July 11, 2012 ~ Dr. John Wei is a urologist and professor at the University of Michigan in Ann Arbor. His latest research, published June 20, 2012 in the New England Journal of Medicine (NEJM), (here) concludes that implanting a mid-urethral sling to treat incontinence while the woman is undergoing prolapse surgery cuts in half the risk of the leakage from incontinence even though she may not be experiencing that problem.
“What we found is that by putting in a sling, the risk of having leakage is halved,” he says.
The conclusions were controversial and many readers of MDND commented that the findings were outrageous, especially those women suffering extreme complications from a sling. Dr. Wei was made aware of the comments and the website and graciously agreed to an interview. He has a pleasant speaking style and an eagerness to explain, sort of like the professor he is at the university. He agreed that keeping a dialogue open is important.
What’s interesting is that Dr. Wei does not implant any sort of mesh in women; he was simply the head of this trial which the University of Michigan had submitted to the NIH for consideration and was approved for study.
His practice is limited to urological problems in men.
The OPUS Trial – The trial is called Outcomes Following Vaginal Prolapse Repair and MidUrethral Sling (OPUS) and it took six years to conduct at seven sites around the country, none in Ann Arbor where Dr. Wei is located. The support came from grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the NIH office of Research on Women’s Health.
The follow-up lasted only one year and the Gynecare TVT (Johnson & Johnson) sling was used exclusively. Dr. Wei says Gynecare did not influence the study or even pay for the slings which were chosen because they were the most popular incontinence sling at the time.
The Pelvic Floor Disorder Network (PFDN) is an NIH-sponsored clinical trials network made up of clinicians from eight centers. (More on this later) See their website here.
Here is a description of the design of the trial, highlighting key design features including the patient preference trial (PPT) and the cost-effectiveness analysis (CEA).
By way of background the PFDN is a network of eight centers with clinical scientists trained to do clinical trials important for women’s health. This pelvic floor disorders network looks at leakage, prolapse, and fecal incontinence.
The PFDN did an NIH study called a CARE study which involved abdominal surgery using the Burch procedure for the treatment of pelvic organ prolapse to see whether it decreased stress urinary incontinence. Through the abdomen they lifted up the bladder and stopped the leakage. The study showed doing an anti – leakage procedure, the Burch colposuspension, as a precaution in women without incontinence undergoing surgery for prolapse reduced the symptoms of incontinence.
In the OPUS trial the bladder procedure was done through the vagina not through the abdomen and it involved the placement of a Gynecare TVT sling.
The OPUS Study
In his study, Dr. Wei involved 337 women who were scheduled for prolapse surgery. Half were treated with the Gynecare TVT sling, made by Ethicon, a division of Johnson & Johnson (J&J).
After a three-month period, 23.6% of the sling recipients had developed incontinence while 49.4% without the sling had urinary incontinence. The benefits lasted for the full year the women were followed. On the flip side, 7% of the women with the sling had a bladder perforation while 31% of the women with slings had urinary tract infections compared to 18.3 % of those without the sling.
The study was published June 20, 2012 in the NEJM here. Dr. Wei talks about the OPUS study with MDND.
Q: Dr. Wei, tell us about the study?
Dr. Wei: “Many women have prolapse. It is a form of hernia where the pelvic organs fall out of place and a woman notices it because a bulge occurs coming through their vagina.
“How do we fix it? We can open up the abdomen. We make an incision in the belly area and we reach down and bring the bladder back up.
“The more minimally invasive way is through the vagina. It’s become the current practice to prevent a side effect. So its value is in preventing a common side effect – leakage of urine.
“By putting the bladder back you may experience leakage, in other words, the surgery unmasks the leakage problem. When a bladder falls out of place it kinks and when you straighten it you start to leak.
“Normally in a healthy young woman in her 20s, the urine channel is not kinked and the control is there. They also don’t leak. As women and men get older there is a tendency for muscle and connect tissue to leak. In women when the bladder falls out of place it causes a kinking to decrease the leakage. We fix the bladder and she starts leaking which would have happened anyway.
“Anyway, with this trial, by sewing in a material under the urine channel, it decreases the leakage. If it diminishes a little bit, understanding side effects, it’s not worth it. In a randomized clinical trial, she’s given a 50/50 chance to get a little sling.
“The group that did not get the sling had a 49.4 percent risk of having leakage after the surgery. In the sling group, that number went 23.6 percent, almost half, saving about half of the women from having leakage by putting in the sling. So in terms of effectiveness, it’s pretty effective. We looked at that by three months, but we waiting a year and at one year we did something interesting.
“If a woman wanted to have some treatment for the leakage, she could have it. This suggests putting in the sling seems to help. That part came across as fairly convincing.”
Q: What about Adverse Events?
“Between those who got the sling and those who didn’t get it, there were no differences in serious adverse events (such as death) in the two groups. There are side effects that could happen, adverse events didn’t differ.
