RIOTT 2010.

Methods	Allocation: Randomisation was undertaken independently by the Clinical Trials Unit (IoP).  Blindness: Researchers unblinded to treatment allocation, informed both clinicians and patients together of treatment allocation prior to treatment commencing. Duration of treatment within the study: 6 months
Participants	Diagnosis:regular heroin injecting no active significant medical condition N=127 Age= Aged between 18 and 65 years at recruitment to study History= >3 years injecting, in treatment >6 months Mental state= no active significant psychiatric conditions
Interventions	experimental group:supervised injectable heroin (SIH) attendance at clinic twice daily for prescribed split daily dose of injectable heroin; self‐administered under supervision; supplementary oral methadone available (as take‐home dose at clinician's discretion). experimental group :supervised injectable methadone (SIM) attendance at clinic once daily for prescribed single daily dose of injectable methadone; self‐administered under supervision; supplementary oral methadone available (as take‐home dose at clinician's discretion); control group:optimised oral methadone (OOM) enhanced oral methadone treatment, daily doses of >80mg actively encouraged, consumed under supervision on >5 days per week for 3 months; thereafter frequency of supervision reduced if clinically appropriate;
Outcomes	Reduction of regular use of street‐heroin : 1.a. objective: (operationally defined as urinalysis negative for street‐heroin for 50% or more of weekly random urines between weeks 14‐26); 1.b. subjective: self‐reported street‐heroin use (over 30 days prior to interview) was elicited through face‐to‐face research interviews with patients and 1.undertaken by independent researchers at baseline, three‐months and six months.
Notes	Country: UK 2005‐2008 Website:http://www.iop.kcl.ac.uk/projects/?id=10114
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Eligible consenting patients were randomised by minimisation in the ratio (1:1:1) to one of three treatment options (OOM, SIM, SIH), with stratification for a) regular cocaine/crack use (>50% days in previous 4 weeks), b) previous optimised oral methadone treatment (doses of >80mg/day; supervised >5 days/week) and c) clinic site (London, Darlington, Brighton). Randomisation was undertaken independently by the Clinical Trials Unit (IoP).
Allocation concealment (selection bias)	Unclear risk	Researchers unblinded to treatment allocation, informed both clinicians and patients together of treatment allocation prior to treatment commencing
Incomplete outcome data (attrition bias) All outcomes	Low risk	For the primary outcome measure, missing data were handled using multiple imputation in cases where missing urines occurred due to hospitalisation, imprisonment, pre‐agreed absence (holiday), safety reasons or clinical omission/error. Missing urines from a patient who attempted abstinence were similarly managed. Urine samples not provided due to non‐compliance (refusal to provide or unplanned non‐attendance) were presumed positive. Data were analysed on an Intention‐To‐Treat basis for the primary analysis (all patients randomised included in analyses). Per‐Protocol analyses (only patients who received trial interventions according to protocol) were also conducted: any substantial differences in findings are reported alongside the primary ITT analyses. All the data for each of the groups to which participants were randomised were presented so that the risk of bias of multiple‐intervention study are minimised.
Selective reporting (reporting bias)	Low risk	Protocol published and study registered see table 3.
Blinding (objective outcomes: drop out, use of substances measured by urine analysis)	Low risk	Urinalysis (primary outcome measure) was preformed by laboratory personnel blinded to treatment allocation and the statistician was blinded to injectable group.
Blinding (subjective outcomes: use of substances as measured by self report, side effects)	Low risk	Interviews with patients and undertaken by independent researchers at baseline, three‐months and six months.