Of the adverse events studied at the time of the initial premarket approval submission, the pivotal study (STOP 2000) demonstrated that 1 year after insertion, 3.8% of patients reported abdominal pain or cramping, 9.0% reported back or low back pain, and 2.9% reported unspecified pain. Some have argued that both the premarket and postmarket studies for Essure were not significantly rigorous for the device's indication of permanent sterilization given the nonblinded study design, lack of comparator group, and short follow-up.7 Despite these limitations, Essure was approved by the FDA with the recommendation of the Obstetrics and Gynecological Devices Advisory Panel committee on the condition of two postapproval studies detailed in Table 1.6
The FDA mandated a study (ESS205) to examine the rates of successful bilateral Essure placement for 40 new trainees for 20 patients each (goal of 800 patients), but ultimately enrolled only 585 participants with a 3% adverse event rate. The second postmarketing study required continued evaluation of all women participating in both the STOP 10 and STOP 2000 studies for a total of 5 years. The 5-year follow-up for STOP 10 included only 75% of the original enrolled patients (171/227), whereas the original pivotal study included 71% of initial enrollees (366/518) and was only recently published in 2015.8
ESSURE AND UNINTENDED PREGNANCY
There were no pregnancies after 5 years in both the STOP 10 or STOP 2000 studies (n=632) excluding luteal-phase pregnancies; these pregnancies preceded Essure placement and were undetected at the time of insertion. Review of the scientific literature demonstrated the rate of unintended pregnancy for patients relying exclusively on Essure is comparable with other methods of permanent sterilization.9 Many of the unintended pregnancies of Essure are attributed to patient nonadherence with alternative contraception before the 3-month confirmatory test, implant expulsion, perforation, or physician misinterpretation of the confirmatory test.10 However, there are literature reports of unintended intrauterine pregnancies11,12 and ectopic pregnancies,13,14 even after successful confirmatory testing. Based on a review of the Medical Device Reports submitted to the FDA, 127 entries cite an intrauterine pregnancy (76 live births, 32 miscarriages, 19 elective termination) and 69 record ectopic pregnancies. The circumstances and extent of patient or physician noncompliance compared with true device failure in the setting of these pregnancies remain unclear.
OTHER ADVERSE EVENTS AND COMPLICATIONS
There were six uterine or fallopian tube perforations in the STOP 10 study with an additional perforation detected at 5-year follow-up. In the STOP 2000 study, there was a 1.1% perforation rate (5/476). Reports in the scientific literature show perforation rates from less than 1%12,15 to 3.6%.16 Medical Device Reports documented 33 intraoperative and 266 postprocedural perforations.
In the 5-year STOP 10 postmarketing study, less than 2% of patients reported dysmenorrhea (4/171), dyspareunia (1/171), pelvic pain (3/171), and pain otherwise unspecified (2/171). Among STOP 2000 study patients, dysmenorrhea, dyspareunia, and pain were reported at slightly higher levels (Table 1) compared with STOP 10. Of note, patients with chronic pain syndromes were excluded from both studies at the time of enrollment. Subsequent studies have shown increased rates of long-term postimplantation pain in patients with a history of chronic pain.17
Although chronic pain was uncommon in the STOP 10 and STOP 2000 studies, pain or cramping represented the majority (3,516/5,093 [69%]) of Medical Device Reports. Medical Device Reports do not necessarily reflect a causative relationship between device and pain as a result of lack of details regarding timing, location, and severity of symptoms.18 Within the FDA's executive summary on Essure, an analysis of the Medical Device Reports shows that 90% of women (176/196) reported the resolution of improvement of a wide range of symptoms (eg, pain, hair loss, headaches, visual changes) after the device was removed.2 Assessment of chronic pain after Essure device placement in the scientific literature is limited given the lack of control groups and retrospective study design. One study evaluating insurance claims data demonstrated that 0.9% (236/26,927) of women reported chronic pelvic pain after hysteroscopic sterilization at a mean follow-up of 275 days. This was not statistically different from those with pelvic pain after laparoscopic sterilization.19 Of note, this study included sterilization by either Essure or the Adiana device; Adiana was another hysteroscopic device that utilized radiofrequency energy and a silicone matrix to achieve tubal occlusion,20 which was withdrawn from the market in 2012 for reasons unrelated to device safety or efficacy.
Among STOP 2000 participants at 5-year follow-up, 11.7% reported irregular menses and 7.5% reported intermenstrual bleeding; only 0.5% (2/377) reported persistent heavier menstrual flow. Change in menstrual patterns (intermenstrual bleeding, heavier menses, or menstrual irregularities) accounted for 37% (1,861/5,093) of Essure-related Medical Device Reports. These reports may reflect more than one code per patient, so the rate of bleeding changes is difficult to interpret. In comparison, prior studies on tubal ligation have demonstrated that 10.4% of women exhibit heavy menstrual bleeding 3–4 years after sterilization.21 Finally, no deaths were attributed to Essure placement or use in either the STOP 10 or STOP 2000 clinical studies after 5 years. Of the 11 Medical Device Reports reporting deaths associated with Essure, 5 were fetal deaths and 4 were patient deaths. These deaths included group A streptococci infection 2 days after placement, cardiopulmonary arrest during insertion secondary to paradoxical air embolism, pulmonary embolism after hysterectomy for the removal of Essure, and suicide.22 A detailed review of other postmarketing studies not directly involving the manufacturer is summarized in the executive summary published by the FDA and Bayer HealthCare.2,23
APPROVAL FOR A NEW ESSURE MODEL
Medical devices are unique from pharmaceuticals because they typically undergo postmarketing labeling, design, or material changes, which can be reviewed and approved through an expedited supplement process. Essure, like many other high-risk obstetrics–gynecology devices,1 has had more than 40 supplements since its initial approval. The supplement process allows for the expected iterative process inherent to device design. However, multiple incremental supplements over time potentially lead to a distinctly different device than what was initially approved,24 a phenomenon known as device creep. In recent history, changes approved through the supplement process for high-risk cardiac devices have led to several high-profile device recalls (eg, Sprint Fidelis and Riata defibrillator leads).25
In 2007, a new Essure model was approved through a premarketing approval supplement (ESS305, Premarket Approval Supplement 12); modifications were made to the device to improve visibility, decrease distension fluid backsplash, and improve coil deployment. Approval of this model occurred without prospective data. Instead, the FDA required a new study to assess the rate of successful insertion on a first attempt for the new model. In an executive summary provided by Bayer, bilateral placement was achieved in 96% of women (593/619)23; an independent analysis of the same data revealed similar conclusions with a 97% bilateral implant rate.26
RISE IN PATIENT-REPORTED COMPLAINTS
In 2012, the FDA received only 152 Medical Device Reports associated with Essure, approximately half of which were voluntary. In the next year, the total number of Medical Device Reports increased by more than 400% (817 Medical Device Reports), with 89% being voluntary. As of 2015, there have been more than 5,000 (4,608 patient injury reports, 474 device malfunctions, and 11 deaths) patient-submitted complaints.2 In response, the FDA convened with the Obstetrics and Gynecology Advisory Committee and reevaluated patient reports from the original clinical trials driven, in part, by a Citizen Petition alleging alteration of subject trial experiences.27 The FDA found no evidence of intentional or methodical changes to participant experiences to provide a more favorable perception of the device. However, the FDA did conclude that the premarketing studies, postmarketing studies, and available scientific literature all exhibited shortcomings; many of these concerns related to the lack of comparator arms and retrospective nature of the available data.2
Beyond the new black box warning, the FDA also proposed a new consent process to include a “Patient Decision Checklist” to facilitate the conversation between patients and health care providers before Essure insertion.4 Most significantly, the FDA ordered the manufacturer to conduct an additional postmarketing study known as a 522 study. The FDA has the authority to order additional studies for class II or III devices even after approval if device failure represents a high risk of causing serious adverse health consequences. The details of the new 522 study, released in September 2016, will enroll a total of 2,800 women to compare Essure with laparoscopic tubal sterilization for a period of 36 months. The primary efficacy endpoint is pregnancy, whereas the primary safety endpoints will include: chronic abdominal or pelvic pain, abnormal uterine bleeding, hypersensitivity or allergic reactions, and surgeries requiring removal of the device.28 This would represent the most scientifically rigorous and comprehensive study of Essure to date. Some contend that Essure safety concerns may have been detected earlier with a more stringent and proactive approach to both premarketing and postmarketing surveillance.7 There have been calls by consumer groups in both the United States and Canada for removal of the device from the market and possible class action litigation.29,30 Representative Michael Fitzpatrick (R-PA) even introduced the “E-free bill” in November 2015 calling for the withdrawal of Essure's FDA approval.31
POSTMARKETING SURVEILLANCE SYSTEMS FOR HIGH-RISK DEVICES
The FDA's Manufacturer and User Facility Device Experience database is a repository of information to track adverse events related to device use but is limited in its ability to draw inferences of causality or incidence. Despite mandatory manufacturer reporting, there is discretion in determining whether the device was responsible for an adverse event, creating a disincentive to reporting device-related problems32; voluntary reports by patients and physicians are underreported and may be incomplete or unverified.18 The Medical Device Guardians Act, a bill recently introduced in the House of Representatives, would require physicians to report medical device safety concerns.33 Beyond Manufacturer and User Facility Device Experience, the FDA also operates the Medical Product Safety Network. The Medical Product Safety Network consists of a network of facilities specifically trained in collecting and submitting adverse events, which theoretically produces higher quality reporting.18 However, the Medical Product Safety Network only represents a fraction of health care service providers. In 2010, the FDA initiated a public–private partnership known as MDEpiNet to recommend improvements in medical device safety.34 The partnership has developed several initiatives, including device registry building and a surveillance mechanism of electronic health records to detect safety concerns, but serves predominantly in an advisory role.
