want to do these studies to allay the fears about rupture or any of
the other issues that are there. And I think we have to be honest
with ourselves that part of the reason for that is the context of ex-
treme liability risks in the world, and that any business who has
a general counsel is going to say, "We'd better look at this very
closely before we decide to pursue this further."
But I think we may be able to make a breakthrough here in an
area that affects that fairly significantly by parsing a little more
carefullv the different concerns that. Dr. Kessler, you raised in
some 01 my questions earlier. I was talking with you a great deal
about the studies on autoimmime deficiencies, and I think you cor-
rectly indicated your concern about rupture and that there weren't
sufficient studies there.
Turning back to the question of autoimmune disease, given that
there are these 17 studies that Dr. Ganske mentioned and that
there is a good record in that area, can't we have the agency, at
this point, make a statement that we don't think there's a risk of
autoimmune disease; we still want to get the data on rupture, and
we're still waiting for the National Cancer Institute study on can-
cer to nail that down for sure â although I have the impression that
people are a lot less concerned about that risk than they were in
the early 1990's.
Dr. I^SSLER. Mr. Mcintosh, let me let you hear from an expert,
Dr. Brown. First of all, when you say 17 studies, there is â I as-
sume, Dr. Brown â a range of different quality within those 17
But from an epidemiological, scientific point of view, you ask me
to make a statement that there is no risk associated.
Mr. McIntosh. Let me rephrase that. No relative risk, given the
fact that there are women who, this hearing has indicated, are
being discouraged from receiving treatment.
Dr. Kessler. With regard to typical connective tissue disease,
Fve tried to be clear today â and, again. Dr. Brown can correct my
wordsâ but I think, based on a scientific analysis of those studies,
what those studies provide is a reasonable assurance that there is
not a large increased risk of typical connective tissue disease. They
don't rule out a small, but significant risk of typical connective tis-
sue disease, and don't really address this question about atypical
connective tissue disease.
Dr. Brown is the expert, and she can correct me.
Dr. Brown. We review these studies as they are published, and
we have reviewed the studies that have been mentioned this morn-
ing, the Mayo study, the nurses study; there's another study which
is on scleroderma. Connective tissue disease is not a single entity.
There are connective tissue diseases which are extremely rare, like
scleroderma, and there are other connective tissue diseases which
are more common, Hke rheumatoid arthritis.
So the studies that have been done by Mayo CHnic and the Har-
vard Nurses Study have ruled out a large increase in connective
tissue diseases, in general, but they have not ruled out specifically
such diseases as scleroderma, which are very, very rare.
The types of studies that were done by Mayo and the Harvard
Nurses Study are cohort studies, and these studies typically are
very good for finding out relationships between the outcome and
something that may be causing it, when it's very common, but they
are not as good at detecting rare outcomes.
Mr. McIntosh. Did the Harvard Nurses Study have a single in-
cidence of scleroderma that was in the woman who had breast can-
Dr. Brown. I don't recall whether there was a single incident or
not. There may have been.
Mr. McIntosh. My recollection, upon reading it, is that there
Dr. Brown. OK Scleroderma is an extremely rare disease, and
so the Harvard Nurses Study had, roughly, I think it was 83,000
women in it. You would not expect to find many women, in 83,000
women, who had scleroderma. The Harvard Nurses is a study
which is better prepared to detect more common diseases such as,
perhaps, rheumatoid arthritis, but it is not as well equipped to de-
The type of study which is used in order to detect very rare dis-
eases is a case-controll study. In this type of study what they do
is, they find many women who have the disease and they look for
the exposure, in this case, breast implant. In the single published
study, which is by Dr. Engler in Australia, they were able to rule
out a large increase in risk, along the lines of fivefold, for
scleroderma, but they were not able to rule out a smaller risk,
which may be significant, for women who have breast implants.
So these are all pieces of the puzzle.
Mr. McIntosh. So the Australian study did address scleroderma
and it ruled out a large risk, but there might be a small risk associ-
ated with it.
Dr. Brown. Yes, that's correct.
Mr. McIntosh. Let me turn now to Dr. Kessler on this question.
