US House of Representatives
Government Reform Committee
October 2006

The FDA and RU-486: Lowering the Standard for Women's Health

http://www.access.gpo.gov/congress/house/house07ch109.html

http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgidbname=109_house_hearings&docid=f:31397.pdf

http://reform.house.gov/UploadedFiles/RU-486%20Final%20Report%20PDF%20Version.pdf

The report on FDA and RU-486 can be found by going to http://reform.house.gov and clicking on "Reports" on the top of the page.
 
http://reform.house.gov/UploadedFiles/Hausknecht%20DANCO%20October%2027,%202006%20Response.pdf
Responses to Questions for the Record by Richard Hausknecht, MD, Medical Director, DANCO Laboratories (pdf)

Serial No. 109-202 -- RU-486: Demonstrating a Low Standard for Women's Health? - TEXT 183K | PDF 30M

http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=109_house_hearings&docid=f:31397.wais

Excerpts: 

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 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...
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.
    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...

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.
    In a number of issues lately, I have been accused of being
anti-science 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...

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
abortion 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. 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 t