent of the cases in the study, doctors

would not give patients a time estimate if asked. In 40 percent of

the cases, physicians said they would knowingly give an inaccurate

estimate. Three-fourths of those physicians said they would paint

a more positive picture than they really believed. Researchers speculated that physicians were afraid that giving bad news would be

making a patient’s condition worse.

[The information referred to follows:]

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Mr. BURTON. This is a very touchy issue. Patients should be told

the truth, in a compassionate, and as much as possible, in a positive way when asked questions about their situation. I believe that

doctors can deliver accurate information with compassion. I also believe that your doctor should also be your strongest advocate. He

or she should offer information on all treatment options available—

standard treatments, alternative therapies, and experimental treatments. Unfortunately, this does not happen. Many times doctors

are not aware of the latest treatment options or do not take the

time to be informed. This is not how our health care system should

function.

The decision on what course of action to take should always be

the patient’s. If the standard therapies fail, they may seek access

to experimental treatments. Increasingly, individuals will seek an

integrative approach, combining conventional and complementary

therapies in an effort to treat the whole person, not just the disease

or the tumor. A patient’s desire to try an integrated approach

should be respected and allowed.

I repeat—the decision on what course of action to take is the patient’s. After given the facts, if someone with a life-threatening or

terminal illness wants to seek treatments that may offer a cure or

a slowdown in the progression of disease, then Federal agencies

and red tape should not stand in their way.

Today’s hearing will focus on compassionate access to experimental drugs. Science dictates a gradual process of information

gathering that often takes 12 to 15 years from inception to product

approval. When research moves to the point of human subject involvement, an investigational new drug [IND] application is submitted to the Food and Drug Administration. There is careful review of the preliminary safety data and protocol designed before

the trials can move forward, and that is as it should be.

Clinical trials are carefully designed to collect information about

product safety and efficacy. Access to experimental treatments

through clinical trials is the best route. However, not all cancer

and AIDS patients fit protocol designs. Their disease may be more

advanced, they may be the wrong age, or have had too many

rounds of chemotherapy or radiation. Whenever feasible, when a

patient is not able to participate in a clinical trial, they should not

be excluded from access if there is some hope that a drug may save

or extend their life.

We are going to hear today from Dr. Robert Temple of the FDA,

that the term the public uses, ‘‘compassionate use,’’ is actually an

umbrella term for a myriad of mechanisms available to provide patients access to drugs outside of clinical trials.

To an individual who needs access to an experimental drug, they

do not really care if it is through a special exemption IND, a treatment IND, or a single-patient IND. They just want access to the

treatment. They want to live. They want a chance to live.

In the past few weeks we have seen a media focus on the plight

of individuals who sought access to experimental treatments.

Frank Burroughs’ 21-year-old daughter, Abigail, lost her battle

with cancer just 11 days ago. And he has our sympathy, as does

his whole family. He will share their story of trying to access exVerDate 11-MAY-2000 11:55 Mar 19, 2002 Jkt 000000 PO 00000 Frm 00020 Fmt 6633 Sfmt 6633 C:\DOCS\77088.TXT HGOVREF1 PsN: HGOVREF1
17

perimental drugs that Abigail’s oncologist thought would be helpful.

Fred Santino’s wife, Ruth-Ann, fought a 21⁄2 year battle with

colorectal cancer. She withstood numerous surgeries and chemotherapy treatments, but continued to have progression of her disease. She sought access to experimental treatments. One option she

sought was C225. This product is being developed by ImClone Systems, had been shown in phase II studies to be effective in treating

colon cancer with metastases. She was not able to access the treatment, and she died in May.

And one of the things that concerns me about clinical trials,

which are very, very important, is whether or not either financial

interests or statistical data being gathered in the clinical trials is

the reason that they do not give people compassionate use of some

of these drugs. And if that is the case, one of the things that I

would like to suggest today is that the clinical trial be walled off

completely, so that no adverse information from a compassionate

use be included or have any impact on the clinical trial. And the

reason I say that is I understand the financial problems a small

company would have to be involved in if this information was put

into the clinical trials. It could destroy the company, it could cause

the clinical trial to be skewed, it could be a real problem.

But on the other hand, if it is being effective and being shown

to be effective, and that leaks out into the public domain, as it has

in the C225 case, you have people out there who may be without

hope; their doctor may have said, ‘‘You are going to die’’, and they

want to have at least a chance to survive. And so compassionate

use of that drug should be considered for that individual.

And if the other concerns are viable concerns, then the clinical

trial should be walled off and we should find a way to give hope

to the person who’s dying and have a chance to get that treatment.

And I will tell you that in my life, I have known people in the

medical profession, very highly regarded people, people in our government who were the heads of major agencies that deal with our

health care, who were against using treatments outside of conventional medicine. And yet when their loved one, their wife, became

terminally ill, they tried everything. They went out of the country,

they did everything, because it is different when you are talking

about the masses of people and people who are suffering from a

disease that is incurable, when there is a new drug that may save

their life, and when it is in your family, when your wife or your

daughter or your son is terminally ill with a disease and there is

no hope except that long, long bomb that we are talking about, that

you might throw in a football game, with a new drug that might

save their life.

And so that is why I think we ought to look at walling off clinical

trials from the compassionate use if that is what is necessary to

give every person every chance to survive.

What these two families learned, the ones I just mentioned, is

that many companies do not have clear guidelines on when compassionate access is going to be provided. Some companies such as

AstraZeneca have clearly defined programs that are posted on their

Web site. AstraZeneca, one of the largest pharmaceutical companies in the world, developed an expanded access protocol for

18

IRESSA, a lung cancer treatment they have in development. They

set this program up with a third party, the National Organization

for Rare Disorders.

ImClone, a relatively small company, had no established program, and when researchers started talking about their positive effects, they were overwhelmed with requests, and as a result, have

closed their compassionate access program. And we understand the

problems they are facing. And we are not here to be judgmental

today. We are here to try to find some answers for people who are

terminally ill.

Dr. Waksal, the president of ImClone, will share their story of

the challenges today.

We will also hear from one of the fortunate ones, a lady named

Shannon Kellum. Shannon, at age 28, was diagnosed with colon

cancer. She was the first colon cancer patient to try C225, through

compassionate access. She lucked out because her physician had

done some of the preclinical research on C225 and was able to use

that knowledge to convince ImClone that she should have access to

the treatment.

Doug Baxter’s 16-year-old son, David, was recently diagnosed

with colon cancer. He will tell us about their ongoing struggle to

access experimental treatments and save David’s life.

David Barr is living with AIDS. He will share his perspectives

on how the AIDS community worked together to force the FDA’s

hand on expanding access to experimental treatments.

How can we improve compassionate access to experimental

drugs? How can we give hope to people? And hope is a very strong

ingredient in survival. How can we give hope to people who have

been told, in effect, that they are terminally ill? Does the FDA need

to allow companies to manufacture a larger supply of the experimental product during the developmental process? Is money an

issue? Are the reporting requirements on efficacy data outside clinical trials a barrier? And once again, that is why I suggested that

maybe you wall off the clinical trial.

There are many people who have had an opinion on this topic.

We received written testimony from the National Breast Cancer

Coalition, and I ask that it be included in the hearing record. And

without objection, so ordered.

[The information referred to follows:]

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Mr. BURTON. We will keep the hearing record open until July 6

for those who would like to submit written testimony, and we will

continue seeking input from organizations, manufacturers and families, about how to improve access to experimental treatments.

Whatever it takes, regulatory or legislative changes, or better information sharing, we as the Congress cannot ignore the needs of

those with life-threatening illnesses. And I speak with some personal knowledge of this.

[The prepared statement of Hon. Dan Burton follows:]

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Mr. BURTON. I now recognize the ranking minority member, Mr.

Waxman.

Mr. WAXMAN. Thank you very much, Mr. Chairman, and I want

to thank you for holding this hearing. This is an important hearing, and I think we have got a record to make and a job to do.

Today we are going to hear about personal experiences that no

one should ever have to experience. We are going to hear about

people who have fatal cancers and no treatment options until they

hear about a promising treatment in the clinical trial process. They

appeal to the manufacturer for compassionate use of a drug, and

they are denied. They know that other people are getting the drug

on a compassionate use basis, but they cannot. We will hear about

their bravery as they faced this situation, not giving up and continuing to fight for access to this treatment until the end.

We will hear from the CEO of a company that makes this new

drug. He will tell us about the promise of this drug and the

progress of the clinical trials. He will tell us that when the promise

of the drug became known, 10,000 people applied to use the drug

under a compassionate use IND. However, this is a difficult drug

to make, and because it is still in the clinical trial process, and the

overwhelming bulk of the drug that was available needed to go to

the clinical trial, the company could not meet that demand.

We will also hear from people who have had some success in getting access to drugs that have not yet been approved, and we will

hear different perspectives about what the impediments to access

to drugs in clinical trials are.

Our job today, as Members of Congress, is to understand how the

compassionate use system works and whether there is anything we

can do to improve it. It is important to do this. Many patients are

desperately ill, and they do not have the time to wait for a drug

to make it through the clinical trials and approval process.

As we will hear today from our witnesses, access to drugs

through compassionate use can save lives, but there are many limits on this system. One limit is the availability of the drug in the

clinical trial stage. Often companies produce only limited amounts

of an experimental drug. Sometimes that is because materials are

in short supply, sometimes because a process is difficult, sometimes

because they do not want to invest in a product with an uncertain

future.

Then there are the limits of science. If a treatment is approved

after phase II clinical trials, this would usually increase access to

the treatment. In rare instances the data are so dramatic and the

statistics so clear, that this is possible. For example, Gleevec, a

treatment for certain types of leukemia, was recently approved

after phase II trials. And ImClone is seeking approval of C225 for

colorectal cancer after its phase II trials as well. But in most cases,

it is necessary to conduct the larger-scale phase III trial to understand fully whether and how well a drug works and what the possible adverse effects are. It would be unethical to allow companies

to market a drug as a treatment unless and until it has been appropriately tested for safety and efficacy. This is especially true in

the case of life-saving treatments against such diseases as cancer

and AIDS. So we are left with a very difficult situation, where

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there are desperate patients trying so hard to get limited amounts

of potentially life-saving drugs that are in clinical trials.

This hearing will raise important questions. How do we help patients get access to drugs that may help them? How do we assure

that drugs are thoroughly tested for safety and efficacy, and how

can companies be encouraged to consider treatment INDs at the

early stages of the clinical trials so that patients can have access

to a treatment as quickly as possible?

There are no easy answers here, but with the new and exciting

developments in biotechnology, and important treatments on the

horizon, these are the issues we have to address to make sure that

as many people as possible are helped by these therapies.

I want to thank the witnesses for being here, particularly people

on this first panel who are going to tell us about their own experiences. Mr. Chairman, I want to thank them all for being here, and

I am looking forward to their testimony.

I do want to explain however, from a personal point of view, that

there is a conflict that I have because of the California energy crisis. Our Governor’s meeting with us at 1:30, so I am going to have

to leave to attend that meeting, but I will get back here as quickly

as I can.

We will have your testimony on the record. I will have a chance

to review it. By having it on the record and your being here today,

we can take what you have to say and go to our colleagues and tell

them about any potential legislation or any other moves that we

should be taking to solve the kind of situation that you have faced

and try to make this problem one that will not be repeated over

and over again.

So I want to apologize in advance for not being here for the

whole hearing. I will try to get back as quickly as I can. But, Mr.

Chairman, I want to thank you for this hearing. It is an important

one, and I look forward to working with you on this very important

issue.

Mr. BURTON. Thank you, Mr. Waxman. Mrs. Davis, did you have

an opening statement you would like to make?

Mrs. JO ANN DAVIS OF VIRGINIA. No, thank you, Mr. Chairman.

Mr. BURTON. Mr. Kucinich.

Mr. KUCINICH. I wanted to thank the Chair for calling this hearing and welcome the witnesses. Certainly those of you who have a

personal story to tell to this committee, who have experienced in

a very profound and heartfelt way the impact of policies which

have denied loved ones the opportunity to get help which was believed to be available, certainly have much to communicate to this

Congress. I think that as Mr. Waxman said, your testimony will

help guide the Congress in a direction which needs to be taken. In

order to make sure that the access which has been denied people

in the past can—the question of access can be resolved. So again,

I want to thank the Chair for his sensitivity to these issues. I appreciate your ongoing commitment to public health. Thank you.

Mr. BURTON. Thank you, Mr. Kucinich. Mr. Cummings.

Mr. CUMMINGS. Thank you very much, Mr. Chairman, for your

sensitivity to these issues. These are very, very important issues.

And we as the Congress of this great country have a duty, I think,

to address them.

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The patients and their family members are frequently in search

of information about the latest drugs being researched for effective

treatment, and I represent the district in which Johns Hopkins is

located, and, of course, we just had a major episode involving one

of my constituents who died during the process of clinical trials. I

guess that is how you would describe it. The people in the audience

would know better than I do. But it shows the problems that we

run into. We have to be very careful about the drugs and how they

are used and when they are used. But on the other hand, we have

situations where people are facing some very difficult circumstances in their lives, and I would imagine that at times people

feel that perhaps the Federal Government goes too far in these

trials.

To be very frank with you, I do not know that we will answer

that question today, exactly where do you draw the line and where

does a balance come? But the fact remains that there is a woman,

a young woman in Baltimore, who was alive not very long ago, and

now she is gone. She was healthy. And now she is gone.

And so I think this, Mr. Chairman, is an appropriate time for us

to be looking at this issue. I am interested because I know that

there are so many people who find themselves in the difficult circumstances that some of our witnesses do today, or their family

members have.

And to our witnesses, I want to thank you for being a part of this

hearing. In order for the Congress to do its work, we have to put

a real face on our policy. So often we look at statistics and we hear

numbers, but the real testimony comes when we are face-to-face

with people who have been places where we have not gone. And so

it makes it better for us to formulate policy when we hear from

you. And so we take this moment as a Congress to thank you for

being with us today, and I look forward to the testimony.

Mr. BURTON. Thank you, Mr. Cummings.

Mr. Santino, Mr. Burroughs, Mr. Baxter, Ms. Kellum, and Mr.

Barr, we swear our witnesses, so would you stand and raise your

right hands, please?

[Witnesses sworn.]

Mr. BURTON. Be seated. Mr. Santino, would you like to start?

And I know that it is tough to say everything you want to say in

5 minutes, but if you could get as close to that as possible, we

would appreciate it.

STATEMENTS OF FRED SANTINO, ARLINGTON, MA; FRANK

BURROUGHS, ARLINGTON, VA; DOUG BAXTER, WOODLAND,

CA; SHANNON KELLUM, FT. MYERS, FL; AND DAVID BARR,

NEW YORK, NY

Mr. SANTINO. My name is Fred Santino. I am the husband of

Ruth-Ann Santino, who just passed away May 5th. I have it boiled

down to basically four points here: obtaining compassionate use,

the information provided, the responsibility of drug manufacturers

to communicate with patients, and manufacturers not being penalized for providing drugs to very sick people.

As far as the compassionate use, obtaining it, I do not feel there

is any criteria by the government, by the hospitals, by anybody. I

think there should be some criteria. When a new product is estabVerDate 11-MAY-2000 11:55 Mar 19, 2002 Jkt 000000 PO 00000 Frm 00034 Fmt 6633 Sfmt 6633 C:\DOCS\77088.TXT HGOVREF1 PsN: HGOVREF1
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lished, part of the business plan ought to be what criteria am I

going to have once we have success? In other words, they assume

they are going to have success at some point when they make the

drug. I assume that they are thinking that way, so let us have that

as part of the business plan and let us demand it as a government,

that we do that. I work for the government. We have policies. We

have rules. We have to live by them.

Another point is how to find out about compassionate use. We

found it is very difficult. It is not listed on any Web sites. It is not

really clear where you would find out about it, how you would sign

up for it. I happen to run four Web sites, and I had trouble finding

the information. There are so many Web sites—I put it in my testimony, how many different Web sites there are. They are not

linked. Some of them disagree. Some of them say trials are open.

We were given a choice of four trials. None of them were listed. I

do not know any of them as far as what manufacturers they were.

I could not find anything about them, what side effects they were,

anything like that. So I would like to see more information, and I

would like to see the information managed somehow. Have one

Web site tie them all together and have some sort of an update.

If I am in the drug business and I am having a trial, I have got

to update what is happening. Has there been serious side effects?

Has there been successes? I would like to know, because a doctor

offers me XQY322, I want to know what it is. I want to know who

makes it, I want to know whether it is successful or not. I do not

want it to be my decision.

The other thing is we were terribly ignored by a company,

ImClone. I understand they were overwhelmed with responses, but

in our case, three of my wife’s letters were ignored. We wanted to

know yes or no, can I have the drug? That is all. That is all we

wanted was an answer, yes or no. I would have sent them the 34

cents to give me a postcard back. That is all I needed, but we were

ignored. My sons wrote letters. I did not get a letter or anything

back until we got a privilege number from the FDA and my wife

was able to call the company, and she got a call back from a doctor

saying that she would not qualify because she was too sick. Well,

that took 3 months to get that answer, and we had other options.

We could have gone to another drug at Sloane Kettering in the

process, but we did not do that.

So I feel drug companies, if they are in the drug business, they

have a responsibility to communicate with the patient. I happen to

work for the Air Force. We put out an RFP for businesses, I do not

know if 3,000 businesses are going to want that RFP, but we have

to answer every one of them. So if I am in the drug business, I deal

with patients, and those patients ought to be answered, and it

ought to be mandatory. Otherwise, get out of the business.

My wife was sick. She said, ‘‘I’m a dying mother, and I want this

drug. Can’t you tell me yes or no?’’ How can you ignore a dying

mother? How can you, Mr. Waksal? I don’t understand how you can

do it. My two sons wrote letters and you ignored them. How can

you do that? Just say yes or no. I will give you 34 cents.

