Hodi 2014.

Study characteristics
Methods	Phase III parallel‐group RCT. Open label study. Multicentre trial.
Participants	Untreated and previously treated (1 chemotherapy was allowed) metastatic melanoma. Patients randomised: 245.
Interventions	Two‐arm study: ipilimumab, 10 mg/kg, every 3 weeks IV for 4 doses then every 12 weeks + sargramostim (yeast‐derived, rhu GM‐CSF), 250 μg total dose SC on days 1 to14 of 21‐day cycle (N = 123); ipilimumab, 10 mg/kg, every 3 weeks IV for 4 doses then every 12 weeks (N = 122).
Outcomes	Overall survival. Progression‐free survival. Tumour response. Toxicity.
Notes	Cross‐over: not allowed. Quality of life: not reported. Participants with brain metastasis: excluded. Median follow‐up: 13 months.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Stratified randomization based on permuted blocks within strata with dynamic institution balancing was used." Comment: Randomisation method was adequate.
Allocation concealment (selection bias)	Low risk	Quote: "Treatment assignments were obtained from the central randomization desk at the ECOG coordinating center." Comment: 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	Quote: "Tumor responses were determined by the investigators using RECIST (Response Evaluation Criteria in Solid Tumors) criteria and were audited as a part of ECOG‐ACRIN (American College of Radiology Imaging Network) standard procedures." Comment: It was unclear if this method was sufficient to ensure 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.