RU–486: DEMONSTRATING A LOW STANDARD FOR

WOMEN’S HEALTH?

HEARING

BEFORE THE

SUBCOMMITTEE ON CRIMINAL JUSTICE,

DRUG POLICY, AND HUMAN RESOURCES

OF THE

COMMITTEE ON

GOVERNMENT REFORM

HOUSE OF REPRESENTATIVES

ONE HUNDRED NINTH CONGRESS

SECOND SESSION

MAY 17, 2006

Serial No. 109–202

Printed for the use of the Committee on Government Reform

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RU–486: DEMONSTRATING A LOW STANDARD FOR WOMEN’S HEALTH?

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RU–486: DEMONSTRATING A LOW STANDARD FOR

WOMEN’S HEALTH?

HEARING

BEFORE THE

SUBCOMMITTEE ON CRIMINAL JUSTICE,

DRUG POLICY, AND HUMAN RESOURCES

OF THE

COMMITTEE ON

GOVERNMENT REFORM

HOUSE OF REPRESENTATIVES

ONE HUNDRED NINTH CONGRESS

SECOND SESSION

MAY 17, 2006

Serial No. 109–202

Printed for the use of the Committee on Government Reform

(

Available via the World Wide Web: http://www.gpoaccess.gov/congress/index.html

http://www.house.gov/reform

(II)

COMMITTEE ON GOVERNMENT REFORM

TOM DAVIS, Virginia, Chairman

CHRISTOPHER SHAYS, Connecticut

DAN BURTON, Indiana

ILEANA ROS-LEHTINEN, Florida

JOHN M. MCHUGH, New York

JOHN L. MICA, Florida

GIL GUTKNECHT, Minnesota

MARK E. SOUDER, Indiana

STEVEN C. LATOURETTE, Ohio

TODD RUSSELL PLATTS, Pennsylvania

CHRIS CANNON, Utah

JOHN J. DUNCAN, JR., Tennessee

CANDICE S. MILLER, Michigan

MICHAEL R. TURNER, Ohio

DARRELL E. ISSA, California

JON C. PORTER, Nevada

KENNY MARCHANT, Texas

LYNN A. WESTMORELAND, Georgia

PATRICK T. MCHENRY, North Carolina

CHARLES W. DENT, Pennsylvania

VIRGINIA FOXX, North Carolina

JEAN SCHMIDT, Ohio

——— ———

HENRY A. WAXMAN, California

TOM LANTOS, California

MAJOR R. OWENS, New York

EDOLPHUS TOWNS, New York

PAUL E. KANJORSKI, Pennsylvania

CAROLYN B. MALONEY, New York

ELIJAH E. CUMMINGS, Maryland

DENNIS J. KUCINICH, Ohio

DANNY K. DAVIS, Illinois

WM. LACY CLAY, Missouri

DIANE E. WATSON, California

STEPHEN F. LYNCH, Massachusetts

CHRIS VAN HOLLEN, Maryland

LINDA T. SANCHEZ, California

C.A. DUTCH RUPPERSBERGER, Maryland

BRIAN HIGGINS, New York

ELEANOR HOLMES NORTON, District of

Columbia

———

BERNARD SANDERS, Vermont

(Independent)

DAVID MARIN, Staff Director

LAWRENCE HALLORAN, Deputy Staff Director

TERESA AUSTIN, Chief Clerk

PHIL BARNETT, Minority Chief of Staff/Chief Counsel

SUBCOMMITTEE ON CRIMINAL JUSTICE, DRUG POLICY, AND HUMAN RESOURCES

MARK E. SOUDER, Indiana, Chairman

PATRICK T. MCHENRY, North Carolina

DAN BURTON, Indiana

JOHN L. MICA, Florida

GIL GUTKNECHT, Minnesota

STEVEN C. LATOURETTE, Ohio

CHRIS CANNON, Utah

CANDICE S. MILLER, Michigan

VIRGINIA FOXX, North Carolina

JEAN SCHMIDT, Ohio

ELIJAH E. CUMMINGS, Maryland

BERNARD SANDERS, Vermont

DANNY K. DAVIS, Illinois

DIANE E. WATSON, California

LINDA T. SANCHEZ, California

C.A. DUTCH RUPPERSBERGER, Maryland

MAJOR R. OWENS, New York

ELEANOR HOLMES NORTON, District of

Columbia

EX OFFICIO

TOM DAVIS, Virginia HENRY A. WAXMAN, California

MARC WHEAT, Staff Director

MICHELLE GRESS, Professional Staff Member

MALIA HOLST, Clerk

RICHARD BUTCHER, Minority Professional Staff Member

(III)

C O N T E N T S

Page

Hearing held on May 17, 2006 ............................................................................... 1

Statement of:

Harrison, Donna J., M.D., member, Mifeprex Subcommittee of American

Association of Prolife Obstetricians and Gynecologists ............................. 135

Patterson, Monty L., Livermore, CA ............................................................... 117

Rarick, Lisa D., M.D., RAR Consulting, LLC ................................................. 128

Snead, O. Carter, associate professor, University of Notre Dame Law

School, and former general counsel for the President’s Council on Bioethics .............................................................................................................. 338

Wood, Susan F., former Assistant Commissioner for Women’s Health

and Director of the Office of Women’s Health, Food and Drug Administration ............................................................................................................ 122

Woodcock, Janet, M.D., Deputy Commissioner for Operations, Food and

Drug Administration, U.S. Department of Health and Human Services . 87

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

Cummings, Hon. Elijah E., a Representative in Congress from the State

of Maryland, prepared statement of ............................................................ 75

Harrison, Donna J., M.D., member, Mifeprex Subcommittee of American

Association of Prolife Obstetricians and Gynecologists, prepared statement of ........................................................................................................... 137

Patterson, Monty L., Livermore, CA, prepared statement of ....................... 120

Rarick, Lisa D., M.D., RAR Consulting, LLC, prepared statement of ......... 131

Ruppersberger, Hon. C.A. Dutch, a Representative in Congress from the

State of Maryland, prepared statement of .................................................. 85

Snead, O. Carter, associate professor, University of Notre Dame Law

School, and former general counsel for the President’s Council on Bioethics, prepared statement of ....................................................................... 340

Souder, Hon. Mark E., a Representative in Congress from the State

of Indiana:

Information concerning lower standards for RU–486 ............................ 112

Judicial Watch Report ............................................................................... 3

Prepared statement of ............................................................................... 69

Waxman, Hon. Henry A., a Representative in Congress from the State

of California, prepared statement of ........................................................... 81

Wood, Susan F., former Assistant Commissioner for Women’s Health

and Director of the Office of Women’s Health, Food and Drug Administration, prepared statement of ..................................................................... 125

Woodcock, Janet, M.D., Deputy Commissioner for Operations, Food and

Drug Administration, U.S. Department of Health and Human Services,

prepared statement of ................................................................................... 90

(1)

RU–486: DEMONSTRATING A LOW STANDARD

FOR WOMEN’S HEALTH?

WEDNESDAY, MAY 17, 2006

HOUSE OF REPRESENTATIVES, SUBCOMMITTEE ON CRIMINAL JUSTICE, DRUG POLICY, AND HUMAN RESOURCES, COMMITTEE ON GOVERNMENT REFORM, Washington, DC.

The subcommittee met, pursuant to notice, at 2:04 p.m., in room

2203, Rayburn House Office Building, Hon. Mark E. Souder (chairman of the subcommittee) presiding.

Present: Representatives Souder, Schmidt, Shays, Cummings,

Davis, Watson, Ruppersberger, Norton, and Waxman.

Staff present: Marc Wheat, staff director and chief counsel;

Michelle Gress, professional staff member and counsel; Malia

Holst, clerk; Karen Lightfoot, minority senior policy advisor and

communications director; Sarah Despres, Tony Haywood, Kimberly

Trinca, Naomi Seiler, minority counsels; Richard Butcher, minority

professional staff member; and Teresa Coufal, minority assistant

clerk.

Mr. SOUDER. The subcommittee will come to order. We are here

today because there is a drug on the market associated with the

deaths of at least 8 women, 9 life-threatening incidents, 232 hospitalizations, 116 blood transfusions, and 88 cases of infection.

There are more than 950 adverse event cases associated with RU–

486 out of only 575,000 prescriptions, at most. Adverse events are

typically under-reported, since they are offered voluntarily by consumers and health care professionals, so it is most likely that there

are many more cases that we don’t even know about.

It is very clear that there is a serious problem with RU–486. In

failing to address this problem by disguising it, ignoring it, minimizing it, or causing confusion, it is a shameful failure for anyone

with the ability and desire to protect women from needless harm.

RU–486 is a common name for Mifeprex. It is produced by Danco

Laboratories, a corporate entity located in the Cayman Islands

which produces only that single drug and nothing else. Mifeprex is

approved by the FDA for the termination of pregnancy through 49

days of development. It is used in combination with another drug

called Misoprostol, which causes uterine contractions that expel the

dead fetus. This is an off-label use for the Misoprostol, which contains a black box warning against using the drug during pregnancy.

At least five of the deaths following the use of RU–486 have been

the result of toxic shock-like syndrome initiated by the bacteria

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Clostridium Sordellii. This bacteria is thought to exist in low numbers in the reproductive tracts of many women and is normally

combatted by the immune system. Experts in immunology, pharmacology, and maternal-fetal medicine have suggested that because

RU–486 interferes with the innate immune response, the bacteria,

if present, is allowed to flourish, causing a widespread multi-organ

infection in the woman. These infections are not accompanied by a

fever and the symptoms match those that are expected after taking

the RU–486 regime, including cramping, pain, bleeding, nausea,

vomiting. Each of the women infected with C. Sordellii after taking

RU–486 were dead within 5 to 7 days.

To investigate the nature of this bacteria, the CDC and FDA held

a scientific workshop last week called ‘‘Emerging Clostridial Disease.’’ The workshop panelists noted that the rapid growth of the

C. Sordellii bacteria in the RU–486 context likely forecloses effective treatment and that there is no currently identifiable window

of opportunity for treatment once a woman is infected, even with

major interventions such as a hysterectomy. The fatality rate has

been 100 percent for the women who have contracted C. Sordellii

infection after using RU–486.

Any other drug associated with a 100 percent fatal septic infection that kills otherwise healthy adults within days, with no apparent window for treatment, and associated with an exponential

amount of severe reactions would normally prompt an immediate

withdrawal. But we are talking about a drug regimen that is administered to cause an abortion, manufactured by a drug company

based in the Cayman Islands with no other drugs on the market,

and therefore no incentive to voluntarily withdraw its product, no

matter how dangerous.

Many abortion advocates feel they have to defend RU–486 because it is an alternative to surgical abortion. However, with eight

deaths that we know about, RU–486 is 10 to 14 times more likely

to be fatal than surgical abortion during the first 7 weeks of pregnancy, the period during which the drug is administered. To continue defending this dangerous drug in light of the mounting scientific evidence, injury, and death is to allow one’s zeal for abortion

to truly distort their view about what is right for women’s health.

The 10-times-more-deadly danger posed by RU–486 should not be

considered an acceptable risk that justifies keeping this drug on

the market.

The approval of RU–486 was made under extreme political pressure from the Clinton administration, which is well documented in

a recent report by Judicial Watch entitled ‘‘The Clinton RU–486

Files.’’ I ask that this report be included in the hearing record.

[The information referred to follows:]

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Mr. SOUDER. RU–486 was forced through the FDA using an extraordinary provision called Subpart H, reserved only for drugs

that treat life-threatening illnesses and for which existing treatments are insufficient. It was obvious even to the drug’s sponsor

that RU–486 did not fall within the narrow scope of Subpart H,

saying the FDA’s imposition of Subpart H was unlawful, unnecessary, and undesirable. But that did not deter the FDA in its extraordinary political complicity with President Clinton’s administration from forcing an abortion pill onto the market, no matter

how distorted the approval process was or what the price.

We are paying that price now. Almost 1,000 women have suffered adverse effects after taking RU–486. We know that eight

have died. We have a responsibility to consider the dangers that

this drug poses and question whether the FDA has the authority

to remove it from the market in the light of the severe problems

associated with this drug and the manufacturer’s failure to comply

with post-marketing restrictions.

I anticipate that the defenders of RU–486 will try to detract from

the cold, hard facts or cause confusion by talking about other septic

infections in other pregnancy situations. This tactic ignores what

the panelists reported at last week’s CDC conference, that Mifeprex

compromises the innate immune system, providing an environment

for rapid growth of the deadly infection.

C. Sordellii infection in the RU–486 context is 100 percent fatal,

with no opportunity for intervention. To ignore the immune system

connection with Mifeprex, or to say that there have been only five

such deaths and advocate only for better surveillance and informed

consent will be no comfort to the family of the next women who

dies suddenly after taking RU–486.

To the shallow objection that those of us who are pro-life have

no business looking into the problems associated with RU–486, let

me respond that this is a smokescreen and is incredibly shameful.

Anyone who honestly cares about women’s health has to take a

critical look at the potential dangers of this drug. To argue otherwise, on the basis that it is simply an abortion issue, is to demonstrate a blind allegiance to abortion at any cost, including women’s lives.

Representing the FDA on the first panel is Dr. Janet Woodcock,

Deputy Commissioner for Operations.

On our second panel, we will hear from Monty Patterson, the father of Holly Patterson, who was 18 years old when she died after

taking RU–486; Dr. Susan Wood, former FDA Assistant Commissioner for Women’s Health; Dr. Lisa Rarick of RAR Consulting; Dr.

Donna Harrison, a member of the Mifeprex Subcommittee of the

American Association of Prolife Obstetricians and Gynecologists,

and Carter Snead, Associate Professor of Law at Notre Dame and

former General Counsel for the President’s Council on Bioethics.

I wish to note that the medical director for Danco, the Cayman

Islands-based manufacturer for RU–486, initially agreed to testify

at this hearing, but pulled out 2 days ago. I intend to followup with

Danco to request answers in a sworn affidavit to critical questions

regarding Danco’s failure to comply with the post-marketing restrictions for RU–486.

68

Last of all, I want to note that I notified the FDA last December

that this subcommittee would conduct a hearing into RU–486.

FDA’s compliance with this oversight committee’s document requests has been quite frustrating. We were getting critical documents related to our December request as late as last night. This

hearing is not the end of our document requests and I invite better

cooperation from the agency moving forward. Now that we are here

and we have most of the documents we requested 5 months ago,

it is time to seek some answers about what can be done to protect

women from this deadly drug.

[The prepared statement of Hon. Mark E. Souder follows:]

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Mr. SOUDER. Now I yield to the ranking member, Mr. Cummings,

for his opening statement.

Mr. CUMMINGS. Thank you very much, Mr. Chairman. I want to

join you in welcoming all of our witnesses testifying this afternoon

on a very important subject, protecting women’s health.

And particularly, I want to acknowledge Mr. Monty Patterson,

who lost his 18-year-old daughter, Holly, when she died as a result

of a rare bacterial infection. I offer my sincere condolences to the

Patterson family and want to commend Mr. Patterson and his family for their efforts to become well-versed in this subject area in the

wake of a terrible family tragedy.

As you know, Mr. Chairman, C. Sordellii is a bacterium that normally resides in soil. Although cases of human illness are rare, the

effect is usually fatal when the bacteria produces toxins that cause

rapid onset of shock that physicians are powerless to curtail.

To date, medical literature reflects a total of approximately 30

reported fatalities from C. Sordellii infection. Cases of infection

have involved both males and females of all ages. At least eight of

the reported fatalities occurred in women who had just given birth,

and two occurred after miscarriages.

The selective focus of today’s hearing centers on five fatal cases

that have occurred over the past 5 years and also involved pregnancy. Four of these cases occurred in California, the other in Canada. The key factor linking this small subset of cases is that they

occurred in women who underwent medical abortion.

Last week, the Centers for Disease Control, as you said, convened a scientific meeting on C. Sordellii and another related bacterium. The meeting served to underscore just how little is known

about the cause of human C. Sordellii infections. Although a number of theories were advanced and debated, the meeting produced

no solid answers as to how the infection is acquired. The only consensus was that much more needs to be learned if additional

deaths are to be prevented.

Despite the overwhelming scientific uncertainty among experts,

a number of policymakers and policy shapers apparently have already arrived at the conclusion that the drug Mifepristone, also

known as RU–486 and marketed in the United States under the

name Mifeprex, is the likely cause of the infection in the five cases

involving patients who underwent medical abortion. Consequently,

they are advocating the FDA’s immediate withdrawal of Mifeprex

from the market. What is the basis for this belief? Is it science, or

is it something else?

