Dr. Aileen Gariepy began noticing about a decade ago that the results she was seeing after implanting Essure were very different from the claims the company made about the product.
Not only was the process to insert the Essure coils more difficult than advertised, the OBG-YN was concerned by how often women needed to return to the office to make sure it was working effectively.
“I became skeptical,” said Gariepy, who at the time practiced in Pittsburgh. Her philosophy is "trust, but verify.”
She began conducting her own research, and in 2011 published a study in the journal Obstetrics and Gynecology that found the success rate of the permanent birth control device was both lower than advertised and lower than the alternative—surgical tubal ligation.
The results led Gariepy, now an assistant professor of obstetrics, gynecology and reproductive sciences at the Yale School of Medicine, to more aggressively emphasize the risks, which she felt had been downplayed by the devicemaker. "Now, I may have only one woman a year who wants it,” she said. Before then, about 75% of her patients were opting for Essure.
On Monday, the U.S. Food and Drug Administration recommended that labeling for Bayer's Essure should also aggressively emphasize the risks, through a black boxed warning and a checklist that would require patients to initial that they understand a suite of potential adverse events. These include abdominal pain, the possibility of getting pregnant despite implanting the device, or developing subsequent problems that might require surgical removal of the product.
“The FDA believes that some women are not receiving or understanding information regarding the risks and benefits,” the agency said in the draft recommendation (PDF). “We have determined that a boxed warning and patient decision checklist are particularly effective means of communicating this information.”
While the agency says the device remains an appropriate option for the majority of women, the black box could be a game-changer for clinicians who previously used it.
A warning as strong as a black box, the most serious given by the FDA, means “suggestive evidence is compelling and consequences are high,” notes Dr. Terry Fairbanks, director of MedStar Health's National Center for Human Factors in Healthcare, which evaluates the human element of medical devices.
“In actual practice, a black box warning effectively eliminates use of devices and drugs by practitioners,” he explained, because they may “consider the products too difficult to justify or defend.”
Regulations on boxed warnings were first instituted in 1979 as a means of calling attention to drugs or devices with serious or life-threatening risks to patients.
The FDA could not say how many regulated products include boxed warnings. However the openFDA website says more than 9,900 prescription drug labels carry one. Half of all new black-box warnings appear only after a drug has been on the market for 12 years, according to a 2014 Health Affairs study headlined "Era of faster FDA drug approval has also seen increased black-box warnings and market withdrawals."
The FDA said the exact number of medical devices carrying black box warnings is not readily available. "Every drug and device is evaluated on its own in regard to benefit and risk," an agency spokesman told Modern Healthcare. "There wouldn't be much use, from a regulatory standpoint, to keep track of a number overall."
Last year, Essure raised red flags when the FDA's Manufacturer and User Facility Device Experience, or MAUDE database, found more than 5,000 reports of adverse events related to the device, including unintended pregnancies, complications during removal and fetal deaths. Bayer later revealed it had received more than 17,000 adverse-event reports from women around the globe.
The company estimates there are about 750,000 women using Essure around the world. About 70% of them are in the U.S.
The draft FDA guidance recommends a warning that says Essure has resulted in “perforation of the uterus and/or fallopian tubes, intra-abdominal or pelvic device migration, persistent pain, and allergy or hypersensitivity reaction.” It also notes that some of these reported events have resulted in abdominal surgery to have Essure removed.
Whether or not a black box truly affects Essure sales remains to be seen. While the risks associated with the device are gaining more attention, there are also benefits. It remains the only nonsurgical, non-hormonal form of permanent birth control on the market and it does not require general anesthesia to implant, noted Dr. William Maisel, deputy director for science at the FDA's Center for Devices and Radiological Health, during an announcement Monday.
The Essure device rapidly gained popularity when it hit the market in 2002, because for years, patients and physicians had been waiting for a nonsurgical approach to sterilization. Within five years, the original manufacturer, Conceptus, saw net sales top $15 million. Sales soared to $140 million by 2012.
“It's a good example of how physicians allowed ourselves to be duped by information that we wanted,” Gariepy believes. “We cannot rely on pharmaceutical representatives to tell us whether or not something is really beneficial for our patients.”
Fewer women opting for the device would demonstrate that clinicians are getting more effective at communicating the risks, said Dr. Elizabeth Micks, a member of the panel that authored a 2013 practice bulletin on the benefits and risks of sterilization for the American College of Obstetrics and Gynecology.
The black box warning should be a strong reminder to physicians that the product is not right for everyone, she said. For example, it may not be ideal for patients with a history of pelvic pain, or those who are not reliable at taking birth control, which is needed until a follow-up test confirms the device is effective.
The warning checklist should also be a reminder to physicians about the importance of the recommended three-month follow-up, Micks said. Early statistics that touted the product as “highly effective” and “on par with vasectomy” may have misled physicians. “It turns out it's not that effective if patients do not have their follow-up to ensure the inserts are in the right place.”
As part of the draft FDA guidance, Bayer must also conduct a new post-market surveillance observational study on the risks of the device in a real-world setting. Within the next 15 days, the company must present to the FDA a design for a study that includes more than 2,000 patients who will compare the Essure device to tubal ligation. That could pose a problem if fewer women opt for the device following this latest news.
The FDA said the manufacturer must follow the patients for a minimum of three years. The manufacturer said this week that it is cooperating with the FDA.
Training to properly implant and remove the device is another issue the FDA-mandated study will require the company to look into. In July, Bayer told Modern Healthcare that there is no specific training for doctors on how to remove the Essure device. Dr. Edio Zampaglione, Bayer's vice president of medical affairs for women's health said the company was "not in the business of training physicians,” adding that physicians should already have those skills.
However, the need to retrain physicians on a device that has been on the market for over a decade is troubling from an engineering perspective. “Training is not a reliable method to overcome confusing design,” said Fairbanks of MedStar. “The safer solution is a redesign.”