Sternberg 2010.

Study characteristics
Methods	Study type: multicentre RCT Phase: 3 Accrual period: April 2006 to April 2007 Blinding: double‐blind, placebo‐controlled Strata: ECOG PS 0vs1; nephrectomy status; prior cytokine IMC: responsible for safety monitoring and to review interim overall survival data Crossover: allowed from placebo to active treatment
Participants	Histology: clear cell Prior systemic therapy: 1 line of cytokines permitted. Measurable disease: required Non metastatic %: < 18 M/F: 307/128 Eligible PS: ECOG 0 to 1 Age median(range): 59 (25 to 85) Prior nephrectomy: 385 Prognostic strata: system, good/intermediate/poor risk %: MSKCC; 39/54/3
Interventions	(1) PAZOPANIB 800 mg PO daily, vs (2) matched PLACEBO (2:1 randomization) Cross‐over 48%
Outcomes	PFS: primary endpoint OS: principal secondary end point AE: toxicity table available, additional secondary end point QoL: reported RR: additional secondary end point Other: ‐
Funding Sources	Industry sponsored
Declarations of interest	Reported
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were centrally randomly assigned in a 2:1 ratio..."; central randomisation
Allocation concealment (selection bias)	Low risk	"Patients were centrally randomly assigned in a 2:1 ratio..."; central randomisation
Blinding of participants and personnel (performance bias) Objective outcomes	Low risk	"was a placebo‐controlled, randomized, double‐blind, global, multicenter, phase III study"; participants and personnel were masked to treatment
Blinding of participants and personnel (performance bias) Subjective outcomes	Low risk	"was a placebo‐controlled, randomized, double‐blind, global, multicenter, phase III study"; participants and personnel were masked to treatment
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	"All imaging scans were evaluated by an independent imaging‐review committee (IRC) blinded to study treatment"
Blinding of outcome assessment (detection bias) Subjective outcomes	Low risk	"All imaging scans were evaluated by an independent imaging‐review committee (IRC) blinded to study treatment"
Incomplete outcome data (attrition bias) PFS, OS	Low risk	All patients accounted for, losses 6% (investigational) and 3% (control) unlikely significant, “completion rates > 90% across most of the assessment time points”
Incomplete outcome data (attrition bias) Response rate	Low risk	All patients accounted for, losses 6% (investigational) and 3% (control) unlikely significant, “completion rates > 90% across most of the assessment time points”
Incomplete outcome data (attrition bias) Serious and minor adverse events	Low risk	All treated participants analysed
Incomplete outcome data (attrition bias) Quality of life	Low risk	"Completion rates for QoL questionnaires were high across most of the assessment time points for each instrument"
Selective reporting (reporting bias)	Low risk	All protocol specified endpoints reported
Other bias	Low risk	Planned accrual completed

AE: adverse event; ECOG: Eastern Cooperative Oncology Group; F: female; IMC: independent monitoring committee; IMDC: International Metastatic Renal Cell Carcinoma Database Consortium; ITT: intention to treat; M: male; MSKCC: Memorial Sloan Kettering Cancer Center; OS: overall survival; PFS: progression‐free survival; PS: performance status; QoL: quality of life; RCT: randomised controlled trial; RR: response rate; wks: weeks