Autism Research - 2023 - Yang - Randomized controlled trial of a mixed early start Denver model for toddlers and

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RE S EARCH ART I C L E
Randomized, controlled trial of a mixed early start Denver model
for toddlers and preschoolers with autism
Yanyan Yang1 | Hongan Wang2 | Haiping Xu1 | Meiling Yao1 | Dongchuan Yu1,2
1Henan Provincial Medical Key Lab of Child
Developmental Behavior and Learning, The
Third Affiliated Hospital of Zhengzhou
University, Zhengzhou, Henan, China
2Key Laboratory of Child Development and
Learning Science of Ministry of Education,
School of Biological Science and Medical
Engineering, Southeast University, Nanjing,
China
Correspondence
Dongchuan Yu, Henan Provincial Medical Key
Lab of Child Developmental Behavior and
Learning, The Third Affiliated Hospital of
Zhengzhou University, Zhengzhou 450052,
Henan, China.
Email: 13951992570@163.com
Funding information
National Natural Science Foundation of China,
Grant/Award Numbers: 62073077, 61673113;
Guangdong Key Project in “Development of
new tools for diagnosis and treatment of
Autism”, Grant/Award Number:
2018B030335001
Abstract
The early start Denver model (ESDM) has been extensively studied as a promis-
ing early intervention approach for young children with autism spectrum disorder
(ASD). Various methodological drawbacks from earlier ESDM investigations
must be rectified to expand the application scopes. For this purpose, the present
study recruited a very large sample of 249 autistic children (aged 24–47 months),
and used a randomized controlled design to compare outcomes from a mixed
ESDM (M-ESDM) intervention with a mixed discrete trial teaching (M-DTT)
intervention which remains one of the most commonly-used programming for
early intervention. Over the course of a 12-week period, both groups (i.e., M-
ESDM and M-DTT groups) received 25 h of intensive intervention per week
using individual, group, and parent coaching techniques. Findings showed that:
(i) the M-ESDM significantly outperformed the M-DTT in enhancing children’s
developmental abilities in gross motor and personal-social skills for toddlers and
preschoolers, as well as in language for preschoolers with mild/moderate ASD
and toddlers; and (ii) the M-ESDM dramatically reduced the severity of autistic
symptoms in toddlers with severe ASD only, when compared to the M-DTT.
However, the M-ESDM did not outperform the M-DTT in terms of improving
children’s developmental abilities in adaptability and fine motor for toddlers and
preschoolers, as well as in language for preschoolers with severe ASD. In addi-
tion, when compared to the M-DTT, the M-ESDM did not show an advantage in
reducing the severity of autistic symptoms in toddlers with mild/moderate ASD
and preschoolers. Clinical Trial Registration: Chinese Clinical Trial Registry.
Registration number ChiCTR200039492.
Lay Summary
Early intervention has a substantial impact on enhancing development for chil-
dren with autism. The discrete trial teaching (DTT) has been widely used for early
intervention, but has various drawbacks that might be solved by the early start
Denver model (ESDM). By recruiting a very large sample of 249 autistic children
(aged 24–47 months) and adopting a randomized controlled design, this study
showed that the ESDM outperformed the DTT in enhancing developmental abili-
ties and reducing the severity of autistic symptoms.
KEYWORDS
autism spectrum disorder, discrete trial teaching, early intervention, early start Denver model,
randomized controlled trial
INTRODUCTION
Autism spectrum disorder (ASD) is a life-long neurodeve-
lopmental disorder characterized by deficits in social-
communicative functioning and the presence of repetitiveYanyan Yang, Hongan Wang, and Haiping Xu contributed equally to this study.
Received: 14 December 2022 Accepted: 22 July 2023
DOI: 10.1002/aur.3006
© 2023 International Society for Autism Research and Wiley Periodicals LLC.
1640 Autism Research. 2023;16:1640–1649.wileyonlinelibrary.com/journal/aur
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and restricted behaviors, interests, and activities
(American Psychiatric Association, 2013). Over the past
10 years, there has been a sharp rise in the prevalence of
ASD, which was estimated to be 1 in 44 for US children
aged 8 in 2018 (Maenner et al., 2021). Early intervention
on autistic children (Chu et al., 2017; Kdm et al., 2016;
Rollins et al., 2016; Salomone et al., 2016; Wainer
et al., 2017) may have positive impact on both short- and
long-term outcomes, likely due to greater brain plasticity
during early development. In addition, effective early
intervention may reduce societal costs spent over the life-
time to aid persons with ASD (Cidav et al., 2017; Penner
et al., 2015). For these reasons, there is an urgent need for
effective early intervention for young autistic children in
countries like China with limited ASD-related early public
health and educational services (Zhou et al., 2020).
