Inequity in smoking cessation clinical trials testing pharmacotherapies: exclusion of smokers with mental health disorders.

OBJECTIVES: People suffering from mental health disorder (MHDs) are often under-represented in clinical research though the reasons for their exclusion are rarely recorded. As they have higher rates of smoking and nicotine dependence, it is crucial that they are adequately represented in clinical trials of established pharmacotherapy interventions for smoking cessation. This review aims to examine the practice of excluding smokers with MHDs and reasons for such exclusion in clinical trials evaluating pharmacotherapy treatments for smoking cessation. DATA SOURCE: The Cochrane database of systematic reviews was searched until September 2020 for reviews on smoking cessation using pharmacotherapies. STUDY SELECTION: Randomised controlled trials (RCTs) within the selected Cochrane reviews were included. DATA EXTRACTION: Conducted by one author and independently verified by three authors. DATA SYNTHESIS: We included 279 RCTs from 13 Cochrane reviews. Of all studies, 51 (18.3%) explicitly excluded participants with any MHDs, 152 (54.5%) conditionally excluded based on certain MHD criteria and 76 (27.2%) provided insufficient information to ascertain either inclusion or exclusion. Studies of antidepressant medications used for smoking cessation were found to be 3.33 times more likely (95% CI 1.38 to 8.01, p=0.007) to conditionally exclude smokers with MHDs than explicitly exclude compared with studies of nicotine replacement therapy. CONCLUSION: Smokers with MHDs are not sufficiently represented in RCTs examining the safety and effectiveness of smoking cessation medications. Greater access to clinical trial participation needs to be facilitated for this group to better address access to appropriate pharmacotherapeutic interventions in this vulnerable population.

Effect of Cytisine vs Varenicline on Smoking Cessation: A Randomized Clinical Trial.

Importance: Cytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy. Objective: To examine whether standard cytisine treatment (25 days) was at least as effective as standard varenicline treatment (84 days) for smoking cessation. Design, Setting, and Participants: This noninferiority, open-label randomized clinical trial with allocation concealment and blinded outcome assessment was undertaken in Australia from November 2017 through May 2019; follow-up was completed in January 2020. A total of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data collection was conducted primarily by computer-assisted telephone interview, but there was an in-person visit to validate the primary outcome. Interventions: Treatments were provided in accordance with the manufacturers' recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially then gradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to 1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard telephone behavioral support. Main Outcomes and Measures: The primary outcome was 6-month continuous abstinence verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin was set at 5% and the 1-sided significance threshold was set at .025. Results: Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years; 742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk difference, -1.62% [1-sided 97.5% CI, -5.02% to ∞]; P = .03 for noninferiority). Self-reported adverse events occurred less frequently in the cytisine group (997 events among 482 participants) compared with the varenicline group (1206 events among 510 participants) and the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P = .002). Conclusions and Relevance: Among daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation. Trial Registration: anzctr.org.au Identifier: ACTRN12616001654448.