Avril 2004.

Study characteristics
Methods	Phase III parallel‐group RCT. Open label study. Multicentre trial.
Participants	Untreated metastatic melanoma. Participants randomised: 229.
Interventions	Two‐arm trial: Fotemustine 100 mg/m² weekly for 3 consecutive weeks (days 1, 8, and 15) followed by a 5‐week rest period (N = 112); Dacarbazine 250 mg/m² daily for 5 days every 4 weeks (N = 117).
Outcomes	Progression‐free survival. Overall survival. Tumour response. Toxicity.
Notes	Cross‐over: not allowed. Quality of life: no significant difference was observed between treatment arms. Participants with brain metastasis: included. Median follow‐up: not available.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomly assigned". Comment: Risk was likely low because this was a multicentre trial with centralised randomisation.
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	Unclear risk	Quote: "An independent centralized radiologic committee (two radiologists not involved in the study) performed a blinded review of all radiologic files of patients who had CR, PR, or stable disease on the investigator’s evaluation. Imaging of patients declared progressive disease (PD) as a best response were not reviewed." 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 in across intervention groups, with similar reasons for missing data across groups.
Selective reporting (reporting bias)	Unclear risk	Published reports included all expected outcomes. However, no protocol was available so it was unclear if all planned outcomes were reported.
Other bias	Low risk	The study appeared to be free of other sources of bias.