The US Food and Drug Administration (FDA) is evaluating the efficacy and safety of currently marketed vaginal mesh products for treating pelvic organ prolapse.
On February 12, 2019, the FDA's Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee met to advise the agency on how to evaluate data from ongoing studies of three vaginal mesh devices currently on the US market, as well as any future candidate mesh devices indicated specifically for transvaginal repair of pelvic organ prolapse in the anterior vaginal compartment.
The three mesh devices available in the United States are two from Boston Scientific, the Uphold LITE and Xenform, and Coloplast's Restorelle DirectFix Anterior. All three are indicated for anterior and apical vaginal compartment repair.
The panel was not tasked with evaluating data for the individual devices, nor with advising the FDA on whether or not they should stay on the US market.
Rather, the agency sought the panel's guidance on a variety of issues related to ongoing trials. These included whether vaginal mesh manufacturers should be required to demonstrate that their products are more effective or simply noninferior to native tissue repair; whether both objective and subjective outcomes should be required; what types of adverse event data should be collected to evaluate safety; what factors should be used to determine whether a patient should undergo a mesh placement versus native tissue repair; and the effect of surgeon experience on outcomes.
Newer Mesh Products Safer, Manufacturers Say
The regulatory situation for these devices is unique. Following a series of warnings about adverse events with mesh products used for vaginal repair of pelvic organ prolapse, in 2011 FDA re-classified the devices from class II (moderate risk) to class III, a higher risk category. The switch meant that going forward manufacturers would need to collect efficacy and safety data for each individual product, including those already cleared with a less-strict standard.
Starting in 2012, FDA issued orders to 34 separate vaginal mesh manufacturers, requiring postmarketing data collection — known as "522 studies" — on effectiveness and safety outcomes at 12, 24, and 36 months, including comparisons to native tissue repair. Following that ruling, all but Boston Scientific and Coloplast withdrew their devices from the market.
At the advisory meeting this week, representatives from both companies emphasized that their currently marketed mesh devices are newer and safer than the ones that previously prompted concern because of improved features such as lower density and single-incision insertion.
Speaking on behalf of Boston Scientific, Miles Murphy, MD, associate medical director of the Institute for Female Pelvic Medicine & Reconstructive Surgery, North Wales, Pennsylvania, reported that the 12-month data for both the Uphold LITE and Xenform showed noninferiority to native tissue repair on a composite efficacy outcome of anatomic repair, subjective success, and no retreatment, with low serious adverse event rates.
Although an FDA literature review — also presented at the meeting — yielded a mesh exposure rate of 11% to 12% for all devices that were previously marketed, those rates for trials of the Uphold LITE were 0% to 8%. Similarly, data for the Coloplast product showed exposure/extrusion rates of 0% to 7.3% across studies.
In addition to improvements in the newer-generation products themselves, Murphy noted, "Proper surgical techniques, experience, and training have led to improved outcomes."
Transvaginal Mesh Still Seen as Option for Some Patients
During the meeting, representatives from three professional societies — the American College of Obstetricians and Gynecologists (ACOG), American Urogynecologic Society, and Society of Gynecologic Surgeons — each presented a risk–benefit analysis concluding that, although native tissue repair is generally the preferred surgical approach for anterior prolapse, transvaginal mesh is still a reasonable choice for certain patients.
The procedure involves inserting a net-like fabric into the vagina to support the bladder, uterus, or bowel.
Cheryl Iglesia, MD, director of the Section of Female Pelvic Medicine and Reconstructive Surgery at MedStar Washington Hospital Center and professor in the Departments of Obstetrics and Gynecology and Urology at Georgetown University School of Medicine, Washington, DC, spoke on behalf of ACOG.
"There are unique advantages and complications associated with synthetic mesh when used in pelvic organ prolapse surgery," she said.
Transvaginal mesh improves anatomic outcomes as well as some subjective outcomes including decreased awareness of prolapse (ie, "bulge"), and it reduces risk of repeat surgery for prolapse, as well as the risk of recurrence compared with native-tissue repair.
On the other hand, Iglesia noted, unique complications associated with synthetic mesh when used in pelvic organ prolapse surgery include mesh contracture, vaginal exposure, and erosion into the urethra, bladder, and rectum. And when those mesh-related complications occur, multiple procedures often are required to manage them.
"Given these potential complications, pelvic organ prolapse vaginal mesh repair should be limited to high-risk individuals in whom the benefit of mesh placement may justify the risk," she emphasized, including patients with recurrent prolapse or with medical comorbidities that preclude more invasive and lengthier open and endoscopic procedures.
Trial Interpretation: Patient-Reported Outcomes Considered Key
The panel spent several hours deliberating over eight multi-layered questions regarding how FDA should interpret the ongoing 522 trial results. One area of general consensus was that manufacturers should be required to show improvement in both objective/anatomic and subjective/patient-reported outcomes, but more weight should be given to the latter. Panel members also endorsed the use of validated questionnaires for this purpose.
There was some disagreement over whether FDA should require superiority or noninferiority of mesh effectiveness over native tissue repair; the majority endorsed the requirement for superiority except in certain patient subgroups.
Regarding safety, the panel generally endorsed a list of adverse events that FDA has already required for the 522 studies, including pelvic pain, erosion/exposure, dyspareunia, de novo voiding dysfunction (ie, incontinence), infection, and various anatomic abnormalities including vaginal shortening, scarring, and fistula formation.
Members also advised that careful pre-operative assessment is vital so that it is possible to later confirm that any adverse event is actually device-related.
There was some debate about the length of follow-up for efficacy and safety, but the panel settled on a minimum of 3 years, with longer follow-up as necessary.
Panel members also spent a good deal of time discussing surgeon training and experience, and agreed that because this variable could affect outcomes, FDA should find a way to account for it.
While data from the 522 studies, randomized clinical trials, and registries are being collected, patients should be educated about all nonsurgical and surgical treatment options and informed consent obtained, Iglesia advised.
"The risk–benefit ratio is very individualized, underscoring the important role of patient counseling, education, and shared decision-making for patients contemplating anterior pelvic organ prolapse repair with transvaginal mesh," she concluded.
FDA advisory panel members are vetted for conflicts of interest and are granted waivers if necessary. None were granted for this meeting. Murphy has received grant/research support from Boston Scientific and Coloplast, and is a consultant for Boston Scientific and Johnson & Johnson. Iglesia has reported no relevant financial relationships.
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Cite this: FDA Advisory Panel Tackles Tough Questions on Vaginal Mesh - Medscape - Feb 14, 2019.