Table 1.

Summary of characteristics of included studies and Risk of Bias (RoB)

Study ID (Design, Country)	Participants	Intervention	Study’s primary outcomes	Risk of Bias (RoB)
Yancovitz et al. 1991 (Randomized Controlled Trial (RCT), USA) [44]	301 participants: 149 Treatment group 152 Frequent contact group	Interim Clinic: Methadone administered by a nurse 5 days a week. Saturday medication and one take-home were provided at another site in the same building + AIDS education + free condoms. Minimal counseling on an ad hoc basis. Biweekly urine samples. Maintenance dose of 80 mg/d approximately Control: Waiting list, biweekly follow-up and urine samples, and free condoms. Time spent limited to one month and then switched into experimental group	Change in heroin use	Random sequence generation: Unclear Allocation concealment: Low Blinding of participants and personnel: High Blinding of outcome assessment (objective outcomes): Unclear Blinding of outcome assessment (subjective outcomes): Unclear Incomplete data outcome: High Selective reporting bias: Unclear
Schwartz et al. 2006 (RCT, USA) [21]	319 participants: 199 Treatment group 120 Waiting list	Interim Treatment: Methadone provided under direct observation, participants attended 7 days a week (as the federal regulation required). 3 consecutive unexcused missed doses resulted in discharge from treatment. Mean dose of methadone was 78.4 mg/d Control: Waiting list; no further contact with clinical staff unless their name came up on the waiting list	Entry into comprehensive methadone treatment Self-reported days of heroin use Self-reported days of cocaine use Self-reported criminal behavior Number of urine drug test results positive for heroin and cocaine Retention in treatment	Random sequence generation: Low Allocation concealment: Low Blinding of participants and personnel: High Blinding of outcome assessment (objective outcomes): Low Blinding of outcome assessment (subjective outcomes): High Incomplete data outcome: High Selective reporting bias: Unclear
NCT02360007 (RCT, USA) [41]	50 participants: 25 Treatment group 25 Waiting list	Interim Treatment: Interim buprenorphine treatment (IBT) participants will complete buprenorphine (BUP) induction in Week 1 (or longer if required), during which they will attend the clinic daily. Thereafter, during Weeks 2–12 IBT participants will visit the clinic every two weeks to take their BUP dose, provide a urine specimen and receive their remaining doses in a secure dispenser that makes each day’s dose available during a 3-h window Control: Waitlist control (WLC) participants will remain on the waitlist for their treatment of choice. They will visit the clinic to complete follow-up assessments and provide staff-observed urines according to the same schedule as IBT participants Participants in both conditions will complete follow-up assessments and provide a urine specimen at 4, 8, 12, 18 and 24 weeks after trial entry. WLC participants who have not entered treatment by Week 12 will be offered IBT at that time, providing an additional within-subject evaluation of IBT effects. Thus the overall possible study duration may vary between 12—28 weeks	Negative results for illicit opioids	Random sequence generation: Low Allocation concealment: Unclear Blinding of participants and personnel: High Blinding of outcome assessment (objective outcomes): Unclear Blinding of outcome assessment (subjective outcomes): Unclear Incomplete data outcome: High Selective reporting bias: High
NCT00712036 (RCT, USA) [37]	230 participants: 99 Treatment group (IM) 104 Control condition 1 (SM) 27 Control condition 2 (RM)	Interim Treatment (IM): Methadone treatment for up to 4 months with emergency counseling only. Treatment was provided following federal regulations. Mean methadone dose of 91.8 mg/d (SD 21.3) Control: 1. Scheduled counseling/Standard Methadone Treatment (SM): Methadone treatment with counseling as usual. Methadone treatment programs (MTPs) usual practices, which permitted take-home doses contingent upon tenure and progress in treatment (e.g., negative drug tests), required regularly scheduled counseling, treatment planning, other psychosocial treatment as needed, and more frequent drug testing than in IM. Mean methadone dose of 79.4 mg/d (SD 22.3) 2. Restored Methadone Treatment (RM): Methadone treatment with counseling provided by a clinician with a lower caseload than counseling as usual. That counselor carried a reduced case load not to exceed 25 patients and was instructed to see the participants as frequently as the participants wanted and the counselor deemed appropriate. Mean methadone dose of 64.7 mg/d (SD 15.6)	Opiate positive drug test	Random sequence generation: Low Allocation concealment: Low Blinding of participants and personnel: High Blinding of outcome assessment (objective outcomes): Low Blinding of outcome assessment (subjective outcomes): High Incomplete data outcome: Low Selective reporting bias: Low
Krook et al. 2002 (RCT, Norway) [35]	106 participants: 55 Treatment group 51 Control condition	Buprenorphine: Buprenorphine without additional rehabilitation or support. 4 mg Subutex® on the first day, increased to 16 mg/d on the following 8 days. At the 12th week, dosage was scaled down to 4 mg/d Control: Placebo without additional rehabilitation or support. 4 mg of Subutex® on the first day and then the dose was decreased to 0 in 9 days and thereafter replaced by placebo	Retention (is the patient still in the project?) Compliance (how many of the total number of doses had been taken?)	Random sequence generation: Low Allocation concealment: Low Blinding of participants and personnel: Low Blinding of outcome assessment (objective outcomes): Low Blinding of outcome assessment (subjective outcomes): Low Incomplete data outcome: Unclear Selective reporting bias: Low
Friedmann et al. 1994 (Cohort study, USA) [33]	977 participants: 314 Treatment group 663 Control condition	Interim Methadone Treatment: A physical examination on admission was performed by a physician, methadone was administered by a registered nurse six days per week with one take-home dose for Sunday, and education about AIDS-risk reduction was provided. Only crisis counseling services were provided, and the focus of the interim clinic counselors was otherwise limited to AIDS-risk reduction. The clinic had a capacity of 150 patients, thus providing a ratio of 1 counselor to 75 patients Control: The comparison group includes all consecutive 1990 and 1991 admissions to Beth Israel's traditional methadone clinics located in the same immediate area as the interim clinic	Retention rate in treatment	Confounding: Serious Selection of participants: Serious Classification of intervention: Low Deviation from intended intervention: Serious Missing outcome data: Low Measurement of the outcome: Low Selection of the reported result: Low