FDA Should Ban the Dangerous Female Sterilization Device Essure Immediately!

Health Letter, August 2018

By Azza AbuDagga, M.H.A., Ph.D.

On July 20, Food and Drug Administration (FDA) commissioner Dr. Scott Gottlieb announced that the agency had been notified by Bayer, the manufacturer of the female sterilization device Essure, that it will no longer sell or distribute the risky device in the U.S. after December 31, 2018.

The manufacturer’s voluntary decision comes 10 months after it removed Essure from the European market. It also follows thousands of adverse events reports associated with the device that the FDA has received and a plethora of related lawsuits against Bayer in the U.S. and elsewhere.

The inadequate safety data that supported the FDA’s initial approval of Essure and subsequent FDA actions once the dangers of the device became apparent demonstrate that the agency has accommodated, and continues to accommodate, the manufacturer, instead of banning this device immediately to protect U.S women.

About Essure

Essure consists of flexible coils made of nickel and other metals that are inserted with a catheter through the vagina and into the fallopian tubes. Within three months of insertion, scar tissue forms around the coils, creating a barrier that keeps sperm from reaching the eggs and, thus, preventing pregnancy.

Approved in the U.S. in 2002, Essure is the only female sterilization device that does not require a surgical incision. It has been promoted as a better alternative to tubal ligation, a permanent birth control procedure that involves making a surgical incision in the abdomen to reach the fallopian tubes and tie them up, cut them or burn a portion of them to prevent pregnancy.

Essure accounted for 43 percent of the sterilization procedures performed among commercially insured U.S. women from 2009 to 2011.[1] According to the manufacturer, the device has been implanted in more than 750,000 women worldwide.

Insufficient supporting evidence

The FDA reviewed Essure’s premarket approval application on an expedited basis, which permitted the manufacturer to secure approval using data from a limited number of subjects from suboptimal clinical trials, despite the high-risk (class III) nature of this medical device.

Specifically, all of the women in the small phase 2 and phase 3 clinical trials that supported Essure’s approval received the device, and there was no control group of women who received the traditional procedure (tubal ligation).[2]

The manufacturer claimed that zero pregnancies occurred in the aforementioned trials, but this claim covers only pregnancies among women whose device placement procedure was determined to be successful.[3] In practice, Essure’s effectiveness has been far from perfect: There have been close to 750 reports of unintended pregnancies with Essure since the device was approved in 2002, and many additional pregnancies likely have gone unreported.[1] Some studies have estimated that when unsuccessful placement and reported failure rates are considered, Essure is actually less successful at preventing pregnancy than other available surgical alternatives.[5],[6]

The FDA’s premarket review of Essure failed to emphasize important safety issues. For example, in the phase 3 clinical trial, the manufacturer reported that 2 to 3 percent of women experienced new, severe pelvic pain or cramping and 9 percent experienced back pain during the first year after receiving the device.[7] Moreover, 20 of the 682 women who received implants in the premarketing trials had hysterectomies within the first five years after insertion in order to remove the device, mostly due to abnormal bleeding or pain.[8]

The postmarketing study that followed subjects from the aforementioned phase 3 trial reported no pregnancies among Essure users who maintained enrollment in the trial for five years.[9] However, this study conveniently focused on subjects with successful placement of the device rather than all of those who attempted the device: Removing subjects with unsuccessful device placement from the study’s denominator “makes the proportion of successful procedures appear higher than it actually is,” wrote some subject-matter researchers who commented on the study.[10] Importantly, 30 percent of the subjects of this study dropped out before the end of the five-year follow-up period.[11] As acknowledged by the study researchers, the women who did not complete the study may represent a different group than those who dropped out of the study due to pregnancy or other complications.

A 2015 observational study that compared patients who chose to use Essure with those who chose tubal ligation from 2005 to 2013 found that Essure users had a 10-fold greater risk of undergoing a subsequent surgical operation within the first year.[12] The study also found that half of the 8,048 Essure patients had the device implanted under general anesthesia, a finding that negates the purported “office-based” nature of the device implantation procedure.

In 2016, the FDA mandated a new postmarketing open-label, observational study of women who choose Essure versus those who opt to undergo tubal ligation. However, the final results of this ongoing study are not expected until September 2023.

Adverse event reports

The FDA indicated that it had received nearly 26,773 adverse event reports related to Essure since the device’s approval in 2002 through 2017. Ninety-three percent of these reports used terms related to device removal. Several device problems were common in these reports, including possible nickel allergy (17 percent), device migration (11 percent), dislodged or dislocated device (5 percent) and device breakage (4 percent). Additionally, 7 percent of these reports referenced pregnancies, nearly half of which were miscarriages. Among the most common adverse events in these reports were pain or abdominal pain (79 percent), heavy menses or menstrual irregularities (37 percent), headache (27 percent), fatigue (22 percent) and weight fluctuations (19 percent).

Although sales of Essure in the U.S. dropped by 70 percent since the 2016 black-box warning, the FDA received nearly 12,000 adverse event reports associated with the device in 2017. This was an increase from the nearly 5,000 total Essure-related reports received by the agency in 2016. However, the agency noted that nearly 80 percent of these reports cited litigation, so they may have referenced reports that had been submitted previously.

FDA’s leniency with Essure’s manufacturer

The FDA has been aware of serious adverse events associated with use of Essure for several years and convened an advisory committee to evaluate the device’s risks in September 2015.[13] Yet the agency did not mandate that a black-box warning — the strongest warning that it can require — be added to Essure’s labeling until November 2016 to alert consumers about serious adverse events associated with the device, including perforation of the uterus or fallopian tubes, migration of the device to the abdominal or pelvic cavity, persistent pain, and allergic or hypersensitivity reactions. The warning also cautions that a surgical procedure will be required to remove the device if any of these adverse events occur.