“You would expect to see them more in the group that got the TVT and when we put in the TVT device we use a little needle device. Sometimes because it’s close to the bladder the needle may poke a hole in the bladder. We call that a perforation but little insults like that heal quickly and easily.
“I’m a urologist, I do surgery on the bladder all the time. When there is a little hole in the bladder and you recognize it you drain the bladder and it heals. We call it bladder perforation. It is more common in the sling group.
“Next, we worry about mesh erosion. We were sensitive to this mesh issue before it hit the news. We wanted to identify mesh erosion before the trial; fortunately there wasn’t any. Why? Because our expert surgeons tended to steer away from materials that cause the erosion. There are kits you can use.
“I don’t do prolapse surgeries, but apparently there are some meshes that tend to erode. But it is not all techniques. You can fix a prolapse and not put in any mesh. Our surgeons were careful and there were no mesh erosions in our trial up to one year.
“Now you have UTI (urinary tract infection) and it was a slightly higher than expected side effect and bleeding was a little higher by 3% as well as bladder emptying. Sometimes when you put in a sling the lady doesn’t urinate right away and it’s an expected side effect. Even without the sling they can have this problem.
“In Table 4, what we have found is that really bad adverse events didn’t differ between the groups. The expected events were more common in the group with the TVT.”
Q: And as to potential side effects down the road after one year?
“I’m not trying to trivialize it, but two to four years down the road I can’t speak to that the data because it stops at one year. Had we known that there would be all this hoopla six years ago, had we known there would be such an interest, we would have set the follow-up to be longer. You can’t change a study at the drop of a hat.”
Q: Might the women now come back if they have side effects?
“I’m the lead investigator but none of these women are my patients. We had 7 sites around the country with all leading experts in gynecology, but none were in Ann Arbor. I’m a professor of urology.”
Q: Why choose the TVT?
“Back 5-6 years ago, we asked what was the most commonly used product for prolapse. It was the TVT (tension-free transvaginal tape). The TOT (transobturator sling) was just starting to come in then.”
A: Who would have thought prophylactically? What is the genesis of that?
“In the CARE trial, published in the New England Journal of Medicine in 2006, that trial showed by doing an abdominal repair of prolapse using stitches we decreased leakage. That was a strong indicator of doing it at the time of a prolapse repair. We then moved to a vaginal approach which is minimally invasive.
See CARE trial here:
“Because of that, if we have to do vaginal surgeries to fix prolapse the question became, ‘Should we do it or not?’ Abdominal and vaginal approaches are two different things, so there is a debate.
“I did a talk in Europe last year where they said, “We would never do that; we wait until the women come in with a leakage problem.” In the U.S. we do it all the time and there’s evidence in the CARE trial we should be doing it.”
Q: Did industry have any influence in the CARE trial?
“Zero, just like the OPUS zero. All the funding, buying and paying for the TVT was paid for by NIH. There was no influence by industry to design the study. We didn’t talk to anyone at Gynecare or anyone in industry. They are all professors.”
Q: Is the Pelvic Floor Disorders Network the same every time?
“No it doesn’t remain the same. The way they work is in three to five year cycles. The participants in this network have to compete and that way it’s a good approach because no one is comfortable. You keep everyone on their toes. The best science wins every five years.
“We know what’s required so everyone is on the same page; an independent group of scientists not participating and they sit in a room and critique everyone’s application. The highest group gets funded.”
Q: Are there conflict of interest restrictions when considering who to bring into it?
“That is not a criterion in terms of the NIH (National Institutes of Health). We can’t tell what is going to be a conflict. Who would have guessed mesh erosions would have been a problem. So it’s hard to predict in the future what might be a conflict. Just in talking to my friends, NIH has strict rules. If I work for NIH, I can’t take money. It’s so strict they can’t even have the University of Michigan buy them a meal.”
Q: Are you aware of the work of Dr. Donald Ostergard who said mesh is not inert?
“I can’t speak to that. I’ll tell you why. I’m a urologist and generally don’t put in meshes, gynecologists do. You’re putting in a sling which is a treatment for leakage. Vaginal meshes are big pieces of mesh put in to lift pelvic organs. I don’t do that kind of surgery. Those are the meshes that seem to have a higher risk of erosion.”
Q: FDA hasn’t taken the slings off the hook though.
“They have different levels of concern; high concern and lower concern. I look at the FDA as a practical group. With the negative press they tend to do the right thing for people. If something was causing harm and they found out, they would pull it off the market. There are a number of examples where they post warnings.
“So the FDA looks at these kinds of meshes, like TVT for leakage problem which has been around for a longer time. It can have side effects too but the FDA is speaking of big meshes, the sling erosion problem rate is lower.
“I have to make it clear our study uses TVT which is not, as far as I know, of interest of FDA as far as what they are going after. Johnson & Johnson is pulling prolapse mesh kits off the market because they are causing the controversy. Don’t ask me why some do and some don’t.”
Part 2- continues (here) Dr. Wei Addresses comments from readers. #