It is difficult to overlook the fact that adherents to this point of

view generally opposed the introduction of Mifepristone into the

United States in the first place, or to ignore the fact that they did

so on an ideological grounds, knowing that there had been no reported fatalities among as many as 2 million users of the drug in

Europe.

To bolster their argument, proponents of withdrawing FDA approval suggest that the FDA, in effect, rushed the drug to market.

But the record shows that the approval process was thorough and

unusually lengthy. However, it resulted in more stringent restrictions on distribution than apply to most other drugs.

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Mr. Chairman, I hope it is fair and correct to presume that not

one participant in today’s hearing takes the health of women lightly. As a matter of fact, every single one of us take women’s health

very seriously. My own concern for both women’s health and women’s rights leads me to wonder, however, why the narrow focus on

these cases and on this drug as the suspected culprit? Why not concern ourselves with all the possible causes of infection in not only

these 5 cases, but also the other 9 or 10 reported cases in which

pregnancy was the common denominator?

If ensuring a high standard of health care for American women

is our pure objective, it just seems to me, Mr. Chairman, that our

focus should be seeking the truth concerning the cause of C.

Sordellii infection rather than attempting to bully the FDA into

taking action, unsupported by science, that would have just one

certain impact, limiting access to abortion for many, many women.

Therefore, I hope today’s hearing can serve the purpose of promoting thorough scientific inquiry and supporting a research agenda that will lead us to answers that can prevent infection and

death from infection.

Concentrating on five cases involving medical abortion to the exclusion of a larger number of equally tragic cases appears to serve

the narrow purpose of whittling away at a women’s constitutional

right to choose by limiting practical access to abortion. I only hope

that, in this case, appearances are deceiving.

I look forward to the testimony and I thank the witnesses for

being with us, and with that, Mr. Chairman, I yield back.

[The prepared statement of Hon. Elijah E. Cummings follows:]

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Mr. SOUDER. I now yield to other Members wishing to make

opening statements. Mr. Waxman, do you have an opening statement? I am going to ask for this process. It has been a practice if

Members are members of the full committee but not the subcommittee, that we let them participate, and I ask unanimous consent that Mr. Shays be allowed to participate, and he will go to the

back of the rest of everybody else’s opening statements.

I yield to Mr. Waxman.

Mr. WAXMAN. Thank you very much, Mr. Chairman. I appreciate

this chance to make an opening statement and to attend this hearing because this is an important hearing. It gives us a chance to

talk about the deaths of several women who had taken

Mifepristone, RU–486—we all have been stumbling over that

word—which is the medical abortion pill. These deaths were tragic

and I also want to join in extending my deepest sympathies to the

Patterson family, who lost their daughter, and thank you for coming today.

We are going to discuss these cases as part of a broader pattern

of C. Sordellii infection. This is an infection that has killed men,

women, and children. It has killed women who have just given

birth, women who had miscarriages, and women who had not even

been pregnant. As with any infection we do not yet understand

well, we need better research and surveillance to fight it.

But before we begin this discussion, I would like to say something about another reason I believe we are here. There are people

who have wanted RU–486 to be pulled off the market since the day

it was approved. In fact, they didn’t want it to be approved. I respect their judgment because they are very strongly against an

abortion, whether it be by RU–486 or by a medical procedure.

But that is not the issue of safety and it is not an issue of science

and it is not an issue of data. That makes it an ideological opposition to a woman’s right to choose abortion. And, in fact, many of

those who want to take this drug off the market want women to

have virtually zero access to any kind of abortion, whether it be

medical or surgical.

I need not remind people what happened before abortion became

legal and safe in the United States. Hundreds of thousands of

women per year sought out illegal abortions or tried to induce abortions themselves. Tens of thousands suffered major infections and

other injuries. And even after the introduction of antibiotics, hundreds of women died every year before abortion was made legal and

safe.

There are many who want us to have States’ rights to pass the

kind of law that was just adopted in South Dakota, to ban all abortions, even in the case of rape or incest, or even to preserve the

health and well-being of the mother. That is the ultimate expression of their point of view, but it is not the point of view I share

and it is not the point of view that I think most people would

share.

This drug, which is the subject of today’s hearing, has some

promising characteristics. It offers women an alternative to surgery

for early termination of pregnancy. It is available to many women

who do not have access to surgical abortions. And it has been widely and safely used in Europe.

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On the other hand, questions have been raised about whether

there may be a link between the drug and the tragic deaths of several young women. That is the question. Is there a link between

this drug and those deaths? And that is a scientific issue, not an

ideological one, and it is an issue that we ought to leave to the

Food and Drug Administration scientists to look at the evidence.

Now, it has been asserted by the chairman that the side effects

may be understated because there is voluntary disclosure. Well,

that is true of all drugs—there is voluntary disclosure of adverse

effects—but not this drug, because the drug had a lengthy period

of time during which it was under surveillance at the Food and

Drug Administration. It was approved ultimately under Subpart H,

which put a lot of restrictions in place on the use of this drug

which are not in place for the use of other drugs that are available

on the market today in the United States. And one of the limits

to its use was that a physician had to agree in advance to report

any adverse consequences from use of this drug to the manufacturer and the manufacturer is obligated under law to report it to

the FDA. So we have a pretty clear picture of what has been going

on.

This is not like the Plan B drug, which has not been approved

by the FDA for over-the-counter use because of political pressure

on the FDA. This drug was not approved by political pressure, it

was approved under the usual standards of safety and efficacy.

Now, other drugs have been approved under that status and

have been taken off when we saw that there were consequences to

it which changed the balance of whether it was a safe and efficacious drug, and that is the issue of whether this drug should remain available to women. It should be resolved based on scientific

assessment of its benefits and dangers. If the best scientific evidence turns out to demonstrate that the risks do, in fact, outweigh

the benefits, then the FDA should make a decision accordingly. But

it should be kept on the market or removed using the same legal

and scientific standards that are used for all other drugs.

For today, let us take a close and serious look at C. Sordellii infection. We must encourage our scientists to figure out why these

women and the other victims of this bacteria, which had no relationship that we know of to RU–486, why they died, and we should

do everything we can to improve detection and treatment. But in

the end, we need to make sure any regulatory decision about RU–

486 is based on the science and the law and not the politics of the

abortion debate.

Thank you, Mr. Chairman.

[The prepared statement of Hon. Henry A. Waxman follows:]

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Mr. SOUDER. Ms. Holmes Norton, do you have an opening statement?

Ms. HOLMES NORTON. Thank you very much, Mr. Chairman. Mr.

Chairman, first, I want to say that if there is a drug, if it is a contraceptive drug, if it is a drug related in any way to the health of

women, that scientists tell us causes death or injury of any kind,

that drug should have no approval.

I don’t think this committee is qualified to make that judgment.

I think that judgment has to be committed to the kind of scientific

study you would do if you were serious about these eight deaths.

The most important thing we can do is to find out causation here,

because then we know how to prevent the deaths or injury. Anything that stands in the way of that link is not a serious attempt

to deal with it. Anything that jumps over the appropriate scientific

inquiry is not serious about these eight deaths.

I think RU–486 has been very important in preventing abortions

and in getting to where American women are going to get anyway.

We simply will never be able to keep this kind of drug, which has

not been shown to be harmful by scientists, out of the hands of people. So if it is going to get into the hands of people, one thing we

want to know is what causes it.

What we don’t want is to investigate scientists, for example, who

give us answers contrary to our personal or moral or religious beliefs. We want to leave them free and unfettered to tell us what

the scientific method reveals to them.

Finally, Mr. Chairman, I particularly regret not being able to

stay throughout this hearing because of other hearings, but I do

want to go on the record indicating the unthinkable series we have

witnessed during this term that show the unmitigated

politicization of the one area that Americans always held off from

politics, and that is science itself. Whether Schiavo or creationism

renamed intelligent design or stem cell research or, God help us,

global warming itself, there are views floating around this Congress that essentially reach conclusions on these matters of huge

scientific moment based on their own personal belief.

I never thought that the country that has stood at the forefront

of science in the world would ever reduce science to personal, political, and religious views and opinions and I don’t believe that, in effect, that is what the country is going to let us do when they see

the long list before them of bills, of things we now can’t do, of

things we do do, only because of the personal, political, and religious views of some Members. When they see that the attempts

that have been made during this session of Congress and during

this administration to burden scientists with the personal views of

Members of Congress, it is a shameful day for American science

and I think we have to wipe it away if we do nothing else.

Thank you, Mr. Chairman.

Mr. SOUDER. Mr. Davis.

Mr. DAVIS OF ILLINOIS. Thank you very much, Mr. Chairman,

and I shall be brief. Let me just thank you for calling this hearing.

I think that every single one of us are indeed concerned about the

health, safety, and well-being of every single individual as they

make use of a drug, medical procedure, or pattern of treatment. I

would hope especially given the fact that we are talking about safeVerDate 11-MAY-2000 10:35 Jan 26, 2007 Jkt 000000 PO 00000 Frm 00091 Fmt 6633 Sfmt 6633 D:\DOCS\31397.TXT HGOVREF1 PsN: HGOVREF1
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ty of a drug, that we discuss and debate the science and not the

ideological expressions of individuals who may be bent one way or

another around the question and the issue of abortion.

And so I look forward to the witnesses and look forward to the

information that is going to be presented and I yield back the balance of my time.

Mr. SOUDER. Mr. Ruppersberger.

Mr. RUPPERSBERGER. Thank you, Mr. Chairman, for having this

hearing. We know the issue of abortion is a very difficult issue for

many citizens in this country and there are different people that

have different points of view. One of the issues it looks like—you

can’t hear? That is probably a good thing. [Laughter.]

Starting again, we know the abortion issue is a very difficult

issue and we also know that individuals, no matter which side of

the issue you are on with respect to abortion, is something that you

are probably not going to change. It would be more positive for our

whole country if we could come to some resolution, but I don’t

think that is going to happen.

But I think in today’s hearing it is important that we really don’t

use the political issue of abortion but focus on this RU–486. With

that in mind, RU–486 underwent a vigorous, a rigorous 4-year review process at the FDA, more rigorous than most drugs. As you

know, it was considered under a select set of regulations called

Subpart H, which allowed the FDA to add more conditions on the

drug’s distribution and use.

But since its approval in the year 2000, nearly 600,000 women

in the United States have used RU–486. It has proven to be a safe

and effective means of terminating early pregnancy. Because of

this medical option, millions of women worldwide, including survivors of sexual assault, have had the right to end an early pregnancy with privacy and dignity.

Tragically, there have been four confirmed deaths in the United

States from bacterial infection in women who used RU–486. At this

point, we do not know what caused these infections or if these

deaths are at all related to the use of RU–486.

Fortunately, the CDC and FDA have moved quickly to investigate these incidents. Early this month, RU–486 scientists from

the Nation’s leading public health agencies gathered in Atlanta to

discuss the bacteria that caused these deaths and the risk it poses

to pregnant women. Career scientists and doctors are the best

equipped to investigate this issue and I know they will get to the

bottom of it. We must rely on accepted medical standards for determining the safety and efficacy of a medication. The future of RU–

486 should lie with the FDA and the medical community, not with

Congress, who do not have yet the full picture and have scientific

data before us to make a decision on women’s health.

I yield back.

[The prepared statement of Hon. C.A. Dutch Ruppersberger follows:]

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Mr. SOUDER. Ms. Watson.

Ms. WATSON. I want to thank you, Mr. Chairman. I applaud the

subcommittee for bringing this topic up to educate the American

public.

It is very important that the FDA, our drug watchdog agency, is

engaged with the scientific community and the population at large

in order to provide informed choices for the women of the United

States. Mifepristone, or RU–486, has been utilized for nearly two

decades by women all over the globe. This drug provides an early

abortion option that does not require surgery. It has been reported

that since the FDA approved RU–486 in 2000, significantly more

than half a million American women have used this medication.

Mr. Chairman, let us be very clear during this hearing today.

Ideological debate pro or anti-abortion is a discussion that we have

been afforded the free speech right to talk about. Medical process

and drug effectiveness should not be subject to any debate of that

style. It is imperative to the health of our Nation that Congress,

the FDA, health care delivery professionals, and the scientific community and patients approach the utilization of any drug from an

educated, scientifically tested, and unbiased perspective.

So I am interested to hear the testimony of our witnesses because oversight is a serious responsibility that we undertake on behalf of the American people, and the use of RU–486 is a subject

that must be treated with unbiased integrity and regard for the

overall health of women.

Four women have died of sepsis. All four were infected by the

same type of bacteria. What does the medical and scientific community say to this situation? Is Mifeprex responsible? So our decision

should be based on education and scientific investigation and I look

forward to hearing about that information.

I yield back my time, Mr. Chairman. Thank you very much.

Mr. SOUDER. Thank you. Mr. Shays.

Mr. SHAYS. Thank you, Mr. Chairman. I want to thank you, one,

for having a hearing on this issue, to encourage you to use that

same logic to have a hearing on Plan B, which is a related drug

that doesn’t require an abortion but can accomplish the same task.

I want to say that I have extraordinary respect for you, and in

spite of your bias one way and my bias the other, I am convinced

that this will be a fair hearing and I appreciate that.

I guess I would just end by saying that I appreciate particularly

the thoughtful statement of your ranking member, Mr. Cummings,

and the ranking member of the full committee. I think others have

said the same thing, but I think they covered it well. If I could

have written a statement in time, I would have been pleased to

have written either of those two statements, so I would like to

stand on their statements.

Again, thank you for allowing me to participate.

Mr. SOUDER. Thank you, and the record needs to show that there

have been 8 women, at least, who have died, 950 adverse events,

and not all are necessarily associated with the other infection.

Also, I would like to ban abortion, but this isn’t about abortion.

We can’t ban abortion. This is a health question. Just because scientists disagree doesn’t mean that one person is trying to put an

ideological view on it and other people have a scientific view.

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In a number of issues lately, I have been accused of being antiscience because the scientists I support disagree with the scientists

who another group support. In fact, this drug was cleared in an expedited process, not using mostly U.S. research, and we have a

right to look into this drug and we should be looking into this drug.

Scientists disagree and we should hear the debate. Just because

one group of scientists is political doesn’t mean that the other

group of scientists aren’t political, too. We all know that science requires judgments, as well. If it was just an ideological view, we

couldn’t hold this hearing. We are not hearing from ideological people, we are hearing from medical people, we are hearing from researchers, and we will hear the debate and I am looking forward

to that debate.

I ask unanimous consent that all Members have 5 legislative

days to submit written statements and questions for the hearing

record and that any answers to written questions provided by the

witnesses also be included for the record. Without objection, it is

so ordered.

I also ask unanimous consent that all exhibits, documents, and

other materials referred to by Members and the witnesses may be

included in the hearing record, that all Members be permitted to

revise and extend their remarks, and without objection, it is so ordered.

Our first panel is composed of Janet Woodcock. Dr. Woodcock is

Deputy Commissioner for Operations at the FDA. If you could come

forward, remain standing. As an oversight committee, it is our

standard procedure to swear in our witnesses. If you will raise your

right hand.

[Witness sworn.]

Mr. SOUDER. Let the record show that the witness responded in

the affirmative.

We thank you for coming today and we are looking forward to

your testimony.

STATEMENT OF JANET WOODCOCK, M.D., DEPUTY COMMISSIONER FOR OPERATIONS, FOOD AND DRUG ADMINISTRATION, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Dr. WOODCOCK. Good afternoon, Mr. Chairman, Congressman

Cummings, and Members of the subcommittee. I am Janet

Woodcock, Deputy Commissioner for Operations at the Food and

Drug Administration. Today, I will discuss the approval history

and the current regulatory status of the product Mifepristone, currently marketed in the United States under the trade name

Mifeprex and indicated for termination of early pregnancy.

First, I would like to correct any misconceptions that may exist

about the initial approval of the drug. Mifeprex was approved in

September 2000 after extensive FDA review of the application,

which included three adequate and well-controlled trials documenting the efficacy and safety profile of the drug when used for this

indication. In addition, post-market experience in Europe included

over 620,000 exposures for pregnancy termination, of which

415,000 were in combination with Misoprostol. These data fully

conform with FDA’s standards for approval.

