Hudes 2007.

Study characteristics
Methods	Study type: multicentre RCT Phase: 3 Accrual period: June 2003 to April 2005 Blinding: imaging Strata: according to the geographic location of the centre and nephrectomy status IMC: an independent data and safety monitoring committee reviewed the study at 6‐month intervals Crossover: not allowed
Participants	Histology: all histologies Prior therapy: naïve Measurable disease: required (RECIST)Non metastatic %: <20M/F: 432/194 Eligible PS: Karnofsky > 50; actual KPS( > 70) = 17% Age median (range): 59 (23 to 86) Prior nephrectomy: 419 Prognostic strata: system, % good/intermediate/poor risk: MSKCC, ‐/26/74%
Interventions	TEMSIROLIMUS 25mg IV weekly, Interferon‐a2a 3‐18MU sc tiw, or both
Outcomes	PFS: secondary endpoint OS: primary endpoint AE: reported in toxicity table QoL: reported RR: (RECIST) Other: ‐
Funding Sources	Industry sponsored
Declarations of interest	Reported in main publication
Notes	Only poor risk (76%) and intermediate risk (26%) patients included in trial
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were randomly assigned in equal proportions, with the use of permuted blocks of three, to one of three treatment groups." Central randomisation presumed
Allocation concealment (selection bias)	Low risk	"Patients were randomly assigned in equal proportions, with the use of permuted blocks of three, to one of three treatment groups." Central randomisation presumed
Blinding of participants and personnel (performance bias) Objective outcomes	Low risk	Participants and personnel were not blinded to treatment, no effects on OS expected
Blinding of participants and personnel (performance bias) Subjective outcomes	High risk	Participants and personnel were not blinded to treatment, active treatment in all 3 groups
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Unblinded clinical investigator assessment, no effects on OS expected
Blinding of outcome assessment (detection bias) Subjective outcomes	High risk	Shorter investigator assessed PFS in comparison to independent radiologic assessment; which is explained by different inclusion criteria
Incomplete outcome data (attrition bias) PFS, OS	Low risk	Intention‐to‐treat population reported
Incomplete outcome data (attrition bias) Response rate	High risk	82% of ITT population reported; only selected participants included in analysis which underwent tumour assessment after the baseline
Incomplete outcome data (attrition bias) Serious and minor adverse events	Low risk	All treated participants reported
Incomplete outcome data (attrition bias) Quality of life	High risk	65% of participants were evaluable for QoL analysis
Selective reporting (reporting bias)	Low risk	All planned outcomes reported
Other bias	Low risk	Completed planned accrual; stopped early at the second interim analysis