The FDA can also require manufacturers to conduct additional postmarketing approval studies either as a condition of device approval (postmarketing approval study) or as an additional 522 study, both of which have been used in the case of Essure. However, postmarketing studies have limitations. In one analysis that considered all postmarketing studies from 2007 to 2012, 88% of studies were considered inactive; in 37% of these cases, manufacturers consolidated multiple postmarketing studies into one, even if this meant inclusion of several different models of the same device (eg, multiple versions of a metal-on-metal implant).35 There remain significant shortcomings in the timely execution and dissemination of postmarketing studies; only 6% of 522 studies initiated between 2005 and 2012 achieved completion or adequate progress.36 Moreover, the final publication rate of studies related to both premarketing and postmarketing approval studies remains low.37
NEW EFFORTS TO IMPROVE DEVICE SAFETY
One of the FDA's main strategic initiatives for 2017 involves the creation of a National Evaluation System for Health Technology.38 The FDA envisions this system as a public–private partnership combining disparate “real-world” sources of data on medical devices, including electronic health records, device registries, and insurance claims.39 Building this infrastructure would also connect multiple existing postmarketing surveillance resources such as the National Patient-Centered Clinical Research Network and Sentinel, a data surveillance system of insurance claims.40 The FDA has already initiated funding for the National Evaluation System for Health Technology by awarding $3 million to the Medical Device Innovation Consortium, a public-private partnership dedicated to advancing regulatory science, to act as the initial coordination center. Additionally, a recently published draft guidance of the next iteration of the Medical Device User Fee Amendments to be submitted to Congress and enacted for fiscal years 2018–2022 includes language that would direct industry-derived user fees to support the National Evaluation System.41
Success of the new system is contingent on several considerations relevant to the Essure debate. The first is coordination and expansion of device registries. When expanded across large data sets, registries provide insights to device safety concerns that even the best designed prospective studies are unable to detect. However, the inherent retrospective nature of registries limits their utility, and they should not replace rigorously designed prospective studies, particularly when assessing device efficacy. For registries to be effective, they must accurately identify the devices used given that devices undergo alterations through the supplement pathway, of which Essure is no exception. Thus, broadening implementation of unique device identifiers enables rapid identification of medical devices in multiple real-world sources, including different device models approved through the supplement process. Through a graduated process, the FDA initially required unique device identifiers to be assigned for all medical devices in 2013.18 As of 2015, implantable, life-supporting, and life-sustaining devices require a unique device identifier. However, adding identifiers to devices is only the first step. They must be paired with clinical data such as a patient's demographics and comorbidities to derive meaningful insights into a device's true efficacy and risk. Beyond pairing to medical records, connecting device identifiers to insurance claims would enable a larger, population-based surveillance system. The advantage of insurance claims is standardization, which facilitates the aggregation of data across different health care providers and health systems for millions of patients.42 In fact, the future success of the National Evaluation System for Health Technology to incorporate data from the FDA's Sentinel program depends on the broader implementation of unique device identifiers with insurance claims. Multiple stakeholders, including insurers (Aetna), think tanks (The Pew Charitable Trusts), physician organizations (American College of Cardiology), and the Centers for Medicare and Medicaid Services, have all argued for the inclusion of unique device identifiers in insurance claims to improve postmarketing device surveillance.43,44 See Table 2 for a summary of existing postmarketing surveillance mechanisms.
