Eton 2002.

Study characteristics
Methods	Phase III parallel‐group RCT. Open label study.
Participants	Untreated metastatic melanoma. Number of participants: 183.
Interventions	Two‐arm trial: Chemotherapy: cisplatin 20 mg/m² on days 1 to 4 and 22 to 25, vinblastine 2 mg/m² on days 1 to 4 and 22‐25, and dacarbazine 800 mg/m² on days 1 and 22, 2 x 21‐day cycles over a 6‐week period (N = 92); Biochemotherapy: cisplatin 20 mg/m² on days 1 to 4 and 22 to 25, vinblastine 1.5 mg/m² on days 1 to 4 and 22‐25, and dacarbazine 800 mg/m² on days 1 and 22, IL‐2 9 mIU/m² 24 h continuous infusion on days 5 to 8, 17 to 20, and 26 to 29, and IFN‐α 5 mU/m² SC on days 5 to 9, 17 to 21, and 26 to 30, 2 x 21‐day cycles over a 6‐week period (N = 91).
Outcomes	Progression‐free survival. Overall survival. Tumour response. Toxicity.
Notes	Cross‐over: allowed at disease progression. Quality of life: not reported. Participants with brain metastasis: excluded. Median follow‐up: 52 months
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "...randomly assigned". Comment: There was insufficient information about the sequence generation process to permit judgment.
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 judgement.
Incomplete outcome data (attrition bias) All outcomes	Low risk	There was insufficient information to permit judgment.
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.