Study: FDA should have banned pelvic mesh long before it did

Researchers who conducted a long-term study of women implanted with transvaginal mesh to treat pelvic organ prolapse (POP) concluded that the FDA should have banned the product sooner than it did.

The study of 54,194 women in New York State revealed that women treated with mesh had an 8.8% risk of reintervention 5 years after surgery, compared with 6.3% in the same size group of women treated differently for the same condition. This 40% increased risk was observed across all levels of hospital volume in performing POP procedures, the researchers reported.

The observational study paired more than 12,000 women in each group and is a follow-up to the same researchers’ review of patients 12 months after implantation. The research team — which included medical doctors from Weill Cornell Medical College-New York Presbyterian in New York, the University of Oxford in the UK, the Warren Alpert Medical School of Brown University in Rhode Island, and the Women & Infants Hospital in Providence, R.I. — published their results in the journal Obstetrics & Gynecology.

The governments of Scotland and the UK noted the risks to women of pelvic mesh in 2017, with the UK National Institute for Health and Care Excellence concluding that these procedures should be confined to research. Health officials in Australia and New Zealand effectively banned the mesh their markets that same year.

The FDA reported more than 1,000 adverse events related to pelvic mesh in 2008, and reclassified the product from moderate-risk Class II designation to high-risk Class III in 2016. Postmarket studies the FDA requested from mesh manufacturers beginning in 2012 failed to attract enough participation from surgeons, the researchers reported. The agency ordered manufacturers to stop selling the product in the U.S. in April 2019, citing a lack of manufacturers providing “reasonable assurance” of the long-term safety and effectiveness using the mesh for POP.

“The United States was late in the removal of mesh implants for POP despite the numerous safety warnings and adverse events reported from patients’ narratives,” the researchers said. “Even though transvaginal mesh has been removed from the market, our data suggest that the risk of mesh complications does not diminish over time and these women warrant close follow-up.”

The FDA’s April 2019 order was the culmination of a multi-year regulatory process required by statute, according to an agency spokesperson. The agency said it 131 postmarket surveillance study orders in 2012 to 34 manufacturers, requiring them to collect data to address specific safety and effectiveness. Most manufacturers opted to stop manufacturing transvaginal mesh.

After the FDA reclassified the devices to Class III, requiring premarket authorization, multiple PMAs were submitted and the regulatory process allowed continued marketing of such products during the agency’s review, the spokesperson said in an email to MassDevice. None of the companies demonstrated a reasonable assurance of safety and effectiveness for their devices.

“All along, the FDA has been transparent about our concerns with the public,” the spokesperson added. “The FDA issued safety communications in 2008 and 2011 based on our review of reports of complications and held public panel meetings in 2011 and 2019 where safety and effectiveness was discussed openly with experts. Our goal was to keep patients informed of the risks of these products while we moved through our multi-year regulatory process.”

In the new study, 18.5% of mesh patients who had reinterventions underwent a procedure for mesh-related complications, with the remaining 81.5% receiving reinterventions related to new or recurrent prolapse, urinary complications and other reasons.

The results also controverted the traditional belief that mesh procedures reduce the recurrence of POP through good apical support, the authors said. Their findings showed a higher rate of repeat POP surgery overall in women with mesh (652 patients or 5.3% of all patients) than in women without mesh (513 patients or 4.2% of all patients).

Complications reported from pelvic mesh include chronic inflammation, mesh shrinkage and embedding in scar tissue, infection, bleeding, pain during sexual intercourse, organ perforation, protrusion through the vaginal wall and urinary problems. Mesh manufacturers have paid millions of dollars in legal judgments and settlements, and the lawsuits keep coming.

The researchers said mesh erosion appears to present an “ongoing risk,” as they found no decline in mesh erosion rates over the study period. The rates they discovered almost double those published by a Cochrane Review in 2016, in which only 8% of repeat surgical interventions were for mesh-related complications. That study covered 37 randomized controlled trials following 4,023 women, comparing outcomes for pelvic mesh with native tissue repair for POP.

“This rate of mesh complication may actually be underestimated given that only women who underwent reintervention are captured and not any of the women who had mesh erosions and complications that were conservatively managed in the office setting,” the researchers in the new study said.

“Continued surveillance of mesh in POP repairs is essential to ensure safety for the women who have already been implanted,” they concluded. “Registries should include comprehensive information about the nature and burden of POP recurrence, different types of re-treatment, patient-reported outcomes, and information about implanting surgeons.”