Unanimous support for novel mesh device
Contributing Writer
BETHESDA, Md. -- An FDA advisory committee unanimously agreed at a Thursday meeting that the benefits of an implantable surgical mesh device for women with fecal incontinence outweigh the risks.
The so-called TOPAS device, developed by ASTORA Women's Health (a subsidiary of Endo International), is intended for women who have failed more conservative treatment options, such as diet changes, pharmacologic therapies, or pelvic floor muscle training. It is a "non-bioabsorbable mesh device" approximately 45 cm in length that's inserted parallel to the puborectalis muscle below the anorectum, according to FDA briefing documents.
Members of the FDA's Gastroenterology and Urology Devices advisory committee voted 8-0 that the TOPAS treatment for fecal incontinence provides "a reasonable assurance of safety" and of effectiveness, and that the risks -- which are not insubstantial -- are tolerable given the relief seen in clinical trials.
The panel recommended postmarket studies, adequate training of surgeons, and labeling to indicate use in women 18 years or older who are not pregnant. (Some panelists suggested an additional warning for those who may become pregnant.)
While the mechanism of action is still unclear, the TOPAS system is thought to help support the puborectalis muscle, which appears to weaken in people with fecal incontinence. This weakening causes a change in the anorectal angle, which allows stool to move down the rectum involuntarily, a member of FDA's technical staff explained.
Agency briefing documents further clarified the theory that "the fixation of the mesh implant provides the physical support of the anatomy." In time, tissue growth around the device occurs, as the body heals, further enhancing this support.
In the product's main clinical trial, 52 of 80 participants completing the efficacy trial showed at least a 50% reduction in fecal incontinence episodes over a 12-month period, the study's primary endpoint (65%, P=0.0048). The device also met several secondary endpoints, such as long-term effectiveness, a reduction in incontinent days, fecal incontinence episodes, and symptom severity.
However, 72 of the 152 patients in all who received the implant reported adverse events related to the device (47%). Of these, the most common was pain (45%) followed by infection (27%), and 12% reported new or worsening pelvic organ prolapse.
At the heart of the committee's decision were a few unknowns: how much pain is a woman willing to tolerate to improve her continence? Is pelvic organ prolapse worth the risk of gaining back continence?
Susan Kalota, MD, a urologist in Tucson, Ariz., said most women would agree to risk some pain in exchange for continence. "So it's just, how many are in the debilitating, God-awful pain?" she asked.
As for the second question, Kalota added, "The vast majority of women would easily trade prolapse for continence."
The committee's patient representative agreed. "Wetting your pants is not nearly as difficult as defecating in your pants," said Barbara Berney, from Rockford, Ill.
On the other hand, Jonathan Efron, PhD, a professor of urology and surgery at Johns Hopkins University in Baltimore, reminded the panel that a patient might have pain or prolapse without benefit from the surgery. Those patients "probably wouldn't be happy." Nevertheless, he agreed with other panel members that the benefits outweighed the risks overall.
In its presentations, the sponsor sought to distinguish the TOPAS system from transvaginal mesh devices, which have been associated with severe pelvic pain and organ perforation. The transvaginal mesh devices were also entrenched in countless lawsuits and a complex scam involving unscrupulous health plans who profited from their removal.
Unlike the transvaginal mesh devices which are inserted on top of the vagina, the TOPAS system is placed two centimeters from the anal rectum with a cushion of fat in between, the sponsor explained. The sponsor emphasized that to date none of its devices have required revisions or removal.
Asked if the device was possible to remove, the sponsor's representative said the device is intended to be permanent. But one of the firm's consultants later stated that it would be possible to explant the device, and that an ultrasound could be used to help locate the mesh.
Several panelists seemed skeptical about the possibility of complete removal because of in-growth around the device.
There also appeared to be a disparity in adverse events depending on who performed the surgery -- colorectal surgeons versus urogynecologists -- which favored the latter. But other factors, such as stretching regimens followed by participants prior to the surgery at some centers and not others, may have accounted for such differences.
Jason Connor, PhD, a statistician based in Orlando, Fla., recommended conducting more research on the effect of stretching on adverse events.
The committee spent some time discussing the lack of a control group in the pivotal study. At the time it was conducted, no other therapies or treatments were available to serve as a comparator and using a sham device as a comparator was considered "unreasonable," because it would require a control group to undergo anesthesia and receive incisions.
