Grading the strength of evidence
We graded the strength of evidence for the association between use of nitazoxanide and the outcomes of interest as high, moderate, low, or very-low using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) rating system [11,12]. In the GRADE system, RCTs begin as high-quality evidence but may be downrated according to the risk of bias assessment, inconsistency, indirectness, imprecision in the results, and publication bias [13]. Certainty is uprated for estimates with large (RR > 2.0 or RR < 0.5) or very-large (RR > 5.0 or RR < 0.2) magnitude of effect.
Although the funnel plot asymmetry was not evaluated, we reduced the potential for publication bias planning a comprehensive search including grey-literature without restrictions. In this criterion, we analyzed discrepancies in findings between studies and the influence of small trials (< 100 patients per arm) on estimated treatment effects. The influence of small trials on the pooled estimates was analyzed using a “leave-one-out” sensitivity approach [14].