Articles

Effectiveness of the parent-mediated intervention for

children with autism spectrum disorder in south Asia in
India and Pakistan (PASS): a randomised controlled trial
Atif Rahman, Gauri Divan, Syed Usman Hamdani, Vivek Vajaratkar, Carol Taylor, Kathy Leadbitter, Catherine Aldred, Ayesha Minhas, Percy Cardozo,
Richard Emsley, Vikram Patel*, Jonathan Green*

Summary
Background Autism spectrum disorder affects more than 5 million children in south Asia. Although early interventions Lancet Psychiatry 2015
have been used for the treatment of children in high-income countries, no substantive trials have been done of the Published Online
interventions adapted for use in low-income and middle-income countries (LMICs). We therefore assessed the December 15, 2015
http://dx.doi.org/10.1016/
feasibility and acceptability of the parent-mediated intervention for autism spectrum disorder in south Asia (PASS) in
S2215-0366(15)00388-0
India and Pakistan.
See Online/Comment
http://dx.doi.org/10.1016/
Methods A single-blind randomised trial of the comparison of 12 sessions of PASS (plus treatment as usual) with S2215-0366(15)00453-8
treatment as usual alone delivered by non-specialist health workers was done at two centres in Goa, India, and *Joint senior authors
Rawalpindi, Pakistan. Children aged 2–9 years with autism spectrum disorder were randomly assigned (1:1) by use of University of Liverpool,
probabilistic minimisation, controlling for treatment centre (Goa or Rawalpindi), age (<6 years or ≥6 years), and Institute of Psychology,
functional impairment (Vineland Adaptive Behaviour Scale Composite score <65 or ≥65). The primary outcome was Health and Society, Academic
Child Mental Health Unit, Alder
quality of parent–child interaction on the Dyadic Communication Measure for Autism at 8 months. Analysis was by Hey Children’s NHS Foundation
intention to treat. The study is registered with ISRCTN, number ISRCTN79675498. Trust, Liverpool, UK
(Prof A Rahman PhD); Sangath,
Findings From Jan 1 to July 30, 2013, 65 children were randomly allocated, 32 to the PASS group (15 in Goa and 17 in Goa, India (G Divan MRCPCH,
V Vajaratkar MOT, P Cardozo MA,
Rawalpindi) and 33 to the treatment-as-usual group (15 in Goa and 18 in Rawalpindi). 26 (81%) of 32 participants Prof V Patel FMedSci); Human
completed the intervention. After adjustment for minimisation factors and baseline outcome, the primary outcome Development Research
showed a treatment effect in favour of PASS in parental synchrony (adjusted mean difference 0·25 [95% CI Foundation, Islamabad,
0·14 to 0·36]; effect size 1∙61 [95% CI 0·90 to 2·32]) and initiation of communication by the child with the parent (0·15 Pakistan (S U Hamdani MBBS);
University of Manchester,
[0·04 to 0·26]; effect size 0∙99 [0·29 to 1·68]), but time in mutual shared attention was reduced (–0·16 [–0·26 to –0·05]; Institute of Brain, Behaviour
effect size –0∙70 [–1·16 to –0·23]). and Mental Health, Manchester,
UK (C Taylor PhD,
Interpretation Our results show the feasibility of adapting and task-shifting an intervention used in a high-income K Leadbitter PhD);
Stockport Foundation Trust,
context to LMICs. The findings also replicate the positive primary outcome treatment effects of a parent-mediated Stepping Hill Hospital,
communication-focused intervention in the original UK Preschool Autism Communication Trial, with one negative Stockport, UK (C Aldred PhD);
effect not reported previously. Institute of Psychiatry,
Rawalpindi Medical College,
Pakistan (A Minhas FCPS); Centre
Funding Autism Speaks, USA. for Biostatistics, Institute of
Population Health, University of
Introduction disorder aged between 2–9 years in India.7 The two key Manchester, Manchester
Academic Health Science Centre,
Autism spectrum disorder is a neurodevelopmental barriers to treatment access are a lack of evidence for
Manchester, UK (R Emsley PhD);
disability that is associated with impairments in social interventions that have been adapted and assessed for London School of Hygiene &
reciprocity, communication, and behaviour and has an feasibility in low-income countries, and shortage of Tropical Medicine, London, UK
estimated global prevalence of 0·5–1%.1 It has a severe specialist personnel to deliver interventions to the large (Prof V Patel); and University of
Manchester and Manchester
effect on the social development of children into populations who are not near specialist centres.8 The
Academic Health Sciences
adulthood,2 with substantial economic consequences in treatment gap for community interventions in the region Centre, Royal Manchester
terms of service and family-related costs—more than is nearly 100% and research to address barriers to care for Children’s Hospital, Manchester,
£31 billion per year in the UK in childhood,3 higher than mental health disorders in children is described as one of UK (Prof J Green FRCPsych)
for asthma, diabetes, or intellectual disability. Autism the top five grand challenges in global mental health.5 Correspondence to:
Prof Jonathan Green, University of
spectrum disorder is therefore a priority for the global Important innovations to reduce the treatment gap for
Manchester and Manchester
mental health agenda4,5 and in the WHO mental health other mental disorders are the adaptation of interventions Academic Health Sciences Centre,
Gap Action Programme.6 tested in high-income countries to local needs and the Royal Manchester Children’s
Most children with autism spectrum disorder live in delivery of these interventions by non-specialist health Hospital, Room 3.311, Jean
McFarlane Building, Oxford Road,
low-income countries and have no access to treatment. workers.9
Manchester M13 9PL, UK
South Asia is home to the largest number of children with In high-income countries, research into interventions jonathan.green@manchester.
this disorder worldwide, with a recent national estimate of for autism spectrum disorder has accelerated, with ac.uk
more than 5 million children with autism spectrum synthesis of studies for a range of interventions in the

www.thelancet.com/psychiatry Published online December 15, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00388-0 1

 Articles
Research in context
Evidence before this study
In low-income countries, the treatment gap for autism
spectrum disorder is almost 100%. Effective parent-mediated
interventions for autism spectrum disorder have been
developed in high-income settings, but research to adapt and
assess such interventions in low-income countries is scarce. We
searched PsycINFO, Scopus, MEDLINE, CINAHL, and the
Cochrane Central Register for Controlled Trials with the terms
“autism spectrum disorder”, “pervasive developmental
disorder”, “developing countries”, “low income countries”, “low
and middle income countries”, “parent mediated”,
“nonspecialist delivered”, “teacher delivered”, and “aide
delivered”. We restricted our search to reports of randomised
controlled trials and systematic reviews published in English
only. From this search and relevant systematic reviews of the
scientific literature up to June 30, 2013, we identified three
small randomised controlled trials of psychosocial interventions
for autistic spectrum disorder delivered by non-specialists in
low-income and middle-income countries (LMICs; each with
fewer than 34 participants): two parent-education programmes
in China and one parent-mediated child intervention in
Thailand. In an updated search from June 30, 2013, to Jan 31,
2015, using the same criteria and restricted to LMICs and
autistic spectrum disorder, we did not find further studies.
UK National Institute for Health and Care Excellence
(NICE) guidelines,10 and Cochrane11 and other reviews.12
In the 2013 NICE guidelines, social communication
interventions were the only options recommended for
the treatment of core symptoms in children. In
high-income countries, social communication inter-
ventions have been tested in randomised trials in the
preschool period,13–15 in the early school years,16 and
recently in the infancy prodrome.17 Results from these
trials showed improvements in immediate parent–child
social interactions. The findings from one study
showing an effect on language13 were not replicated. A
meta-analysis10 of two studies from our group14,17 showed
that social communication interventions had a modest
effect on autism symptoms, with confidence intervals
including the null value.
Very little testing of interventions has been done in low-
income and middle-income countries (LMICs). Systematic
reviews published between January, 1990, and June,
2013,11,18,19 identified only three small studies (each with
fewer than 34 participants) of psychosocial intervention
for symptoms of autism spectrum disorder delivered by
non-specialists in LMICs.20–22 In an updated search from
June 30, 2013, to Jan 31, 2015, with the same criteria, we
identified no subsequent studies. Brief parent-training
programmes (5 h and 20 h long) were assessed in two
studies from China,20,21 and a 3-month DIR (developmental,
individual-differences, and relationship-based model)
floor-time intervention was compared with usual care in
2 www.thelancet.com/psychiatry Published online December 15, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00388-0
Added value of this study
Our study is the first substantive randomised controlled trial
of an evidence-based intervention delivered by non-specialists
in two low-income countries in south Asia. We adapted an
intervention (parent-mediated communication-focused
intervention) used in a UK trial for delivery by non-specialist
workers in LMICs and tested it in a randomised trial in India
and Pakistan. The intervention was successfully delivered with
fidelity by the non-specialists and produced significant
improvements in parent–child communication in two of three
primary outcome measures for quality of parent–child
interaction on the Dyadic Communication Measure for
Autism at 8 months, replicating the findings from the UK
trial.
Implications of all the available evidence
Non-specialist delivered interventions for autistic spectrum