We needed the information to make decisions and we were not

given it in time, so we missed out on other options, and I can see

the drug business. I have a relative in the business, and I underVerDate 11-MAY-2000 11:55 Mar 19, 2002 Jkt 000000 PO 00000 Frm 00035 Fmt 6633 Sfmt 6633 C:\DOCS\77088.TXT HGOVREF1 PsN: HGOVREF1
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stand their problems, but do not go in the business if you cannot

communicate with people, and you cannot handle the business the

way everybody else does. Go out of business. Let somebody else

take you over.

I do not think you ought to be penalized for giving drugs to sick

people. If my wife is real sick, give her the drug. Do not say my

wife is too sick to have a drug. What is a drug for? I mean, really.

We were told by ImClone that my wife had seven treatments and

that would not qualify her. She was also told that by another clinical director at a hospital in Boston, that she could not get another

drug, SU5416, she had too many treatments. But what are the

drugs for if they are not for sick people, I mean, really?

That is pretty much all I have to say, and I think it can be improved by getting the information together, getting the people in a

room like this. I thank Congressman Burton and the rest of the

members of the committee for having this meeting, and I really

think something ought to be done. And the reason I am here is I

hope it will help other people, and nobody else has to suffer the

way my family did. And I am really going to stay in this business

for good until something does happen, so if anybody else needs my

help, please call on me. I will be glad to help you.

Thank you.

[The prepared statement of Mr. Santino follows:]

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Mr. BURTON. I really, really appreciate you being here today. I

knew about your story beforehand, and we will have some questions for you, but thank you very much.

Mr. Burroughs.

Mr. BURROUGHS. Good afternoon, Mr. Chairman and distinguished members of the committee and guests. I am Frank Burroughs, but for the past 21 years I have been better known as the

father of Abigail Kathleen Burroughs.

Since February of this year Abigail ran out of options in her battle against cancer, which had spread to her neck and her lungs. I

and others began to try and find treatment with experimental

EGFR targeted cancer drugs.

We tried to get Abigail into narrowly defined clinical trials, but

she did not qualify for them. We worked very hard to acquire the

drugs on a compassionate-use basis, but got nowhere.

The drugs that we needed, the EGFR drugs that we needed were

AstraZeneca’s IRESSA and ImClone Systems C225, which statistically, and according to her oncologist, Dr. Maura L. Gillison at

Johns Hopkins, showed a significant chance of helping her beat her

cancer.

My only child, dear, sweet, loving, talented and compassionate

Abigail died at 2:30 p.m. two Saturdays ago, June 9th. The loss of

my beautiful compassionate child has left a hole in my life. Her

mother, Kathleen, who took such good care of her, is of course, also

very saddened, as is her dear stepfather, Gene Krueger.

There was hope, but no compassionate use of AstraZeneca’s

IRESSA or ImClone System’s C225.

Abigail was compassionate. In her senior year in high school she

won the distinguished Harry F. Byrd, Jr. Award for Leadership

and Community Service for the Eight Virginia Congressional District. Abigail was an Echols honor student at the University of Virginia. Abigail cleaned toilets and changed beds in men’s homeless

shelters. Abigail worked in a poor neighborhood in Syracuse, NY,

fixing up houses and running a free day camp for inner city children. Abigail started a major tutoring program for middle school

children who were having learning problems. And this is the short

list. Abigail was compassionate.

The world has lost a brilliant young woman who would have

done great things.

I am here today because the issue of the wider use of compassionate use of drugs is a very important issue, because it touches

tens of thousands of lives. Compassionate Abigail wants us to keep

this issue alive, although we could not keep Abigail alive.

I know this is a money issue. I do not have all the answers, by

the way, but I know it is a money issue, because some large pharmaceutical companies do have wider compassionate-use programs

than others.

ImClone Systems has no compassionate use program. Multibillion dollar AstraZeneca has a very narrowly defined program, and

it is very small. And Abigail, young Abigail, did not qualify for

AstraZeneca’s compassionate use program.

A very important role of industry and government is to help people and to save lives. We did not have a chance to get to save compassionate Abigail.

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One idea I am working on I shared with Abigail on Thursday before she died. She fought till the end. She was a sweetheart. She

was brave. She really liked the idea. Now, it is going to need some

fine tuning. The idea is to set up a foundation or another vehicle

to raise money from private sources, from the huge pharmaceutical

industry, and from the U.S. Government, to provide money so that

we can produce more of these new promising experimental drugs

and have them available on a compassionate use basis.

From the knowledge I have, there needs to be a clear line drawn

between clinical trials and compassionate use.

I am honored here to be with everybody on this panel, but Doug

Baxter and I have become friends. Recently his 16-year-old son is

fighting a battle with colorectal cancer. He has many difficulties

getting into trials.

Abigail was compassionate. Abigail is now in the arms of God.

Others, with the strength of Abigail’s memory, beautiful memory,

and I, will keep this issue alive so others may have a chance to

live, a chance that Abigail, compassionate Abigail, did not have.

Thank you for inviting me here today, and thank you, dear Abigail, for giving me the strength to make it here today. Thank you.

[The prepared statement of Mr. Burroughs follows:]

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Mr. BURTON. Thank you very much, Mr. Burroughs. And I really

appreciate you being here, and I feel very sorry that you had to

give this testimony.

Mr. Baxter.

Mr. BAXTER. Thank you. Honored Chairman, and committee

members, I appreciate the opportunity to testify to you regarding

our struggle with a pharmaceutical company to obtain a drug that

my son needs.

It has been a difficult journey to get to this point, a difficult but

short journey. In early March of this year, I took my son to Phoenix

for our annual week-long trip to major league baseball training in

Phoenix. We had a wonderful time. As usual, my son got a lot of

autographs. It was a time of sunshine, joy, fun, normalcy.

The following week, David complained of some back pain, and

the world was turned upside down when he was diagnosed with

colorectal cancer. The doctors said they had never heard of this in

a kid. It only got worse the next week when we found out that it

had spread to his liver and lymph nodes.

He immediately started treatment and is now fighting the side

effects of these treatments. He has had a positive attitude, but his

smile has been few and far between lately as he struggles through

this time.

David has doctors that have been great. We were excited as

treatment began, only to cry as we saw the impact of these treatments. At times, David sleeps almost all day on the couch, only to

get up when it is absolutely necessary, and to frequently take the

morphine to make the pain bearable. Picture your child so sick and

in such pain, wanting to help him, you just cry.

Cancer does not kill. It first embarks on a mission of relentless,

relentless torture of hundreds of people, family members, friends,

and strangers, compassionate strangers that step forward, wanting

to help. His entire family suffers as David struggles. Because a

child is hurting, his parents are consumed by the impacts of this

process. We are consumed by trying to find help for David. Imagine

the emotional extremes that we experienced, hearing David’s doctor

telling us of a promising drug that he was treating other patients

with, that he even had that drug in his possession as part of a

head and neck cancer trial. But he could not give it to David, because he could not give David the drug without the permission of

ImClone Systems, Inc., a permission that ImClone has not yet allowed. ImClone has previously approved David’s doctor to be a current investigator for this very same drug for neck cancer. ImClone

has approved the facility where this doctor works, the Sutter Cancer Center in Sacramento. His doctor has provided a written request to the drug manufacturer requesting that he be approved as

a co-investigator so he can participate in the colorectal cancer trial

also, so my son could gain access to this.

There has been some discussions about perhaps having my son

go East to participate in the colorectal cancer, where all of these

clinical trials are being conducted on the East Coast only. But for

a 16-year-old son, who has a prognosis of just a few months, it

would be extremely cruel to take my son away from his family and

friends to go back East and live in a hotel to do a colorectal trial.

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For this reason, we would like to have permission for this cancer

trial to be done also out West, where also people out our way could

have access to this drug. We understand that there is a limited

supply, and that this drug is important to move forward quickly.

David’s doctor believes that he could expedite the approvals

through their investigational review board and not slow up the

process. I hope that this can be looked into.

There are a number of possible things that we can consider.

Compassionate use is a very important item, especially where there

is available drug to be able to use that. But where the drug is in

short supply, I think it is also important for the committee to look

at ways of having this drug allowed in other geographical locations

so that children such as mine can have the opportunity to participate in these clinical trials as well.

I thank you for the opportunity to speak with you this day, and

I ask that the remainder of my testimony be entered into the

record. Thank you.

[The prepared statement of Mr. Baxter follows:]

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Mr. BURTON. Thank you, Mr. Baxter, and I wish you well with

David. Tell him that we understand, and that there is a lot of people up here thinking about him, and hopefully praying for him.

Ms. Kellum.

Ms. KELLUM. I am here today to share my testimony on how

C225 has enabled me to be here today.

I was originally diagnosed in April 1998 at the age of 28. I was

diagnosed with metastatic Stage IV colon cancer. It had started in

the colon, but had already spread to other parts of the body.

Throughout the next year, until April 1999, I received all standard

therapies, as well as trials that were currently available that I was

eligible for, none of which were able to even stabilize this disease

at all.

In April 1999, there were no other options available. I was not

eligible for surgery, and there was nothing out there that I qualified for. At that time my doctor introduced the idea of C225. At the

same time he also mentioned that it had never been used in colon

cancer before, and that I would be the first patient to receive it,

but he would have to get approval from ImClone and go through

the necessary process.

Fortunately, that answer was yes, and I started my first treatment of C225 in late April 1999. After four treatments, I received

over a 50 percent reduction in the tumors, which nothing else had

even phased. I continued to receive C225 over the next several

months, having a total reduction of 80 percent. At that time my tumors became stable, and so I researched the possibility of surgery,

which was necessary in the liver. That is where the disease was.

I was eligible for liver surgery and had that in January 2000.

I am obviously very fortunate to be here today. It could very easily be my husband up here representing me and me not telling my

story. If it was not for C225, I would not be here right now, and

there would not be the opportunity for other people to have received it and for the knowledge that we have gained through this,

and I am here representing all of you, and we need to get this drug

approved, because no one should have to die.

Thank you for allowing me to share this testimony.

[The prepared statement of Ms. Kellum follows:]

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Mr. BURTON. Thank you, Ms. Kellum, and we are very happy

that you are here as well, and you look like you are doing well.

Mr. Barr.

Mr. BARR. Thank you. My name is David Barr. I would like to

thank you for the opportunity to speak with you today.

Mr. BURTON. Could you pull the mic just a little closer, please?

Thank you.

Mr. BARR. I am a person with AIDS, and I am also an advocate

for people with AIDS, and I have been working specifically on

issues regarding treatment access since 1987. Access to experimental drugs is a particular concern to people with AIDS, because

the disease is so deadly and its death so painful and humiliating.

Most important, when AIDS first appeared as a new infectious disease in 1981, there were no standard treatments. All treatment

was experimental, and early access programs were our only way of

obtaining treatment. As research and drug development has progressed, there are now many treatments for HIV. However, these

treatments are not a cure, they have limited effectiveness and can

be too toxic for many patients to tolerate. And therefore, access to

experimental treatments remains an important concern for people

living with AIDS.

Beginning in 1989, the FDA began to work in earnest with patient advocates to develop standard for improved access to experimental drugs under compassionate use mechanisms and for accelerated approval of drugs to treat life-threatening illnesses.

Patient advocates are often included now as members or consultants on drug review panels, and directly involved at FDA’s request

in policy-setting discussions. Determining how to provide access to

experimental treatments requires balancing several considerations.

First there is the seriousness of the condition. In HIV we have patients who are on the verge of death and patients who will not feel

ill at all for many years. These patients have different needs and

need different solutions.

Second, one needs to consider what standard treatment is available and the usefulness of that treatment for the patient. If an approved therapy is available, there is no reason to risk taking a drug

of unknown safety and efficacy.

And, finally, one must consider what is known about the safety,

efficacy and dosing of the new drug. In weighing these considerations, one must take into account both the individual needs of a

particular patient and the effect of access on a broader group of patients. An individual patient, faced with terminal illness, and often

living in great fear and discomfort, may be more willing to risk taking an experimental treatment with little safety or efficacy data.

However, making those decisions are never easy, and we usually

make them with much less information than we would like to have.

Make no mistake. Although the FDA and drug companies may

have an interest in the data from both studies in anecdotal use, no

one needs this data more than patients. We are the ones who

struggle with these life and death decisions. I would strongly urge

that such data collection be continued, and in many cases strengthened.

Certainly, any member of the panel, when considering whether

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viously someone had toxic reactions and what success if any the

drug had offered to other people.

I believe that industry claims that they are reluctant to participate in early access programs because of data submission requirements by the FDA are false ones. Such requirements are usually

reasonable, not overly burdensome, and can provide useful information about the drug.

While the FDA can set standards for approval of early access

programs and can later the proposed protocols under which experimental drugs can be made available, the agency has no authority

to compel a company or sponsor to provide their drug to patients.

Companies are often reluctant to do so. They are uncomfortable

with any loss of control in the use of an experimental product.

However, that is not FDA’s fault. Prohibiting the FDA from collecting data in these situations would not likely increase a company’s

participation in early access programs. Companies are less concerned with data collection than they are with control over all the

data and with drug supply. In fact, drug supply, particularly for

drugs in phase II studies, is probably the most important and difficult obstacle. Patient advocates in HIV and other diseases have

learned the immense value of working with companies as new

drugs are developed. We have tracked the development of all HIV

drugs from a concept to a test tube, through animal studies and

into people, and we begin discussing the needs in terms of early access programs with companies as soon as phase I studies begin.

And in this way, there is time to negotiate the real concerns about

safety, dosing, patient entry criteria and rug supply, and it is only

through those negotiations that such programs are a success. Rarely in my discussions with industry have concerns about the FDA

and data collection been raised as barriers to early access development.

It would be unusual for a company to develop one policy around

when or how to make experimental drugs available. Each drug

needs to be considered independently based on the needs of patient

population, what is known about safety and efficacy, dosing, and

how the drug is manufactured.

I do not want to go over.

Mr. BURTON. Take your time. We just try to stay as close to 5

minutes as we can. We are not going to shoot you. [Laughter.]

Mr. BARR. Thanks. Thank you.

Patient advocates will often meet with company representatives

while phase I studies are under way to discuss when and how an

early access program can be created. The sooner those discussions

begin, the better. When companies have refused to include early access mechanisms in their development plans, advocates have initiated letter-writing campaigns, demonstrations, and even boycotts

to urge the company to reconsider. At least in HIV drug development most companies will bow to such pressure. However, the

speed at which these programs are developed and the scope of who

they reach, often leave much to be desired. Sometimes an early access program will not begin until an NDA is filed. And this means

that the program will only run for a few months. Another situation

is the entry criteria are so strict that many patients who need the

drug are not eligible. Patient advocates to work with companies to

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develop entry criteria that best meet patient needs. And very often

the entry criteria will broaden as the program gets under way, and

in this way, the company can determine if the demand for the drug

will be greater than they are able to provide.

Again, the FDA has no authority to make these programs broader or begin earlier. The successes of single patient programs are

more difficult to track because of the individual nature of the program. A treatment IND will include a protocol that will provide

drug to all patients who meet the entry criteria, and physicians

will enroll patients in the program and drug are distributed to the

patients through the physicians.

Compassionate use single-patient programs are done on a caseby-case basis. There is no standard protocol, and that makes advocacy more difficult. Each individual doctor and patient must find

a way for the company to provide the drug. Information about drug

development in clinical studies is often available through patient

advocacy organizations. And most important, is the new program

from the National Library of Medicine, that has an online clinical

trial directory, listing all public and private clinical trials in the

United States.

The dire needs of one patient should not be used to set policy

that can affect all patients. The difficult act of balancing the needs

of an individual and the needs of many is fraught with problems.

My impression is that the FDA, with scarce resources, frankly,

does a good job at balancing those concerns. Most important, the

idea that data collection is an obstacle to drug provision is false

and harmful to patients. Data provides us with the only tools that

we have in making extremely difficult life and death decisions.

Thank you.

[The prepared statement of Mr. Barr follows:]

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Mr. BURTON. Thank you, Mr. Barr. We will start out questions.

We will proceed under the 5-minute rule so all Members have a

chance. Let me start with you, Mr. Santino, Mr. Burroughs, and

then the others, Mr. Baxter and Ms. Kellum can respond as well.

Did your wife and your son—your son and your daughter, start

off with traditional chemotherapy treatment?

Mr. SANTINO. In my case, my wife started with standard treatment at a community hospital. And we thought everything was

fine, and then 6 months later the cancer came back. She had to

have another surgery. She had initial surgery, radiation and chemotherapy; 6 months she was free and clear, and then the cancer

came back.

Mr. BURTON. But how long after she had her chemotherapy and

radiation?

Mr. SANTINO. About 6 months it came back again.

Mr. BURTON. So was it in her lymph nodes; had it metastasized?

Mr. SANTINO. Not really. Initially it had not been, but then it

went to her lymph nodes, and then when we ran out of options as

far as standard treatment. We started looking around, other hospitals, other cities, other cancer centers, other whatever, to try to

find something because at that point we were desperate.

Mr. BURTON. Then you started running into the wall.

Mr. SANTINO. Right, exactly.

Mr. BURTON. Mr. Burroughs.

Mr. BURROUGHS. Abigail had a rare type of cancer, that interestingly enough is starting to show up in young women at a greater

rate almost monthly. It is still not a very common cancer. It started

in her tongue, and it is the kind of cancer old men get who have

been smoking and drinking their whole lives, very unusual in a

young woman who was healthy.

We used surgery. They did not want to use chemotherapy or radiation because they thought there was no need to, it actually could

cause more harm to her than not. Her cancer though came back

last summer. She had surgery and major chemotherapy and radiation. It seemed to clear up for a while, and it came back in February of this year and got progressively worse. We ran out of other

traditional drugs, chemotherapy drugs did not work for her. So we

were down to the last wire, trying to get a EGFR targeted agent.

The frustration was that these drugs, the kind of cancer she had

and the cancer cells she had, and the high EGFR emissions that

the cells gave off showed a real promise of reacting to these new

drugs. It was very frustrating. It was like there was a lifeboat

there, but we could not get to it.

Mr. BURTON. So when did you start trying to get the access to

the——

Mr. BURROUGHS. We actually started trying to get the access in

February, ahead of time, in case the chemotherapy she was on

failed. And it did. And we continued our efforts. She was under another protocol, and that failed. And we continued trying to get

these EGFR-targeted agents, which interestingly enough, showed

greater promise for her than what was left on the conventional cancer shelf that was approved.

