We found similar results when modeling secondary cessation outcomes (smoking quantity across 8 weeks, point-prevalent abstinence at 8 weeks, and continuous abstinence over 90 days). Fast metabolizers receiving placebo escalate their smoking significantly more quickly than do fast metabolizers on active medication and slow metabolizers on active medication or placebo (β=0.14, t=3.13, df=1, p=0.0020, Figure 3A). When comparing the four subgroups of subjects formed by crossing NRT vs. placebo with CYP2A6 estimated fast vs. slow metabolizer conditions, we found a 3-way interaction of NRT condition, CYP2A6 activity, and time (interaction effect size=-0.17, 95%CI=-0.33-0.0025, p=0.053, Figure 3B) reflecting that smoking escalated especially quickly amongst fast metabolizers receiving no NRT. The interaction between CYP2A6 and NRT only approached significance for point-prevalent abstinence at 8 weeks (interaction effect size=0.69, 95%CI=0.33-1.46, p=0.33), but was significant for continuous abstinence over 90 days (interaction effect size=0.37, 95%CI=0.18-0.78, p=0.0091; Table S3), reflecting that fast metabolizers on placebo were especially unlikely to be abstinent from smoking for the whole 90-day period.
