A multisite trial of atomoxetine and parent training in children with autism spectrum disorders: Rationale and design challenges

• This paper reviews the rationale for a double-blind, placebo-controlled RCT.
• It tests whether ATX and parent training is superior to single treatment/placebo.
• Challenges include: study design, blindness, outcome measures and data analysis.
• Our goal is to assist researchers planning multimodal RCTs for children with ASD.

Several randomized controlled trials (RCTs) involving children with autism spectrum disorder (ASD) have examined effectiveness of mono-therapies for problem behavior. However, results have not been as encouraging as in typically developing children. For example, when prescribed stimulants, children with ASD and hyperactivity/inattentiveness, show only moderately reduced symptoms, with frequent side effects. Therefore, alternative treatments or combinations of treatments are needed. The Children's Hyperactivity and Autism Research Treatment Study (CHARTS) is a randomized clinical trial comparing the individual and combined effects of atomoxetine and parent training to treat hyperactivity, inattentiveness, and noncompliance in children with ASD. Design challenges included the overall study design, targeting of different outcomes by different treatments, and data analysis. This article details options for addressing a number of these methodological issues in the context of conducting a large multicenter RCT with an ASD population.