Bissonnette 2010.

Methods	Parallel‐group, placebo‐controlled, randomised study with participants who initially responded in a previous BACH study (Ruzicka 2008), but who relapsed in the observational period This study was carried out in a secondary care setting This was a multi‐centre study conducted in Canada, France, and Germany
Participants	117 participants with chronic hand eczema who relapsed after they were successfully treated with alitretinoin 30 mg, 10 mg, or placebo Dropouts: 24 Inclusion criteria of the trial Participants who relapsed after successful treatment with alitretinoin or placebo in a previous trial (Ruzicka 2008) Exclusion criteria of the trial Well defined Study population Gender: placebo group 23 female, 24 male; alitretinoin 10 mg 5 female, 15 male; alitretinoin 30 mg 24 female, 25 male Age: mean placebo group 50.4 years; alitretinoin 10 mg 49.0 years; alitretinoin 30 mg 52.0 years
Interventions	Intervention • Alitretinoin 10 mg once daily for 12 to 24 weeks in 21 participants • Alitretinoin 30 mg once daily for 12 to 24 weeks in 49 participants Control intervention • Placebo for 12 to 24 weeks in 47 participants Participants were re‐treated with the same dose that they had received in the previous study, or they were treated with placebo Participants who were initially treated with placebo in the first trial were treated with placebo again No other topical or systemic therapy for hand eczema was allowed Duration 12 to 24 weeks
Outcomes	Primary outcome of the trial Physician's Global Assessment (PGA): whereby physician global assessment is categorised as clear, almost clear, mild, moderate, severe. Responders were defined as clear or almost clear at week 12 or last evaluation Other outcomes Patient's Global Assessment (PaGA) Modified Total Lesion Symptom Score (mTLSS) Extent of disease Time to response Adverse events
Notes	Study included participants who relapsed after successful treatment in a previous study (Ruzicka 2008). No other active treatment as comparator. Analysis of efficacy based on intention‐to‐treat principle. Study included a safety assessment by careful medical and laboratory monitoring. The primary outcome percentages of participants with self‐rated good/excellent and secondary outcome reduction in severity, investigator‐rated scoring were included in the study, but we were unable to reproduce the data Study authors were contacted and referred us for further information to GSK, which provided additional information Declarations of interest: various study authors were investigators or consultants for Basilea Pharmaceutica International Ltd. Funding: the study was supported and funded by Basilea Pharmaceutica International Ltd, Basel, Switzerland, the manufacturer of alitretinoin. Study authors were investigators in Basilea clinical trials, or were consultants or employees of Basilea Pharmaceutica International Ltd. Sample size rationale: not stated Quote: "the sample size was not prespecified, and all relapsing patients from the BACH trial were eligible for trial screening"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "patients were randomised to the same dose they received in the BACH study or to placebo" Comment: no further details given. In personal communication, the study authors clarified: "the study was a follow on from the BACH study BAP00089, which was a randomised double blind placebo controlled study of subjects in a 2:2:1 randomisation of treatment to alitretinoin 30 mg, alitretinoin 10 mg, or placebo, respectively. Patients who responded in study BAP00089 and relapsed during the posttreatment observation period were assigned to the same dose they had received or to placebo in a 2:1 ratio. Responding patients who had received placebo in study BAP00089 were assigned to continue receiving placebo. Each was assigned a coded allocation of study drug containing either placebo or a dosage of active drug. The randomisation was computer generated"
Allocation concealment (selection bias)	Unclear risk	No details about how allocation was concealed from participants and investigators. In personal communication, the study authors stated: "it is unclear how this knowledge was imparted, but it is clear from the protocols that those subjects who had received placebo in the original trial BAP00089, and who had been successfully treated but had subsequently relapsed, would upon entering this study be given placebo again, as it was considered unethical to expose them unnecessarily to drug"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "the investigator, sponsor and all participants remained blinded throughout the course of the BACH and re‐treatment studies" Comment: Study authors stated that they conducted a double‐blind study but made no statements about how this was done Quote: "the placebo and active drug were indistinguishable and packaged in the same way" Comment: use of identical packages is a sufficient form of blinding; however it is unclear whether site staff were also blinded because the study was a follow‐up study in which most participants received the same treatment as in the previous study Personal communication clarified: "a list of treatment assignments was sealed and kept in a central repository by the Biometrics Department and by the Drug Safety Department. No open key to the code was available at the Study Center, or to monitors or members of the project team"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Investigators were blinded throughout the study; however no details regarding blinding were given. The observers might have been the same as in the study of Ruzicka 2008. Personal communication clarified: "the investigator had access to coded, sealed envelopes for each participant to be used in an emergency that would have required knowledge of the study medication to manage the emergency. If the investigator wished to know the identity of the treatment given to study subjects for any other purpose, this request was first to be discussed with Basilea Pharmaceutica"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "efficacy evaluations are based on the intention‐to‐treat population, which included all randomized patients" Comment: intention‐to‐treat analysis
Selective reporting (reporting bias)	Low risk	The trial was registered at clinicialtrials.gov (NCT00124436 and BAP00091 and EUCTR2004‐000432‐85‐HU). No major changes in primary or secondary outcomes. The only difference is that the trial registration states enrolment of 300 participants, and the actual trial included only 117 participants; this was done so all participants from the BACH study who relapsed could be included
Other bias	Low risk	Baseline comparison of disease severity in table, but no significance of differences in tests provided. Personal communication clarified that there were no statistically significant differences Diagnostic certainty: yes The study was completed