Methodological and Reporting Quality of Noninferiority Randomized Controlled Trials Comparing Antiretroviral Therapies: A Systematic Review.

BACKGROUND: It is unclear whether the reporting quality of antiretroviral (ARV) noninferiority (NI) randomized controlled trials (RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year. METHODS: We searched Medline, Embase, and Cochrane Central from inception to 14 November 2022. We included NI-RCTs comparing ≥2 ARV regimens used for human immunodeficiency virus treatment or prophylaxis. We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias. Screening and data extraction were performed blinded and in duplicate. Descriptive statistics were used to summarize data; statistical tests were 2 sided, with significance defined as P < .05. The systematic review was prospectively registered (PROSPERO CRD42022328586), and not funded. RESULTS: We included 160 articles reporting 171 trials. Of these articles, 101 (63.1%) did not justify the NI margin used, and 28 (17.5%) did not provide sufficient information for sample size calculation. Eighty-nine of 160 (55.6%) reported both intention-to-treat and per-protocol analyses, while 118 (73.8%) described missing data handling. Ten of 171 trials (5.9%) reported potentially misleading results. Pharmaceutical industry-funded trials were more likely to be double-blinded (28.1% vs 10.3%; P = .03) and to describe missing data handling (78.5% vs 59.0%; P = .02). The overall risk of bias was low in 96 of 160 studies (60.0%). CONCLUSIONS: ARV NI-RCTs should improve NI margin justification, reporting of intention-to-treat and per-protocol analyses, and missing data handling to increase CONSORT adherence.

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. (Systematic Review Registration Number PROSPERO CRD42020219497).

Secondary Analysis of a Systematic Review: Are Antifungal Noninferiority Trials at Risk of Eroding Effectiveness Because of Biocreep?

Noninferiority randomized controlled trial (RCT) effectiveness may erode when results favor the active control over time and when a decreasingly effective control arm is used in serial trials. We analyzed 32 antifungal noninferiority RCTs (NI-RCTs) for these scenarios in this secondary analysis of a systematic review. Our exploratory analysis suggests that the erosion risk in the effectiveness of antifungal noninferiority trials is uncommon. Findings are limited by small sample size and overall risk of bias.