FDA Discusses Benefit Risk Profile of Transvaginal Mesh
Drug/Device: Device, transvaginal surgical mesh (Uphold LITE, Xenform, Restorelle DirectFix Anterior, and Pelvic Floor Repair Matrix)
Sponsors/manufacturers: Boston Scientific, Coloplast, and Acell Matristem
Committee: Medical Devices Advisory Committee – Obstetrics and Genecology Device Panel
Indications: Effectiveness and safety of transvaginal surgical mesh for the treatment of pelvic organ prolapse (POP)
Question: Does the panel agree that the efficacy of this device should show superiority to native tissue repair given the known risks, and at what time should superiority be demonstrated?
Vote Results: Most panel members agreed that the efficacy of the device should show superiority to native tissue repair and that the superiority must be demonstrated at 12, 24, and 36 months post-op; 2 members voted against superiority, stating that demonstration of non-interiority is sufficient
Related Documents:
Background:
Ever since receiving its first 510(k) clearance in 2002, the benefit/risk profile of the surgical mesh has been continuously questioned. Post-market surveillance indicated numerous adverse events including pelvic pain, infection, bleeding, urinary tract infection (UTI), disability, and neurological deficit or dysfunction. Following extensive rounds of reviews and strong evidence of excess adverse events spanning the 13 year period, in 2016, the FDA ordered transvaginal mesh to be reclassified from class-II (low to moderate risk devices) to class-III (high risk devices). This also meant that the device required the filling of premarket approval (PMA), which is the agency’s most stringent device review pathway, for surgical mesh for transvaginal POP repair. Currently, Boston Scientific’s Uphold LITE and Xenform, as well as Coloplast’s Restorelle Direct Fx are the only devices being marketed in the United States. Since 2014, countries such as Canada and the U.K. have either placed heavy regulations or completely paused the use of vaginal mesh in treatment of POP. The FDA is not asking the panel to determine the safety and effectiveness of a specific device, but to draw general conclusions to such measures of transvaginal mesh placed in the anterior vaginal compartment in POP treatment.
Unique Challenges:
The FDA conducted an elaborate systematic literature review covering the period of 2008 – 2018, aimed at synthesizing evidence to assess the safety and effectiveness outcomes associated with vaginal mesh in treatment of POP. The date range was chosen to align with the FDA 510(k) clearance in 2002, allowing for sufficient time following the clearance, for any clinical studies to be completed and published. Notably, the FDA’s search focussed on comparing the use of mesh or NTR for primary repair of POP in the anterior vaginal compartment but not for recurrent prolapse. The agency further performed database search within the Medical Device Report (MDR) database (RWD) to identify trends and types of commonly submitted adverse events related to the device and whether they matched with published evidence.
Effect and risk profiles of the device compared with NTR were assessed via meta-analysis of the published evidence. The effectiveness outcome assessed both the objective (via POP-Q scale) and subjective measurements (via patient reported outcomes or recurrent prolapse) of the procedure. The analyses were stratified by study design and subsequently by time followed up. The FDA also attempted to address whether effectiveness and safety outcomes differed by device and patient characteristics, concomitant procedures, as well as characteristics of the operating physician.
With regard to effectiveness, the FDA has concluded that following up between 1-3 years after, mesh may have a slight advantage over NTR in objective, but not subjective, outcomes but the effect diminished after 5 years of follow-up. In terms of safety, the FDA has found that NTR is favored over mesh, at any follow-up point in time, and that mesh related complications continued beyond year 5 post-operation.
Based on aforementioned evidence, the FDA has concluded that the use of surgical mesh in the anterior vaginal compartment does not offer a consistent effectiveness benefit compared to native tissue repair, particularly when considering the subjective outcomes. The risks of using mesh in the anterior vaginal compartment are greater than NTR, particularly with respect to re-surgery for all indications (recurrence and mesh complications).
Risk/benefit assessment
As evident from the literature review, the risk profile for mesh is less favorable than NTR. Given its increased risk, the FDA believes that use of mesh for treatment of POP should be more effective (i.e. statistically superior) than NTR. The FDA also believes that both anatomical (objective) and subjective outcomes should be considered when assessing effectiveness. Safety considerations of mesh should be comparable to that of NTR in terms of all adverse events, not just those associated with the device or the procedure. The risk/benefit profile should remain unchanged beyond 12 months post-op, as the life expectancy of the device is semi-permanent if biologic and permanent if synthetic.