Tailoring Treatment Targets for Early Autism Intervention in Africa
Phase: NA
Conditions: Autism Spectrum Disorder
Sponsor: Duke University

 
 
 
 
 
 
 
 
 
Tailoring Treatment Targets for Early Autism Intervention in Africa 
Document Date: July 26, 2019 
NCT04068688 

Purpose of the Study 
 
Naturalistic Developmental Behavioral Interventions (NDBIs), an evidence-based early autism 
spectrum disorder (ASD) intervention approach, target key behaviors that help language development. 
While efforts to use NDBIs are increasing worldwide, important gaps in our knowledge remain on 
whether the behaviors targeted by NDBIs are cross-culturally valid. Our study in South Africa, a multi- 
cultural setting, will provide critical information on NDBI treatment targets and a novel digital outcome 
measure of treatment response. 
 
Aim 1: Characterize NDBI child treatment targets in South African children with ASD using standardized 
assessments and digital technology, and determine whether these patterns differentiate children with 
ASD from their peers with developmental delay and typical development. An exploratory component of 
Aim 1 will assess whether 12 sessions of NDBI caregiver coaching result in changes in child treatment 
targets assessed using digital technology. 
 
Aim 2: In the ASD group, determine the caregiver-child context for South African dyads, by identifying 
common family routines and characteristics of caregiver-child dyadic exchanges. 
 
Aim 3: In the ASD group, describe strategies caregivers use during caregiver-child interactions and 
evaluate whether there are changes in caregiver-specific strategies following NDBI caregiver coaching. 
 
Aim 4: Adapt the NDBI caregiver coaching intervention and assessment of caregiver NDBI strategies for 
telehealth delivery in order to maintain services for young children with ASD impacted by COVID-19. 
Explore the acceptability, feasibility, and appropriateness of the adapted intervention and assessment 
approach.  
 
Background 
 
Autism early detection and intervention is increasingly recognized as a critical public health 
focus globally. Early detection and intervention can result in positive gains in cognitive, social, language, 
and adaptive behaviors, and as well as decreases in the long-term costs of special education, sheltered 
living and supported employment. Naturalistic developmental behavioral interventions (NDBIs), a type 
of empirically-based early intervention methods, are derived from the principles of applied behavior 
analysis and developmental science.4 Caregiver use of NDBI strategies during caregiver-child 
interactions, promotes child joint attention and affective engagement, which promote language 
acquisition—a key predictor of long-term functional outcomes. Efforts to implement NDBIs in 
community settings are increasing worldwide. 
Limited research examines the underlying assumptions of NDBIs outside of Western contexts. 
The majority of behavioral and developmental research is conducted in non-representative populations, 
as less than 3% of participants come from Africa, Central and South America, Asia, and the Middle East. 
In addition, autism spectrum disorder (ASD) research has disproportionately low representation 
from minority groups, multilingual families, and participants with lower socioeconomic status. 
Anthropological theorists posit that many of the social constructs targeted in NDBIs have varied norms 

and baseline frequencies across cultures. Cross-cultural variation in eye contact, facial expressions, play, 
and language use may result in biases in ASD symptom recognition in culturally-diverse groups when 
using instruments normed on Western samples. NDBIs are carried out in daily routines, using materials 
that families have in their homes. However, current NDBIs are based on Western cultural contexts, and 
cross-cultural variations in materials and adult participants in routines have been reported. In addition, 
cross-cultural variations have been reported in caregiver-child dyadic exchanges, including the degree to 
which mothers focus on face-to-face interaction and object-based play with their young children, as well 
as maternal reactions to child communicative cues. 
The evidence base for determining whether NDBIs improve outcomes across cultures is lacking, 
and certainly not as strong as the evidence for their efficacy in monolingual, English-speaking, middle- 
socio-economic status participants from Western cultural contexts. As such, important research gaps 
exist and what remains unknown is whether NDBI treatment targets are valid in non-Western contexts, 
particularly when caregivers are the ones delivering NDBI strategies to their child. 
Assessment of child response to NDBI-intervention is a significant challenge in low-resource 
settings. ‘Gold standard’ tools are costly, administered by professionals, and may not be culturally valid. 
mHealth tools that assess ASD behavioral risk markers can help address this challenges, by enabling 
point-of-care detection by non-specialists. Atypical eye gaze is one of the most promising behavioral risk 
marker of ASD. In addition, studies suggest that individuals with ASD show a reduction in certain facial 
expressions in response to stimuli. Portable, low-cost technologies that perform eye tracking and 
automatically analyze facial expressions are being developed and piloted. Some of this piloting has 
occurred in South Africa. Exploring whether digital health tools, can overcome barriers to assessing child 
treatment response is an exciting and necessary avenue of discovery in global health. The rapid 
developments in technologies around the globe, and increasing global access to the internet and mobile 
technologies, make this a particularly important avenue for exploration. 
Fidelity of intervention delivery, the degree to which programs are implemented as intended by 
program developers, is an important implementation outcome because it can moderate the impact of 
an intervention on targeted health outcomes. Use of NDBI strategies by caregivers during joint activity 
routines with their child, at fidelity, is important to track because it can result in changes in child social- 
communication outcomes. However, measurement of acquisition of caregiver NDBI strategies presents 
a significant challenge in low-resource settings as fidelity measurement is time consuming and 
conducted by highly skilled clinicians, which are a limited resource in most parts of the world. If 
widespread community implementation of NDBI is to occur, tools need to be developed that enable 
point-of-care detection of growth in caregiver NDBI strategies in response to intervention.  

Dr. Franz (PI) is currently leading a study on NDBI-informed caregiver coaching in South Africa. 
The study aims to adapt a caregiver coaching version of the Early Start Denver Model (ESDM), an NDBI, 
for implementation by non-specialist early childhood development workers, employed by the 
Department of Education. South Africa is a multi-cultural, multi-lingual nation, marked by stark health 
disparities, where policies have emerged on the importance of early detection and intervention for 
developmental disorders, including ASD. The South African adapted intervention utilizes Community 
ESDM materials, which are currently being piloted in rural, low resource parts of the U.S. The session 
skill is introduced by “Help is in your hands” Community ESDM videos, then early childhood 
development workers coach caregivers on the session skill and support caregiver reflection and skill 
generalization. A pre-pilot with 2 caregiver-child dyads has recently concluded. The pre-pilot yielded 
promising early indications that the intervention training and supervision are feasible, and that the 
measures used to assess child clinical outcomes are sensitive to change. Both child participants in the 
pre-pilot demonstrated significant growth in social and communication subscale scores on the Griffiths 
Scales of Child Development and the Vineland Adaptive Behavior Scales, following 12 sessions of NDBI- 
informed caregiver coaching, delivered by non-specialists. 
Alongside efforts to implement NDBIs in multi-cultural settings, we need to ensure that our 
treatment targets are valid, and that NDBIs are relevant to family life of diverse cultural groups. The 
overall objective of the R21 is to assess the validity of NDBI treatment targets and determine whether 
scalable digital technology can assess treatment response in a multicultural, low resource South African 
setting. Addressing this main research question is critical to designing effective early interventions that 
may be adapted for pilot testing across sub-Saharan Africa. 
Understanding the validity of NDBI targets across diverse populations will help match 
interventions to increasingly diverse populations in the U.S. In the U.S. African American and 
Hispanic/Latino children are diagnosed and access services at a later age as compared to Caucasian 
children. The majority of states have passed legislation that mandates insurance benefits for early 
intervention and there are increasing efforts to implement NDBIs in diverse communities. However, 
knowledge of how to tailor these interventions to diverse communities is incomplete. As such, the R21 
aligns with NIMH Strategic Objective 4: To strengthen the public health impact of NIMH-supported 
research; and objectives of the Federal Interagency Autism Coordinating Committee Strategic Plan: To 
reduce disparities in early detection and outcomes for underserved populations. 
 
