Essure: What One Dangerous Device Tells Us About a Broken System
Health Letter, January 2016
By Sarah Sorscher, J.D. M.P.H.
When Kim Hudak enrolled in a clinical trial in 2000, she was excited to be part of a study exploring a potentially revolutionary new birth control product for women.[1]
Fifteen years later — after overcoming chronic, debilitating pain; fatigue; and other symptoms that eventually led to a hysterectomy — Hudak stood before the Food and Drug Administration (FDA) and pleaded with the agency to ban the device.[2] At her worst point, she told a panel of FDA advisers, “I couldn’t work and can barely function as a mother. … Please don’t let this happen to other women.”
Hudak is one of thousands of women who have contacted the FDA to report problems with the Essure permanent sterilization device.[3] The story of this device sheds light on deep problems with the regulation of devices in the U.S., which fails to ensure that even the most complex and risky permanently implanted devices are adequately tested before being put on the market.
As the Essure device comes under attack in Congress and elsewhere, less rigorous standards have been proposed as part of the 21st Century Cures Act that would further undermine the quality of testing for the highest-risk devices. The 21st Century Cures Act lays the groundwork for more dangerous device approvals, meaning the failures that led to the approval of the Essure device could become much more common.
A broken system
Experts have strongly criticized the current system that is used to regulate medical devices, which allows manufacturers of many moderate- and even high-risk implantable devices to sell them without testing for safety and effectiveness.[4]
But Essure underwent the most rigorous review provided to the highest-risk devices by the FDA: premarket approval (PMA). This process often is regarded as similar to the review process used for approving new drugs,[5] but in reality, even this relatively high standard still falls far short of what is needed to ensure that devices are safe and effective.
For a new drug approval, the FDA generally requires drugmakers to conduct two randomized, blinded, controlled clinical trials — the gold standard for medical research. These trials are typically large, enrolling hundreds or thousands of patients.[6]
Such trials are uncommon for medical devices: At best, one in five devices approved under a PMA application, the riskiest device type, is approved based on one or more gold-standard clinical trials,[7],[8] and many device trials involve a relatively small number of patients (a few dozen in some cases) tested for just a few months.[9],[10] This system lowers the quality of FDA review, making it possible for dangerous devices to slip through.
Essure approval
Essure is a permanent sterilization device made of two tiny metal coils that are inserted into a woman’s fallopian tubes. The coils contain a material that stimulates inflammation and scarring, causing the tubes to close up and stop sperm from reaching the woman’s eggs, preventing pregnancy.[11]
The main clinical trial testing the safety and effectiveness of Essure was not a gold standard randomized controlled trial. Instead, all of the women in the trial received the device, and there was no control group with women who received another standard surgical sterilization procedure available at the time.[12]
The manufacturer claimed that zero pregnancies occurred in the main Essure clinical trial and another, smaller pre-market trial, but this claim covers only pregnancies among women whose device placement procedure was determined to be successful.[13] In practice, Essure’s effectiveness has been far from perfect: there have been close to 750 reports of unintended patient pregnancies with Essure since the device was approved, and many additional pregnancies likely have gone unreported.[14] 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.[15],[16]
The FDA’s premarket review also failed to detect important safety issues. In the pivotal clinical trial, the manufacturer reported that 2 to 3 percent of women experienced new, severe pelvic pain or cramping, and another 9 percent experience back pain, during the first year after receiving the device.[17] The actual percentage of women who experience severe pain is likely higher, as other types of severe pain, such as severe abdominal pain, were not reported separately. The total number of women who experienced pain in any area was also not reported, although these data were collected by the company.[18] In addition, 20 of the 682 women who received implants had hysterectomies within the first five years to remove the device during premarket clinical testing, mostly for abnormal pain or bleeding.[19]
Post-approval controversy
Kim Hudak and other research subjects have raised questions about the biased nature of the tools used to evaluate the device by patients in the main Essure clinical trial.[20] They have joined a larger group of Essure patients who suffer from chronic pain and other symptoms and have organized themselves around the common goal of pressuring the FDA to remove Essure from the market. The group has encouraged patients who have received the device and experienced problems to submit adverse event reports to the FDA describing their symptoms.[21]
Since the Essure device was approved in 2002, the FDA has received over 5,000 patient reports claiming injuries from the device.[22] Most of these reports involved pain, bleeding, headache, fatigue and weight changes. Women also have reported new allergic reactions to nickel, a metal found in the device.[23],[24] Four death cases of Essure users have been were also reported to the FDA, including those of three women who died from complications following procedures to insert or remove the device, and one who committed suicide.[25]
Yet some doctors who continue to use Essure in permanent sterilization procedures have argued that the problems patients report are common even in women who are not treated with Essure.[26] Without a randomized trial comparing Essure to no treatment or sterilization alternatives, this argument will remain difficult to disprove.