As head of the agency, are you going to require them to do that
type of study for every single one of these rare connective tissue
disorders, or when is enough enough on connective tissue disorders
and autoimmune deficiency?
Dr. Kessler. Let me let Dr. Burlington answer that question.
Mr. McIntosh. You're going to defer to her in making that deci-
Dr. Kessler. Dr. Burlington.
Mr. McIntosh. Sorry. To him.
Dr. Kessler. Yes, I defer.
Mr. McIntosh. So if he says enough is enough, you're going to
say, "OK. Fine. We're going to say we're satisfied."
Dr. Kessler. Dr. Burlington makes the decision of whether â I
mean, every day he has final sign-off on whether a device is ap-
proved or not today.
Dr. Burlington. Mr. Chairman, thank you.
On this issue, it's very hard, because there are, as we all know,
a number of questions that have been raised about atypical
rheumatologic disorders, about poorly defined rheumatologic dis-
orders, about something that has been tentatively labeled "silicone
disease," which is a collection of symptoms which is not even itself
well-defined. Those are questions we would have to consider.
I think we do have a substantial bodv of evidence that is useful
in providing information to women on classic connective tissue dis-
eases. In contemplating moving forward on an application, what we
would do is go back to an advisory committee to get a broad input
from the biomedical community and say, "What about all the rest
of this? If we don't have specific studies on it, nonetheless, are we
at a point where it makes sense to label the product describes that
which we do not know and put it out in the market for regular
Now, in order to get there â and I think this is one of the ques-
tions that Chairman Shays has been asking â we would certainly
anticipate looking at additional information on rupture rate and
other local reactions, and then we will be prepared to report.
Mr. McIntosh. Dr. Burlington, let me interrupt you for just 1
second. How long would that process take? And my question is,
can't you take a step short of issuing a product approval and make
a very clear statement by the agency that there isn't a safety risk
here, so that businesses would come forward and provide you with
the data on rupture?
Dr. Burlington. Mr. Chairman, we have disseminated to the
Members, we have disseminated to the companies involved, as well
as to consumers, information on the agency's assessment that sub-
stantial reassurance is offered by the emerging epidemiologic data.
We recognize that some of it is yet to come, the Cancer Institute
study that Dr. Briton is doing. But, to date, we do have that sub-
stantial reassurance, and we have tried to make that as clear as
Mr. McIntosh. Well, apparently, it's not clear enough, because
there's a great deal of uncertainty out there about what the agen-
cy's views are.
Do you think the cancer study will provide additional data in this
area that will be satisfactory to make a categorical statement that
the relative risks are acceptable?
Dr. Burlington. We look at the risks of products in their total-
ity. It certainly will address things within the scope of the study.
It, I expect, will augment the existing body of evidence on classic
connective tissue diseases, which tells me that we have excluded a
hi^ level of increased risk, but we will never get to perfection. We
can't prove a negative, as the Congpressman testified earlier, and we
woul(m't seek to.
Mr. McIntosh. After the cancer study, even if it came back with
a conclusion that there are no significant risks, you would not, at
that point, say, "We're satisfied that we can say there's not a risk
of autoimmune disease caused by this product that is significant
enough that we're going to keep it out of women who have breast
Dr. Burlington. Mr. Chairman, I appreciate your having quali-
fied the start of your sentence with â this basically gets to the ques-
tion of, are we satisfied that we have enough information that we
can adequately label these products we can say there is a residual,
unknown risk, and that that's information that we communicate to
women contemplating having one of these products.
That seems an appropriate position. It, however, has to be looked
at in the totality. It has to be accompanied by reasonable informa-
tion on what the durability of the product is. When something is
knowable, through readily available techniques â a million women
have these products â ^fin(fing out what the rupture rates are should
Mr. McIntosh. So you're sajdng you're not willing to address the
safety issue until you're satisfied about the rupture question, which
to me is a disservice to American women.
Dr. Burlington. Mr. Chairman, I believe we have substantially
addressed the safety issue to the extent that data is available to
Dr. I&SSLER. We will address the question when the data is sub-
mitted to the agency and we can review it in the marketing con-
text. We have an obligation to women who have these devices in
them today to keep them informed. That's very important, because
they want the answers.
