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

Background Antibiotic non-inferiority randomized controlled trials (RCTs) are used for approval of new antibiotics and making changes to antibiotic prescribing in clinical practice. We conducted a systematic review to assess the methodological and reporting quality of antibiotic non-inferiority RCTs. Methods We searched MEDLINE, Embase, the Cochrane Database of Systematic Reviews and the FDA drug database from inception until Nov 22, 2019 for non-inferiority RCTs comparing different systemic antibiotic therapies. Comparisons between antibiotic types, doses, administration routes or durations were included. Methodological and reporting quality indicators were based on the CONSORT reporting guidelines. Two independent reviewers extracted the data. Results The systematic review included 227 studies. Of these, 135 (59.5%) studies were supported by pharmaceutical industry. Only 83 (36.6%) studies provided a justification for the non-inferiority margin. Reporting of both intention-to-treat (ITT) and per-protocol (PP) analyses were done in 165 (72.7%) studies. The conclusion was misleading in 34 (15.0%) studies. The studies funded by pharmaceutical industry were less likely to be stopped early due to logistical reasons (3.0% vs. 19.1%, OR=0.13 95% CI 0.04-0.37) and to show inconclusive results (11.1% vs. 42.9%, OR=0.17 95% CI 0.08-0.33). The quality of studies decreased over time with respect to blinding, early stopping, reporting of ITT with PP analysis and having misleading conclusions. Conclusions There is room for improvement in the methodology and reporting of antibiotic non-inferiority trials. Quality can be improved across the entire spectrum from investigators, funding agencies, as well as during the peer-review process.