September 2016 | Volume 4 | Article 991
CLINICAL STUDY PROTOCOL
published: 26 September 2016
doi: 10.3389/fped.2016.00099
Frontiers in Pediatrics | www.frontiersin.org
Edited by:
Yuri Bozzi,
University of Trento, Italy
Reviewed by:
Munis Dundar,
Erciyes University, Turkey
Umberto Balottin,
University of Pavia, Italy
*Correspondence:
David Cohen
david.cohen@aphp.fr
†
The members of the GPIS
Study Group are listed
at the end of the article.
Specialty section:
This article was submitted to Child
and Adolescent Psychiatry,
a section of the journal
Frontiers in Pediatrics
Received: 06July2016
Accepted: 05September2016
Published: 26September2016
Citation:
TanetA, Hubert-BarthelemyA,
CrespinGC, BodeauN, CohenD,
Saint-GeorgesC and
TheGPISStudy Group (2016)
ADevelopmental and Sequenced
One-to-One Educational Intervention
for Autism Spectrum Disorder:
A Randomized Single-Blind
Controlled Trial.
Front. Pediatr. 4:99.
doi: 10.3389/fped.2016.00099
A Developmental and Sequenced
One-to-One Educational Intervention
for Autism Spectrum Disorder:
A Randomized Single-Blind
Controlled Trial
Antoine Tanet
1,2,3
, Annik Hubert-Barthelemy
3
, Graciela C. Crespin
4
, Nicolas Bodeau
2
,
David Cohen
1,2
*, Catherine Saint-Georges
1,2,5
and The GPIS Study Group
†
1
Institut des Systèmes Intelligents et de Robotiques, Université Pierre et Marie Curie, Paris, France,
2
Departement de
Psychiatrie de l’Enfant et de l’Adolescent, APHP, Groupe Hospitalier Pitié-Salpêtrière et Université Pierre et Marie Curie,
Paris, France,
3
Croix Rouge Française, Paris, France,
4
Association Programme de Recherche et d’Etudes sur l’Autisme,
Paris, France,
5
Hôpital de jour Centre André Boulloche, Paris, France
Introduction: Individuals with autism spectrum disorder (ASD) who also exhibit
severe-to-moderate ranges of intellectual disability (ID) still face many challenges (i.e.,
less evidence-based trials, less inclusion in school with peers).
Methods: We implemented a novel model called the “Developmental and Sequenced
One-to-One Educational Intervention” (DS1-EI) in 5- to 9-year-old children with
co-occurring ASD and ID. The treatment protocol was adapted for school implementation
by designing it using an educational agenda. The intervention was based on intensity,
regular assessments, updating objectives, encouraging spontaneous communication,
promoting skills through play with peers, supporting positive behaviors, providing
supervision, capitalizing on teachers’ unique skills, and providing developmental and
sequenced learning. Developmental learning implies that the focus of training is what
is close to the developmental expectations given a child’s development in a specic
domain. Sequenced learning means that the teacher changes the learning activities
every 10–15min to maintain the child’s attention in the context of an anticipated time
agenda. We selected 11 French institutions in which we implemented the model in small
classrooms. Each institution recruited participants per dyads matched by age, sex, and
developmental quotient. Patients from each dyad were then randomized to a DS1-EI
group or a Treatment as usual (TAU) group for 36months. The primary variables – the
Childhood Autism Rating scale (CARS) and the psychoeducational prole (PEP-3) – will
be blindly assessed by independent raters at the 18-month and 36-month follow-up.
Discussion and baseline description: We enrolled 75 participants: 38 were random-
ized to the DS1-EI and 37 to the TAU groups. At enrollment, we found no signicant
differences in participants’ characteristics between groups. As expected, exposure to
school was the only signicant difference [9.4 (±4.1) h/week in the DS1-EI group vs. 3.4
(±4.5) h/week in the TAU group, Student’s t-test, t=5.83, p<0.001].
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Tanet et al. A Developmental and Sequenced One-to-One Educational Intervention
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Ethics and dissemination: The protocol was authorized by the competent national
regulatory authority (Agence nationale de sécurité du médicament et des produits de
santé) and approved by the local Ethics Committee (Comité de Protection des Personnes)
at the University Hospital Saint-Antoine (May 7, 2013). The ndings will be disseminated
through peer-reviewed journals and national and international conferences.