Mr. McIntosh. Dr. Kessler, let me say, I think you're failing on
the safety issue by moving the ball, first from cancer to auto-
immune disease, now to rupture, and saying, "We can't give you a
categorical statement." It reminds me of Charlie Brown and Lucy,
where every time he comes up and he tries to kick the football,
she's going to move it down the goal post.
Dr. Kessler. Mr. Chairman, can I just disagree?
Mr. Shays. If I could just interrupt a second. I think this is im-
portant to follow. I'm going to apologize to you as the panelists. We
will be going for another 10 minutes. I just want to make sure Mr.
Gutknecht and Mr. Fox get to ask â and I'm the guilty party here;
I asked too many questions. So, at any rate, were going to go a
Dr. Kessler. Can I just answer this?
Mr. Shays. You have time to answer the question. We don't want
to put words in your mouth.
Dr. Kessler. If I can just answer the chairman's question. If you
look, in 1992, the three questions that we asked the panel on Feb-
ruary 7, 1992, "Does the newly available information â " and that's
the information from the Dow documents that we presented, as
well as other information â "does the newly available information
on the incidence and hazards of rupture and bleed increase your
concern and/or uncertainty about these products?" That was the
The second question: "Is the evidence of a possible link between
silicone gel-filled implants and autoimmune disorders strong
enough to increase your concern and/or uncertainty about these
products?" That was the second question.
The third question: "Does the industry's record in testing, report-
ing, and marketing these implants over the last 30 years â " in ref-
erence to the documents before it â ^"increase your concerns and/or
uncertainty about these products?"
Those were good questions back in 1992; they are the same ques-
tions I'm asking today in 1995.
Mr. McIntosh. And my position is, that second question could be
answered today and it's not, and that is a disservice to the Amer-
Dr. Kessler. Mr. Chairman, if you're asking me to answer that
question beyond what the science allows me to answer, I can't.
Mr. McIntosh. I'm asking you to take an honest and fair look
at the science.
Dr. Kessler. And we have, and I think I've stated it. I've said,
on that question, based on the published studies â and I've not
looked behind those studies at the data; we normally do that. I
think I've made it very clear how we view those published studies
You may not agree with my statement, but I said there is reason-
able assurance that there is not a large increase in typical connec-
tive tissue disease. I've also said they don't rule out a small but
statistically significant increase in typical and it doesn't address
Now, other scientists are free to disagree. That's the best judg-
ment. When I talk to our scientists, that's what they tell me the
current state of the science allows us to conclude. I'm not sure
what more I can do than tell you how we read the published stud-
ies to date.
Mr. McIntosh. I will defer to the chairman.
Mr. Shays. I thank the gentleman.
Mr. Gutknecht and Mr. Fox, you both have questions.
Mr. Gutknecht. Yes, Mr. Chairman, I will try to be brief, be-
cause there are some other witnesses, and one, in particular, that
I want to hear from.
The chairman liked my story of the railroads, and I will share
another story, because I think it fits what we're talking about here.
I think it was President Harry Truman who said what he wanted
more than anything else was a one-armed economist, because he
sÂ£ud they would go through these long presentations about what
was going to happen with the economy, and when they would fi-
nally reach what he thought was a conclusion, they would say,
"But on the other hand."
And I think that's sort of the fi-ustration that we have up here,
and I think a lot of the people in the industry have, is that once
they think they have satisfied all of your questions, then it's like,
"Oh, but on the other hand," there's this whole new set.
We don't want an adversarial relationship. I think the Congress
wants to work with you. I think we have the same goals. But there
is a high degree of frustration, and it's not just with this particular
issue, but I think it's with a lot of the new medical technologies
and new products.
This really isn't a question as much as just an invitation to try
and work with you. Because, I must tell you, I hear from an awful
lot of folks who are incredibly fi'ustrated. In fact, one of the most
troubling things that I've heard is from a venture capitalist in my
district â or in my State â who does a lot of investment in things
like this, but he won't invest now in any product or procedure or
new technology that requires FDA approval. He says it's just not
worth it. The return is way down the road, the costs are too great,
and it's just not worth it.
