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.