American Journal of Drug and Alcohol Abuse 2011;37(5):392-399. [doi: 10.3109/00952990.2011.596979]
Lirio S. Covey, PhD (Columbia University Medical Center, GNY Node), Mei-Chen Hu, PhD (Columbia University, GNY Node), Carla A. Green, PhD, MPH (Kaiser Permanente Northwest, WS Node), Gregory S. Brigham, PhD (Maryhaven, Inc.), Richard D. Hurt, MD (Mayo Clinic, OV Node), Lenard A. Adler, MD (VA New York Harbor Healthcare System, GNY), Theresa M. Winhusen, PhD (University of Cincinnati/CinARC, OV Node).
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) (protocol CTN-0029), three types of sites were selected according to their clinical research specialty (ADHD, smoking cessation, and general mental health). 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. 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. 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 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, while only a weak effect was observed in the tobacco dependence clinics. Accordingly, had the study only been conducted in tobacco dependence clinics, an erroneous null or, at best, weak effect of OROS-MPH on ADHD symptoms might have emerged.
Conclusions: OROS-MPH benefit varied by site for reducing ADHD symptoms but not for improving smoking abstinence. The uneven presence of site-type effects, observed in this analysis, affirms the need for a priori consideration and measurement of potentially influential site-related factors in the design and analysis of multisite trials. Scientific 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. (Article (Peer-Reviewed), PDF, English, 2011)
Keywords: Attention Deficit Hyperactivity Disorder (ADHD) | Community health services | Concerta | CTN platform/ancillary study | Nicotine replacement therapy | Osmotic-Release Methylphenidate (OROS-MPH) | Pharmacological therapy | Research design | American Journal of Drug and Alcohol Abuse (journal)
Document No: 726, PMID: 21854282, PMCID: PMC3510007.
Submitted by CTN Dissemination Librarians, 8/23/2011.