Varuna Srinivasan, MBBS, MPH, National Center for Health Research
Thank you for the opportunity to speak today. My name is Dr. Varuna Srinivasan and I am speaking on behalf of members of the Patient, Consumer, and Public Health Coalition. The Coalition includes non-profit organizations representing millions of patients, consumers, researchers, and doctors united to ensure that medical treatments are safe and effective. The Coalition does not have paid staff and does not accept funding from any outside sources, so I have no conflicts of interest.
Our Coalition strongly supports FDA’s decision to require a pre-market approval review, including clinical trials, to determine the long-term safety and effectiveness of trans-vaginal mesh for pelvic organ prolapse repair. These products were initially allowed on to the market as substantially equivalent to mesh used in other parts of the body, under the 510(k) approval pathway that does not usually require clinical trials or direct scientific evidence of safety or effectiveness.
Mesh devices used in the repair of pelvic organ prolapse (POP) are permanent and are made out of synthetic material that has been proven to sometimes incite a foreign body response. It is likely to shrink over time, which can result in it degrading into the surrounding tissue making it painful as well as impossible to fix. As a result, thousands of women have reported serious injury to the FDA from surgical mesh implanted as part of POP surgeries using either the anterior or posterior vaginal compartment.
Almost 100 submissions by mesh manufacturers between 2008 and 2013 were cleared by the FDA through 510(k) processes for pelvic organ prolapse repair. Despite those decisions as well as thousands of MAUDE adverse events reports, the FDA has concluded that “the risk/benefit profile of mesh has not been well established.”[i]
Research studies included in the recent FDA literature review were designed to compare POP surgery with mesh over native tissue repair but almost all of the studies used a range of primary effectiveness endpoints, most of which followed patients for only 1-3 years and many of which did not include quality of life indicators. When comparing the safety and effectiveness of these surgeries with or without mesh, most showed that on average mesh surgeries were less safe than native tissue repair. Although the initial surgery with native tissue was somewhat less effective than initial surgery with mesh, many complications occurred within the initial months of surgery with mesh for which very little data are available on the long-term risks. The studies included in the FDA review focused on either anterior compartment repair or a combination of anterior and posterior compartment repair and because the review was not limited to studies of anterior procedures, the FDA review could not conclude whether POP surgery with mesh was safe and effective specifically for anterior compartment repair.
The data the FDA provided are not sufficient to predict whether there are some women for whom the benefits of anterior mesh POP procedures are likely to outweigh the risks. The effectiveness summary suggests that “mesh may have ‘some’ advantage over native tissue repair for anatomic POP evaluation and reoperation”,1 but this possible advantage comes with significant risks: women who undergo POP surgery with mesh are more likely to have numerous reoperations due to serious complications such as mesh erosion and exposure.
A Cochrane review published in 2016 concluded that anterior POP surgery with mesh was not a better option than native tissue repair. They examined data on the use of different types of mesh in surgical repair of pelvic organ prolapse. The review looked exclusively at 33 randomized controlled trials that included more than 3000 surgeries, comparing traditional native tissue anterior repair versus other surgical options. Sixteen of those studies compared native repair to permanent polypropylene mesh. They concluded that “Biological graft repair or absorbable mesh provides minimal advantage compared with native tissue repair.”[ii] The Cochrane scientists pointed out that although women who had native tissue repair had more repeated surgeries for prolapse rectification; they had a much-reduced risk of bladder injury, mesh exposure, and erosion. In summary, they concluded that the evidence does not support the use of mesh for anterior vaginal compartment repair in pelvic organ prolapse.
Concurrently, other regulatory agencies such as Health Canada concluded that POP procedures have a higher risk of complications compared to native tissue repair and mesh placed abdominally. In December 2017, Australia removed all POP mesh products from the market after concluding that the “benefits of using transvaginal mesh products in the treatment of pelvic organ prolapse do not outweigh the risks these products pose to patients.” 1 In 2018, the UK and Ireland placed a pause on the use of all surgical mesh placed transvaginally for POP and stress incontinence.
Meanwhile, we are still hearing from many women who have been terribly harmed by POP surgery with mesh. Many have experienced terrible, debilitating pain as a result of their initial surgery, and have undergone many additional surgeries to try to reduce the pain and regain some of their quality of life. Due to the lack of good data, we don’t know how often that happens, but it is a very terrible outcome for those women.
The American College of Obstetrics (ACOG) and Urogynecological Society (AUGS) have stated that restricting the use of mesh would be detrimental to women for whom no other options exist. However, they have failed to provide clear scientific evidence that for most women the benefits of the use of mesh in this surgery outweighs the risks.
We want to be clear that we are on the side of evidence-based medicine. If specific companies can provide irrefutable scientific evidence that the benefits outweigh the risks of using mesh for POP surgery, then we will support POP mesh surgeries if patients are provided with informed consent ensuring that they know that the adverse events can result in chronic, life-changing pain.
While the FDA is focusing on how to evaluate and review post market surveillance from the 3 companies, we urge the FDA to ensure that POP mesh research must include long-term studies which have reliable and validated quality of life indicators. Studies should include quantitative data such as number of surgeries, as well as more subjective data regarding pain, activities of daily living, and quality of life. Studies should be randomized and potential confounding variables should be statistically controlled. The companies should also conduct subgroup analyses aimed at determining whether certain types of patients are most likely to have benefits that outweigh the harms, or vice versa.
As a doctor, I strongly believe that doctors owe it to their patients to ensure that the devices being implanted in their bodies are safe and that adequate prior pre-clinical testing has been conducted. I hope you will agree.
[i] US Food and Drug Administration. FDA report: Surgical Mesh for Transvaginal Repair of Pelvic Organ Prolapse in the Anterior Vaginal Compartment FDA Executive Summary.Silver Spring, MD: US Food and Drug Administration; 2019. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ObstetricsandGynecologyDevices/UCM630949.pdf
[ii] Maher C, Feiner B, Baessler K, Christmann‐Schmid C, Haya N, Brown J. Surgery for women with anterior compartment prolapse. Cochrane Database of Systematic Reviews 2016, Issue 11. Art. No.: CD004014. DOI: 10.1002/14651858.CD004014.pub6.
The advisory committee panel deliberated and provided input on specific questions prepared by the FDA on effectiveness, safety and patient population for the evaluation of the surgical mesh currently available on the market used for trans-vaginal POP repair in the anterior and anterior/apical compartment. The FDA 24 hour summary of the meeting and questions can be found here.