The wrong direction for device regulation
The FDA recently convened an advisory committee meeting to consider injury reports related to the device, but the panel was not asked to discuss withdrawing approval.[27] Congressman Michael Fitzpatrick (R-Pa.) introduced a bill in Congress in November that would specifically require the FDA to ban the device.[28]
Yet this effort to target Essure does little to stop the approval of future dangerous devices. And while members of Congress may be sympathetic to injured patients, they also are moving forward with a new bill that will result in more potentially dangerous devices being sold. The bill, the 21st Century Cures Act, would pressure the FDA to approve even more high-risk devices without randomized, controlled clinical trials. In fact, the bill would allow the FDA to make approvals based on medical anecdotes describing the use of the device in just a few patients.[29]
Also, the bill would authorize the FDA to approve medical devices based on articles published in medical journals. These articles often are not carefully vetted and can contain important omissions, misrepresentations and outright fraud. For example, in one recent study looking at clinical trials in which the FDA had discovered serious problems, these issues were reported in medical journal articles written about the trials only 4 percent of the time.[30]
In addition to weakening approval standards, the 21st Century Cures bill would allow device manufacturers to become certified (by private contractors) to decide for themselves whether high- and moderate-risk devices remain safe and effective each time a new change is made. Currently, the FDA must be notified of all changes, and the agency sometimes requests additional information or safety and effectiveness tests.[31] The 21st Century Cures Act would take this regulatory power away from the FDA and allow manufacturers to regulate themselves.
Fortunately, there is still time for Congress to change course. The 21st Century Cures Act sailed easily through the House of Representatives in July, bolstered by a major industry-funded lobbying and public relations push and the promise of a temporary boost in funding for the National Institutes of Health.[32],[33] But the bill has stalled in the Senate, where a draft has not yet been released and concerns over safety, drug costs and funding for implementation have proven harder to overcome. These issues may prove challenging enough to kill the bill, although some provisions may be resurrected in future legislation.
Congress needs to hear from individual consumers that medical device safety is important. Contact your senators today and tell them to vote “no” on any legislation similar to the 21st Century Cures Act that was passed by the House.
References
[1] Food and Drug Administration. Center for Devices and Radiological Health Medical Devices Advisory Committee, Obstetrics and Gynecology Devices Panel, September 24, 2015. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ObstetricsandGynecologyDevices/UCM467456.pdf. Accessed 11/19/2015.
[2] Food and Drug Administration. Center for Devices and Radiological Health Medical Devices Advisory Committee, Obstetrics and Gynecology Devices Panel, September 24, 2015. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ObstetricsandGynecologyDevices/UCM467456.pdf. Accessed 11/19/2015.
[3] Food and Drug Administration. FDA Activities: FDA’s Review of Reported Problems. Updated September 16, 2015. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/EssurePermanentBirthControl/ucm452254.htm.
[4] Institute of Medicine. Report: Medical Devices and the Public’s Health: The FDA 510(k) Clearance Process at 35 Years. July 29, 2011. http://iom.nationalacademies.org/Reports/2011/Medical-Devices-and-the-Publics-Health-The-FDA-510k-Clearance-Process-at-35-Years.aspx#sthash.ao05Mpj8.dpuf. Accessed November 19, 2015.
[5] Bikowski J, Drais B, Divining the details of device clearance: Breaking through confusion to uncover the facts about FDA regulations for various marketed products. Practical Derm. 2008;(April):52-55.
[6] Food and Drug Administration. Step 3: Clinical Research. Updated October 19, 2015. http://www.fda.gov/forpatients/approvals/drugs/ucm405622.htm. Accessed November 19, 2015.
[7] Dhruva SS, Bero LA, Redberg RF. Strength of study evidence examined by the FDA in premarket approval of cardiovascular devices. JAMA. 2009;302(24):2679-2685.
[8] Rathi VK, Krumholz HM, Masoudi FA, Ross JS. Characteristics of clinical studies conducted over a total product life cycle of high-risk therapeutic medical devices receiving FDA premarket approval in 2010 and 2011. JAMA. 2015;314(6):604-612.
[9] Dhruva SS, Bero LA, Redberg RF. Strength of study evidence examined by the FDA in premarket approval of cardiovascular devices. JAMA. 2009;302(24):2679-2685.
[10] Rathi VK, Krumholz HM, Masoudi FA, Ross JS. Characteristics of clinical studies conducted over a total product life cycle of high-risk therapeutic medical devices receiving FDA premarket approval in 2010 and 2011. JAMA. 2015;314(6):604-612.
[11] 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). http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/medicaldevices/medicaldevicesadvisorycommittee/obstetricsandgynecologydevices/ucm463486.pdf. Accessed November 19, 2015.
[12] 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). http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/medicaldevices/medicaldevicesadvisorycommittee/obstetricsandgynecologydevices/ucm463486.pdf. Accessed November 19, 2015.
[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). http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/medicaldevices/medicaldevicesadvisorycommittee/obstetricsandgynecologydevices/ucm463486.pdf. Accessed November 19, 2015.
[14] 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). http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/medicaldevices/medicaldevicesadvisorycommittee/obstetricsandgynecologydevices/ucm463486.pdf. Accessed November 19, 2015.
[15] 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.
[16] 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.
[17] 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). http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/medicaldevices/medicaldevicesadvisorycommittee/obstetricsandgynecologydevices/ucm463486.pdf. Accessed November 19, 2015.
[18] 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). http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/medicaldevices/medicaldevicesadvisorycommittee/obstetricsandgynecologydevices/ucm463486.pdf. Accessed November 19, 2015.
[19] 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). http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/medicaldevices/medicaldevicesadvisorycommittee/obstetricsandgynecologydevices/ucm463486.pdf. Accessed November 19, 2015.
[20] Food and Drug Administration. Center for Devices and Radiological Health Medical Devices Advisory Committee, Obstetrics and Gynecology Devices Panel, September 24, 2015. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ObstetricsandGynecologyDevices/UCM467456.pdf. Accessed 11/19/2015.
[21] Bahk C, Goshgarian M, Donahue K, et al. Increasing patient engagement in pharmacovigilance through online community outreach and mobile reporting applications: an analysis of adverse event reporting for the Essure device in the US. Pharm Med 2015;29(6):331-340.
[22] Food and Drug Administration. FDA activities: FDA’s review of reported problems. Updated September 16, 2015. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/EssurePermanentBirthControl/ucm452254.htm. Accessed November 19, 2015.
[23] Food and Drug Administration. FDA activities: FDA’s review of reported problems. Updated September 16, 2015. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/EssurePermanentBirthControl/ucm452254.htm. Accessed November 19, 2015.
[24] Lane A, Tyson A, Thurston E, Providing re-ESSURE-ance to the nickel allergic patient considering hysteroscompic sterilization. J Minim Invasive Gynecol. 2015 Aug 7.
[25] Food and Drug Administration. FDA activities: FDA’s review of reported problems. Updated September 16, 2015. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/EssurePermanentBirthControl/ucm452254.htm. Accessed November 19, 2015.
[26] Food and Drug Administration. Center for Devices and Radiological Health Medical Devices Advisory Committee, Obstetrics and Gynecology Devices Panel, September 24, 2015. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ObstetricsandGynecologyDevices/UCM467456.pdf. Accessed 11/19/2015.
[27] Food and Drug Administration. FDA Postmarket Questions to the Panel. Meeting materials for the September 24, 2015, meeting of the Obstetrics and Gynecology Devices Panel. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ObstetricsandGynecologyDevices/UCM463463.pdf. Accessed November 19, 2015.
[28] H.R. 3920 – E-Free Act. November 2015. https://www.gpo.gov/fdsys/pkg/BILLS-114hr3920ih/pdf/BILLS-114hr3920ih.pdf. Accessed December 10, 2015.
[29] Redberg R, Dhruva S, The FDA’s Medical Device Problem. New York Times. July 17, 2015. http://www.nytimes.com/2015/07/17/opinion/the-fdas-medical-device-problem.html’ref=todayspaper&_r=2. Accessed December 16, 2015.
[30] Seife C. Research misconduct identified by the US Food and Drug Administration. JAMA Intern Med. 2015;175(4):567-577.
[31] Rome B, Kramer D, Kesselheim A. FDA approval of cardiac implantable electronic devices via original and supplemental premarket approval pathways, 1979-2012. JAMA. 2014;311(4):385-391.
[32] MacGillis A, Would Washington’s FDA fix cure the patients or the drug industry? ProPublica. October 20, 2015. http://www.propublica.org/article/would-washingtons-fda-fix-cure-the-patients-or-the-drug-industry. Accessed November 19, 2015.
[33] ASBMB Policy Blotter. 21st Century Cures Act passes committee. May 21, 2015. http://policy.asbmb.org/2015/05/21/21st-century-cures-act-passes-committee/.