Mr. BURTON. But you ran into the wall, what, in February,

March, where you could not get any positive response?

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Mr. BURROUGHS. That is correct. We tried to get the drug, get

her into trials. She did not qualify for the trials. The trials are very

narrowly defined both for AstraZenica and ImClone. You know,

prior treatments have an effect. For instance, AstraZenica’s

IRESSA, it is only for lung cancer that started in your lungs. Abigail’s was in her lungs and her neck and elsewhere, but it did not

start in her lungs, so she could not get into their compassionate

use program, which, by the way, is very small. A lot of ImClone’s

trials, there are a lot of parameters, what kind of chemo had you

had before, when had you had the chemotherapy, whether you

could get into the trial.

Mr. BURTON. I understand. Mr. Baxter, is your son on traditional

treatments, chemotherapy?

Mr. BAXTER. Yes, he is. David’s cancer was quite advanced when

they discovered it, because it is a cancer that you just do not look

for in kids. And it had already metastasized by the time he was

diagnosed, into his liver and lymph nodes. They started with radiation and 5-FU. That was not effective and showed continued

growth during that time. And he has gone through some CPT–11

treatment. And what the CEA test levels are showing is that is still

increasing as well.

Mr. BURTON. Have you tried to get some experimental drugs like

through ImClone or AstraZenica?

Mr. BAXTER. Yes.

Mr. BURTON. And what kind of response have—— Mr. BAXTER. We and his doctor have requested C225.

Mr. BURTON. And what happened?

Mr. BAXTER. We got an e-mail message back. Also I received a

phone call from the vice president of clinical affairs. It was courteous. He just simply explained that they believe that they could

not do it.

Mr. BURTON. And, of course, you, Ms. Kellum, did get C225 after

you had gone through traditional therapies?

Ms. KELLUM. Correct. I had already gone through all the standard therapies as well as any clinical trials that I was eligible for,

and researched the option of surgery, which I was not eligible for

at the time, and that is when I began C225.

Mr. BURTON. Well, I see my time has expired, and I will yield

to my colleagues, but I want to find out today from you and from

the ImClone company, and others, is why is this wall there, and

whether or not the clinical trials—they may feel the clinical trials

are jeopardized by giving it to people who would not qualify in the

narrow definition of what the clinical trial is going to be. And if

that is the case—and I would like to ask you this real quick if my

colleagues let me ask one more question—did any of you get the

feeling that they were worried about the clinical trial being jeopardized by giving you the drug, or did they give any explanation

or do you have any idea about that? Because if that is the case,

then what we want to try to do is figure out some way to protect

the clinical trial while still giving the treatment to people for compassionate use.

Thank you, my colleagues, for letting me ask this question.

Mr. SANTINO. Congressman Burton, we got the feeling from one

trial that we tried to get into, that my wife was too sick to get into

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that trial. It was not C225. It was another trial of a drug called

SU–5416. I got a referral from the FDA. They told me about it.

And we did not have any idea whether it would be successful or

not. It was just another drug that we could try, but the doctor

point blank said, ‘‘No, your wife is too sick. She cannot get into this

trial.’’ But we felt behind the scenes it was the fact that the company did not want to risk their approval process possibly or mess

up the statistics in the trial.

C225, we never got an answer on anything. Now, maybe they are

protecting themselves by not responding, but we finally did talk to

the doctor. When my wife talked in person to the vice president of

clinical affairs, and he gave her a flat, ‘‘No, you could not do it.’’ ‘‘There is a clinical trial coming up at Dana Farber’’—this was

this spring—‘‘but you do not qualify. You will not get in it.’’ And

her doctor had been trying to get that drug for 6 months for—three

doctors had called ImClone trying to get it.

Mr. BURTON. OK. Mr. Burroughs.

Mr. BURROUGHS. Thank you, Chairman. Something that is interesting is that in a ‘‘60 Minutes’’ piece that was aired on May 6th,

some—first of all, the two pharmaceutical companies, ImClone and

AstraZenica, refused to be interviewed for that program. There was

a quote—I assume it is correct—from AstraZenica, and that was

that they were worried that compassionate use of their drug would

interfere with the data from the trials. I am not an expert on FDA

issues, but that was pretty accurate what their quote was on ‘‘60

Minutes’’, AstraZenica’s.

If you think about it, you know, the data and the trial is data

in the trial, it is empirical data, and that is what you use to get

approval of the drug. Something outside of it is just extra data.

They do not have to be tied together. Now, is that a problem?

Maybe we will learn that from the FDA testimony. But on the surface, it looks like they should be two separate things. Thank you.

Mr. BURTON. Mr. Baxter, do you have any comment on that?

Mr. BAXTER. Well, I believe that in relationship to the C225,

what I have been told is there is basically a shortage, and they

would like to provide more of the drug to more people, but there

is a shortage. They are building a large manufacturing facility. I

certainly wish that could have started a few months earlier. Perhaps that needs to be looked at as to how we can increase production of these type of things earlier in the process, so that the Davids and others do not have to go through this process, because

more of the drug would be available.

In my particular case, it goes beyond just compassionate use. It

gets into compassionate co-investigators, allowing clinical trials not

to be grouped in, you know, the Eastern part of the country, but

allow access to other very experienced, very talented doctors such

as David’s doctor, who has already been approved by them. And we

would like to know if——

Mr. BURTON. Out West.

Mr. BAXTER [continuing]. To know if there is a way that we can

provide greater accessibility to these clinical trials through requiring more co-investigation locations.

Mr. BURTON. Did you have a comment, Ms. Kellum?

Ms. KELLUM. No, thank you.

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Mr. BURTON. Mr. Horn, any questions?

Mr. HORN. Thank you, Mr. Chairman. I have appreciated the testimony that each of you have given. And I want to start with Mr.

Santino.

You showed a picture of your family the day before Ruth-Ann

passed. Your son told us that the hospice social worker arranged

for the school principal to come to your home and give David his

diploma so his mother could see him graduate. I know that must

have been very important for Ruth-Ann. We hear a lot of reports

that doctors do not make a referral to hospice soon enough. A report this week in the medical literature mentions that the doctors

often times do not give accurate information about life expectancy

when patients ask. What was your experience with this?

Mr. SANTINO. Well, right up to the end we had hoped that she

would be somehow cured of all this. The last couple of weeks the

doctor started talking hospice. He said, ‘‘You only have 2 weeks to

live.’’ And right away, you know, we went through the roof. You

know, we had to tell the kids, ‘‘This is it. Mom is not going to be

around any longer.’’ And then the doctor changed his mind. He

said, ‘‘Maybe you can qualify for another trial.’’ And her condition

got a little bit better. But we were still ready for the hospice. The

hospice was there. Her condition did get—the doctor was wrong.

The condition did get worse. His initial diagnosis was right.

The hospice arranged for the high school principal to come to her

bedside in my house the day before she died, very important to her.

She perked right up. My son felt that she was there at his graduation, and he got the diploma, and we had a little ceremony, and I

think she was in peace after that. I think that was driving her to

stay alive, to be at her son’s graduation.

Mr. HORN. We also hear a great deal about cancer pain being

poorly managed. What was your family’s experience on the managing of the pain?

Mr. SANTINO. Well, the hospice helped manage the pain. They

were experts in that part. When you go to hospice, you are saying,

‘‘I am not going to live any more. I just want to be comfortable.’’

And they did a very good job at that. Everything was comfortable.

Everything was counseling for the family, and I really cannot say

enough for hospice. It was really much better than we would have

had without them. I cannot say enough.

And we did not realize it was going to happen, but the hospice

was there around us all the time, and every time I talked to them,

I said, ‘‘Oh, no, I think you are wrong,’’ but in the end they were

right, and I am glad we had them, and managing the pain was

definitely a good factor.

Mr. HORN. Mr. Santino, in the 1997 Food and Drug Modernization Act, Congress required the Department of Health and Human

Services, through the NIH, to establish a registry of clinical trials

for both federally and privately funded trials of experimental treatments for serious or life-threatening diseases or conditions. The

Web site available at the clinicaltrials.gov, certainly lists about

5,200 clinical trials. Was this a resource you consulted? And if so,

did you find it useful?

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ful at all, because the information is not exactly accurate. If you

go to the Web site, you will find that there are trials that are being

offered—in our case, in Boston, Dana Farber, that are right there,

that are being offered to you saying, ‘‘Do you want this trial?’’ You

cannot find on any Web site anywhere. We were given four trials,

basically alphabet soup to me, you know, just names. And I asked

the doctor, ‘‘What do you know about these drugs?’’ ‘‘I do not know

that much about them. They are just phase I trials.’’ They are not

listed on the Web site anywhere. I could not find anything about

it. And that is when really the Web site would be helpful to me.

On the other hand, my wife was given a drug called oxily platin

on compassionate use. That was not listed on any Web site, so she

was actually able to get compassionate use of that drug, but it was

not listed anywhere. So there are things happening out there

maybe too fast. I do not know. Maybe the Web site is a good idea,

but it is not happening in a timely manner. Now, I think that is

a Web problem, I do not think it is a drug problem. You find probably 50 Web sites, 49 out of them are out of date. So I do not blame

the drug industry for that.

Mr. HORN. I believe we have a vote now, do we?

Mr. BURTON. Yes, we do. We have about 71⁄2 minutes on the

clock, so Members can go ahead and vote. And if you come back—

I apologize to the panel. I hope you will bear with us. We will be

back in about 10 minutes. We have to run to the floor for a vote,

and we will be right back. And after we finish with you, we will

go to the second panel.

We stand in recess.

[Recess.]

Mr. BURTON. We will call the committee to order, and would the

witnesses please come back?

Is Mr. Burroughs out for now or did he leave? OK, well, we will

wait just a moment on him then. Well, I will tell you, while we are

waiting, why don’t I go ahead and ask Mr. Santino a question.

Mr. Santino, did you and your wife look at complementary alternative therapies as well?

Mr. SANTINO. You mean like health food store, that type of

thing?

Mr. BURTON. Well, yeah, and——

Mr. SANTINO. We talked to somebody at the Marino Center in

Cambridge, MA, which is known for alternative treatments, but

nothing really caught us. And the other thing is it interferes with

chemotherapy. My wife was under chemotherapy all the time, so

there were health food store type treatments available that are

being used in Canada, but we never really—I think we bought one

of them, but we never used it because——

Mr. BURTON. She was on conventional therapy.

Mr. SANTINO. Yes, and you have to be off chemotherapy for a

while to use it, and we were not willing to experiment on our own.

We were relying on the doctors primarily. If a doctor had told me

to use it, I would have gone for it probably. But without the advice

of a doctor, I would not do it.

Mr. BURTON. Was the chemotherapy—you said it was helpful at

the beginning.

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Mr. SANTINO. Yes. The very first treatment she had back in

1999. She had surgery April 1999 to remove the first tumor, and

she had radiation and the standard 5-FU treatment, and that was

very effective. She had no cancer for probably 6 months, and then

November 1999, she had a tumor, another tumor growing, and she

had to have a complete colostomy at that point, where she had only

had what they call a resection of her colon. She still had use of her

colon. But then she had a colostomy because of the surgery that

came up just a few months after. She ended the treatment in August 1999, and the cancer reappeared in November 1999.

Mr. BURTON. But the doctors told her that the cancer was gone,

and she——

Mr. SANTINO. Right, yes. We did not expect it to come back at

all. It was worse than the first time because we thought we were

out of the woods, and then, you know, summer of 1999, we were

just, you know, soon as the chemotherapy and the radiation is over,

we are back in business again as a family.

My wife actually went back to work in 1999. She was a teacher.

Mr. BURTON. I see.

Mr. SANTINO. She went to work for a couple of days, and then

she was very sick. We are not even sure what she had at the time,

and the tumor was probably starting, whatever was going on at the

time. And she could not work again until fall of 1999.

Mr. BURTON. I see. Mr. Burroughs, did your daughter try any

complementary or alternative therapies in addition to the traditional therapy she was using?

Mr. BURROUGHS. She was on a drug late in the game at Johns

Hopkins called Herceptin, and I think that is a fairly new drug, if

I am not mistaken. But we really were not able to get any of the

new advanced experimental drugs.

Mr. BURTON. I was not just talking about the experimental

drugs. I was talking about, you know, health remedies and things.

Mr. BURROUGHS. Going through this, is of course, a very difficult

experience, and we just got flooded with nutritional information.

‘‘You should try oak bark juice.’’ Sure. It has cyanide in it. Hello.

You know, just everybody was trying to help, I guess, or maybe sell

something or whatever, but there was just so much nutritional information, you start feeling like, am I overlooking something that

could save her life? Then you realize there is no empirical data on

it, and then you even look into some of it and find out that it is

actually quite dangerous, or that it just plain does not work. But

you feel like you have to sift through all this various piles of nutritional information that is coming to you from friends and wherever,

because that could save her life, it could be some secret key here.

Well, if it was so amazing, why have we not heard more about it?

Mr. BURTON. If you had one recommendation to make to the committee or the Food and Drug Administration or to the pharmaceutical companies, and I think that is probably one of the most

important things we can ask you, what would you suggest? Because you have all been through it. What would you suggest?

Mr. BURROUGHS. That we do about the problem?

Mr. BURTON. Yes, as far as getting whatever is necessary to help

your loved one or yourself in the treatment of cancer?

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Mr. BURROUGHS. Well, you know, obviously, I have lost a treasure, my only child, and a beautiful child that she was—well, she

is, but in a different world now. We need to have these experimental drugs available to more people now, or as soon as possible.

If it is a money issue—I presented that in my testimony—that

there are ways that we can put together some sort of vehicle or

foundation or whatever to finance more production of these drugs.

If it is a small company, they could even use the facilities of a larger company. There are ways I think to solve this problem.

Mr. BURTON. Production.

Mr. BURROUGHS. Yes.

Mr. BURTON. Mr. Santino, you have any?

Mr. SANTINO. I second what he is saying. I also think they have

to be fair to people. You cannot be giving it out to one person and

not giving it to another, especially at the same hospital. When my

wife found out that somebody at Dana Farber at Boston was getting C225, and we were just anticipating it would not be available

till November of that year, we went berserk, because here we are

waiting for a drug for the fall. We got to keep my wife alive till

the fall, and we find out somebody’s already got it, right in the next

chair to her. I mean, my God, how can a company be unfair like

that? So, I mean, give it out to nobody, or give it out to all, and

put the word out. Call the doctors at Dana Farber and say, ‘‘C225

not available.’’ Then I don’t have to write a letter. My wife wrote

three letters, and none of them were answered. All a doctor had to

do at the company was call Dana Farber and say that C225 is not

available. We would have got the word from the doctor, because she

went there every week.

I think the communications is lacking, I really do. I think they

are not understanding that cancer patients are people. My wife was

a wonderful person and she was a person. She was not just a name

and an address and maybe a profit center. I mean, you are in the

drug business, there are people there. So that is all I can say, is

be fair to people and understand that there are people out there.

Mr. BURTON. Mr. Baxter, do you have any recommendations to

the committee?

Mr. BAXTER. Well, I think that in the case of some of these pharmaceutical companies, that the request far, far exceeds the demand. And to take the position if you do not give it to everybody,

do not give it—if you cannot help everybody, do not help anybody,

is not being compassionate to anybody along the way. If they have

an extra 200 pills, then put them to good use. I think that maybe

the companies need to set a priority for compassionate use. We do

not send children to war. I think we ought to take the extra step

to make sure we protect children, that in establishing criteria, that

children ought to have, for example, priority, those who have the

best prognosis for a lengthy remission should have priority, and

those who will, in all likelihood, die before the drug is approved

should have the highest priority.

And then from that end you have to have some definition like

that of who to help, but I do not think it would be right to say,

OK, drug company, if you do not have enough drug to help everybody, do not help anybody, because that gives the drug company

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a very easy way out of just denying compassionate use to everybody if that is done.

I think in large degree, it is a production issue. I believe that a

company will not embark on a venture of hundreds of millions of

dollars to build a facility to produce these drugs in a high-production mode until they know it is a slam dunk, that they have got

it. And, you know, I think that perhaps we need to look at a—we

have FDA approval, which we need to maintain that level of standard, but maybe there needs to be some kind of initial FDA approval, such as a probable approval level, in which a company, once

they have reached that point, they can go ahead and start building

their manufacturing facility with the blessing of the government as

a backing. And should that drug not be approved, basically the cost

incurred would be offset by a tax credit or something like that. We

have to start production earlier in order to provide the most opportunity for the most people to participate in clinical trials and also

to be able to receive compassionate use. We got to increase production earlier.

Mr. BURTON. Ms. Kellum, you have a—— Ms. KELLUM. Obviously, I am in a different situation than these

gentlemen because I am here, and that is because I did receive

C225. And I think what we all need to look at is this disease is

what is unfair. I do not know if there is a fair or an unfair way

of administering this drug, and I do not think ImClone liked saying

no. But we need—I think we need to look at the common goal here

and that is to find a cure for cancer, because if we do not have the

cure, people are going to continue to die. And what is the answer

to finding a cure. And I do not have that answer. I wish we all had

a crystal ball that had the formula in it, but we do not. And I may

be simplifying it, but I think we need to, you know, with a drug

that has had this success, we need to get it approved as fast as possible and get it out to everyone. But denying some people the opportunity I do not think is the answer, because had I not gotten

it, I would not be here today, and we would not have the knowledge or the capacity to give it to other individuals, so I think we

need to take that into consideration as well. And, again, the common goal here is to find a cure, and whatever way we can do that,

I think is in the best interest of all of us.

Thank you.

Mr. BURTON. Mr. Baxter, several years ago, a San Francisco police officer named Rick Schiff, his young daughter was diagnosed

with a brain cancer. Her oncologist was aware of an experimental

treatment that was showing some success in her type of cancer, but

he opted not to inform the family of this treatment, instead pushing for another treatment option. Do you think doctors should provide families all of the options, standard, alternative, and experimental, and let the family decide?

