Hordinsky 2010.

Methods	Randomised controlled, parallel‐group design This was a multi‐centre study conducted at 57 centres in 7 countries (Austria, Canada, Denmark, Hungary, Italy, Norway, USA)
Participants	652 (246 male, 406 female) with diagnosis of mild to moderate hand dermatitis as defined by IGA 555 participants completed the double‐blind phase, 544 (269 in the pimecrolimus group and 275 in vehicle group) entered the open extension phase, and 512 (248 and 264, respectively) completed the study Inclusion criteria of the trial History of hand eczema (according to IGA: mild to moderate) of at least 90 days' duration Minimum age of 18 years Exclusion criteria of the trial Medication or concomitant conditions that could interfere with conduct of the study or results Immunocompromised participants History of malignant disease Endogenous dermatoses: dyshidrotic dermatitis, psoriasis of the hands, flares of atopic dermatitis Study population Gender: pimecrolimus group 185 female, 130 male; vehicle group 211 female, 116 male Age: pimecrolimus group mean 43.9 years, SD 14.4 years, range 18 to 84 years; vehicle group mean 44.1 years, SD 15.1 years, range 18 to 85 years
Interventions	Intervention • Pimecrolimus 1% ointment twice daily with daily occlusion by use of vinyl gloves of at least 6 hours after second (evening) application for up to 43 weeks in 325 participants Control intervention • Vehicle ointment twice daily with daily occlusion by use of vinyl gloves of at least 6 hours after second (evening) application for up to 43 weeks in 327 participants Duration Up to 43 weeks
Outcomes	Primary outcome of the trial Investigators Global Assessment (IGA) of the target hand at day 43 or at time of early discontinuation (according to trial registration, not clear from article) (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe) Other outcomes Observer rated: clear or almost clear of hand dermatitis at end of trial as defined by IGA (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe) at weekly intervals Participant‐rated: pruritus severity 0 to 3 (0 = absent, 3 = severe) at weekly intervals Participant‐rated: burning sensation/severity of burning 0 to 3 (0 = absent, 3 = severe) Safety and tolerability (adverse events)
Notes	Participants could enter open‐label phase before 42nd day if hand dermatitis had remained cleared on 2 consecutive weekly assessments. However, efficacy comparisons were made at day 42 in intention‐to‐treat analysis. Not clear how many participants were blind to treatment during assessments at days 29, 36, and 43, as open‐label phase could already have started We were unable to obtain additional information from study authors Declarations of interest: one study author was an employee of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Funding: the study was supported by Novartis Pharma AG, manufacturer of the study drug Sample size rationale: provided
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "eligible patients were randomized in a 1:1 ratio to receive..." Quote: "randomization was performed using a validated automated system and was stratified by baseline IGA score at each centre" Comment: randomisation method was considered adequate
Allocation concealment (selection bias)	Unclear risk	No details about how allocation was concealed from participants and clinicians
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "...double‐blind and vehicle‐controlled..." Comment: study authors state double‐blinded design, although unclear whether pimecrolimus and vehicle were identical in appearance
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "...double‐blind and vehicle‐controlled..." Comment: double‐blind study; however, insufficient details are given about investigator blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "all the efficacy assessments were done in the intent‐to‐treat population using a last observation carried forward approach" Comment: intention‐to‐treat analysis
Selective reporting (reporting bias)	Unclear risk	Trial registration was found on clinicaltrials.gov (NCT00226707) Work productivity and activity impairment questionnaires are included in the trial registration but are not mentioned in the article The trial register stated that the primary outcome was IGA on day 43, although this is not clearly stated in the article
Other bias	Low risk	Baseline comparisons conducted: "there were no clinically relevant differences in baseline demographic characteristics or disease history between the pimecrolimus cream 1% and vehicle groups" Diagnostic certainty: yes The study was completed