Previous scandals, concerns about adverse events surround TOPAS System
byContributing Writer
The safety, efficacy, and relative benefits of the investigational TOPAS System, a medical device using implantable surgical mesh to treat female fecal incontinence after more conservative treatments have failed, will be the subject of an FDA advisory panel meeting on Thursday.
Because no medical device currently exists to treat this problem, ASTORA Women's Health (which produces the TOPAS System) was required to submit a premarket approval application, including a clinical trial to test the device's efficacy and safety. The trial achieved its primary endpoint, but, as FDA staff noted in briefing documents released ahead of the meeting, questions still remain about its safety.
The TRANSFORM trial needed to achieve a ≥50% reduction in the rate of female fecal incontinence episodes over a 12-month period compared to baseline, as documented by a 14-day diary. Overall, 52 of 80 participants completing the efficacy trial achieved this primary endpoint (65%, P=0.0048) at some point during 3 years of follow-up. The device also achieved 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.
Implantable surgical mesh in the pelvic region is certainly no stranger to controversy, with the FDA recently classifying transvaginal mesh for pelvic organ prolapse as a class III medical device. Manufacturers of this device -- versions of which have been the subject of numerous lawsuits -- are now required to undergo a rigorous premarket approval application to address concerns about adverse events. At issue for the FDA will be the safety profile of the TOPAS System, including concerns about the causes of the pain and the association of pelvic organ prolapse with this procedure.
The clinical trial for the TOPAS System required patients to be 18 years of age or older, not be pregnant or planning to become pregnant and to have tried other more conservative therapies to treat fecal incontinence, such as dietary modifications, pharmacologic therapies, or pelvic floor muscle training. The advisory committee will be asked whether the product should be labeled with these restrictions.
As there was a trend toward fewer adverse events when the device was implanted by a urogynecologist as opposed to a colorectal surgeon, FDA officials will also ask panelists for their opinions on the clinical training or experience required for clinicians to implant this device.
The agency also has concerns about the potential performance goals being proposed for two planned post-approval studies of the TOPAS System. ASTORA has a stated 25% performance goal for an extended follow-up of the existing cohort for a period of to 60 months and a 20% performance goal for a new cohort of patients followed for a period up to 36 months.
"These performance goals are based on the performance of a different device that does not modify the anatomical structure of the pelvic muscles," agency staff wrote. "The FDA recommends the applicant take into consideration the nature of the implanted device, the risk/benefit ratio, and the results from the TOPAS premarket study when developing the performance goal for the post-approval study."
Panel members will not be asked to vote explicitly on whether the device should be approved, but the three voting questions on the agenda are whether they believe the product is safe, whether it's effective, and whether the benefits outweigh the risks.
The FDA is not required to follow advisory committee recommendations but it usually does.
Because no medical device currently exists to treat this problem, ASTORA Women's Health (which produces the TOPAS System) was required to submit a premarket approval application, including a clinical trial to test the device's efficacy and safety. The trial achieved its primary endpoint, but, as FDA staff noted in briefing documents released ahead of the meeting, questions still remain about its safety.
The TRANSFORM trial needed to achieve a ≥50% reduction in the rate of female fecal incontinence episodes over a 12-month period compared to baseline, as documented by a 14-day diary. Overall, 52 of 80 participants completing the efficacy trial achieved this primary endpoint (65%, P=0.0048) at some point during 3 years of follow-up. The device also achieved 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.
Implantable surgical mesh in the pelvic region is certainly no stranger to controversy, with the FDA recently classifying transvaginal mesh for pelvic organ prolapse as a class III medical device. Manufacturers of this device -- versions of which have been the subject of numerous lawsuits -- are now required to undergo a rigorous premarket approval application to address concerns about adverse events. At issue for the FDA will be the safety profile of the TOPAS System, including concerns about the causes of the pain and the association of pelvic organ prolapse with this procedure.
The clinical trial for the TOPAS System required patients to be 18 years of age or older, not be pregnant or planning to become pregnant and to have tried other more conservative therapies to treat fecal incontinence, such as dietary modifications, pharmacologic therapies, or pelvic floor muscle training. The advisory committee will be asked whether the product should be labeled with these restrictions.
As there was a trend toward fewer adverse events when the device was implanted by a urogynecologist as opposed to a colorectal surgeon, FDA officials will also ask panelists for their opinions on the clinical training or experience required for clinicians to implant this device.
"These performance goals are based on the performance of a different device that does not modify the anatomical structure of the pelvic muscles," agency staff wrote. "The FDA recommends the applicant take into consideration the nature of the implanted device, the risk/benefit ratio, and the results from the TOPAS premarket study when developing the performance goal for the post-approval study."
Panel members will not be asked to vote explicitly on whether the device should be approved, but the three voting questions on the agenda are whether they believe the product is safe, whether it's effective, and whether the benefits outweigh the risks.
The FDA is not required to follow advisory committee recommendations but it usually does.
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