Carter 1975.

Study characteristics
Methods	Phase III parallel‐group RCT. Open label study.
Participants	Untreated and previously treated metastatic melanoma. Number of participants:270.
Interventions	Four‐arm trial: Dacarbazine 4.5 mg/kg IV days 1 to 10 (N = 48); Dacarbazine 2.7 mg/kg IV days 1 to 5, lomustine 1.5 mg/kg orally day 2, and vincristine 0.027 mg/kg IV days 1, 5 every 6 weeks (N = 67); Dacarbazine 2.7 mg/kg IV days 1 to 5, carmustine 2.0 mg/kg IV day 2, and vincristine 0.027 mg/kg IV days 1, 5 every 6 weeks (N = 64); Dacarbazine 2.7 mg/kg IV days 1 to 5, carmustine 2.0 mg/kg IV day 2, and hydroxyurea 30 mg/kg IV days 2, 5, 9, 12, 16, 19 (N = 63).
Outcomes	Progression‐free survival. Overall survival. Tumour response. Toxicity.
Notes	Cross‐over: not allowed. Quality of life: not reported. Participants with brain metastasis: included. Median follow‐up: not available.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomised". Comment: There was insufficient information 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 judgment.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	There was insufficient information to permit judgment.
Selective reporting (reporting bias)	Unclear risk	There was insufficient information to permit judgment.
Other bias	Unclear risk	There was insufficient information to permit judgment.