Danson 2003.

Study characteristics
Methods	Phase II parallel‐group RCT. Open label study.
Participants	Untreated metastatic melanoma. Number of participants: 181.
Interventions	Three‐arm trial: Temozolomide 200 mg/m² orally at 8‐hour intervals, 5 doses every 4 weeks (N = 59); Temozolomide 200 mg/m² orally once daily for 5 days, IFN‐α‐2b 5 mIU SC every Monday, Wednesday, and Friday for 5 doses every 4 weeks (N = 62); Temozolomide 150 mg/m² orally once daily for 5 days, thalidomide 100 mg given orally once daily for 28 doses every 4 weeks (N = 60).
Outcomes	Progression‐free survival. Overall survival. Tumour response. Toxicity.
Notes	Cross‐over: not allowed. Quality of life: no significant difference was noted between arms. Participants with brain metastasis: included. Median follow‐up: 6 months.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomly assigned, using permuted blocks". Comment: Randomisation method was adequate.
Allocation concealment (selection bias)	Unclear risk	There was insufficient information to permit judgment.
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	There was insufficient information to permit judgement.
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)	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.