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In order to assure that Mifeprex was used by qualified specialists, FDA and the sponsor agreed that the drug would be approved

under 21 CFR 314.520. This section of Subpart H concerns safety,

not effectiveness. This infrequently used regulatory provision allows approval of a drug with restrictions to assure safe use. In this

case, distribution of Mifeprex is restricted to physicians qualified to

supervise medical abortion and its complications and who have

agreed to fully inform patients and obtain their written agreement

to provide an FDA-approved patient information sheet and agreed

to report serious adverse events to the sponsor.

This product met the requirements of all applicable laws and regulations, including Subpart H. As FDA made clear in the preamble

to the final rule, the Subpart H regulations were intended to apply

to serious or life-threatening conditions, such as depression, not

only to diseases. Approval of Mifeprex under restricted distribution

had nothing to do with accelerated approval based on a surrogate

end point, which is a separate provision of the regulations.

FDA has monitored reports of Mifeprex-related adverse events

very carefully after marketing. As of March 31, 2006, 950 cases related to the approved use were submitted to FDA. Consistent with

the clinical trials’ experience and the drug label, heavy vaginal

bleeding was the most frequently reported adverse event, with 422

cases, followed by incomplete abortion, with approximately 400

cases. Other serious events included 88 instances of infection, with

18 of them considered severe, and 27 ectopic pregnancies. This adverse event profile was consistent with prior experience with medical termination of pregnancy.

Since approval, FDA has evaluated nine reports of death in the

United States potentially associated with the approved indication.

Three of these have either been found or appear to be unrelated to

medical abortion. An additional death was due to a ruptured ectopic pregnancy. The use of Mifeprex is contraindicated in ectopic

pregnancy. Five deaths were due to a rapidly fatal toxin mediated

shock syndrome. One of these was caused by infection with Clostridium Perfringens. The four additional deaths, all in California,

were caused by infection with a rare anaerobic bacterium, Clostridium Sordellii. An additional Clostridium Sordellii fatality previously occurred in a clinical trial in Canada.

This rapidly fatal toxin mediated shock syndrome was not anticipated to be a complication of medical abortion. It has not been reported in the extensive European experience to date, estimated

over 1.5 million uses of the drug. Eight previous U.S. cases of fatal

shock due to C. Sordellii, primarily after vaginal delivery or Caesarian delivery, have been reported in the obstetrical literature.

FDA responded aggressively to the reports, with extensive followup and expert consultation. Last week, NIH, CDC, and FDA cosponsored a scientific workshop on potential emerging Clostridium

infections. CDC researchers identified three additional C. Sordellii

cases, two fatal, that occurred after spontaneous abortion. CDC has

also instituted an investigation in California looking into 321 unexplained pregnancy-associated deaths between 2000 and 2003. They

have excluded 303 cases from being related to toxic shock-related

syndrome and are further investigating 18 more.

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Given that the information on this infection and its epidemiology

is still emerging, it is not possible at this time to determine whether the current Mifepristone/Misoprostol regimen for medical abortion results in an increased risk of C. Sordellii infection or whether

the reporting requirements under the Mifeprex approval and subsequent intensive investigations have uncovered what is an emerging

risk in pregnancy overall. FDA is collaborating with the CDC and

NIH on further research into this infection and will continue to

provide timely public information.

I will be happy to answer your questions.

[The prepared statement of Dr. Woodcock follows:]

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Mr. SOUDER. Let me ask this first question as a multi-part. This

drug went through a different type of an approval process than others, Subpart H in the approval process, and it allows the FDA to

impose certain restrictions on the distribution of Mifeprex, which

you covered in your written testimony. How do you monitor Danco’s

compliance with each of these restrictions and what do you do

when they are not in compliance? Furthermore, are they absolutely

required to report all the incidents?

Dr. WOODCOCK. Yes. FDA has, once the drug was approved

under these provisions, put into place an inspectional system for

FDA to inspect the manufacturer to assure they were complying

with the provisions of the approval, and we have done frequent inspections to oversee their compliance with this program.

Mr. SOUDER. And are they required under the law to report all

adverse effects?

Dr. WOODCOCK. All manufacturers are required under the law to

report adverse events that they find out about with drugs that they

manufacture or distribute to the FDA.

Mr. SOUDER. Are you tracking that?

Dr. WOODCOCK. Yes.

Mr. SOUDER. And then if you are, how did the manufacturer not

know about some of the things that you referred to, or did you discover those through the manufacturer? Have they reported any of

these? Do you view them as cooperative?

Dr. WOODCOCK. The vast majority of reports that we have received, which are over 1,000, counting duplicates, have come directly from the manufacturer. The physicians who have signed the

physician agreement are instructed to report adverse events to the

manufacturer.

Mr. SOUDER. We heard a number of the opening statements refer

to that there is a regimen, but yet RU–486 is frequently used past

the 49 days as it is recommended and it is administered at a dosage of 200 rather than the FDA-approved 600 dosage. It is often

prescribed without the required patient agreement form and its

counterpart, Misoprostol, is used vaginally despite its approval for

oral use only. Furthermore, although the manufacturer is required

to have the ability to track its use to the patient level, the manufacturer estimates to arrive at usage rates for the purposes of safety and promotional material, WHO, Planned Parenthood, and a

number of these are not following your regimen. Would it be fair

for one to conclude from this evidence that RU–486 is not being

used according to the restriction that you imposed on it in Subpart

H?

Dr. WOODCOCK. There is no restriction in the approval letter or

in the physician agreement that says the physician must use a

specified dose or regimen. The manufacturer, who FDA regulates,

is complying with the restrictions that were placed on the drug distribution at the time of approval.

Mr. SOUDER. So you are saying that individuals are—let me ask

this. Would it be fair for one to conclude that the restrictions

placed on RU–486 have failed to ensure that the drug will be used

in a manner consistent with the FDA’s opinion on safe use? In

other words, when you cleared the drug, it was cleared on the basis

of the usage. Now what you are telling me is there is no checking

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to see that it is being used in the way you approved it, and could

not that explain some of the problem?

Dr. WOODCOCK. The restriction program was pub in place to ensure that physicians who prescribe the drug could date a pregnancy—that is a very important aspect of using this regimen—

could rule out with professional experience an ectopic pregnancy,

and were manage the complications of medical abortion, which include requirements for surgical intervention. So that was the purpose of the restriction program.

FDA reviews data that is submitted to it when FDA approves a

dose and a regimen in an approved indication for use of the drug.

Subsequently, based on medical literature, physicians may deviate

from the recommended dose and this occurs very frequently. The

restricted distribution program had to do with distribution to physicians who were qualified. So the drug is not available in pharmacies. It cannot be prescribed by physicians who are not qualified

and have not gone through the program.

Mr. SOUDER. So let me see if I can understand, see if this is an

oversimplification of what you just said. You said you tested it with

one regimen. Then you didn’t put that in force because you concluded after the tests, based on information that regimen wasn’t essential to the safety of the individuals?

Dr. WOODCOCK. FDA——

Mr. SOUDER. Because the regimen dealt with other subjects other

than the safety.

Dr. WOODCOCK. FDA reviewed the data based on the safety and

effectiveness information that was included in the application. That

was the recommended regimen, the approved regimen that is in the

drug label. The patient agreement and so forth discuss that regimen. All the approved patient labeling discusses that regimen. It

is quite common in the United States, however—a recent article

showed that about 21 percent of drug usage in the United States

deviates somewhat from the label directions——

Mr. SOUDER. Let me, because my time is up, when I came as a

freshman, I was vice chair of Mr. Shays’ subcommittee and I remember on the secondary use of drugs one of the huge questions

is the FDA, however, does not give its blessing to non-approved

regimens and non-prescribed ways of doing it. And I would also

like to insert in the record at this point a history of other drugs

where with one or two deaths, they have been pulled off the market. Usually, scientific research does not go forth while there is a

question on a drug, and I think an exception has been made in this

for political reasons. It is exactly the reverse of what has been

charged.

[The information referred to follows:]

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Mr. SOUDER. I yield to Mr. Cummings.

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

First of all, thank you for being with us, Dr. Woodcock. Dr.

Woodcock, there have been allegations that there was something

unusual about the approval of Mifeprex. You were the Director of

the Center for Drug Evaluation and Research back then, is that not

correct?

Dr. WOODCOCK. That is true.

Mr. CUMMINGS. And did the FDA treat Mifeprex using the appropriate scientific and legal standards for safety and efficacy?

Dr. WOODCOCK. We used the scientific and legal standards that

we use for every drug that we evaluate.

Mr. CUMMINGS. Now, anti-choice advocates have criticized the

approval on a number of grounds, including the fact that there was

no double-blind placebo controlled study of this drug. But it is hard

for me to imagine how someone could conduct a placebo-controlled

study of an abortion drug. That would mean giving the women

seeking an abortion a placebo that would not terminate the pregnancy, is that right?

Dr. WOODCOCK. I suppose. The need for a placebo occurs when

there is a tremendous variability in the outcome, and so you can’t

tell whether the outcome was due to the intervention or other

events. For many types of interventions, such as anesthesia, all

right, we don’t have a randomized control group because you can

easily tell whether people are unconscious and they don’t become

unconscious spontaneously very often. The same is true for contraceptives, where we have a very good background rate of pregnancy

with unprotected intercourse. So in various situations, a totally accurate control is what is called a historical control, where we know

what happens in that situation without an intervention.

Mr. CUMMINGS. There seems to be confusion about the way that

Mifeprex was approved. It was approved under provisions known

as Subpart H, is that correct?

Dr. WOODCOCK. Yes.

Mr. CUMMINGS. Some of these provisions provide for an accelerated approval of drugs for life-threatening conditions. But a different part of Subpart H guides not expedited approval but the restricted distribution of certain products. Why was Subpart H used

in the case of Mifeprex?

Dr. WOODCOCK. For Mifeprex, it was felt important that the distribution be limited to qualified practitioners, because although the

intervention was found to be safe and effective, it was in the hands

of individuals in the clinical trials who were able to diagnose pregnancy and date it properly, who were able to rule out ectopic pregnancy with a high degree of accuracy, and who were able to deal

with the complications of medical abortion, including incomplete

abortion. The drug would not be safe in the hands of practitioners

who did not routinely take care of pregnant women, for example.

So that is why these restrictions were put into place.

Mr. CUMMINGS. So this had nothing to do with accelerating approval?

Dr. WOODCOCK. Nothing to do with it. The evidence on effectiveness for Mifeprex was submitted in three trials that FDA found to

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be adequate and well-controlled trials for the purpose of demonstrating termination of pregnancy.

Mr. CUMMINGS. Well, the marketing application was submitted

in March 1996, is that correct?

Dr. WOODCOCK. Yes.

Mr. CUMMINGS. But the drug wasn’t approved until September

2000. That is like 41⁄2 years later. The average time for approval

is about 18 months, is that correct?

Dr. WOODCOCK. Yes.

Mr. CUMMINGS. So why did the approval process take so long?

Dr. WOODCOCK. FDA asked many questions and subjected this

application, everything from the manufacturing of the drug, the

pharmacology, the distribution of the drug, and the safety and efficacy to a very thorough review, such as we would for any drug, and

in this case, it took that long.

Mr. CUMMINGS. I mean, what is the record, do you know, length

of time?

Dr. WOODCOCK. Longer.

Mr. CUMMINGS. All right. I see my time is about up so I will submit questions.

Mr. SOUDER. Let me ask Congresswoman Schmidt and Congressman Shays, did you want to ask questions of this witness?

Mrs. SCHMIDT. I do.

Mr. SOUDER. Do you have questions, as well, Mr. Shays?

Mr. SHAYS. I don’t want to ask her to have to stay after an hour

of hearings after our votes.

Mr. SOUDER. We are going to have about an hour’s worth of

votes, so Mrs. Schmidt, why don’t you ask some of your questions

here.

Will you answer any written questions that we give you from the

different Members, because it is going to be a long voting stretch,

probably at least an hour here.

Dr. WOODCOCK. Certainly.

Mr. SOUDER. Mrs. Schmidt.

Mrs. SCHMIDT. Thank you, Mr. Chairman. What I am understanding is that there are seven deaths recorded from this drug. As

a woman, why aren’t we pulling this drug from the market?

Dr. WOODCOCK. You have to distinguish, first of all, and I know

it is very confusing, you have to distinguish reports to the FDA,

deaths that are actually occurred or related to administration of

the drug in some way, and then where there is a causal relationship between administration of the drug and the death.

FDA actually has nine reports of death related to medical abortion in the United States. Three of those we find unrelated to administration of the drug. In one case, we cannot—either the patient

is not documented to have taken the drug or other reasons unrelated. One death was due to ruptured ectopic pregnancy. Ruptured

ectopic pregnancy, if the patient doesn’t seek medical care rapidly,

can be fatal. The ectopic pregnancy itself was a preexisting condition, was not caused by administration of Mifepristone and

Misoprostol.

There were five deaths were due to sepsis, to infection, and what

we don’t know is whether or not medical abortion increases the

probability of getting this infection. This infection has occurred

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after vaginal delivery, after Caesarian section, and after spontaneous abortion or so-called miscarriage, and there are documented

cases in each of those instances. So we do not know if in medical

abortion there is an increased rate of this infection or whether or

not we are simply seeing these because of our intense scrutiny of

outcomes after medical abortion due to the restricted distribution.

Mrs. SCHMIDT. May I have a followup, sir? I am having a problem with your explanation and I will tell you why. The ectopic

pregnancy, the drug should never have been administered if she

had an ectopic pregnancy, period, case closed. I don’t care what the

reason why the drug was administered. It was administered wrongly. That woman died because of it. So there is a problem.

But more importantly, the five of the infections, just because you

don’t know how the infection occurred, we do know they took the

drug and they died. To me—I am from a farm community—it

sounds like you need to pull the drug until you can be absolutely

sure that there are no deaths related.

I have a whole list here of drugs that have been pulled from the

market either voluntarily or involuntarily. There has just been a

contact solution that has been pulled from the market because of

serious eye infection, including the loss of sight. So we are real

careful about other things about our body, but when it comes to a

woman’s body, I am just finding a problem that we are just not

that careful.

I think this drug needs to be pulled from the market. It needs

to be pulled from the market now and it is time that the FDA does

something about it.

Mr. SOUDER. Thank you. We will send you some additional questions. May I ask you quickly, the FDA reported 116 cases of blood

transfusion. Do you believe Mifeprex caused these hemorrhage

cases?

Dr. WOODCOCK. Hemorrhage is a common complication of childbirth, spontaneous abortion, surgical abortion, and medical abortion. So when a woman is pregnant, she faces a possibility of experiencing hemorrhaging after childbirth and so forth. Yes, we

expected——

Mr. SOUDER. So you believe these were common hemorrhaging

cases, not extraordinary hemorrhaging cases?

Dr. WOODCOCK. It was expected and was observed in the clinical

trial. There was a case of needing transfusion, so it was expected

that some women after the medical abortion regimen would have

bleeding requiring transfusion. That is correct.

Mr. SOUDER. So you believe that 116 cases in 575,000 is roughly

similar to the population that would normally have it?

Dr. WOODCOCK. Yes. We feel that all the side effects except the

Sordellii are within what we would expect in this population.

Mr. SOUDER. Thank you. We will submit——

Mr. SHAYS. Mr. Chairman.

Mr. SOUDER. Yes, Mr. Shays.

Mr. SHAYS. If I could submit questions in writing, because I do

have questions. I just don’t want to hold her for an hour.

Mr. SOUDER. OK.

Mr. SHAYS. So I will have questions. I will submit them through

you.

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Mr. SOUDER. Thank you.

Mr. SHAYS. Thank you.

Mr. SOUDER. The subcommittee stands recessed until we get

back from votes.

[Recess.]

Mr. SOUDER. The subcommittee is back in session.

If the second panel could come forward. The second panel is

Monty Patterson, father of Holly Patterson, who was 18 years old

when she died taking RU–486; Dr. Susan Wood, former FDA Assistant Commissioner for Women’s Health; Dr. Lisa Rarick, RAR

Consulting; Dr. Donna Harrison, a member of the Mifeprex Subcommittee of the American Association of Prolife Obstetricians and

Gynecologists; and law professor O. Carter Snead from the University of Notre Dame, former general counsel for the President’s

Council on Bioethics.

As an oversight committee, it is our customary practice to swear

in each of the witnesses. Will you raise your right hands.

[Witnesses sworn.]

Mr. SOUDER. Let the record show that each of the witnesses responded in the affirmative.

