Comeron W. Ghobadi

Hysteroscopic Sterilization With Essure: Summary of the U.S. Food and Drug Administration Actions and Policy Implications for Postmarketing Surveillance

In September 2015, the U.S. Food and Drug Administration (FDA) convened a meeting of the Obstetrics and Gynecology Advisory Board Committee to address the sudden increase of patient-reported adverse events surrounding Essure, a Class III device offering a less invasive method for permanent female sterilization. After a review of the premarketing and postmarketing data and existing scientific literature, the FDA concluded there was insufficient evidence to remove the device from the market. However, the FDA did release a new guidance document requiring a black box warning for the device and ordered a new postmarketing study comparing Essures safety and efficacy with laparoscopic tubal sterilization. The device was first approved in 2002 based on nonrandomized, single-arm prospective clinical studies. Since its approval, the device has grown in popularity, particularly in the United States. The driving forces for the sudden increase in adverse event reporting starting in 2013 related to the device remain unclear. Until completion of the new postmarketing study, there will continue to be significant uncertainty of the technologys risk-benefit profile. The controversy with Essure underscores the need for obstetricians and gynecologists to be actively involved in the lifecycle of medical devices. This includes actively reporting adverse events associated with devices to the FDA, supporting the implementation of unique device identifiers enriched with clinical records and paired with insurance claims, and stewarding robust device-specific registries.

Medical Device Approvals Through the Premarket Approval Pathway in Obstetrics and Gynecology From 2000 to 2015: Process and Problems.

Recent controversies surrounding obstetrics and gynecology devices, including a permanent sterilization device, pelvic meshes, and laparoscopic morcellators, highlight the need for deeper understanding of obstetrics and gynecology medical device regulation. The U.S. Food and Drug Administration premarket approval database was queried for approvals assigned to the obstetrics and gynecology advisory committee from January 2000 to December 2015. Eighteen device approvals occurred in the time period studied. The most common clinical indications included endometrial ablation (33%), contraception (28%), and fetal monitoring (17%). The median approval time was 290 days (range 178-1,399 days). Regarding the pivotal trials leading to approval, there were 11 randomized controlled trials, one randomized crossover study, five nonrandomized prospective studies, and two human factor studies. Fourteen devices (78%) met their primary clinical efficacy endpoint. Only 12 of 18 devices were required to conduct postmarket surveillance. A significant proportion of devices (42%) were approved on the basis of nonrandomized controlled trials. Three devices have been withdrawn after approval, all of which were either not referred or not recommended for approval by the obstetrics and gynecology advisory committee. Of the three devices withdrawn from the market, two failed to demonstrate clinical benefit in their pivotal trials. One device was not required to undergo postmarketing surveillance and was subsequently withdrawn as a result of patient safety concerns. Our results reveal significant weaknesses in the preapproval and postapproval regulation of high-risk obstetrics and gynecology devices. Greater specialty group involvement is necessary to ensure the development of safe and clinically effective devices.

Overview of Class I Device Recalls in Diagnostic Radiology, 2002-2015

PURPOSE To assess class I radiological device recalls using the FDA medical device recall database and provide a detailed analysis, including recall trends, regulatory changes, and policy implications for the future. METHODS This institutional review board-exempt study utilized the FDA Center for Devices and Radiological Health database for class I diagnostic radiological device recalls from November 1, 2002 to July 12, 2015. Recall characteristics, as well as market entry data, were collected for each device. RESULTS Thirteen class I radiological device recalls were identified, with 12 of them occurring after 2011. SPECT nuclear medicine systems were the most common, followed by fluoroscopic x-ray and MRI systems. Eleven of the recalls were attributed to premarket-related issues. One recall event occurred in response to the death of a patient during a nuclear scan. Twelve of the devices were cleared under the 510(k) pathway. A median of 213 devices (range: 2 to 12,968) were recalled per event, and all but two devices had a worldwide distribution at the time of recall. CONCLUSIONS We found that policy changes to the FDA were temporally related to class I radiological recall events. Additionally, class I radiological device recalls share characteristics: device modality, reason for recall, market entry, and product distribution. These recalls have broad implications and highlight the need for continued regulatory oversight as imaging technologies continue to advance.

Deep Learning in Radiology

As radiology is inherently a data-driven specialty, it is especially conducive to utilizing data processing techniques. One such technique, deep learning (DL), has become a remarkably powerful tool for image processing in recent years. In this work, the Association of University Radiologists Radiology Research Alliance Task Force on Deep Learning provides an overview of DL for the radiologist. This article aims to present an overview of DL in a manner that is understandable to radiologists; to examine past, present, and future applications; as well as to evaluate how radiologists may benefit from this remarkable new tool. We describe several areas within radiology in which DL techniques are having the most significant impact: lesion or disease detection, classification, quantification, and segmentation. The legal and ethical hurdles to implementation are also discussed. By taking advantage of this powerful tool, radiologists can become increasingly more accurate in their interpretations with fewer errors and spend more time to focus on patient care.