Originally, based on the early work of Ivar Lovaas, the
discrete trial training (DTT) (Bolton & Mayer, 2008;
Smith, 2001) has been studied extensively and remains one
of the most commonly used teaching procedures and
models for early intervention. However, the standard
DTT method has potential limitations, such as a possible
lack of generalization, prompt dependency, a lack of spon-
taneity, and an increase in challenging behaviors associ-
ated with escape and avoidance of the training (Wang
et al., 2018). To address these limitations, the naturalistic
developmental-behavioral interventions (NDBI) approach
has been proposed for young autistic children, which may
gain better outcomes than the DTT (Schreibman, 2005;
Schreibman et al., 2015). Among others, the early start
Denver model (ESDM) has been well documented as a
promising NDBI program to enhance learning abilities for
social attention and motivation, initiation of interactions,
nonverbal and verbal communication, symbolic play, and
imitation (Baril & Humphreys, 2017; Colombi et al., 2018;
Contaldo et al., 2020; Dawson et al., 2010; Fuller &
Kaiser, 2020; Hoogenhout, 2012; Lin et al., 2020;
Rogers & Dawson, 2009; Sinai-Gavrilov et al., 2020;
Waddington et al., 2016). However, some methodological
issues from earlier ESDM investigations need to be
addressed to broaden the application scopes.
First, the sizes of samples in previous studies (Baril &
Humphreys, 2017; Fuller & Kaiser, 2020; Waddington
et al., 2016) were relatively small. Indeed, there were only
seven studies worldwide with samples bigger than
100 (Baril & Humphreys, 2017; Fuller & Kaiser, 2020;
Waddington et al., 2016). This drawback might affect the
data interpretation and generalization due to the com-
plexity and heterogeneity of ASD.
Second, the most previous studies did not apply a strict
experimental design for a variety of reasons. For those
(Baril & Humphreys, 2017; Colombi et al., 2018; Fuller &
Kaiser, 2020; Waddington et al., 2016) that used treatment-
as-usual (TAU) as a control condition, the TAU group did
not always have the same treatment dosage or intervention
quality (dependent on therapists’ professional training and
experience), as did the ESDM group.
Third and finally, the ESDM (Baril &
Humphreys, 2017; Fuller & Kaiser, 2020; Waddington
et al., 2016) can be delivered by a range of people: (i) It
can be implemented by therapists, parents, teachers, and
others; (ii) It can be implemented in clinics, homes,
and child care centers, in early intervention centers in the
community, or in preschool-based environment; (iii) It
can be provided in periods of short or long duration, with
high or low intensity; and (iv) It can be provided in
individual- or group-based intervention settings for thera-
pists, as well as implemented by parents during everyday
life with support by live or long-distance coaching. How-
ever, intervention effects of ESDM (and other interven-
tion as well) may vary depending on the delivery models
and important subjectsfor empirical investigation. A
mixed ESDM delivered by both therapists and primary
caregivers (e.g., parents) may make sense and might be a
feature of clinical practice. However, thus far, this
“mixed delivery” model has not been well studied.
Taken together, this study sought to solve the techni-
cal drawbacks in past ESDM studies and highlight the
strengths of ESDM over DTT. For this purpose, we
recruited a fairly large sample of 249 autistic children
(aged 24–47 months), and proposed a mixed ESDM
(M-ESDM) model to administer intervention by both
therapists and parents for a 12-week period at a rate of
25 h per week. Then, utilizing a randomized controlled
trial, we implemented a strict experimental design for the
M-ESDM model, and compare outcomes from
the M-ESDM intervention with a mixed DTT (M-DTT)
intervention for a 12-week period at a rate of 25 h per
week. Finally, this study aimed to investigate whether the
M-ESDM would be more effective than the M-DTT at
enhancing developmental abilities and reducing ASD
symptoms.
METHODS
The Medical Ethics Committee of the Third Affiliated
Hospital of Zhengzhou University gave its approval
(No. 39 in 2019) to all study protocols and research tech-
niques, ensuring that they adhered to the World Medical
Association’s Declaration of Helsinki regarding the use
of humans in testing. All participating children’s parents
gave their informed consent, and each participant gave
their oral consent. This study had been registered in the
Chinese Clinical Trial Registry (ChiCTR) with Registra-
tion number ChiCTR200039492. All experimental data
had been prospectively registered in the ChiCTR data-
base, which could be publicly accessible.
Study design and participants
All participating children were recruited from clinical
cases in the Department of Child Developmental
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Behavior, the Third Affiliated Hospital of Zhengzhou
University, Zhengzhou, Henan Province, China. To be
eligible for this study, children had to have mothers with
at least a junior college degree, have just received their
initial DSM-5 diagnosis of ASD, and be between the ages
of 24 and 47 months at the time of participation. We only
recruited boys to participate in the current study in order
to limit the influence of gender. The exclusion criteria
included the following conditions: (a) extra intervention
from the community, kindergarten, or any other institu-
tions; (b) the co-occurring of physical health conditions;
and (c) incomplete clinical data related to the processing
of evaluation and intervention.
Based on inclusion and exclusion criteria above, a
total number of 249 autistic children (aged 24–
47 months) were enrolled in the study. A coin toss was
used to allocate each participating child at random to
either the M-ESDM group (experimental group) or the
M-DTT group (control group). The outcome was 125 for
the M-ESDM group and 124 for the M-DTT group,
respectively.
Measures
Gesell developmental schedules-third edition
The Chinese version of Gesell developmental schedules-
third edition (GDS-3) (Dror et al., 2009; Meinzen-Derr
et al., 2011; Wang et al., 2018; Yang, 2016) is a popular
and psychometrically valid scale in China, which pro-
vides a developmental profile for children aged from
16 days to 6 years old in five domains (i.e., gross motor,
fine motor, adaptability, language, and personal social
behavior). Gross motor domain involves an individual’s
postural reaction, for example, head stability, sitting,
standing, crawling, and walking; while fine motor
domain reflects an individual’s ability to grasp, manip-
ulate objects, and coordinate hands and eyes. Adapt-
ability domain reflects an individual’s ability to:
(i) percept the organization and relationship of objects
(e.g., toys); and (ii) decompose the whole of an object
into its components, and recompose these components
into a whole in a meaningful way. Language domain
involves receptive and expressive language skills; while
personal-social domain reflects an individual’s abilities
in interpersonal communication and self-care. Develop-
mental quotients (DQs) in five domains were used to
evaluate the performance of GDS-3 (Meinzen-Derr
et al., 2011).
Childhood autism rating scale
This study adopted the original version (i.e., the first edi-
tion) of the childhood autism rating scale (CARS) scale
(Schopler et al., 1980), which was a 15-iem scale and
conducted by highly trained raters (Pilowsky et al., 1998;
Rellini et al., 2004). It evaluates behavior in 14 domains
that are typically affected by severe autism-related issues
as well as one general category of impressions of autism,
with the goal of differentiating autistic children from
those with other developmental disorders. The assess-
ment was based on data gathered through a variety of
techniques, including direct observation, parent inter-
views, and analysis of previously collected clinical data.
Scores for each item range from 1 to 4, with 1 denoting
behavior appropriate for the age level and 4 denoting
extreme deviation from the expected behavior for the age
level. According to the total CARS score (i.e., the sum of
the scores for all items), each child may be labeled as
“not autistic” (score below 30), “mild or moderately
autistic” (scoring between 30 and 36), or “severely autis-
tic” (score above 36). The reliability and validity of
CARS scale in the Chinese population were 0.73 and
0.97, respectively (Lu et al., 2004).
Social maturity scale
The Social maturity scale (SMS) scale (Yu et al., 2014;
Zhang et al., 1995) is derived and revised from the
Japanese version of the Vineland social maturity scale
(Sparrow et al., 2005), and has been widely used in China
to evaluate the social adaptive capability of children aged
6 months to 14 years old. The SMS scale is a 132-item
behavior-rating scale and is comprised of six subscales
(i.e., self-help, locomotion, occupation, communication,
socialization, and self-direction), where each item of the
SMS is scored on a 2-point Likert scale. A standardiza-
tion study of SMS showed that the consistency and valid-
ity of SMS in Chinese population were 0.98 and 0.95,
respectively (Zhang et al., 1995). It should be noted that
the current study utilized an interview of primary care-
givers to improve the fidelity of the evaluation using
the SMS.
Intervention groups
Both groups (i.e., M-ESDM and M-DTT group) adopted
the same treatment dosage and delivered intervention in
a mixed individual, group and live parent coaching set-
ting during their 25 weekly hours, over a 12-week period,
which included: (i) 1 h a day of child therapy from
Monday to Saturday in an individual-based setting;
(ii) 3 h a day of child therapy from Monday to Saturday
in a group-based setting, where each group was com-
prised only of five children with ASD; and (iii) 1 h of
parent-implemented intervention on Sunday under thera-
pist coaching. The therapists of both groups (i.e., M-
ESDM and M-DTT groups) used their curriculum
frameworks to complete their intervention targets,
respectively.
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M-ESDM Group
The M-ESDM group was provided with intervention
using the M-ESDM curriculum (Rogers &
Dawson, 2009). Target skills in the M-ESDM curriculum
included receptive and expressive communication,joint
attention, imitation, social skills, play skills, and motor
skills. In the individual-based setting, the therapists
applied naturalistic and developmentally oriented strate-
gies to improve the skills that were crucial to learning
and development, such as enhancing motivation, promot-
ing spontaneity and imitation, and focusing on social ini-
tiations. During intervention, the therapists typically paid
attention to how each child responded to their surround-
ings, assessed how long the next activity should last, and
actively supported each child in engaging in curriculum.
Each child received enough training opportunities from
the therapists to become proficient in the desired skills.
