An Exploration of Site Effects in a Multisite Trial of OROS-Methylphenidate for Smokers with Attention Deficit/Hyperactivity Disorder

Abstract

Background: Multisite trials, the gold standard for conducting studies in community-based settings, can mask variability across sites resulting in misrepresentation of effects in specific sites. In a placebo-controlled trial of osmotic-release oral system methylphenidate (OROS-MPH) as augmentation treatment for smokers with attention deficit hyperactivity/impulsivity disorder (ADHD), three types of sites were selected according to their clinical research specialty (ADHD, smoking cessation, and general mental health). Objective: Analysis was conducted to determine if clinical outcomes, that is, reduction in ADHD symptoms and smoking cessation rates, and the effect of treatment on these outcomes would differ by type of site. Method: A total of 255 adult smokers diagnosed with ADHD were enrolled in three clinic types: 72 in ADHD, 79 in tobacco dependence, and 104 in the mental health clinics. Results: The three site-types were similar in demographic characteristics, smoking history, baseline level of ADHD symptoms, and history of psychiatric illness. Site-type but not a site-type by treatment interaction predicted prolonged smoking abstinence. A significant three-way interaction of site-type, treatment, and time-predicted improvement in ADHD symptoms. Moderate to strong effects of OROS-MPH relative to placebo were observed in the mental health and the ADHD clinics; a weak effect was observed in the tobacco dependence clinics. Conclusion: OROS-MPH benefit varied by site for reducing ADHD symptoms but not for improving smoking abstinence. Scientific Significance: Assessment of site-type effects can indicate the generalizability of findings from multisite trials and should be routinely incorporated in the design of multisite trials.

• multisite trials
• site effects
• OROS-methylphenidate
• smokers with ADHD

ACKNOWLEDGMENTS

Preparation of this manuscript was supported in part by a National Institute on Drug Abuse (NIDA) Administrative Supplement to U10-DA013732 and 2U10-DA013035-09. The parent multisite trial was conducted through the Clinical Trials Network of the NI DA with funding support from U10-DA015831 and K24 DA022288 to Harvard University; U10-DA013035 and K24 DA022412 to New York State Psychiatric Institute; U10-DA013046 to New York University; U10-DA013036 to Oregon Health and Science University; and U10-DA013732 to the University of Cincinnati.