Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials

J Am Acad Child Adolesc Psychiatry. 2003 Dec;42(12):1443-50. doi: 10.1097/00004583-200312000-00011.

Abstract

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.

Method: 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Affect
  • Aggression
  • Autistic Disorder / drug therapy*
  • Autistic Disorder / psychology
  • Child
  • Clinical Trials as Topic*
  • Dopamine Antagonists / pharmacology
  • Dopamine Antagonists / therapeutic use*
  • Double-Blind Method
  • Endpoint Determination
  • Female
  • Humans
  • Male
  • Observer Variation
  • Parent-Child Relations*
  • Placebos
  • Research Design
  • Risperidone / pharmacology
  • Risperidone / therapeutic use*
  • Severity of Illness Index
  • Stereotyped Behavior
  • Treatment Outcome

Substances

  • Dopamine Antagonists
  • Placebos
  • Risperidone