1. Alcohol, Other Drugs, and Health: Current Evidence
Journal Club
Alcohol, Other Drugs, and Health: Current Evidence
September-October, 2016

2. Rosenthal RN, et al. JAMA. 2016;316(3):282–290.
Featured Article
Effect of buprenorphine implants on illicit opioid use among abstinent adults with opioid dependence treated with sublingual buprenorphine: a randomized clinical trial.
Rosenthal RN, et al. JAMA. 2016;316(3):282–290.

3. Study Objectives
To determine the non-inferiority of 6-month buprenorphine implants compared with sublingual buprenorphine for the treatment of opioid use disorder among patients with DSM-IV opioid dependence who are currently receiving 8 mg or less of buprenorphine with abstinence for greater than 90 days.

4. Study Design
Randomized, active-controlled, 24-week, double-blind, double-dummy study among 117 participants receiving treatment at 21 office-based buprenorphine outpatient treatment sites.
Patients randomized to receive sublingual buprenorphine plus 4 placebo implants or sublingual placebo plus four 80-mg buprenorphine hydrochloride implants.

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?

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?

7. 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?

8. Were patients randomized?
Yes.
Participants were randomized in a 1:1 ratio within a block size of 4 using a computerized system without stratification.

9. Was randomization concealed?
Yes.
The study was double-blinded.

10. Were patients analyzed in the groups to which they were randomized?
Yes.

11. Were the patients in the treatment and control groups similar?
Yes. The characteristics of the groups at baseline were similar.

12. Were patients aware of group allocation?
No, patients were blinded to group allocation.

13. Were clinicians aware of group allocation?
No, clinicians were blinded to group allocation.
“staff involved in implant insertion and removal at 6 months did not participate in study evaluation as active and placebo implants varied slightly in appearance.”

14. Were outcome assessors aware of group allocation?
No.

15. Was follow-up complete?
81/87 (93%) randomized to receive buprenorphine implant completed follow-up
84/90 (93%) randomized to receive sublingual buprenorphine completed follow-up

16. How large was the treatment effect?
What Are the Results?
How large was the treatment effect?
How precise was the estimate of the treatment effect?

17. How large and precise was the treatment effect?
Primary endpoint was proportion of responders. Responders were defined as those with > 4 of 6 months without opioid-positive urine test result and self-report
Responder rates for the intention-to-treat population:
Implant group (81/84, 96%)
Sublingual group (78/89, 88%)
Difference: 8.8% (95% CI, to ∞) 17

18. 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?

19. Were the study patients similar to those in my practice?
“…the majority of the participants enrolled were white, employed, with at least a high school education, and dependent on prescription opioids”
Participants…
had DSM-IV opioid dependence
were aged 18 to 65 years
received sublingual buprenorphine for at least 24 weeks as an outpatient at a stable dosage of ≤8 mg/d
showed no evidence of opioid withdrawal or illicit opioid-positive urine samples for ≥90 days prior to study entry
Female participants of childbearing potential agreed to use contraception during the study.

20. Were all clinically important outcomes considered?
No mention of patient satisfaction.

21. Are the likely treatment benefits worth the potential harm and costs?
Serious adverse events occurred in 5 participants, 3 in the sub-lingual buprenorphine group and 2 in the buprenorphine implant group.
23% of buprenorphine implant patients vs. 14% of sub-lingual buprenorphine patients had > implant site related adverse event
Costs were not reported.