Device Safety Implications of the Clinical Data Leading to US Food and Drug Administration Approval of Soft-Tissue Fillers: A Systematic Review

Importance The US Food and Drug Administration (FDA) recently issued a safety warning regarding soft-tissue fillers (STFs) based on the risk of blindness and facial necrosis. Objective To examine the quality of evidence leading to FDA approval of STFs. Evidence Review All original approvals for STFs were mined using the publicly available FDA database. The Cochrane Collaboration’s risk of bias assessment tool was applied to all randomized clinical trials (RCTs). Findings A total of 14 STF approvals were identified. Of those, 10 pivotal studies (71%) were RCTs and 9 (60%) were masked. The median number of patients per trial was 144 (range, 30-439). Eleven of 12 studies (92%) met their primary end point. Ten of 14 trials (71%) involved injections solely of the nasolabial folds or cheeks; only 4 trials involved treatment of other facial regions. All 10 RCTs had an unclear risk of selection bias. Only 2 RCTs reported exclusions and attrition. Conclusions and Relevance Safety warnings relate more to the off-label use of STFs, which has not been sufficiently studied prospectively. Although STFs remain a safe device, with approval based mostly on RCT outcomes, implementation of unique device identifiers and greater use of physician-led registries would ensure physician, consumer, and regulatory confidence in STF safety.

Overview of high-risk medical device recalls in obstetrics and gynecology from 2002 through 2016: implications for device safety

&NA; The field of womens health has endured numerous recent controversies involving medical devices such as pelvic meshes, laparoscopic morcellators, and a hysteroscopic sterilization device. With the recent passage of the 21st Century Cures Act, new legislation will change how the Food and Drug Administration regulates medical devices. Given these controversies and new changes, we investigated high‐risk, class I recalls in womens health from 2002 through 2016. Class I recalls for medical devices are defined by the Food and Drug Administration as the most serious recall events and are designated for situations when there is a reasonable probability of serious adverse health consequences or death. We defined a recall event as a group of unique Food and Drug Administration recalls that share a similar reason for recall and occurred within a 1‐month time frame. In total, 7 class I recall events were identified encompassing 83 unique recalls affecting >88,000 medical devices in distribution. Recalls involved a broad range of devices used in womens health including diagnostic assays for chlamydia and gonorrhea, a laparoscopic tissue morcellator, and obstetrical/gynecological surgical kits. Four of 7 (57%) recall events were due to postmarketing problems such as improper packaging and labeling while the remaining 3 (43%) recalls were due to premarketing problems (eg, software issues). Additionally, 3 of 7 (43%) recall events were cleared via the 510(k) pathway, while the remaining were essentially exempt from any form of premarket approval. Two recall events involved sterility concerns of 71 surgical kits used in obstetrics and gynecological surgeries representing the majority of affected devices (78,423) in distribution. Class I medical device recalls are rare but serious events. Most recalled devices in womens health had minimal preapproval regulation and were recalled due to both premarketing and postmarketing reasons. Future regulatory efforts to improve postmarketing surveillance may mitigate the potential impact and frequency of class I recalls, but do not replace the need for a higher burden of proof for both safety and efficacy prior to medical device approval.

Major FDA medical device recalls in ophthalmology from 2003 to 2015

OBJECTIVE To assess recent high-risk ophthalmic medical device recalls. METHODS The publicly available Food and Drug Administration Center for Devices and Radiological Health database was mined for Class I (high-risk) ophthalmic device recalls from January 1, 2003 to December 31, 2015. The number of Class I ophthalmic device recalls was quantified. Additionally, recall characteristics and market entry data were determined for each device. RESULTS Twelve Class I ophthalmic device recall events were identified, collectively affecting over 68 million units in distribution. A median of 147,491 units (range 20 to 57,252,581) were recalled per event. 9 out of 12 recalls (75%) had at least one documented occurrence of an adverse event to a patient. Pre-market related issues accounted for one device recall (8%), post-market related issues accounted for nine device recalls (75%), and two device recalls (17%) were indeterminate. 510(k) clearance was the most common pathway to market, accounting for 50% of Class I recalls. Three devices were approved through pre-market approval (PMA) pathway, two devices were exempt from review, and one device failed to register with the FDA. CONCLUSION Class I recalls surrounding ophthalmology are relatively infrequent compared to other medical specialties. However, given the impact of Class I recalls in the field, ophthalmologists have an impetus to advocate for stronger device regulation particularly in the context of post-marketing surveillance.

Retrospective Study of the FDA Database for High Risk Medical Device Approvals in Obstetrics & Gynecology [8E]

INTRODUCTION: The newly proposed 21st Century Cures Act would lead to significant changes to medical device regulation. Recent controversies surrounding pelvic meshes and morcellators highlight the need for better understanding surrounding the regulation and approval of high-risk devices in Obstetrics and Gynecology (OBGYN). METHODS: The FDA database was reviewed for device approvals assigned to the OBGYN advisory committee along the pre-market approval pathway from 2000–2015. The quality of the pivotal studies leading to approval were extracted from the summary of safety and effectiveness data. RESULTS: There were 18 approvals between 2000–2015. The OBGYN advisory committee recommended nine devices for approval and recommended against approval for two devices. Seven devices were not referred for formal review. Three devices have been withdrawn following approval, all of which were either not referred or initially rejected by the committee. Four devices were granted expedited status. The median approval time was 290 days (range 178–1,399). Indications included endometrial ablation (33%), contraception (28%) and fetal monitoring (17%). In total, there were 11 randomized controlled trials, one randomized cross-over study, five non-randomized prospective studies and two human factor studies. 13 of 18 devices required post-market surveillance. CONCLUSION: Compared to other medical specialties, OBGYN ranked 9th out of 17 specialties in high-risk device approvals from 2000–2015. These devices were more likely to be approved based on RCTs compared to prior studies on Cardiology and Gastroenterology devices. The last six years have led to only one device approval suggesting the need to spur device innovation in OBGYN.