On Thursday, a FDA advisory committee of outside experts held a public hearing in Silver Spring, Md., to address questions about the safety and effectiveness of Essure, which was approved in 2002. Some women’s health care advocates want the device pulled off the market, and a citizen petition filed with the FDA by a Florida law firm says that the approval process and clinical trials were “replete with fraud.”
Users have filed 5,093 complaints with the FDA citing chronic pelvic pain, debilitating periods, pregnancies that occurred with Essure including five that ended in fetal death, hysterectomies to remove devices that moved to other organs or broke apart, and four patient deaths, including one by suicide.
Officials with Bayer HealthCare Pharmaceuticals, which purchased Essure in 2013 for $1.1 billion from the company that developed it, Conceptus Inc., said they have full confidence in the device and are not concerned about alterations in medical records.
“It seems like the proper clinical practice procedures were followed,” said Dr. Edio Zampaglione, Bayer’s vice president for United States medical affairs and women’s affairs who has not seen all the clinical trial records. “If a mistake was identified, it was crossed out, initialed and dated. … There was full transparency.”
Officials at the Cleveland Clinic echoed that statement. The investigator, Dr. Linda Bradley, refused requests for an interview, but a clinic spokeswoman said that “it is common practice” to update documentation over the course of a clinical trial “to reflect all possibilities related to medical events.”
The FDA noted in its briefing materials for Thursday’s hearing it was aware of the allegations from women that records had been altered but said its monitoring of the study showed no evidence of that.
But a commentary in the New England Journal of Medicine on Wednesday offered harsh criticism of the clinical trials on the implant. “Though Essure offers possible advantages to women seeking sterilization, the evidence suggests that it is neither as effective nor as safe as the pre-marketing approval evaluation indicated,” Drs. Sanket S. Dhruva, Joseph S. Ross and Aileen M. Gariepy wrote.
The physicians criticized the lack of a comparison group and the rush to approve the permanent implant after only a year of followup for most clinical trial participants. They also noted concerns “about incomplete followup and biased results” in longer-term studies, and they suggested the fact that nearly one-third of the trial participants did not complete the trial meant that “adverse events including unintended pregnancies were probably missed.”
Changes In The Charts
The Essure implants consist of small coils, made of a nickel alloy and a polyester-like fiber that are placed in the Fallopian tubes, where they trigger inflammation that causes scar tissue to form, blocking the tubes and preventing conception.
Bayer refuses to say how many devices have been used in the United States, but says over one million units have been sold worldwide and 750,000 women use them.
Hudak, the mother of one son, joined an early Essure trial. She said that researchers did not think the symptoms she developed were related to the device. She said she was surprised, however, to find in her records that the answers she gave in response to questions about side effects had been altered, with 'no' changed to 'yes' and vice versa. Some answers had been crossed out completely. All of the changes were initialed and dated, according to the copies she provided to a reporter.
In those records, Bradley wrote on her chart on Jan. 28, 2002, that the cause of the back pain, which was worse before her menstrual period, was unknown but “does not appear to be gynecologic.”
Hudak said that over the years, she started to suffer from migraines, rashes, joint pain and fatigue. But she said that after she got the implants removed, “that pain I had in my back all those years, every single day, went away.”
Side Effects Dismissed
Several other clinical trial participants who developed serious health complications said they were also told the problems were not related to the device.
But that raises concerns among some experts such as Dr. Diana Zuckerman, president of the National Center for Health Research, a nonprofit consumer think tank and research group based in Washington, D.C. “The whole point of a trial is to capture things you wouldn’t know would happen. It doesn’t matter if you think the symptoms are related or not. They should be counted,” she said.
A clinical trial participant at the Greenville, S.C., trial site said she was dropped from the study after complaining of acute pain. Crystal Johnson Brown, now 39, said investigators told her the pain came from pelvic inflammatory disease, an infection of the female reproductive organs, and since it was a sexually transmitted disease, she should seek treatment elsewhere.
“After that, they never called me no more,” she said in a recent interview. “I never heard from them again.”
Brown said she still has severe debilitating lower back and pelvic pain and often seeks help at emergency rooms because she has no insurance. But Zuckerman says that her infection, like all health problems, should have been recorded in the trial data.
No Comparison Group
One of the problems with clinical trials of medical devices is that there is rarely a control group of similar women for comparison, which is standard in clinical trials of drugs, where a comparison group receives a placebo, said Dr. William Maisel, the chief scientist and deputy center director for science at the FDA’s Center for Devices and Radiological Health.
“These studies did not have a comparison group of women who did not get the Essure device, so the ability to conclude the relative rates of symptoms in Essure patients compared to other patients can’t be correctly done through these studies,” Maisel said.
Maisel said the FDA believes the benefits of Essure still outweigh the risks, and that all birth control choices have risks as well as benefits.
But to Zuckerman, telling a patient that the pain in the pelvis is definitely not related to the device is not defensible. “If you put something in the pelvic area, it’s ridiculous to assume that pelvic pain has nothing to do with it,” she said.
One in four women who use birth control choose sterilization. In a joint statement released after the FDA public hearing, the American College of Obstetricians and Gynecologists, Planned Parenthood and Physicians for Reproductive Health said that "Essure is the only permanent contraception that can be performed non-surgically."
While the groups supported the FDA in looking at "the safety of Essure and ... the steps that the agency and the industry can take" so that the device can be used more safely, "we urge the FDA to recognize that restricting women's access to certain methods of birth control will limit their choices and, in some cases, expose them to additional risk."
Wired reports that the FDA is unlikely to pull Essure off the market, but "the agency can require more studies and updated labels reflecting increased risks."