The group-based setting involved a variety of topics
(e.g., emotional perception, role-playing, and music). The
therapists typically adopted object-based interactive
games to maximize children’s arousal and sensory
response through toy selection, voice tone, and different
activity levels, then, encouraged children to participate in
each other to strengthen their ability to imitate, share
attention, and display with both therapists and other chil-
dren. In addition, they also applied peer-based interactive
games to encourage children to intentionally interact with
therapists and other children. In the therapist coaching
setting, parents were required to interact with their chil-
dren while the therapists monitored over them. The ther-
apists typically taught parents how to increase their
children’s enthusiasm for active engagement, enhance the
communication awareness with their children in daily
life, and promote the generalization of the skills in
daily life.
M-DTT Group
The M-DTT group was provided with intervention using
the M-DTT curriculum (Bolton & Mayer, 2008;
Smith, 2001). Target skills in the M-DTT curriculum
included receptive and expressive communication, play,
and social behavior. In the individual-based setting, the
therapists applied highly structured methods, in which
skills were broken down into separate components and
taught one at a time in discrete trials, until the desired
behavior was acquired. The therapists adopted different
curriculum content and training goals dependent on each
child’s developmental levels. The group-based setting
involved a variety of topics (e.g., language, game, sce-
nario, and music). The therapists typically initiated the
training and arranged children to take turns participating
in the response. Children who responded correctly were
given external reinforcement, such as food, toys, or
praise; those who reacted incorrectly or did not respond
should receive prompt assistance, which should be gradu-
ally withheld once children had mastered the necessary
skills. In the therapist coaching setting, parents were
required to interact with their children while the thera-
pists monitored over them. The therapists typically
taught parents how to present an instruction or discrimi-
native stimulus, wait for the child to respond, provide an
immediate consequence if the child response correctly
(otherwise, provide more prompts and training to help
children respond correctly), and provide reinforcement
(e.g., food items, leisure materials, or tokens) with appro-
priate target, way and schedule.
Quality control
A senior expert (with professional experience more than
10 years) was naïve to group assignment and carried out
the pre- and post-intervention measures for all children.
The senior expert had training in administration of all
tools used in this study. All therapists in both groups
(i.e., the M-ESDM and M-DTT groups) were senior with
more than 8 years of professional experience.
Before beginning the study, the M-ESDM therapists
(n = 12) attended the introductory and advanced ESDM
workshop held by Professor Sally J. Rogers’ team, and
were trained in the workshop to ensure fidelity on all pro-
cedures and maintained 80% or better fidelity scores eval-
uated by the ESDM Fidelity Coding Sheet (Rogers &
Dawson, 2009). In this study, the fidelity of M-ESDM
implementation by therapists was examined at two-week
intervals and was 90.56 ± 3.43.
The M-DTT therapists (n = 12) had certificates
authorized by the China Association of Rehabilitation of
Disabled Persons (CARD), which is an authoritative
department in charge of rehabilitation of the disabled in
China; and they were trained to maintained 80% or better
fidelity scores during the M-DTT intervention. In this
study, the fidelity of M-DTT implementation by thera-
pists was examined at 2-week intervals and was 88.72
± 2.79. The fidelity of parent coaching sessions was
examined at 2-week intervals via video samples and
coded by a supervisor. In this study, the fidelity of parent
coaching sessions in M-ESDM and M-DTT intervention
was 73.68% ±1.63 and 76.47% ±1.92, respectively.
Statistical analysis
This study considered seven metrics to response the inter-
vention outcomes, including five Gesell subscale-scores
(i.e., Gross-Motor DQ, Fine-Motor DQ, Adaptability
DQ, Language DQ, and Personal-Social DQ), total
CARS score, and total SMS score. By subtracting the
pre-intervention score from the post-intervention score,
we were able to compute the gain on each metric as a
result of the intervention.
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As the main motivation, this study aimed to
explore whether and how the age and autism severity
affected the gain difference between two methods
(i.e., M-ESDM and M-DTT) for each of the seven
metrics. For this purpose, we first examined our data
to determine appropriate statistical models (paramet-
ric vs. non-parametric). After confirming that our data
passed the normality test and variance homogeneity
test, we performed a number of parametric three-
factor (age, autism severity, and intervention-type)
ANOVA tests and t-tests for post hoc multiple com-
parisons, where age (toddlers vs. preschoolers) and
autism severity (mild/moderate vs. severe) were intra-
group factors; and intervention-type (M-ESDM vs. M-
DTT) was an inter-group factor. In addition, for post
hoc multiple comparisons, we utilized the Bonferroni
correction to p-values to control the false discovery
rate (FDR).
All statistical analysis above was conducted with R
language (version 4.0.2) and the significance level α was
set at 0.05. In particular, R package “rstatix”
(Kassambara, 2021) was used.
RESULTS
Demographic information of participants
The present study included 249 boys (aged 24–
37 months) in total. According to age (24–35 months
vs. 36–47 months) and autism severity (severe vs. mild/
moderate), children in each group (M-ESDM or
M-DTT) were further divided into four subgroups
(i.e., toddlers with mild/moderate ASD, preschoolers
with mild/moderate ASD, toddlers with severe ASD, and
preschoolers with severe ASD). Each subgroup from
M-ESDM and its counterpart from M-DTT created a
pair of subgroups (thus four pairs totally). Tables 1 and 2
summarized the detailed demographic characteristics of
children. For each pair of subgroups, Table 2 showed
that there were no significant differences in these 7 metrics
at baseline (p’s > 0.05).
