Using a Patient-Centered Outcome Measure to Test Methylphenidate Versus Placebo in Children with Autism Spectrum Disorder.

Objectives: Parent rating scales are commonly used to evaluate change in clinical trials. Despite advantages, these measures may not capture parental impression of the child's most salient problems. We examine the use of parent target problems (PTPs) in a randomized trial of methylphenidate (MPH) in children with autism spectrum disorder and symptoms of attention-deficit/hyperactivity disorder.

Methods: This multisite, 4-week, randomized crossover trial compared three dose levels (low, medium, and high) of MPH with placebo. At baseline, the independent evaluator (IE) asked parents to nominate the child's two biggest problems. For each problem, the IE and parent coconstructed a brief narrative of the behavior and the impact on family life. The IE and parents reviewed and revised the narratives at subsequent visits. A panel of four judges, blind to treatment condition, independently reviewed the narratives to rate change from baseline on a 9-point scale: 1, normal; 2, markedly improved; 3, definitely improved; 4, equivocally improved; 5, no change; 6, possibly worse; 7, definitely worse; 8, markedly worse; 9, disastrously worse. The mean of the four raters was compared with primary and key secondary ratings from the original study.

Results: Two PTPs were recorded at baseline for 60 participants. The inter-rater reliability of the four judges across all PTPs and time points was excellent (intraclass correlation = 0.95). On the primary outcome measure (Aberrant Behavior Checklist Hyperactivity subscale), the medium and high-dose levels were superior to placebo. On the mean PTP rating, only the high dose was superior to placebo. We also compared PTP cutoff scores 3.0 (definitely improved), 3.25, and 3.5 with the rate of positive response on the Improvement item of the Clinical Global Impressions scale in the original study. Sensitivities ranged from 68% to 88%.

Conclusions: The parent target problem method offers a systematic way to identify and track patient-centered outcomes.