Thestrup‐Pedersen 2001.

Methods	Parallel‐group, randomised controlled trial This study was conducted in a secondary care setting at 4 dermatology departments or clinics in Denmark
Participants	29 participants (21 male, 8 female) with hyperkeratotic eczema on palms, patch‐test negative or irrelevant No dropouts Inclusion criteria of the trial Hand eczema based on clinical diagnosis Exclusion criteria of the trial Allergic contact dermatitis Study population Gender: 8 female, 21 male Age: median 54 years, range 30 to 76 years
Interventions	Intervention • Acitretin orally 30 mg daily for 8 weeks in 14/14 participants Control intervention • Placebo capsules for 8 weeks in 15/15 participants Both groups were allowed to use topical emollients Duration 8 weeks
Outcomes	Primary outcomes of the trial Not defined Other outcomes Mean observer‐rated severity scores (0 = absent, 1 = slight, 2 = moderate, 3 = severe) combined of these signs: hyperkeratosis, fissures, scaling, itch, redness, and vesicles at week 4 and at week 8 Change in biochemical parameters (Hb, hepatic function, cholesterol, triglyceride) Adverse events
Notes	We contacted the study author for additional information by letter; however he was unable to respond to all of our questions No overall scores were presented as outcomes. Details of biochemical parameters were not given A proper between‐group comparison was not conducted; only within‐group comparisons with Wilcoxon‐rank sum test were conducted The study did include the secondary outcomes ‐ reduction in severity, participant‐ and investigator‐rated ‐ although we were unable to include these data because of missing data Declarations of interest: none declared Funding: Roche A/S, Copenhagen, supplied the study drug free of charge, but the investigators did not receive financial support nor consultant fees from Roche Sample size rationale: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "they were asked to take three 10‐mg capsules of acitretin once daily for 8 weeks or identically looking placebo capsules" Comment: from the article, it is unclear whether the study was randomised at all. Personal communication with study authors clarified that randomisation was done by a third party according to a pre‐defined randomisation list
Allocation concealment (selection bias)	Low risk	No details about how allocation was concealed from participants and clinicians. Personal communication clarified that the sponsor shipped 4 identical boxes to all participating centres, which could at random be dispensed to participants. The investigators were unaware of the content of the boxes; therefore we judged this as low risk
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "they were asked to take three 10‐mg capsules of acitretin once daily for 8 weeks or identically looking placebo capsules" Comment: the study contained an identical looking placebo in an attempt to blind participants, and randomisation and dispensation of drugs were done at a remote site by a third party. Therefore we judged this as adequate blinding of participants
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "as several patients in the active treatment group experienced dryness of the lips, we have called our study single‐blind" Comment: study authors declared this a single‐blind study because the observers could have guessed the acitretin group due to adverse events of acitretin
Incomplete outcome data (attrition bias) All outcomes	Low risk	None of the participants dropped out, and all participants were included in the analyses
Selective reporting (reporting bias)	Low risk	No trial registration found. However we found no major discrepancies between Methods and Results sections
Other bias	Unclear risk	Baseline comparisons: not stated whether there was a significant difference in disease severity between groups Diagnostic certainty: yes The study was completed