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.

ABSTRACT

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.