Postow 2015.

Study characteristics
Methods	Phase I dose‐escalation parallel‐group RCT. Double‐blinded study.
Participants	Untreated metastatic melanoma. Participants randomised: 142.
Interventions	Two‐arm trial: Nivolumab 1 mg/kg every 3 weeks, and ipilimumab 3 mg/kg every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg every 2 weeks for cycle 3 and beyond (N = 95); Ipilimumab 3 mg/kg every 3 weeks for 4 doses, followed by placebo every 2 weeks for cycle 3 and beyond (N = 47).
Outcomes	Progression‐free survival. Tumour response. Toxicity.
Notes	Cross‐over: cross‐over was allowed at disease progression. Quality of life: not reported. Participants with brain metastasis: excluded. Median follow‐up: > 11 months.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were 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	Quote: "Double‐blind trial". Comment: The method ensured low risk of performance bias.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Double‐blind trial". Comment: The method ensured low risk of detection bias.
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)	Low risk	No differences between protocol and published report.
Other bias	Low risk	The study appeared to be free of other sources of bias.