O'Day 2011.

Study characteristics
Methods	Phase II parallel‐group RCT. Double‐blind study.
Participants	Untreated metastatic melanoma. Randomised participants: 129.
Interventions	Four‐arm study: Dacarbazine 1000 mg/m² every 3 week (N = 32): Dacarbazine 1000 mg/m² and intetumumab 10 mg/kg every 3 weeks (N = 32); Intetumumab 10 mg/kg every 3 weeks (N = 33); Intetumumab 5 mg/kg every 3 weeks (N = 32).
Outcomes	Progression‐free survival. Overall survival. Tumour response. Toxicity.
Notes	Cross‐over: quote "Patients in the blinded dacarbazine‐containing arms who could not tolerate dacarbazine were allowed to cross‐over to open‐label 10 mg/kg intetumumab monotherapy, and those on dacarbazine monotherapy who experienced progressive disease (PD) were allowed to cross over to open‐label dacarbazine plus10 mg/kg intetumumab". Quality of life: not reported. Participants with brain metastasis: excluded. Median follow‐up: 24 months.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Randomisation was stratified". 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	Quote: "...blinded". Comment: The method ensured low risk of performance bias.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "...blinded". 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.