Even after the manufacturer’s decision in September 2017 to halt the sale of Essure in Europe — as a result of the device’s temporary suspension by regulatory authorities in the European Union — the FDA still did not demand the manufacturer take the same action in the U.S.

Instead, on April 9, 2018, the FDA ordered new restrictions that limit the sale and distribution of Essure to health care professionals and facilities that agree to provide standardized information about its risks and benefits to women who are considering using the device. These restrictions require health care professionals to review an FDA-approved educational guide that includes a form — called “Patient-Doctor Discussion Checklist: Acceptance of Risk and Informed Decision Acknowledgement” — with each prospective Essure patient before implanting the device. In addition to describing Essure’s purported benefits, the guide describes the device’s adverse events that are included in the black-box warning. It also enumerates other adverse events including ectopic pregnancy (when the pregnancy occurs outside the uterus, which can be life-threatening) and less severe adverse events such as hair loss, headache, fatigue, mood changes (including depression) and weight changes. The FDA restrictions require health care professionals and patients to sign a “Confirmation of Discussion of Risks” form to document that prospective Essure patients have received the information and discussed it with a health care professional before getting the device.

On July 20, the FDA commissioner announced that Bayer had informed the agency of its voluntary decision to stop the sale of Essure in the U.S. after December 31, 2018. The only assurance that the commissioner offered the tens of thousands of U.S. women who had received the Essure implant is that the FDA will continue to monitor the postmarketing safety of the device. He stated that women who have been using the device successfully can continue to do so and that those who suspect they may be having symptoms related to the device, such as persistent pain, should consult with their doctors on what steps may be appropriate for them to take. Finally, the commissioner indicated that the agency will continue to assess data from the ongoing postmarketing study of Essure.

Time to ban Essure!

At least 16,000 lawsuits have been filed against Bayer in the U.S. alone alleging that severe problems and adverse events have been caused by Essure.

Interestingly, the manufacturer attributed its decision to withdraw Essure from the European and the U.S. markets to commercial reasons — arguing that the risk-benefit profile of the device remains positive and alluding to an “unfavorable environment” for the device given the media coverage of stories about dissatisfied Essure users.

Instead of accommodating the manufacturer, the FDA should have banned Essure long ago and certainly by the time Bayer stopped the sale of the device in Europe in September 2017.

The FDA further accommodated the manufacturer in April when the agency limited its actions to requiring patient education about Essure’s risks.

The agency now continues to accommodate the manufacturer by allowing it to set its own date for removing the device from the U.S. market. And why December 31, 2018? Is that for any other reason than meeting a financial goal for the company by the end of the year?

More importantly, why should more U.S. women be put at unacceptable risk until then?

Continuing to leave Essure on the U.S. market, given that its risks far outweigh its benefits and that the device has been withdrawn throughout Europe nearly a year ago, is outrageous!

The FDA should rid the U.S. of Essure immediately to protect American women from the serious harms of this device, which never should have been approved in the first place.


References

[1] Carney PI, Lin J, Xia F, Law A. Temporal trend in the use of hysteroscopic vs laparoscopic sterilization and the characteristics of commercially insured and Medicaid-insured females in the US who have had the procedures. Int J Womens Heal. 2016;8(May 10):137-144.

[2] Food and Drug Administration. FDA review document: Review of the Essure system of hysteroscopic sterilization. Prepared for the September 24, 2015, meeting of the Obstetrics and Gynecology Devices Advisory Panel Center for Devices and Radiological Health (CDRH).

[3] Ibid.

[4] Ibid.

[5] Gariepy AM, Creinin MD, Schwarz EB, Smith KJ. Reliability of laparoscopic compared with hysteroscopic sterilization at 1 year: A decision analysis. Obstet Gynecol. 2011;118(2): 273-279.

[6] Gariepy AM, Creinin MD, Smith KJ, Xu X. Probability of pregnancy after sterilization: A comparison of hysteroscopic versus laparoscopic sterilization. Contraception. 2014;90:174-181.

[7] Food and Drug Administration. FDA review document: Review of the Essure system of hysteroscopic sterilization. Prepared for the September 24, 2015, meeting of the Obstetrics and Gynecology Devices Advisory Panel Center for Devices and Radiological Health (CDRH).

[8] Ibid.

[9] Chudnoff SG, Nichols JE, Levie M. Hysteroscopic Essure inserts for permanent contraception: Extended follow-up results of a phase III multicenter international study. J Minim Invasive Gynecol. 2015;22(6):951-960.

[10] Gariepy AM, Xu X, Creinin MD, et al. Comment on hysteroscopic Essure inserts for permanent contraception: Extended follow-up results of a phase III multicenter international study. J Minim Invasive Gynecol. 2015;23(1):137-138.

[11] Chudnoff SG, Nichols JE, Levie M. Hysteroscopic Essure inserts for permanent contraception: Extended follow-up results of a phase III multicenter international study. J Minim Invasive Gynecol. 2015;22(6):951-960.

[12] Mao J, Pfeifer S, Schlegel P, Sedrakyan A. Safety and efficacy of hysteroscopic sterilization compared with laparoscopic sterilization: An observational cohort study. BMJ. 2015;351(October 13):h5162.

[13] Food and Drug Administration. FDA review document: Review of the Essure system of hysteroscopic sterilization. Prepared for the September 24, 2015, meeting of the Obstetrics and Gynecology Devices Advisory Panel Center for Devices and Radiological Health (CDRH).