Palmedo 2003

Methods	Randomised open trial.
Participants	N = 64 men with prostate cancer. Metastatic bone lesions confirmed by 99mTcMDP bone scan and x‐ray. Patients had to suffer from multifocal pain and with at least five different sites of bone metastases. (32 on single injection of 188ReHEDP, 32 on two injections of 188ReHEDP).
Interventions	1. 188ReHEDP single injection of 1.1 MCi (40.7 MBq)/kg of body weight). 2. 188ReHEDP in two injections separated by 8 weeks. Follow up: until death of patient.
Outcomes	Pain relief assessed daily by the patient through a 0‐10 VAS. Pain medication index assessed daily by the patient . PSA levels assessed monthly. Toxicity assessed monthly by the National Cancer Institute Common Toxicity Criteria. Survival.
Notes	Patients were randomised 7 weeks after first injection. 2 patients lost from follow up in single injection group, 4 patients lost to follow up in double injection group.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described.
Allocation concealment (selection bias)	Unclear risk	Not described.
Blinding (performance bias and detection bias) Patients	High risk	Open trial.
Blinding (performance bias and detection bias) Study researchers	High risk	Open trial.
Blinding (performance bias and detection bias) Outcome assessment	High risk	Open trial.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Patients lost and not assessed are described for each group, with reasons for loss. Number of losses is similar between groups.