- FDA is seeking better evidence to assess how safety and effectiveness outcomes from native tissue repairs stack up against those from certain transvaginal mesh implants among pelvic organ prolapse (POP) patients, the subject of class action lawsuits and international regulatory scrutiny for more than a decade. A randomized controlled clinical trial is needed to compare the benefit/risk and safety of mesh products compared to native tissue treatment to repair POP, according to documents released ahead of a meeting of the obstetrics and gynecology device advisory panel Feb. 12.
- In conjunction with shifting the devices to the highest-risk Class III review category in 2016, FDA required manufacturers seeking to remain on the market to submit premarket approval applications, a step taken by Boston Scientific and Danish company Coloplast.
- Citing a review of medical literature and more than 11,000 adverse event reports, agency staff noted that "evidence from RCTs demonstrate that at 12, 24 and 36 months, safety outcomes favor native tissue repair." FDA is seeking expert input on study design, including how to weigh anatomical versus subjective factors, what constitutes an optimal patient population and physician training.
Surgical mesh has been used for decades, with the first transvaginal product for pelvic organ prolapse repair officially cleared as a Class II device by FDA in 2002. The implants are used as reinforcement when muscles and tissue of the pelvic floor weaken and displace, often years after child birth.
Between January 2008 and October 2018, the agency found 10,391 Medical Device Reports citing serious injury, 806 citing device malfunction, and 77 citing death related to the products. FDA also noted that its review found mesh erosion or exposure occurs for between roughly 11% to 18% of patients who undergo mesh-based repair.
FDA flagged issues surrounding surgical mesh for transvaginal repair of POP in a 2008 public health notification. Adverse effects include pelvic pain, infection, bleeding and vaginal scarring, and a JAMA study published in January said women who experience these complications may be at higher risk for new-onset depression or self-harm.
The agency argues that safety and effectiveness outcomes for mesh products must be studied beyond 12 months, with follow up to examine long-term adverse events and durability.
"The FDA understands that patients and physicians may be willing to take on greater safety risk with increased likelihood or magnitude of effectiveness (e.g., patients with recurrent prolapse). Because this device type is an implant, the FDA believes that favorable/benefit risk should be established long term," FDA said in a document released Friday morning.
In 2011, FDA issued a safety communication and followed it up with a risks/benefits consideration meeting, from which the agency went on to issue 131 orders for postmarket surveillance studies to 34 manufacturers, most of whom chose to instead cease marketing their products, FDA said. In 2014, FDA issued proposed orders to reclassify the devices, which became official in 2016.
PMA applications to remain on the market were due by July 5, 2018. All manufacturers of products for posterior prolapse exited the market, while Boston Scientific and Coloplast moved forward with anterior prolapse devices.
FDA said there are currently four ongoing studies for five devices, results of which FDA will consider in evaluating safety and effectiveness of Boston Scientific Uphold LITE, Boston Scientific Xenform, and Coloplast Restorelle DirectFix Anterior.
Coloplast in prepared materials argued that "patients and surgeons need options," which Boston Scientific echoed in saying that treatment options ought not be considered "one-size-fits-all." Boston Scientific also said its required postmarket surveillance studies "demonstrate improved efficacy and fewer complications compared to much of the literature presented during the 2011 FDA panel meeting" and that the company's mesh devices "demonstrate a favorable benefit/risk profile for properly chosen patients in the hands of properly trained surgeons."
Notably absent from PMA consideration is Johnson & Johnson, whose Ethicon pelvic meshes have resulted in at least 37,000 product liability claims against the company, according to a recent quarterly regulatory filing.
The American Urogyencologic Society, among the professional group presenters, affirmed its support for continued market availability of these devices in its prepared testimony released ahead of the meeting.
The group said restricting products from the market would adversely impact registries that have been set up to compare outcomes from different types of mesh and that in decreasing access to regulated devices, the medical community would lose the benefit of having "surveillance and benchmarking analyses."
"If mesh devices marketed for prolapse were to be removed, we would lose the ability to use Unique Device Identifiers it is likely that some surgeons would, in their advocacy for their patients, feel the need to return to practice of devising their own techniques, which would curtail our ability to perform device surveillance and benchmarking analyses," the society wrote.
Missy Lavender, founder of women's pelvic health education group Below Your Belt, told MedTech Dive that transvaginal mesh products have "been overused and understudied," but she's glad "the pendulum is swinging back” toward longer studies and a stronger science-based approach.
Conversely, Michael Carome, director of Public Citizen's health research group, was unmoved by FDA's push for greater clinical trials, calling transvaginal mesh products the "poster child example of what’s wrong with FDA oversight of medical devices."
"Our views on these devices are unchanged after reviewing the materials," Carome told MedTech Dive. "We believe like we did in 2011 that all of these devices should be off the market."
More broadly, FDA called out technologies related to women's health as among the important focuses of last year's Medical Device Safety Action Plan. FDA said it wants to build a public-private registry network to better capture real world evidence.