We thank you each for coming. Thank you for your patience of

putting up with the congressional procedure of having multiple

amendments and bills. It makes for a long afternoon but one that

we can never predict when we schedule a hearing.

We will start with Mr. Patterson. Thank you for coming, and

once again, we express from all of us in the committee our sympathies for the loss of your daughter.

STATEMENT OF MONTY L. PATTERSON, LIVERMORE, CA

Mr. PATTERSON. Thank you very much. First of all, I just want

to show you a picture of Holly so you know that we are talking

about my daughter and who she is.

Mr. SOUDER. Why don’t you pull the mic closer to you.

Mr. PATTERSON. I said I wanted to show you a picture of my

daughter so at least you see what I have lost and actually what she

lost.

I owe and dedicate my presence here to those who have no voice

and particularly to my daughter, Holly, who died at 18, and the

other women who have died or have been seriously hurt by taking

the RU–486 medical abortion drug regimen as a solution to their

unplanned pregnancy.

I am here to testify about my personal experience as the father

of a victim of this drug and my consequent knowledge, experiences,

and views pertaining to RU–486, the drug. I want to be clear that

my views and testimony should be divorced from any debate about

abortion. I feel we must examine the dangers associated with RU–

486 for early medical pregnancy termination that are separate and

apart from any particular view about a women’s right to access and

choice.

Twelve days after Holly’s 18th birthday, on September 10, 2003,

she walked into a Planned Parenthood clinic to be administered an

RU–486 medical abortion regimen. By the 4th day, she was admitted to the emergency room of a local hospital. She was examined.

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She was given pain killers. She complained of bleeding, cramping,

constipation, and pain, but subsequently, she was sent home.

Seven days after taking RU–486, Holly returned to the same

emergency room hospital complaining of weakness, vomiting, abdominal pain. Hours later, I was called to the hospital, where I

found her surrounded by doctors and nurses, barely conscious and

struggling to breathe. Holly was so weak she could barely hold onto

my hand. Feeling utter belief and desperation, I watched Holly succumb to a massive bacterial infection as a result of a drug-induced

abortion with RU–486.

With the support of my family and friends, I have spent thousands of hours researching medical and scientific journals, talking

to doctors, legislators, State and Federal agencies, and to learn

about the drug RU–486, otherwise known as Mifepristone.

I believe that RU–486 is the substantial contributing factor responsible for Holly’s death. Currently, there have been eight deaths

reported by the FDA linked with the drug. Furthermore, there are

900 or more serious health consequences associated with RU–486.

One year after Holly’s death, I met with FDA and White House

officials, in September 2004, to discuss concerns over the drug’s

safety and health issues. Two months later, the FDA announced

additional black box warnings highlighting serious infections and

death.

On May 11, 2006, I attended the CDC-FDA-NIH scientific conference in Atlanta whose main purpose was to discuss the safety

of the drug regimen RU–486 to terminate early pregnancies. I presented a compilation of nearly 400 medical and scientific publications as a result of my 21⁄2 years of extensive research. It is my

hope this work will help to facilitate the understanding and causal

relationship of RU–486 and medical abortion infections. Medical experts, Dr. Esther Sternberg, Dr. James McGregor, and Dr. Ralph

Miech presented their concurring studies that RU–486 has serious

and lethal medical implications as evidenced through animal models. I have brought that disk here today for the subcommittee for

their review.

The FDA is responsible for protecting public health and, therefore, must reconsider the use of RU–486 in early medical pregnancy terminations. It should explore active epidemiology and

study animal models that show the alteration of the immune response by its reaction with RU–486 as it relates to serious and lethal infections. The FDA needs to provide the medical community

reliable means and methods to recognize cases of serious adverse

events associated with RU–486. Finally, the FDA needs to implement a confident reporting apparatus of these events so they can

accurately evaluate the safety and health consequences with the

use of the drug.

Patients, families, and their physicians are entitled to have all

the information necessary to make informed choices. The safety,

health, and welfare of women considering medical abortion with

RU–486 is paramount and should not be jeopardized with a drug

that can seriously cause them harm or death. Women have paid

the ultimate price with their health and their lives. How many

must die needlessly before this drug is removed from the market?

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Women have been and are still relying upon what they think is

truthful information concerning the limited risk involved with a

medical abortion. Yet, does the average patient, a teenager like

Holly, understand she may be risking her life taking RU–486 when

she is repeatedly exposed to statements like, ‘‘It is what women

have wanted for years. It is the first FDA-approved pill providing

women with a safe and effective non-surgical option for ending

early pregnancy.’’

There are no quick fixes or magical pills to make an unplanned

pregnancy go away. My family, friends, and community were deeply saddened and are forever marred by Holly’s preventable and

tragic death. It is my vibrant memory of Holly and her premature

death that have inspired me to make the public aware of the serious and lethal effects of the RU–486 regimen. Not a day goes by

that I do not recall her brilliant blue eyes, engaging smile, laughter, and sheer gentle beauty.

Holly’s personal drive and unwavering determination continue to

inspire me and give me strength to pursue these critical issues in

her name. It is a natural instinct to protect our loved ones and

speak for those who cannot speak for themselves. Thank you.

Mr. SOUDER. Thank you, and thank you for your willingness to

speak out.

[The prepared statement of Mr. Patterson follows:]

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Mr. SOUDER. Dr. Wood.

STATEMENT OF SUSAN F. WOOD, FORMER ASSISTANT COMMISSIONER FOR WOMEN’S HEALTH AND DIRECTOR OF THE

OFFICE OF WOMEN’S HEALTH, FOOD AND DRUG ADMINISTRATION

Ms. WOOD. Thank you, Mr. Chairman, and thank you, members

of the subcommittee. My name is Susan Wood and for the last 15

years, I have worked in women’s health policy within the Federal

Government. In each of my positions, I have advocated for the promotion of women’s health through increased research, services, and

prevention.

From November 2000 through August 2005, I was the Assistant

Commissioner for Women’s Health and Director of the Office of

Women’s Health at the U.S. Food and Drug Administration. Prior

to that, I was Director of Policy and Program Development at the

Department of Health and Human Services Office on Women’s

Health.

But I began my work in women’s health in 1990 as congressional

staffer for the bipartisan Congressional Caucus for Women’s Issues.

My scientific training is as a Ph.D. in biology and my research focused on basic cell biology and biochemistry, carried out at Boston

University and at Johns Hopkins University School of Medicine.

Over the last 15 years, I have been proud to be part of the following advances we have made in women’s health: expanded research

at the NIH in areas such as breast and ovarian cancer,

osteoporosis, heart disease, HIV/AIDS, and menopause; more inclusion of women in clinical research studies funded by NIH and regulated by the FDA; increased screening of women for cancer and for

sexually transmitted diseases that lead to infertility; better quality

mammography; coverage for preventive screenings by Medicare;

and improved prevention and services for victims of domestic violence.

While I was at FDA, the Office of Women’s Health supported

groundbreaking research, including research on medications taken

during pregnancy, to help find out about the proper doses of different medications that should be taken during the different stages

of pregnancy. We also funded important health outreach programs

in areas such as safe medication use, diabetes, menopause, and

hormone therapy. The office also worked to implement and track

the inclusion of women in clinical studies reviewed by FDA and to

ensure the analysis of the data for important sex differences in

safety and efficacy.

These advances and more were made through the concerted efforts of Members of Congress, the various agencies of the Department of Health and Human Services, the research and clinical communities, and women’s health advocates across the country. One of

the core principles that led to this progress was and remains ensure that we move forward based on the best available scientific

and medical evidence, and when that evidence is lacking, go out

and do the studies necessary to get it.

My commitment to women’s health is founded on these scientific

principles, knowing that this is the best way to expand our knowledge and improve the health of women and men both here in the

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United States and abroad. My commitment to women’s health, particularly to drug safety, is also founded in personal experience. I

lost my much-loved sister to cancer at age 34, caused directly by

a drug given to our mother while she was pregnant, the drug DES,

also known as diethylstilbestrol. I can assure you that my commitment to drug safety for women is deeply felt and always at the

forefront of my mind.

I appreciate your invitation to testify before this subcommittee

on the issue of Mifepristone and whether or not FDA has held this

drug to the best standard of review on safety and efficacy.

Let me point out that Mifepristone is not Plan B emergency contraception, which prevents unintended pregnancy and the need for

abortion, but Mifepristone, RU–486, is a medication that causes

abortion in the first few weeks of pregnancy.

Now, I was working at the Department of Health and Human

Services Office on Women’s Health at the time of the Mifepristone

review. I, therefore, have no direct knowledge of the evaluation and

the review that was happening at FDA, and that is exactly how it

should be. The FDA was working independently, reaching its conclusions and decisions based on its usual processes and evaluation

of the data. In fact, there was curiosity among many of us at the

Department level about the subject, but we were given clear instruction by senior management of the Department that we were

not to inquire, even informally, of our women’s health colleagues at

FDA about the status of the Mifepristone application. This was to

ensure that there was not even a perception of Departmental influence on this highly visible application.

Upon my arrival at FDA in the fall of 2000 as head of women’s

health there, this independence of decisionmaking was confirmed to

me by the professional staff that was directly involved in the review. The evidence presented to the FDA and the subsequent experience with the marketed product in the United States tells us that

this is a safe and effective method for early termination of pregnancy.

Now, the recent deaths due to Clostridium Sordellii in women

who have had a medical abortion are truly tragic and I do offer my

sincere condolences to Mr. Patterson, his family, and the families

of all the women. These deaths due to this bacterial infection have

put us on notice that health professionals and women need to be

aware of this potential risk.

More importantly, the close surveillance of adverse events associated with the use of Mifepristone have alerted us that this bacterial infection is present and caused the death of other women

who have given birth or had a miscarriage—more, in fact, than the

number of women who underwent a medical abortion. This pattern

of infections and deaths after pregnancy is indeed disturbing and

tells us once again that we need to do more to ensure safe pregnancy and safe motherhood. This is not limited to women who have

been exposed to Mifepristone, and to focus solely on the women

who have had a medical abortion is to miss the real threat to the

health of women.

Our surveillance systems for maternal mortality and morbidity

have been limited over the years due to limited funding and lower

priority. These systems need to be improved and expanded to capVerDate 11-MAY-2000 10:35 Jan 26, 2007 Jkt 000000 PO 00000 Frm 00131 Fmt 6633 Sfmt 6633 D:\DOCS\31397.TXT HGOVREF1 PsN: HGOVREF1
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ture not only the impacts of Clostridium, but also so that we can

understand and prevent the other risks that women face with pregnancy.

With Mifepristone, we can be confident that we have identified

all or most of the adverse events and deaths. We cannot say the

same for infections and deaths caused by C. Sordellii in women

who have given birth or had a miscarriage, and those numbers may

indeed be higher.

I applaud the CDC, FDA, and NIH for holding the scientific

meeting on May 11th to begin the process of examining the data

that we currently have on the nature of these infections, potential

strategies for prevention, early detection, and effective treatment,

and the research agenda that needs to be undertaken to answer

the critical questions that exist. Although I did not attend, I understand that meeting participants presented current information and

discussed the future needs to address this emerging infection.

Questions have been raised about whether Mifepristone is involved through changes of the immune system. These are serious

questions that need to be studied, but at this point do not seem to

be the compelling mechanism. Experts at CDC, FDA, and NIH reviewed the current information and appear to recognize that the infections and death due to C. Sordellii are not due to a simple drug

effect. Rather, this is a complex situation that involves multiple

factors that are linked to pregnancy. Getting to the bottom of what

puts women at risk for this infection and what can be done to prevent and treat it is of the highest importance.

The experts at the meeting last week identified several clear

areas of research that are needed, including improved surveillance

of infection in women who have given birth or had a miscarriage,

improved diagnosis, the role of antibiotics, the possible development of an antitoxin or other therapies, and further research on

the nature of the Clostridium bacterium itself.

I strongly urge the subcommittee to support this research and

surveillance agenda to address this threat to women’s health. By

doing so, we can improve the health outcome of all pregnant

women and also help ensure improved maternal outcomes. Please

do not allow politics to trump science once again when the health

of women is at stake. Thank you.

Mr. SOUDER. Thank you.

[The prepared statement of Ms. Wood follows:]

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Mr. SOUDER. Dr. Rarick.

STATEMENT OF LISA D. RARICK, M.D., RAR CONSULTING, LLC

Dr. RARICK. Good afternoon, and thank you, Mr. Chairman and

members of the subcommittee, for the opportunity to provide testimony in this important discussion of the use of Mifepristone for

medical abortion.

My name is Lisa Rarick. I am a medical doctor with training and

board certification in obstetrics and gynecology. I received my medical degree from Loma Linda University School of Medicine and my

OB/GYN training at Georgetown University. After my residency, I

remained on the faculty of the Department of OB/GYN at Georgetown and soon also began to work at the U.S. Food and Drug Administration.

Although my work at the FDA began as a part-time position in

the Center for Drug Evaluation and Research looking into fetal effects of drug exposure, I quickly grew interested in CDER’s broader

mission of protecting and promoting public health through pharmaceutical regulation.

I transitioned to full-time employment at the FDA by September

1989. My work at CDER progressed from the review and analysis

of fetal exposure information to work as a primary medical reviewer, also called medical officer, for new drugs in the Division of

Metabolic and Endocrine Drug Products. As a medical officer, I had

responsibility for the review of investigational and approved drugs

used in various conditions for women’s health.

In 1996, a new division, the Division of Reproductive and Urologic Drug Products, was created. I was named as its first Director.

During that time, I was well acquainted with the application for

Mifepristone and participated in the review as well as the Advisory

Committee meeting discussions regarding this product. I was actively involved in the regulatory actions taken for this product during my tenure as Division Director.

By the year 2000, I continued to move up CDER’s organizational

ladder in various positions and I spent my final year at the FDA,

July 2002 to July 2003, in FDA’s Office of Women’s Health.

My conclusions after review of the available scientific information regarding Mifepristone while at the agency, as well as my subsequent review, are consistent with the FDA’s conclusions. The approval of Mifepristone in September 2000, more than 4 years after

its application was submitted, was based on more than the necessary number of studies submitted and reviewed by the division

of which I was Director. As many are aware, an application submitted to the FDA to support a new drug approval must contain adequate and well-controlled studies to confirm efficacy and safety.

Generally, the word ‘‘studies’’ is interpreted as requiring two adequate studies. Although there are some instances where one study

is acceptable, most applications contain the usual two confirmatory

clinical trials. In the case of Mifepristone, three studies were submitted in order to establish efficacy and safety for early intrauterine pregnancy termination.

The clinical review of this product included an analysis of all

human studies utilizing Mifepristone, including these three large

Phase 3 studies involving close to 2,500 women. The Reproductive

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Health Drugs Advisory Committee was convened in 1996 and

asked to discuss and provide recommendations during the review

of this application. The committee reviewed these Phase 3 studies.

They also heard from over 30 speakers during the open public

hearing portion of that meeting. They recommended by a vote of

six-to-nothing, with two abstentions, that benefits exceeded risk.

The approval action taken by the agency in September 2000 utilized the regulatory option of Subpart H restrictions for this product. Contrary to the assertion that Subpart H designation was

based on a desire for accelerated approval of Mifepristone, this is

clearly not the case. In this case, the application of Subpart H regulations actually provided FDA with more rigorous oversight and

allowed for the formal imposition of restricted distribution. In essence, a Subpart H approval is meant to restrict the use of

Mifepristone, not accelerate its availability.

Clearly, since approval, the FDA has remained extremely vigilant in its regulatory oversight of Mifepristone. The labeling has

been revised three times since its year 2000 approval. Each of

these labeling change actions followed a complete FDA review of

the clinical studies and post-marketing information available for

Mifepristone and resulted in updated presentations of scientific information for consideration by prescribers and patients. Labeling

revisions such as these are an important and expected part of drug

regulation and indicate active and appropriate review of post-approval information.

As with any medication, when reports of serious adverse events

associated with Mifepristone use are received by FDA, they are

carefully analyzed and rigorous investigation is employed to ascertain the relationship, if any, between the drug and the event as

well as to ascertain mechanisms to prevent similar events in the

future.

