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.

Keywords: clinical trials; epidemiologic studies; public health.

Figure 1

Prevalence of smoking according to expired carbon monoxide (ECO) level. The distribution of ECO concentrations for self-reporting smokers and self-reported non-smokers are visually depicted by the orange and blue curves, respectively. Self-reported smokers ECO levels ranged from 0 to 102 parts per million (ppm) (orange) whereas self-reported non-smokers ECO levels ranged from 0 to 28 ppm (blue).

Figure 2

Expired carbon monoxide (ECO) by self-reported mean number of cigarettes smoked in the past 7 days. Due to several readings for the same average cigarette intake, multiple values are superimposed. The prediction ellipse represents an iso-contour of the Gaussian distribution, defining a region of paired data containing 95% of reported measures. ppm, parts per million.

Figure 3

Sensitivity and specificity of expired carbon monoxide (ECO) for validating self-reported smoking status. At lower thresholds, ECO measurements are more sensitive and thus better for detecting greater numbers of smokers, whereas at higher thresholds, ECO measurements are more specific and thus better for discriminating smokers from non-smokers. Specificity (orange) and sensitivity (blue) intersect at an ECO value of 6 parts per million (ppm), such that both sensitivity (84%) and specificity (84%) are maximised with respect to each other.