Abortion (New)

FDA and RU-486: Lowering the Standard for Women's Health (Testimony,10/06)

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 regi

men
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 ASSOCI

ATION 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 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—-
    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 life-threatening hemorrhages, it is basically 54 life-
threatening hemorrhages altogether as of July 2005.
    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 then tries to resolve whatever dispute or
questions that there might be.

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 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 connection 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.

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 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.

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
cardiac-related 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.
    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 safegua

rds 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. 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. 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…