Design & Procedures 
 
The R21 will build on collaborations and infrastructure established in Dr. Franz’s NIMH K01. The 
K01 aims to adapt a caregiver coaching version of the Early Start Denver Model (ESDM), an NDBI and the 
first empirically-validated comprehensive intervention for toddlers with ASD, for implementation by 
non-specialists in South Africa. Following a significant amount of formative work and capacity building, a 
pilot study will begin in January 2019, and enroll 20 ASD caregiver-child dyads from culturally diverse, 
low-resource backgrounds. 
The R21 will evaluate NDBI child, caregiver-child, and caregiver treatment targets, and a digital 
outcome measure of treatment response. The study design will include both a baseline cross-sectional 
phase and a longitudinal pre-post phase, nested within the ongoing K01. The R21 will extend ASD group 
recruitment by 1 year, allowing for 30 ASD caregiver-child dyads to be recruited in total. In addition, the 
R21 will facilitate recruitment of 30 children with developmental delay and 30 with typical development 

who, along with the ASD group, will participate in the baseline cross-sectional phase of the study. The 
ASD group will then participate in the longitudinal pre-post phase of the study, where they will receive 
12 NDBI-informed caregiver coaching sessions delivered by non-specialists. 
COVID-19 adaptations: Transition to telehealth will only occur for the ASD group who receive 
the caregiver coaching intervention. Baseline assessments of the TD and DD group will be on hold until 
COVID-19 in-person restrictions are lifted by the University of Cape Town IRB. 
The intervention all children in the ASD group (only) will receive is ESDM-informed caregiver 
coaching, delivered to the caregiver-child dyad by a non-specialist early childhood development 
practitioner. All children who receive intervention have a diagnosis of ASD. Twelve, one-hour sessions of 
individual caregiver coaching occur. In the 12 sessions, the session skill is introduced by “Help is in your 
hands” Community ESDM videos. Session skills include specific strategies caregivers can use to increase 
their child’s attention to people and their child’s communication; strategies to identify, create and use 
joint activity routines to engage with and teach their child; in addition to ways to use the ABCs of 
learning to teach their child new behaviors. “Help is in your hands” Community ESDM materials also 
provide video examples of other caregivers using the session skill with their child. The early childhood 
development practitioner then coaches the caregiver in the session skill, in at least two activities. The 
goal of coaching was to provide enough support for the caregiver to experience success in implementing 
the new skill with their child. Coaching is followed by caregiver reflection and a discussion of 
generalization of the new skill across various daily activities, using a daily activities visual aid. 
In the baseline cross-sectional phase 30 caregiver-child dyads with ASD, 30 with typical 
development, and 30 with developmental delay will be recruited. ASD caregiver-child dyads will 
continue to be recruited from Western Cape Department of Education Autism Schools (as per K01 
recruitment approach). Children with developmental delay will be recruited from Neurodevelopmental 
Clinics at Red Cross Children's Hospital. Children with typical development will be recruited from Early 
Childhood Development Centers. Inclusion criteria are as follows: (1) the child is between 18 and 72 
months of age; (2) the subject’s family speak isiXhosa, isiZulu, Afrikaans, or English (~ 97% of all 
household languages spoken in the Western Cape province); (3) the child’s ethnicity/race is African or 
Coloured (a South African term for mixed race); and (4) the child lives within an area served by the 
recruitment sites. Additional inclusion criteria are group specific. For the ASD group: (1) the child meets 
criteria for an ASD diagnosis based upon DSM-5 criteria and informed by the ADOS-257 administered by 
research reliable raters; and (2) the caregiver is ≥ 18 years old. For the developmental delay group: (1) 
the child screens positive on the Ten Questions; (2) screens negative on the autism behavior checklist 
(ABC); and (3) has been diagnosed with developmental delay by a developmental pediatrician. For the 
typically developing group: The child (1) screens negative for a developmental delay on the Ten 
Questions; and (2) screens negative on the autism behavior checklist (ABC). 
COVID-19 adaptations: Because we aim to assess the acceptability, feasibility, and 
appropriateness of the adapted telehealth coaching intervention - views of multiple stakeholders 
involved in the implementation of the intervention will be assessed. This includes the child's caregiver, 
Early Childhood Development Practitioners, Early Childhood Development Practitioner School 
Supervisors, and ESDM therapists who provide supervision and oversight of the caregiver coaching 
session. Inclusion criteria are as follows: For the Early Childhood Development Practitioners (n=2) and 
Early Childhood Development Practitioner School Supervisors (n=2) group: the ECD worker and/or 
school supervisor are 1) employed by our participating recruitment partners (Western Cape Education 
Department Schools) and 2) involved in delivery of the caregiver coaching sessions, either in person or 

remotely. For the Early Start Denver Model supervisors (n=3): the local supervisors are 1) trained ESDM 
therapist, 2) supervise weekly coaching sessions in the schools, and/or 3) supervise remote intervention 
delivery sessions. 
Exclusion criteria for the ASD group include: (1) the presence of a neurological disorder of 
known etiology (e.g., Fragile X); and (2) a caregiver-child dyad that is unable to attend assessments and 
12 coaching sessions. Exclusionary criteria for all groups include: (1) significant sensory or motor 
impairment; (2) major physical abnormalities; and a (3) history of serious head injury and/or 
neurological disease. 
The baseline cross-sectional phase will be used to investigate Specific Aim 1: Validity of child 
NDBI treatment targets, and Specific Aim 2: Characterization of caregiver-child NDBI treatment targets. 
Specific Aim 1 will utilize all the groups of participants (ASD, developmental delay, and typical 
development). Specific Aim 2 will only utilize the ASD group. 
 
Baseline assessments in the ASD group include: 
 
• 
Demographic questions (completed by caregiver) 
• 
The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3): (completed by clinician) The 
Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) is an individually-administered 
measure of adaptive behavior that is widely used to assess individuals with intellectual, 
developmental, and other disabilities. The Vineland-3 contains 5 domains each with 2-3 
subdomains. The main domains are: Communication, Daily Living Skills, Socialization, Motor 
Skills, and Maladaptive Behavior. The Caregiver Interview Form uses the Vineland 
semistructured interview technique to elicit information about the examinee’s adaptive 
functioning from a parent or caregiver. Sparrow, S.S., Cichetti, D.V., & Saulnier, C.A. (2016). 
Vineland Adaptive Behavior Scales, Third Edition. San Antonio, TX: Pearson. 
• 
Griffiths Scales of Child Development, Third Edition (Griffiths III): (completed by clinician) The 
Griffiths Scales of Child Development, Third Edition (Griffiths III) is a comprehensive, 
developmental measure for continuous use from birth to 6 years (72 months). Although not 
standardized in South Africa (standardization samples are from the United Kingdom and 
Ireland), this developmental assessment is widely used in South Africa. The Griffiths III provides 
an overall measure of a child’s development, as well as an individual profile of strengths and 
needs across five areas: Foundations of Learning; Language and Communication; Eye and Hand 
Coordination; Personal–Social–Emotional; and Gross Motor. Green, E., Stroud, L., Bloomfield, S., 
Cronje, J., Foxcroft, C., Hurter, K., Lane, H., Marals, R., Marx, C., McAlinden, P., Paradice, R., 
Venter, D. (2015). Griffiths Scales of Child Development, Third Edition. 2015. WPS. 
• 
Autism Diagnostic Observational Schedule – Second Edition (ADOS-2): (completed by clinician) 
Semi structured standardized observation that measures autism symptoms in social relatedness, 
communication, play and repetitive behaviors. A standardized severity score based on codes 
within these domains can be calculated to compare autism symptoms across modules. Lord, C., 
Rutter, M., DiLavore, PC., Risi, S., Gotham, K., Bishop, S. Autism diagnostic observation schedule, 
Second Edition. Torrance, CA: Western Psychological Services; 2012. 
• 
Child Mental Health: The Strengths and Difficulties Questionnaire: (completed by caregiver) 25- 
item emotional and behavioral screening measure for children. R. Goodman, The extended 
version of the Strengths and Difficulties Questionnaire as a guide to child psychiatric caseness 