Mr. BAXTER. I think that is very important. I feel I am very

blessed with Dr. Rosenberg being my son’s doctor. I believe that he

has kept us in the loop. We have tossed some things off the Internet to him. He had explained why this would or would not be beneficial to my son, and we have been very blessed in having that type

of relationship. And certainly, I would think personally it would be

unethical for a doctor not to provide that information. It is exVerDate 11-MAY-2000 11:55 Mar 19, 2002 Jkt 000000 PO 00000 Frm 00078 Fmt 6633 Sfmt 6633 C:\DOCS\77088.TXT HGOVREF1 PsN: HGOVREF1
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tremely difficult though for a family to evaluate that, and so with

that information needs to come the doctor’s professional recommendations as well.

Mr. BURTON. Well, what we are talking about is making sure

that everything that is open or possible to help—— Mr. BAXTER. Yes, indeed.

Mr. BURTON. Ms. Kellum, what do you say to those who haven’t

been able to access these experimental treatments or—I mean, you

are very fortunate.

Ms. KELLUM. I am very, very fortunate, and I thank God for

every additional day that I have, and it is very difficult for me to

stand up here. And in some ways I do feel guilty because I am still

here, but I am human, and that guilt is there. But I also feel that

this is a chance for me to help get these drugs approved quicker

and to share my testimony, and to just do whatever possible to find

a cure. And again I go back to that. We do not have a cure, and

I think that is why we are all here, is to find one.

Mr. BARR. Excuse me. Could I address the fairness issue that

you asked?

Mr. BURTON. Sure.

Mr. BARR. I think that there are two issues. One is that the FDA

really needs to discuss with sponsors the need for an expanded access program at the earliest possible stage, at the submission of an

IND.

Mr. BURTON. And they did that with the AIDS epidemic.

Mr. BARR. And I think making sure that those discussions happen—and a company might do it, a company might not do it, but

urging from the agency is really important. And the treatment IND

mechanism is probably the best way for insuring fairness in decisionmaking across the board, because there what the treatment

IND mechanism does is it provides both the agency and the sponsor and the patients with an infrastructure for how decisions are

made because a protocol gets created and you want the protocol to

not interfere with clinical trial enrollment, and you want it to

reach those patients who have no other treatment options and who

need this most of all. So using that mechanism is probably the best

way for providing a framework for decisionmaking that then is not

arbitrary and helps some patients and not others.

Mr. BURTON. Well, let me followup what you just said with a couple of questions. The AIDS community has shown the world that

when life is at stake, sometimes rules do not matter quite as much.

There were peaceful protests, sit-ins, coming together as a community to demand access to care. So what do you say to those who

would say that providing access to experimental drugs outside clinical trials may be dangerous?

Mr. BARR. Well, I was the coordinator of a demonstration at the

FDA in 1988, and the demonstration was, I guess, my idea, where

we actually seized control of the FDA because we felt that they

were not doing what they needed to do to provide us with the ability to make decisions about whether or not to take risks. What we

were able to show—and through the work that—through the advocacy work that was done, the agency really began to move and

change its position. And at least if you look at the expanded access

programs, early access programs that have been used in HIV, we

76

have been able to show that those programs do not interfere with

clinical trial enrollment, and they do not interfere with the running

of the clinical trials. Any efficacy data that would come out of an

expanded access program would really have no effect on a clinical

study. Safety issues might have an effect on a clinical study, if, for

example, you had an adverse event come out of a drug that was

being given on a compassionate use that was not seen in a clinical

trial. That might affect what happens in the clinical trials, but

then again you might want it to because the adverse event could

be very, very serious, and you would certainly want to at least incorporate looking for that toxicity in the clinical study. But those

programs have not affected clinical studies in HIV in a negative

way.

Mr. BURTON. Bastyr University, which trains naturopathic doctors was the first naturopathic college to receive NIH funding.

Their research center was funded to look at alternative medicine

use in the HIV/AIDS community. Do you integrate complementary

and alternative therapies into experimental treatment?

Do you integrate complementary and alternative therapies into

your treatment protocol, and what advice would you or do you

share with others about different approaches to health maintenance while living with AIDS? And I think all of this is relevant

to the cancer question.

Mr. BARR. The issue of alternative therapies is I think very complex because there is growing interest among patients in using alternative therapies, unusually as complementary drugs or therapies to what their doctor is prescribing. Very often the doctor will

not have very much information about alternative therapies, sometimes just because it is not an area of expertise for the doctor, but

most often because we do not have very much data on the use, on

the effectiveness and safety of alternative therapies, which can be

just as toxic as any pill produced by Merck or Bristol Myers

Squibb, and AIDS advocates have strongly urged that alternative

therapies be subject to the same kinds of rigorous controlled clinical studies to determine what their safety and efficacy is as any

other kind of drug.

I think what is most important is for doctors to always ask their

patients about whether or not they are using a complementary

therapy or an alternative therapy, and then look into the possibility of dangerous drug interactions and what possible side effects

might arise from the alternative therapy. Very often patients feel

that those kinds of therapies are beneficial to, if not the disease

that they have, in alleviating some of the side effects from the

drugs that they are taking for their cancer or for their AIDS. And

I think also that those kinds of treatments are very important in

helping patients feel more empowered in taking more control over

their medical situation, but it is really important that they discuss

them with their doctors and that doctors ask about that stuff.

Mr. BURTON. Mr. Burroughs, for our record here, did AstraZenica

and ImClone Systems communicate clearly with you?

Mr. BURROUGHS. That was a big problem we had. No, they did

not. We got an awful lot of run-around, ‘‘Oh, call this 1–800 number. No, call that 1–800 number. I’m sorry. This person is on vacaVerDate 11-MAY-2000 11:55 Mar 19, 2002 Jkt 000000 PO 00000 Frm 00080 Fmt 6633 Sfmt 6633 C:\DOCS\77088.TXT HGOVREF1 PsN: HGOVREF1
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tion.’’ ‘‘Well, is there someone that can cover for them?’’ ‘‘No, they

will be back in a week.’’ There was really poor communications. It was ridiculous. That is

the short version of the story, that it took so long to get feedback

on a question.

For instance, with AstraZenica, maybe I mentioned it earlier,

that Abigail’s story, her situation, was actually brought up at a

board of directors meeting in London, and I never heard any feedback from it, what was decided. You know, what did they say? Why

couldn’t you tell me that, tell me something? Communications was

very slow. It was confused. And I was never able to get something

printed like, ‘‘Here is our policy on compassionate use,’’ or ‘‘Here

is our definition of our compassionate use policy,’’ and ‘‘These are

a list of trials of our drugs,’’ either from ImClone or from

AstraZenica.

Mr. BURTON. So they really were almost nonresponsive?

Mr. BURROUGHS. Well, it took a long time to get answers to a

question like, ‘‘What is AstraZenica’s trial about?’’ And it took, you

know, a week and a half to find out that it is only a few people

in it, it is just for people who have lung cancer and only lung cancer, but it took me a week and a half to find that out. I found out

from ImClone, someone at ImClone, after going through a number

of different people, that there was a clinical trial in Fairfax, VA.

And I find out that, oh, great, so I have this great hope. But that

is all the information I had. ‘‘Well, here is the number to call in

Fairfax.’’ And I call the Oncology Center of Fairfax, and find out

that Abigail does not meet the parameters of the trials. Why can’t

this information be clearly communicated on a few pieces of paper

or whatever to me, or an e-mail or whatever?

Mr. BURTON. So I guess the next question is irrelevant. ImClone

and AstraZenica did not provide clear enough dated information to

you on the company sponsored trials?

Mr. BURROUGHS. That is correct.

Mr. BURTON. And they did not give you any information on the

requirements that she would need to get into the trials?

Mr. BURROUGHS. We had to find those out for ourselves.

Mr. BURTON. OK. Anything else? Mrs. Morella. OK, Mrs.

Morella, go ahead.

Mrs. MORELLA. Thank you, Mr. Chairman. Thank you for arranging this hearing. I want to thank all of you who have testified on

this first panel, for sharing your stories with us. Indeed, you bring

a real human dimension to the issue, and that helps focus attention on it through the stories that you have told.

Mr. Santino and Mr. Burroughs, I offer my sympathy to you on

the loss of your daughter and your wife. And reading about and

hearing about your son, Mr. Baxter. And the fact that you are

doing well, because of C225. And, Mr. Barr, I hope that you will

continue to do well. It is an area I have been very much involved

with, that area of HIV and AIDS, and what we can do.

Mr. Santino, I grew up in Somerville, MA. Matter of fact, I know

St. Clement School. I read the article that your son wrote about it,

so I can identify very much with——

Mr. SANTINO. What a coincidence.

Mrs. MORELLA. I am sorry?

78

Mr. SANTINO. What a coincidence.

Mrs. MORELLA. It is indeed. That brings us even closer together.

I also have the National Institutes of Health in my district and

FDA, Food and Drug Administration.

And I was listening to your response to the questions that the

chairman has asked, and they are pretty much some of the concerns I had, trying to figure out before we go to our administrators,

FDA and ImClone on the next panel, but what you see needs to be

done. And I guess I can deduct from what you have said—and you

can tell me whether I am right or whether something should be

added—but first of all, there is, I think as you have said, Mr. Barr,

no standard protocol for compassionate use of new drugs. If you are

not in a clinical trial, then it is helter skelter whether your doctor

knows about it, whether you find a Web site that happens to be

accurate at that moment, whether there is someone else who links

you up with a possibility of being looked at on a case-by-case basis

for being eligible, whether there is an adequate supply that is

available.

And so it seems to me that maybe one of the questions we will

want to ask the second panel is, ‘‘Are you working on establishing

some process that people would know about and making sure that

there is information available?’’

I also discern that not all doctors know about the various clinical

trials in those areas, so it seems as though maybe the professional

reaccreditation or what doctors do to get the professional training,

should make sure they are including how to be up to date in those

particular areas.

So I want to give you an opportunity to comment. Is there anything I am missing in that dimension when I look to what we

would ask the next panel to help to clarify this situation, Mr. Burroughs?

Mr. BURROUGHS. Thank you. Something I tried to bring out in

my testimony was that I do think that part of this issue is money.

Isn’t that something that affects so many things? I think that, for

instance, what I also brought out in my testimony is that some

companies do wider compassionate use of drugs than others. Some

do not do any. It is an issue of money. The companies do not want

to spend the money to make more of this drug, because they are

not going to make any money off of it. But there is a way to solve

that problem. And not to make anybody the bad guy here, why do

we not all work together? Why do we not have the pharmaceutical

industry, the government, other private sources or whatever, solve

the money problem, because it is expensive to make these drugs.

I do not have the exact answer, but I brought that out in my testimony that some sort of foundation or other vehicle to provide the

funding to make more of these experimental drugs.

In the case of Abigail, statistically, there was a 54 percent that

AstraZenica’s IRESSA could have saved her life, and we could not

get the drug. On the other hand, there are companies like Pfizer

and Bristol Myers Squibb and Burroughs-Wellcome, do quite a bit

of compassionate use of drugs. I think it is a money issue.

Mrs. MORELLA. Maybe it would be appropriate to have a conference or some kind of a meeting where you get these partnerVerDate 11-MAY-2000 11:55 Mar 19, 2002 Jkt 000000 PO 00000 Frm 00082 Fmt 6633 Sfmt 6633 C:\DOCS\77088.TXT HGOVREF1 PsN: HGOVREF1
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ships, the Federal Government for its role, the private sector, individuals, who could come together and—— Mr. BURROUGHS. Pharmaceutical industry. Yes, I think that we

do not want to make anybody here the enemy. That never does

anybody any good, but we want to take the resources we have in

the pharmaceutical industry and government and elsewhere, and

come up with a funding to help make more of these drugs. If there

are FDA rules that affect the application or the availability of compassionate use, let us solve that problem. I think it is a solvable

problem. Thank you.

Mrs. MORELLA. Would anyone else like to comment? Mr. Santino.

Mr. SANTINO. Mrs. Morella, I question the process. Why does

somebody like myself or Mr. Burroughs have to go off on their own

and do the research, when it should be a medical person? I do not

even know what I am talking about when I look at a medical Web

site, like make a call to a company. I did not know what carcinoma

was, for example. How would I know what that is? Because I am

an engineer. Why should I—I mean, if I have an aspirin, I ask the

doctor, and he says, ‘‘Take the aspirin, OK?’’ I do not have to call

the company and say, ‘‘Is it all right for me to take the aspirin?’’ You know, I deal through an intermediary who is a medical person.

I mean this is such an awful disease we are talking about, in my

case, my wife’s colon cancer. Why should I be on the phone calling

companies or writing letters or, you know, making ImClone the bad

guy, when maybe the medical community should have solved that

way before. So when ImClone is offering the drug under compassionate use, let them tell Dana Farber Cancer Center or whatever

cancer center, about that, and take me out of the loop. I mean,

now, I do not have a wife. I do not have an advocate. If I get cancer, I have to do it myself while I am sick. I did it for my wife because I was well and she was sick. I could do it. I could do all the

research and the digging and whatnot, but I question why does the

family have to do that in the first place? Is this the same for every

disease? I mean, I do not even know.

Mrs. MORELLA. Dissemination of the correct information to the

parties involved has definitely got to be one of the major points

that will come from your testimony.

I just want to—I’m sorry. Mr. Baxter.

Mr. BAXTER. I believe that FDA is endeavoring to do a very good

job within the framework that they now exist, and the approval

process is obviously important for society at large, but I think that

also it is important to look at the risk factors versus approval. As

a drug goes toward approval, progressively they know more and

more about it. Progressively they know the risk and stuff like that.

And so you get up to a point where, OK, this is FDA approved. But

at the same time, it is like my son having a scratch on his arm,

and the other arm being chopped off and bleeding to death. I mean,

while we want to make sure you are not going to get any infection

in this scratch while he is bleeding.

I think it is important also to realize that progressively my son’s

prognosis is becoming progressively more skeptical, and so the risk

of him dying becomes greater and greater all the time. So at some

point, especially—I do not know if there is another step or another

classification of approval, say, for terminally ill patients that FDA

80

approval could be authorized for those patients that have been classified, and which by far the risk of death from the actual cancer

far exceeds any potential side effects and stuff like that. But I

think that for the terminally ill, that type of hope, because if a patient does not have hope, they are lost, you know? They need to

have a level of approval perhaps that is a little bit different for

those who are terminally ill, and maybe that is something that

needs to be looked at as well.

Mrs. MORELLA. That is a very good point, and I think it is one

that should be posed to the second panel. Thank you, Mr. Chairman.

Mr. BURTON. Mrs. Davis.

Mrs. JO ANN DAVIS OF VIRGINIA. Thank you, Mr. Chairman, and

thank you all for coming and testifying today. I know it has to be

difficult for some of you. And, Ms. Kellum, I would just encourage

you to not feel guilty because you were able to be helped, because

I think it is good that you have the testimony that the drug did

help, so that now it can hopefully help others.

And Mrs. Morella touched a little bit on what I wanted to ask,

was until—actually, until I read the article about your daughter,

Mr. Burroughs, I was not familiar with compassionate use drugs.

And I guess my curiosity, my question is, how did you—how did

any of you know about compassionate use drugs? I mean, how did

you know who to contact? How did you know who had them and

whatever, because if I remember correctly, in the article, the first

two, ImClone and—— Mr. BURROUGHS. AstraZenica.

Mrs. JO ANN DAVIS OF VIRGINIA [continuing]. You could not get,

but then I think the week before she passed away, another pharmaceutical company heard about her case and came up with a

drug, but it was too late.

Mr. BURROUGHS. About 2 weeks before Abigail died, she got into

a trial of OSI Pharmaceuticals, OSI–774 in San Antonio, TX. They

are a very, very small company, but I will tell you, they really kept

in touch with us, and as soon as they had the drug manufactured,

as soon as they had a trial open, they called us. Now, I know they

are small, but I think a big company can have good communications too. These people were absolutely wonderful. The problem we

had was it was too little too late. Abigail was not strong enough

to make it to San Antonio to be—she could not even do the traveling let alone be in the trial. She died 2 weeks after we got that

news. But that was OSI Pharmaceutical, very small, little company.

Mrs. JO ANN DAVIS OF VIRGINIA. And I guess that brings to the

question of how did you know? How would you have known to have

contacted OSI? I mean, how did any of you know to contact——

Mr. BURROUGHS. What is interesting, what you do is you learn

a lot from working and talking to people. You keep gaining more

and more knowledge. Initially we knew about ImClone’s C225 and

AstraZenica’s IRESSA from her oncologist, Dr. Maura L. Gillison

at Johns Hopkins. And she says, ‘‘It is going to be hard getting

these if you can get them at all. You better get working ahead of

time before Abigail is off of the current chemotherapy as a backup

in case it does not work.’’

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We got to work right away, believe me. And we started learning

how difficult it was to get into narrowly defined trials, how compassionate use is almost nonexistent in both companies—well, it is

nonexistent in ImClone. It is almost nonexistent in AstraZenica.

OSI Pharmaceutical is a very tiny little company. They were, like

I said, wonderful, but the way we found out about them was I

made a phone call from a suggestion from a friend of mine to call

the Dana Farber Cancer Center up in Boston at Harvard University, and I got hold of some nice people there that said, ‘‘Have you

heard of OSI Pharmaceutical?’’ I said, ‘‘I have done a lot of Web

site searches on EGFR-targeted agents, believe me, and I have had

people—and they just did not show up on the radar screen.’’ And

they were a late player in the game, but they came through for us

once they had the drug manufactured and helped us—kept in touch

with us. They were wonderful people, very good communications.

Mrs. JO ANN DAVIS OF VIRGINIA. Mr. Chairman, I guess that is

my point I wanted to have made, was that when I was speaking

to a young lady in my office who had cancer, and she, by the luck

of the draw, someone she knew had heard that she had cancer, and

she happened to have been on a Web site and saw a drug, and then

told her about it, and then she was able to go and get into an experimental program and had success like Ms. Kellum did. Not the

same type of cancer, but that is the point, and I think Mrs. Morella

touched on it, is that as, you know, the people who have cancer in

their families, why are they having to search the Web site to find

out if there is anything that can help them?

