Transvaginal surgical mesh for the treatment of pelvic organ prolapse (POP), and its checkered safety history, will once again come before an FDA advisory panel Tuesday.
Although three devices indicated for anterior transvaginal POP repair are currently on the market today — Boston Scientific Uphold LITE, Boston Scientific Xenform, and Coloplast Restorelle DirectFix Anterior — the benefit/risk profile of surgical mesh has been questioned more than once since the first device’s 510(k) clearance in 2002.
Since then, numerous adverse events with mesh were reported, and the FDA took multiple steps over the years to manage safety concerns. The FDA requested that the Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee convene to weigh in on the benefit/risk profile specifically for anterior-placed mesh in the vaginal compartment for POP repair.
The panel is tasked with voting on whether they agree that the efficacy of this device should show superiority to native tissue repair given the known risks, and at what time superiority should be demonstrated.
However, in briefing documents for the Tuesday meeting, the FDA noted that it is asking the panel to assess transvaginal surgical mesh placed in the anterior vaginal compartment as a whole, but not evaluate the safety and efficacy of three devices already on the market.
“The FDA intends to use the recommendations from the Panel to complete its review of the [ongoing] postmarket surveillance study results for the Boston Scientific Uphold LITE, Boston Scientific Xenform, and Coloplast Restorelle DirectFix Anterior,” according to the briefing.
The mesh is indicated for treatment of POP, which occurs when one of the female pelvic organs drop from their normal position, often due to older age or childbirth. The four types of surgical mesh materials are:
- Non-absorbable synthetic mesh made of polypropylene or polyester
- Absorbable synthetic mesh including poly(lactic-co-glycolic acid) or poly(caprolactone)
- Biologic mesh such as acellular collagen derived from bovine or porcine sources
- A composite of all three
Adverse events with mesh identified through postmarket surveillance included pelvic pain, erosion or exposure of the mesh , infection, injury, incontinence, scar tissue formation, bleeding, urinary tract infection (UTI), disability, and neurological deficit or dysfunction. The FDA issued a safety warning in July 2011 addressing these safety concerns, stating such serious complications were “not rare.” The safety warning also updated their views on the mesh, and discussed the uncertainty of whether this type of mesh provides any greater efficacy versus traditional non-mesh vaginal repair.
The FDA convened an advisory panel in September 2011 to further evaluate safety and efficacy, which led to the reclassification of the mesh as a high-risk class III device from a low- to moderate-risk class II label. At the time, the panel stated that more data were still required on the safety and efficacy of the devices, and called for more postmarket surveillance studies, otherwise known as the 522 studies.
This included 131 postmarket study orders to 34 various manufacturers, and calling for a randomized controlled study or parallel cohort study to compare their mesh with native tissue repair. At the time, most manufacturers ceased marketing the devices, and ceased marketing of surgical mesh for transvaginal posterior POP repair, which has the highest risk indication.
The FDA reclassified transvaginal mesh products as class III devices in January 2016, and ordered the submission of a premarket approval application for such devices. Devices already on the market also had to obtain approval to remain on the market, which Boston Scientific and Coloplast have completed.
Along with the postmarket study orders, the FDA identified 11,274 adverse events from medical device reports from 2008 to 2018. These events included over 10,000 serious injuries, over 800 device malfunctions, as well as 77 deaths reported.
The FDA conducted a literature review that included randomized controlled trials and prospective cohort studies from 2008 through 2018. They looked at the three devices indicated for anterior placement currently on the market. However, the FDA noted that this review focused on primary repair of POP, as there is limited data on recurrent prolapse despite all three devices on the market today being used for both primary and secondary repair.
Based on this review, the FDA explained in the briefing documents that the “risk profile for mesh is less favorable compared to native tissue repair,” reinforced by the safety findings from randomized controlled trials at 12, 24, and 26 months, which also favored native tissue repair.
The panel will provide input on the specific types of adverse events that should be used when assessing safety, as well as how those events should be evaluated. They will also recommend whether the safety profile of mesh should be “comparable” to native tissue repair and weigh in on when comparable safety should be apparent.
Other topics of discussion will be how to select appropriate patients to receive these devices, as well as required training for surgeons.