and consequent burden. Journal of child psychology and psychiatry, and allied disciplines 40, 
791-799 (1999); published online EpubJul 
• 
The Patient Health Questionnaire: (completed by caregiver) 9-item depression scale K. Kroenke, 
R. L. Spitzer, J. B. Williams, The PHQ-9: validity of a brief depression severity measure. Journal of 
general internal medicine 16, 606-613 (2001); published online EpubSep 
• 
The Generalized Anxiety Disorder 7-Item Scale: (completed by caregiver) 7-item screener for 
Generalized Anxiety Disorder. R. L. Spitzer, K. Kroenke, J. B. Williams, B. Lowe, A brief measure 
for assessing generalized anxiety disorder: the GAD-7. Archives of internal medicine 166, 1092- 
1097 (2006); published online EpubMay 22 10.1001/archinte.166.10.1092). 
• 
The Alcohol Use Identification Test Scale: (completed by caregiver) 10-item screener designed to 
identify hazardous drinking T. F. Barbor, J. C. Higgens-Biddle, J. B. Saunders, M. G. Monterio, The 
Alcohol Use Disorders identification Test. Guidelines for use in primary care. (World Health 
Organization, Department of Mental Health and Substance Dependence, Geneva, 2001). 
• 
The Life Stressor Checklist-Revised: (completed by caregiver) 30 item measure of traumatic life 
events. J. Wolfe, R. Kimberling, in Assessing psychological trauma and PTSD, J. Wilson, T. M. 
Keane, Eds. (Guilford, New York, 1997), pp. 192-238. 
• 
Caregiver competence: The Parent Sense of Comptence Scale - (completed by caregiver) 16-item 
caregivers confidence and quality of affect associated with parenting C. Johnston, E. J. Mash, A 
measure of parenting satisfaction and efficacy. Journal of Clinical Child 
Psychology 18, 
167-175 (1989). 
• 
The Parenting Stress Index – Short Form: (completed by caregiver) 36 items magnitude of stress 
in the caregiver-child system R. Abidin, Parenting Stress Index Professional Manual. Third 
Edition. (Psychological Assessment Resources Inc, 1995) 
• 
SenseToKnow App (completed by child) Total time to complete: 10 minutes SenseToKnow is an 
app developed for mobile devices that is designed to elicit autism risk behaviors. In order to 
administer the app, children sit on the parent’s/guardian’s lap with the mobile device at eye 
level for the child. The frontal camera in the iPad records video throughout the stimuli 
presentations at 1280 x 720 resolution, 30 frames/sec. The app is comprised of a set of stimuli 
(videos and games) that are designed to elicit autism spectrum disorder (ASD) symptoms, such 
as facial expressions. Stimuli consist of a series of video clips including toys that make noise, a 
man blowing bubbles, bubbles cascading and popping, and a puppy video with unexpected 
events (for example, the ‘Make Me Laugh’ video). Stimuli in total take 6 min. 40 secs. to 
administer. At three pre-specified times, an examiner positioned behind the child calls the 
child’s name. Movies can be stopped and re-started if the child is fussy. Actors are of diverse 
ethnic/racial backgrounds. Right versus Left placement of the stimuli (counter-balanced across 
movies) takes into account the sensors and computer vision anlaysis capabilities (e.g. ability to 
track gaze to R vs. L side of screen). Overall, the entire task takes approximately 10 minutes. 
Children are allowed to take breaks between videos and games as needed. A research assistant 
is present at all times to answer questions. Stimuli included in the app have been informed by 
previous studies overseen by investigators of this protocol [1-6]. Dependent variables include 
multiple behaviors, all of which have been found in previous studies to be present in children 
with ASD, including total duration attending to screen; duration of attention to social vs. 
nonsocial stimuli; frequency and latency to orient to name; frequency of social referencing; 
range, frequency, intensity, and duration of facial affect; and postural sway. 

o In the study, we will evaluate the reliability and validity of SenseToKnow for eliciting 
autism symptoms by comparing the responses to the app in children with and without 
autism. In addition to evaluating group differences, the SenseToKnow app will be 
piloted to assess treatment response, following 12 sessions of caregiver coaching, 
delivered by non-specialists. The study will not make any determination of diagnosis 
using the SenseToKnow app. Diagnoses will only be made by using already established 
and validated methods and communicated by trained clinicians. 
o While the study team does not anticipate any direct risk related to use of the 
SenseToKnow app, the following precautions will be taken to protect the privacy of 
participants and maintain confidentiality of research data. Data that is collected by the 
SenseToKnow app will be stored locally on the devices until data is securely moved by 
trained study staff. Project staff at the University of Cape Town will upload data to a 
secure shared Duke Box folder, from where Duke project staff will transfer the data to a 
secure folder on the file server at Duke University. Data stored on the device will be 
automatically erased immediately after data transfer to the secure database is 
completed by a trained staff member. The devices will be hardened according to 
guidelines from Duke Office of IT Security. For additional security we will add a user 
password to this application so that no one other than those that were given the 
password set on the device can have access to this data through the device itself. Study 
team members and collaborators will have access to data according to their roles and 
responsibilities as determined by the Principal Investigator, described in the research 
summary, and delegation of authority logs. This transfer of data would not occur prior 
to University of Cape Town and Duke University Institutional Review Board approval. 
• 
Technology Questionnaire and Qualitative Interview of SenseToKnow App 
feasibility/appropriateness (completed by caregiver) 
• 
Joint Engagement Rating Inventory (JERI): (Video recorded caregiver child interaction. Coded by 
trained coder) The Joint Engagement Rating Inventory (JERI) contains seventeen 7 point Likert 
scale items that characterize various aspects of joint engagement. The items span the range of 
possibilities observed during interactions with 18 to 30 month typically developing children and 
similarly aged and older children with developmental delay, including ASD. In order to assess 
joint engagement, a 10-minute video-recorded caregiver-child interaction will be scored in a 
Likert scale by a trained rater, blind to child diagnosis. Items focus on engagement states, child- 
specific codes, caregiver-specific codes, and shared topics. All individuals coding the JERI in this 
study will undergo reliability training involving dual coding of video-recorded caregiver-child 
interactions. Using Nvivo coding software, videos will be coded using the JERI coding manual. 
Nvivo coding software allows coder inconsistencies to be identified during reliability training so 
that each difference can be discussed until consensus is reached. This process will continue for 
each coder until 80% reliability is achieved. After training, 15% of JERI study data will be double 
coded to ensure maintenance of reliability. Adamson, L.B., et al., Rating parent-child 
interactions: joint engagement, communication dynamics, and shared topics in autism, Down 
syndrome, and typical development. J Autism Dev Disord, 2012. 42(12): p. 2622-35. 
• 
Early Social Communication Scales (ESCS) (Completed by child, with support from clinician. 
Video recorded and coded by trained coder). Mundy, P., Delgado, C., Block, J., Venezia, A. and 
Siebert, J., 2003, Early Social Communication Scales (Coral Gables, FL: University of Miami). Joint 

attention skills will be measured using the Early Social Communication Scales (ESCS). The ESCS 
assesses nonverbal communication skills, is normed for typically developing children 18 to 30 
months of age in addition to children with developmental delay expressive language level is in 
approximately the same range. Scores are assigned from video recordings of child behavior 
during a series of tasks administered by a trained examiner. Administration takes between 15-25 
minutes. All individuals coding the ESCS in this study will undergo reliability training involving 
dual coding of ten ESCS administrations. Using Nvivo coding software, child behaviors video 
recorded during the ESCS will be coded in each frame using the ESCS coding manual. This time 
stamped software will allow for coder inconsistencies to be identified during reliability training 
so that each difference can be discussed until consensus is achieved. This process will continue 
for each coder until 80% reliability is achieved on initial codes. After the training, 20% of ESCS 
study data will be double coded to ensure maintenance of reliability. 
• 
Parent Survey of Home and Family Experiences (Completed by caregiver) Balton, S., 2009, 
Family-based activity settings of typically developing three to-five year old children in a low 
income African context, Electronic Thesis and Dissertations, University of Pretoria, UP Space. 
URN no: etd-10172009-122119. A structured interview schedule consisting of a written list of 
closed ended and open-ended questions to assess child home and family routines. 
 
COVID-19 Adaptations: Remote baseline assessments in the ASD group who will include the 
following approved measures from above: a, b, j, m. n, p. Note that n. is coded by a trained coder from 
video-recorded caregiver child interaction. It would not be feasible to complete the full battery of 
measures remotely. 
 
