CDRH Oversight of Device Safety Hurts Women: WaPo

[Analysis by Jim Dickinson] “It seems every two or three years we have another controversy in women’s health,” a 7/30 Washington Post Magazine article quotes Northwestern University health policy researcher Steven Xu as saying, about the ongoing controversy over Bayer’s permanent contraceptive device Essure. Xu co-authored a critical study of CDRH device approval requirements in Obstetrics and Gynecology last year and elaborated: “We have pelvic mesh, we have concerns with morcellators … and then with Essure, it’s like, here we go again.

The lengthy Post article, by New York-based investigative journalist Jennifer Block, delves into the history of FDA medical device safety regulation, which ironically began with the 1976 Medical Device Amendments Act following controversy over another contraceptive product, the intrauterine device Dalkon Shield marketed by the A.H. Robins pharmaceutical company. Until that time, except for a handful of medical devices regulated by FDA as drugs, all other devices had been exempted from premarket review and approval by the 1938 Food, Drug and Cosmetic Act; FDA’s only authority over them was under the law’s adulteration and misbranding provisions.

Medical device safety standards were deliberately made less stringent than the FD&C Act’s standards for drugs. Block’s article quotes former FDA associate chief counsel Patricia Zettler (now at Georgia State University) as saying the legal standard for approving a drug “explicitly requires adequate and well-controlled clinical investigations” whereas the standard for device is “reasonable assurance” of safety and effective, which is subject to interpretation.

Prodded by an industry protected from state tort litigation by the 2008 Supreme Court Riegel v. Medtronic decision, CDRH’s exercise of that interpretational latitude has been shown to be lenient in numerous cases over the years. Obvious examples, in addition to pelvic mesh and morcellators, include the Center’s serial refusals to apply stronger proof-of-safety requirements on LASIK devices and dental amalgam, despite pressure from injured patients. The most it will normally do is modify product labeling.

Sometimes called “bureaucratic ossification,” CDRH’s decision-making in reviewing products and postmarketing safety issues too often proves immune to revision, even in the face of new data. This trait is graphically illustrated in a revealing chapter of a yet-to-be published book by former CDRH engineer Leroy Hamilton, who four years ago persuaded the Center to revise its Form FDA 3429 device classification questionnaire to prevent devices from being needlessly steered into Class III. Hamilton’s chapter describes how the Center diverts legitimate complaints to escape accountability for its mistakes.

In the case of gynecologic devices, CDRH’s decision-making posture falls hardest on women. In a written statement to Block about the expedited approval of Essure, FDA said it did not believe a control group was necessary because, at the time (2002) “effectiveness and safety outcomes for laparoscopic tubal ligation were well known from years of clinical use” and could be used for comparison.

But Block found Sanket Dhruva, a Yale University cardiologist and researcher of high-risk medical devices, who strongly disagreed. “we all know the most rigorous data in clinical medicine is through randomization,” control groups and follow-through, she quoted him as saying. Dhruva recommended comparative studies in 1,000-patient cohorts, but Essure was studied only in 439 women, none of whom became pregnant, for a 100% effectiveness rate.

In a 2015 New England Journal of Medicine opinion piece, Dhruva and colleagues cited “large numbers” of reported adverse events with Essure, and faulted FDA for accepting “substandard data,” according to Block’s article.

It also reported on an Essure patient activist group’s discovery that Cindy Domecus, vice president of Essure developer Conceptus, presented at a CDRH advisory panel reviewing the Essure PMA on which four of the nine members had sat with her when she had previously been a nonvoting industry member of that panel. Block quoted National Center for Health Research president Diana Zuckerman as saying sitting on a panel gives industry members advantages by allowing them to build relationships and gain “a better understanding of how to influence the vote.”