Evaluating the impact of varying expired carbon monoxide thresholds on smoking relapse identification: insights from the E3 trial on e-cigarette efficacy for smoking cessation.

OBJECTIVES: Expired carbon monoxide (ECO) is often used in smoking cessation trials to biochemically validate self-reported smoking status. The optimal ECO threshold to distinguish individuals who smoke from those who do not is debated. DESIGN: The data from the 'Evaluating the Efficacy of E-Cigarette use for Smoking Cessation (E3) Trial' were used; the E3 trial was a randomised controlled trial that examined e-cigarettes efficacy for smoking cessation. SETTINGS: Participants were recruited from 17 Canadian sites across 4 provinces. PARTICIPANTS: This substudy included data from participants who returned for at least one of the clinical visits at week 4 (291), 12 (257) or 24 (218) and provided both self-reported smoking status and ECO measures. Analyses were based on 766 paired measures (ie, self-reported smoking status with corresponding ECO). RESULTS: The ability of ECO measurements to discriminate between adults who reported smoking and those who reported abstinence varied with the threshold used. ECO thresholds of 6, 7, 8 and 9 parts per million (ppm) yielded the greatest area under the receiver operating characteristic curve (0.84). These thresholds produced sensitivities of 84%, 82%, 78% and 76% and specificities of 84%, 87%, 90% and 91%, respectively. However, at a threshold of 6 ppm, intersecting sensitivity (84%) and specificity (84%) were maximised with respect to each other. Biochemical validation had the highest agreement with self-report at an ECO threshold of 6 ppm (κ=0.57; 95% CI, 0.51 to 0.64). CONCLUSION: The classification of participants' smoking status depends on the ECO threshold used for biochemical validation. We recommend that future smoking cessation trial investigators analyse and report the impact that varying ECO thresholds has on trial results. TRIAL REGISTRATION NUMBER: NCT02417467.

Efficacy and Safety of E-Cigarette Use for Smoking Cessation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: People who smoke conventional cigarettes are increasingly turning to electronic cigarettes (e-cigarettes) as a pathway to quitting. However, the efficacy and safety of e-cigarettes for smoking cessation remains controversial. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), identified through a systematic search of the MEDLINE, EMBASE, and Cochrane CENTRAL databases. Inclusion was restricted to RCTs with a follow-up duration ≥6 months. The primary endpoint was the most rigorous criterion of biochemically validated abstinence at maximum follow-up, and the primary comparison was nicotine e-cigarettes versus any conventional (ie, non-e-cigarette) smoking cessation therapy. The Cochrane Risk of Bias Tool was used to assess bias. Count data were pooled across trials using random-effects models with inverse variance weighting to estimate relative risks (RRs) and corresponding 95% confidence intervals (CIs). We registered the study protocol with the Open Science Framework Registries (osf.io/26fkq). RESULTS: A total of 5 RCTs (n = 3253) were included. Compared with conventional smoking cessation therapies, the use of nicotine e-cigarettes was associated with an increase in abstinence, defined by the most rigorous criterion of abstinence reported (RR 1.77; 95% CI, 1.29-2.44). Nicotine e-cigarettes also increased abstinence (defined by the most rigorous criterion) compared with non-nicotine e-cigarettes (RR 1.56; 95% CI, 1.13-2.15). The incidence of death or serious adverse events was low across all trials at maximum follow-up. CONCLUSIONS: Among individuals attempting to quit smoking, nicotine e-cigarettes are more efficacious than conventional nicotine replacement or behavioral smoking cessation therapies, and may prove beneficial in reducing smoking-related health risks.