Main effect analysis
For gain on each measure, we conducted a three-factor
ANOVA to test the main effects and their interaction.
The main effect analysis results were listed as follows:
1. Gain on adaptability DQ: The main effect of age was
significant, but the main effects of severity and
intervention-type were not; while, there was an inter-
action effect for age and autism severity (age:
F[1,226] = 9.30, p = 0.003, η2 = 0.04; severity:
F[1,226] = 3.55, p = 0.06, η2 = 0.02; intervention-type:
F[1,226] = 0.19, p = 0.66, η2 = 0.0008; age*severity:F[1,226] = 9.61, p = 0.002, η2 = 0.04).
2. Gain on gross-motor DQ: The main effects of severity
and intervention-type were significant, but the main
effect of age was not; while, there were no interaction
effects among age, severity, and intervention-type
(age: F[1,226] = 3.59, p = 0.06, η2 = 0.02; severity:
F[1,226] = 6.06, p = 0.02, η2 = 0.03; intervention-type:
F[1,226] = 8.44, p = 0.004, η2 = 0.04).
3. Gain on fine-motor DQ: The main effects of age, sever-
ity, and intervention-type were not significant; while,
there were no interaction effects among age, severity,
and intervention-type (Age: F[1,226] = 2.78, p = 0.10,
η2 = 0.01; Severity: F[1,226] = 0.92, p = 0.34, η2 =
0.004; Intervention-type: F[1,226] = 1.54, p = 0.22,
η2 = 0.007).
4. Gain on language DQ: The main effects of age and
intervention-type were significant, but the main effect of
severity was not; while, there was an interaction effect
for severity and intervention-type (age: F[1,226] = 6.80,
p = 0.01, η2 = 0.03; severity: F[1,226] = 1.01, p = 0.32,
η2 = 0.0004; intervention-type: F[1,226] = 31.33,
p 0.05).
DISCUSSION
To address some technical drawbacks in earlier ESDM
studies, this article recruited a very large sample of
249 autistic children (aged 24–47 months), and random-
ized them into two groups (i.e., a mixed [therapist and
parent delivered] ESDM intervention and a mixed DTT
intervention), for a 12-week period for 25 hper week. By
adopting a well-controlled experimental design with a
randomized controlled trial, the present study aimed to
test whether the M-ESDM may obtain larger gains in
improving developmental abilities and reducing ASD
symptoms than the M-DTT (a highly structured
method).
It has been found (Asta & Persico, 2022; Reichow &
Wolery, 2009; Shi et al., 2021) that early intensive behav-
ioral intervention (EIBI), mainly based on DTT,
achieved higher outcome (particularly in relation to intel-
lectual functioning, measured as IQ or DQ) as compared
to children receiving less intensive behavioral interven-
tion. However, no comparisons between EIBI and other
widely recognized treatment programs have been pub-
lished (Reichow & Wolery, 2009; Shi et al., 2021; Asta &
Persico, 2022). Furthermore, although effective in teach-
ing new skills, numerous studies (Schreibman et al., 2015;
Wang et al., 2018) has shown that EIBI (mainly based on
DTT) as highly structured interventions may have limita-
tions, such as children having difficulties in generalizing
F I GURE 1 The gain difference of both methods (i.e., mixed early
start Denver model [M-ESDM] and mixed early start Denver model
[M-DTT]) in improving the gross-motor developmental quotient
(DQ). **pto measure gains on developmen-
tal abilities, ASD symptoms, and social adaptive capabil-
ity, respectively. In future studies, it is recommended
(Hoogenhout, 2012; Zhou et al., 2018) that studies use
ADOS-2 to describe ASD symptoms, and use the Grif-
fiths or Mullen scale to measure developmental abilities.
Given the strengths of the current study in terms of
positive effects of M-ESDM findings and sample size,
ESDM appears to hold promise as an early intervention
approach for young autistic children from the data that
currently exist.
AUTHOR CONTRIBUTIONS
Conception and design: Yanyan Yang, Hongan Wang,
Haiping Xu, Meiling Yao, Dongchuan Yu. Data acquisi-
tion: Yanyan Yang, Hongan Wang, Haiping Xu, Meiling
Yao. Data analysis: Yanyan Yang, Hongan Wang,
Dongchuan Yu. Data interpretation: Yanyan Yang, Hon-
gan Wang, Dongchuan Yu. Original draft: Yanyan
Yang, Hongan Wang, Dongchuan Yu.
ACKNOWLEDGMENTS
The authors would like to thank Sally J. Rogers for her
insightful suggestions and proofreading when preparing
the manuscript.
FUNDING INFORMATION
This work was supported by the National Natural Sci-
ence Foundation of China under Grant Nos. 62073077
and 61673113, and by the Guangdong Key Project in
(Grant No. 2018B030335001).
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are avail-
able from the corresponding author upon reasonable
request.
ORCID
Dongchuan Yu https://orcid.org/0000-0001-5576-441X
REFERENCES
American Psychiatric Association. (2013). Diagnostic and statistical man-
ual of mental disorders (5th ed.). American Psychiatric Publishing.
Asta, L., & Persico, A. M. (2022). Differential predictors of response to
early start Denver model vs. early intensive behavioral interven-
tion in young children with autism spectrum disorder: A system-
atic review and meta-analysis. Brain Sciences, 12(11), 1499.
Baril, E. M., & Humphreys, B. P. (2017). An evaluation of the research
evidence on the early start Denver model. Journal of Early Inter-
vention, 39, 321–338.
Bolton, J., & Mayer, M. D. (2008). Promoting the generalization of
paraprofessional discrete trial teaching skills. Focus on Autism and
Other Developmental Disabilities, 23(2), 103–111.
Chu, C. L., Chiang, C. H., Wu, C. C., Hou, Y. M., & Liu, J. H. (2017).
Service system and cognitive outcomes for young children with
autism spectrum disorders in a rural area of Taiwan. Autism,
21(5), 581–591.
Cidav, Z., Munson, J., Estes, A., Dawson, G., Rogers, S., &
Mandell, D. (2017). Cost offset associated with early start Denver
model for children with autism. Journal of the American Academy
of Child and Adolescent Psychiatry, 56, 777–783.
Colombi, C., Narzisi, A., Ruta, L., Cigala, V., Gagliano, A.,
Pioggia, G., Siracusano, R., Rogers, S. J., Muratori, F., & Prima
Pietra Team. (2018). Implementation of the early start Denver
model in an Italian community. Autism, 22(2), 126–133.
Contaldo, A., Colombi, C., Pierotti, C., Masoni, P., & Muratori, F.
(2020). Outcomes and moderators of early start Denver model
intervention in young children with autism spectrum disorder
delivered in a mixed individual and group setting. Autism, 24(3),
718–729.
Dawson, G., Rogers, S., Munson, J., Smith, M., Winter, J.,
Greenson, J., Donaldson, A., & Varley, J. (2010). Randomized,
controlled trial of an intervention for toddlers with autism: The
early start Denver model. Pediatrics, 125(1), e17–e23.
Dror, R., Malinger, G., Ben-Sira, L., Lev, D., Pick, C. G., & Lerman-
Sagie, T. (2009). Developmental outcome of children with enlarge-
ment of the cisterna magna identified in utero. Journal of Child
Neurology, 24, 1486–1492.
Fuller, E. A., & Kaiser, A. P. (2020). The effects of early intervention
on social communication outcomes for children with autism spec-
trum disorder: A meta-analysis. Journal of Autism and Develop-
mental Disorders, 50(5), 1683–1700.
Fulton, E., Eapen, V., Crnčec, R., Walter, A., & Rogers, S. (2014).
Reducing maladaptive behaviors in preschool-aged children with
autism spectrum disorder using the early start Denver model.
Frontiers in Pediatrics, 2, 40s.
Gao, D., Yu, T., Li, C. L., Jia, F. Y., & Li, H. H. (2020). Effect of
parental training based on early start Denver model combined
with intensive training on children with autism spectrum disorder
and its impact on parenting stress. Chinese Journal of Contempo-
rary Pediatrics, 22(2), 158–163.
Hoogenhout, M. (2012). Early intervention for autism: The early start
Denver model in South Africa. International Journal of Psychol-
ogy, 47, 278–279.
Kassambara, A. (2021). Rstatix: Pipe-friendly framework for basic sta-
tistical tests. https://cran.r-project.org/web/packages/rstatix/index.
html
Kdm, D. P., Srinath, D. S., Seshadri, D., et al. (2016). Lost time-need
for more awareness in early intervention of autism spectrum disor-
der. Asian Journal of Psychiatry, 25, 13–15.
Li, H. H., Li, C. L., Gao, D., Pan, X. Y., du, L., & Jia, F. Y. (2018).
Preliminary application of early start Denver model in children
with autism spectrum disorder. Chinese Journal of Contemporary
Pediatrics, 20(10), 793–798.
Lin, T. L., Chiang, C. H., Ho, S. Y., Wu, H. C., & Wong, C. C. (2020).
Preliminary clinical outcomes of a short-term low-intensity early
start Denver model implemented in the Taiwanese public health
system. Autism, 24(5), 1300–1306.
Lu, J. P., Yang, Z. W., Shu, M. Y., & Su, L. Y. (2004). Reliability,
validity analysis of the childhood autism rating scale. Chinese
Mental Health Journal, 25(1), 14–19.
Maenner, M. J., Shaw, K. A., Bakian, A. V., Bilder, D. A.,
Durkin, M. S., Esler, A., et al. (2021). Prevalence and characteris-
tics of autism spectrum disorder among children aged 8 years—
autism and developmental disabilities monitoring network, 11 sites,
United States, 2018. MMWR Surveillance Summaries, 65(3), 1–23.
