Journal Club

1. Journal Club Alcohol, Other Drugs, and Health: Current Evidence September–October 2008 www.aodhealth.org

2. Featured Article Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, placebo-controlled trial Schottenfeld RS, et al. Lancet. 2008;371(9631):2192–2200. www.aodhealth.org

3. Study Objective • To compare the efficacy of naltrexone versus buprenorphine for maintenance of heroin abstinence, prevention of relapse, and reduction of HIV risk behaviors www.aodhealth.org

4. Study Design • A randomized, double-blind, placebo-controlled trial of 126 patients who: • completed a14-day residential detoxification for heroin dependence and • received weekly manual-guided drug counseling. • Patients were assigned to either… • placebo (n=39) • oral naltrexone (n=43), or • sublingual buprenorphine (n=44). www.aodhealth.org

5. Study Design - II • Primary outcomes, assessed by urine testing 3 times per week, were: • days to first heroin use • days to heroin relapse • 3 consecutive opioid-positive urine tests • maximum consecutive days of heroin abstinence • reductions in HIV risk behaviors www.aodhealth.org

6. Assessing Validity of an Article about Therapy • Are the results valid? • What are the results? • How can I apply the results to patient care? www.aodhealth.org

7. Are the Results Valid? • Were patients randomized? • Was randomization concealed? • Were patients analyzed in the groups to which they were randomized? • Were patients in the treatment and control groups similar with respect to known prognostic variables? www.aodhealth.org

8. Are the Results Valid?(cont‘d) • Were patients aware of group allocation? • Were clinicians aware of group allocation? • Were outcome assessors aware of group allocation? • Was follow-up complete? www.aodhealth.org

9. Were patients randomized? • Yes. • The patients were randomized to either oral naltrexone, sublingual buprenorphine, or placebo. www.aodhealth.org

10. Was randomization concealed? • Yes. • Randomization was concealed. www.aodhealth.org

11. Were patients analyzed in the groups to which they were randomized? • Yes. • Patients were analyzed in the groups to which they were randomized (intention to treat). www.aodhealth.org

12. Were the patients in the treatment and control groups similar? • Yes. • Baseline clinical and demographic characteristics were similar across the 3 treatment groups. www.aodhealth.org

13. Were patients aware of group allocation? • No. • Patients were unaware of group allocation. • All patients ingested oral capsules (containing either naltrexone or placebo) and dissolved sublingual tablets (containing either buprenorphine or placebo), under direct observation. • Patients gargled with a mentholated antiseptic mouthwash before taking the sublingual tablets to mask taste differences between active and placebo buprenorphine tablets. www.aodhealth.org

14. Were clinicians aware of group allocation? • No. • Clinicians were unaware of group allocation. www.aodhealth.org

15. Were outcome assessors aware of group allocation? • No. • Outcome assessors were unaware of group allocation. www.aodhealth.org

16. Was follow-up complete? • Six month follow-up was obtained in: • 36 of 44 patients randomized to buprenorphine. • 29 of 42 patients randomized to naltrexone. • 23 of 39 patients randomized to placebo. • Urine tests on patients not available for follow-up were presumed to be positive for opiates given the high likelihood of relapse to drug use. • The study was halted early due to an interim safety analysis. At the time the study was halted, researchers had complete follow-up on 103 of an anticipated sample size of 180 patients. www.aodhealth.org

17. What Are the Results? • How large was the treatment effect? • How precise was the estimate of the treatment effect? www.aodhealth.org

18. How large was the treatment effect? • Buprenorphine was associated with greater time to first heroin use than naltrexone (hazard ratio [HR], 1.9) or placebo (HR, 2.0). • Compared with placebo, buprenorphine was associated with greater time to heroin relapse (HR, 2.2) and more consecutive days abstinent (59 versus 24 days). • Retention, time to first heroin use, and time to relapse did not differ significantly between naltrexone and placebo. • HIV risk behaviors did not differ between any of the groups. www.aodhealth.org

19. How precise was the estimate of the treatment effect? • The 95% confidence intervals were narrow, indicating a precise estimate of the treatment effect. • Buprenorphine was associated with greater time to first heroin use than: • Naltrexone (HR, 1.9 [95% CI, 1.21–2.88]) • Placebo (HR, 2.0 [95% CI, 1.29–3.16]) • Compared with placebo only, buprenorphine was associated withgreater time to heroin relapse, (HR, 2.2 [95% CI, 1.38–3.42]). www.aodhealth.org

20. How Can I Apply the Results to Patient Care? • Were the study patients similar to the patients in my practice? • Were all clinically important outcomes considered? • Are the likely treatment benefits worth the potential harm and costs? www.aodhealth.org

21. Were the study patients similar to those in my practice? • Patients were recruited from an urban community in Malaysia. Sixty-eight percent were of Malay ethnic origin. • The majority were in their late 30s and had been using heroin for approximately 15 years. • Gender is not specified. www.aodhealth.org

22. Were all clinically important outcomes considered? • Yes. • The primary and secondary outcomes included heroin use, relapse, and HIV risk behaviors. www.aodhealth.org

23. Are the likely treatment benefits worth the potential harm and costs? • No substantive harms were noted with buprenorphine treatment. • Patients receiving buprenorphine were more likely to report constipation, drowsiness, urinary hesitancy, or sweating, but these reports were only present in 1–2.5% of encounters. • Costs were not considered in this analysis. Prior evaluations have found buprenorphine to be cost-effective. www.aodhealth.org