This four-year multisite project will advance outcome measurement of anxiety in future clinical trials in youth with autism spectrum disorders (ASDs). Program announcement (PAR-11-045) declares that the dearth of outcome measures in developmentally disabled populations is a major impediment for drug research in developmentally disabled populations. Impairing anxiety is common in youth with ASDs and a plausible treatment target, but poorly studied (White et al., 2009; van Steensel et al., 2011; King et al., 2009). There are well-accepted outcome measures for anxiety in typically developing youth (RUPP Anxiety Group, 2001; Walkup et al., 2008). Given the language and cognitive deficits in ASDs, these measures are not suitable for youth with ASDs without modification. The need for outcome measures for anxiety in youth with ASDs has also been noted by consumer groups (www. autismspeaks.org). We have assembled an outstanding team of investigators and consultants to develop a parent-rated and a clinician-rated instrument for measuring anxiety in youth with ASDs who participate in clinical trials. We propose a mixed method approach in line with the FDA monograph: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (www.Fda.Gov/Cder /Guidance). In Yr 1, focus groups with parents will explore the manifestations of anxiety in children with ASDs. This information will be used to refine the CASI Anxiety scale (DSM-IV-based parent-rating) and modify the clinician-rated Pediatric Anxiety Rating Scale (PARS). Yr 2 will collect data on the revised CASI Anx scale (20-25 items) in 900 children with ASD ages 5 to 17 years on a secure web site. We will examine the distribution, internal consistency, factor structure and item analysis of this parent-rated scale. Test-retest reliability of the scale will be evaluated in a subsample of online respondents and a sample of subjects assessed in person. Validity of the CASI Anx scale will be evaluated by contrasting the correlations with another parent-rated measure of anxiety (convergent validity) and with measures of repetitive behavior, social disability and irritability (divergent validity). The revised PARS will be collected via in person assessments of 90 subjects to evaluate reliability (inter-rater, internal consistency) and validity in Yr 3. In Yrs 34, a high anxiety subgroup (above threshold on the CASI Anx scale) will be compared to controls (ASD with low anxiety) on physiological measures of heart rate [HR], heart rate variability [HRV] and electrodermal activity [EDA]). HR, HRV and EDA will be measured at rest and under mildly anxiety provoking conditions. Results from this exploratory investigation may identify read outs for early testing of compounds for anxiety in ASDs. The project has four deliverables: focus group results (Yr 2); a reliable and valid parent-rated anxiety outcome measure (Yr 3); a reliable and valid clinician-rated anxiety measure (Yr 4); preliminary HRV and EDA findings (soon after the grant period).
Autism Spectrum Disorders (ASDs) are disabling conditions affecting an estimated 9 per 1000 children (roughly 450,000 American children between age 5 and 17 years). At least a third (150,000) of youth with ASDs is further disabled by anxiety problems. This project is focused on outcome measurement of anxiety in youth with ASDs, which is a prerequisite for advancing drug and psychosocial treatments.
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