Trial registration numbers: ANSM130282B-31 (April 16 2013) and
ACTRN12616000592448 (May 6 2016).
Keywords: autism, intellectual disability, randomized controlled trial
BACKGROUND
Autism spectrum disorder (ASD) is characterized by the presence
of atypical social communicative interaction and behaviors. e
role of some genetic factors in ASD is known. However, there
is a growing body of neurobiological research that indicates the
presence of complex gene–environment interactions. Despite
these ndings, there is no approved biological treatment for this
disorder and the rst-line treatments pertain to psychosocial
domains (1). Typically, ASD is diagnosed by means of a behavio-
ral analysis during the 3- to 5-year-old age range; once diagnosed,
the treatment is primarily delivered through behavioral interven-
tions following dierent models. In essence, these models try to
promote cognitive, communication, and behavioral skills that are
considered essential to improve social skills in the long run (2, 3).
Several global interventions for core decits in ASD have
been proposed and assessed within clinical trials. e Treatment
and Education of Autistic and Communication Handicapped
Children (TEACCH) program uses many technical interventions
to meet the individual needs of people with autism. e work
program is tailored to some seminal aspects of ASD. First, it is
centered on the individual. Individual needs are assessed through
a comprehensive assessment of several developmental dimen-
sions while taking into account emerging capacities. Second, it
requires an understanding of autism, the adoption of appropri-
ate adaptations and a broadly based intervention strategy (e.g.,
structured teaching, visual understanding, object manipulation,
social communication skills) that builds on existing skills and
interests. ird, the environment is organized to help children
and adults understand and remember what to do (e.g., visual
agendas, making expectations clear, and explicit, visual materi-
als, structured architecture). e focus is on positive strategies to
support behavioral and teaching strategies (4, 5).
Applied Behavioral Analysis (ABA) is a one-to-one intensive
method that uses reinforcement of adaptative and acquired skills
(6). e rst structured attempts by Lovaas (7) were criticized
(diculties in generalization of learned behaviors; mechanical
responses; lack of spontaneity) despite their encouraging rst
results. ese criticisms led to the development of Pivotal Response
Training [PRT], a more naturalistic behavioral treatment that
has good documented eectiveness (8). PRT is a home-based
intervention that includes parents in the routines. e method is
based on choosing “pivotal” skills as the target of the treatment;
following the child’s choice of activities and games; reinforcing
not only the correct answer expected by the professional but
also all (meaning complete or incomplete) forms of attempts to
respond; alternating between acquisition and maintenance; and
using intrinsic reinforcers.
e Early Start Denver Model (ESDM) is an early and intensive
intervention approach for young children. e interventions are
based on the following: (i) a curriculum that evaluates the child’s
development across dierent developmental domains; (ii) specic
procedures for learning and incorporating ABA principles, such
as PRT; (iii) sessions focusing on interactions with children, inter-
personal exchanges, and shared commitment with materials and
activities of daily living; (iv) a positive aect, adults being responsive
and sensitive to child cues; (v) verbal and non-verbal communica-
tion cues; (vi) proximal developmental windows, meaning that the
focus of training is what is close to the developmental expectations
given a child’s development in the according domain; and (vii) par-
ents’ involvement. is program is implemented in small groups or
individually at a specialized center or at home (3, 9).
e Developmental, Individual Dierences, and Relationship-
based (DIR) method is built on three axes: (i) the level of
functional and emotional development reached by the child; (ii)
the individual dierences in information processing and motor
planning; and (iii) the types of interactions that the child estab-
lishes with his/her partners (10). Floor Time is the core of the DIR
method. It consists of sequences of guided play (15–20min) that
are repeated several times by parents throughout the day and are
supervised by an expert. e DIR principles that should always be
respected are to follow the child’s lead and support his/her initia-
tive; to focus on joint attention; to close circles of communication;
to create semi-structured problem solving; to contrast repetitive-
ness with playful obstruction; to support visual attention; and to
work on imitation (10, 11).
In an attempt to capture the common components among these
models and what could be learned from evidence-based studies,
Narzisi and colleagues (12) delineated the following principles:
the rst group regards timing: (1) starting as early as possible; (2)
minimizing the gap between diagnosis and treatment; (3) being
intensive (not less than 3–4h of treatment per day); the second
group is based on viewing parents as partners and involving
family; the third group gathers principles related to treatment
program: (1) providing regular assessments, supervision and
updating the goals of treatment; (2) encouraging spontaneous
communication; (3) promoting skills through play with peers;
(4)nalizing the acquisition of new skills and their generalization
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and maintenance in natural contexts; and (5) supporting positive
behaviors rather than tackling challenging behaviors.
Why Should We Implement a
School-Based Intervention?
Despite the encouraging results presented earlier, most of those
programs (a notable exception being TEACCH) do not target
school-aged children and are not proposed to occur in a school
setting. is is unfortunate because schools are a favorable loca-
tion for autism interventions (13). Additionally, many children
with ASD do not receive a sucient amount of treatment (14),
even in countries with free access to health care (15). Because chil-
dren with ASD benet from being with other peers at school, the
gap between education research and education practice (16) may
be a missed opportunity to oer more support to these children.
Additionally, larger doses of treatment could be oered in school
contexts, especially when interventions are administered 1:1 (17).
Several agencies have recommended conducting interventions in
school-based settings (18, 19). Two objectives should be com-
bined: school-based core decit interventions and school-based
social communication practice (20). ere are already several
studies that have shown that school-based interventions are able
to reach larger numbers of children with ASD. is may improve
challenges with generalization by using learned skills regarding
communication in a natural environment, such as in the class-
room (21, 22). Additionally, the preschool context seems to oer
opportunities to develop communication skills (23, 24), and by
oering opportunities to enter into play groups, teachers can
supply reinforcements of the non-verbal ASD child requests (25).
However, there are very few school-based social communica-
tion interventions, and in many cases, teachers at school do their
best without guided specic interventions for ASD children in the
classroom. Consequently, there is a lack of response from teachers
to the communicative acts produced by children with ASD (26).
General educational teachers provide infrequent verbal prompt-
ing with ASD children (27), and they more frequently engage in
functional play than symbolic play (28). ey also lack supervision
(20). us, there is a paradox between the need for appropriate
intensive interventions for ASD and what is proposed in most
school settings. For example, Mudford and colleagues (29) showed
that the implementation of an evidence-based ABA program in
preschoolers was not complete: 93% of the participants were not
provided the dose of treatment (40h/week). Additionally, from
an eciency perspective, although several programs support the
concept of tailoring interventions to the child’s needs and skills, to
our knowledge, no one has questioned whether programs could
be adapted according to teaching local skills.
Why Should We Study Children with ASD
and Intellectual Disability?
As expressed in the dimensional approach of the new classications
in the DSM-5 (30), intellectual disability (ID) is a frequent chal-
lenge and comorbidity in ASD. According to studies, ID co-occurs
in 50 to 75% of ASD cases (31). Risk factors of comorbid ID in
ASD are gender (despite the high number of males with ASD,
the male/female ratio decreases in ASD comorbid with ID) and
the existence of seizures or of a neurodevelopmental or genetic
syndrome (32, 33). e co-occurrence of ID also appears to be a
prognostic factor for long-term outcomes of ASD (12, 34) and a
risk factor of the incidence of challenging behaviors that provoke
severe morbidity in some cases (35). To date, very few models
have specically addressed ASD comorbid with ID, in particular
when ID is in the severe-to-moderate range. erefore, the need
to focus on this understudied population is warranted. Here, we
wonder whether or not children with comorbid ASD and severe
ID may be receptive to a pedagogical content? For such children
over 5years, could an adapted and one-to-one cognitive program
in school be a road to improve non-verbal and verbal communi-
cation and to promote social skills?
METHODS/DESIGN
Objectives
In this paper, our aims are to describe a school-based intervention
program (a developmental and sequenced one-to-one educational
intervention, DS1-EI) that was adapted to the French health and
education system; to justify the principles that were followed to
implement the method and adapt it to a low-functioning popula-
tion (i.e., ASD comorbid with ID); to describe the randomized
controlled trial we began; and to present the sociodemographic
and clinical characteristics of the participants at baseline.
