The public health impact of autism spectrum disorder (ASD) is gaining global recognition. Early intervention for ASD is of critical importance because it improves outcomes and lessons long-term costs. Naturalistic Developmental Behavioral Interventions (NDBIs), are a type of empirically-based early ASD intervention methods that can be taught to caregivers, via caregiver-coaching. Caregiver use of NDBI strategies can promote child joint attention and affective engagement, which promote language acquisition - a key predictor of long-term functional outcomes. However, very little behavioral and developmental research that examines the principles and underlying assumptions of NDBIs has been performed outside of Western contexts. In addition, ASD research has disproportionately low representation from minority groups, multilingual families, and participants from lower socioeconomic status. Importantly, cross-cultural variation has been reported in NDBI treatment targets, such as core ASD symptoms and features of caregiver-child interactions. Fundamental gaps in our knowledge therefore remain on the validity of NDBI treatment targets, especially in multi-cultural settings. In addition, objectively assessing NDBI response is a significant challenge. 'Gold standard' tools are costly, require trained professionals, and may not be culturally valid. MHealth tools that assess ASD biomarkers may help address this challenge by enabling point-of-care detection by non-specialists. Efforts to implement NDBIs in multi-cultural community settings is increasing worldwide. Alongside these efforts, it is crucial to ensure that our treatment targets are valid and that we can measure treatment response. The R21 builds upon work conducted in an NIMH-funded K01 (PI: Franz). In the first study of its kind on the African continent, Dr Franz has adapted a caregiver-coaching NDBI for delivery by non-specialists, and 'gold standard' clinical outcomes as well as implementation outcomes are being assessed. The R21 aims to extend this work by evaluating NDBI treatment targets and a novel digital outcome measure of treatment response, following 12 sessions of NDBI-informed caregiver coaching, delivered by non-specialists in South Africa. South Africa, a multi-cultural nation marked by health disparities, is an innovative study location because it provides a unique opportunity to assess feasibility and impact of a scalable intervention, in an environment with significant contextual challenges. The R21 is a joint project between Duke University and the University of Cape Town (UCT). While all research activities will be conducted in Cape Town, South Africa, ASD clinical research capacity building will include both UCT and Kilimanjaro Christian Medical Center (KCMC) in Tanzania, via a South-to-South collaboration. Both sites are included in order to prepare our team to develop an R01 application for a regionally-focused randomized ASD early intervention clinical trial, which will include sites in both South Africa and Tanzania and allow for further refinement of innovative clinical outcome measures.

Naturalistic Developmental Behavioral lnterventions (NDBls), an evidence-based early autism spectrum disorder intervention approach, target key behaviors that help language development. While efforts to use NDBls are increasing worldwide, important gaps in our knowledge remain on whether the behaviors targeted by NDBls are cross-culturally valid. Our study in South Africa, a multi-cultural setting, will provide critical information on NDBl treatment targets and a novel digital outcome measure of treatment response.