And, Mr. Baxter, I will tell you, I have a 19-year-old son, and I

cannot imagine what you are going through, and my prayers will

certainly be with you.

Mr. BAXTER. Thank you.

Mr. BURTON. Thank you very much. I appreciate your patience.

Mrs. JO ANN DAVIS OF VIRGINIA. I think we have another comment, Mr. Chairman.

Mr. BURTON. Oh, I am sorry.

Mrs. JO ANN DAVIS OF VIRGINIA. Not me. Mr. Santino.

Mr. SANTINO. On the compassionate use, we had both the good

and the bad. And the way it should work is the way it worked for

us the first time. My wife had been at Beth Israel Hospital in Boston. That was her second hospital she had been to when she was

taking CPT–11, which is one of the standard treatments that was

not working. And the doctor there had a friend at Dana Farber,

and he said, ‘‘I think there is a drug, oxily platin that they are giving out in compassionate use. We do not have it here at Beth

Israel, but I think you should go to my friend, Dr. whatever, at

Dana Farber and take it.’’ And the minute we got over to Dana

Farber, they put her right on the oxily platin, and it was a compassionate use drug. We had never heard of compassionate use. We

had never heard of oxily platin, but the doctors arranged it for her.

Then we got into the C225 and the other drugs, which we had

to do all the work. I feel that it should be doctor to doctor, not me

and a Web site or Mr. Burroughs or whoever, because we do not

know what we are doing. We are wasting time. We are wasting

money for the insurance company. The insurance company paid for

my wife to go to Sloane Kettering to get all her information sent

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there and whatever. We never even used it. She died before. We

did it on our own. We arranged to go to Sloane Kettering. I arranged other types of things on my own because I thought they

were worth a try. But I guess I am questioning, why am I in the

loop, why not a management person who is a medical doctor, just

the way oxily platin worked? You know, I never heard of compassionate use. It did not matter. It was a treatment she needed, and

the two doctors worked it out together, and that was—I think that

is the moral for what I would propose. Everybody should know

about it, and the doctors should have access to the information

somehow, and take us out of the look, really, because who knows

if we are doing the right thing? And we are wasting money. We are

wasting insurance companies’ money. We are wasting time, and

maybe we are not going to go down the right path.

So oxily platin was not even on a Web site anywhere when we

got it, so it was the right thing. It worked for a while, but it did

not work a long enough time for her, but she was able to get about

6 months of relief with the oxily platin, and that is my statement

on it.

Mr. BURTON. Thank you, Mrs. Davis.

I really appreciate your testimony. Before you leave, I want to

put some things in the record. I would like to submit into the

record an article published in the ‘‘Boston Globe’’ by David Santino

about his mother, and we will put that into the congressional

record.

[The information referred to follows:]

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Mr. BURTON. I would also like to submit to the record a series

of articles from the ‘‘Washington Post’’ on cancer issues, including

one today about pediatric cancer patients not being given adequate

end-of-life care.

And this comes in conjunction with one of my colleagues, Debra

Price’s daughter, who was treated for cancer, and had a terrible

time with it.

And I have copies of statistics by State of cancer incidence and

cancer mortality that I want to submit to the record.

And for anybody’s information, in Indiana, it was estimated last

year that 27,000 new cases of cancer were diagnosed, and 12,600

people died from it. And just you wonder how many could have

been saved had they had a chance to have some compassionate use

from these clinical trials.

In any event, God bless all of you. Thank you very much for

being here. We really appreciate it. And hopefully because of your

testimony and the testimony of others, we will come to some conclusion on how to deal with this problem. Thank you very much.

Glad you made it. Thank you.

[The information referred to follows:]

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Mr. BAXTER. Thank you.

Mr. BURTON. Our next panel will be Dr. Waksal, Dr. Temple, and

Ms. Delaney. Would you please come forward?

If you could, would you please stand, so I can have you sworn?

[Witnesses sworn.]

Mr. BURTON. Dr. Temple, do you have an opening statement?

Dr. TEMPLE. Yes, I do.

STATEMENTS OF ROBERT J. TEMPLE, M.D., ASSOCIATE DIRECTOR FOR MEDICAL POLICY, CENTER FOR DRUG EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION,

DEPARTMENT OF HEALTH AND HUMAN SERVICES; AND PATRICIA C. DELANEY, PUBLIC HEALTH SPECIALIST, OFFICE

OF SPECIAL HEALTH ISSUES, OFFICE OF INTERNATIONAL

AND CONSTITUENT RELATIONS, OFFICE OF THE COMMISSIONER, FOOD AND DRUG ADMINISTRATION; AND SAMUEL

D. WAKSAL, Ph.D., PRESIDENT AND CHIEF EXECUTIVE OFFICER, ImCLONE SYSTEMS, INC.

Dr. TEMPLE. Mr. Chairman, members of the committee, I am Dr.

Robert Temple. I am Associate Director for Medical Policy at the

Center for Drug Evaluation and Research of FDA. I am also Director of the Office of Drug Evaluation I, which is where the Division

of Oncology Drug Products resides.

With me today is Ms. Patricia Delaney from FDA’s Office of Special Health Issues, the cancer liaison program, and I have submitted my full statement for the record.

I would like to highlight three main aspects of the use of investigational drugs to treat seriously ill patients, who have no satisfactory alternative, an arrangement sometimes called compassionate

use, but that we call treatment use.

The first point I want to make is that FDA has, for many years,

supported access to potentially useful drugs that are still under

study. Since the 1970’s, in fact, we have allowed, and even encouraged, treatment use of investigational—that is, drugs that are not

approved yet—drugs.

Many believe this kind of availability began with AIDS, but in

fact, we had allowed manufacturers of a number of kinds of drugs

to make them very widely available before that, notably a kind of

beta blocker for angina called cardio-selective, a wide range of new

anti-arrhythmic drugs, and probably the largest of all, the calcium

channel blocker, nifedipine, which was used to treat coronary artery spasm. Well over 20,000 people were treated with nifedipine

before it was approved.

In all of these cases there was reasonably mature evidence of

benefit and an acceptable safety record, and vigorous drug development efforts were going on.

In 1983 we proposed, and in 1987 formally promulgated, the

treatment IND regulation, which was an effort to formalize premarketing availability of certain drugs that seemed particularly

promising, and I want to mention several features of that rule.

It was explicitly intended to make promising new drugs available

for treatment use as early in the drug development process as possible. It was expected, though, that availability would usually be

relatively late in that process, in phase 3, except that it might be

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earlier, during phase 2, for immediately life-threatening diseases,

which cancer generally is. The rule requires the drug to be under

active investigation by a sponsor who is actively pursuing marketing, and a treatment IND for a life-threatening illness must be

based on a showing that the drug may be effective. That is the

standard. The rule also requires that availability of the drug would

not expose patients to unreasonable and significant additional risk.

Thus, a certain amount of data is needed even to support early use

under a treatment protocol.

FDA can stop an expanded access study if it is interfering with

the conduct of the controlled trials of the drug. Sponsors who make

drugs available under a treatment IND can recover costs once

there is adequate enrollment in the controlled trials. Whether to

offer a drug for use in a treatment protocol is solely within the discretion of its sponsor, although we sometimes suggest this pathway

to the sponsor.

It was expected from the beginning that sponsors would make information about a treatment IND, about its existence, widely available to people, although we did not specify the ways that they

would do that. In a treatment protocol access is usually open to any

physician/patient combination that meets the protocol requirements, not just to selected patients or physicians identified by the

company.

When we proposed the regulation in 1983, we were concerned

that access to promising drugs had been available only to certain

people who were ‘‘in the know,’’ and we thought that if a drug was

ready for this kind of use, any appropriate patient should have access and any appropriately qualified physician should be able to

give the drug. We are aware that in some cases when supplies of

drugs were limited, sponsors have used lotteries to choose among

the people who had sought to get the drugs.

When we first began the process, we thought that all treatment

use would be under treatment INDs, but that was probably unrealistic and has not proved to be true. Rather, a wide range of other

kinds of requests for treatment use, especially treatment uses in

specific individuals, which is sometimes called compassionate use,

have emerged. Commercial sponsors are not required to agree to

supply drug in those cases, but if they do, what is called a singlepatient IND may come to us. In some cases a single-patient exception to the sponsor’s ordinary protocol may be submitted to an existing IND. That is how many of these so-called compassionate uses

occur.

Although we thought drugs would be available for treatment use

only if there was a reasonable amount of data on safety and effectiveness, in oncology particularly, but in other cases too, critically

ill patients and families sometimes seek treatments that have very

little evidence supporting their value or safety, perhaps on the

basis of animal studies or persuasive theories. As a general rule,

unless there is a clearly better therapy for the patient, or clearly

inadequate evidence of safety, our practice has been, and is, to

allow these uses, at least in a modest number of a patients. But

this is a matter that deserves careful scrutiny.

And that leads me to my second point, which is that allowing

very early access to drugs, that is, access before there is really any

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evidence at all that they work, is a very complicated matter and

does not necessarily represent a benefit to patients. As patients run

out of treatment options, some will search out a new treatment,

every one not yet well tested. But we have experience with this.

Typical early studies of new cancer drugs, are carved out in patients who have exhausted available therapy. It turns out that

when the new agents are given to those patients, they are usually

not very helpful, and significant responses are extremely unusual.

Moreover, in most cancer chemotherapy trials, toxicity can be considerable, especially early, before approaches to managing toxicity

are well established and before an appropriate dose is chosen.

It should also be appreciated that reasonable hypotheses do not

always work out, as the current controversy over high-dose chemotherapy with bone marrow or stem cell research illustrates.

That said, I want to mention something that arose in the previous discussions. One of the things companies are sometimes

asked to do is try a drug that is already being developed for one

disease in treatment of a different tumor, perhaps in one or a small

number of patients. Doing that is not unusual and actually resembles ordinary drug development. The proposed new use is like what

is called a phase 2 study in cancer development parlance. And if

a patient with a novel, a different tumor, such as a head and neck

tumor, were to be incorporated into a study as a single patient for

a drug that is being predominantly worked up for, say, lung cancer,

that would not be a very unusual thing to do, and it would rarely

give us any difficulty, even if there was not yet much information

about the new use.

Because early access to drugs has both potential value and potentially serious risks, in December of last year and June of this

year, FDA asked its Oncology Drugs Advisory Committee to consider when it is appropriate for FDA to allow investigational drugs

to be used to treat individual cancer patients. The issue is obviously a complex one, but several speakers were surprisingly skeptical about individual patient use at very early stages. The statement of the National Breast Cancer Coalition [NBCC], for example,

which I understand you have talked to, urged that access to investigational interventions outside of clinical trials be very limited,

and expressed concern about unreasonable expectations created for

women who have exhausted standard treatment. They feared that

too-ready access would undermine clinical trials and the principle

of evidence-based medicine, and might actually be harmful to patients.

The NBCC also thought that making access fair was very difficult, given practical and economic constraints. On the other hand,

they strongly endorsed wide availability for patients not eligible for

existing trials through a formal expanded access program when the

therapy showed some effectiveness and low risk in phase 2 trials.

They were very enthusiastic about the treatment IND.

They also urged that off-trial access, even at early stages, when

it occurs, be in the form of an expanded access protocol, not

through single-patient INDs. Many of the FDA’s Oncology Drug

Advisory Committee members expressed similar views.

Now, these are obviously complex and difficult issues that require balancing competing values and interests. We plan to hold a

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broadly based workshop involving regulators, NCI academics, patient groups and individual patients to discuss these issues further.

I believe, based on what I’ve heard today, we will also try to address formally the question of how to make information available

about expanded access programs once they do exist.

The last point I want to emphasize, as others have today, is that

fairness is extremely important. Any suggestion of unfairness in

the way access to last-resort drugs is provided is extremely troublesome to everyone involved. It is becoming clear that any manufacturer with a drug that is arousing interest among patients and

physicians should consider an organized program for providing

whatever level of access it considers appropriate at a given stage

of development. Access may have to be limited because of lack of

data, insufficient drug supplies, or concern about use by physicians

not experienced in how to use the drug. Or access may be more extensive, if that is supported by sufficient efficacy and safety data.

But in any case, there ought to be a plan and people can find out

what the plan is.

We have begun to urge companies developing cancer drugs to pay

far more attention to this aspect of expanded access, and Ms.

Delaney can tell you more about that later. For patients in search

of treatment, a clear statement from sponsors as to what access is

available is critical. Patients and family members have told us,

time and time again, as they just told you, that they want clear answers. Even if the answer is no, knowing that answer sooner rather

than later can allow patients to pursue other options.

That is the end of what I had prepared. I have a couple of comments in response to what I heard a little earlier, which I will do

now if you like, or later.

One of the concerns people had was that companies might fear

that data from access programs would contaminate their data and

in some way impede approval of their application. I do not think,

and I note Mr. Barr said this too, there is any real chance that

would happen. We completely recognize that the efficacy data from

an expanded access program is not the same as, or is to be mixed

with, the efficacy data from an organized clinical trial. The expanded access patients have many reasons for being less responsive, and I do not believe anybody should have anxiety that we

would confuse the two populations. It is true that if, in a wider access program, adverse effects were seen that had not been seen

previously, we would want to know about those. But I think everybody would want to know about those. So I do not believe there

should be a ‘‘fire wall’’ between those two kinds of studies. But I

cannot think of a drug whose fate has been damaged by an adverse

effect in an expanded access program. It could happen. Wider access, as we know, after drugs are marketed sometimes reveal

things that we did not know from the smaller data base of drug

development.

I guess the third point is that we do not just tolerate wider use

of drugs prior to approval. I’ve already mentioned the treatment

IND; in addition, we also actively support wider use prior to approval more generally. I used to call this phase 31⁄2, and we used

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able so that in fact there would be more safety and conceivably efficacy data available. So this is in no sense grudging. We think it

is a good idea.

Finally, just briefly, the standards for approval of oncologic drugs

are shaped unequivocally by the nature of the disease. The amount

of data, the level of evidence that is required is usually far less

than it would be for drugs for comparatively trivial illnesses. So we

share the view that greater risks are acceptable for people who are

facing the rigors of cancer.

Anyway, thank you, Mr. Chairman, and we will be glad to answer any questions.

[The prepared statement of Dr. Temple follows:]

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Mr. BURTON. Thank you, Dr. Temple.

Ms. Delaney, do you have an opening statement?

Ms. DELANEY. I do not have formal remarks, but I am available

for questions.

Mr. BURTON. OK. Dr. Waksal.

Dr. WAKSAL. Good afternoon. Thank you.

Mr. Chairman, my name is Dr. Samuel Waksal, and I am the

president and chief executive officer of ImClone Systems. I appreciate the opportunity to testify before the committee this afternoon.

Before I go on with the rest of my testimony, I just want to briefly interrupt and say that is a very difficult situation to ever deal

with with patients, with family members of patients who have cancer and our sincere—and our hearts go out to these patients. There

is no answer to give to husbands and fathers and other family

members of patients who have died of cancer. And this is not

meant as a rebuttal to anyone. We are here to talk about what we

are trying to do in the same way that this committee interests allies, in looking forward to figuring out how to best deal with this

very difficult disease, and we share this committee’s goal and a

commitment to all of that. In fact, ImClone scientists have spent

the greater part of their careers moving forward and trying to discover these new approaches to the treatment of cancer that we

hope will change the way cancer is treated in this next millennium.

I want to discuss today our experience with the treatment IND

or compassionate use IND that we have been talking about, and

our experience is with the development of our first therapeutic

agent, IMC-C225, and I hope that what we tell you here today will

help this committee look at the very difficult issues that we are

talking about.

We are currently going through the FDA approval process to get

IMC-C225 approved and out into the market, and we have been

testing this drug in patients now since January 1995. We have

been looking at a variety of cancers. We have been using IMC-C225

in the area of head and neck cancer, in colorectal cancer, in pancreatic cancer and lung cancer. And in May 2000 we had data that

was presented at the American Society for Clinical Oncology that

showed great promise for this drug in colorectal cancer and head

and neck cancer in patients who had failed conventional chemotherapy, and there was a lot of media attention at that time on our

drug because of the results that were presented.

Because of all of that we had really an onslaught of requests for

compassionate use protocols for IMC-C225, and we have been moving forward and completed, in effect, this last year, our phase II

studies for the use of our drug in colorectal cancer in patients who

had failed conventional therapies. The FDA has given us fast-track

designation to move this forward, and we expect to move it forward

with a biologics license application very soon.

For us the critical issue has not been money. For us the critical

issue is not that we are afraid of contaminating our clinical trials,

and in fact are moving forward with our clinical trials, and believe

that our first obligation, obviously, is to prove that this drug is safe

and is effective in standard clinical protocols that we put together

in conjunction with the FDA.

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For us the critical issue has been manufacturing. This is a biologic. It is a protein-based drug. Unlike small molecules that most

pharmaceutical companies developed and are developing of the

kind that AstraZenica or OSI Pharmaceuticals make, this is a protein-based drug that has very stringent biologic manufacturing

standards. And in effect, we are so committed, that early on, before

we really knew that this drug was going to have any activity, when

it was still in preclinical studies, we built a pilot manufacturing facility that would allow us to move forward in clinical trials, and we

did that back in 1994. Moreover, at the present time, we only have

enough clinical supply to give us about 10 weeks of additional therapy for each of the patients on our clinical protocols.

Also we have a contract manufacturer that we have gone out to

find because we are living in a world right now where there is not

enough manufacturing capacity for these types of protein-based

drugs, and there has been a lot of news about that over the past

several months. So, in effect, we do have a contract with a thirdparty manufacturer, and again, money has not been an issue. We

have requested every single run that they might have in their facility to make our product and are doing that as we move forward.

However, this supply is limited and our obligation and the obligation to the future of—to future cancer patients is to move forward

through clinical trials, prove that the drug is safe and effective,

and get it on the market.

