Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials.
OBJECTIVE
A consumer-oriented efficacy assessment in clinical trials should measure changes in chief complaint and consumer request (symptoms of most concern to patient/caregiver), which may be diluted in change scores of multisymptom scales.


METHODS
In the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network 8-week double-blind trial of risperidone versus placebo, the chief concerns of parents were collected at 0, 4, and 8 weeks (endpoint), in addition to standardized primary measures. Blinded clinical judges rated change from baseline to 4 and 8 weeks on a 9-point scale (1 = normalized, 5 = unchanged, 9 = disastrous); 94 participants had usable data.


RESULTS
The most common symptoms identified by parents were tantrums, aggression, and hyperactivity. Interrater reliability was excellent. Mean ratings at endpoint were 2.8 +/- 1.2 on risperidone and 4.5 +/- 1.3 on placebo (p <.001). Ratings were collinear with Clinical Global Impression-Improvement and Aberrant Behavior Checklist Irritability subscale (primary dimensional measure). Effect size d was 1.4, compared to 1.2 on the Aberrant Behavior Checklist Irritability subscale. Effect sizes varied twofold by symptom category, largest for self-injury (2.11) and tantrums (1.95).


CONCLUSIONS
Risperidone was superior to placebo in reducing symptoms of most concern to parents of autistic children with irritable behavior. Rating individualized participant-chosen target symptoms seems a reliable, sensitive, efficient, and consumer-friendly way to assess treatment effect and might have clinical application.
Arnold
L Eugene
LE
Ohio State University, 479 S. Galena Road, Sunbury, OH 43074, USA. arnold.6@osu.edu
Vitiello
Benedetto
B
McDougle
Christopher
C
Scahill
Larry
L
Shah
Bhavik
B
Gonzalez
Nilda M
NM
Chuang
Shirley
S
Davies
Mark
M
Hollway
Jill
J
Aman
Michael G
MG
Cronin
Pegeen
P
Koenig
Kathleen
K
Kohn
Arlene E
AE
McMahon
Donald J
DJ
Tierney
Elaine
E
D000293:Adolescent; D000328:Adult; D000339:Affect; D000374:Aggression; D001321:Autistic Disorder / Q000188:drug therapy* / Q000523:psychology; D002648:Child; D002986:Clinical Trials as Topic; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008297:Male; D015588:Observer Variation; D010287:Parent-Child Relations; D010919:Placebos; D012107:Research Design; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013239:Stereotyped Behavior; D016896:Treatment Outcome
D018492:Dopamine Antagonists; D010919:Placebos; D018967:Risperidone