Baseline assessments in the Typically Developing and Developmental Delay groups include: 
 
• 
Demographic Questions (Completed by caregiver) 
• 
The Ten Questions Questionnaire (TQ) (Completed by caregiver) The Ten Questions 
Questionnaire (TQ) is a disability screening tool, extensively used in both 
epidemiological studies and clinically in low resource settings, including South Africa. 
The TQ consists of 10 questions; one each addressing the child's vision, hearing, 
movement and seizures, six on cognition competence, and one extra question regarding 
other serious health problems. Durkin, M.S., et al., Evaluating a ten questions screen for 
childhood disability: reliability and internal structure in different cultures. J Clin 
Epidemiol, 1995. 48(5): p. 657-66. 
• 
Autism Behavior Checklist (ABC) (Completed by caregiver) The Autism Behavior Checklist 
(ABC) will be used to exclude autism spectrum disorder in the typically developing and 
developmental delay groups. The ABC is the most widely used screening tools for ASD in 
low and middle income countries; and the ABC age range aligns with our target 
recruitment age range. The ABC provides a checklist of 47 behaviors typical of autistic 
individuals for use during the initial screening process Krug, D., J. Arick, and P. Almond, 
Autism Screening Instrument for Educational Planning (3rd ed.). 2008, Austin, TX: Pro-Ed 
Copyrighted Instrument: https://www.proedincom/Products/12742/asiep3-autism- 
behavior-checklist-record-forms-25.aspx 

• 
Griffiths Scales of Child Development, Third Edition (Griffiths III) – described in baseline 
assessments (ASD group) 
• 
Joint Engagement Rating Inventory (JERI) – described in baseline assessments (ASD 
group) 
• 
Early Social Communication Scales (ESCS) – described in baseline assessments (ASD 
group) 
• 
SenseToKnow App – described in baseline assessments (ASD group) 
• 
Technology Questionnaire and Qualitative Interview of SenseToKnow App 
feasibility/appropriateness 
• 
In the longitudinal pre-post phase of the study all 30 ASD caregiver-child dyads will 
receive 12, 1-hour ESDM-informed caregiver coaching sessions delivered by non- 
specialist Early Childhood Development practitioners. The longitudinal phase has a 
single study arm, and all ASD caregiver-child dyads will receive the same assessments 
and the same intervention. The longitudinal pre-post phase of the study will be used to 
investigate the exploratory component of Aim 1: Changes in child treatment targets 
measured with SenseToKnow app; and Aim 3: Changes in caregiver strategies targeted 
by the intervention. 
 
Longitudinal pre-post phase assessments in the ASD group include: 
 
• 
Caregiver Early Start Denver Model Implementation Fidelity: (Completed by clinician) 
Likert-based five-point rating system used to assess caregiver mastery of ESDM 
techniques S. Rogers, G. Dawson, L. Vismara, ESDM Parent Fidelity Tool (unpublished 
work). (2012). 
• 
Non-Specialist Coaching Fidelity: (Completed by clinician) Likert-based four-point rating 
system used to assess therapist mastery of parent coaching techniques. S. Rogers, G. 
Dawson, L. Vismara, ESDM Parent Fidelity Tool (unpublished work). (2012). 
• 
The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) – described in 
baseline assessments 
• 
Griffiths Scales of Child Development, Third Edition (Griffiths III) – described in baseline 
assessments 
• 
Caregiver competence: The Parent Sense of Competence Scale– described in baseline 
assessments 
• 
Caregiver stress: The Parenting Stress Index – Short Form– described in baseline 
assessments 
• 
SenseToKnow App – described in baseline assessments 
• 
Joint Engagement Rating Inventory (JERI) – described in baseline assessments 
• 
Qualitative Interview of Caregiver Strategies used during Caregiver-child Interactions 
(post-intervention in ASD group) 
 
COVID-19 Adaptations: Remote follow-up assessments in the ASD group who will include the 
following approved measures from above: a, b, c, e, h, i. Note that a,b,h are coded by a trained coder 
from video-recorded caregiver child interactions. It would not be feasible to complete the full battery of 
measures remotely. We aim to evaluate implementation outcomes (acceptability, appropriateness, 

feasibility) of the telehealth-delivered caregiver coaching approach. Acceptability, appropriateness, and 
feasibility will be quantitatively assessed using 4-item, pragmatic scales: The Acceptability of 
Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of 
Intervention Measure (FIM). Readability is at the 5th grade level. Higher scores indicate greater 
acceptability, appropriateness, and feasibility. In addition, acceptability, appropriateness and feasibility 
will be assessed qualitatively with stakeholder individual interviews. Questions in the interview guide 
will be tailored to stakeholder group and will be informed by previous studies that have examined 
implementation barriers and facilitators during the implementation of new treatment approach. 
 
Specific Aims and Research Methodology 
 
The overall goal of the R21 is to determine the validity of NDBI treatment targets and whether 
scalable digital technology can be used to assess child treatment response in a multicultural, low 
resource South African environment. 
COVID-19 adaptations: We aim to develop and implement telehealth NDBI coaching and utilize a 
mixed methods approach to gather implementation and preliminary effectiveness data on the 
telehealth intervention. 
 
We plan to accomplish this overall objective by pursuing the following three specific aims: 
 
Aim 1: Characterize NDBI child treatment targets in South African children with ASD using standardized 
assessments and digital technology, and determine whether these patterns differentiate children with 
ASD from their peers with developmental delay and typical development. An exploratory component of 
Aim 1 will assess whether 12 sessions of NDBI caregiver coaching result in changes in child treatment 
targets assessed using digital technology. 
This aim will utilize two phases of the study: firstly, the baseline cross-sectional phase, and 
secondly, the longitudinal pre-post phase. In the baseline cross-sectional phase, we will evaluate and 
compare joint attention, engagement states, and explore biomarkers indexing children’s facial affective 
expressions and attention/orienting in South African children with ASD (n=30), developmental delay 
(n=30) and typical development (n=30). We hypothesize that, similar to children in Western cultures, 
South African children with ASD will show decreased responsivity to social bids for attention, make 
fewer intentional social overtures (cumulatively known as joint attention, assessed with the Early Social 
Communication Scales, ESCS), and will show decreased periods of joint engagement (assessed using the 
Joint Engagement Rating Inventory, JERI)15 as compared to South African children with developmental 
delay and typical development. Through the use of an app, child social interest, orienting, attention, and 
affect will be measured in the three groups. We will explore whether children in the ASD group show 
lower attention to social stimuli, consistency in orienting to name calls, and positive affective response 
to stimuli in relation to the developmentally delayed and typically developing groups. We hypothesize 
that, these behaviors will differentiate children with ASD from their peers. 
Frequency scores for initiation of and response to joint attention (IJA and RJA), will be derived 
from behavioral observations during a series of tasks presented by an examiner blind to child diagnosis. 
In order to assess joint engagement, child engagement states will be coded from video-recorded 
caregiver-child interactions and scored in a Likert scale by a trained rater, blind to child diagnosis. For 
joint attention and joint engagement, the primary statistical comparisons will be to evaluate whether 

the ASD group score lower on three co-primary endpoints: IJA and RJA for joint attention, and joint 
engagement. Our power calculation was based on a two-sample t-test with unequal variances, using as a 
reference the observed IJA scores from a similar sample of ASD and typically developing children from a 
Western setting. With two groups of 30, assuming mean (SD) IJA score of 16 (8) among typically 
developing children, we will have 90% power to detect a difference in mean scores of at least 7 between 
ASD and typically developing children. A similar analytic approach will be used for RJA and joint 
engagement. If a difference is observed, between the ASD and typically developing groups, a secondary 
comparison will be conducted to compare the ASD group and the developmentally delayed group, using 
a multiple comparisons adjustment to control for Type I error. In collaboration with experts at Duke, 
using digital technology, we will explore biomarkers indexing children’s facial affective expressions and 
attention/orienting. Using the same statistical analysis approach described above, we will explore 
whether children with ASD show lower attention to social stimuli, consistency in orienting to name calls 
and positive affective response to stimuli in relation to the developmentally delayed and typically 
developing groups. 
In the second phase, we will conduct a longitudinal pre-post study with children in the ASD 
group who receive 12 sessions of intervention. In order to account for the estimated 15% attrition, and 
ensure a final total sample size of 30 caregiver-child dyads in the ASD group for the pre-post phase of 
the study, 35 caregiver-child dyads will initially be recruited. Using digital technology we will re-assess 
child social interest, orienting, attention, and affect post-intervention and explore patterns of change in 
individual trajectories of these behaviors. Paired t-tests (or Wilcoxon rank-sum tests if appropriate), in 
conjunction with exploratory graphical analyses of individual trajectories over time, will be conducted to 
assess the pre versus post change following 12 sessions of NDBI-informed caregiver coaching. 
 