POLICY IMPLICATIONS FOR MEDICAL DEVICE SAFETY
Ultimately, the regulation of high-risk medical devices has been criticized for a lack of rigor, particularly compared with pharmaceuticals.32,34,45,46 Previously, we have demonstrated that the clinical evidence leading to approval of obstetrics–gynecology devices has significant weaknesses.1 The same has been shown in multiple other specialties, including cardiology and gastroenterology, suggesting a broad issue that is not specialty-specific.47,48 In the case of Essure, safety concerns have been driven by publicly generated reports spurred by intense media attention. Some have argued that these reports only tell part of the story and may not represent the true safety risk of medical devices.49 Previous work from one large medical center demonstrated that electronic medical records and insurance claims data can reveal longitudinal safety data for Essure in a matter of hours, not years.44 The authors note this was possible only because Essure was tied to one common procedural terminology code (Current Procedural Terminology code 58565) aside from a brief period of time from 2009 to 2012 when the Adiana system was on the market. It took approximately 3 years from the increase in complaints related to Essure before the FDA responded. Likely, it will be several more years before the 522 postmarketing study is complete and its results disseminated. A National Evaluation System for Health Technology is a step in the right direction to strengthen the limitations of the current system.
From an individual clinician perspective, there remains persistent underreporting to the Manufacturer and User Facility Device Experience for adverse events associated with medical devices.18 Obstetrician–gynecologists using Essure should be aware that timely, complete documentation surrounding suspected adverse events can be submitted to the FDA (FDA 3500 form) through a mobile application as well as fax or regular mail.50 As a specialty, obstetrics–gynecology has an opportunity to play a critical role in the implementation of unique device identifiers for high-risk devices in women's health. Approximately half of the 141,000 Medical Device Reports analyzed in 2007 lacked details on the specific device of concern.18 In Essure's case, the unique device identifier would have discerned whether the original model or updated versions approved as supplements were overrepresented in Manufacturer and User Facility Device Experience reports or peer-reviewed studies.
There should be an increase in the specialty's participation in registries, particularly for high-risk implantable devices like Essure. The Pelvic Floor Disorders Registry represents one example of how the American Urogynecologic Society successfully worked with pelvic mesh manufacturers to create a national registry to effectively respond to an FDA mandate.40 The American College of Cardiology's National Cardiovascular Data Registry incorporates specific registries for atrial fibrillation implantation, implantable cardiac defibrillators, and transcatheter valve replacements. The Transcatheter Aortic Valve Registry was used to detect deviations in clinical practice that posed a device safety risk.34 Device registries led by physician specialty groups have several advantages. There is inherent understanding of disease severity and associated comorbidities. Moreover, there is less concern of bias associated with manufacturer-led registries.51 However, registries do require a commitment of time, resources, and active participation. In the case of Essure, well-maintained registries could have provided valuable information to either support or allay concerns.
The American College of Obstetricians and Gynecologists justifiably argues that Essure offers a less invasive and potentially safer permanent contraception solution for many women who are poor surgical candidates.52 Premature recalling of the device may subsequently expose women to the risks of surgical sterilization, which carries an estimated mortality rate of 1–2 per 100,000 surgeries.53 The best available evidence, albeit with significant limitations, and concerns over data transparency and completeness,7 suggests Essure is safe and effective. However, without well-designed premarketing and postmarketing clinical studies, it is difficult to know whether patient-generated reports represent an unreasonable risk–benefit tradeoff. The debate will likely continue until the completion and dissemination of the current 522 study. The controversy surrounding Essure underscores the need for obstetrician–gynecologists to be actively involved in the lifecycle of medical devices.
1. Walter JR, Hayman E, Tsai S, Ghobadi CW, Xu S. Medical device approvals through the premarket approval pathway in obstetrics and gynecology from 2000 to 2015: process and problems. Obstet Gynecol 2016;127:1110–7.
2. Review of the Essure system for hysteroscopic sterilization. FDA review document. Silver Spring (MD): U.S. Food and Drug Administration; 2015. p. 1–89.
3. Veersema S, Vleugels M, Koks C, Thurkow A, van der Vaart H, Brolmann H. Confirmation of Essure placement using transvaginal ultrasound. J Minim Invasive Gynecol 2011;18:164–8.
4. Labeling for permanent hysteroscopically-placed tubal implants intended for sterilization: draft guidance for industry and food and drug administration staff. Silver Spring (MD): U.S. Food and Drug Administration; 2016.
5. Summary of safety and effectiveness data. Contraceptive tubal occlusion device and delivery system: P020014. Silver Spring (MD): U.S. Food and Drug Administration; 2002. p. 1–24.
