Findings from an FDA literature review covering the same period and also focusing on anterior and/or apical repair show that synthetic mesh may have some advantage over native tissue repair for objective effectiveness outcomes – but not necessarily subjective outcomes – over 1-3 years of follow-up. And the risks of using mesh are greater, particularly with respect to reoperation for recurrence and mesh complications, the latter of which continued beyond the first year of follow-up and through 5 years, the agency said.
Although the review may help the FDA frame its questions moving forward, it has limited utility beyond that, according to urogynecologic surgeons who testified on behalf of three professional societies. The review does not delineate differences between the newer materials used today and older mesh materials that were of heavier weight/higher mesh density and often placed using more invasive delivery systems. Nor does it offer any insight on the use of mesh for secondary repair.
“Much of the existing data on the use of transvaginal mesh in POP surgery comes from low to moderate quality, short-term studies of synthetic mesh that is no longer used in clinical practice,” said Cheryl Iglesia, MD, a Washington-based ob.gyn. who spoke to the advisory panel on behalf of the American College of Obstetricians and Gynecologists. “There’s a critical need for data from high-quality studies on the use of the newer, lightweight type 1 transvaginal meshes used in POP surgery.”
The FDA’s 522 orders requested that manufacturers conduct a randomized, controlled study or parallel cohort study comparing their device to native tissue repair. Requested effectiveness endpoints included anatomic success, subjective success, and retreatment for prolapse. For safety endpoints, the agency requested all device- and procedure-related adverse events, as well as the rate of individual adverse events, such as mesh erosion and de novo dyspareunia and urinary dysfunction. The FDA asked for all endpoints at 6-month intervals out to 24 months and at 36 months.
The panel advised that superiority should be the standard for the general population of women with POP – that mesh used in the anterior/apical vaginal compartment should be shown to be superior to native tissue repair at each time point. In specific patient populations for whom native tissue repair is not deemed feasible or appropriate, demonstrating equivalence is sufficient, they advised.
They called for “more diligent” presurgical assessments of sexual function and activity, as well as other symptoms that will be assessed later. And the panel agreed with the FDA that concomitant procedures (for example, hysterectomy and sling placement) and certain preexisting medical conditions and patient characteristics (such as obesity and diabetes) can affect outcomes and should be delineated and considered in the FDA’s evaluations and interpretation of study results.
Regarding surgeon characteristics, the panel’s biostatisticians and physicians (largely urogynecologists, but also one community ob.gyn.) advised the FDA to pay attention to surgeon training, experience, and volume, but they declined to offer any specific recommendations. Discussions often came back to the value of a registry that would capture both surgeon data and patient experience. And throughout the panel’s discussion, surgeons stepped away from the main questions at hand and emphasized the individualized nature of risk-benefit ratios and decision making.
Registries have been successfully used for cardiology and orthopedic implants and, within obstetrics and gynecology, for assisted reproductive technologies, Dr. Iglesia said in an interview after the meeting. “We have models … we just need to make it easy for physicians, using our EMRs. But I’m hopeful.”