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].