FOOD AND DRUG ADMINISTRATION,
CENTER FOR DEVICES AND RADIOLOGICAL HEALTH,
OBSTETRICS AND GYNECOLOGY DEVICES PANEL, 62nd MEETING
Tuesday, January 25, 2000
Meeting to discuss the FDA Guidance Document on Devices
for Surgical Adhesions.
Full transcript can be found here
Scanned pdf can be found at:
A / Transcript
B / Transcript C
Presentation by Dr. David Wiseman, International
Adhesions Society begins on page 127:
We will go ahead and move on to the next speaker
on the list, and this is Dr. David Wiseman, speaking
the International Adhesions Society.
DR. WISEMAN: Yes. Thank you, Mr. Chairman.
Thank you for allowing me to make this presentation
today. I am wearing a couple of hats today. Next
Firstly, the International Adhesions Society is an
internet-based support group for patients with postoperative
adhesions. In addition, I have my own consulting company
that's devoted to the development of adhesion prevention
products, and in that regard I have received compensation
and have worked with a number of companies that are
represented here today and/or have financial interest
in some of those companies. Next slide, please.
Briefly, the International Adhesions Society, the
mission is stated here. It's for more awareness, to
provide support to patients, and to promote and conduct
Next slide, please.
The membership consists of men and women who suffer
from adhesion-related disease. The youngest age is
6 and the oldest is 90 we have, covering a variety
of medical specialties, predominantly in North America
but also throughout the world.
The typical problems are shown here. I want to highlight
the second bullet there to emphasize Dr. Schwaitzberg's
presentation, that many of our members have had multiple
procedures, anywhere from 4 to 20. These procedures
are hazardous, time-consuming and very expensive, and
there are a number of problems in accessing health
care for people that have adhesions. Next slide please.
This, briefly, this is not the worst patient, but when
I drafted my presentation I sent it out to everyone
for comment, and somewhere down there this lady says
has had an adhesion between the omentum and the vagina
which has been cut two or three times, and the problem
that it causes goes away, and then it comes back again
once that adhesion grows back again. Next slide.
I want to address just two points in this part of
the presentation, one regarding clinical endpoints.
We have discussed that already. There is plenty of
circumstantial evidence, as Dr. Burns has pointed out,
that links adhesions and the endpoints, and we all
understand now, I think, that it's scientifically difficult
to study these endpoints in a validated type of method.
If these endpoints were made a condition of approval,
it would delay the approval of agents that might help
our patients, and furthermore discourage manufacturers
to develop products that could be of benefit. And so
we request that the approval of anti-adhesion agents
should not be contingent upon studies with these endpoints.
Furthermore, to emphasize the previous speakers, adhesions
in and of themselves are an endpoint, and the study
of Ellis has been mentioned, that adhesions are a direct
cause of hospital readmissions in such a number which
rivals admissions for common procedures such as bypass,
coronary artery bypass, appendectomy and hip replacement,
ell as being--adhesions are a financial burden on the
Most importantly, because adhesion corrective surgery
is often hazardous and always time-consuming, it is
sometimes not even attempted, and so the lack of availability
of products such as the ones we're talking about means
that patients who suffer from these problems don't
even have the ability to go in for second, third, or
21st looks to correct their problems. So therefore,
again, we believe that adhesion reduction itself is
a valid scientific and clinically meaningful endpoint.
This is just listing some comments that I have received.
You can see patients have had procedures anywhere 4
in number to 18 I think is the highest number on that
slide. Next, please.
The next comment we want to make is that we urge the
panel to consider carefully imposing any requirement
on companies or scientists that has no scientific basis.
And the issue, the main issue at hand here is the issue
of laparoscopy versus laparotomy, and we believe that
the same standards of valid scientific evidence that
FDA requires - the law requires from sponsors must
also apply to FDA when it imposes additional requirements
on the sponsors, and we believe that such a policy
may be implemented without
ompromising patient safety.
And if you go to the number two, Bonnie, Dr. Burns
has asked me to go into a little more detail on the
laparoscopy issue. It's about the 10th slide down,
so keep going. Okay.
In the guidance document, this is a quote from the
guidance document, it says, "Due to significant
differences, both quantitative and qualitative, in
adhesion formation, the FDA's guidance document suggests
that there are differences between laparotomy and laparoscopy,
and it quotes two papers, Lundorff and the Operative
Laparoscopy Study Group. Next slide, please.
I reviewed both studies. In fact, we reviewed them
for our meta analysis, the one that we cited earlier
that I conducted together with Drs. Diamond and Trout.
The first study that is cited by the guidance document
is Lundorff, and indeed they found that more adhesions
were in laparotomy than laparoscopy.
However, a large number of patients, almost 30 percent,
which were randomized through treatment did not undergo
second-look laparoscopy. And since the group assignment
of these patients was unstated and no intensive (intent-to-treat)
treatment analysis was performed, it's very difficult
to reach any kind of conclusion as to whether in fact
were more adhesions in laparotomy than laparoscopy.
The second study that is cited is in fact a study
which is only on laparoscopy, and in the discussion
it makes some comparisons between laparoscopy and laparotomy.
At that time in 1991 the classification of de novo
adhesionswas ambiguous, and Dr. Burns has mentioned
that there are two different types of de novo adhesions,
1-A and 1-B. We don't have into what that means at
this moment, but suffice it to say that since this
classification is ambiguous, it's difficult to make
any comment on that.
And, lastly, in later review of this study, it has
turned out that some of the patients in that study
treated with Dextrand (Dextran) 70, and so it's difficult
to make any kind of conclusion from that study about
whether laparoscopy or laparotomy has more adhesions.
Next slide, please.
Furthermore, the guidance document or I believe the
questions to the panel suggest that some studies have
shown that the same barrier might not work well in
laparoscopic surgical environments, and we are unaware
of any studies that are like that. The only possible
thing that we could think of is in regard to one particular
adhesion barrier where there are four – there
are many studies showing its efficacy in laparotomy,
there are four studies in laparoscopy that show its
effectiveness, one study that shows it is not effective,
and yet one other study where the product was inappropriately
applied and it's difficult to draw any kind of conclusions
in that particular study. So we are unaware, we would
like to be made aware if the data exists, as to the
basis for this comment. Next, please.
So to summarize, there are some, even with the caveats
that I have mentioned, there are some studies that
suggest adhesions form less frequently in laparoscopy,
the Lundorff study that I mentioned, and secondly there
are some studies that suggest that adhesions form more
frequently in laparoscopy, and our meta analysis suggested
there was a slight increase but it was not statistically
significant, essentially the same. We thought that
that was due to the reduced ability to handle tissues
atraumatically. There may be some issues of gases being
used during laparoscopy, and also possible effects
of cautery combustion products. Next slide, please.
But there is no--but, despite these things, there
really is no evidence that the rates of adhesion development
are any different, other than this one unique category
of adhesions. There is no difference that the pathobiology
is any different. There is no ability--there is no
evidence that adhesion barriers work any differently
in laparotomy or laparoscopy.
And, based on the product, the one product that's
n the market, been on the market for 10 years now,
there's no evidence of differences in product safety.
In fact, Dr. Malinak, who is in the audience today,
will recall a study that he presented a few years ago
saying that this particular product, 60 percent of
its use is off-label in laparoscopy. and clearly there
have been no safety concerns with that.
So we believe that there is no justification to require
separate efficacy evaluations in laparotomy and laparoscopy.
There are some safeguards, of course. Next slide please.
That there should be adequate studies to show the
safe and effective deployment of the device. Where
concerns :hat a product may be compromised in the presence
of bleeding, the labeling should indicate that the
surgeon checks hemostasis by partial desiccation (desufflation)
prior to deployment of the device. And safety concerns
can also be addressed by safety studies and/or postmarket
And I think that's it.
DR. BLANCO: All right. Thank you very much.
DR. WISEMAN: Thank you.
second presentation was made starting on page
223 by Dr. Wiseman, in his capacity as president