Certainty of evidence
The certainty (quality) of the evidence of efficacy, safety and economic impact was rated for each outcome as high, moderate, low or very low, following the GRADE approach and the standard GRADE domains (risk of bias, imprecision, inconsistency, indirectness, and publication bias) (24,25). For the evaluation of imprecision for each outcome the following thresholds for the minimal important difference (MID) were considered when available: 8.7 points for Scoring Atopic Dermatitis (SCORAD) (26,27); 6.6 points for Eczema Area and Severity Index (EASI) (27,28); 4 points for Patient-Oriented Eczema Measure (POEM) (27,29); 4 points for the Dermatology Life Quality Index (DLQI) (30); 6 points for Children’s DLQI (CDLQI) (31); 3 points for numerical rating scale (NRS) for adults (32,33) and 4 points for adolescents (31); 8 points or less for the Hospital Anxiety and Depression Scale of anxiety (HAD-A) or depression (HADS-D) (34).