Methodological and reporting quality of non-inferiority randomized controlled trials comparing antifungal therapies: a systematic review

Background: Detailed reporting is essential in non-inferiority randomized controlled trials (NI-RCTs) to assess evidence quality, as these trials inform standards of care. Objectives: The primary objective was to evaluate the methodological and reporting quality of antifungal NI-RCTs. Data sources: Medline, EMBASE, the Cochrane CENTRAL and the United States Federal Drug Administration (FDA) drugs database were searched to 9 September 2020. Study eligibility criteria: NI-RCTs differing by antifungal formulation, type, dose, administration and/or duration were included. Articles were independently assessed in duplicate using quality indicators developed by the Consolidated Standards of Reporting Trials (CONSORT) group. Participants: Patients enrolled in antifungal trials for prophylactic and therapeutic use. Methods: The Cochrane RoB 2.0 tool was used to assess risk of bias. Descriptive statistics were used; all statistical tests were two sided. Results: Of 32 included studies, 22 (68.7%) did not justify the NIM. Handling of missing data was not described in 20 (62.5%). Intention-to-treat (ITT) and per-protocol (PP) analyses were both reported in 12/32 (37.5%) studies. Eleven of 32 studies (34.3%) reported potentially misleading conclusions. Industry-financed studies were more likely to report only the ITT analysis (n = 14/27, 51.9%). Methodological and reporting quality was unaffected by publication year; risk of bias from missing data changed over time. Overall risk of bias across included studies was moderate to high, with high risk in randomization process (n = 8/32, 25%), missing outcome data (n = 5/32, 15.6%), and selection of reported result (n = 9/32, 28.1%). Conclusions: Justification of the non-inferiority margin, reporting of ITT and PP analyses, missing data handling description, and ensuring conclusions are consistent with reported data is necessary to improve CONSORT adherence. Small sample size and overall risk of bias are study limitations. (C) 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.