Systematic evaluation of non-inferiority and equivalence randomized trials of anti-infective drugs.

The non-inferiority (NI) and equivalence (EQ) design is used widely in the clinical trials of anti-infective drugs, but still many arguments for, and against, conducting active control NI/EQ trials rather than simple placebo controlled trials. We searched Pubmed database and conducted a systematic literature review (1992-2011) to assess the methodological aspects of NI and EQ randomized trials of anti-infective drugs. A total of 335 publications with 337 trials were included. Of them, 235 trials reported a pre-specified margin of 10-15%. A proportion (e.g., cure, successful, failure) was used as the primary outcome in 316 trials (93.8%). Test treatments were non-inferior or equivalent to the control treatment in 325 trials (93.4%). The historical evidence for the effect of the control drug was specified in 38 trials (11.3%). For the literature of NI/EQ trials in anti-infective treatment, aspects that need improvement include the description of study participation, trial implementation, historical evidence and endpoint for the efficacy of control, inclusion of flow diagrams and figures that present margins and confidence intervals according to CONSORT criteria.