That is a very troubling thing for me. Somehow, I think we've
got to work together to get the trains running on time, rather than
having them all sitting there looking at each other. So, basically,
1 would just offer this invitation to you and your department: We
want to work with you to come up with some ways that we can get
the trains ninning, get the technology happening here in the Unit-
ed States, to get the investment back in the United States, to get
the jobs back in the United States.
And I think we have to look at that whole big picture, because
right now I'm afraid the system is not working the way it's sup-
posed to, and it's almost a dysfunctional system as it relates to new
technologies coming on line.
I would yield back to the Chair.
Mr. Shays. I thank the gentleman.
Mr. Fox. Thank you, Mr. Chairman.
As a follow-up to what Congressman Gutknecht was talking
about, in trying to get an end point to where we are on research
and the conclusions of the agency, if I were to give you a check
today, Dr. Kessler â I'm sure you'd like to have that from Congress,
because we're not quick on giving checks â but assume it came from
me personally, how long would it take you to design, implement,
and conclude a study to determine the rupture rate and under-
stand the associated complications? Can you give me a timeframe?
Dr. Kessler. If you gave us the resources to do it and we had
the research capability to do that?
Mr. Fox. Is there a time?
Dr. Kessler. Having all the research capability and having the
fiinds to do it?
Dr. Burlington. Mr. Congressman, we would attempt to look at
that in two ways: In one way, we would say, "Let's find out what
the general experience with similar products is out there among
the many women who have received these."
That would be an epidemiological study that would probably take
several months to get up and ready to run, a period of data collec-
tion, and then a period of data analysis, perhaps IV2 years, maybe
2 years for a typical epidemiological study on a substantial scale.
With sufficient resources, that can be accelerated.
The other side of it is, we would look and say, "Is there a prod-
uct-specific issue?" And if it were, for instance, the Mentor product,
which, as we have heard, has been under prospective data collec-
tion for a couple years already, it may be that that data could be
similarly collected from the existing experience of women who have
today received implants. If it's a company that has to start from
today moving forward with new implants, we would be looking at
early experience to say, "Is there a manufacturing problem inher-
ent in that?"
So, taken together, I would say it depends on the company, but
that realistically that could easily be done in IV2 years, and with
sufficient interest and resources tnat could be accelerated.
Mr. Fox. Well, I appreciate your agency answer, but the fact is,
I think that some would say that the information already exists
upon which you can make such conclusions. I think the problem
that the Congress is haying, whether it be silicone breast implants
or drug approyal or disapproyal, we need to speed up the process
for prompt resolution, for the public's purpose.
Let me just get, if I can, to Dr. Kessler about one more question.
You said you're reluctant to get inyolyed in certain ways that
would cause more litigation. I would submit to you â and you may
have a different point of view â ^that the fact that you have not con-
cluded, with regard to the silicone breast implant, some of these
concluding statements that the women in the United States are
looking for, that we are actually helping some of the litigation at-
torneys move forward because of the lack of action by the FDA.
Dr. Kessler. I would certainly let other people who are more ex-
pert than me comment on what influences litigation. Again, I see
ads run in the paper. I see a lot of things going on, and I certainly
would leave it to other experts to know what influences litigation.
I've been reluctant to get dragged in over the last several
months. There is a lot at stake for all sides in this, and that's one
of the reasons I try to be prudent. Congressman. It's not easy.
Mr. Fox. I understand that. What we're trying to have you look
at, as we move forward from this hearing to try and help the pub-
lic, is that we try to do, with all resolute dispatch, the concluding
information that women need in order to make intelligent decisions
with informed choices.
Dr. Kessler. Congressman, you're 100 percent correct. That is
our mutual goal.
Mr. Fox. Thank you, Mr. Chairman.
Mr. Shays. Dr. Kessler, you have been a very agreeable witness
and spent a great deal of time, as have your assistants, and we ap-
preciate it. I think this has been a helpful dialog back and forth.