Aim 2: In the ASD group, determine the caregiver-child context for South African dyads, by identifying 
common family routines and characteristics of caregiver-child dyadic exchanges. 
Because NDBIs are delivered in the context of common family routines, it is essential to 
understand how such routines present in South African families. This provides key information about 
how to embed NDBI strategies within family life. K01 pilot data includes descriptions of caregiver-child 
interactions, primarily during play, from 22 ethnically diverse caregivers of young children with ASD in 
South Africa. Data indicated that caregivers regularly interact with their young child with ASD during 
object-based play and sensory social routines. During object-based play, caregivers described dyadic 
interactions, where they joined with their child in child-preferred activities and tried to incorporate 
learning into those interactions. During sensory-social routines, caregivers reported awareness of child 
affect and social communication cues, and a variety of adult and child play participants. Additional data 
is needed to examine family routines; however, caregivers did spontaneously describe interactions with 
their child during family routines of mealtime and bath time. 
During the baseline cross-sectional phase of the study, a mixed methods approach will assess 
caregiver-child context in the ASD group (30 caregiver-child dyads). Quantitative and qualitative data 
will be collected in a simultaneous, balanced arrangement, with equal importance being given to both. 
Quantitative data will describe characteristics of the caregiver-child context using standardized tools. 
Qualitative data will explore culturally-relevant categories not included in the standardized tools, 
developed for Western contexts. At the interpretation phase, results will be triangulated. The process of 
conceptual triangulation will be followed. This involves: (1) conducting qualitative and quantitative 
research, (2) distinguishing salient results, (3) examining confidence in the results, (4) developing criteria 

for inclusion of results, and (5) constructing conceptual models describing the caregiver-child context in 
which NDBI strategies can be embedded. 
Quantitative data will describe types of family routines (assessed via the Family Routines 
Inventory) and characteristics of caregiver-child dyadic exchanges (assessed via the JERI). Routine 
frequency scores will be derived from the Family Routines Inventory. Caregiver-child dyadic exchanges 
will be scored on a Likert scale by a trained rater, from video-recorded caregiver-child interactions, for 
(1) fluency and connectedness, and (2) shared routines and rituals.15 Exploratory graphical assessments 
will be used to understand and represent the distribution and patterns in family routines and dyadic 
interaction item scores. 
Qualitative individual interviews, conducted with caregivers using a semi-structured interview 
guide, will facilitate a broader understanding of South African family routines. Questions will be derived 
from routine categories included in the Family Routines Inventory. Probes will elicit caregiver narratives 
on additional family routines, and routine participants. Individual interviews will be audio-recorded, 
transcribed verbatim and cross-checked for accuracy. Data will be inductively analyzed via content 
analysis using NVivo software. 
 
Aim 3: In the ASD group, describe strategies caregivers use during caregiver-child interactions and 
evaluate whether there are changes in caregiver-specific strategies following NDBI caregiver coaching. 
 
K01 pilot data suggests caregivers can implement Early Start Denver Model (ESDM) strategies as a result 
of 12 sessions of caregiver coaching by non-specialists. In the K01 pre-pilot, the first caregiver almost 
reached 80% fidelity, while the second caregiver surpassed 80% fidelity. This suggests potential for 
successful caregiver implementation of ESDM strategies as a result of the adapted intervention. 
Using a mixed methods approach we will utilize both the baseline cross-sectional phase and the 
longitudinal pre-post phase of the study in the ASD group (30 caregiver-child dyads), to assess caregiver 
strategies. Our approach will be similar to that described in Aim 2. A conceptual model of South African 
caregiver strategies will be constructed. Since the caregiver plays a key role in delivering NDBIs, it is 
essential to understand strategies used by South African caregivers, how readily these strategies change 
when NDBI-informed interventions are delivered, and caregivers’ perception of the NDBI strategies 
used. 
Quantitative assessment of caregiver strategies at baseline and follow-up will be via the JERI, 
and include: (1) scaffolding, (2) following in on a child’s focus, and (3) caregiver affect. These items will 
be scored on a Likert scale by a trained rater, from video-recorded caregiver-child interactions. We 
hypothesize that 12 sessions of NDBI-informed caregiver coaching will result in significant changes in the 
frequency and quality of caregiver strategies. Quantitative data will be analyzed with a paired t-test (or 
Wilcoxon rank-sum test if appropriate) to evaluate the change in caregivers strategies pre versus post 
intervention. In order to account for the estimated 15% attrition, and ensure a final total sample size of 
30 caregiver-child dyads in the ASD group for the pre-post phase of the study, 35 caregiver-child dyads 
will initially be recruited. We will thus have 90% power to detect a standardized effect size (Cohen’s d) 
of 0.60 using a paired t-test, assuming we standardize the difference between pre and post scores to 
have mean 0 and standard deviation 1. 
Qualitative caregiver perceptions of strategies used during caregiver-child interactions will be 
collected at follow-up. Interview scripts will be developed to facilitate a broader understanding of 
strategies that are culturally-relevant to South African caregivers. Individual interviews will be audio- 

recorded. Data will be transcribed verbatim and cross-checked for accuracy, and inductively analyzed via 
content analysis utilizing NVivo. 
 
Aim 4: Adapt the NDBI caregiver coaching intervention and assessment of caregiver NDBI strategies for 
telehealth delivery in order to maintain services for young children with ASD impacted by COVID-19. 
Explore the acceptability, feasibility, and appropriateness of the adapted intervention and assessment 
approach.  
The study team will adapt current session content for a telehealth platform. Each session skills 
will be adapted for delivery using simple pictures with few words via a WhattsApp message. The session 
structure will be maintained as best possible; as it supports adult learning. Sessions will include 12 
telephone-based coaching sessions with: (1) Joint viewing and supported caregiver reflection of pre- 
recorded caregiver-child interaction; (2) Joint review of simple pictorial session skill sent to the caregiver 
via a WhatsApp message; and (3) Facilitated discussion of skill generalization across various caregiver- 
child daily routines. 
We aim to evaluate implementation outcomes (acceptability, appropriateness, feasibility) of this 
adapted approach. Views of multiple stakeholders, including: (1) Caregivers; (2) Early Childhood 
Development Practitioners; (3) Early Childhood Development Practitioner School Supervisors; and (4) 
Early Start Denver Model supervisors will be assessed. Mixed methods will be used to understand the 
implementation processes, and the barriers and facilitators associated with the approach. Acceptability, 
appropriateness, and feasibility will be quantitatively assessed using 4-item, pragmatic scales: The 
Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and 
Feasibility of Intervention Measure (FIM). In addition, acceptability, appropriateness and feasibility will 
be assessed qualitatively with stakeholder individual interviews. Questions in the interview guide will be 
tailored to stakeholder group and be informed by previous studies that have examined implementation 
barriers and facilitators during the implementation of a new treatment approach. 
Remote baseline assessments will include questions about demographics; questions about 
technology use; a caregiver-child interaction that will be recorded on the caregivers’ smart phone and 
uploaded to a HIPPA compliant Duke Box folder; and the VABS-3. Audio-recorded individual interviews 
will be conducted with caregivers in the ASD group at baseline to assess family routines and strategies 
they use to interact with their child. In addition, these caregivers will complete the Family Routines 
Inventory. Remote post-intervention assessment in the ASD group will include a caregiver-child 
interaction will be recorded on the caregivers’ smart phone and uploaded to a HIPPA compliant Duke 
Box folder; and the VABS-3. Following each telephone-based coaching session a caregiver-child 
interaction will be recorded on the caregivers’ smart phone and uploaded to a HIPPA compliant Duke 
Box folder. The recorded caregiver-child interactions will occur in authentic environments of the child, 
with every day materials that the child are caregiver are familiar with. 
Once Covid-19 restrictions are lifted and the risk of seeing participants are judged as acceptable 
by our partner sights and University of Cape Town IRB we will offer participants a choice of in-person 

caregiver-coaching delivery. Should restrictions be reinstated the above procedures and methods will be 
implemented as necessary. 
 
