Introduction Transvaginal mesh devices are approved in the USA by the Food and Drug Administration (FDA), through the 510(k) system. However, there is uncertainty about the benefit to harm balance of mesh approved for pelvic organ prolapse. We, therefore, assessed the evidence at the time of approval for transvaginal mesh products and the impact of safety studies the FDA mandated in 2012 because of emerging harms.
Methods We used FDA databases to determine the evidence for approval of transvaginal mesh. To create a ‘family tree’ of device equivalence, we used the 510(k) regulatory approval of the 1985 Mersilene Mesh (Ethicon) and the 1996 ProteGen Sling (Boston Scientific), searched for all subsequently related device approvals, and for the first published randomised trial evidence. We assessed compliance with all FDA 522 orders issued in 2012 requiring postmarketing surveillance studies.
Results We found 61 devices whose approval ultimately relied on claimed equivalence to the Mersilene Mesh and the ProteGen Sling. We found no clinical trials evidence for these 61 devices at the time of approval. Publication of randomised clinical trials occurred at a median of 5 years after device approval (range 1–14 years). Analysis of 119 FDA 522 orders revealed that in 79 (66%) the manufacturer ceased market distribution of the device, and in 26 (22%) the manufacturer had changed the indication. Only seven studies (six cohorts and new randomised controlled trial) covering 11 orders were recruiting participants (none had reported outcomes).
Conclusions Transvaginal mesh products for pelvic organ prolapse have been approved on the basis of weak evidence over the last 20 years. Devices have inherited approval status from a few products. A publicly accessible registry of licensed invasive devices, with details of marketing status and linked evidence, should be created and maintained at the time of approval.
- regulatory approval
- transvaginal mesh
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Contributors CJH designed the study, collected the data and drafted the first version for the manuscript. IO, BG, AP, JKA, TJ and KRM contributed to the data interpretation and development of the manuscript and approved the final draft. CJH is the guarantor.
Disclaimer The views expressed are those of the authors.
Competing interests CJH is an expert witness in a current medical device legal case and has received financial remuneration from an asbestos legal case. He has received expenses in the past from the US FDA to attend a working group on device regulation. CJH and BG receive funding from the National Institute of Health Research (NIHR) School of Primary Care. BG receives funding from the Laura and John Arnold Foundation and reports personal fees from intermittent additional personal income from speaking and writing for lay audiences on problems in science and medicine including regulatory shortcomings. TJ and CJH were recipients of a UK National Institute for Health Research grant for a Cochrane review of neuraminidase inhibitors for preventing and treating influenza. Also, TJ receives royalties from his books published by Il Pensiero Scientifico Editore, Rome and Blackwells. TJ is occasionally interviewed by market research companies about phase I or II pharmaceutical products. In 2011-2013, TJ acted as an expert witness in a litigation case related to the antiviral oseltamivir, in two litigation cases on potential vaccine-related damage, and in a labour case on influenza vaccines in healthcare workers in Canada. He has acted as a consultant for Roche (1997-1999), GSK (2001-2002), Sanofi-Synthelabo (2003) and IMS Health (2013), and in 2014 was retained as a scientific adviser to a legal team acting on oseltamivir. In 2014-2016 TJ was a member of three advisory boards for Boehringer Ingelheim and is the holder of a Cochrane Methods Innovations Fund grant to develop guidance on the use of regulatory data in Cochrane reviews. In 2016-2017 TJ was a member of an independent data monitoring committee for a Sanofi Pasteur clinical trial on an influenza vaccine. JKA has published papers and edited textbooks on adverse drug reactions; he has also acted as an expert witness in cases related to adverse drug reactions.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement A spreadsheet recording the individual 522 orders is available on request from the corresponding author.
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