Journal Club

1. Journal Club Alcohol, Other Drugs, and Health: Current Evidence September–October 2009 www.aodhealth.org

2. Featured Article Diacetylmorphine versus Methadone for the Treatment of Opioid Addiction Oviedo-Joekes E, et al. N Engl J Med. 2009; 361(8):777–786. www.aodhealth.org

3. Study Objective • To determine whether diacetylmorphine, the active ingredient in heroin, can be an effective treatment for chronic, relapsing opioid dependence. www.aodhealth.org

4. Study Design • Open-label phase-3 randomized controlled trial. • Long-term heroin users from 2 Canadian sites who had not benefited from ≥2 previous attempts at treatment (including at least 1 methadone treatment) were randomly assigned to: • injectable diacetylmorphine (n=115), or • oral methadone maintenance therapy (n=111).* • Outcomes assessed at 12 months included: • retention in treatment, and • reduction in illicit-drug use or other illegal activity. *An additional 25 subjects were randomized to receive injectable hydromorphone to facilitate validation of self-reported heroin use by urine tests. www.aodhealth.org

5. 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

6. 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

7. Are the Results Valid? (cont.) • 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

8. Were patients randomized? • Yes. • Computer-generated randomization was used to assign patients to treatment groups. www.aodhealth.org

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

10. Were patients analyzed in the groups to which they were randomized? • Yes. • Retention and response rates were calculated on an intention-to-treat basis. www.aodhealth.org

11. Were the patients in the treatment and control groups similar? • Yes. • Baseline characteristics of the groups were similar. www.aodhealth.org

12. Were patients and clinicians aware of group allocation? • Yes, for the main comparison. • Investigators and participants knew whether the prescribed drug was oral methadone or an inject-able medication. • Neither investigators nor participants knew whether the injectable medication was diacetyl-morphine or hydromorphone. www.aodhealth.org

13. Were outcome assessors aware of group allocation? • Outcomes were assessed at research offices that operated independently from the treatment clinics. No information is pre-sented that indicates that assessors were not aware of group allocation. www.aodhealth.org

14. Was follow-up complete? • Of the 111 patients who received methadone, • 106 had retention data available. • 104 had response data available. • Of the 115 patients who received diacetylmorphine, • 114 had retention data available. • 111 had response data available. • Of the 25 patients who received hydromorphone, • 25 had retention and response data available. www.aodhealth.org

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

16. How large was the treatment effect and how precise was the estimate of treatment effect? • The rate of retention in treatment in the diacetylmorphine group was 87.8% compared with 54.1% in the methadone group (rate ratio, 1.62; 95% CI, 1.35 to 1.95; p<0.001). • For the outcome of a reduction in illicit-drug use or other illegal activities, 67% of the patients in the diacetylmor-phine group were classified as having a response compared with 47.7% of patients in the methadone group (rate ratio, 1.40; 95% CI, 1.11 to 1.77; p=0.004). • Twenty-three patients (20%) originally assigned to diacetylmorphine switched to methadone. www.aodhealth.org

17. 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

18. Were the study patients similar to those in my practice? • Participants were largely middle-aged men who were marginally housed, did not complete high school, had a record of illegal activities, and reported opioid use for 16 to 19 years. www.aodhealth.org

19. Were all clinically important outcomes considered? • The primary outcomes, retention in treatment at 12 months and reduction in illicit-drug use or other illegal activities, are clinically important. www.aodhealth.org

20. Are the likely treatment benefits worth the potential harm and costs? • A total of 24 adverse events occurred among patients in the diacetylmorphine group (including 11 overdoses and 7 seizures). None occurred in the methadone group. This raises substantial concerns regarding the potential harms associated with diacetylmorphine treatment. www.aodhealth.org