The FDA continues to monitor the safety of Essure. The FDA continues to believe that the benefits of the device outweigh its risks, and that Essure’s updated labeling helps to assure that women are appropriately informed of the risks. The following is an overview of some of the FDA’s efforts to monitor the safety of Essure.
Reviewing Ongoing Clinical Study to Gather More Information on Essure Benefits and Risks
The FDA ordered Bayer, the company that makes Essure, to conduct a postmarket surveillance study to gather more data about Essure’s benefits and risks. The FDA approved the study plan on September 2, 2016, and will make interim study results and updates available on the Essure Postmarket Surveillance Study page. The FDA believes clinical data will help to better understand certain patient complications that may be experienced by women who have Essure permanent birth control when compared to women who undergo tubal ligation.
Results collected from the approved study plan will also help the agency better understand the underlying reasons that may prevent completion of the third step of the Essure System method (confirmation of proper location/occlusion). Findings from the study may serve to inform future FDA actions.
Issued Final Guidance to Improve Labeling for Essure and Similar Devices
On October 31, 2016, the FDA issued the final guidance, “Labeling for Permanent Hysteroscopically-Placed Tubal Implants Intended for Sterilization” after carefully considering public comments. To view the comments received, go to the Public Docket and search Docket # FDA-2016-D-0435. Updated Essure Labeling Information for Patients and Health Care Providers is available online.
In issuing this guidance, the FDA considered feedback from the 2015 Advisory Committee meeting, as well as comments FDA received through open public dockets. Panel members and the public indicated that medical device labeling for permanent birth control methods, including Essure, is not clear and many patients do not receive enough information before making a decision. Panel members recommended changes to the patient and physician labeling and more aggressive methods to ensure patients are well-informed of risks before choosing a permanent birth control method.
To help address these concerns, the FDA identifies content and format for certain information to be included in the patient and physician labeling to guide conversations between women and their health care providers about the benefits and risks of this type of device:
- A boxed warning with safety statements to better communicate to patients and providers the significant side effects or complications associated with these devices and information about the potential need for removal;
- A Decision Checklist with key items about the device, its use, and safety and effectiveness outcomes, which the patient should be aware of as they consider permanent birth control options.
Completed Evaluation of the Trade Complaint Regarding Allegations Initially Made in a Citizen Petition
The Citizen Petition, which included allegations related to Essure, was referred to the Office of Compliance within the Center for Devices and Radiological Health (CDRH). CDRH closed the Citizen Petition, and the Office of Compliance has completed its investigation of the trade complaint.
Allegations in the trade complaint included clinical trial misconduct, notably that clinical trial participants’ medical records were altered to reflect more favorable data about participants’ experiences. Additionally, the complaint alleged that the sponsor violated the terms of the PMA approval order and violated laws that relate to the manufacturing and marketing of Essure.
The FDA inspected Bayer as part of the complaint investigation. In addition, Bayer provided the FDA with the available case report forms that documented patient experiences during Essure clinical trials.
The FDA analyzed these forms to evaluate the incidence of cross-outs and discrepancies regarding patient-reported pain, comfort and satisfaction ratings to assess whether modifications favored Essure safety and effectiveness. The Agency found that less than 1 percent of case report form data pertaining to pain, bleeding, device placement/movement and pregnancy were changed during the clinical trials. Although modifications to the case report forms were identified, our analysis did not find evidence the sponsor purposefully modified patient responses to reflect more favorable data for Essure. More information about the Agency’s case report form analysis can be found in the Summary and Key Findings document.
Also as part of the Agency’s complaint investigation, CDRH evaluated Bayer’s labeling of the device, taking into account the allegations in the complaint, as well as the feedback received during the September 2015 Advisory Committee meeting and from public comments received in response to the public docket. With the issuance of the final guidance and the subsequent approval of Bayer’s labeling changes that are consistent with the recommendations in the guidance, the Agency considers its investigation of the trade complaint completed. CDRH Office of Compliance will ensure that Bayer’s revisions to their marketing and promotional materials are consistent with the updated labeling.
Continued Reviews of Reported Problems
The FDA relies on a variety of postmarket surveillance data sources to monitor the safety and effectiveness of medical devices. The FDA continues to review the available information about Essure and the experiences of patients who have had Essure since the FDA approved it in 2002. This includes experiences of patients who have had positive outcomes with Essure as well as those who have experienced problems. Postmarket surveillance activities for Essure include:
Analyzing Essure patient reports of problems (including Web-based testimonials) and reports of problems submitted to the FDA from other sources, including doctors, patients, and the manufacturer of Essure
Adverse event and product problem reports submitted to the FDA are one source we use to monitor marketed medical devices. These reports may contribute to the detection of potential device-related safety issues as well as to the benefit-risk assessments of these devices. While such reports are a valuable source of information, this type of reporting system has notable limitations, including the potential submission of incomplete, inaccurate, untimely, unverified, or biased data. Complaints or adverse event reports do not necessarily directly indicate a faulty or defective medical device, and adverse event reports alone cannot be used to establish or compare rates of event occurrence. Additionally, we may receive multiple reports related to the same event making it difficult to determine actual numbers of events.
