Toward personalized smoking-cessation treatment: Using a predictive modeling approach to guide decisions regarding stimulant medication treatment of attention-deficit/hyperactivity disorder (ADHD) in smokers

Abstract

Background and objectives: Osmotic-release oral system methylphenidate (OROS-MPH) did not show overall benefit as an adjunct smoking cessation treatment for adult smokers with ADHD in a randomized, placebo-controlled, multicenter clinical trial. A secondary analysis revealed a significant interaction between ADHD symptom severity and treatment-response to OROS-MPH, but did not account for other baseline covariates or estimate the magnitude of improvement in outcome if treatment were optimized. This present study addressed the gaps in how this relationship should inform clinical practice.

Methods: Using data from the Adult Smokers with ADHD Trial (N = 255, six sites in five US States), we build predictive models to calculate the probability of achieving prolonged abstinence, verified by self-report, and expired carbon monoxide measurement. We evaluate the potential improvement in achieving prolonged abstinence with and without stratification on baseline ADHD severity.

Results: Predictive modeling demonstrates that the interaction between baseline ADHD severity and treatment group is not affected by adjusting for other baseline covariates. A clinical trial simulation shows that giving OROS-MPH to patients with baseline Adult ADHD Symptom Rating Scale (ADHD-RS) >35 and placebo to those with ADHD-RS ≤35 would significantly improve the prolonged abstinence rate (52 ± 8% vs. 42 ± 5%, p < .001).

Conclusions and scientific significance: In smokers with ADHD, utilization of a simple decision rule that stratifies patients based on baseline ADHD severity can enhance overall achievement of prolonged smoking abstinence. Similar analysis methods should be considered for future clinical trials for other substance use disorders.

Trial registration: ClinicalTrials.gov NCT00253747.

© American Academy of Addiction Psychiatry.

Figures

FIGURE 1

Estimated probability of achieving prolonged abstinence. Box plot of estimated probability of prolonged abstinence with 10-fold cross validation, as a function of baseline ADHD severity rating score. As illustrated, when patients have a low-modest baseline ADHD severity, placebos appear superior to OROS-MPH. This effect is reversed at high baseline ADHD severity. The point of treatment efficacy equivalence is at ADHD-RS = 35. ADHD-RS, baseline ADHD severity rating score; OROS-MPH, osmotic-release methylphenidate.

FIGURE 2

Estimating the improvement of clinical outcome with stratification of baseline severity (a) schematic for a clinical trial simulation analysis for comparing the effectiveness of a patient stratification decision as an intervention to improve outcome. (b) Results of the analysis show that if the “correct” medication were given, there is a significant improvement of overall rate of sustained abstinence (asterisks showing p < 1E-3, with Bonferroni correction). ADHD-RS, baseline ADHD severity rating score; NS, not significant.

FIGURE 3

Performances of predictive models for prolonged smoke cessation (a) ROC Curves for comparing the predictive performances for cross-validated predictions for three different types of models, showing a modest predictive performance for individual treatment response. Models that do not incorporate the interaction term (in black solid line) do not perform better than chance. (b) Quantification of predictive performance comparing the three types of models, showing a modest, but statistically significant performance improvement with a model incorporating many covariates baseline covariates using L1-regularization, but only the small number of patients that the model is most confident about (p < 1E-3, with Bonferroni correction). ROC, Receiver Operating Characteristics; ADHD-RS, baseline ADHD severity rating score.