Kim Hudak was a young mother who was done having children when she volunteered for a clinical trial to an experimental birth control implant designed to make her sterile without tube tying surgery.
But soon after Hudak, 28 at the time, got the Essure implants in 2000, she said she developed health problems, including severe pelvic and lower back pain, difficult menstrual periods and pain during intercourse.
She complained to researchers at the Cleveland Clinic and was told her problems were not related to the implant. In an affidavit to the Food and Drug Administration, Hudak alleges that answers she gave researchers in response to questions about pain, adverse health effects and even whether her period was late had been altered on her medical record, without her knowledge. Those statements were part of the usual data collection for FDA approval of the device.
“I realized something could go wrong in a clinical trial, but I thought they would take care of me, and that if something wasn’t right, they’d fix it,” said Hudak, who eventually had a hysterectomy to remove the implants in 2013 and has filed a claim against Essure’s manufacturer for compensation for her injuries.
Hudak is one of several clinical trial participants who say that when they experienced complications with the implant, doctors and nurses ignored or belittled their symptoms, insisted they could not possibly have been caused by Essure, and referred them elsewhere for treatment.
On Thursday, a FDA advisory committee will hold 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 pain, adverse health effects and even whether her period was late 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.”
Later that year, on Nov. 14, Hudak called to report she had been bleeding after intercourse for the past two months, and the clinic note says Bradley referred Hudak to “her regular gyn.”
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.”
Kimberly Lira Huddleston says she found her records also did not reflect her answers to researchers at Women’s Health Research in Phoenix. After getting the implants in 2000, she says she was in constant pain. She complained to the clinical investigators for three years, she said, finally showing up at the research center and demanding they remove the implants. The researchers ordered her to leave the premises, she recalled.
“They had no concern for me,” said Huddleston, now 39, who still has chronic pelvic pain. “Once I wanted the implants out, I was of no use to them.”
When Huddleston, who has not filed a lawsuit or statements with the FDA, obtained her records from the study recently, she said she found a document signed by the principal investigator stating that she had no problems with Essure but had withdrawn from the trial and couldn’t be found, despite numerous attempts to reach her.
The clinical trial record she provided to a reporter shows the word “severe” crossed out from her report of “severe menstrual cramping.” The word “ongoing” was crossed out from a response about abdominal cramping. The changes were initialed and dated by researchers.
Officials at the Phoenix center did not respond to repeated phone calls. The founder of the center, the late Dr. Jay M. Cooper, is one of the chief authors of research papers on Essure. He noted in those publications that he owned equity stock in the company.
Patricia Reese Rhodes was also a participant in the trial at the Phoenix center. Born in 1976, she discovered that her medical record listed her birth year as 1956, as she points out in an affidavit to the FDA, making it appear she was in her mid-40s rather than in her mid-20s when she was sterilized.
While clinical trials generally prefer young healthy participants who are less likely to develop complications, the FDA required that women as old as 44 be represented in the Essure trial.
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.
Gabriella Avina, a study participant at a San Ramon, Calif., trial site, was so enthusiastic about Essure that she became a paid spokeswoman for Conceptus for several years, answering questions women wrote in to “Ask Gaby.”
Avina was in her mid-30s when she had Essure implanted in 2000. Just a few months after getting the implant, Avina developed a thyroid disease, which is not uncommon among women. Then, in 2002, she started bruising and was diagnosed with the blood platelet disorder thrombocytopenia, and in 2004, she was diagnosed with celiac disease. In 2009, she started falling and was diagnosed with myasthenia gravis, and in 2011, she was diagnosed with Sjogren’s Syndrome, which causes dry eyes and dry mouth.
All five of the diseases are auto-immune diseases. Avina, a nurse who will be testifying at the FDA hearing, said that even though there is no evidence the conditions were triggered by an immune response to the implant, they should have been recorded in the clinical data. She said researchers were unable to locate her records when she sought to get them, but she does not believe they noted the other problems she was encountering. She has always been unable to wear cheap jewelry that contains nickel, and thinks her problems may have been related to a possible response to the nickel in the device.
“The interesting thing is that because I worked in the clinical research center, they knew I was sick,” said Avina, who had a hysterectomy to remove the implants last year. Her health conditions have not resolved.
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.