Participants and Recruitment
All participants were recruited in outpatient French health care
institutions that are specialized in treating children with autism
and intellectual handicaps. At the request of the French national
health regulatory authority [Agence nationale de sécurité du
médicament et des produits de santé (ANSM)] and the main spon-
sor [Caisse Nationale de Solidarité pour l’Autonomie (CNSA)], we
balanced day care hospitals and special education clinics to have
a representative sample of French institutions. In each institution,
we obtained a specic commitment to accept the implementation
of a DS1-EI school-based program as described below and to
recruit the same number of participants to be randomized into
a DS1-EI exposed group (called the DS1-EI group) or a treat-
ment as usual (TAU) group who would serve as controls. e
commitment also entailed having the required resources from
local school authorities to implement the DS1-EI and to have the
leading teacher from the classroom be supervised. To avoid bias
in the TAU group as a result of the diversity of institutions, we
decided to randomize participants by site. Figure1 summarizes
the list of institutions involved in the protocol and the number of
patients by site. In total, we enrolled 75 participants.
Each parent provided informed written consent before inclu-
sion. e inclusion criteria were a current diagnosis of ASD
conrmed by a clinical assessment based on the International
Classication of Diseases, 10th edition criteria and the Autism
Diagnostic Interview-Revised (ADI-R) (36); an intellectual hand-
icap with nancial compensation from local agencies [Maison
Départementale du Handicap (MDPH)]; being aged between 5
and 9years; and having a communication developmental age of
24months and under based on a Vineland assessment or a 3-year
speech delay based on a Psycho-Educational Prole, third edition.
FIGURE 1 | Institutions and participants’ enrollment in the DS1-EI trial by site. HDJ, Hopital de Jour (Day care medical center); IME, Institut Medico-Educatif
(Special education center).
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We did not exclude children with known organic syndromes and/
or non-stabilized neuropaediatric (e.g., seizures) or medical (e.g.,
diabetes mellitus) comorbidities. However, during the medical
assessment, we specically listed comorbidities. e exclusion
criteria were limited to parents’ refusal to participate; family’s
plans to change institutions in the short term for any reason; and
patient’s severe behavioral impairments that would challenge
treatment adherence. Of note, this last exclusion criterion was
based on local institution sta decision. Before randomization,
each site was requested to assess the IQ of the participants based
on the Kaufman Assessment Battery for Children second edition
(KABC-II) or, failing that, Vineland scores. Based on these results,
dyads of participants matched for sex, age, and developmental
quotient (DQ) were formed to limit the risk of bias between
groups. Randomization before group allocation to TAU or DS1-EI
group was performed by drawing lots in each dyad per site so that
each site could have a TAU group and a DS1-EI group of three
to four participants each. Randomization was performed by the
methodological coordinating team at the Salpêtrière Hospital and
was independent from local inclusion sites. TAU was dened as
all therapeutic interventions given to a specic child. Given the
study duration, we did not recommend not to change children’s
therapeutic protocol in the TAU group during the study period.
e trial duration was dened as 36months but included 12-, 18-,
and 24-month intermediate assessments.
DS1-EI Treatment Principles
Participants randomized to the DS1-EI group received the spe-
cic experimental protocol four mornings per week (2h 30min);
the rest of the week they continued to receive the usual protocol
of each site. e treatment principles are summarized in Table1.
e setting was a small classroom with four pupils, but an adapted
environment was proposed. Following the principles of TEACCH
(5), each child was oered a desk, two chairs (one for the child,
one for the adult working with the child), a screen where pic-
tures of the child’s schedule and activities were provided, and a
locker with his or her picture. In contrast to TEACCH, the child
sat with his back close to the wall where the screen was placed
(see pictures in the supplementary material S1). e setting also
included a large table for mid-session group collaboration and
a place oering benches and carpets where group participants
(both children and adults) met at the beginning and ending of a
session. Although the program did not reach the 40h per week
recommended by some programs (37), it remained intensive,
with 10h of DS1-EI plus other therapeutic practices according
to each institution (e.g., occupational therapy; speech therapy;
social skill group activities). e program followed develop-
mental rules, meaning the training was focused on the nearest
expected activity/skill of a given child’s development in a specic
domain as recommended by the ESDM (9). In terms of timing,
the program was sequenced in two ways. First, as in TEACCH,
TABLE 1 | A developmental and sequenced one-to-one educational intervention (DS1-EI) for autism spectrum disorder: main principles.
