Rationale, design, and methods of the Preschool ADHD Treatment Study (PATS).
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.
Kollins
Scott
S
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.
Greenhill
Laurence
L
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.
Swanson
James
J
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.
Wigal
Sharon
S
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.
Abikoff
Howard
H
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.
McCRACKEN
James
J
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.
Riddle
Mark
M
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.
McGOUGH
James
J
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.
Vitiello
Benedetto
B
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.
Wigal
Tim
T
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.
Skrobala
Anne
A
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.
Posner
Kelly
K
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.
Ghuman
Jaswinder
J
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.
Davies
Mark
M
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.
Cunningham
Charles
C
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.
Bauzo
Audrey
A
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.
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
D000697:Central Nervous System Stimulants; D008774:Methylphenidate