I applaud the FDA’s efforts to better understand the recent findings of serious bacterial infection reported in a small number of

women after Mifepristone use and in other pregnancy-related conditions. In particular, as you have heard, the FDA, CDC, and NIH

held a joint meeting on May 11th of this year. This meeting was

an effort in which experts came together to better understand reports of morbidity and mortality associated with Clostridial infections. My understanding from those who attended the meeting is

that the rare cases of Clostridial infection and death reported in

Mifepristone users are, at this time, not explained by a simple

drug-based association. In fact, the presentations and the discussion made it clear that these infections are occurring in various

pregnancy-related conditions, not only post-abortion settings.

I say this not to dismiss the fact that some infections are occurring in women who have chosen medical abortion but to emphasize

that the agencies must and are looking at the infection trends more

broadly. Further investigation and understanding of these infections and various pregnancy-related outcomes is essential.

In conclusion, I urge this subcommittee to allow the FDA to continue to do its job. There is no evidence that FDA is shying away

from the difficult questions of risk and benefit for this indication.

Risks are being investigated. Adverse event reporting for medical

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plored risks related to pregnancy and post-pregnancy events. Let

us all continue to support the FDA and others as they fulfill their

mission to protect and promote the public health.

The public can only have confidence in the FDA’s conclusion if

it knows that it is impervious to political pressure. I urge us to resist the temptation to interfere in this instance and instead for

Congress to allow the dedicated public health professionals at the

FDA to do their jobs, continue their investigations, and take any

actions that might be needed to protect and promote women’s

health. Thank you.

Mr. SOUDER. Thank you.

[The prepared statement of Dr. Rarick follows:]

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Mr. SOUDER. Dr. Harrison.

STATEMENT OF DONNA J. HARRISON, M.D., MEMBER,

MIFEPREX SUBCOMMITTEE OF AMERICAN ASSOCIATION OF

PROLIFE OBSTETRICIANS AND GYNECOLOGISTS

Dr. HARRISON. Chairman Souder, Mr. Waxman, Ranking Member Cummings, and distinguished members of the committee, I

present my testimony based on my observations and research as a

board-certified obstetrician-gynecologist who has personally examined 850 of the 950 adverse event cases reported to the FDA after

RU–486 abortions and also based on data from the CDC presented

at the CDC workshop in Atlanta last week, which I attended.

The FDA outlined areas of consideration prior to withdrawing

approval of RU–486 and these are as follows: Examining the evidence that RU–486 caused the adverse events; how soon these

events occurred after RU–486; how severe these events are; can

these adverse events be predicted or avoided; and how safe is the

alternative treatment, surgical abortion?

I will speak first about the five Clostridium Sordellii deaths. At

the CDC-FDA workshop in Atlanta last week, Drs. Sternberg,

Miech, and McGregor detailed the evidence that RU–486 interferes

with the body’s ability to fight infection by blocking glucocorticoid

receptors in the immune system. One of the many studies demonstrated that mice injected with a certain bacterial product die at

a rate of 13 percent, but when these mice are given even tiny doses

of RU–486, 100 percent of the mice die. The five women who died

from infection with C. Sordellii during their RU–486 abortions

tragically illustrate the same concept, as illustrated by data from

the CDC presented by Drs. Fischer and McGregor.

The statement has been made by some spokespeople from the

FDA that the C. Sordellii deaths may be due to a change in the

bacteria itself. This question was specifically addressed and specifically refuted by CDC data presented by Dr. McDonald. Some FDA

spokespeople have implied that there are comparable numbers of

deaths from C. Sordellii in term pregnancy. This is epidemiological

nonsense. Dr. Fischer reported CDC data which revealed 5 deaths

from C. Sordellii in 550,000 RU–486 abortions. Dr. Fischer reported 8 deaths from C. Sordellii in 30 years out of well over 70

million deliveries. The risk of death from C. Sordellii with RU–486

is well over 50 times greater.

Dr. Fischer reported no deaths from C. Sordellii in 30 years of

surgical abortion data. Dr. Greene reported 25 deaths from other

causes of infections in 13,161,608 surgical abortions. The risk of

death from Clostridium Sordellii with RU–486 is 10 times greater

than the risk of death from all other kinds of infections in surgical

abortion. Dr. Greene from Harvard recently published this data.

Remember also that the women who died during their RU–486

abortions were all healthy. They had no risk factors predisposing

them to death, especially from a bacteria that rarely causes death

in humans with a normal immune system. The CDC-FDA panelists

were unable to identify any risk factors to predict who is more likely to die from C. Sordellii infection, nor could they identify any

treatment that would save a woman once she was diagnosed with

C. Sordellii infection. C. Sordellii infection during an RU–486 aborVerDate 11-MAY-2000 10:35 Jan 26, 2007 Jkt 000000 PO 00000 Frm 00143 Fmt 6633 Sfmt 6633 D:\DOCS\31397.TXT HGOVREF1 PsN: HGOVREF1
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tion is 100 percent fatal, despite any and all treatment. These

deaths are completely preventable.

But septic deaths are not the only health hazard posed by RU–

486 abortions. At least 116 women have been transfused from massive bleeding, and at least 54 of them lost over one-half of their

blood volume. The medical literature states that 1 to 2 out of every

1,000 women will need to be transfused for massive hemorrhage.

Studies that compared surgical and RU–486 abortions show much

higher rates of blood loss in RU–486 abortions. These are detailed

in my written testimony. And there is no way to predict who will

hemorrhage.

The hazards to women’s health from just the infections and hemorrhages alone due to RU–486 clearly constitute ample cause for

the FDA to withdraw approval from RU–486. Thank you.

Mr. SOUDER. Thank you.

[The prepared statement of Dr. Harrison follows:]

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Mr. SOUDER. Professor Snead.

STATEMENT OF O. CARTER SNEAD, ASSOCIATE PROFESSOR,

UNIVERSITY OF NOTRE DAME LAW SCHOOL, AND FORMER

GENERAL COUNSEL FOR THE PRESIDENT’S COUNCIL ON

BIOETHICS

Mr. SNEAD. Thank you very much. Thank you, Chairman Souder,

Ranking Member Cummings, Ranking Member Waxman, Congresswoman Schmidt. Thank you very much for inviting me today

to discuss the legal dimensions of this question, which I think are

not controversial and not contentious despite the contentious nature of the underlying issue that we are discussing.

In my written comments, I lay out for the committee the various

regulatory options that the FDA would have and also that the Secretary of Health and Human Services would have if they were to

decide that the circumstances warranted intervention in this matter beyond the changing in labeling and the public health

advisories that have already been undertaken.

The central conclusion that I reach in my written testimony is

that the FDA is well equipped to respond forcefully to the concerns

raised by the co-panelists today regarding the safety of

Mifepristone should it decide that such a response is warranted,

and I focus on three principal mechanisms in my written testimony

that are available both to the FDA and to the Secretary of Health

and Human Services. In my oral testimony, I am going to focus on

the one mechanism that is unique to Mifepristone given the circumstances of its approval, that is to say under Subpart H, which

has received some discussion today already.

Subpart H was devised by the FDA to permit the approval of

drugs intended to treat serious or life-threatening illnesses where

such drugs imposed a greater-than-normal acceptable risk to the

patient. That is, Subpart H was designed in part as an alternative

means of approval for useful drugs that would otherwise fail the

traditional risk-benefit calculus required for FDA approval. Subpart H facilitated approval of such drugs by imposing additional

post-marketing restrictions above and beyond what was required in

the normal mechanisms of approval, as has been mentioned by numerous panelists.

These post-market restrictions are absolutely crucial both in

terms of their effectiveness and in terms of compliance with those

restrictions if the mechanism of Subpart H is to serve its purpose.

As the FDA has said in its own final rule, and I am quoting from

the final rule, ‘‘For drugs approved under the accelerated procedure

regulations, the risk-benefit assessment is dependent upon the likelihood that post-marketing restrictions will enable safe use.’’

Most important for present purposes, it is clear that Subpart H

provides a mechanism for expedited withdrawal of approval upon

a finding that the post-marketing restrictions are either ineffective

or are not being observed by the manufacturer. As the FDA noted

in its final rule also, if the restrictions do not lead to safe use, the

risk-benefit assessment for these drugs changes significantly. FDA

believes that if that occurs, rapid withdrawal of approval as set

forth in this rule is important to the public health.

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So this is a unique mechanism, and as the representatives and

former representatives of the FDA have noted already, Subpart H

is intended to facilitate the move to market of drugs through the

imposition of these additional post-market restrictions. It is not difficult to see the implications of Subpart H for the case of

Mifepristone.

Danco Laboratories benefited from these unique approval regulations, the cost of which was a promise to comply with the post-market restrictions that the FDA thought appropriate under the circumstances. Thus, if the FDA—and I formulate this as a conditional because I am not privy to any facts that would go to this conclusion, this is a judgment that would have to be made based upon

an evaluation of Danco’s behavior—if, in fact, the FDA were to conclude that Danco was not in compliance with these post-market restrictions, or alternatively that the post-market restrictions themselves were not effective to render the drug safe for its approved

use, then the FDA would be within its authority to withdraw approval following notice and an opportunity for hearing for the drug

itself.

And, in fact, it would be difficult to imagine that if FDA did come

to that conclusion, that they would not regard it as its duty to

withdraw approval, because in the absence of effective post-market

restrictions, Mifepristone would presumably not be able to satisfy

the statutory criteria for safety. If this were not the case,

Mifepristone would have been approved under the traditional provisions rather than under Subpart H.

So essentially, among the mechanisms that I discuss in my written testimony, Subpart H provides a unique opportunity for the

FDA to maintain control over the use of Mifepristone, and if under

its own inquiries the FDA finds that the post-marketing restrictions are not effective or are not being observed, then the truncated

and expedited withdrawal provisions would be activated and FDA

would be fully authorized to withdraw approval.

As has been suggested, I agree, I think FDA would have the obligation to answer any open questions regarding the efficacy of the

post-market restrictions and also to answer—to inquire about and

answer any questions and respond appropriately to any concerns

regarding Danco’s compliance with the post-marketing restrictions.

Thank you very much.

Mr. SOUDER. Thank you.

[The prepared statement of Mr. Snead follows:]

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Mr. SOUDER. I would like to start with a question for Dr. Wood

and Dr. Rarick. In your testimony, you pretty aggressively said,

both of you, that there was no evidence to support the hypothesis

that Mifeprex interferes with the immune response. NIH researcher Esther Sternberg’s studies directly conflict with your assertion. Dr. Sternberg has conducted animal studies that demonstrate that RU–486 can suppress natural immune response. Dr.

James McGregor of Los Angeles Women’s and Children’s Hospital

has published work hypothesizing the pathway by which C.

Sordellii causes multi-organ infection after suppressing the immune response. Ralph Miech of Brown University describes a

mechanism whereby RU–486 suppresses the immune system and

causes shock.

Have either of you read in entirety any of these papers, not just

a summary, but have read those papers, and are you aware of any

research that calls into question Sternberg, McGregor, and Miech’s

conclusion that Mifepristone may interfere with the immune response? You made a flat assertion. What about those studies?

Ms. WOOD. I will say, no, I have not read those studies in full.

However, I spoke to Dr. Sternberg and discussed her findings and

I would agree with you that there are certain—this is certainly a

pathway that needs to be investigated. I think the issues and the

use of the questions that arise about studies is that they are not

questioning the studies themselves or even the outcomes of their

studies, but they are, in fact, limited to particular species of rat

and mouse and do not apply across even the different species of

rats and mice. There is great variability in the level of the responses to different things.

This is an extraordinarily complex issue of how the immune system is regulated, either regulated up or regulated down by

various——

Mr. SOUDER. So let me ask you——

Ms. WOOD. This is complex, and I agree with you, there are——

Mr. SOUDER. Let me ask you this question. So I don’t misrepresent what you said, you said you have talked to Dr. Sternberg and

you think that it is inconclusive, but in fact, in certain types of animals, the study shows that it suppresses?

Ms. WOOD. In her animal studies, it shows what it shows——

Mr. SOUDER. And——

Ms. WOOD [continuing]. But it is very preliminary——

Mr. SOUDER [continuing]. You are not familiar with McGregor or

Miech’s studies?

Ms. WOOD. I have——

Mr. SOUDER. Then how in the world under oath could you make

an assertion like you did, under oath?

Ms. WOOD. I asserted that this is a very worthwhile and serious

pathway to explore——

Mr. SOUDER. You said there was no evidence.

Ms. WOOD [continuing]. But it does not look like——

Mr. SOUDER. Under oath, you said there was no evidence.

Ms. WOOD. I did not say that.

Mr. SOUDER. OK.

Ms. WOOD. I said there is not compelling evidence.

Mr. SOUDER. Dr. Rarick——

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Ms. WOOD. I said there needs to be further research.

Mr. SOUDER. Dr. Rarick, are you familiar with these studies?

Have you read them through and——

Dr. RARICK. No, and I did not attend the meeting at the CDC.

I similarly looked at some of the slides from the CDC presentation.

I think the last part of your question was the most key word, which

you said, don’t you agree that they may be—that there may be a

mechanism. I don’t think we are disputing that there may be some

mechanism of Mifepristone on glucocorticoid receptor issues and

that the science in animals may have both sides of this story. Pregnancy, as you well know, is a complicated hormonal milieu with all

kinds of receptor activations and inactivations of the various hormones that are happening during a pregnancy and pregnancy.

I think the last part of your question, which was ‘‘may,’’ do we

know that Mifepristone is causing an immune reaction in women?

No. Might they? Possibly.

Mr. SOUDER. Well, it is very important because I was subjected

to opening statement after opening statement with the implication

that we are inserting politics. You in your statement said—it is

really interesting, because if you want to restore the faith of the

American people, they have to feel that there is actually an honest

debate going on, and there is an increasing feeling that certain people who get control of the establishment research want to jam their

views down everybody else and not listen to alternative research.

And the assertion was made that there is no contradiction. There

is a debate going on. We need to make sure that debate goes

through.

Now, I was blown off in a question, quite frankly, to the Assistant Commissioner on the blood question. Dr. Harrison, my understanding of what you—did you go through the different cases on

those who were reported? You seem to imply that these were transfusion cases and fairly serious bleeding, whereas I got the impression, oh, bleeding is common. This wasn’t extraordinary bleeding.

Dr. HARRISON. I have had a chance, an opportunity to review 850

of the 950 cases, which we obtained by Freedom of Information Act.

Of those 950 cases, I reviewed 68 women who were transfused. Of

those 68 women who were transfused, we have 9 transfusion cases

where the women received over four units of blood. We have 10

cases where they received over three units of blood and 38 cases

where two units of blood were transfused. And there were also 10

cases where the adverse event report to the FDA did not document

the number of cases transfused, and this is in settings where the

clinical picture in the adverse event report was consistent with

massive hemorrhage, which to me is unconscionable if you are actively trying to give the description of how much bleeding is there,

to not even have a hemoglobin concentration or not even have an

amount of blood transfused.

In addition to those that I reported in my paper, which is what

I just quoted, there were an additional 12 in the adverse event

cases from September 2004 to July 2005, and I would refer you to

my spreadsheets that I gave you. And of those cases, the 12 that

I mentioned were life-threatening hemorrhages. So of the lifethreatening hemorrhages, it is basically 54 life-threatening hemorrhages altogether as of July 2005.

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When I use the CTCIE criteria for coding these, that is a criteria

that is used by the—developed by the National Cancer Institute to

grade adverse events and to determine how serious they are so that

you can compare them. What I used was a criteria of a women with

a documented hemoglobin of less than 7—remember, the normal

hemoglobin is 13—and transfused at least two units. So these are

women who have lost over half of their blood volume.

I have in that time, from September 2000 to July 2005, 54 cases.

Now, if you look at that compared to the number that the FDA reports, which is 119, that is almost half of the women who were

transfused were in life-threatening situations. That is not the kind

of bleeding that you normally expect from surgical abortion. It is

also not the kind of bleeding that you normally expect from a spontaneous abortion. In fact, it is more comparable to the kind of

bleeding you see in major motor vehicle accidents. So this bleeding

that is being said as normal and expected is a large amount of

blood.

Mr. SOUDER. Thank you, and one question for Mr. Snead. Is

there a way that during additional research, and maybe Dr. Rarick

or Dr. Wood would be able to answer, under normal research, that

a drug cannot be taken—to me, taken off the market implies it is

not coming back on, but could be suspended while additional research is done?

Mr. SNEAD. Sure. I take up three mechanisms in my testimony,

two of which are mechanisms that require notice and an opportunity for a hearing before the actual approval is withdrawn. But

the third option that I take up is actually an option that is exercisable only by the Secretary of Health and Human Services. It is

a non-delegatable authority vested in the Secretary of Health and

Human Services to declare a particular an imminent hazard. If he

does so, the effect of that is to immediately suspend the approval

of the drug and then the manufacturer then provided an expedited

sort of post facto hearing to make their case for why it was improvidently declared an imminent hazard.

Mr. SOUDER. What about if—that still puts the burden on—because this is obviously a very explosive political question because

it is abortion. Whether I like it or not or whether anybody likes it

or not, it is a legal process and we don’t have a right to stop it.

I personally have my views on RU–486. Other members have their

views on RU–486. The question is to say that it is being stopped

and then the manufacturer has to make a case is different than

saying additional research needs to be done, because that would

imply that the government has determined that it is unsafe as opposed to additional research needs to be done.

Mr. SNEAD. That is right. In order to effect the imminent hazard

privilege the Secretary enjoys, he would have to make a determination that it does, in fact, present an imminent threat, which is a

judgment about the safety of the drug itself. There is a provision

in the regulations for an administrative stay. The Secretary or the

Commissioner has the authority to stay the effective date of any

decision at any point in the process, which I think is more of what

you are talking about, which is sort of—it is the equivalent in civil

litigation to a temporary restraining order or a permanent injunction which sort of holds in place—which freezes the status quo and

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then tries to resolve whatever dispute or questions that there

might be.

Mr. SOUDER. Mr. Cummings.

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

Dr. Wood, I want to go back for a moment. I have always been

one to—I don’t like to leave things hanging. It seems like you were

trying to say something and I want to give you an opportunity. The

chairman asked you some questions and implied that you said

something that you said you didn’t say. I just wanted to give you

the opportunity to clear that up if you would like. If you don’t want

to, that is fine.

Ms. WOOD. I would just make the point that I actually agree

with the chairman and also with Mr. Patterson about the need for

answering all of these questions. Is the immune system involved or

compromised? What is it that causes this bacteria to become so virulent in women? What is it about pregnancy, either the ending of

pregnancy either through termination or through childbirth, that

has led to these deaths and these infections?

So I actually would agree that more research is necessary and

my statement in my written statement and I believe orally was

that I just don’t—my reading of it at the point is that the evidence

is not compelling to be conclusive that is the answer, but I certainly would urge any and all research to address these questions.

Mr. CUMMINGS. Thank you very much. Let me just go on from

there. Tell me, Dr. Wood, could you explain why some women

would prefer Mifeprex over a surgical abortion?

Ms. WOOD. Mifeprex is available to women much earlier in the

course of pregnancies and so the termination of the pregnancy can

be done in a matter of days after the pregnancy is established, of

implantation in the womb, and up to several weeks. This is much

earlier than a regular surgical abortion, which is required to wait

a few more weeks. So this provides an earlier option if the women

is determined to end pregnancy. It is also one that can be more private and also avoid surgery, which certainly many people prefer in

making a decision.

I would also agree that access to all information about any

known risks as they become known for any type of medical procedure needs to be available to women, and in the case of Mifeprex,

because of the patient information that is required under the distribution restrictions on Mifeprex, that, in fact, we can work to assure that all women do get up-to-date information on any risk of

any medical abortion.

Mr. CUMMINGS. It seems that as I listen to Mr. Snead and I am

listening to your testimony and others, it seems as if the key question is where is the line drawn with regard to taking a drug off the

market and I am just trying to figure out, what is taken into account when determining whether a drug should stay on the market, like this, for example? It seems that Mr. Snead has very eloquently stated all the options that could happen if the line is

crossed. The question, it seems to me, is where is the line and

when is it crossed.

Ms. WOOD. That question is the type of question that FDA has

to deal with every day looking at every product when they get in

a report of adverse events or deaths. And it is not simply the report

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of the deaths, but it is whether or not there are causal links, the

magnitude of the response, how many people are affected in terms

of the baseline use. There are many factors in trying to determine

when a product should come off the market. It is not a simple question, but it is that balance of risks and benefits, and that is something the scientists and clinicians at FDA do every day and I would

just urge that they be allowed to continue what they are doing,

which is investigating this, evaluating it, and making their determinations without intervention.

Mr. CUMMINGS. Now, have you ever been in a position, you or Dr.

Rarick, where you are, say for example, any position and certain

evidence was presented to you and you were the person who suggested that we, or had the power to suggest that FDA take another

look at a drug to determine whether or not it stays on the market

at all, either one of you?

Dr. RARICK. I think I can speak to that, thank you. FDA does

that kind of determination all the time. Every time you see a new

labeling come out on a product, that means the FDA has relooked

at the studies as well as the post-marketing events to assess it.

Maybe there is a new safety issue that needs to be put on the label

or not. When those discussions happen, there is always the option

of considering withdrawal of the product if those risks outweigh

benefits and that calculation is done often for all the products that

are available.

Mr. CUMMINGS. I see my time is up, but just one last question.

You heard Dr. Harrison.

Dr. RARICK. Yes.

Mr. CUMMINGS. Is there anything that she said that would make

you all say, well, you know, maybe—I am just trying to be fair

here—make you all say, well, maybe this is something we need to

take another look at? I am just curious. Have you heard something,

anything here today that causes you any kind of radar to go up?

Dr. RARICK. My perspective is what I have heard here today is

extremely important, but it is all information that the FDA is well

aware of.

Mr. CUMMINGS. OK.

Dr. RARICK. The adverse event reporting that Dr. Harrison is

quoting is from the FDA.

Mr. CUMMINGS. OK.

Dr. RARICK. They are looking at this every day. They were involved in the CDC meeting last week. My impression from this discussion is that, yes, FDA is on the case. It is looking into this.

These are really important questions and they should take an action that is appropriate with the data.

Mr. CUMMINGS. Thank you very much.

Mr. SOUDER. I want to make sure in the record that we are clear.

Dr. Wood stated, this is a question to be studied, and to the degree

I said there was—you said there was no evidence, that was incorrect. But you did say, if the immune system were suppressed, we

would expect to see, and we didn’t. We would expect to have seen

this, and we didn’t. Somewhere, we would expect to see this, and

we didn’t. Thus far, this pattern has not emerged. Basically, what

you said was there was no evidence, and what I asked you was

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about three studies. Then you said those studies need to be studied

further.

And then on top of that, you had denied, in effect, what was the

consensus of the CDC panel, that there was, in fact, evidence. Dr.

Rarick said in her statement, to date, there is no evidence that has

emerged to support the hypothesis, which did not refute either of

the three studies or the fact that the scientific community at a recent panel of which neither of you were present concluded the opposite conclusion.

Now, more research needs to be done on it, I will grant that, and

I think that has been clear today. But it was not a false assertion

that I made about Dr. Rarick said specifically in her testimony, no

evidence, and Dr. Wood basically didn’t cite any evidence. But I

think we all agree more study needs to be done to see how common

and how you disaggregate the two types of things.

Mr. CUMMINGS. Would the gentleman yield just for 1 second for

a clarification?

Mr. SOUDER. Yes.

Mr. CUMMINGS. Mr. Chairman, all I was trying to do when I

asked the question is I don’t like for witnesses—I think when people are—these are professional people and I don’t want them to

ever be in the position where they come before the committee and

for whatever reason they don’t get a chance to explain something

that puts into question what they have said, their credibility. I just

think it is, as one human being to another, bad to do that. That

is all.

Mr. SOUDER. And I understand the gentleman’s concern, but you

also know in a 5-minute rule that she had answered the question

and she was then off to another. I didn’t mean to cutoff her ability

to respond, and that is why I want to grant that you, in fact, said

more study was needed and the direct ‘‘there was no evidence’’

quote was actually Dr. Rarick’s, not Dr. Wood’s, but Dr. Wood had

a series of things that suggested it wasn’t. I want to make sure the

record reflects accurately, as you did.

Mrs. Schmidt.

Mrs. SCHMIDT. Thank you, Mr. Chairman. I actually have questions for Dr. Rarick, Dr. Harrison, and Mr. Patterson, if that is all

right.

Dr. Rarick, Dr. Wood stated that politics—she didn’t want to see

politics triumphing science once again, and none of us want to see

that. My concern is how this product came to market in 2000. Dr.

Wood stated that controlled trials were performed in support of the

RU–486 FDA application. Could you tell us what the control group

was in those trials that made those trials controlled? More specifically, was there a double-blind study, and if so, how did it result?

Dr. RARICK. Certainly. In this area of pregnancy-related conditions, including contraception or birth control, oftentimes the FDA

accepts clinical trial designs that are appropriate and use historical

controls. So, for example, you can’t have women who come in and

want to contracept and suggest that they should be blinded and

randomized to placebo versus a contraceptive that you expect to

work and expect that to be an ethical trial design.

Similarly, in medical abortion, when a woman comes in with a

request to terminate a pregnancy, you can’t suggest to her, well, we

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think this pill will terminate your pregnancy based on all the

science, but we want you to sign a consent form that states you will

be randomized to a pill that we know has no effect—a sugar pill,

a placebo pill—on your pregnancy and then let us know if you

abort or not. That is just simply not a reasonable trial design.

In this setting, you know if you don’t do anything, there is almost

a 100 percent chance that they will continue to be pregnant, although there is a miscarriage rate, as you well know. But in an

early intrauterine pregnancy termination, you can’t expect placebo

to have any potential effect. So you go back to the sort of historical

control concept, that if you didn’t give the woman anything, what

would be the chances of her aborting versus giving her something.

Mrs. SCHMIDT. Mr. Chairman, I have to comment on this because

I am troubled by this statement. In 1995, my father was involved

in a very critical car wreck and he almost died and they put him

on a clinical trial regarding getting him off of oxygen, because the

longer you stay on oxygen the harder it is to get off the oxygen.

It was a double-blind study. We didn’t know whether they were

giving him the opportunity to wean off quicker or not. The alternative obviously is more of an opportunity to die.

So the argument that a double-blind study can’t be used in this

case but it can be used in a life or death case of a man in an ICU

unit at University Hospital, that just doesn’t fly in my face and

that is what makes me concerned with all of this, is that I believe

politics was there in 2000. I think that while I was back home in

another role in my life, I think that there was a rush to judgment

to get this drug to market and what we are seeing now are some

problems that are arising from it.

My concern is we don’t have adequate knowledge one way or another whether RU–486 has a direct or an indirect cause for death.

We do know that there is a relationship between the death and the

taking of the drug. We don’t know whether it is direct or indirect.

But we do know that there is a relationship. And my concern is

that politics, once again, is playing out.

But my next question is actually for Dr. Harrison. Your colleagues say that if the theory were true that Mifeprex comprised

the immune system, then we would see a higher rate of other kinds

of infections. Your colleagues say this. What is your response to

that?

Dr. HARRISON. Well, I think the focus of the CDC meeting and

most of our discussion today has been on the infectious deaths, but

there were actually at least 7 other life-threatening infections to

date in the 850 severe adverse event reports that I reviewed, 1 of

them being a 15-year-old who spent several weeks in the intensive

care unit but lived.

So there is an issue of critically looking at those infection-related

complications and there is a secondary issue in even identifying

those infection-related complications, because if Mifepristone suppresses the immune system, the infection may not be pelvic, and

if it is not pelvic, it may not be recognized as being related to the

Mifepristone abortion and, therefore, never reported. So we have a

number of women walking around potentially with a decreased immune system or decreased ability to fight off infection whose conVerDate 11-MAY-2000 10:35 Jan 26, 2007 Jkt 000000 PO 00000 Frm 00360 Fmt 6633 Sfmt 6633 D:\DOCS\31397.TXT HGOVREF1 PsN: HGOVREF1
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nection with their Mifepristone abortion will not be known, and

that is a big concern.

Mrs. SCHMIDT. Thank you, and my final question is for you, Mr.

Patterson. I am so glad that you are brave enough to bring this to

our attention and I know that your daughter is smiling down on

you. You are a very brave person.

What do you have to say about the assertion that the benefits

for RU–486 weigh the risks associated with it and what do you

think should be done to protect other families from the same tragic

fate that your family continues to experience?

Mr. PATTERSON. I think if you were to ask Holly here today, had

she lived, if the benefit outweighed the risk, I think she would disagree. I have spent many, many hours researching this drug and

I can tell you that I feel very strongly about the link that this drug

does impair the innate immune system and predisposes women to

these—and can predispose these women to serious and lethal infections. There has been a lot of discussion of that at the CDC, FDA,

and NIH conference.

I think the research is absolutely necessary. I think we have information that has come out from very well renown and respected

doctors. It is very compelling that we need to pursue this research

to answer these questions.

Had Holly been given all the information in the very beginning,

you know, talking about the risk-benefit profile and weighing those

options, I think that had she been given all the information she

needed, she certainly would not have chosen an RU–486 abortion

because Holly was not the kind of young lady that would risk her

life for any reason whatsoever. Being the pinnacle of fitness and

the type of healthy individual that she was, she would have chosen

an alternate method and I can’t say enough that it is all about having all the information to make an informed choice that is in the

best interest of that particular individual and the family that are

making those decisions.

Mr. SOUDER. Mr. Waxman.

Mr. WAXMAN. Thank you, Mr. Chairman.

I am trying to sort out these different positions and I guess the

first thing we are talking about is an infection that has proved to

be fatal in some cases and this infection is called C. Sordellii. The

first question is, is this infection caused by this drug? People who

didn’t use this drug have had this infection, is that accurate, Dr.

Rarick?

Dr. RARICK. Yes.

Mr. WAXMAN. So it is not related exclusively to this drug. Now,

we know that some people who used this drug had the infection.

We don’t know whether it caused the infection, is that accurate?

Dr. RARICK. Correct.

Mr. WAXMAN. So we need to get an answer to that. If the theory

is that the immune system is suppressed because of the RU–486,

wouldn’t we have a lot of evidence more of other infections besides

this one, because this is a fairly rare kind of infection, isn’t it?

Dr. RARICK. It is a very rare infection and I think this situation

is that it seems to be cropping up in pregnancy-related events, not

just medical abortion, but deliveries, vaginal and Caesarian, and

other conditions of post-pregnancy conditions. I think the FDA is

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actively looking at whether they agree or not that Mifepristone has

any component of making it a higher risk in women who are using

it for medical abortion versus other kinds of miscarriages or pregnancy termination.

Mr. WAXMAN. Well, this is not an issue that Congressmen should

decide. This is a very clear scientific issue. Evidence ought to be

reviewed very carefully. The Food and Drug Administration, the

Centers for Disease Control, the National Institutes of Health all

met on this issue this last week, is that correct, Dr. Wood?

Ms. WOOD. Yes.

Mr. WAXMAN. So they are looking at it. Dr. Harrison, do you

have any information that the FDA does not have?

Dr. HARRISON. No. I have less information than the FDA does.

My information on the adverse event reports were obtained by

FOIA——

Mr. WAXMAN. From the FDA?

Dr. HARRISON [continuing]. From the FDA, and my information

that I presented on the risk of C. Sordellii was directly from the

notes that I took from the meeting in Atlanta on——

Mr. WAXMAN. Were you able to share——

Dr. HARRISON [continuing]. Dr. Fischer and Dr. McGregor’s testimony, who both are from the CDC.

Mr. WAXMAN. Were you able to share your views with people at

the FDA and perhaps at that meeting last week?

Dr. HARRISON. I was not a participant and the panelists, the

speakers and those who were in research, were segregated from the

rest of the observers. I was in an observer spot and not allowed to

talk with the speakers until after.

Mr. WAXMAN. Are you able to submit your views to them in writing?

Dr. HARRISON. Someone from the FDA has requested a reprint

of my adverse event analysis that was printed in January and I

think that was the last request that I had or contact with the FDA.

Mr. WAXMAN. You are listed on our list of witnesses today as a

member of the Mifeprex Subcommittee of the American Association

of Prolife Obstetricians and Gynecologists. In January 2001, your

organization issued a statement—this was several months after the

FDA’s approval of Mifepristone. The statement said, ‘‘The American Association of Prolife Obstetricians and Gynecologists opposes

the destruction of an unborn human being at any stage of development. Therefore, we oppose pharmaceutical abortion with the same

vigor that we oppose surgical abortion.’’ Would your organization

hold the same position on Mifepristone no matter what the safety

data said?

Dr. HARRISON. I did not write that statement, although I am a

member of the American Association of Prolife Obstetricians and

Gynecologists. We characterize ourselves as pro-woman and prolife

and this is a women’s health issue. When it becomes clear that a

method of abortion is 10 to 50 times more risky than its alternative, then this takes it out of the realm of the abortion debate

and puts it into the realm of the women’s health debate——

Mr. WAXMAN. No doubt about it, but your organization—excuse

me, your organization——

Dr. HARRISON. I would like to finish, please.