Prior to May 2000, when very few people who knew about this

drug, the only compassionate use requests that we got were from

clinicians that were in our clinical trials and had experience with

our drug. Between January 1995 and May 2000, we had very few

compassionate use requests, and we put 15 patients on compassionate use protocols up until May 2000. After May 2000 and until

January of this year, when we ended our compassionate use program, we treated an additional 15 people. But the requests were

very different. Instead of physicians that really knew how to use

this drug and knew about the drug, it was more the media and a

lot of word-of-mouth because of clinical data that was being presented at conferences that really drove a huge amount of these

types of requests, and as we put into our testimony, we have had

almost 10,000 requests for this drug, about 8,000 different patients

that have requested IMC-C225 for various types of cancers, and

this has been a very difficult thing for us because as compassionate

as we are, we are a small biotech company, not a big pharmaceutical company, and it is very difficult to process that kind of request, those kinds of requests by this many patients.

Initially what we did was really try to set up a hotline right after

May 2000 to deal with some of these requests, and we really feel

badly. We probably should have put a form letter together. We

were unexperienced at the time, and the data that we had generated was really new to us at that point, and in effect, perhaps

we should have put a form letter together to get back to these patients to tell them that there were limited amounts of slots available for these compassionate use programs. Indeed, what we initially put together was a list of first come-first serve, and when

that got too big and we were afraid that we were going to give false

hope to anybody that even got on the list, we finally ended our proVerDate 11-MAY-2000 11:55 Mar 19, 2002 Jkt 000000 PO 00000 Frm 00118 Fmt 6633 Sfmt 6633 C:\DOCS\77088.TXT HGOVREF1 PsN: HGOVREF1
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gram and decided to concentrate on getting the drug approved because we felt that was the best way to get this drug out to as many

people as possible in an approved fashion.

So after having to turn away all these people, we are now concentrating on a couple of things. One, is we have, even before we

had the further data that our drug was working in colorectal cancer in the refractory setting in patients who had failed conventional

therapies, and in the setting of head and neck cancer, in January

2000 we broke ground on a very large manufacturing facility. So

we took that huge risk ourselves. No one helped us. We were not

partnering this drug with a big pharmaceutical company at the

time, and we took the risk to make sure that a major facility could

be built that would make this drug available to cancer patients in

the future. We just completed the physical completion of that facility in record time, I might say, and now we are beginning to get

ready to make it in that facility, under very strict FDA guidelines,

so that facility can later be approved and we can have material

available for patients after the drug is approved, and also to revisit

how we would put together an expanded access program for even

more patients.

So would we do things differently in the future or would we have

done things differently in the past? The answer is yes. We were a

very young and inexperienced company, concentrating on putting

together and discovering new novel therapeutics for the future

treatment of cancer that were different than the kinds of therapies

that had been discovered in the past, and we are happy to say that

we, as pioneers in that area, have pioneered a new approach of targeted oncology to get these new kinds of drugs out there. We are

in the last stages of dealing with the FDA and moving forward in

conjunction with the FDA to try to get this product approved, and

at the same time, expending our meager resources—and they are

far less than big pharmaceutical companies—but expending all the

moneys that we can to make sure that we have the manufacturing

capability available, to have drug availability for these individuals,

and to do everything we can to treat disease that are heart wrenching in every individual aspect. And what we are trying to do is get

out there and serve the thousands of patients in the future that

need our drug.

Thank you, Mr. Chairman.

[The prepared statement of Dr. Waksal follows:]

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Mr. BURTON. Thank you, doctor.

Dr. Temple, Ms. Delaney, given the information that Dr. Waksal

just gave us, how long would it take from this point on to have the

C225 approved and ready for dissemination to the populace? They

started the clinical trials, I guess, in 1995; is that what you said?

Dr. WAKSAL. Yes. We started clinical trials in 1995, but—— Mr. BURTON. So in 1995. Now we are 6 years into it, and it is

showing some promise, and, you know, having 130,000 cases of

colorectal cancer this year, and every one of those people, knowing

that it has some positive results, would probably like to have this

product. So how long does it take the FDA to get that done?

Dr. TEMPLE. Well, I cannot speak about that biologic for a number of reasons. For one thing it is reviewed in a different center.

Mr. BURTON. Wait a minute. Excuse me. It is in a different center? I thought when—we wanted FDA to send some people up here

that were familiar with this particular product.

Dr. TEMPLE. Well, this may be a terrible error on our part, and

if so, I am sorry, but the request to us—— Mr. BURTON. You mean there is nobody here from FDA that can

tell us anything about—— Dr. TEMPLE. About this drug? That is, I am sorry to say, correct.

The request for information was quite a generic one about general

policies, so we assumed that the specific request for me was deliberate, and I did not know that you wanted someone who could talk

about C225, and I really cannot. But I can tell you some things

about the approval rates for cancer drugs and how long things

take. As you undoubtedly know, we approved Gleevec in 2.4

months. The data was very good and very powerful. for any drug

that is a fast-track drug, as this one apparently is, we have a response time of 6 months. We essentially always meet that goal, so

that once C225 is before us, I am quite sure there will be an answer in that time or less.

Mr. BURTON. So the timeframe you are talking about in a generic

way is about 6 months?

Dr. TEMPLE. Well, that is the time for response. The answer

could be yes or no.

Mr. BURTON. So the data will be reviewed within 6 months?

Dr. TEMPLE. Yes. That is our goal date for any drug that receives

priority—— Mr. BURTON. And then after 6 months, if there is a problem with

the drug, then there is a continued reevaluation?

Dr. TEMPLE. Well, our initial response is one of three things at

the present time. It is, ‘‘you’re approved,’’ and here is the label that

is approved; you are ‘‘approvable’’ with modest amounts of additional information—the amount of information can be changes in

labeling or something more important. If it is just changes in labeling, we respond to the resubmission in 2 months. If it is more, we

respond within 6 months. Or it could be nonapproval because people do not believe the data are persuasive. I have no idea what the

outcome on C225 will be. From what everyone says, they seem optimistic, but I cannot tell you any more than that.

Mr. BURTON. Can we make a formal request that we get that information from FDA, whoever is in charge of that, so we can take

a look at that?

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Dr. TEMPLE. OK. I will ask them to provide what they can. It

may have to be provided to you in confidence, because those are

commercial considerations, but we will certainly get you what we

can.

Mr. BURTON. Well, I can understand the ramifications.

Dr. TEMPLE. Let me mention one other thing. I do not know that

they are ready to do this and I do not know what we would say

in response to it, but if the company wanted a treatment protocol

approved, we respond to those requests within 30 days, and that

has been in the rule since 1987.

Mr. BURTON. Dr. Waksal, have you requested that treatment protocol?

Dr. WAKSAL. What we are doing right now, and we have consulted with advocacy groups and talked to the FDA, we do not have

yet the manufacturing capability, according to FDA guidelines, that

will make enough of this drug available in a treatment protocol.

Mr. BURTON. I am not familiar with how all of this works, so I

am kind of a neophyte in this area. But let us say that you had

not necessarily your drug, but some drug that showed promise, and

you knew that there were 130,000 people a year that were suffering from this and it had been shown to be pretty successful. Can

you subcontract with a major manufacturer of pharmaceuticals to

get that to the market while at the same time you are working on

getting approval for your new facility?

Dr. WAKSAL. Yes, one could, and that is exactly what we have

done with IMC-C225. What we did, because we knew that we had

to build a larger facility and we did not want to wait, there is— now, it is a little different than from the—in the Bureau of Biologics, where we are dealing with our protein-based drug, than the

group that Dr. Temple normally deals with. So each of the facilities

that make our particular drug have to be licensed by the FDA for

our particular drug. So we went to a group that does contract manufacturing, Lanza Biologics, to put together an agreement, where

they would make our product for us under contract, and we have

put together—for our approval process, we used their facility as the

site that made our drug for our FDA application which we are

going to put in very soon. Our own facility being completed right

now will have to go through the same type of approval process,

that is, that we, as we scale up and begin to make our drug in our

own facility later this summer, we will go through and make three

consistency lots, and then apply for that facility to be approved,

and then have more drug available for these kinds of programs.

Mr. BURTON. But the contractor that you are using right now to

produce the product is limited in the amount that they can

produce.

Dr. WAKSAL. That is correct.

Mr. BURTON. And that is why you stopped compassionate use?

Dr. WAKSAL. That is correct. Right now, even the contract manufacturer that we are working with, has one 5,000-liter—just to give

you size dimensions—one 5,000-liter fermenter committed for about

25 runs, you know, this year. Our facility that we are building has

three 12,500-liter fermenters with 10,000 liters of capacity each. So

we have invested a good deal of moneys to try to get enough of this

drug available later so that we can make this available for all the

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people that need it. And even with that, that is not going to be

enough for the future, we do not think, and we will be breaking

ground in the future for an even larger facility.

Mr. BURTON. How many people are in your clinical trials right

now; do you know?

Dr. WAKSAL. We have treated thus far, between January 1995

and now, over 700 patients.

Mr. BURTON. 700, and you have treated 30 approximately for

compassionate use.

Dr. WAKSAL. Yes, about 4 percent.

Mr. BURTON. And the capacity of the production facility is taxed

with just that number?

Dr. WAKSAL. That is right. Sadly enough, we are looking at opening up new clinical trials, and I must say that the really sad thing

is, for every patient that gets the drug in a compassionate fashion,

patients on the clinical trials do not get the drug when we are limited by the type of drug, a protein-based drug that we are making,

we are so constrained right now, that we are limiting the amount

of clinical trials that we would otherwise be able to do simply because of the lack of drug.

Mr. BURTON. Is there anything that could be done—and this is

a generic question—the FDA has to approve these things. And I

mean, obviously, that is something that I think we all agree needs

to be done. You do not want a contaminated product put in the

market that is going to kill people rather than help them. But is

there anything we could do to speed up the process from your producer now, and whatever company, and I do not want you to get

in trouble with the FDA and have them give you a hard time because of what you are going to say. But I would like to know if

there is anything that can be done to speed up the process for these

new promising drugs like this one?

Dr. WAKSAL. Look, actually, we have had a very good working relationship with the FDA.

Mr. BURTON. Do not be diplomatic.

Dr. WAKSAL. No, I am not being diplomatic. I am telling that we

have gotten fast-track designation. They have worked with us to

try to help direct us what we need to do in our new manufacturing

facility. I am sure there is lots of things that the FDA could do to

speed up the process in terms of what we believe is going on, but

I am sure that they are as constrained as we are in timing.

Nevertheless, we are moving forward. We believe that this product is moving forward very rapidly through the FDA approval process, and could very well be on the market sometime in the first half

of next year.

Mr. BURTON. First half of next year.

Dr. WAKSAL. Yes.

Mr. BURTON. But it still will be limited because of your production facility.

Dr. WAKSAL. Well, the new facility, we hope will be up and will

be going through the approval process, so that we can make

enough drug available for the approval process after launch.

Mr. BURTON. I have some more questions. Mrs. Davis, do you

have some questions?

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Mrs. JO ANN DAVIS OF VIRGINIA. Thank you, Mr. Chairman. I

guess I have one, and it relates to Mr. Baxter’s son. As I heard in

his testimony, his son’s doctor has the drug out in, I believe, California, and I guess I am curious as—and I understand that he is

16, and that you are not allowed to give it to—I guess you could

not give it to anyone under 18, but, you know, granted this is a

disease that you do not expect to find in a 16-year-old. And I guess

my question is, if the doctor has the drug, could you not then ask

the FDA to make an exception and let you give it to this 16-yearold, whose prognosis is just a couple months? He cannot wait till

the first half of next year.

Dr. WAKSAL. No. That is absolutely true. That is not the issue

here. One, we will go to—we would go to the FDA, and we made

it clear that we would go to the FDA to lower the age requirement,

and I am sure the FDA would comply in that particular case. I do

not think that is the issue here. And the issue of clinical trial sites

is one, where we do these clinical trials all over the country. We

have clinical trials going on in California out West, obviously. Dr.

Rosenberg is one of our investigators in our head and neck trial.

Unfortunately, in the colorectal study, the closest state to the Baxter family is Indiana. We have one of the clinical trials going on

in Indianapolis right now. But it is very difficult to open up a new

site, not knowing still whether David is a candidate yet for C225.

We have no idea yet. He has not failed his conventional therapy

yet, and we do not know whether he is positive for the molecule

that our particular antibody attacks, the EGF receptor. So we cannot open up a site prior to knowing whether or not a patient is a

candidate. So it is still unclear right now, and we do try to be as

accommodating as possible in this particular situation, but again,

it is a very difficult situation. You cannot open up a site for a single patient prior to knowing whether or not the patient is going to

be eligible for one of those trials, and it takes a good deal of time

to do just that, to open up one of these sites and to go through the

approval process for those institutions.

Mrs. JO ANN DAVIS OF VIRGINIA. And I guess that brings me to

the question, back to, I guess, Mr. Santino. I believe his wife was

denied because she was, from his testimony, too sick or had too

many treatments. And could you explain that to me so I could understand it a little better?

Dr. WAKSAL. Well, first of all at the time, unfortunately, and I

feel terrible about Mrs. Santino, but we had no compassionate use

protocol in place after January. We ended it because of number of

patients that we had. We could not successfully deal with the list

any longer. We did not really have enough drug to make it available after that. The list had gotten too long. And I am very sorry

that, unfortunately, from the point of view of the Santino family,

that we did not communicate that properly, and probably should

have had letters sent out. Unfortunately, our medical affairs director tried to answer all of these phone calls personally, and it was

not something that was acceptable to the Santino family.

But at the point in time that we design these trials, these trials

have very fixed criteria, and we cannot deviate from those criteria.

Those criteria are negotiated with the FDA, and once they are set,

they are set, and the people that enter those trials have to fit the

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age, the disease stage, and etc. All of the criteria that we negotiate

with the FDA to move these drugs forward in a proper fashion so

that the clinical community and the FDA can assess whether or not

these drugs are going to be useful to the population at large, to the

clinical population that we are talking about.

So, in effect, sometimes patients are too sick to get on one of

these trials, because their health does play a role in all of these

things, and obviously, that is who we are dealing with, sick patients, but the clinical trial protocols are so defined, that there are

patients that cannot enter them.

Mrs. JO ANN DAVIS OF VIRGINIA. Thank you. And I agree with

what Ms. Kellum said in her testimony. I think we all would like

to find a cure to this terrible disease. It has affected my family and

my husband’s family. And it is just something that I wish you the

best, and if there is anything you can do to help David, I would

appreciate that.

Dr. WAKSAL. We are trying.

Mrs. JO ANN DAVIS OF VIRGINIA. Thank you, Mr. Chairman.

Mr. BURTON. Thank you, Mrs. Davis.

How do you determine if someone is positive for the EGF?

Dr. WAKSAL. There is a test that is done that is a pathological

test, where we utilize a marker that sort of lights up the molecule

if it is there, and then the pathologist can say that the patient’s

tumor is either positive for this receptor or not.

Mr. BURTON. OK. We have had a number of cases in my family,

one that is current. And I have been in a lot of facilities where they

administer chemotherapy on a regular basis. And a lot of people

who get chemotherapy, their immune systems are depressed while

the tumors are being killed hopefully. And I just wondered, if people go through a complete series of chemotherapy treatments, does

it make them more likely to be able to take C225 or less likely?

Dr. WAKSAL. Well, our drug——

Mr. BURTON. Does it depress their immune system to such a degree that they would not qualify?

Dr. WAKSAL. No. And if—— Mr. BURTON. Or can you give me a comparison, those who—and

I do not know if you have this kind of information—those who have

taken C225 without chemotherapy being first administered, and

those who have had it administered?

Dr. WAKSAL. Well, some of the first studies that we have done

are obviously in patients that have become refractory to chemotherapy, that no longer respond to their chemotherapy. And then

they get to IMC-C225 in combination with the therapeutic agent

that they failed. So the earliest responses we have seen have been

in patient populations that have already failed all the existing and

approved chemotherapeutic agents. We have data, earlier data that

suggests that in patients that have not necessarily failed but are

more stable disease patients, that we may even have a better response. And the whole purpose of—— Mr. BURTON. Do I interpret that to mean that those who may not

have had chemotherapy?

Dr. WAKSAL. Well, those who are not failing chemotherapy, but

are taking the chemo and the chemo is having some effect. In those

patients there may even be a better response, and in fact, that is

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our approach to this whole process of getting approval. We are first

applying for approval on the phase II data using the fast-track designation that Dr. Temple talked about for cancer drugs, but it is

provisional, sort of conditional approval. And the next thing that

we are going to be doing and that we are opening up right away

is an earlier stage study, a very large clinical trial in patients who

have never received chemotherapy and who have just been newly

diagnosed with these types of tumors with colorectal cancer.

Mr. BURTON. So you are starting a new study right now on people who have not taken chemotherapy, but—— Dr. WAKSAL. Who are chemo-naive, that is correct.

Mr. BURTON. To see if C225 is more effective or less effective. I

see, OK.

Let me ask Dr. Temple or Ms. Delaney. Ms. Delaney, we have

not been able to get you to answer any questions. But one of the

things that I think that Mrs. Davis, Representative Davis talked

about and the people of the first panel talked about, was the lack

of answers, the lack of communication. What can FDA do in conjunction with these manufacturers of new drugs to get this information on the Internet so that people can find it? And if they do

not have—if they are not Internet literate or computer literate, as

many people are not in this country, how they can get a hold of

this information by contacting the FDA. I know that you have a lot

to do over there, but it seems to me that one of the most hopeless

things people go through is seeing a loved one or themselves being

in this situation, and they say, ‘‘What is available? What can we

try? What can we do to save their life?’’ And they cannot find the

answers. I mean, that has got to just drive them up a wall, especially if after the fact, after somebody dies, or they are so depressed

and their immune system is so depressed that they cannot survive,

they find out there was something out there and they could not

find it. And we had a couple of people on the panel before you that

mentioned that.

So what can FDA do in conjunction with the private sector to

make sure all that knowledge is accessible?

Ms. DELANEY. Well, actually, the scenario that you just presented, Mr. Chairman, is pretty much the standard phone call that

we get to our office every day. And it is people who are pretty much

out of options, or many people believe once they are diagnosed they

are out of options. They are very confused and upset by what has

happened.

