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

Abstract

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. To examine the quality of evidence leading to FDA approval of STFs. 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). 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. 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.