Schwartzentruber 2011a.

Study characteristics
Methods	Phase III parallel‐group RCT. Open label study. Multicentre trial.
Participants	Untreated metastatic melanoma. Randomised participants: 185.
Interventions	Two‐arm trial: IL‐2 720,000 IU/kg every 8 hours up to a maximum of 12 doses per cycle every 3 weeks (N = 94); gp100:209‐217(210M) plus incomplete Freund’s adjuvant once per cycle, followed by IL‐2 720,000 IU/kg every 8 hours up to a maximum of 12 doses per cycle every 3 weeks (N = 91).
Outcomes	Overall survival. Progression‐free survival. Tumour response. Toxicity.
Notes	Quality of life: not reported. Cross‐over: not allowed. Participants with brain metastasis: excluded. Median follow‐up: 41 months.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Stratified randomization was performed with the use of random block sizes to ensure balance with respect to a potentially important prognostic feature." Comment: Randomisation method was adequate.
Allocation concealment (selection bias)	Low risk	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	Low risk	Quote: "...blinded central radiologic review". 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.