There is significant interest in defining objective measures of social behavior or cognition, as well as valid, reliable biomarkers to assess clinically relevant change in the core symptoms of ASD [
42,
43]. Objective measures of behavior include eye tracking and machine learning applied to video recordings of non-verbal communication or social interactions [
44]. Neurocognitive testing could also reveal reliable changes in social information processing or cognition; however, it is important to evaluate the frequency of testing required and sensitivity to change of these measures [
45]. Additional biomarkers include electroencephalography and functional magnetic resonance imaging [
43,
46]. These approaches require further research to assess their translatability as indicators of clinically relevant change, and do not necessarily index change in real-world function, which may support FDA or European Medicines Agency approval [
47,
48]. Several initiatives, including those led by the European Autism Interventions-A Multicentre Study for Developing New Medications (EU-AIMS) and the Autism Biomarkers Consortium for Clinical Trials (ABC-CT), aim to characterize and validate biomarkers for use in ASD trials [
33,
46]. Other ongoing studies, including oRBiting (NCT03611075), aim to characterize biomarkers and outcome measures primarily for the assessment of restricted and repetitive behaviors in addition to social communication and interaction [
49]. The development of digital health technology tools has a strong potential to integrate into clinical research and may be a robust and sensitive means to measure efficacy of pharmacologic interventions [
50]. Digital health technology tools may also enable the assessment of ASD characteristics in everyday settings to capture clinically meaningful change. Based upon the Autism and Beyond and iOS ResearchKit studies, a digital app was developed for caregivers to collect videos of their children while watching a movie. The videos can be uploaded and then analyzed to quantify children’s behaviors and emotions [
51]. The Janssen Autism Knowledge Engine (JAKE
®) has been developed to measure the core and associated symptoms of ASD, comprising a mobile app and wearable sensors to track progress, core symptoms, and physiologic characteristics [
52]. Roche has started to develop a suite of assessments collected via consumer smartphones and wearables to allow objective and daily assessment of ASD core symptoms and potential underlying adaptive and cognitive skills, with an aim of using these assessments to monitor ASD symptoms in RCTs [
53]. Digital health technology tools are also being explored as a means to support social communication in autistic individuals [
54]. Other avenues that could be explored include novel outcome measures such as the Brief Observation of Social Communication Change, which was developed for young autistic children and aims to quantify subtle changes in social communication [
55]. Caregiver- and participant-reported exit interviews may also be a valuable way to obtain both qualitative and quantitative data, which may support the development of novel measurement strategies, such as biomarkers, to evaluate meaningful change in ASD outcomes.