title: Rationale, design, and methods of the Preschool ADHD Treatment Study (PATS).
abstract: OBJECTIVE
  To describe the rationale and design of the Preschool ADHD Treatment Study (PATS).
  
  
  METHODS
  PATS was a National Institutes of Mental Health-funded, multicenter, randomized, efficacy trial designed to evaluate the short-term (5 weeks) efficacy and long-term (40 weeks) safety of methylphenidate (MPH) in preschoolers with attention-deficit/hyperactivity disorder (ADHD). Three hundred three subjects ages 3 to 5.5 years old who met criteria for a primary DSM-IV diagnosis of ADHD entered the trial. Subjects participated in an 8-phase, 70-week trial that included screening, parent training, baseline, open-label safety lead-in, double-blind crossover titration, double-blind parallel efficacy, open-label maintenance, and double-blind discontinuation. Medication response was assessed during the crossover titration phase using a combination of parent and teacher ratings. Special ethical considerations throughout the trial warranted a number of design changes.
  
  
  RESULTS
  This report describes the design of this trial, the rationale for reevaluation and modification of the design, and the methods used to conduct the trial.
  
  
  CONCLUSIONS
  The PATS adds to a limited literature and improves our understanding of the safety and efficacy of MPH in the treatment of preschoolers with ADHD, but changes in the design and problems in implementation of this study impose some specific limitations that need to be addressed in future studies.
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.. Electronic address: kolli001@mc.duke.edu.
authors.forename: Scott
authors.initials: S
authors.lastname: Kollins
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Laurence
authors.initials: L
authors.lastname: Greenhill
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: James
authors.initials: J
authors.lastname: Swanson
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Sharon
authors.initials: S
authors.lastname: Wigal
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Howard
authors.initials: H
authors.lastname: Abikoff
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: James
authors.initials: J
authors.lastname: McCRACKEN
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Mark
authors.initials: M
authors.lastname: Riddle
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: James
authors.initials: J
authors.lastname: McGOUGH
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Tim
authors.initials: T
authors.lastname: Wigal
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Anne
authors.initials: A
authors.lastname: Skrobala
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Kelly
authors.initials: K
authors.lastname: Posner
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Jaswinder
authors.initials: J
authors.lastname: Ghuman
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Mark
authors.initials: M
authors.lastname: Davies
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Charles
authors.initials: C
authors.lastname: Cunningham
authors.affiliation: Dr. Kollins is with Duke University Medical Center, Durham, NC; Drs. Greenhill and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Drs. Swanson, S. Wigal, and T. Wigal are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; and Ms. Bauzo is with the Nathan Kline Institute, Orangeburg, NY.
authors.forename: Audrey
authors.initials: A
authors.lastname: Bauzo
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D012107:Research Design
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate