Poor methods, incomplete data, reporting errors. Prospective or retrospective. RCT, randomized controlled trial. Table 11 | GRADE system for grading quality of evidence Step 1: Starting grade for quality of evidence based on study design Step 2: Reduce grade Step 3: Raise grade Final grade for quality of evidence and definition Randomized trials = High Observational study = Low Study quality 1 level if serious limitations 2 levels if very serious limitations Consistency 1 level if important inconsistency Directness 1 level if some uncertainty 2 levels if major uncertainty Other 1 level if sparse or imprecise datac 1 level if high probability of reporting bias Strength of association +1 level if stronga , no plausible confounders +2 levels if very strongb , no major threats to validity Other +1 level if evidence of a dose response gradient +1 level if all residual plausible confounders would have reduced the observed effect High = Further research is unlikely to change confidence in the estimate of the effect Moderate = Further research is likely to have an important impact on confidence in the estimate of effect, and may change the estimate Low = Further research is very likely to have an important impact on confidence in the estimate, and may change the estimate Any other evidence = Very Low Very Low = Any estimate of effect is very uncertain GRADE, Grading of Recommendations Assessment, Development and Evaluation. a Strong evidence of association is defined as significant relative risk of 42 (o0.5) based on consistent evidence from two or more observational studies, with no plausible confounders. b Very strong evidence of association is defined as significant relative risk of 45 (o0.2) based on direct evidence with no major threats to validity. c Sparse if there is only one study or if total N o500. 