The FDA conducted a search of the Manufacturer and User Facility Device Experience (MAUDE) database. From November 4, 2002, Essure's approval date, through December 31, 2016, the FDA received 14,919 medical device reports related to Essure. While the majority of reports received since 2013 have been voluntary reports, mostly from women who received Essure implants, in 2016, approximately 57 percent of reports came from the manufacturer.
The total number of medical device reports received related to Essure in 2016 is 5,019, a decrease from the total number received in 2015 (6,176). The nature and severity of the reports remain generally consistent with prior reports. The FDA continues to believe the benefits of the device outweigh its risks, and that Essure’s updated labeling helps to assure that patients are appropriately informed of the risks.
The most frequently reported patient problems during this period were pain/abdominal pain (10,746), heavier menses/menstrual irregularities (5,377), headache (4,396), fatigue (3,560), and weight fluctuations (3,270). Most of the reports received listed multiple patient problems in each report. The most frequent device problems reported were patient-device incompatibility (2,402) (for example, possible nickel allergy), migration of the device or device component (1,485), device operating differently than expected (663), device breakage (617), device difficult to remove (304), malposition of the device (261), and device difficult to insert (257). Multiple device problems can also be listed in each report.
Through December 31, 2016, there have been 38 reports coded by the submitter as death. Eight of these were incorrectly coded, as there was no indication of death in the report. Of the remaining 30, six reports relate to four adult deaths; 21 reports relate to 18 incidences of pregnancy loss; two reports relate to two incidents of a death of an infant after live birth; and one report specifies a death but does not indicate whether the death was before or after birth.
The FDA has received 1,077 reports that included 1,113 pregnancies in patients with Essure. Some reports contained information on multiple pregnancies. Of the total pregnancies reported: 253 live births were reported; 386 did not indicate whether the pregnancy resulted in a live birth or pregnancy loss; and 474 pregnancy losses were reported.
Among the 474 pregnancy losses reported: 138 were reported as ectopic pregnancies; 75 were reported as elective terminations of pregnancies, and 261 were reported as other pregnancy losses.
Confirming whether a device actually caused a specific event can be difficult based solely on information provided in a given report.
Reviewing results from Post-Approval Studies (PAS)
Essure’s 2002 approval required two PAS. PAS I was conducted to gather five-year follow up information on the participants in two groups of patients that were part of premarket clinical trials (known as Phase 2 trial and Pivotal Trial). The study evaluated:
- how well Essure prevented pregnancy;
- the safety of the procedure used to place Essure; and,
- the safety of Essure once implanted, including patient comfort.
Although there is evidence of complications, as there are with many medical devices, overall results from this study did not demonstrate any new safety problems or an increased incidence of problems since the time of device approval.
PAS II was conducted to evaluate bilateral placement rate (insert placement in both the right and the left Fallopian tubes at first attempt) for newly trained physicians in the U.S. Data from this study were used to evaluate the training procedures and to update labeling.
Subsequent to the product’s approval in 2002, three PMA supplements were approved with post-approval studies required as conditions of approval. One supplement was related to device modifications; the other two supplements supported labeling modifications. Details on the study protocols and status are posted on the Post-Approval Study Status web page.
Evaluating the available clinical literature to better understand long-term complications
FDA sought to determine what long-term complications may be associated with Essure more than five years after placement, because the post-approval study evaluated safety and effectiveness only up to five years. The Executive Summary prepared for the Advisory Committee meeting provides a comprehensive overview of clinical literature, in which we found no conclusive evidence indicating any new or more widespread complications definitely associated with Essure occurring more than five years after Essure placement.
Convened FDA Advisory Committee to discuss Essure Safety and Effectiveness
As part of examining safety concerns about Essure raised by patients and cited in Medical Device Reports (MDRs), the FDA convened a meeting of the Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee on September 24, 2015 to:
- discuss currently available scientific data pertaining to Essure’s safety and effectiveness,
- hear expert scientific and clinical opinions on the risks and benefits of the device, and
- hear concerns and experiences of women implanted with Essure.
The Advisory Committee meeting summary provides a comprehensive overview of Essure and the FDA’s review, including post-market information, clinical literature and information from ongoing studies.