In cases like that, when it is a first diagnosis, we recommend

that people first of all talk to their doctor. Second of all, that there

are many, many cancer patient advocacy groups that are out there

to help them, and we have a huge resource list. But the National

Cancer Institute is really—there is a huge educational arm to the

Cancer Institute, and the best place for people to find out information about new drugs in development in their cancer is the Clinical

Trial Registry. It is known by its acronym of PDQ, but it is available through clinicaltrials.gov, and——

Mr. BURTON. Excuse me. I cannot remember which gentleman it

was. I believe you said that you had four Internet sites yourself?

Mr. SANTINO. Well, the——

Mr. BURTON. I know, but you are obviously Internet literate.

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Mr. SANTINO. I do. I have four myself.

Mr. BURTON. You have four yourself. And you went through everything time and again, and you could not find information that

should have been readily available. I think that is what your testimony was.

Mr. SANTINO. What is available it is not on the Web site anyway.

Mr. BURTON. It is not on the Web site.

Ms. DELANEY. But that is just for people that are first diagnosed,

and clearly, Ruth-Ann Santino had been through all the standard

treatment.

And so when we get a call or people want to know about a drug,

and they have exercised all of their options with the standard

treatments, we then try to assist them in finding the different

places where they might look for drugs. There are Web sites, that— actually, when I talked to Ruth-Ann, the Web site we told her

about, which she did not know about prior to that phone call, was

pharma.org, and that is the Pharmaceutical Research and Manufacturer’s Association Web site. They do a publication every other

year in cancer called ‘‘New Drugs in Development in Cancer.’’ There are 402 drugs listed by tumor type, and it is available on the

Internet, and you can search it in a PDF file very easily.

Mr. BURTON. Let me ask you this question. You indicated that

after they have gone through their conventional treatment, what if

they do not want to go through what is called conventional treatment? What if they have an aversion to, say, chemotherapy?

We have a young man, the Thomas Navarros case. I am sure you

are familiar with that. It has been all over the media. And he was

denied access to experimental treatment because he had not first

failed what the FDA said was a standard form of care, chemotherapy and radiation. Why is that and can people get information

if they do not want to take chemotherapy and radiation because

they think there is a—— Ms. DELANEY. I am going to let Dr. Temple answer that question,

but I wanted to—can I tell you about what we do with companies

to make sure on this compassionate use, before he answers that

question? Would that be OK?

Mr. BURTON. Sure, sure, sure.

Ms. DELANEY. When it is clear that there is a number of phone

calls that are coming in on a new drug—for example, this happened with C225 and a number of others in the last 2 years—we

then place a call to the company, and we say, Look, I am sure you

are getting many more calls than we are getting. The National

Cancer Institute is also. We need to sit down and talk about what

is your policy? Do you have one? If you do not have one, please develop one, and we will help you sit down with the patient advocacy

community and make that policy clear to them, so that a phone call

to the Colon Cancer Alliance is the same thing as a phone call to

the National Cancer Institute or a phone call to ImClone. So that

a patient or family member is not having to call all these different

places, that everybody knows that, for example C225 will not be

available. I think Fred Santino said it eloquently. It wastes to

much time.

And so what we have done, not only with ImClone, but we also

have done it with a number of other companies, is to bring everyVerDate 11-MAY-2000 11:55 Mar 19, 2002 Jkt 000000 PO 00000 Frm 00136 Fmt 6633 Sfmt 6633 C:\DOCS\77088.TXT HGOVREF1 PsN: HGOVREF1
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body together. So we are sort of the convener. We do not have a

lot of authority in this area. It is an initiative if you will. But we

convene the groups, and I think Dr. Waksal could talk about what

we did specifically with their company.

Now, I will let you speak to Dr. Temple on the Navarro case.

Mr. BURTON. It sounds like, from the first panel and from other

people I have talked to, that they have difficulty in finding all this

information, and if the FDA and HHS could look into that to see

if there is some way to streamline the process so that on the Internet and through mail if necessary or faxes, that people can get as

much information as quickly as possible might help a lot.

Dr. Temple.

Dr. TEMPLE. It may be those very sites ought to link to each

other somewhat better than they do, for example. We can look into

that.

The cases we have been talking about are all ones in which

someone wants to use a treatment that is under investigation outside of a clinical trial. I would say, as I said before, our usual answer to those requests is yes. Sometimes these are individual cases

that come to us, and sometimes investigators have a program of

making drugs available for such uses.

The one case where we are inclined to say no is when there is

an existing therapy that is surely lifesaving and possibly even if it

is clearly life-prolonging. And in the cases that you are talking

about, we thought that people were going to be denied therapy that

had significant cure potential. Those are the only two cases, where,

to my best knowledge, we have denied them.

Mr. BURTON. Well, I do not want get into a debate about that.

Dr. TEMPLE. I realize there was a debate about that.

Mr. BURTON. Yes, a big debate. But anyhow, go ahead.

Dr. TEMPLE. Right. But I understand there can be differences of

view about whether the toxicity is worth it and a variety of other

questions. But that is the one case where we have trouble.

If one—I am not going to talk about C225, but if we were looking

at someone who wanted to use a drug for colorectal cancer that had

not been well studied but looked promising, we would certainly ask

whether the person had already received fluorouracil-leucovorin

and CPT–11, two treatments that are known to improve survival.

So we would think, at least initially, that it would not be sensible

not to use those first. Now that could be——

Mr. BURTON. Would you deny them access then to the new experimental drug? Because Dr. Waksal said a while ago they are going

to start a new clinical trial on people that did not take chemotherapy.

Dr. TEMPLE. Yes. We are enthusiastic about the trial. And he

also did not say that it was being combined with chemotherapy in

that case, which it is.

Mr. BURTON. It is going to be combined with chemotherapy?

Dr. WAKSAL. Yes, it is.

Dr. TEMPLE. Yes, that would be the usual thing to do. You do

not——

Mr. BURTON. What if the patient does not want chemotherapy,

they cannot get into the clinical trial, they cannot take that C225?

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Dr. TEMPLE. I think that our first responsibility is to get the

drug approved, they patients then and physicians can make available the drug to those patients who do not want chemotherapy. But

this drug works best, like other anticancer agents, in combination

therapies, and when we see it being used in combination with radiation or in combination with other antineoplastic agents, we really

get the most dramatic types of responses.

Mr. BURTON. I see Dr. Weldon has joined us. Did you have any

more comment before we yield to Dr. Weldon? Dr. Weldon, do you

have any questions?

Dr. WELDON. Yes, I do, and I want to thank you, Mr. Chairman,

for calling this hearing. I was unfortunately tied up in another

committee on some space policy issues, which as you know, is very

important for the District that I am in.

But this—I have been—it is kind of been there and done that.

I have seen these cases where you have patients with a problem

that could possibly benefit from a clinical trial drug and does not

meet the qualifications for the clinical trial for a variety of reasons

and is denied. And do we need to seriously look at—maybe I will

ask you, Dr. Temple. You are with FDA, I understand.

Dr. TEMPLE. Right.

Dr. WELDON. I would imagine FDA is coming under increasing

pressure, and NIH, on this issue, as the proliferation of the Internet and the health care consumers, cancer patients getting much

more knowledgeable of what trials are out there and what drugs

are available. Now today, that Internet is so amazing, anybody

could sit down in their living room, particularly if you have a highspeed access, and you can just get incredibly well educated. Literally, what you used to have to hire staff or professionals to research for you, poring through libraries, you can access in minutes.

And do we need to consider changing policies either at the administrative level or the law, to allow more compassionate use of these

compounds?

Dr. TEMPLE. Well, far be it from me to comment on whether you

need a new law without direction from the Department, but our

current policies are very permissive on those matters, as my testimony says. Once a drug looks interesting and promising, there are

many ways to make it widely available if a sponsor wants to. But

as Dr. Waksal has pointed out, there may be impediments to that,

availability of the drug, dilution of their own resources.

And also you could ask about doing it fairly. Any individual case

of a person who has failed other therapy is obviously evocative, as

we have all heard, and quite terrible in many ways.

The question though that comes further is, if you took all people

who had failed the available therapy for colorectal cancer, which

unfortunately is most people with metastatic colorectal cancer, do

we have enough information to make the drug available to all of

them even before the studies are well along? That is a difficult

question. I am not trying to tell you what the answer is, but we

have a system that says that there is supposed to be a certain

amount of evidence before you essentially make the drug available

to the whole population. That is a difficult question.

I actually think that is less of a problem than one might wonder

whether it would be, because the number of drugs that sort of look

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exciting like that at any given time is modest. That is unfortunate

in some sense, because you would like to have more of them. But

for the few drugs that are getting people very excited at the oncology meetings, I believe the system can cope with them, but people

have to be willing and able, and as Dr. Waksal just said, they were

not able. They did not have the drug.

Again, I cannot speak for the particular case, but this is a drug

where an application is imminent or with us? An application is imminent. They finished phase 3 studies, and there appear to be responses. The definition of what is acceptable for a treatment protocol or a treatment IND it has finished all its trials and looks promising in the trials, and treats something that has no other treatment. Well, people who have exhausted standard therapy for

colorectal cancer have no other treatment, so it could very well

meet the requirements for treatment IND. Again, I am not trying

to speak for the Center for Biologics.

But those mechanisms are available to be used. It is not that the

criteria are onerous or anything like that. In fact, you are even allowed to sell the drug.

Dr. WELDON. So these stories that get in the press, they are the

exception?

Dr. TEMPLE. Well, again, I am not going to say that because I

cannot say I know the entire experience. I am sure there are people

who are frustrated by the fact that they have exhausted available

therapy and have nothing to seek. Well, sometimes that is because

there is not anything reasonably well developed to seek. But where

there is, where, as I said, it is sort of exciting people at ASCO,

whether it is Gleevec, it is C225, there are mechanisms to make

those drugs widely available, and we encourage them to be widely

available. There is no reticence on FDA’s part; there really never

has been.

And such arrangements do exist, but, you know, distributing the

drug to 10,000 people one-by-one, investigator-by-investigator, is a

lot of work for a drug company. They may or may not want to do

it, and they want to devote their resources to gaining approval and

making the drug available to everybody. It is a complex judgment.

I would not want to have to make it for them.

Ms. DELANEY. May I add to that? From the cancer patient advocacy community perspective, this whole issue—and I think in other

disease areas as well—there is unanimity of agreement, that a

much broader public discussion needs to be had because there are

so many questions that are—some are beyond our agency’s authority. The ethical issues that are involved here, disease by disease

differences. I mean, it is interesting to see. In the advocacy community, the positions are more rigid in opposition to compassionate

use in the disease areas where there are a lot of treatment options.

But in the disease areas where there are fewer treatment options,

they have much more liberal views about this. And so it is something that, you know, that a lot of the advocates feel needs a much,

much larger discussion that would involve the government, the industry, and the patient advocacy community in many disease.

Dr. WELDON. Thank you, Mr. Chairman.

Mr. BURTON. Thank you.

Mrs. Davis, you have any more questions right now?

136

I have a few more questions. It is going to take a little bit of

time. In other countries, there is different therapies and treatments

that are being utilized today that have not yet been approved by

the Food and Drug Administration in this country. Many patients

are going to other countries because they want to try these other

therapies which have not been approved by our health agencies.

Do you share any information or talk to these other countries

like Germany or other countries where they are providing treatments which have—some of them have some pretty good track

records because we checked into those? Do you talk to them? Do

your health experts at FDA and HHS communicate with them at

all?

Dr. TEMPLE. We do not necessarily talk to them about a specific

drug that is available. What triggers our interest generally is an

application from a company to market a drug or to study it. If

there are drugs that are very promising that are not even under

study in the United States, I am not aware of any. We are aware

of some drugs that are marketed elsewhere that have for one reason or another not been approved. And we are committed, actually,

to encouraging a manufacturer of any drug that looks promising

abroad and that is not here, to come in. We have only a limited

capacity to be encouraging. Nobody has to come to us if they do not

want to, but in the cancer program we outlined some years ago, we

made a commitment to do that. And we have not found very many

that we are not aware of or that are not at least under study here.

But, you know, you may have found some we do not know about.

Mr. BURTON. You serve as adviser to the National Center for

Complementary and Alternative Medicine, do you not?

Dr. TEMPLE. I am one of our representatives, right.

Mr. BURTON. How much involvement have you had with offering

advice on research to them?

Dr. TEMPLE. Well, when people want to study an alternative

therapy and submit an IND to us, which we encourage them to do,

we definitely give advice on how to do the trials and how to make

them optimal. I can give one example. It is outside the oncology

area. When the NIMH, in conjunction with NCCAM, wanted to

study St. John’s Wort for depression, they came to us with a trial,

and they were going to do a direct comparison of St. John’s Wort

and placebo. We advised them that they ought to include an active

control standard agent as a treatment also because we knew that

many trials of good design cannot tell active drugs from placebo.

So they are doing a three-arm trial that will give a much more definitive answer than the recent trial that compared St. John’s Wort

with only placebo. So we try to give the best advice we can.

Mr. BURTON. Do you think patients should have the right to go

completely alternative in their treatment of cancer, or should they

go with a conventional treatment, chemotherapy, radiation?

Dr. TEMPLE. Well, they have the right. I mean, these things are

available.

Mr. BURTON. I was asking your opinion.

Dr. TEMPLE. Oh, I think they should have the right as a sort of

freedom issue, and in any event, the law allows them that right.

So do I think it is wise, is a different question? But I think I will

not offer a comment.

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Mr. BURTON. Do you remember the young man we were talking

about a little bit earlier, Thomas Navarro? His parents and he

wanted to have that right, and they were denied that right and had

to go through the other processes.

Dr. TEMPLE. Well, I probably misspoke. This is a drug, although

it is alternative in some sense. It is a drug that is being studied

for its ability to treat cancer. And it has been—its use has been allowed in hundreds of people despite not a great deal of evidence of

effectiveness, and we have not tried to discourage that at all.

Mr. BURTON. Only after the traditional therapies were used.

Dr. TEMPLE. Or if there are not good therapies. There are many

tumors where there are not good therapies. The cases where we

have objected were where curative therapy was being denied.

Again, I accept the idea that people can disagree on that, but I

think our principles were fairly clear.

Mr. BURTON. There may be disagreement, but when you are the

person that has the cancer of the pharynx or the husband or the

wife of the person that has the cancer, it takes on a little different

dimension. The former head of HHS had one view of a cancer therapy treatment when he was Governor. Then when his wife became

ill with cancer, he tried all these other treatments that were not

approved because he wanted to save her life. So, you know, when

your ox is gored, it is a little bit different.

For instance, let us take you for instance. Are you married?

Dr. TEMPLE. Yeah.

Mr. BURTON. If you are married and conventional treatment is

not helping your wife and she is going to die, would you try other

things?

Dr. TEMPLE. Well, that is not the question we are talking about

here. We have not hesitated to allow the treatment you are talking

about in people who have exhausted other therapy.

Mr. BURTON. After they have exhausted other therapies.

Dr. TEMPLE. Well, that is what you asked me about. If my wife

had something and had not responded to available therapy, would

I try something else? My answer is I probably would not, but I am

mulish that way, and besides, she would be the one to decide. That

is how it works in my house anyway.

Mr. BURTON. Do you think an individual ought to be allowed to

opt out of chemotherapy and radiation, and then go straight to

treatments while they are experimental, that might be less toxic?

Dr. TEMPLE. Well, again, when that issue has arisen, where the

therapy is importantly effective—this is what I am talking about—

there are many cancer therapies where the effect is modest or uncertain, and we have not insisted that people try those. It is only

where the available treatment was curable. In the two cases we are

talking about, the cancers were curable by available therapy. That

is not a very common situation in widespread cancer, unfortunately.

One was Hodgkin’s disease and one was a malignant glio. So, you

know, we just could not, as physicians and as regulators, think

that was reasonable.

Mr. BURTON. Have you heard of the National Foundation for Alternative Therapies?

Dr. TEMPLE. I am not sure.

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Mr. BURTON. A former colleague of ours is the head of that, and

I think they have examined, I think, 73 different clinics and facilities around the world that provide alternative therapies, and they

found some that have some fairly great results, one in particular

in Germany that has been very successful. And I guess the question I asked a while ago I would like to ask again, how do you communicate with these other clinics and other facilities around the

world that may have had some success by using a different approach to dealing with things like cancer?

Dr. TEMPLE. Well, again, what triggers our interest in something

is that someone wants to use it here, wants to use it under an investigational program or market it. When they do that, they bring

forth the data that they think supports this use. We strongly encourage investigation of alternative methods or bringing the data

and seeing whether it needs to be investigated further. We are,

perhaps surprisingly, non-dogmatic about theories of cure. We are

skeptical about all of them. So we like to see people bring forth the

data, and alternative treatments can be studied just as regular

ones can.

Mr. BURTON. But there is no outreach program. I mean, you wait

till they come to you with alternative or complementary or new

therapies or new—there is no program by FDA to reach out to

other facilities and other governments around the world that may

have tried a different approach that has been successful. And I

guess my question is: why is that? It seems to me that that might

be a resource that our health agencies haven’t been tapping. Why

would you not talk to the people over in Germany, or England, or

France or other countries, Spain, where they have had some very

positive results with other therapies? Why do you wait until they

come to the United States and have to go through the bureaucracy

of the FDA?

Dr. TEMPLE. Well, our bureaucracy with respect to studying

things is de minimis. It is very easy to get into clinical trials, and

someone has to want to do that.

Mr. BURTON. I understand, but they have been in this clinical

trial mode since 1995. We are 6 years later. Hundreds of thousands

of people have died from colon cancer probably during that time period. If there is a facility in Germany or someplace else that has

had some success with that, why isn’t there an outreach program

that would eliminate a six or 7-year delay while clinical trials are

going on? Why would we not at least try to find out about it?

Dr. TEMPLE. I am not following that. This is how long it has

taken to develop C225.

Mr. BURTON. He said that they started the clinical trials, did you

not say, in 1995?

Dr. WAKSAL. That is correct.

Mr. BURTON. OK. 1995. It is 6 years. It takes a long time for a

drug to be improved even if the efficacy of it is proven. It takes a

while. It takes about 5 or 6 years. And so what I am—— Dr. TEMPLE. Wait, wait, wait. We have got to be sure we are

talking about the same thing.

