title: Methodological issues in designing a multisite trial of risperidone in children and adolescents with autism.
abstract: OBJECTIVE
  To describe the methodological challenges and decisions made in developing a multisite, controlled study of risperidone in children and adolescents with autism.
  
  
  METHODS
  Review the design considerations for clinical trials in children with autistic disorder accompanied by severe tantrums, aggressive and/or self-injurious behaviors. These design considerations include the definition of inclusion criteria that are relevant to clinical practice and matching study design to the goal of evaluating short- and long-term effects. Additional ethical and scientific issues concern the length of trial and sample size.
  
  
  RESULTS
  We undertook a short-term, placebo-controlled study to evaluate the efficacy and safety of risperidone in children and adolescents with autistic disorder. This trial design was followed by an extended open-label maintenance on risperidone to confirm durability of treatment effects and to monitor safety. Finally, a placebo-controlled discontinuation study tested the need for continuous treatment.
  
  
  CONCLUSIONS
  In the absence of standard pharmacological treatment for children with autistic disorder, a placebo-controlled study remains the most appropriate method of testing efficacy and safety. The clinical relevance of this study is enhanced by the addition of an extended maintenance phase followed by a placebo discontinuation.
authors.affiliation: Research Unit on Pediatric Psychopharmacology Yale University, New Haven, Connecticut 06520, USA. lawrence.scahill@yale.edu
authors.forename: L
authors.initials: L
authors.lastname: Scahill
authors.forename: J
authors.initials: J
authors.lastname: McCracken
authors.forename: C J
authors.initials: CJ
authors.lastname: McDougle
authors.forename: M
authors.initials: M
authors.lastname: Aman
authors.forename: L E
authors.initials: LE
authors.lastname: Arnold
authors.forename: E
authors.initials: E
authors.lastname: Tierney
authors.forename: P
authors.initials: P
authors.lastname: Cronin
authors.forename: M
authors.initials: M
authors.lastname: Davies
authors.forename: J
authors.initials: J
authors.lastname: Ghuman
authors.forename: N
authors.initials: N
authors.lastname: Gonzalez
authors.forename: K
authors.initials: K
authors.lastname: Koenig
authors.forename: R
authors.initials: R
authors.lastname: Lindsay
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: McGough
authors.forename: D J
authors.initials: DJ
authors.lastname: Posey
authors.forename: N
authors.initials: N
authors.lastname: Swiezy
authors.forename: F
authors.initials: F
authors.lastname: Volkmar
authors.forename: L
authors.initials: L
authors.lastname: Ritz
authors.forename: B
authors.initials: B
authors.lastname: Vitiello
mesh_terms: D000293:Adolescent; D000367:Age Factors; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001321:Autistic Disorder / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D018849:Controlled Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D015337:Multicenter Studies as Topic; D010934:Planning Techniques; D012107:Research Design; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone