Dockery 2009.

Methods	Start date, end date of recruitment: unclear Follow‐up period: All participants had atrial stiffness measures at baseline and at 12 and 24 weeks Design: randomised controlled trial
Participants	Population/Inclusion criteria: men with localised prostate cancer who were deemed as requiring hormonal treatment by local urology or oncology services Setting: single centre Geographical location: UK (London) Exclusion criteria: metastatic cancer, atrial fibrillation, severe hepatic renal or cardiac failure, any acute illness and any recent (in the preceding 12 months) hormone treatment Total number randomly assigned: 43 Baseline imbalances: balanced Number of participants with non‐metastatic disease: 42 Number of participants with metastatic disease: 0 Age (mean ± SD): intervention: 71.1 ± 6.1 years; control: 71.3 ± 6.6 years PSA: not reported Subgroup measured: no
Interventions	Intervention Description/Timing: bicalutamide 150 mg once daily for 6 months Number randomly assigned to this group: 21 (1 participant excluded) Control Description/Timing: goserelin depot injection 10.8 mg 3 times monthly (1 injection preceded by 2 weeks of flutamide, an androgen receptor blocker, 250 mg 3 times daily, as per standard guidelines) Number randomly assigned to this group: 21
Outcomes	Overall survival Outcome not measured/reported Cancer‐specific mortality Outcome not measured/reported Treatment discontinuation due to adverse events Comparison: non‐steroidal antiandrogen versus castration Subgroup: no Time points measured: at 6 months Time points reported: at 3 months Number of participants randomly assigned: intervention: 22; control: 21 Number of participants in evaluation for ITT: intervention: 21; control: 21 Clinical progression Outcome not measured/reported Biochemical progression Outcome not measured/reported Treatment failure Outcome not measured/reported Adverse events Outcome not measured/reported Other outcomes reported Metabolic parameters, carotid‐femoral and carotid‐radial pulse wave velocity, blood pressure
Notes	Study funding source: educational grant from AstraZeneca Possible conflict of interest: Sponsor had no role in any aspect of the study plan, conduct or analysis; interpretation of data; or writing of manuscript
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was computer‐generated and was balanced for every 6 participants
Allocation concealment (selection bias)	Unclear risk	Randomly allocated; no other statement reported
Blinding of participants and personnel (performance bias) overall survival, cancer‐specific mortality, biochemical progression	Unclear risk	Not measured/reported
Blinding of participants and personnel (performance bias) treatment discontinuation due to adverse events, clinical progression, treatment failure, adverse events	High risk	No blinding for treatment discontinuation due to adverse events. Blinding was not possible because of different interventions provided. We judge that the outcome of treatment discontinuation due to adverse events is likely to be influenced by lack of blinding
Blinding of outcome assessment (detection bias) overall survival, cancer‐specific mortality, biochemical progression	Unclear risk	Not measured/reported
Blinding of outcome assessment (detection bias) treatment discontinuation due to adverse events, clinical progression, treatment failure, adverse events	High risk	No blinding for treatment discontinuation due to adverse events. Blinding was not possible because of different interventions provided, and study authors reported insufficient information only. We judge that it is likely that outcome assessment for treatment discontinuation due to adverse events is influenced by lack of blinding
Incomplete outcome data (attrition bias) overall survival, cancer‐specific mortality	Unclear risk	Not measured/reported
Incomplete outcome data (attrition bias) treatment discontinuation due to adverse events, adverse events	Low risk	One man in intervention arm dropped out after his baseline visit, leaving 42 participants available for analysis. The proportion of missing outcomes compared with observed event risk is not enough to induce clinically relevant bias in intervention effect estimate
Incomplete outcome data (attrition bias) clinical progression, biochemical progression	Unclear risk	Not measured/reported
Incomplete outcome data (attrition bias) treatment failure	Unclear risk	Not measured/reported
Selective reporting (reporting bias)	High risk	Only adverse events leading to discontinuation reported; no other adverse events reported
Other bias	Unclear risk	Unclear risk for conflict of interest