WASHINGTON — The FDA recently announced changes to a postmarket study of the controversial sterilization device Essure — including a significant extension in the follow-up period — but patient advocates still aren’t satisfied.
FDA Commissioner Scott Gottlieb, MD, said in a recent statement that the postmarket surveillance study the agency ordered in 2016 will now follow study participants for 5 years, beyond the 3 years required by law. This will provide “longer-term information on adverse risks” of the device, they said.
The revised study protocol will also require blood tests of all patient participants to measure levels of “inflammatory markers” and to determine if such markers may be related to symptoms reported by patients. The FDA also said they are requiring the manufacturer, Bayer, to continue to enroll patients who might receive the device prior to its full discontinuation in the U.S. market.
Essure is a permanent sterilization device intended for women who have decided against any, or any more, pregnancies. The aim of the permanent implant is to trigger tissue growth that blocks the fallopian tubes and prevents sperm from entering the ducts.
The device is at the crux of a long-standing dispute between Bayer, the FDA, and women who experienced adverse events while using the implant. In a public meeting in 2015 regarding Essure, patients described severe abdominal pain, bleeding irregularities, migraines, painful sex, auto-immune disorders, extreme fatigue, psoriasis, perforation of the uterus, and even narcolepsy and cataplexy — all symptoms they attributed to the implantation of the Essure System. Lawsuits over the product number in the thousands.
In July, Bayer announced that it would cease all U.S. sales of Essure at the end of 2018. At that point, Essure had already been pulled from foreign markets. The company stressed that it was voluntarily discontinuing selling the product for business and not safety reasons, citing a decline in sales.
‘Bend Over Backwards for Industry’
But patient advocates contacted by MedPage Today remained skeptical. Angie Firmalino, a founder of the Facebook group “Essure Problems,” shared a statement attributed to the administrators of the group, noting that she and her colleagues have long expressed concern about the “validity and feasibility” of the Essure post-market study.
“While we agree with the FDA taking steps to lengthen the time frame to study the clinical trial participants from three to five years and ordering more specific blood tests to look at autoimmunity factors, the fact of the matter is that Bayer is still running the show and has a vested interest in providing favorable results,” Firmalino wrote.
Firmalino also argued that the FDA has the authority to remove all device kits from the shelves and “yet it refuses to do so.” While sales of Essure kits end on December 31, physicians still have up to a year to implant them, she explained to MedPage Today in a message.
“We are fighting to prevent that from continuing,” she wrote.
Firmalino also said that the FDA allowed Bayer to reduce its enrollment numbers for the study and “escape violation of the study order.” She added that some clinical investigators are “highly paid consultants to Bayer” and they have already been cited for various “protocol deviations” in past studies. Firmalino noted that two women have reported to the “Essure Problems” group that they were dropped from the postmarket study after reporting problems with the implants.
“We simply cannot comprehend why the FDA continues to bend over backwards for industry while women continue to be implanted and potentially harmed without holding Bayer accountable,” Firmalino wrote.
Researcher Questions Changes
Diana Zuckerman, PhD, president of the National Center for Health Research, is a co-investigator of a team funded by the Patient-Centered Outcomes Research Institute (PCORI) that is conducting a large, retrospective study of women who previously underwent sterilization with Essure or tubal ligation. She said in an email to MedPage Today that a 5-year study was “preferable” to a 3 year one, “but given the much smaller number of patients enrolled, it is unclear how useful the data will be.”
She also stressed the FDA’s “poor record” of gathering meaningful data through post-market research on medical devices, citing incomplete studies of breast implants and gastric lap bands.
“In addition to the other data, data based on blood tests could be useful as well, although we’d like more information about what that entails and how often that would be made public,” Zuckerman wrote.
Given that Bayer’s previous public statement implied the end of sales after December 31, Zuckerman expressed concern about the agency appearing to cast an eye towards more enrollment.
She noted that “the statement specifies that Bayer is encouraged to enroll patients ‘in advance of its full discontinuation from the market,'” but that it is unclear whether Gottlieb was referring to the last 11 days of the year (since the statement was dated December 20) or if patients will continue to get Essure past December 31.
“If the latter is true, then it is crucial that any patients enrolled to receive Essure in the post-market study be clearly informed that the company is no longer selling Essure, so that patients can make an informed decision about whether they want to obtain Essure as part of a study,” Zuckerman wrote.
“Similarly, any patients obtaining Essure from physicians wanting to use up their stock of Essure devices that they previously purchased [should] also clearly inform patients that Essure is no longer being sold. When I say clearly informed, I mean not just a written explanation that patients sign, but also a discussion between the patient and physician, taped to ensure informed consent,” she added.
Agency’s Mounting Efforts
In its recent press release, the FDA said the goal of the postmarket study is to “help patients and providers make more informed decisions and also support regulatory actions that reduce any potential risks to patients.”
Other actions cited by the FDA include:
- Monitoring a post-approval study of pregnancies in women who received transvaginal ultrasounds meant to ensure proper placement of the implant
- Analyzing post-approval study data of ongoing research meant to better understand device removals
- Reviewing more than 15,000 medical device reports sent to the agency from 2017 through June 2018, the majority of which cite device removals
It’s also worth noting that when Bayer announced it would “voluntarily discontinue” selling the device in July, Gottlieb highlighted the agency’s role in bringing about that decision through its own actions against the device maker — including requiring a boxed warning, a postmarket study, and an informational brochure and patient consent form. He further noted the 70% decline in U.S. sales following these measures.
The FDA was contacted for questions regarding this story, but a media contact was unable to respond before press time due to the government shutdown.
For a timeline of major events in Essure’s product life, click here.
Dori F. Zaleznik, MD Associate Clinical Professor of Medicine (Retired), Harvard Medical School, Boston