International Adhesions Society





FDA Panel & Adhesions



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:

Transcript 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 for 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 slide, please.
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 research.
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 that she
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. Next, please.

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, as
ell as being--adhesions are a financial burden on the system.

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. Next, please.

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 there
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 were
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 surveillance.
And I think that's it.

DR. BLANCO: All right. Thank you very much.
DR. WISEMAN: Thank you.

A second presentation was made starting on page 223 by Dr. Wiseman, in his capacity as president of Synechion, Inc



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