Zheng Sarah Y, Dhruva Sanket S, Redberg Rita F
Department of Psychiatry, University of California, San Francisco.
Robert Wood Johnson Foundation Clinical Scholars Program, Yale School of Medicine, New Haven, Connecticut.
JAMA. 2017 Aug 15;318(7):619-625. doi: 10.1001/jama.2017.9414.
High-risk medical devices often undergo modifications, which are approved by the US Food and Drug Administration (FDA) through various kinds of premarket approval (PMA) supplements. There have been multiple high-profile recalls of devices approved as PMA supplements.
To characterize the quality of the clinical studies and data (strength of evidence) used to support FDA approval of panel-track supplements (a type of PMA supplement pathway that is used for significant changes in a device or indication for use and always requires clinical data).
Descriptive study of clinical studies supporting panel-track supplements approved by the FDA between April 19, 2006, and October 9, 2015.
Panel-track supplement approval.
Methodological quality of studies including randomization, blinding, type of controls, clinical vs surrogate primary end points, use of post hoc analyses, and reporting of age and sex.
Eighty-three clinical studies supported the approval of 78 panel-track supplements, with 71 panel-track supplements (91%) supported by a single study. Of the 83 studies, 37 (45%) were randomized clinical trials and 25 (30%) were blinded. The median number of patients per study was 185 (interquartile range, 75-305), and the median follow-up duration was 180 days (interquartile range, 84-270 days). There were a total of 150 primary end points (mean [SD], 1.8 [1.2] per study), and 57 primary end points (38%) were compared with controls. Of primary end points with controls, 6 (11%) were retrospective controls and 51 (89%) were active controls. One hundred twenty-one primary end points (81%) were surrogate end points. Thirty-three studies (40%) did not report age and 25 (30%) did not report sex for all enrolled patients. The FDA required postapproval studies for 29 of 78 (37%) panel-track supplements.
Among clinical studies used to support FDA approval of high-risk medical device modifications, fewer than half were randomized, blinded, or controlled, and most primary outcomes were based on surrogate end points. These findings suggest that the quality of studies and data evaluated to support approval by the FDA of modifications of high-risk devices should be improved.
高风险医疗器械经常进行改进，这些改进由美国食品药品监督管理局（FDA）通过各种上市前批准（PMA）补充申请予以批准。已经有多起作为PMA补充申请获批的器械被高调召回的事件。
描述用于支持FDA批准专家组跟踪补充申请（一种PMA补充申请途径，用于器械或使用适应症的重大变更，且始终需要临床数据）的临床研究和数据的质量（证据强度）。
对2006年4月19日至2015年10月9日期间支持FDA批准的专家组跟踪补充申请的临床研究进行描述性研究。
专家组跟踪补充申请获批。
研究的方法学质量，包括随机化、盲法、对照类型、临床与替代主要终点、事后分析的使用以及年龄和性别的报告情况。
83项临床研究支持了78项专家组跟踪补充申请的批准，其中71项专家组跟踪补充申请（91%）由单项研究支持。在这83项研究中，37项（45%）为随机临床试验，25项（30%）采用了盲法。每项研究的患者中位数为185例（四分位间距，75 - 305），中位随访时间为180天（四分位间距，84 - 270天）。共有150个主要终点（均值[标准差]，每项研究1.8[1.2]个），其中57个主要终点（38%）与对照进行了比较。在有对照的主要终点中，6个（11%）为回顾性对照，51个（89%）为活性对照。一百二十一个主要终点（81%）为替代终点。33项研究（40%）未报告所有纳入患者的年龄，25项研究（30%）未报告性别。FDA要求对78项专家组跟踪补充申请中的29项（37%）进行批准后研究。
在用于支持FDA批准高风险医疗器械改进的临床研究中，不到一半的研究采用了随机化、盲法或对照，且大多数主要结局基于替代终点。这些发现表明，为支持FDA批准高风险器械改进而评估的研究和数据质量应予以提高。