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Mr. WAXMAN. No, no, let me, because I only have a very limited

time. Your organization’s position is that you oppose destruction of

an unborn human being at any stage of development, whether it

is a pharmaceutical abortion or a surgical abortion. So if that is

your organization’s position, it is really unrelated to how safe or

unsafe this may be. I gather what you are saying is in addition to

that, you feel it is unsafe, but your organization started off with

the position that you don’t want any abortions under any circumstances. Do you subscribe to that view?

Dr. HARRISON. I wouldn’t agree with the way you said it, no.

What I would say is that in this particular——

Mr. SOUDER. Dr. Harrison.

Dr. HARRISON. Yes, sir?

Mr. SOUDER. You do not have to state your position on abortion

or I am going to ask all the witnesses their position on abortion.

Mr. WAXMAN. Well, Mr. Chairman——

Mr. SOUDER. The question is what the——

Mr. WAXMAN. Mr. Chairman——

Mr. SOUDER [continuing]. Issue at hand is, not what her personal

position on abortion is.

Mr. WAXMAN. Mr. Chairman, she is here representing an organization and that organization has taken a position against abortion

under any circumstances. And they took that position when RU–

486 was approved without any of these other complications or possible causations or connections ever came about. And so my question of her is since they took that position, no matter what the safety data said, how I should view that as a representative from that

organization. Did you agree with the organization’s position even if

the safety data didn’t convince you further that this is a possible

problem with this drug?

Dr. HARRISON. If the issue were whether or not there is a human

being being destroyed during the RU–486 abortion process, that is

a separate and completely different issue than the issue this committee is authorized and mandated to look at, which is oversight

of the FDA process by which this drug was approved, and are they

doing their job to take an unsafe drug off the market.

Mr. WAXMAN. Well, I appreciate that. I appreciate that, and our

job is to make sure that the FDA is doing its job. But FDA is a

scientifically based organization. They have to follow the science. It

may lead to a conclusion one way or it may lead to a conclusion

another way, but I want them to follow the science, not some preconceived notion, and I think that is the important point that I

would make.

I see my time is up and I will conclude on that note.

Dr. HARRISON. May I respond to that?

Mr. WAXMAN. Well, no, because we are not going to argue that

issue. The position, it seems to me, is there may be a problem that

is related to this drug. There may be a problem that has no relationship to this drug. Let us get the truth. Let us get to the scientific evidence and let the scientists decide it, not politicians, no

matter what our views may be on the abortion question, because

this is strictly, to me, a scientific question.

Thank you, Mr. Chairman.

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Mr. SOUDER. Mr. Waxman and I fence a lot in the media, even

though we have tremendous personal respect for each other and get

along real well, and it is awkward when we have deeply held views

of he believes that I and others are trying to impose our political

views and I and others believe the political views have been imposed on the system already.

But what I really find disconcerting, and I understand where you

were headed here, because there are two issues. We can’t undo

whatever abortion rights are in America. This is a question about

this drug. But you cannot possibly hold the position that prolife

people who oppose abortion can’t participate in a debate——

Mr. WAXMAN. And I wouldn’t take that position.

Mr. SOUDER. Then what——

Mr. WAXMAN. I certainly wouldn’t take that position.

Mr. SOUDER. What is the relevance of her position on RU–486,

because if you are asking her, can she be neutral on the research,

that is the question, not what her position is.

Mr. WAXMAN. My question related to the fact that if she is representing an organization that took the position, we don’t care

about safety data, we are just against the drug accomplishing the

purpose for which it is intended, which was to terminate a pregnancy, if that is your position—let us put it the other way. If you

had somebody who said, I want to terminate all pregnancies

whether anybody wants to do it, which is not my position, by the

way. I don’t want to see abortions, but I don’t want the decision

made by you or Mr. Cummings or myself. It ought to be made by

the individual with the consultation with a physician and an

ethicist and others. It is a personal decision, not one to be decided

in Washington.

But if somebody takes the position that they are from an organization that is against RU–486 under any circumstances, even if it

were safe, then you sort of wonder, well, if they come in and say,

well, we don’t want this drug because it is unsafe, I think their

views ought to be submitted to the FDA and they ought to evaluate

them.

Mr. SOUDER. I don’t think that is a—I think that, in effect, that

is why so many conservatives have a deep distrust of our current

research structure when we hear that it is nonpolitical, because, in

fact, what you just outlined was something—a position that somebody who deeply believes that all babies are human cannot detach

that view or should be somehow demeaned if they belong to any

organization that is pro-life as if we are under extra scrutiny as a

doctor, as a researcher, as a politician, that somehow, then, we are

not allowed to have a scientific discussion without wondering

whether our motives are impure.

Mr. WAXMAN. Well, she is not here as a well-known doctor, as

I understand it. She is listed as here representing that organization. Now, if she happened to be somebody from NIH or a researcher very well known in the field and she is here for her expertise alone, that is one thing. But she is here representing an organization.

Mr. SOUDER. It is really interesting, because she gave very compelling testimony, very detailed testimony on the individual cases,

more than we got by far on blood transfusion actually from FDA,

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and that rather than debate about her testimony, you choose to attack the witness.

Mr. WAXMAN. No, I am not attacking her, but Mr. Patterson’s

daughter didn’t die from hemorrhaging. She died from this particular infection and this infection is a very dangerous infection and we

need to know if it is connected to this drug. If it is, even though

I am pro-choice, I would be the first, along with you, to say it ought

to be taken off the market, or it ought to be labeled as such. But

if it is not a safety threat, then I don’t think it ought to be accused

of being a problem just because it shouldn’t have been approved in

the first place by the people who want to take it off the market.

Mr. SOUDER. Furthermore, she is a published author in research

documents. I——

Mrs. SCHMIDT. Mr. Chairman, I think in fairness, I want to know

where everybody stands on the issue of abortion——

Mr. SOUDER. I don’t think——

Mr. WAXMAN. Do you want to start off with yourself?

Mrs. SCHMIDT. Sure. I would be more than happy to.

Mr. SOUDER. Reclaiming, I think the line of questioning was inappropriate. I made my statement. Mr. Waxman is the senior ranking member of the full committee. He is free to do that. I think the

public can judge whether that was a fair approach, but it certainly

will reinforce people across the country who are watching, a feeling

that there is a discrimination against people who are pro-life from

being able to participate in research, and that is some of why there

is so much questioning about this whole science debate.

Mr. WAXMAN. Would you yield to me just for me to make one

comment? I appreciate your views. I don’t agree with you. But the

only comment I would make is that the Government Accountability

Office did an evaluation of FDA’s action on the Plan B contraceptive drug, and even though the scientific committee appointed to

review it said it should be approved, even though the researchers

at NIH said it should be approved, it appeared that a political judgment was made because of the Bush administration that it

shouldn’t be approved and its approval is now in limbo. Many of

us look at that as clear politics when the science points in a different direction.

I want to know what the science says about this issue. You say

it is compelling. It is not compelling if scientists are still evaluating

the matter. I want them to see whether it is compelling, whether

there is a clear case made, and I don’t want politics interfering

with science.

Mr. SOUDER. You can keep repeating that, but the funny thing

is, I have been a staffer here, I have been a member here. We all

know who requested the GAO study, who has picked on the GAO

study, which is heavily steered. GAO will do a study on either side

depending on who basically pushes it and what mixes are. We have

gone into this.

Mr. WAXMAN. Well, now you are attacking the GAO’s credibility

just because it came up with a study that you disagreed with.

Mr. SOUDER. No, I am questioning——

Mr. WAXMAN. That is more of an attack than I ever did with Dr.

Harrison.

Mr. SOUDER. As the GAO——

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Mr. WAXMAN. And I didn’t mean—I attacked the research——

Mr. SOUDER. As I have said, when you get into controversial political subjects, the GAO, how you phrase the question, who does

it, in any honest—forget here for a second that the TV is on—you

know full well that we have problems in the GAO as far as what

kind of study you get back, and to act like it is a pure scientific

study out of the GAO—they do good research, they research it, but

they are going to have a bias based on who is put on a given study

and who is requesting the different study. And if I request it with

Republicans, you are going to get a slightly different study back

than you do.

There are subjects where they aren’t that kind of laden with the

political overlay on this and the GAO will be very forthright. You

can go through the researchers they contracted. You can look at the

footnotes. You can look at the previously published records of it. I

am saying the GAO is transparent on it, but when you go through

the evaluation, you will see who they hired as a contractor will determine what research they get back.

Mr. WAXMAN. We have another Member who wants to ask

questions——

Mr. SOUDER. Yes, I——

Mr. WAXMAN [continuing]. But I just want to defend GAO. Requesting a study by GAO doesn’t mean that they have to come out

with your preferred conclusion. I think they have a lot more integrity and honesty than you are suggesting. They can decide who

they are going to do the investigation. I think they are a reputable

source of information. Sometimes they come up with conclusions I

like, sometimes not, but they come up with the facts and then we

can draw the conclusions. I want the science reviewed and then we

can let the appropriate policymakers reach the conclusion, but——

Mr. SOUDER. Ms. Watson——

Mr. WAXMAN [continuing]. Ms. Watson has been very nice here.

Ms. WATSON. I came in late and I am sorry about that. I would

like to know what we are investigating and looking at in this particular meeting. Now, reading from the information that was given

to us, it says ‘‘RU–486: Demonstrating a Low Standard for Women’s Health?’’ May I ask, I would maybe ask Dr. Rarick or Dr. Harrison, the question. Let me start with Dr. Rarick.

Are we talking about a low standard for women’s health, and if

so, what is that? And are you agreeing that we have seen more

women die after using this drug than women who die after having

abortions? I just want to focus this discussion. I think we have gotten off the track. So can you respond to that, because we are looking at a low standard for women’s health. At least, that is what I

thought this meeting was about and not our beliefs and what sides

we are taking. So can you answer that question, the low standard

question?

Dr. RARICK. Certainly. I will start with that. Mifepristone in its

review at the FDA was held to the highest standards, similar to

any drug product that is reviewed in the Center for Drugs. It was

reviewed in a rigorous way. It took over 4 years from its submission to its approval. It was appropriately labeled. It was held to the

highest standards for women’s or men’s health at the FDA and I

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believe they are still treating it that way. They are looking at the

issues that you are asking about.

Are there more deaths reported with Mifepristone than with surgical abortion? Some would say that there is tenfold more deaths.

I think we just heard that reported. But again, we have to think

about how they are looking at this data. Is there a way to get more

accurate data on surgical abortions, etc.? Is there a way to understand the Mifepristone-associated deaths so that they can be prevented? The issue is risk and benefit. They are looking at that very

seriously and I think it is being held to the appropriate and high

standards.

Ms. WATSON. As the department of government that looks at

drugs and their usage and results, what would be the next step if

you then conclude that there appears to be a higher number of

deaths associated with the approval and the use of this particular

drug? What is the next step?

Dr. RARICK. Well, the next steps would be to look into those

types of deaths in all pregnancy-related events to try to understand

those better, make providers aware of those infections and that potential, understand how to prevent it, understand how to treat it,

do women the service of understanding pregnancy-related deaths in

the broader sense, not just related to Mifepristone. Many more

women die from childbirth than die from using Mifepristone for

medical abortion. Putting money into those questions, surveillance

into maternal mortality, appropriate money to explore maternal

mortality in its broadest sense, those would be the next steps.

Should the FDA look at all this information? Absolutely. As was

said before, they have all the information and more than Dr. Harrison has referred to. They are looking at it very seriously. If they

believe that—they come to the conclusion that the risks do not outweigh the benefits, they will take appropriate action.

Ms. WATSON. OK. And do you feel that we are demonstrating a

lower standard for women’s health?

Dr. RARICK. Not at all.

Ms. WATSON. All right. I would hope that this committee would

provide the oversight as FDA moves along and we would then look

at the empirical evidence that would emanate from your studies to

address this question. If we are demonstrating a lower standard,

then provide the scientific evidence. I would beg that we don’t discuss the ‘‘A’’ word in terms of looking at this particular drug. It

gets us off track, as it did just about a minute ago. What I want

to be presented with as a decisionmaker is what evidence we might

have that we have approved a drug that lowers the standards for

women. Thank you.

Mr. WAXMAN. Will the gentlelady yield to me?

Ms. WATSON. Yes, I will, certainly.

Mr. WAXMAN. I wasn’t even aware of it until you just pointed it

out. The chairman said it depends on how you ask the question,

but the hearing is titled for today, ‘‘RU–486: Demonstrating a Low

Standard for Women’s Health?’’ so that is the way we are asking

the question. I think we need to see whether there is a—and you

answered that question and I was pleased with your answer, but

I think the question should be, is there a connection between Mr.

Patterson’s daughter and the five people that have died from this

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particular infection and the use of RU–486? That seems to me the

key to it, because if there is a connection with the use of this drug

and getting something as deadly as this infection, that is a serious

matter. So we need to explore it, but evidently it is not so clear

when we find people have had the infection who didn’t have the

drug. So I agree with you. Let us get the science. Let us get the

facts.

Mr. SOUDER. Dr. Rarick, I was a little confused by your response.

You said that if, in fact, there were deaths, you would work for or

believe there should be further notification to doctors. I inserted

this earlier, but Palladone, Purdue Pharma agreed to voluntarily

suspend, and they said, to date, FDA is not aware of any patients

who had life-threatening side effects from drinking alcohol while

taking Palladone, but they took it off the market.

Tysabri Biogen voluntarily suspended marketing of the drug as

well as its use in clinical trials until more detailed information

could be gathered on one death and one other adverse effect.

In NeutroSpec, Palatin Technologies voluntarily suspended sales

and marketing of NeutroSpec. No determination was made regarding the relationship between that and reported adverse effects.

In Cylert, Abbott chose to stop sales and marketing based on 13

reports of liver failure, but they did not grant—and RU–486 had

10 to 14 times more than surgical abortion, even though in this

case liver failure was 10 to 25 greater in the general population.

Bextra, Pfizer voluntarily withdrew Bextra from the market even

though it concluded that the overall risk versus benefit was unfavorable.

In Baycol, they withdrew after reports of 31 deaths. In Roplin,

it was 5 deaths.

In Lontronex, it was a total of 70 cases of adverse effects of

which 34 required hospitalization without surgery and it was

pulled off.

In Orlaam, it was discontinued after a report of severe cardiacrelated events among opiate-addicted patients. They pulled it off

the market, not just warnings.

So is your position that FDA should treat this drug unlike other

drugs, because when there are adverse effects with deaths and so

on, at the very least, you think it would be suspended. That has

been the whole pattern. The problem here is you have a drug company that only has one drug. It is in the Cayman Islands. There

is no incentive to do what all these other companies did which

went off the market. And so what is the responsibility of the Federal Government when the private sector won’t act responsibly like

the others.

Now, I happen to believe, even though I don’t want RU–486 on

the market, that there may be some debate here as to whether it

is the primary, and that is why I was asking questions of can it

be suspended while we find that out. But I see no pattern of FDA

that we leave something on the market while we are doing that

study, because it is clear that it was toxic in a disproportionate

amount if you are using RU–486, that the blood transfusions were

certainly disproportionate, and under any standard of the past, you

would at least suspend, hence the question of the hearing.

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Dr. RARICK. I would simply disagree with you. You can list all

the ones that have been suspended, but you have to think of the

thousands of drugs that are on the market that have post-marketing reports of deaths. The easiest example is Viagra, where we had

at least several hundred deaths during its first year of prescription,

the same company, Pfizer, that you mentioned there for Bextra.

There are all kinds of examples of post-marketing death adverse

event reports and other serious adverse event reports where the

majority are certainly not suspended from marketing.

Mr. SOUDER. Even if it was directly related to that product, the

FDA does—then what standard would you have FDA intervene?

Dr. RARICK. The standard that they use, which is a risk-benefit

analysis for each particular case.

Mr. SOUDER. Mr. Snead, what is your response to that?

Mr. SNEAD. I think, essentially, that is exactly right, namely that

you need a risk-benefit analysis that is undertaken to determine

whether or not a drug is initially approved. But I would like to add

something that I think would be informative to the Members. What

we are talking about here as a legal matter is a drug that has been

approved under Subpart H, and what that means is that creates

an inference that the FDA in approving Mifepristone had a concern, safety concern, that required additional safeguards beyond

the normal safeguards that attend a normal risk-benefit analysis.

