2. Primary outcomes of the enclosed studies.

Study	Definition	Outcome measures
Hartnoll 1980	Total opiate consumption, frequency of injection, involvment with drug subculture.	Interviews (questionnaires not specified), direct observations
Perneger 1998	Self reported drug use, health status , and social functioning	Unpublished questionnaire based on ASI and SF­36.
CCBHA/B 2002	Prespecified dichotomous, multidomain outcome index including physical, mental, social dimensions and also completion of treatment and sustained response.	ASI / MAP‐HSS, Case Report Forms (CRF), Composite International Diagnostic Interview (CIDI),SCL‐90, urinalysis
PEPSA 2003	Dichotomous multidimension outcome (MDO) including general health, quality of life, drug‐addiction‐related problems, nonmedical use of heroin, risk behavior for HIV and HCV, and psychological, family, and social status	The ASI, Opiate Treatment Index, Symptom Checklist‐90, and the 12‐item shortform (SF‐12).
Haasen 2007	Two prespecified dichotomous, multidomain primary outcome measures about health and reduction in illicit drug use, were considered.	EuropASI OTI Health Scale (physical health) GSI (mental health)
NAOMI 2009	Retention in addiction treatment at 12 months (defined as receipt of the study medication on at least 10 of the 14 days before the 12‐month assessment, or confirmation of retention in any other treatment program or abstinence from opioids during this interval). Reduction in illicit drug‐use or other illegal activities	Retention in treatment: Data on daily prescription‐drug use and, when possible, with the use of administrative data and pharmacy and physician records Illicit drug use or other illegal activities: Composite scores on the European Addiction Severity Index17 (see the Supplementary Appendix, available with the full text of this article at NEJM.org),
RIOTT 2010	Reduction of regular use of street heroin defined as 50% or more of negative specimens on urinalysis during weeks 14‐26 (responders). Reduction of regular use of street heroin defined as two, one, or zero positive specimens during weeks 14‐26, and a test of zero positive specimens during weeks 23‐26. Self‐reported abstinence from street heroin (zero use) in the past 30 days.	Urine specimens were obtained at random once a week for 26 weeks; Independent researchers in face‐to‐face interviews with patients at baseline (0 weeks), 13 weeks, and 26 weeks.