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Original Investigation
August 15, 2017

Characteristics of Clinical Studies Used for US Food and Drug Administration Approval of High-Risk Medical Device Supplements

Author Affiliations
  • 1Department of Psychiatry, University of California, San Francisco
  • 2Robert Wood Johnson Foundation Clinical Scholars Program, Yale School of Medicine, New Haven, Connecticut
  • 3Veterans Affairs Connecticut Healthcare System, West Haven
  • 4Division of Cardiology, University of California, San Francisco
JAMA. 2017;318(7):619-625. doi:10.1001/jama.2017.9414
Key Points

Question  What is the quality of clinical studies and data used to approve modifications to high-risk devices by the US Food and Drug Administration (FDA) panel-track supplement pathway?

Findings  In this descriptive study of 83 clinical studies for 78 panel-track supplements approved between 2006 and 2015, 45% were randomized clinical trials and 30% were blinded. Of the 150 primary end points in these studies, 81% were surrogates and 38% were compared with controls.

Meaning  There are limitations in the quality of the studies and data evaluated by the FDA to support modifications of high-risk devices.

Abstract

Importance  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.

Objective  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).

Design and Setting  Descriptive study of clinical studies supporting panel-track supplements approved by the FDA between April 19, 2006, and October 9, 2015.

Exposure  Panel-track supplement approval.

Main Outcomes and Measures  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.

Results  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.

Conclusions and Relevance  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.

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