An independent analysis of FDA MAUDE data shows 303 fetal deaths related to the Bayer contraceptive medical device, but FDA itself has only reported five. A U.S. congressman is officially demanding answers while also alleging that some doctors implanting the device received illegal kickbacks.

Brian Buntz and Chris Newmarker

Something is rotten in the state of FDA's reporting of adverse medical device events.

That seems to be the gist of the latest salvo Rep. Michael Fitzpatrick, R-PA, has fired against FDA over its handling of dangers surrounding Bayer's Essure device.

In a letter dated Tuesday to FDA's top medical device regulator Jeffrey Shuren, MD, Fitzpatrick includes an independent analysis of MAUDE data that shows FDA's own adverse reporting system listing 303 fetal deaths related to the device. FDA has previously said the number was five.

Bayer says that the allegations are unfounded. "It is not true that an investigation revealed 'unreported' deaths with Essure," a Bayer spokesperson said in a statement. The adverse events had been reported to FDA and the referenced data was publicly available. Stating that complications can occur with all types of birth control, the Bayer statement noted that: "It would be irresponsible to suggest that Essure causes fetal deaths when, after an unsuccessful Essure procedure, an undesired pregnancy cannot be carried to term. In the post-market data, there is no data showing any increased risk of miscarriage and other complications compared to pregnancies in similar-age populations."  

"It looks like the data were reported to FDA but some weren't flagged as fetal deaths," says Diana Zuckerman, Ph.D., president of the National Center for Health Research (Washington, D.C.) "One of the questions would be whether ectopic pregnancies were counted as fetal deaths. That's important because ectopic pregnancies are probably caused by Essure and always result in fetal death.  If FDA had decided to count ectopic pregnancies separately from fetal deaths, they should have clarified that."

Along with the analysis, Fitzpatrick included a previously sealed lawsuit complaint from 2013 that alleges that Conceptus (the original developer of Essure later acquired by Bayer) gave doctors kickbacks to implant the device.

The complaint accuses Conceptus of fraudulently billing Medicare and Medicaid in connection with the Essure device. "Beginning no later than December 2010, Conceptus gave substantial and illegal financial inducements to providers to encourage them to use Essure, a procedure that costs the government almost $3500 per patient." The complaint also accuses Conceptus of providing OB-GYNs with free medical equipment valued at $20,000 to doctors who implanted 25 or more Essure devices. In addition, the company is accused of provide OB/GYNs with free marketing and advertising services to further increase use of the device while these doctors also received reimbursement from government healthcare programs.

A Bayer spokesperson said the accusations in the 2013 lawsuit complaint were also unfounded: "These allegations were made over a year ago and the United States Department of Justice thoroughly investigated them. After its investigation, DOJ declined to intervene and prosecute the case. The qui tam plaintiff also voluntarily dismissed the case. DOJ has closed its investigation. The matter is now fully concluded."

Indeed, federal prosecutors agreed to dismissal of the case and unsealing of the complaint in 2015, federal court records show.

FDA spokesperson Deborah Kotz reiterated that ensuring the safety of Essure is a high-priority issue for the FDA. "To date, the FDA has been examining all available sources of information, including the latest studies, expert input and patients' testimony from our panel meeting, and medical device reports to better understand long-term complications," she said in a statement. "We are working expeditiously to conduct an evidence-based review of all available information to inform what future actions may be in the best interest of women using or considering Essure."

Kotz confirmed that FDA has received the letter and data from Fitzpatrick and stated that the agency "will review and respond directly to the congressman."

Fitzpatrick is also lobbying for the so-called E-Free Act or H.R. 3920, which would remove Essure from the market.

FDA has been increasingly responding to claims that something is not right with Essure. In September, an FDA advisory panel recommended more limited use of Bayer's Essure contraceptive device amid complaints of health problems.

Bayer claims that only a small portion of the hundreds of thousands of women implanted with its Essure contraceptive device have had a bad experience with it. But the needle appears to be moving amid vocal criticisms from thousands of women reporting problems.

FDA's MAUDE database listed nearly 6000 reports of problems related to Essure, many listing multiple health problems. They include pain/abdominal pain (3353), menstruation irregularities (1408), headache (1383), fatigue (966), and weight fluctuations (936).

A Need for More-Accurate Reporting?

The analysis of MAUDE reports that Fitzpatrick shared with FDA was produced by Madris Tomes, a former FDA public health analyst who last year founded York, PA-based Device Events and its Web-based tool that searches medical device postmarket surveillance data.