6. U.S. Food and Drug Administration. Essure system: summary of safety and effectiveness data. Silver Spring (MD): U.S. Food and Drug Administration; 2002.
7. Dhruva SS, Ross JS, Gariepy AM. Revisiting Essure—toward safe and effective sterilization. N Engl J Med 2015;373:e17.
8. Chudnoff SG, Nichols JE Jr, Levie M. Hysteroscopic Essure inserts for permanent contraception: extended follow-up results of a phase iii multicenter international study. J Minim Invasive Gynecol 2015;22:951–60.
9. Ouzounelli M, Reaven NL. Essure hysteroscopic sterilization versus interval laparoscopic bilateral tubal ligation: a comparative effectiveness review. J Minim Invasive Gynecol 2015;22:342–52.
10. Cleary TP, Tepper NK, Cwiak C, Whiteman MK, Jamieson DJ, Marchbanks PA, et al.. Pregnancies after hysteroscopic sterilization: a systematic review. Contraception 2013;87:539–48.
11. Lazarus E, Lourenco AP, Casper S, Allen RH. Necessity of hysterosalpingography after Essure microinsert placement for contraception. AJR Am J Roentgenol 2012;198:1460–3.
12. Povedano B, Arjona JE, Velasco E, Monserrat JA, Lorente J, Castelo-Branco C. Complications of hysteroscopic Essure(®) sterilisation: report on 4306 procedures performed in a single centre. BJOG 2012;119:795–9.
13. Bjornsson HM, Graffeo CS, Davis SS. Ruptured ectopic pregnancy after previously confirmed tubal occlusion by the Essure procedure. Ann Emerg Med 2011;57:310–1.
14. Huguelet P. Ectopic pregnancy after hysteroscopic tubal occlusion confirmed by hysterosalpingogram: a case report. J Reprod Med 2013;58:337–40.
15. Grosdemouge I, Engrand JB, Dhainault C, Marchand F, Martigny H, Thevenot J, et al.. Essure implants for tubal sterilisation in France [in French]. Gynecol Obstet Fertil 2009;37:389–95.
16. Thiel J, Suchet I, Tyson N, Price P. Outcomes in the ultrasound follow-up of the Essure micro-insert: complications and proper placement. J Obstet Gynaecol Can 2011;33:134–8.
17. Yunker AC, Ritch JM, Robinson EF, Golish CT. Incidence and risk factors for chronic pelvic pain after hysteroscopic sterilization. J Minim Invasive Gynecol 2015;22:390–4.
18. Rajan PV, Kramer DB, Kesselheim AS. Medical device postapproval safety monitoring: where does the United States stand? Circ Cardiovasc Qual Outcomes 2015;8:124–31.
19. Conover MM, Howell JO, Wu JM, Kinlaw AC, Dasgupta N, Jonsson Funk M. Incidence of opioid-managed pelvic pain after hysteroscopic sterilization versus laparoscopic sterilization, US 2005-2012. Pharmacoepidemiol Drug Saf 2015;24:875–84.
20. Vancaillie TG, Harrington DC, Anderson JM. Mechanism of action of the Adiana(®) device: a histologic perspective. Contraception 2011;84:299–301.
21. Rulin MC, Davidson AR, Philliber SG, Graves WL, Cushman LF. Long-term effect of tubal sterilization on menstrual indices and pelvic pain. Obstet Gynecol 1993;82:118–21.
22. September 2015 Advisory Committee to discuss Essure safety and effectiveness. 2015. Available at: http://http://www.fda.gov
/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/EssurePermanentBirthControl/ucm452254.htm. Retrived March 8, 2016.
23. Bayer HealthCare: ESSURE system for permanent birth control. Executive summary for the FDA Advisory Committee meeting. Berlin (Germany): Bayer HealthCare; 2015.
24. Rome BN, Kramer DB, Kesselheim AS. FDA approval of cardiac implantable electronic devices via original and supplement premarket approval pathways, 1979-2012. JAMA 2014;311:385–91.
25. Zheng SY, Redberg RF. Premarket approval supplement pathway: do we know what we are getting? Ann Intern Med 2014;160:798–9.
26. Levie M, Chudnoff SG. A comparison of novice and experienced physicians performing hysteroscopic sterilization: an analysis of an FDA-mandated trial. Fertil Steril 2011;96:643–8.e1.
