Methodological issues in designing a multisite trial of risperidone in children and adolescents with autism.
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.
Scahill
L
L
Research Unit on Pediatric Psychopharmacology Yale University, New Haven, Connecticut 06520, USA. lawrence.scahill@yale.edu
McCracken
J
J
McDougle
C J
CJ
Aman
M
M
Arnold
L E
LE
Tierney
E
E
Cronin
P
P
Davies
M
M
Ghuman
J
J
Gonzalez
N
N
Koenig
K
K
Lindsay
R
R
Martin
A
A
McGough
J
J
Posey
D J
DJ
Swiezy
N
N
Volkmar
F
F
Ritz
L
L
Vitiello
B
B
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
D014150:Antipsychotic Agents; D018967:Risperidone