Selection of Subjects 
 
The proposed research will be conducted within the Cape Town metropolitan region, South 
Africa, in autism schools, neurodevelopmental clinics, and early childhood development centers. The (1) 
baseline case-control study (autism spectrum disorder: ASD; developmental delay: DD; and typical 
development: TD) and the (2) longitudinal pre-post design intervention study (ASD group only and their 
caregivers) will evaluate naturalistic developmental behavioral intervention (NDBI) treatment targets 
and involve 120 human subjects (30 ASD caregiver-child dyads=60, 30 DD, 30 TD). In order to account 
for the estimated 15% attrition, and ensure a final total sample size of 30 caregiver-child dyads in the 
ASD group for the pre-post phase of the study, 35 caregiver-child dyads will initially be recruited. 
Therefore, 130 participants total will be enrolled in the study. 
Inclusion criteria are as follows: (1) the child is between 18 and 72 months of age; (2) the 
subject’s family speak isiXhosa, isiZulu, Afrikaans, or English (~ 97% of all household languages spoken in 
the Western Cape province); (3) the child’s ethnicity/race is African or Coloured; and (4) the child lives 
within an area served by the recruitment sites. Additional inclusion criteria are group specific. For the 
ASD group: (1) the child meets criteria for an ASD diagnosis based upon DSM-5 criteria and informed by 
the ADOS-257 administered by research reliable raters; and (2) the caregiver is ≥ 18 years old. For the 
developmental delay group: (1) the child screens positive on the Ten Questions and negative on the 
Autism Behavior Checklist (ABC); and (2) has been diagnosed with developmental delay by a 
developmental pediatrician. For the typically developing group: The child screens negative for a 
developmental delay on the Ten Questions and negative for ASD on the ABC. 
COVID-19 adaptations: Because we aim to assess the acceptability, feasibility, and 
appropriateness of the adapted telehealth coaching intervention - views of multiple stakeholders 
involved in the implementation of the intervention will be assessed. This includes the child's caregiver, 
Early Childhood Development Practitioners, Early Childhood Development Practitioner School 
Supervisors, and ESDM therapists who provide supervision and oversight of the caregiver coaching 
session. Inclusion criteria are as follows: For the Early Childhood Development Practitioners (n=2) and 
Early Childhood Development Practitioner School Supervisors (n=2) group: the ECD worker and/or 
school supervisor are 1) employed by our participating recruitment partners (Western Cape Education 
Department Schools) and 2) involved in delivery of the caregiver coaching sessions, either in person or 
remotely. For the Early Start Denver Model supervisors (n=3): the local supervisors are 1) trained ESDM 
therapist, 2) supervise weekly coaching sessions in the schools, and/or 3) supervise remote intervention 
delivery sessions. 
Exclusion criteria for the ASD group include: (1) the presence of a neurological disorder of 
known etiology (e.g., Fragile X); and (2) a caregiver-child dyad that is unable to attend assessments and 
12 coaching sessions. Exclusionary criteria for all groups include: (1) significant sensory or motor 
impairment; (2) major physical abnormalities; and a (3) history of serious head injury and/or 
neurological disease. Exclusionary criteria for the DD and TD groups: (1) an autism diagnosis based on 
DSM 5 criteria. 
 
Subject Recruitment and Compensation 

Recruitment procedures utilized in Dr Franz’s K01 will continue in the R21 and potential subjects 
in the ASD group will be identified by participating recruitment sites, Western Cape Autism, and if 
participants are interested in screening, they will be referred to the Project Coordinator who will meet 
with them in a private location to conduct the screening. Participants will be asked to provide oral 
consent to be screened. The Project Coordinator will then screen participants for most inclusion (ADOS- 
2 will be performed at baseline assessment for the ASD group) and exclusion criteria. Potential subjects 
who meet eligibility criteria will be informed of the study, and invited to participate. 
Similar recruitment procedures will be followed for the DD and TD groups, with potential 
subjects being identified by participating recruitment sites (Neurodevelopmental clinics at Red Cross 
hospital for DD group, and early childhood development centers in the Cape Town metropolitan region 
for TD group). If participants are interested in screening, they will be referred to the Project Coordinator 
who will meet with them in a private location to conduct the screening. Participants will be asked to 
provide oral consent to be screened. The Project Coordinator will screen participants in the DD and TD 
groups using the Ten Questions questionnaire and the Autism Behavior Checklist. For the DD group, the 
child will need to screen positive on one or more questions on the Ten Questions in order to be eligible 
to participate in the study, and screen negative on the Autism Behavior Checklist. For the TD group, the 
child will need to screen negative on all questions on the Ten Questions questionnaire, in addition to 
screening negative on the Autism Behavior Checklist. If a child in the TD group screens positive on the 
Ten Questions, the Project Coordinator (who is an occupational therapist by training) will provide the 
caregiver with appropriate referral information for the Neurodevelopmental clinic at Red Cross hospital. 
If children in the DD or TD group screen positive on the Autism Behavior Checklist, an ADOS-2 will be 
administered by a research reliable South African clinician to help inform decisions on whether the child 
has ASD. If concerns remained for ASD following ADOS-2 administration, the Project Coordinator will 
provide the caregiver with appropriate referral information for the Neurodevelopmental clinic at Red 
Cross hospital. The Project Coordinator will then screen potential subjects in the DD and TD group for 
additional exclusion criteria. Potential subjects who meet eligibility criteria will be informed of the study, 
and invited to participate. 
Participants will be informed throughout the recruitment process and study sessions that 
participation is voluntary and that they may refuse to answer any question for any reason. In addition, 
the caregivers of their child may refuse to participate or withdraw from the study at any time without 
penalty or loss of benefits to which they are otherwise entitled. 
We are aware of the ethical considerations in providing participant compensation to people 
who may be living in poverty because providing cash payments can unintentionally coerce participation 
in research. Thus, we will restrict compensation to cover the basic costs of participation by providing a 
travel reimbursement at each study visit (ZAR 300, for baseline assessment and ZAR 100, for each 
intervention session). 
Covid-19 adaptions: where Covid-19 regulations and restrictions does not allow for in-person 
recruitment and enrollment procedures a system that enables remote enrollment and consent of ASD 
caregiver-child dyads will be developed and implemented. Eligible families, with a child with ASD within 
the age range of 18-72 months will be identified by our participating recruitment partners (Western 
Cape Education Department Schools). Our partner sites have records of children with ASD (who have 
received an ASD diagnostic assessment) who are waiting for public sector special education services. 
Families will be invited to participate in the study by School Staff. Those who are interested will be 

contacted by the Project Coordinator who will explain the study and gather the screener questionnaire 
data. If the child meets checklist criteria and caregiver provides informed consent (though a telephone- 
consent process), the child and family will be enrolled. 
 
Study Interventions 
 
The study aims to adapt a caregiver coaching version of the Early Start Denver Model (ESDM), an 
evidence-based early intervention for autism spectrum disorder, for implementation by non-specialist 
early childhood development workers, employed by the Department of Education. The South African 
adapted intervention utilizes Community ESDM materials, which are currently being piloted in rural, low 
resource parts of the U.S. Participants receive 12, 1 hour, weekly sessions of caregiver coaching. The 
session skill is introduced by “Help is in your hands” Community ESDM44 videos, then early childhood 
development workers coach caregivers on the session skill and support caregiver reflection and skill 
generalization. 
COVID-19 adaptations: The study team will adapt current session content for a telehealth 
platform. Each session skills will be adapted for delivery using simple pictures with few words via a 
WhattsApp message. The session structure will be maintained as best possible; as it supports adult 
learning. Sessions will include 12 telephone-based coaching sessions with: (1) Joint viewing and 
supported caregiver reflection of pre-recorded caregiver-child interaction; (2) Joint review of simple 
pictorial session skill sent to the caregiver via a WhatsApp message; and (3) Facilitated discussion of skill 
generalization across various caregiver-child daily routines. 
 
Data Analysis & Statistical Considerations 
 
Aim 1: Characterize NDBI child treatment targets in South African children with ASD using standardized 
assessments and digital technology, and determine whether these patterns differentiate children with 
ASD from their peers with developmental delay and typical development. An exploratory component of 
Aim 1 will assess whether 12 sessions of NDBI caregiver coaching result in changes in child treatment 
targets assessed using digital technology. 
This aim will utilize two phases of the study: firstly, the baseline cross-sectional phase, and 
secondly, the longitudinal pre-post phase. In the baseline cross-sectional phase, we will evaluate and 
compare joint attention, engagement states, and explore ASD behavioral risk markers indexing 
children’s facial affective expressions, attention/orienting, and postural sway in South African children 
with ASD (n=30), developmental delay (n=30) and typical development (n=30). We hypothesize that, 
similar to children in Western cultures, South African children with ASD will show decreased responsivity 
to social bids for attention, make fewer intentional social overtures (cumulatively known as joint 
attention, assessed with the Early Social Communication Scales, ESCS), and will show decreased periods 
of joint engagement (assessed using the Joint Engagement Rating Inventory, JERI) as compared to South 
African children with developmental delay and typical development. Through the use of an app, child 
social interest, orienting, attention, affect, and postural sway will be measured in the three groups. We 
will explore whether children in the ASD group show lower attention to social stimuli, consistency in 
orienting to name calls, positive affective response to stimuli, and greater postural sway in relation to 
the developmentally delayed and typically developing groups. We hypothesize that, these behaviors will 
differentiate children with ASD from their peers. 

Frequency scores for initiation of and response to joint attention (IJA and RJA), will be derived 
from behavioral observations during a series of tasks presented by an examiner blind to child diagnosis. 
In order to assess joint engagement, child engagement states will be coded from video-recorded 
caregiver-child interactions and scored in a Likert scale by a trained rater, blind to child diagnosis. For 
joint attention and joint engagement, the primary statistical comparisons will be to evaluate whether 
the ASD group score lower on three co-primary endpoints: IJA and RJA for joint attention, and joint 
engagement. Our power calculation was based on a two-sample t-test with unequal variances, using as a 
reference the observed IJA scores from a similar sample of ASD and typically developing children from a 
Western setting. With two groups of 30, assuming mean (SD) IJA score of 16 (8) among typically 
developing children, we will have 90% power to detect a difference in mean scores of at least 7 between 
ASD and typically developing children. A similar analytic approach will be used for RJA and joint 
engagement. If a difference is observed, between the ASD and typically developing groups, a secondary 
comparison will be conducted to compare the ASD group and the developmentally delayed group, using 
a multiple comparisons adjustment to control for Type I error. In collaboration with experts at Duke, 
using digital technology, we will explore ASD behavioral risk makers indexing children’s facial affective 
expressions, attention/orienting, and postural sway. Using the same statistical analysis approach 
described above, we will explore whether children with ASD show lower attention to social stimuli, 
consistency in orienting to name calls and positive affective response, and greater postural sway to 
stimuli in relation to the developmentally delayed and typically developing groups. 
Because the main predictors of response are age, sex and group (ASD, DD, TD), by balancing the 
age and sex distribution across the three groups we will be able to better isolate differences in child 
joint attention, joint engagement, and ASD behavioral symptoms, between the groups that are 
attributable to whether the child is ASD, DD, or TD. This will answer a fundamental question of whether 
our NDBI treatment targets are valid. Addressing this main research question is critical to designing 
effective early interventions that may be adapted for pilot testing across sub-Saharan Africa. 
Our analysis will focus on graphical displays, which will be complemented by appropriate 
inferential statistical procedures. For the graphical displays, we will visualize the distribution of joint 
attention, joint engagement, and ASD behavioral symptoms in histograms to better understand the 
shape and spread of the distribution of each. We will overlay the shape of the distributions (e.g. as 
kernel density plots) in each of the three groups, using the data from the 30 children in each group, with 
each curve plotted in a different color. We will then move from these individual data distributions to the 
pairwise relationships between joint attention, joint engagement, and ASD behavioral symptoms, by 
plotting the values in scatterplots and color-coding the three groups. For example, with initiation of joint 
attention on the horizontal axis and response to joint attention on the vertical we can clearly show the 
distribution of joint attention and how that distribution differs by the three groups. Similarly, we will 
summarize joint attention, joint engagement, and ASD behavioral symptoms and covariates by the three 
groups (ASD, DD, TD) using means and standard deviations, median and interquartile ranges or counts 
and percentages, as appropriate. In terms of inference, we can compare joint attention, joint 
engagement, and ASD behavioral symptoms between the three groups by performing a one-way ANOVA 
on each, or by using the alternative non-parametric Kruskal-Wallis test, if needed. Whilst statistical 
inference is valuable, we anticipate that we will elicit most information through careful data 
visualization. If, in fact, other covariates, such as maternal education or socioeconomic status, are 
identified as being important we will be able to extend to a regression modeling framework in which we 
would separately analyze joint attention, joint engagement, and ASD behavioral symptoms, by 

regressing each on group and adjusting for the additional covariates. We will be cautious about 
adjusting for multiple covariates given the relatively small sample size (30 per group). Nevertheless, as 
noted above, since age and sex are expected to be the strongest predictors, over and above group (ASD 
vs. DD vs. TD), we do not anticipate the need for extensive regression modeling, if any. 
In the second phase, we will conduct a longitudinal pre-post study with children in the ASD 
group who receive 12 sessions of intervention. In order to account for the estimated 15% attrition, and 
ensure a final total sample size of 30 caregiver-child dyads in the ASD group for the pre-post phase of 
the study, caregiver-child dyads will initially be recruited. Using digital technology, we will re-assess child 
social interest, orienting, attention, affect, and postural sway post-intervention and explore patterns of 
change in individual trajectories of these behaviors. Paired t-tests (or Wilcoxon rank-sum tests if 
appropriate), in conjunction with exploratory graphical analyses of individual trajectories over time, will 
be conducted to assess the pre versus post change following 12 sessions of NDBI-informed caregiver 
coaching. 
When focusing on changes in ASD behavioral symptoms and caregiver strategies in the ASD 
group following 12 intervention sessions (exploratory component of Aim 1 and Aim 3) we will again use 
comprehensive data visualization with scatter plots of the pre and post-intervention measures of each 
outcome for the 30 ASD children. For inference, paired t-tests will be used, or if assumptions of the t- 
test are not met, the Wilcoxon signed rank test will be used. Additionally, given that severity (measured 
by ADOS-2 comparison score) may predict changes over time, we will perform stratified analyses 
separately for high severity from low severity children. Specifically, we will examine all data 
visualizations by severity category. Likewise, we will perform inference separately for the high and low 
severity children. We may explore regression modeling strategies where we regress change in each 
outcome measure on severity category (or severity score, if appropriate), a strategy that would allow us 
to additionally adjust for age and/or sex. Nevertheless, we recognize that with a total sample size of 30, 
we will be cautious when performing and interpreting our inferential statistics and, if modeling 
assumptions are not satisfied, we will not proceed with the analysis. As noted above, data visualization 
and summary statistics will provide us with a wealth of information. 
 
