The Autism Biomarkers Consortium for Clinical Trials: Clinical Characteristics and Interim Evaluation of Clinical Measures Commonly Used in Clinical Trials

Background: The investigation of social interventions for ASD has traditionally relied on clinician rating scales and parent surveys, raising concerns about their relation to underlying mechanisms targeted by treatment, sensitivity to treatment-related changes, and potential for bias when used to measure interventions that are difficult to mask from clinicians and families. The ABC-CT provides an opportunity to examine the utility of these measures with respect to construct test-retest reliability, discriminant and convergent validity. The project also provides an opportunity to examine the feasibility of collecting clinical data in a reliable and precise manner across a five-site consortium.

Objectives: To examine the interim characteristics of a large sample, including possible site-specific differences. To examine convergent validity of the clinical battery, particularly for social communication symptoms of ASD. To explore whether standardized lab-based measures of face and emotion recognition discriminate groups and relate to traditional measures of clinical function. To examine interim data for test-retest validity of commonly used clinical measures.

Methods: To date, data are available from the Feasibility phase of the project, which included 25 children with ASD and 26 typically developing controls (4-11 years, FSIQ = 53-133). The presentation will include data from approximately 205 children across two time points at ABC-CT interim analysis.

Results: There were site specific differences in age, but not gender or clinician rating measures: ADOS-2 calibrated severity scores, ADI-R, Vineland-3, or CGI. In terms of convergent validity within the social domain, clinician ratings of social symptom severity (CGI) related to ADOS-2 social affect calibrated severity scores, Vineland-3 socialization, PDDBI Social Pragmatic, and SRS-2 Social Communication (ps < .05), suggesting excellent convergent validity for the CGI with other measures of current social communication symptoms within the group with ASD. The ADI-R social domain, which emphasizes historical symptoms; PDDBI Social Approach; SRS-2 Social Awareness, Social Cognition, Social Motivation; and CASI Autism and Asperger scales were not related to CGI. In contrast, the ADOS-2 social affect calibrated severity score was unrelated to ADI-R social, PDDBI, SRS-2 or CASI scales related to social communication symptoms. Likewise, the ADI-R Social scale was related to only the SRS-2 Social Cognition and Social Motivation and CASI Autism/Asperger’s scales. The Vineland-3 Socialization scale related to all CASI, SRS-2 and PDDBI social and autism scales (ps <.06), and all SRS-2 and PDDBI social scales were related to each other (ps <.05). A standardized lab-based measure of face and emotion recognition (NEPSY-2) discriminated groups (face: t(40)=5.03, p<.001; emotion: t(40)=2.75, p=.009) and face memory related the ADOS-2 social affect scores.

Conclusions: Initial findings from ABC-CT feasibility provide information to guide selection of social measures for clinical trials confirming that traditional measures are feasible in a multisite clinical trial, have varying convergent validity, and are relatively independent from performance-based measures, such as the NEPSY-II. The replication of these findings among a larger sample (N=200), including test-retest reliability over a 6-week period will also be presented.