Meinzen-Derr, J., Wiley, S., Grether, S., & Choo, D. I. (2011). Children
with cochlear implants and developmental disabilities: A language
1648 YANG ET AL.
 19393806, 2023, 8, D
ow
nloaded from
 https://onlinelibrary.w
iley.com
/doi/10.1002/aur.3006 by C
A
PE
S, W
iley O
nline L
ibrary on [15/11/2024]. See the T
erm
s and C
onditions (https://onlinelibrary.w
iley.com
/term
s-and-conditions) on W
iley O
nline L
ibrary for rules of use; O
A
 articles are governed by the applicable C
reative C
om
m
ons L
icense
https://orcid.org/0000-0001-5576-441X
https://orcid.org/0000-0001-5576-441X
https://cran.r-project.org/web/packages/rstatix/index.html
https://cran.r-project.org/web/packages/rstatix/index.html
skills study with developmentally matched hearing peers. Research
in Developmental Disabilities, 32, 757–767.
Penner, M., Rayar, M., Bashir, N., Roberts, S. W., Hancock-
Howard, R. L., & Coyte, P. C. (2015). Costeffectiveness analysis
comparing pre-diagnosis autism spectrum disorder (ASD)-targeted
intervention with Ontario’s autism intervention program. Journal
of Autism and Developmental Disorders, 45, 2833–2847.
Pilowsky, T., Yirmiya, N., Shulman, C., & Dover, R. (1998). The
autism diagnostic interview-revised and the childhood autism rat-
ing scale: Differences between diagnostic systems and comparison
between genders. Journal of Autism and Developmental Disorders,
28(2), 143–151.
Reichow, B., & Wolery, M. (2009). Comprehensive synthesis of early
intensive behavioral interventions for young children with autism
based on the UCLA young autism project model. Journal of
Autism and Developmental Disorders, 39(1), 23–41.
Rellini, E., Tortolani, D., Trillo, S., Carbone, S., & Montecchi, F.
(2004). Childhood autism rating scale (CARS) and autism behav-
ior checklist (ABC) correspondence and conflicts with DSM-IV
criteria in diagnosis of autism. Journal of Autism and Developmen-
tal Disorders, 34(6), 703–708.
Rogers, S. J., & Dawson, G. (2009). Early start Denver model for young
children with autism: Promoting language, learning, and engage-
ment. Guilford Press.
Rogers, S. J., Estes, A., Lord, C., Munson, J., Rocha, M., Winter, J.,
Greenson,J., Colombi, C., Dawson, G., Vismara, L. A.,
Sugar, C. A., Hellemann, G., Whelan, F., & Talbott, M. (2019). A
multisite randomized controlled two-phase trial of the early start
Denver model compared to treatment as usual. Journal of the
American Academy of Child and Adolescent Psychiatry, 58,
853–865.
Rogers, S. J., Yoder, P., Estes, A., Warren, Z., McEachin, J.,
Munson, J., Rocha, M., Greenson, J., Wallace, L., Gardner, E.,
Dawson, G., Sugar, C. A., Hellemann, G., & Whelan, F. (2021).
A multisite randomized controlled trial comparing the effects of
intervention intensity and intervention style on outcomes for
young children with autism. Journal of the American Academy of
Child and Adolescent Psychiatry, 60, 710–722.
Rollins, P. R., Campbell, M., Hoffman, R. T., & Self, K. (2016). A
community-based early intervention program for toddlers with
autism spectrum disorders. Autism, 20(2), 219–232.
Salomone, E., Beranova, S., & Bonnet-Brilhault, F. (2016). Use of early
intervention for young children with autism spectrum disorder
across Europe. Autism, 20(2), 233–249.
Schopler, E., Reichler, R. J., Devellis, R. F., & Daly, K. (1980). Toward
objective classification of childhood autism: Childhood autism rat-
ing scale (CARS). Journal of Autism and Developmental Disorders,
10(1), 91–103.
Schreibman, L. (2005). The science and fiction of autism. Harvard Uni-
versity Press.
Schreibman, L., Dawson, G., Stahmer, A. C., Landa, R., Rogers, S. J.,
McGee, G. G., Kasari, C., Ingersoll, B., Kaiser, A. P.,
Bruinsma, Y., McNerney, E., Wetherby, A., & Halladay, A.
(2015). Naturalistic developmental behavioral interventions:
Empirically validated treatments for autism spectrum disorder.
Journal of Autism and Developmental Disorders, 45(8), 2411–2428.
Shi, B., Wu, W., Dai, M., Zeng, J., Luo, J., Cai, L., Wan, B., & Jing, J.
(2021). Cognitive, language, and behavioral outcomes in children
with autism spectrum disorders exposed to early comprehensive
treatment models: A meta-analysis and meta-regression. Frontiers
in Psychiatry, 12, 691148.