27. Citizen Petition From Koch Parafinczuk and Wolf, P.A. 2015. Available at: http://http://www.regulations.gov
/document?D=FDA-2015-P-0569-0001. Retrieved June 23, 2016.
28. 522 Postmarket surveillance studies: Essure—P020014. 2016. Available at: http://http://www.accessdata.fda.gov
/scripts/cdrh/cfdocs/cfPMA/pss.cfm?t_id=356&c_id=3854. Retrieved September 19, 2016.
29. Morris R. Erin Brockovic calls for end to Bayer's Essure. BBC News 2014.
30. McKnight Z. ‘Essure’ birth control subject of potential class-action lawsuit in Canada. Toronto Star 2016.
31. E-Free Act. CR H9210; 2015.
32. Fox DM, Zuckerman DM. Regulatory reticence and medical devices. Milbank Q 2014;92:151–9.
33. Levitz J. Bill would require doctors to report medical-device hazards. Wall Street J 2016.
34. Sorenson C, Drummond M. Improving medical device regulation: the United States and Europe in perspective. Milbank Q 2014;92:114–50.
35. FDA ordered postmarket studies to better understand safety issues, and many studies are ongoing. Washington, DC: U.S. Government Accountability Office; 2015.
36. Reynolds IS, Rising JP, Coukell AJ, Paulson KH, Redberg RF. Assessing the safety and effectiveness of devices after US Food and Drug Administration approval: FDA-mandated postapproval studies. JAMA Intern Med 2014;174:1773–9.
37. Hwang TJ, Sokolov E, Franklin JM, Kesselheim AS. Comparison of rates of safety issues and reporting of trial outcomes for medical devices approved in the European Union and United States: cohort study. BMJ 2016;353:i3323.
38. Center for Devices and Radiological Health. 2016–2017 strategic priorities. Silver Spring (MD): U.S. Food and Drug Administration; 2016. p. 1–13.
39. Shuren J, Califf RM. Need for a national evaluation system for health technology. JAMA 2016;316:1153–4.
40. Krucoff MW, Normand SL, Edwards F, Lystig T, Ross E, Berliner E, et al..Recommendations for a national medical device evaluation system. Silver Spring (MD): Medical Device Registry Task Force and the Medical Devices Epidemiology Network; 2015.
41. U.S. Food and Drug Administration. Medical device user fee amendments performance goals and procedures, fiscal years 2018 through 2022–draft guidance. Silver Spring (MD): US Food and Drug Administration; 2016.
42. Why insurance claims should include medical device identification. Washington, DC: Pew Center Trusts; 2016. p. 1–2.
43. Burton TM. Medicare backs ID numbers for medical devices. Wall Street J 2016.
44. Graham J, Cooper S, Dhanya MA. How safety concerns about Essure reveal a path to better device tracking. Health Affairs Blog Available at: http://healthaffairs.org/blog/2015/10/15/how-safety-concerns-about-essure-reveal-a-path-to-better-device-tracking/.
45. Kramer DB, Xu S, Kesselheim AS. Regulation of medical devices in the United States and European Union. N Engl J Med 2012;366:848–55.
46. Kramer DB, Xu S, Kesselheim AS. How does medical device regulation perform in the United States and the European Union? A systematic review. PLoS Med 2012;9:e1001276.
47. Dhruva SS, Bero LA, Redberg RF. Strength of study evidence examined by the FDA in premarket approval of cardiovascular devices. JAMA 2009;302:2679–85.
48. Saleem N, Xu S. Overview of high-risk medical device innovation in gastroenterology from 2000 to 2014: enhancing the pipeline. Dig Dis Sci 2016;61:2165–74.
49. Tracy EE, Bortoletto P. The role of social networks, medical-legal climate, and patient advocacy on surgical options: a new era. Obstet Gynecol 2016;127:758–62.
50. Instructions for completing form FDA 3500A. Available at: http://http://www.fda.gov
/downloads/Safety/MedWatch/HowToReport/DownloadForms/UCM387002.pdf. Retrieved September 17, 2016.
51. Niederlander C, Wahlster P, Kriza C, Kolominsky-Rabas P. Registries of implantable medical devices in Europe. Health Policy 2013;113:20–37.
52. American College of Obstetricians and Gynecologists. ACOG comments to FDA on Essure. Available at: http://http://www.acog.org
/About-ACOG/Announcements/ACOG-Comments-to-FDA-on-Essure. Retrieved September 27, 2016.
© 2017 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
53. Bartz D, Greenberg JA. Sterilization in the United States. Rev Obstet Gynecol 2008;1:23–32.