Aim 2: In the ASD group, determine the caregiver-child context for South African dyads, by identifying 
common family routines and characteristics of caregiver-child dyadic exchanges. 
Because NDBIs are delivered in the context of common family routines, it is essential to 
understand how such routines present in South African families. This provides key information about 
how to embed NDBI strategies within family life. K01 pilot data includes descriptions of caregiver-child 
interactions, primarily during play, from 22 ethnically diverse caregivers of young children with ASD in 
South Africa. Data indicated that caregivers regularly interact with their young child with ASD during 
object-based play and sensory social routines. During object-based play, caregivers described dyadic 
interactions, where they joined with their child in child-preferred activities and tried to incorporate 
learning into those interactions. During sensory-social routines, caregivers reported awareness of child 
affect and social communication cues, and a variety of adult and child play participants. Additional data 
is needed to examine family routines; however, caregivers did spontaneously describe interactions with 
their child during family routines of mealtime and bath time. 
During the baseline cross-sectional phase of the study, a mixed methods approach will assess 
caregiver-child context in the ASD group (30 caregiver-child dyads). Quantitative and qualitative data 
will be collected in a simultaneous, balanced arrangement, with equal importance being given to both. 

Quantitative data will describe characteristics of the caregiver-child context using standardized tools. 
Qualitative data will explore culturally-relevant categories not included in the standardized tools, 
developed for Western contexts. At the interpretation phase, results will be triangulated. The process of 
conceptual triangulation will be followed. This involves: (1) conducting qualitative and quantitative 
research, (2) distinguishing salient results, (3) examining confidence in the results, (4) developing criteria 
for inclusion of results, and (5) constructing conceptual models describing the caregiver-child context in 
which NDBI strategies can be embedded. 
Quantitative data will describe types of family routines (assessed via the Parent Survey of Home 
and Family Experiences) and characteristics of caregiver-child dyadic exchanges (assessed via the 
JERI15). Routine frequency scores will be derived from the Parent Survey of Home and Family 
Experiences. Caregiver-child dyadic exchanges will be scored on a Likert scale by a trained rater, from 
video-recorded caregiver-child interactions, for (1) fluency and connectedness, and (2) shared routines 
and rituals. Exploratory graphical assessments will be used to understand and represent the distribution 
and patterns in family routines and dyadic interaction item scores. 
Qualitative data from open ended questions in the Parent Survey of Home and Family 
Experiences, will facilitate a broader understanding of South African family routines. Probes will elicit 
caregiver narratives on additional family routines, and routine participants. Data will be inductively 
analyzed via content analysis using NVivo software. 
 
Aim 3: In the ASD group, describe strategies caregivers use during caregiver-child interactions and 
evaluate whether there are changes in caregiver-specific strategies following NDBI caregiver coaching. 
K01 pilot data suggests caregivers can implement Early Start Denver Model (ESDM) strategies as 
a result of 12 sessions of caregiver coaching by non-specialists. In the K01 pre-pilot, the first caregiver 
almost reached 80% fidelity, while the second caregiver surpassed 80% fidelity. This suggests potential 
for successful caregiver implementation of ESDM strategies as a result of the adapted intervention. 
Using a mixed methods approach we will utilize both the baseline cross-sectional phase and the 
longitudinal pre-post phase of the study in the ASD group (30 caregiver-child dyads), to assess caregiver 
strategies. Our approach will be similar to that described in Aim 2. A conceptual model of South African 
caregiver strategies will be constructed. Since the caregiver plays a key role in delivering NDBIs, it is 
essential to understand strategies used by South African caregivers, how readily these strategies change 
when NDBI-informed interventions are delivered, and caregivers’ perception of the NDBI strategies 
used. 
Quantitative assessment of caregiver strategies at baseline and follow-up will be via the JERI, 
and include: (1) scaffolding, (2) following in on a child’s focus, and (3) caregiver affect. These items will 
be scored on a Likert scale by a trained rater, from video-recorded caregiver-child interactions. We 
hypothesize that 12 sessions of NDBI-informed caregiver coaching will result in significant changes in the 
frequency and quality of caregiver strategies. Quantitative data will be analyzed with a paired t-test (or 
Wilcoxon rank-sum test if appropriate) to evaluate the change in caregiver strategies pre versus post 
intervention. In order to account for the estimated 15% attrition, and ensure a final total sample size of 
30 caregiver-child dyads in the ASD group for the pre-post phase of the study, 35 caregiver-child dyads 
will initially be recruited. We will thus have 90% power to detect a standardized effect size (Cohen’s d) 
of 0.60 using a paired t-test, assuming we standardize the difference between pre and post scores to 
have mean 0 and standard deviation 1. 

Qualitative caregiver perceptions of strategies used during caregiver-child interactions will be 
collected at follow-up. Interview scripts will be developed to facilitate a broader understanding of 
strategies that are culturally-relevant to South African caregivers. Individual interviews will be audio- 
recorded. Data will be transcribed verbatim and cross-checked for accuracy, and inductively analyzed via 
content analysis utilizing NVivo. 
 
Aim 4: Adapt the NDBI caregiver coaching intervention and assessment of caregiver NDBI strategies for 
telehealth delivery in order to maintain services for young children with ASD impacted by COVID-19. 
Explore the acceptability, feasibility, and appropriateness of the adapted intervention and assessment 
approach.  
Acceptability, feasibility and appropriateness of the telehealth approach will be evaluated. 
Views of multiple stakeholders: (1) Caregivers; (2) Early Childhood Development Practitioners; (3) Early 
Childhood Development Practitioner School Supervisors; and (4) NDBI supervisors will be assessed. 
Mixed methods will be used to understand the implementation process, and barriers and facilitators. 
Acceptability, feasibility, and appropriateness will be quantitatively assessed using the Acceptability of 
Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of 
Intervention Measure (FIM). In addition, acceptability, feasibility and appropriateness will be assessed 
qualitatively. The interview guide will be tailored to the stakeholder group and be informed by previous 
studies that have examined implementation barriers and facilitators during the implementation of a 
new treatment approach; including some of our previous work. At the interpretation phase, results will 
be triangulated. The process of conceptual triangulation will be followed. 
Child social communication will be assessed with the Socialization and Communication standard 
scores from the Vineland Adaptive Behavioral Scale Third Edition (VABS-3). The VABS-3 will be 
administered telephonically at the baseline and follow up. We will evaluate pre-post change on the 
VABS-3 among dyads receiving the telehealth intervention using a paired t-test, under the null 
hypothesis of no change over time (in the case that the outcome data is heavily skewed, a Wilcoxon 
signed rank test will be used instead). Assuming the same standard deviations as the R21 pilot data (7.5 
for Socialization and 8.3 for Communication), we will have 90% power to detect mean pre-post changes 
of at least 5.7 for Socialization and 6.3 for Communication. 
Fidelity of intervention delivery, the degree to which programs are implemented as intended by 
program developers, is an important implementation outcome because it can moderate the impact of 
an intervention on targeted health outcomes. Pilot R21 data (n=10) suggests that South African 
caregivers can learn to implement core NDBI intervention principles. After 12 sessions: mean fidelity 
scores increased from 2.93 to 3.73. However, when interventions are adapted to fit a new target 
population, delivery setting, location or organization, maintaining intervention fidelity is of particular 
importance. As the intervention is adapted for delivery on a telehealth platform, fidelity is critical to 
monitor. Fidelity ratings can be completed from video-recordings of caregiver-child interactions. 
Caregiver child interactions will be recorded on the caregivers’ Smartphone and uploaded to a HIPPA 
compliant Duke Box folder. Caregiver-child interactions will occur in the child’s home, an authentic 
environment of the child, with every day materials that the child are caregiver are familiar with. 
The Caregiver ESDM Fidelity Rating System provides a method for assessing fidelity; namely the 
degree to which a caregiver is using intervention principles in a joint activity routine with their young 
child. The 13 item rating scale includes ratings of performance on core intervention strategies from 1 to 

5; where 1 represents a lack of an effective display of the practices specified, and 5 represents the best 
possible example of this teaching behavior. Fidelity of implementation of NDBI strategies will be 
manually coded by certified ESDM therapists at baseline, for each of the 12 intervention sessions, and at 
follow up. Mean fidelity scores (with SD) will be calculated across study participants in order to assess 
change in NDBI strategies. As with in-person intervention, we expect that caregivers will learn to 
implement core NDBI intervention principles after 12 intervention sessions. Pre-post change in the 
telehealth delivery group will be assessed using a paired t-test (or Wilcoxon signed rank test, as 
appropriate). Assuming the same standard deviation (0.6) as the R21 pilot data, we will have 90% power 
to detect a mean pre-post change of at least 0.5.