Safety Assessment and Power Analyses in Published Anti-Vascular Endothelial Growth Factor Randomized Controlled Trials

Abstract

PURPOSE: To investigate a certain set of methodological limitations in published anti-vascular endothelial growth factor (VEGF) randomized controlled trials (RCTs). DESIGN: Descriptive methodological study. METHODS: We did a PubMed search with the terms bevacizumab OR ranibizumab OR pegaptanib OR aflibercept and the limitations humans and randomized controlled trials in 15 of the highest-impact-factor general medicine and ophthalmology journals. We included only RCTs published as original articles, where an anti-VEGF agent was used to treat eye disease. Two independent observers (O.A., P.K.) read through each article and classified the articles according to a predefined set of criteria. RESULTS: The PubMed search yielded 209 articles, and 93 were classified as eligible. In most of the studies, the study drug was bevacizumab (52.6%, n = 49), followed by ranibizumab (44.1%, n = 41), pegaptanib (7.5%, n = 7), and aflibercept (5.4%, n = 5). Basic epidemiologic data, including sex distribution (2.2%, n = 2) and mean age (3.2%, n = 3), were missing in 3.2% of the published RCTs. The power calculation for efficacy was mentioned in 48% (n = 45) of the published work, and a power calculation for safety was considered in only 1 study (1.1%). Only 6 RCTs (6.5%) reported negative results. CONCLUSIONS: Power calculations for efficacy, an important component of an RCT, were missing in 51% of the RCTs we surveyed, while a power calculation for safety was only present in 1.1%. Around 60% of the published RCTs were labeled as an efficacy and safety trial, and none of those studies had a power calculation for safety. (C) 2016 Elsevier Inc. All rights reserved.