1. Journal Club Alcohol, Other Drugs, and Health: Current Evidence March–April 2015

2. Featured Article Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial Ebbert JO, et al. JAMA. 2015;313(7):687–694.

3. www.aodhealth.org3 Study Objectives To test the efficacy of a reduce-to-quit approach to smoking cessation, comparing treatment with varenicline with placebo.

4. 4 Study Design Randomized, double-blind, placebo-controlled, multinational clinical trial with a 24-week treatment period and 28-week follow-up. 1510 participants willing to reduce smoking were recruited by advertisement from 10 countries. www.aodhealth.org

5. 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. www.aodhealth.org6 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. www.aodhealth.org7 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. www.aodhealth.org8 Were patients randomized? Yes, in a 1:1 ratio using a computer- generated block randomization schedule.

9. www.aodhealth.org9 Was randomization concealed? Yes. –“Participants, investigators, and research personnel were blinded to randomization until after the database was locked.”

10. www.aodhealth.org10 Were patients analyzed in the groups to which they were randomized? Yes.

11. www.aodhealth.org11 Were the patients in the treatment and control groups similar? Yes.

12. www.aodhealth.org12 Were patients aware of group allocation? No.

13. www.aodhealth.org13 Were clinicians aware of group allocation? No.

14. www.aodhealth.org14 Were outcome assessors aware of group allocation? Unknown.

15. www.aodhealth.org15 Was follow-up complete? No. –1510 patients were randomized; 1075 completed the study. 73.6% (559 of 760 participants) in the varenicline group and 68.8% (516 of 750 participants) in the placebo group.

16. www.aodhealth.org16 What Are the Results? How large was the treatment effect? How precise was the estimate of the treatment effect?

17. www.aodhealth.org17 How large was the treatment effect? 47% of varenicline recipients (versus 31% of placebo) reduced tobacco use by ≥ 50% at 4 weeks. 26% of varenicline recipients (versus 15% of placebo) reduced tobacco use by ≥ 75% at 8 weeks. Week 15–24 continuous abstinence rate (CAR) for varenicline group was 32% versus 7% for placebo group (risk difference [RD], 25%). Week 21-52 CAR for varenicline group was 27% versus 10% for placebo group (RD, 17%).

18. www.aodhealth.org18 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. www.aodhealth.org19 Were the study patients similar to those in my practice? The trial was conducted in 61 centers in 10 countries increasing external validity Subjects were recruited through advertisements so motivation may differ from individuals encountered in routine practice Individuals with severe psychiatric, pulmonary, cardiovascular, or cerebrovascular disease were excluded from participating in the study.

20. www.aodhealth.org20 Were the study patients similar to those in my practice? The population was approx. 56% male, 62% white, 44 years old, and started smoking around 17 years of age. In both groups, around 39% of participants had made more than 3 attempts to quit smoking. In the valenicline group, participants scored 5.5 on the Fagerström Test for Nicotine Dependence; participants in the control group scored 5.6.

21. www.aodhealth.org21 Were all clinically important outcomes considered? Yes. Serious adverse events occurred in fewer than 4% of patients and did not differ by treatment group.

22. www.aodhealth.org22 Are the likely treatment benefits worth the potential harm and costs? Costs were not reported.