Belsito 2004.

Methods	Parallel‐group, randomised controlled trial The study was carried out in a secondary care setting This was a multi‐centre study that was conducted in Brazil, Canada, and the USA
Participants	294 participants with mild to moderate chronic hand eczema (117 irritant, 94 endogenous, 32 irritant + endogenous, 32 irritant + allergic, 9 allergic, 4 allergic + endogenous, 4 irritant + allergic + endogenous, 2 unknown aetiology) Dropouts: 22 Inclusion criteria of the trial At least 18 years old Mild to moderate chronic hand eczema for a minimum duration of 6 weeks Exclusion criteria of the trial Pregnancy Treatments that possibly interfere with study evaluations Hand‐foot‐and‐mouth disease Contact urticaria Severe vesicobullous dermatitis of hands Latex allergy Mosaic warts History of malignancies or current pre‐malignant disease of hands Concurrent flaring atopic dermatitis Psoriasis or skin disease of hands requiring therapy Use of systemic therapy in previous month and use of systemic antibiotics for hand infection or topical therapy within the previous 7 days Study population Gender: 176 female, 118 male Age: mean age 44.6 years, range 18 to 86 years
Interventions	Intervention • Pimecrolimus 1% cream twice daily with 6 hours of love occlusion in the evenings for 3 weeks in 140/151 participants Control intervention • Vehicle cream twice daily with 6 hours of glove occlusion in the evenings for 3 weeks in 132/143 participants Barrier creams or emollients were allowed in both groups if applied more than 1 hour before study cream Duration 3 weeks
Outcomes	Primary outcomes of the trial Investigator Global Assessment (IGA) on a 5‐point scale: ranging from 0 = clear to 4 = severe Efficacy measured was proportion of treatment successes at end of study (day 22) in each group; treatment success was defined as an IGA score of 0 (clear) or 1 (almost clear) Other outcomes Adverse events
Notes	Overall efficacy (proportion of treatment successes) for both groups at end of study presented as graph (bar chart); exact figures not given. In separate table, exact figures for treatment successes, with strata of selected groups overlapping ("to identify groups highly responsive") Study authors contacted by email and LinkedIn 27 February 2014, but we were unable to obtain additional information Declarations of interest: some study authors were employees of pharmaceutical companies Funding: the study was supported by a grant from Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, which is the manufacturer of pimecrolimus cream. Four study authors had an ongoing financial relationship with Novartis, and four were employees of Novartis Sample size rationale: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "a multicenter, randomized, vehicle‐controlled 3 week study..." Comment: the article states only that subjects were randomised, without further information. Insufficient information provided to judge the risk of bias
Allocation concealment (selection bias)	Unclear risk	No details about how allocation was concealed from participants and investigators
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "study design ‐ the study was a double‐blind, multicenter, vehicle‐controlled trial of ...." Comment: unclear; participants and personnel probably blinded as this is stated in the paper, but no further details are given. It is unclear whether vehicle and placebo were identical in appearance
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "study design ‐ the study was a double‐blind, multicenter, vehicle‐controlled trial of ...." Comment: no details regarding blinding of observers
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "the intention‐to‐treat (ITT) and safety populations consisted of all randomized patients who received the study medication, and the per‐protocol population included all patients from the ITT population who did not violate the protocol in ways that would affect efficacy evaluations" Comment: intention‐to‐treat analysis
Selective reporting (reporting bias)	Low risk	No trial registration found; however all outcomes listed in the Methods section are described in the Results section
Other bias	Low risk	Baseline comparisons: no significant differences in demographic or disease characteristics between groups Diagnostic certainty: yes The study was completed