Thomson 1993.

Study characteristics
Methods	Phase III parallel‐group RCT. Open label study.
Participants	Untreated metastatic melanoma. Randomised participants: 170.
Interventions	Two‐arm trial: Dacarbazine 800 mg/m² IV on day 1 every 3 weeks (N = 83); Darbazine IV on day 1 every 3 weeks dose was escalated from 200 mg/m² to 400 mg/m² to 800 mg/m² every 3 weeks if blood counts allowed and stayed at this dose thereafter, + IFN SC daily 3 times a week at a staring dose of 3 mU for 3 days, then 9 mU for 67 days, and thereafter 9 mU 3 times a week (N = 87).
Outcomes	Overall survival. Tumour response. Toxicity.
Notes	Quality of life: analysis of quality of life was reported in a different article (Coates 1993). There was no statistically significant difference in quality of life between treatment arms. Cross‐over: not allowed. Participants with brain metastasis: excluded. Median follow‐up: not available.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomised centrally using a dynamic randomisation technique." Comment: This method ensured low risk of selection bias.
Allocation concealment (selection bias)	Unclear risk	There was insufficient information to permit judgment.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	As an open label study, no blinding of participants or personnel was possible. However, we believe that in this setting (metastatic melanoma), with the treatments tested and outcomes assessed, the knowledge of which intervention was received or administered (rather than the intervention itself), could not affect the outcomes under investigation. Therefore, we judged the risk of performance bias as low.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	There was insufficient information to permit judgment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing outcome data were balanced across intervention groups, with similar reasons for missing data across groups.
Selective reporting (reporting bias)	Unclear risk	Published reports included all expected outcomes. However, no protocol was available so it was unclear if all planned outcomes were reported.
Other bias	Low risk	The study appeared to be free of other sources of bias.