Sinai-Gavrilov, Y., Gev, T., Mor-Snir, I., Vivanti, G., & Golan, O.
(2020). Integrating the early start Denver model into Israeli com-
munity autism spectrum disorder preschools: Effectiveness and
treatment response predictors. Autism, 24(8), 2081–2093.
Smith, T. (2001). Discrete trial training in the treatment of autism.
Focus on Autism and Other Developmental Disabilities, 16(2),
86–92.
Sparrow, S. S., Cicchetti, D., & Balla, D. A. (2005). Vineland adaptive
behavior scales. 2nd ed.
Vivanti, G., Prior, M., Williams, K., & Dissanayake, C. (2014). Predic-
tors of outcomes in autism early intervention: Why don’t we know
more? Frontiers in Pediatrics, 2, 58.
Waddington, H., van der Meer, L., & Sigafoos, J. (2016). Effectiveness
of the early start Denver model: A systematic review. Review Jour-
nal of Autism and Developmental Disorders, 3(2), 93–106.
Wainer, A. L., Hepburn, S., & Griffith, E. M. (2017). Remembering
parents in parent-mediated early intervention: An approach to
examining impact on parents and families. Autism, 21(1), 5–17.
Wang, C., Wang, Q., Xiang, B., Chen, S., Xiong, F., & Ji, Y. (2018).
Effects of propranolol on neurodevelopmental outcomes in
patients with infantile hemangioma: A case-control study. BioMed
Research International, 2018, 5821369.
Wang, J. W., Gu, D. D., Sun, Y. Y., Jia, F., & Li, H. (2019). Efficacy
analysis of early start Denver model in children with autism spec-
trum disorder. Chinese Journal of Behavioral Medicine and Brain
Science, 28(8), 684–688.
Xu, X. (2015). Early start Denver model for young children with autism.
Chinese Journal of Applied Clinical Pediatrics, 30(1), 801–802.
Xu, Y., Yang, J., Yao, J., Chen, J., Zhuang, X., Wang, W., Zhang, X., &
Lee, G. T. (2018). A pilot study of a culturally adapted early inter-
vention for young children with autism spectrum disorders in China.
Journal of Early Intervention, 40(1), 52–68.
Xu, Y., Yao, J., & Yang, J. (2017). Application of early start Denver
model for early intervention on autistic children. Chinese Journal
of Clinical Psychology, 25(1), 188–191.
Yang, Y. F. (2016). Rating scales for children’s developmental behavior
and mental health. People’s Medical Publishing House.
Yu, L., Mo, L., Tang, Y., Huang, X., & Tan, J. (2014). Effects of nurs-
ing intervention models on social adaption capability development
in preschool children with malignant tumors: A randomized con-
trol trial. Psycho-Oncology, 23(6), 708–712.
Zhang, Z., Zuo, Q., Lei, Z., Chen, R., Huang, L., He, G., Yuan, Y.,
Li, G., Liu, Q., Zhang, C., Wang, M., & Liu, X. (1995). The restan-
dardization of “the infant junior middle school students question-
naires”. Chinese Journal of Clinical Psychology, 3(1), 12–15.
Zhou, B. R., Xu, Q., Li, H. P., Zhang, Y., Wang, Y., Rogers, S. J., &
Xu, X. (2018). Effects of parent-implemented early start Denver
model intervention on Chinese toddlers with autism spectrum dis-
order: A non-randomized controlled trial. Autism Research, 11(4),
654–666.
Zhou, H., Xu, X., Yan, W., Zou, X., Wu, L., Luo, X., Li, T.,
Huang, Y., Guan, H., Chen, X., Mao, M., Xia, K., Zhang, L.,
Li, E., Ge, X., Zhang, L., Li, C., Zhang, X., Zhou, Y., …
LATENT-NHC Study Team. (2020). Prevalence of autism
spectrum disorder in China: A nationwide multi-center
population-based study among children aged 6 to 12 years. Neuro-
science Bulletin, 36(9), 961–971.
How to cite this article: Yang, Y., Wang, H., Xu,
H., Yao, M., & Yu, D. (2023). Randomized,
controlled trial of a mixed early start Denver
model for toddlers and preschoolers with autism.
Autism Research, 16(8), 1640–1649. https://doi.org/
10.1002/aur.3006
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https://doi.org/10.1002/aur.3006
https://doi.org/10.1002/aur.3006
	Randomized, controlled trial of a mixed early start Denver model for toddlers and preschoolers with autism
	INTRODUCTION
	METHODS
	Study design and participants
	Measures
	Gesell developmental schedules-third edition
	Childhood autism rating scale
	Social maturity scale
	Intervention groups
	M-ESDM Group
	M-DTT Group
	Quality control
	Statistical analysis
	RESULTS
	Demographic information of participants
	Main effect analysis
	Post hoc multiple comparison
	DISCUSSION
	AUTHOR CONTRIBUTIONS
	ACKNOWLEDGMENTS
	FUNDING INFORMATION
	DATA AVAILABILITY STATEMENT
	REFERENCES