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[House Hearing, 107 Congress]
[From the U.S. Government Publishing Office]

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
                                _______

                  U.S. GOVERNMENT PRINTING OFFICE
76-914                     WASHINGTON : 2002

____________________________________________________________________________
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                     COMMITTEE ON GOVERNMENT REFORM

                     DAN BURTON, Indiana, Chairman
BENJAMIN A. GILMAN, New York         HENRY A. WAXMAN, California
CONSTANCE A. MORELLA, Maryland       TOM LANTOS, California
CHRISTOPHER SHAYS, Connecticut       MAJOR R. OWENS, New York
ILEANA ROS-LEHTINEN, Florida         EDOLPHUS TOWNS, New York
JOHN M. McHUGH, New York             PAUL E. KANJORSKI, Pennsylvania
STEPHEN HORN, California             PATSY T. MINK, Hawaii
JOHN L. MICA, Florida                CAROLYN B. MALONEY, New York
THOMAS M. DAVIS, Virginia            ELEANOR HOLMES NORTON, Washington, 
MARK E. SOUDER, Indiana                  DC
JOE SCARBOROUGH, Florida             ELIJAH E. CUMMINGS, Maryland
STEVEN C. LaTOURETTE, Ohio           DENNIS J. KUCINICH, Ohio
BOB BARR, Georgia                    ROD R. BLAGOJEVICH, Illinois
DAN MILLER, Florida                  DANNY K. DAVIS, Illinois
DOUG OSE, California                 JOHN F. TIERNEY, Massachusetts
RON LEWIS, Kentucky                  JIM TURNER, Texas
JO ANN DAVIS, Virginia               THOMAS H. ALLEN, Maine
TODD RUSSELL PLATTS, Pennsylvania    JANICE D. SCHAKOWSKY, Illinois
DAVE WELDON, Florida                 WM. LACY CLAY, Missouri
CHRIS CANNON, Utah                   DIANE E. WATSON, California
ADAM H. PUTNAM, Florida              ------ ------
C.L. ``BUTCH'' OTTER, Idaho                      ------
EDWARD L. SCHROCK, Virginia          BERNARD SANDERS, Vermont 
JOHN J. DUNCAN, Tennessee                (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

                            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

 
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.
    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 experimental drugs that Abigail's 
oncologist thought would be helpful.
    Fred Santino's wife, Ruth-Ann, fought a 2\1/2\ 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 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:]

    [GRAPHIC] [TIFF OMITTED] T7088.014
    
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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 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.
    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 established, 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 
understand 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.
    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.
    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 or not to take an experimental drug, would want to know 
if previously 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 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 
case-by-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?
    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 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.
    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?
    Mr. Santino. I claim to be an expert on Web sites, I guess 
self-proclaimed. But I run four Web sites myself. No, they are 
not helpful 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 7\1/2\ 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.
    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?
    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 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 extremely 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 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 vacation.'' ``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?
    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 
partnerships, 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 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.''
    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 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 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 single-patient 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 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 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 
3\1/2\, and we used to try to get companies to, as they are 
getting their marketing application ready to submit to us, make 
the drug more widely available 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.
    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 third-party 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 program 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?
    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 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?
    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-year-old, 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 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 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.
    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 
everybody 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?
    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 high-speed 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 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?
    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.
    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.
    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 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 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.
    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----
    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----
    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 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 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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