Chapman 1999.

Study characteristics
Methods	Phase III parallel‐group RCT. Open label study. Multicentre trial.
Participants	Untreated metastatic melanoma. Number of randomised participants: 240.
Interventions	Two‐arm study: Polychemotherapy (Dartmouth regimen): Dacarbazine 220 mg/m² IV and cisplatin 25 mg/m² IV days 1 to 3, carmustine 150 mg/m² IV day 1 every other cycle, and tamoxifen 10 mg orally twice daily every 3 weeks (N = 119); Single agent chemotherapy: Dacarbazine 1000 mg/m² IV every 3 weeks (N = 121).
Outcomes	Overall survival. Tumour response. Toxicity.
Notes	Cross‐over: cross‐over to polychemotherapy was allowed at disease progression. Quality of life: not reported. 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 randomized". Comment: Risk was likely low because this was a multicentre trial with centralised randomisation.
Allocation concealment (selection bias)	Low risk	Risk was likely low because this was a multicentre trial with centralised randomisation.
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 judgement.
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.