The committee did not reach consensus on whether studying new comparators was important. One panelist recommended a well-matched prospective cohort to gauge the rate of certain adverse events such as prolapse, without a procedure.
Cheryl Iglesia, MD, a urogynecologist based in Washington, D.C., recommended that a registry be used to conduct postmarket surveillance on surgical outcomes and to determine which surgeons may need additional training. She also suggested the possibility of using imaging to distinguish characteristics of responders and nonresponders.
The sponsor submitted its request for premarket approval in April 2014, received a deficiency letter in July 2014, and then submitted additional information to the FDA in July and October 2015.
The FDA could not say when a final approval decision would be made. It is not required to follow the advice of its advisory committees but it often does.
The so-called TOPAS device, developed by ASTORA Women's Health (a subsidiary of Endo International), is intended for women who have failed more conservative treatment options, such as diet changes, pharmacologic therapies, or pelvic floor muscle training. It is a "non-bioabsorbable mesh device" approximately 45 cm in length that's inserted parallel to the puborectalis muscle below the anorectum, according to FDA briefing documents.
The panel recommended postmarket studies, adequate training of surgeons, and labeling to indicate use in women 18 years or older who are not pregnant. (Some panelists suggested an additional warning for those who may become pregnant.)
While the mechanism of action is still unclear, the TOPAS system is thought to help support the puborectalis muscle, which appears to weaken in people with fecal incontinence. This weakening causes a change in the anorectal angle, which allows stool to move down the rectum involuntarily, a member of FDA's technical staff explained.
Agency briefing documents further clarified the theory that "the fixation of the mesh implant provides the physical support of the anatomy." In time, tissue growth around the device occurs, as the body heals, further enhancing this support.
In the product's main clinical trial, 52 of 80 participants completing the efficacy trial showed at least a 50% reduction in fecal incontinence episodes over a 12-month period, the study's primary endpoint (65%, P=0.0048). The device also met several secondary endpoints, such as long-term effectiveness, a reduction in incontinent days, fecal incontinence episodes, and symptom severity.
At the heart of the committee's decision were a few unknowns: how much pain is a woman willing to tolerate to improve her continence? Is pelvic organ prolapse worth the risk of gaining back continence?
Susan Kalota, MD, a urologist in Tucson, Ariz., said most women would agree to risk some pain in exchange for continence. "So it's just, how many are in the debilitating, God-awful pain?" she asked.
As for the second question, Kalota added, "The vast majority of women would easily trade prolapse for continence."
The committee's patient representative agreed. "Wetting your pants is not nearly as difficult as defecating in your pants," said Barbara Berney, from Rockford, Ill.
In its presentations, the sponsor sought to distinguish the TOPAS system from transvaginal mesh devices, which have been associated with severe pelvic pain and organ perforation. The transvaginal mesh devices were also entrenched in countless lawsuits and a complex scam involving unscrupulous health plans who profited from their removal.
Unlike the transvaginal mesh devices which are inserted on top of the vagina, the TOPAS system is placed two centimeters from the anal rectum with a cushion of fat in between, the sponsor explained. The sponsor emphasized that to date none of its devices have required revisions or removal.
Asked if the device was possible to remove, the sponsor's representative said the device is intended to be permanent. But one of the firm's consultants later stated that it would be possible to explant the device, and that an ultrasound could be used to help locate the mesh.
Several panelists seemed skeptical about the possibility of complete removal because of in-growth around the device.
Jason Connor, PhD, a statistician based in Orlando, Fla., recommended conducting more research on the effect of stretching on adverse events.
The committee spent some time discussing the lack of a control group in the pivotal study. At the time it was conducted, no other therapies or treatments were available to serve as a comparator and using a sham device as a comparator was considered "unreasonable," because it would require a control group to undergo anesthesia and receive incisions.
The committee did not reach consensus on whether studying new comparators was important. One panelist recommended a well-matched prospective cohort to gauge the rate of certain adverse events such as prolapse, without a procedure.
Cheryl Iglesia, MD, a urogynecologist based in Washington, D.C., recommended that a registry be used to conduct postmarket surveillance on surgical outcomes and to determine which surgeons may need additional training. She also suggested the possibility of using imaging to distinguish characteristics of responders and nonresponders.
The FDA could not say when a final approval decision would be made. It is not required to follow the advice of its advisory committees but it often does.
Không có nhận xét nào:
Đăng nhận xét