"I simply built a tool to identify reports in a more sophisticated fashion," Tomes tells Qmed.

There is no checkbox in FDA adverse events reports for fetal death, so Tomes instead searched for Essure reports with the phrases "essure fetal death," "essure ectopic," "essure miscarriage," "essure stillbirth," and "essure stillborn" in the narrative. "FDA staff has the task to 'delete' duplicates, and each report number I provided has a unique report number," Tomes said.

Tomes noted that FDA hasn't released any new Essure death or injury numbers since September. "I felt it was important to share this way of searching the data so that the women of Essure can see that their voices are being heard ... in spite of the near silence from the FDA. If those reports couldn't be re-classified ... shouldn't they at least be considered? Should regulations be stronger, or allow the FDA to identify these issues earlier?" Tomes said.

The problems that appear to have cropped up over Essure-related fetal death reporting could add more fuel to the fire when it comes to calls for actual real-time reporting of medical device problems, versus relying on the medical device companies, health providers, and occasionally patients to voluntarily report problems.

The lack of such real-time reporting was recently cited as a major reason why potentially deadly superbug outbreaks caused by special endoscopes called duodenoscopes failed to get public attention for so long, even though European regulatory authorities were aware of them..

"The failure of FDA's device surveillance system to rapidly identify and respond to duodenoscope-related superbug and antibiotic-resistant infections serves as just one example of the fallacy of a system that is primarily reliant on hospitals and device manufacturers to self-report information to FDA," the office of U.S. Sen. Patty Murray, D-WA, said in the report.

Murray's report calls for legislation to require and promote unique device identifiers (UDIs) in insurance claims, electronic health records, and device registries for faster FDA identification of problems.

"The MAUDE database is a subjective and flawed system", concludes Zuckerman. "For one thing, it is voluntary. A doctor can decide whether something gets reported or not. As an example, if a woman got pregnant after getting Essure, many doctors might think they didn't have to report it." Although Bayer has reported that Essure has 99.9% success rate, if a doctor had one patient who got pregnant out of 10, he or she would have no way of judging if that meant the success rate of Essure is probably lower than was being claimed. " If all doctors reported complications and fetal deaths, that would be important information for patients to have. But in the real world, a lot of doctors wouldn't report those things," Zuckerman says. "They might not report pelvic pain either, because the doctors were told by the company that pelvic pain was unrelated to the device. But if you have a device in the pelvic area and you have pain there, there is a good chance they were related." 

Clinical Trial Questions

One the other controversies surrounding the Essure device is the clinical trial used to help the device win PMA approval in the United States, although this was not specifically mentioned in Fitzpatrick's aforementioned letter. "I have been quite outspoken talking about my concerns that the company did not accurately report adverse events such as pain in the clinical trial used for the Essure PMA," Zuckerman says. In the case of Kim Hudak, the clinical trial participant who has obtained her records from the trial, "it is very clear that the clinical forms didn't accurately represent her experience and that they did not list many painful complications. Whether the information was intentionally omitted or there were a series of mistakes made by people filling out the firms, either way, it resulted in inaccurate information that made the Essure device seem safer than it really was. What made it worse for Kim is that she was told repeatedly that her complications were unrelated to the device.  If she had known, she could have had Essure removed years earlier, and she would have not been in such pain for so long."

"The MAUDE database is not a perfect tool and very difficult to use from a consumer standpoint," says Kim Hudak, who had been one of the clinical trial participants for Essure. "As someone that has been immersed in politics and the inner workings of the FDA due to personal tragedy, my simple answer is the system is tragically broken."

Another problem is the lack of a control group in the clinical trial used to win PMA approval, Zuckerman says. "The company could have compared patients implanted with Essure with patients who underwent tubal ligation." A randomized clinical trial would make it easier to track possible side effects of the device. In this case, Conceptus did not accept that the pelvic pain that some women suffered was related to the device, Zuckerman says. "They just said: well, women have pelvic pain, instead of scientifically comparing whether Essure women were more likely to have chronic pain than women who had their tubes tied.'" The Essure example raises interesting questions about the accuracy of clinical studies used to convince FDA of the safety and efficacy of drugs and devices, Zuckerman says, and "whether the professionals who conduct the studies are trained correctly or if there is pressure on them--internal or external--to do things to please the company." 

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