Characteristics Brief denition Justication
Setting To be implemented in a small classroom with four pupils TEACCH, Barton etal. (13)
In an adapted environment TEACCH
Intensive One-to-one support 10h per week in addition to other treatment practices (e.g., occupational therapy, speech
therapy, psychotherapy)
ABA, ESDM
Developmental The focus of training is what is close to the developmental expectation given a child’s development within a domain ESDM
Sequenced The 2h 30min sessions follow an anticipated and structured agenda TEACCH
Teachers change learning activities every 10–15min to keep a child’s attention Original
Curriculum based A detailed assessment/curriculum is required to follow the developmental approach and to choose the appropriate
cognitive/motor activity to be taught in each domain for preschoolers
ESDM, TEACCH
Educational
objectives
Given the developmental quotient of the targeted children, the educational objectives are those of a second grade
program for preschoolers (see Table2 below for details)
French Ministry for National
Education
Reinforcers Supporting positive behaviors rather than tackling challenging behaviors ABA, ESDM
Using positive emotion engagement from teachers ESDM
Group Group activities are organized within the time schedule to encourage spontaneous communication and promote
social skills through play with peers
Many programs
Supervision Regular supervision of teachers with children’s objectives being updated ESDM, ABA, DIR
Exploiting teachers’
unique skills
Implementation of the program will benet from using teachers’ individual skills, such as their knowledge of a
specic method (e.g., the use of Picture Exchange Program) or of a particular child
COMVOOR
TEACCH, Treatment and Education of Autistic and Communication Handicapped Children; ABA, Applied Behavioral Analysis; ESDM, Early Start Denver Model; DIR, Developmental,
Individual Differences and Relationship-based method; COMVOOR, Voorlopers in Communicatie.
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the 2h 30min sessions followed an anticipated and structured
agenda that was presented for each child on a screen. When a
novel activity started, the corresponding pictogram was shown
on the child’s desk. Second, teachers were asked to change desk
and activities every 10–15min to maintain the child’s attention
and to help him improve by challenging patient’s need of same-
ness. us, each 10–15min, the child has a new activity and a new
teacher. e program was also curriculum based and had specic
educational objectives (see details below).
Academic Training
Because DS1-EI was a program implemented in classrooms, both
the curriculum and the objectives followed academic recom-
mendations from the French Ministry of National Education. e
curriculum was adapted from the French program for nursery
and primary schools and handiscol principles (http://eduscol.
education.fr). is was decided based on the idea that these
recommendations were part of a teacher’s area of expertise and
that it would promote participation in the program. Additionally,
each classroom of N children was under the responsibility of one
teacher helped by (N − 1) assistants, according to the 1-to-1
design of the program. In the same vein, one of the principles of
the program was capitalizing on teachers’ individual skills. We
believed that implementation of the program would benet from
using teachers’ specic knowledge (e.g., the use of the Picture
Exchange Program). A detailed assessment/curriculum was
a prerequisite of each child’s academic program because the
DS1-EI was designed to follow a developmental approach, which
required the selection of appropriate cognitive/motor activities
for training within each domain. e curriculum is described in
detail in the supplementary material S2. Regarding the academic/
educational objectives, they were grouped into four domains:
mathematics, language and communication, intermodality, and
autonomy. Table 2 provides some examples of the activities by
domain and level of child’s performance.
Teachers’ Training and Supervision
Each teacher and each assistant were trained by Annik Hubert-
Barthelemy during a 1-week session. ey were provided with
a method presentation and were trained to use positive aect,
shared engagement, responsiveness, and sensitivity to child
cues, to focus on both verbal and non-verbal communication,
and to support positive behaviors rather than tackle challeng-
ing behaviors. e DS1-EI detailed assessment/curriculum
was explained, including how to keep learning proposals close
to a given child’s developmental needs. e last 2days of the
training session was dedicated to dene new objectives and
adaptations. During the morning, the teacher with the help of
his/her assistants had to fulll children curriculums and to have
related written observation. During the aernoon, curriculum
was discussed and rst learning activities for all domains were
decided for each child.
Supervision was organized in three dierent steps: (i) daily
sessions of verbal exchanges and written observations aer the
class about each child in each domain with all professionals (the
teacher and the assistants); (ii) weekly supervisions by a psycholo-
gist; (iii) monthly supervisions by the main investigator to ensure
the conformity of the program application and to help the teacher
adapting the directives according to each child outcome.
Primary and Secondary Variables
Table 3 summarizes the variables that we planned to measure
at enrollment and at several time points throughout the trial.