In the passage that I read before from the FDA’s final rule, they

said the risk-benefit analysis that yields the conclusion that this

should be approved assumes that these post-marketing requirements will, A) be effective, and B) be observed. So there has been

much discussion about the safety piece of that particular question.

But what seems to be getting lost among the discussion is there is

a second question, a second grounds under Subpart H, which is a

factual question about the compliance with the post-marketing restrictions by Danco Corp.

So I would just draw the committee’s attention back to the fact

that, of course, safety is a principal concern as laid out in the withdrawal approvals of Subpart H as well as with the other withdrawal approvals that I take up in my written testimony, but the

question of compliance is equally important of a question, because

without meaningful compliance by Danco, the risk-benefit analysis

is not what the FDA intended it to be. The risk-benefit analysis depends on the assumption that there is compliance, and if there is

no compliance, then the risk-benefit analysis is substantially different.

Mr. WAXMAN. Mr. Chairman, could you yield to me?

Mr. SOUDER. Yes.

Mr. WAXMAN. Do you have evidence of noncompliance?

Mr. SOUDER. I have no evidence of any kind. I am just simply

describing to you what the considerations are.

Mr. WAXMAN. So you are saying if there hadn’t been compliance

with the limitations——

Mr. SOUDER [continuing]. I am making a conditional statement.

If the FDA were to determine that there was no compliance, then

they would have additional grounds to withdraw approval under

Subpart H.

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Mr. WAXMAN. But I hadn’t heard anybody assert that there

hadn’t been compliance of the approval itself under the Subpart H.

Of course, this is unusual, because most drugs are just approved

and once they are approved, they can be used for any purpose. This

one was approved for limited purposes under limited circumstances

so that there would be extra care taken. I guess I should ask that

question of Dr. Rarick. Am I correct in that? It wasn’t——

Dr. RARICK. Correct——

Mr. WAXMAN [continuing]. Approved like most other drugs, go

ahead and use it——

Dr. RARICK. There was a determination that it shouldn’t be released through pharmacies, that it had to be provided by specific

types of prescribers.

Mr. SOUDER. And I should say for the record that we did invite

Danco so we could address that question and they withdraw 2 days

before the hearing and we didn’t have a chance to get somebody

else to directly address the question, but it is a fair question.

Mr. WAXMAN. It is not a fair question unless you know there has

been some non-compliance.

Mr. SOUDER. No, your question is a fair question, because we

don’t know for sure about compliance. I tried to address that with

FDA. I don’t think, personally, that what was tested has been followed through the way it was tested, but the Assistant Commissioner explained why she thought that was still allowable, but we

don’t have Danco here and we don’t have a substitute for Danco to

follow through that question, but it is a question we need to followup in our written questions and we said at the beginning that I

was going to do that with Danco.

Dr. Harrison, could you talk about the proportionate use effect,

too? Viagra is used over and over. RU–486 would not be. And any

comments you had on Dr. Rarick saying, look, there are other

drugs we allow on the market, because that is a fair point. If there

are lots of drugs on the market that have adverse effects, why

should this be treated differently than those?

Dr. HARRISON. The issue is not the absolute number of adverse

events. The issue is, as is stated in the FDA letter to this committee, the evidence whether or not RU–486 was causally related to

the adverse events, the timing of the event—remember that these

RU–486 septic deaths happened within 7 days. There is no issue

of confounding factors here. These women were healthy. They

didn’t have other medical conditions that could explain why they

would suddenly get an extremely rare bacterial infection that

doesn’t usually kill normally immuno-competent people. How severe these events are—the death is the ultimate severe adverse

event.

And I would have to add that transfusions are also a significant

severe adverse event, and to minimize the significance of having a

blood transfusion is to underestimate the care that goes into clinically judging whether or not this person needs a transfusion.

Transfusions aren’t done lightly. They are done when there is a significant risk to the person’s life.

Can the adverse events be predicted or avoided? The CDC meeting was absolutely clear that at this point in time, there is no way

to predict who is going to get—who is going to die from C. Sordellii.

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Because we can’t predict who and we can’t identify risk factors, we

also can’t avoid C. Sordellii in Mifepristone abortions. There has

been a consistent spontaneous—a consistent rate, excuse me, of

about 1 death for every 100,000 Mifepristone uses. So if that continues unabated while we debate these questions of how much research and who gets the grant money and all that stuff, that

means that for every 1,000 uses of Mifepristone, one more American woman is going to die, and I think that is something that has

to be put into perspective. These are human beings that are being

subjected to a completely unnecessary risk.

Surgical abortion is available and legal and safer, and how safe

is the alternative treatment, and that is the other issue. Surgical

abortion is available. It is legal. And to say that Mifepristone is

being used in cases where surgical abortion isn’t available, think

about what would have happened to these transfusion deaths if

there hadn’t been surgical abortion available. Any place that has

the capability to—excuse me. Any place that doesn’t have the capability to have an abortion clinic also doesn’t have the capability to

do transfusion. We are talking pretty sophisticated medical facilities. So the person you absolutely do not want to use Mifepristone

is the one who has no access to surgical facilities to complete this

under an emergency circumstance, so I think that is kind of a spurious argument.

So that would be my response. Thanks.

Mr. CUMMINGS. Mr. Chairman, may I please——

Mr. SOUDER. Yes.

Mr. CUMMINGS. Thank you.

Mr. SOUDER. Mr. Cummings.

Mr. CUMMINGS. I have sat here and I have listened to all of this

and I was sitting here saying to myself, I am so glad that there

are women making these arguments. I would hate to see a group

of men. They would probably say that we were not as sensitive as

we need to be, and I say that to say this, that I think we are all

concerned about women’s health. As a matter of fact, I know that

we are.

I don’t think that in this country we are talking about low standards. Let us not kid ourselves. This is the United States of America. There is no way that I think any member of this panel would

in any way accept a low standard or even a mediocre standard. The

witnesses, I know you feel the same way. We may differ on your

opinions and what have you.

The key is, Mr. Patterson, is we want to make sure that we do

everything in our power, as I know you want us to do, to make sure

this does not happen to anyone else. That is what this is all about.

And I would hope and I would think that you, Dr. Rarick, when

I asked you the question a little earlier, because I really wanted

to get a sense of exactly—obviously, there is a procedure that you

have there at FDA, and obviously, and you can tell me if I am

wrong, you try to keep the politics out of it because you are talking

about people living and dying, I guess. I trust that you do.

But you have heard the testimony of Dr. Harrison and I would

assume that you would be, as we all are, as sensitive to women’s

health. Is there anything that you have heard that you would question whether you all have a low standard? I know that may be a

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sort of self-serving question and I am not trying to do that, but I

am trying to get to the bottom of this, because sometimes we can

get so caught up in our politics that we forget where we are trying

to get to and we get sort of off-track. The key is that we want to

make sure, all of us, that FDA has a standard which will protect

every woman with regard to her health choices.

So that leads me to this. Somebody said a few minutes ago, I

think it was you, Mr. Patterson—it was you—when you were talking about your daughter, you said if there was information, if she

had access to all the information, she probably would not have

made that choice.

Now, I am asking you, based upon all that you know, Dr. Rarick,

is there anything that you could have or the FDA could have put

on the label or put on the little description of the drug’s side effects, whatever, that should have been there, just based on what

you know to this date? I am not talking about—I know there is still

research to be done and all that kind of stuff—that should have

been on there?

Dr. RARICK. Well, I would stand behind the FDA’s labeling at

each point when they revised their labeling, and if you look at the

current labeling, it does describe that there has been some unusual

and severe bacterial infections and deaths. It describes some of the

way the regimen was given in those cases. It provides that information.

I agree with you that the FDA has to look at this very seriously

and always decide, do the benefits remain to outweigh the risks?

If you ask me about high standards, I would say the FDA holds

this to a very high standard. I believe if you are looking for low

standards in women’s health, it would be that we don’t have very

much information about maternal mortality in general, not just

post-abortal or post-medical abortion mortality, but just infections

and pregnancy outcomes, any events in general.

But in terms of Mifepristone being held to a particularly low

standard, absolutely not. It is held to the highest standards. I

think the FDA is considered the most rigorous regulatory body in

the world and it, of course, meets those needs.

I agree with you that these things are incredibly serious. Nobody

is trying to minimalize any of these events. I believe the FDA is

looking at this from their scientific viewpoint. They at the meeting

last week I think were quoted as saying they initially saw this as

probably a simple drug-based association and they realized when

they looked into it that simply wasn’t true, that it was much more

complicated than just Mifepristone and infection and they are looking at it.

Mr. CUMMINGS. Now, you said the labeling has changed. I am

going to get back to you, Mr. Patterson, in 1 second. I see you shaking your head. But you said the labeling has changed, is that right?

Dr. RARICK. Yes. The labeling has been updated, I think at least

three times since its original approval.

Mr. CUMMINGS. And I take it that when Mr. Patterson’s daughter took the—there have been changes since Mr. Patterson’s daughter used this medication?

Dr. RARICK. Yes.

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Mr. CUMMINGS. Maybe one of you all could tell us, were those the

changes that you just authorized? You said something. I am just

trying to figure out, have we made much progress with regard to

going back to what you said, Mr. Patterson, putting it out there,

as much information as possible that we feel comfortable is accurate?

Mr. PATTERSON. Well, first of all, I would like to say again that

if Holly had all the information to make an informed choice, she

wouldn’t have chosen Mifepristone or an RU–486 medical abortion.

There is evidence that a death did occur in Canada with an infection and she, in fact, did die from C. Sordellii, and that was what

I uncovered in my medical research that was not very well known

or very well published. As a matter of fact, the author of the paper

of the woman who died in Canada was Dr. Christian Sinave. It just

so happens that at the time, my wife and I, when we called Dr.

Sinave, we were the very first person or concerned people to call

about that particular infection as it is associated with RU–486. He

said in his own words that he had been discouraged to write the

paper and that we were like the only ones that had ever showed

any interest, and since then, there has been a considerable interest

over this infection and its relationship with the drug.

To say that this drug, there is no causal relationship, I think is

ridiculous. My daughter took the drug and she died. I mean, it is

that simple. So the medical community was aware of it. Danco was

aware of it. The Population Council was aware of it and there were

studies showing that there were infections as a result of medical

abortion. However, Holly was not indicated in the label and Holly

was not given that information.

Since my daughter died, I have been to Washington. I have discussed my concerns with the FDA over these safety and health concerns. There have been—consequently, there have been four more

women died after Holly and some very shortly, within months,

after Holly. As a matter of fact, with the reporting, it took one of

the deaths right after Holly, it took almost a year and a half to get

reported. That is why today I have discussed there needs to be

some very accurate mechanisms to be able to evaluate from the

FDA’s level what is really going on out there. I am very concerned

that women are dying and these events are not getting reported so

that the FDA can actually do their job.

Mr. CUMMINGS. All right. So there have been—and thank you

very much. Just a last question. There have been some updates

with regard to the warnings, is that right?

Dr. RARICK. Correct.

Mr. CUMMINGS. I think in November 2004, the black box warning

was revised and strengthened to add new information on the risk

of serious bacterial infections, sepsis, bleeding, and death that may

occur following any termination of pregnancy, including Mifeprex.

In July 2005, apparently the FDA approved a labeling supplement

to again strengthen the black box warning on the product, but noting that atypical presentations of serious infection can occur without fever, bacteria, or significant findings on pelvic exam, etc. Is

that accurate?

Dr. RARICK. My review of the label, I believe would agree with

that. I have the label here if you want to see the whole label.

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Mr. CUMMINGS. No problem. I just wanted to make sure that it

is being updated.

Mr. SOUDER. Anything else, Mr. Waxman?

Mr. WAXMAN. This issue of death associated with a drug, when

FDA approves drugs, they look at the safety and they look at the

efficacy, whether the drug accomplishes what it is intended to accomplish. Aren’t there risks associated with a lot of drugs, Dr.

Rarick?

Dr. RARICK. Oh, every drug has risks associated with it, yes.

Mr. WAXMAN. Viagra could cause death. Penicillin could cause

death. They are on the market. But I assume they are on the market because there is a risk-benefit analysis that even though there

may be a rare case of death, it is not so out of control that it diminishes the fact that there is a benefit from those drugs. Is that what

we mean by a risk-benefit analysis?

Dr. RARICK. Correct, that you look at those risks, those death reports and rates in contrast to the benefits.

Mr. WAXMAN. There is a question in my mind about deaths or

harm associated with a drug as opposed to death or harm caused

by the drug. Can you clarify what that means in terms of FDA regulation?

Dr. RARICK. It sounds like a legal term, but I will try. When you

think of cause and causation, you think, you know, if I tell my kid,

don’t touch the hot stove, you are going to get burned, and he

touches the hot stove and gets burned, to me, that is cause and effect. When you look at drugs and the risks associated with them,

it is very rare that you can actually say X drug causes Y, because,

as you know, many, many people take the drugs that don’t get that

effect. The majority of people who take a particular drug won’t

have the side effects that are described in the label, but there are

going to be side effects in many people, and there, you would call

that a side effect that is associated with the use of that product.

Mr. WAXMAN. Well, Mr. Patterson has pointed out, I think appropriately, that he wished his daughter would have known that there

was this potential side effect. Now, FDA has issued public health

advisories in connection with safety concerns related to

Mifepristone in 2004, 2005, and most recently, in March 2006. The

FDA has consistently highlighted the fact that the cases of severe

infection occurred with regimens of Mifepristone and Misoprostol

that were not in approved labeling, although the relationship of the

infections to such use remains unknown. What does that mean?

Could you tell us more about this, if you know?

Dr. RARICK. That means even though the products are being used

outside of their labeled instructions, the FDA wants to make sure

that providers and patients are aware that it has been associated

with these infections. Whether it would be associated with those infections if it had been used as per label, they are not stating. They

are simply saying—they could just say, well, that wasn’t used by

the label. We don’t even need to put it on the label. But instead,

they are saying, no, we need to make sure providers and patients

are aware that in certain circumstances, we have had these reports. They are not suggesting that it is absolutely that circumstance that caused the increased risk, but they want to make

sure that information is available.

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Mr. WAXMAN. Well, I thank you for that clarification and I will

conclude by saying I just hope the FDA will continue to reevaluate

all the evidence, advise people of information that is pertinent, and

if they see there is a real threat to this drug, or any other drug,

they need to take actions, including taking the drug off the market.

But I don’t think they ought to act until they look at the science

and reach some conclusions on this drug or any other drug.

Thank you, Mr. Chairman.

Mr. SOUDER. Thank you. Rather than ask Dr. Harrison the question again, I think we will insert in the record your earlier response on the causal link, that there were multiple things, including alternatives such as surgical abortions and so on, because you

gave a complex answer to that question early on. Did you have

anything you want to add?

Dr. HARRISON. No, that is fine.

Mr. SOUDER. Ms. Watson.

Ms. WATSON. I just hope that we can have, Mr. Chairman, a followup hearing as FDA proceeds along its track to assess the risks

of this drug, that we will do the oversight that we are responsible

for here in Congress, and I would hope that we would base our debate on the results of your studies so that we can come from a scientific base as we discuss this.

So I want to thank the chair for this hearing. I think it has

opened up a debate on the efficacy of this drug that has been approved and we need to see what the effects actually are. So thank

you so much for the hearing and thanks to the panel.

Mr. SOUDER. Thank you, and I want to thank each of the witnesses and I want to say this directly to Dr. Wood and Dr. Rarick.

Whether we agree on the nuances here, or maybe we do long-term

or not, that your work long-term, Dr. Wood particularly but also

Dr. Rarick, on women’s health issues, because certainly it was an

area that was underrepresented in the research, and without aggressive advocacy, we wouldn’t be where we are on breast cancer,

on the whole range of women’s health issues. So regardless of

where we stand on this issue, I appreciate your lengthy career

working with that, Dr. Rarick, as well.

I thank Mr. Patterson for speaking out, Dr. Harrison for giving

us that detailed analysis of each of the type of cases and your rigorous analysis of that, and Mr. Snead for bringing the legal aspects

in and we will find out, particularly if Danco responds, how to address some of their questions legally on whether they have been

following through on the guidelines of FDA.

With that, the subcommittee stands adjourned.

[Whereupon, at 6 p.m., the subcommittee was adjourned.]

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Æ