Mr. BURTON. Well, it takes that long—— Dr. TEMPLE. No. They have been developing the data. They have

only treated 700 people in those 6 years. That is how long it has

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taken them to get data on 700 people. The approval process, once

they submit the data to us, nowadays for a drug that is so-called

fast-tracked or priority review, is something like 6 or 7 months. I

know that for people who are impatient and waiting, even that is

long, but it is not 5 years. The time it takes is to develop the data,

and nobody knows how to do that much faster than it gets done

now. You have to accumulate patients, and you have to start small

and get larger and so on, so that is what we do.

I have to say, if there are curative treatments for colorectal cancer out there, and somebody is hiding them in a clinic, that would

be a really strange thing. I mean, it is a dreadful disease—— Mr. BURTON. No. I am not saying they are hiding in a clinic, but

they have had some success—— Dr. TEMPLE. Well, how would we not know that? I mean, there

must be publications or something. Where is this drug? What could

it be that is curing colorectal cancer and nobody knows about it?

I am skeptical of the existence of those things.

Mr. BURTON. But there is no communication outreach program

from FDA to other governments and other facilities around the

world.

Dr. TEMPLE. We are trying to encourage study of any drug that

is marketed in other countries for cancer. We are interested in

them and have explored how to get it studied. And there are a few

drugs that are approved abroad that are under study.

Mr. BURTON. I am not necessarily just talking about drugs. I am

talking about alternative approaches to—in a yes or no answer,

there really is no outreach or communication program with other

countries and other health—and their health agencies?

Dr. TEMPLE. Well, the answer is no on that question. The other

health agencies do not approve alternative medicines in the same

way as they approve drugs. It is a different system. They do make

botanicals available in Germany in a fairly well characterized way,

but it is not the drug regulatory authority that does that. It is a

different group.

Mr. BURTON. I know. I guess we are splitting hairs here. The

question is if they have a success rate, it seems to me it would be

something that our health agencies would at least take a look at

to see if it could be applicable to people here in the United States.

Let me just ask a couple more questions, then I should be—do

you have any questions? I do not want to monopolize this.

We have been told that companies are owned—sir?

Dr. WELDON. Sorry to interrupt. I did have a sort of a followup

to what you were getting into before.

Mr. BURTON. Sure, go ahead.

Dr. WELDON. I have a little bit of experience in this arena, but

just for the record—and maybe Dr. Waksal can talk about this—

and you alluded to it, Dr. Temple. The time it takes to accumulate

the data. You know, I worked on a drug for ovarian cancer when

I was in medical school, and maybe you can just elaborate on this

a little bit. It is not like you can just go to Wal-Mart and accumulate patients.

Dr. WAKSAL. No, you are absolutely correct. We started our clinical trials in January 1995, and first had to show, both for ourselves

and the FDA, that the drug was safe by itself, and we had a small

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cohort of patients that we treated to show safety and see if there

was any hint of biologic efficacy, whether the drug was working at

all. And as we went forward, we saw that the drug was safe eventually, and we began to use it in a number of different situations,

in combination with almost every chemotherapeutic agent out there

and in combination with radiation. And over—— Dr. WELDON. If I can interrupt you, you could not use the drug

unless somebody failed other treatments, correct? You could not

just——

Dr. WAKSAL. That was not the case, actually. First we went into

patients that had failed prior therapies. But then we put together

trials, for example, in patients that had local, regional—that were

receiving radiation for local, regional disease with head and neck

cancer, that were not surgical candidates, but had not had metastatic spread of that disease. And we used it in combination with

radiation in that patient population before we went off into phase

III studies, to prove statistically that our drug worked in combination better than radiation alone. And we are doing that. And that

trial is moving along.

Dr. WELDON. So you have to accumulate a large enough statistic

sample and you have to have controls and it just takes time for

those patients to come into the system.

Dr. WAKSAL. Absolutely. I mean, one of the things that we have

done, and it is because of the FDA guidelines on unmet medical

needs, is in the colorectal study, we really were not using our drug

in colorectal cancer initially, and it was actually because of the

compassionate use situation with Shannon Kellum and her physician that we learned that our drug had activity, significant activity

in colorectal cancer. We then began a clinical study to see whether

or not in a patient population that ended up being about 139 patients, whether or not in that patient population, where we could

ascertain in statistically significant fashion that this drug was

working. We began that trial last February. We completed enrollment in that trial at the end of last July. We closed the sort of statistical timeframe at the end of January, and we are going to be

imminently filing for approval for that particular indication. So

that is the period of time that it has taken for this particular indication to go through the process from enrollment to completion of

the clinical package. We presented that data at the cancer meetings in May. We are about to file and begin the biologics application process with the FDA, and hope that it will be one that will

be rather expeditious.

Ms. DELANEY. May I just say something about—you are talking

about recruitment, at least alluding to it. And while it was not particularly an issue with C225, the cancer patient advocacy community is deeply concerned about the issue of adult recruitment to

cancer clinical trials. The statistics that is used most often is between 3 and 5 percent of adult cancer patients end up in a trial.

In pediatric cancer, that number is roughly 70 percent. It is at

least 70 percent. And many believe that is the reason that we have

the breakthroughs that we have had in the childhood cancers. This

is a subject that has been studied a lot, about why recruitment is

so difficult. And a lot of studies have been done on it, and there

are a list of reasons, but it is a very difficult problem.

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Dr. WELDON. You wanted to add something?

Dr. TEMPLE. Yes. There is a quirk in the system that tends to

get people late in disease studied sooner than people early in disease. Some years ago, actually, Dr. Waksal referred to this, we

made it clear that we were prepared to approve drugs for refractory

patients, people who have exhausted other options, on the basis of

tumor response alone, that is, shrinking the tumor. Now, tumor response is a surrogate end point that suggests a reasonable likelihood of patient benefit, but it really does not demonstrate it. It is,

however, much easier to demonstrate an effect on tumor size than

it is to show that you have actually improved survival.

Dr. WELDON. So you are talking about you doing a scan or an

ultrasound, some measure—— Dr. TEMPLE. Yeah, right. Shrink the tumor by 50 percent.

Dr. WELDON. Shrinkage, no demonstration of, per se, improved

survival or clinical improvement.

Dr. TEMPLE. Right.

Dr. WELDON. Just purely in imaging.

Dr. TEMPLE. Right. In contrast for approval as initial therapy for,

say, colorectal cancer, we would ask that people show that there is

improved survival or improved symptomatic benefit or something

like that. It is much harder to do those studies. They take longer,

so they are generally left for later. It is not that people ignore that

population, and it is not that if the drug were available, someone

could not use the drug in that population also, but the quickest

route to approval is through treatment of refractory patients. You

could also say they are the most needy in some sense too. So I am

not arguing that is irrational or unreasonable, what we do, but

that is partly why it happens.

Dr. WAKSAL. And that is exactly the approach we have taken,

first to look at that population of unmet medical need, and now

moving forward into first line of therapy, and going to be initiating

a much larger clinical study sowing survival benefit.

Dr. TEMPLE. But if they had wanted to make their first trial

standard therapy plus—not their first trial, but their first clinical

trial—standard therapy plus or minus C225, in the control trial, I

do not want to speak for biologics, but in a drug setting, we would

not object to that. It is OK. But that is a much harder trial to do.

Dr. WELDON. Ms. Delaney, I just want to get back to the issue

you were talking about, the pediatric cases. Could it be that the

vast majority of pediatric oncology cases end up at pediatric teaching hospitals?

Ms. DELANEY. Yes.

Dr. WELDON. Versus adult cancers treated at the community hospital level?

Ms. DELANEY. Well, the pediatric oncology community was real

smart back in the 1960’s. They all got together. They said, ‘‘Look,

you know, we only represent a small percentage of the cases, like

there are 10,000 cases of pediatric cancer in this country out of 1.2

million this year.’’ So if you have got that many, you know, at St.

Luke’s you have got four kids with leukemia and then you have

three with Hodgkin’s disease out here, you know how are we going

to get—so that pediatric oncology community got together and they

formed a cooperative group, and they started——

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Dr. WELDON. Nationwide?

Ms. DELANEY. Yes. And they started pretty much every kid on

a trial, which has resulted in huge breakthroughs in Hodgkin’s disease, in leukemias. You know, not necessarily cures, but way up in

the high percentages of survival with metastatic disease.

What the adult cancer advocacy community wants to do is

achieve those same kinds of cooperations to improve recruitment.

I remember reading—I wish I could get the citation. I cannot find

it again, but after animal studies, the most time consuming aspect

of cancer drug development is the recruitment to the phase 3 trial.

I mean, a drug like C225 is very unusual in the amount of publicity that it has gotten and the attention. So, no, it is not hard to

recruit to a trial like that. But there are some other promising

drugs out there that nobody knows about, that are struggling to try

to get patients to the trial, and also National Cancer Institute

trials, which are new combinations of already approved treatments

that deserve attention. So it is something that the advocacy community is very focused on, that we spend a lot of time in our office

with them on, and with the pharmaceutical industry.

Dr. WELDON. Thank you, Mr. Chairman.

Mr. BURTON. Did you have any more questions, Mrs. Davis?

Mrs. JO ANN DAVIS OF VIRGINIA. I guess something Ms. Delaney

just said struck a chord. You said there is a lot of drugs out there

that would love to have recruitment. But wasn’t that the very thing

that we were asking the question, how do these people know that

there are drugs out there? I mean, we are going back to the same

thing. You know if you had cancer and knew that there was an experimental drug out there, you would certainly want to be recruited I would think.

Ms. DELANEY. Well, one of the ways is for the pharmaceutical industry to place their drug trials in a public access data base and

that is one of the FDAMA laws or rules, section 113, is that once

a drug reaches the point of looking into efficacy, that drug, in life

threatening diseases, needs to be added to a public access data

base. And right now in the National Cancer Institute’s data base

there are about 1,835 clinical trials. Only—well, really, the number

right now is exactly 184, are from the pharmaceutical industry. We

know that here—you know, just abstractly, that there are many,

many more drug trials out there in cancer than that. So we need

to have better cooperation. We are working with them. There is a

draft guidance out for the pharmaceutical industry to use, but we

need to have more of their input—that is how people will learn

about what those drugs are, what trials are out there, is if there

is better cooperation with making the information available at least

at phase 3.

Mr. BURTON. Would you yield to me just a minute? FDA has all

kinds of regulatory authority. Why cannot you just tell or pass a

regulation over there, which you do quite frequently, and say that

the pharmaceutical companies have to do that so that the information is available through FDA to be able to be put on the Internet?

I mean, why say, well, they are out there and they are not telling

us all that stuff. Why don’t you just say that they have to do that.

Ms. DELANEY. Well, there is a draft guidance and it is process

that is——

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Mr. BURTON. Wait a minute. It is a draft guidance and it is in

what process?

Ms. DELANEY. There is a process, and a draft guidance has been

developed, and you know, we have received responses from industry, and it is incorporated. But in the meantime, the advocacy community—and I am not speaking for FDA right now—the advocacy

community has been asking them to cooperate, and it has been difficult.

Mr. BURTON. Who has been asking—you have been asking the

pharmaceutical companies to cooperate?

Ms. DELANEY. Yes.

Dr. TEMPLE. Well, why doesn’t FDA tell them to cooperate? Well,

actually, you told them to. FDAMA has a clear obligation for them

to do it.

Mr. BURTON. Well, if they were told to do it, why are they not?

Are they violating the law?

Dr. TEMPLE. I do not fully know the answer to that. We will find

out what the difficulties are. I cannot tell you off the top of my

head.

Mr. BURTON. Well, the information is extremely important, and

I think the gentlelady asks a very important question. If that is out

there, and there is new therapies and new processes that can be

utilized to help people fight cancer, it is almost criminal not to let

all that information be put on the Internet, or in some way to communicate.

Do you have any other questions?

Mrs. JO ANN DAVIS OF VIRGINIA. Well, I just wonder, are we not

letting the oncology doctors know about it, so that they can give the

information to their patients?

Dr. TEMPLE. My experience is most oncologists, especially at good

centers, are very aware of the latest drugs that look exciting, but

if something is below that level, they may not. I think we have to

find out why not as many things are getting on that site as we

think should, and I do not know the answer. We will look into it.

Mrs. JO ANN DAVIS OF VIRGINIA. Thank you.

Mr. BURTON. We will be following up on this, I promise you. We

will followup on it, we will make sure, and I want to thank you

gentlemen for being here to tell us your stories.

I have two more questions quickly, and then what I would like

to do is submit to you questions for the record because I do not

want to keep you here past midnight, so if you would accede to our

wish to answer some questions we submit to you in writing, we will

not ask you all those questions now.

And, Dr. Waksal, I appreciate very much your candidness with

us today, your candor. You have been very helpful. And I just wish

that there was more ability for you to produce more of your product

so that people could use it for compassionate use. I just—it seems

like to me if it is that effective, it is just a shame that you are not

in that mode yet. But we appreciate your candor.

Dr. WAKSAL. We are working as hard as we can to take care of

that situation.

Mr. BURTON. Well, good. Two questions. We have received a

number of complaints from families, who when reviewing cancer research papers, are dismayed that researchers report patients as

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successes from the treatment even when the patient dies. How can

families be secure that a treatment offers hope when reducing a

tumor is more important than keeping a patient alive in research?

I mean if the patient dies, how can it be a positive in the research?

Dr. TEMPLE. Well, there is a difficult and unpleasant reality in

the treatment of solid tumors that are metastatic, and that is that

cures are extremely rare, even for drugs we consider promising.

The standard therapy, initial therapy for colorectal cancer is

fluorouracil-leucovorin. Now you add a drug called CPT–11.

Mr. BURTON. Chemotherapy.

Dr. TEMPLE. Chemotherapy. Surgery, if you can get the tumor

out, those are sometimes cures, and that is fine. But if the tumor

metastatic, and if it is not removed by the surgery, mortality is almost universal.

Mr. BURTON. In what timeframe?

Dr. TEMPLE. Oh, that varies very much depending on the tumor.

It could be 12 months for some as an average, and it could be 3

years for others. Breast cancer is famous for being much longer.

Success is—it depends on how the study defined it. Success may

mean they shrank the tumor by 50 percent for a period of a certain

number of months. Now, you might not think that is very important if the person then goes on to die at 6 months, and I would not

disagree with you, but it is a proper measure of tumor activity. One

of the things we have learned in other parts of oncology in the

treatment of leukemias and things like that is sometimes you can

find one drug that does a little something, another drug that does

a little more, and put them together and you start to see responses

that are better than you would have predicted from the others, and

that is what everybody is dreaming about.

But so far the treatment of metastatic solid cancers, except for

some odd things like testicular, is grim.

Mr. BURTON. You know, it seems to me that there ought to be

a way to clarify that when you do your statistical analysis. I mean

if a person is judged to be cured for a cancer and they die in 6

months—— Dr. TEMPLE. They are not judged as cured.

Mr. BURTON. Well, whatever the—— Dr. TEMPLE. Well, the usual endpoint in a cancer trial that is

looking at mortality is whether you have delayed death. That is the

endpoint.

Mr. BURTON. Well, then should it not be more clearly defined and

clarified?

Dr. TEMPLE. I would have to see the things that people are upset

about, but——

Mr. BURTON. The reason I say that is because people base their

decisionmaking process on what kind of treatment to get for themselves and their families based upon the statistical data that you

give them, and that is given by FDA to the doctors. You know, because doctors all the time quote, well, 50 percent of these people

live 5 years and 60 percent live this long, and that statistical data

is very, very important and it should be very clear and accurate.

Dr. TEMPLE. Well, I completely agree. The usual measure in a

clinical trial is—well, there is a complicated statistical analysis to

determine whether there was an improvement, but the convenient

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number one gives is median survival. That is how long the average

patient lived. You look at how long the average patient who did get

the drug lived, and you look at how long the patient who did not

get the drug lived. And if you see a difference, that is an improved

survival.

To the extent anybody believes that is cure, they are not understanding the data.

Mr. BURTON. Well, is that explained in the data, that the survival rate is increased by 3 months or 6 months because this drug

was used?

Dr. TEMPLE. All of our labeling would have a figure of something

like that, yes.

Mr. BURTON. One more question, then I will let you go, and I do

appreciate your patience.

I think, Dr. Temple, you stated that doctors are generally aware

of investigational drugs that might benefit their patients. But various reports suggest that fewer than 5 percent of primary care physicians have ever referred a patient to a clinical trial, and far fewer

than half of the physicians associated with teaching hospitals have

referred a patient to a clinical trial. In fact, a member of my staff,

who wrote this question, who was in a clinical trial for a leukemia

drug, did not learn about the drug he is testing, which is called

Gleevec, previously called STI571. He did not learn about that from

his doctor or from a government sanctioned Web site. He learned

about it by an informal Web site that was established by a patient

who was successfully treated in an earlier phase of the drug trials.

His primary care physician knew nothing about it. His oncologist

was somewhat aware of the drug, but vigorously discouraged him

from applying for a clinical trial, stating, ‘‘That drug is in short

supply, and they are not going to waste it on someone of your age.’’

In view of that, do you not agree, Dr. Temple, that a lot of work

remains the help doctors become generally aware of the investigational drugs that might benefit their patients, and thus the Web

site information?

Dr. TEMPLE. Yes. We are very enthusiastic about that. I think

the points that have been made earlier about making sure Web

sites contain these things is important. I actually do not have any

belief that the average doctor necessarily knows about the latest

cancer chemotherapy. I do think most oncologists do know about

the more prominent and promising things. But I think for the family practitioners who may be serving a lot of people, at least initially, more information does need to be available.

Mr. BURTON. Well, let me thank you all. Any more questions?

Well, first of all, thank you very much for being here. Thank you

for your patience. I know it has been a long day. And Dr. Waksal,

thank you very much. Thank you for being here. And we will be

in touch with you for further hearings down the road. Thank you

very much.

We stand adjourned.

[Whereupon, at 5:05 p.m. the committee was adjourned.]

[Additional information submitted for the hearing record follows:]

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