We would like to work with you on helping you understand a little
more clearly how we think your providing more specific guidance,
and even trying to work on some timetable, would be helpful to pa-
tients around the country.
We just have one basic technical question I would like my coun-
sel to ask. It relates to the agreements. First, the agreements with
these two companies, Mentor and McCann, they are both the appli-
cants, have they signed these agreements?
Dr. Kessler. I'm not an expert myself in these agreements.
Mr. Shays. They agreed to these agreements?
Mr. Levitt. Yes.
Mr. Shays. OK
Mr. Halloran. For the record, my question is: The documents
that you provided â and we will copy them and give you back the
originals â in the Mentor agreement, at Section 5, there's a provi-
sion that says, "In a letter to the applicant, dated â " blank â "the
agency denied approval of the applications for use of the device for
Similarly, in the guidance document, which is marked "Draft" â
is that a final, by the way? The guidance document issued in 1992
on studies, is that final?
Mr. Levitt. I believe that's the existing guidance.
Mr. Halloran. OK In the guidance document you say, "On
April 16, 1992, the Commissioner announced all PMA's had been
denied and protocols were being formulated." So, again, we need to
clarify for the record the legal status under which these agree-
ments operated, if indeed PMA's have been, in some sense, denied.
Mr. Levitt. Again, I believe that the chairman read the provi-
sion under which those agreements operate. The PMA's were de-
nied insofar as they relate to the augmentation use. They were ex-
tended under that particular provision of the statute, by agreement
with the companies, for purposes of breast reconstruction following
mastectomy and some other very specific uses, such as afler trau-
ma from an accident, and so forth, and revision for a women who
has an implant rupture.
Mr. Halloran. So these agreements are in force, and they are
the basis of the Commissioner s statement that the companies have
a legal obligation to conduct further studies?
Dr. I^SSLER. My statement is based on the general provisions in
Ms. RoTHSTEiN. Yes, that is the legal basis.
I'm Beverly Rothstein. I'm with the Greneral Counsel's Office of
We also have, if you would also like us to provide to you, the let-
ters dated April 16 to the two sponsors.
Mr. Halloran. That would be helpful, yes.
Ms. Rothstein. I don't have those with me.
Mr. Halloran. There's also an appendix to the Mentor agree-
ment reference, which I think is the list of studies, or there's an
Appendix F reference in the agreement which is not here. Would
you provide that, as well, please?
Ms. Rothstein. Yes. There were, I think, eight attachments to
the agreement. We could get you that.
Mr. Halloran. Thank you.
Mr. Shays. Dr. Kessler, I mean this sincerely, I thank you very
much for being here. You have helped this hearing tremendously,
as Dr. Burlington and the others who have testified. And thank
you, as well, Mr. Levitt.
Dr. Kessler. Thank you very much, Mr. Chairman. We look for-
ward to working with you.
Mr. Shays. Likewise.
Dr. Kessler. Thank you.
Mr. Shays. Thank you. And I mean that sincerely. We do look
forward to working with you.
We have a very patient third panel. It is comprised of basically
nine members; I will call them. We will proceed in this order: John
Sergent, Douglas Shanklin, Sherine Gabriel, Elizabeth Connell,
Linda Ransom and Tara Ransom, Sybil Goldrich, Sharon Green,
and Jama Russano.
If you would all â if they are still here; if they survived â I would
love to have you come ana take the witness stand.
Before I swear the witnesses in, let me just give you a sense of
how we're going to proceed through this panel. We have four physi-
cians, and they will give their testimony. Then we have four pa-
tients who will proceed to give their statements, as well.
Are we missing one of the panelists? Who are we missing? Dr.
Connell is not here. I would like to make sure we have a chair for
her. I will swear all of you in at the same time.
Let me just say that we have Mr. Shadegg here who, like Sen-
ator Kyi, is from Arizona, and would like to take the opportunity
to welcome one of our witnesses.
Tara, that happens to be you. It's very rare when you get a Sen-
ator and a Congressman both who want to welcome you, but I don't
Mr. Shadegg, you have the floor.
Mr. Shadegg. Mr. Chairman, thank you very much.
I appreciate this opportunity and express my appreciation to