title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  OROS-MPH benefit varied by site for reducing ADHD symptoms but not for improving smoking abstinence.
  
  
  CONCLUSIONS
  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.
authors.affiliation: New York State Psychiatric Institute, Department of Psychiatry, Columbia University Medical Center, New York, USA. lsc3@columbia.edu
authors.forename: Lirio S
authors.initials: LS
authors.lastname: Covey
authors.forename: Mei-Chen
authors.initials: MC
authors.lastname: Hu
authors.forename: Carla A
authors.initials: CA
authors.lastname: Green
authors.forename: Gregory
authors.initials: G
authors.lastname: Brigham
authors.forename: Richard D
authors.initials: RD
authors.lastname: Hurt
authors.forename: Lenard
authors.initials: L
authors.lastname: Adler
authors.forename: Theresa
authors.initials: T
authors.lastname: Winhusen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009997:Osmotic Pressure; D012107:Research Design; D016540:Smoking Cessation / Q000379:methods*; D000074606:Smoking Prevention; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate