Relationship Between Early Product Substitution and Harm Reduction in an ENDS Switching Trial for Adults who Smoke

To examine the relationship between early product substitution and harm reduction (HR) in an ENDS switching trial for adults who smoke.

We conducted a longitudinal structural equation analysis of 120 treatment participants who received disposable ENDS for 8 weeks and were assessed every 2weeks. The predictor was w2 ENDS sessions/day. The HR latent construct included 4 binary indicators: cigarettes/day (CPD) ≤5 and carbon monoxide (CO) <10ppm at weeks 6 & 8. We tested an indirect path from w2 ENDS use through w2 CPD reduction to HR, and a direct path from w2 ENDS use to HR, both moderated by w0 CPD.

Mean age was 45.9 years, and 42.7% smoked ≥20 CPD. ENDS use at w2 significantly increased the odds of HR for all participants (p<0.001), mediated through reductions in w2 CPD. The ENDS direct pathway was moderated by w0 CPD (p<0.001). For the total (direct + indirect) association, greater w2 ENDS use increased chances of HR for individuals with w0 CPD>16, decreased the chances of HR for individuals with w0 CPD<7 and had no impact on those in the w0 CPD 7-15. All predictors combined explained 66% of the variance in HR.

In this study, early ENDS use predicted short-term HR, but only for individuals who smoked more heavily. For those with low smoking intensity, early ENDS use predicted decreased short-term chances of HR and increased dual product use. This is a novel finding limited to a small sample of persons with severe mental illness.

If replicated and extended to later HR outcomes, the finding supports a focus on early ENDS use as an intermediate outcome for phase 2 trials of ENDS products, and adaptive treatment designs aimed at early non responders, with a particular focus on persons who smoke heavily.