disorder are feasible, acceptable, and potentially effective in
low-resource countries. These findings suggest that the
processes leading to the development of autistic spectrum
disorder might be similar in the UK, India, and Pakistan, and
strengthen the case for testing similar interventions across
settings after careful adaptation to the local context.
another study in Thailand.22 We planned to systematically
adapt a social communication intervention for childhood
autism that had been used in a high-income country for
use in south Asian countries.
The UK parent-mediated communication-focused
intervention from the Preschool Autism Communication
Trial (PACT)14 had effects on several key aspects of early
dyadic communication between parent and child,
including substantially improving parental synchronous
responses to the child, which are associated with
enhanced social and communication outcomes in
children with and without autism.23 We were confident
that these features of the PACT intervention would be
translatable, feasible, and effective in different
sociocultural contexts. Study teams undertook formative
research24 between May, 2012, and March, 2013, to adapt
the PACT intervention for use in two south Asian
LMICs—India and Pakistan. The research involved
qualitative interviews with parents, stakeholder focus
groups, analyses of case studies or practice cases by
senior staff at the site, and regional expert adaptation
workshops, some of which were also attended by
members of the UK originating team. This formative
research informed the adaptation process of the original
PACT intervention for use in south Asia and addressed
potential barriers to scale-up.24 In the adaptation, the core
aims and procedures of the PACT intervention were
unchanged—ie, targeting social interactive and
communication impairments in autism. A key aim of this

research was the cultural adaptation of the intervention to
be compatible with local beliefs, and to have parenting
practices and procedures that could be delivered by non-
specialist workers.24 The rationale was that children with
autism spectrum disorder would respond with enhanced
communicative and social development to a style of
parent communication adapted to their impairments.
The resulting adapted intervention was called the parent-
mediated intervention for autism spectrum disorder in
south Asia (PASS). PASS was based on the same
theoretical construct as the PACT intervention, with a
naturalistic approach to scaffolding and developing
communication skills in the child with autism spectrum
disorder. Key differences were a flexibility to deliver PASS
to family members besides the parents, in keeping with
the cultural context; some simplification of the language
and preparation of scripts for non-specialist delivery; an
increase in the structured guidance for delivery of
strategies; and a shortened intervention focusing on the
initial 6 months of the intensive phase of treatment, a
period in which maximum therapeutic gains were noted
in PACT14 and that was likely to be practical for families in
Asia.
We did a randomised controlled trial to assess the
feasibility and acceptability of PASS in India and
Pakistan; the success of delivery of the intervention by
non-specialist health workers; and the effectiveness of
the adapted model in replicating positive treatment
effects on dyadic communication noted in the UK PACT.
Methods
Study design and participants
This single-blind, randomised controlled trial was
conducted from two research institutions in Goa, India,
and Rawalpindi, Pakistan, with expertise in implementing
mental health trials.
Children aged 2–9 years were identified through
attendance at specialist centres or after screening within
community education and health services using an
adapted version of the Modified Checklist for Autism in
Toddlers (M-CHAT). All participants met criteria for
autism on the INCLEN Diagnostic Tool for Autism
Spectrum Disorder,25 which was administered by the
research team. The selected age range of the participants
in our study was broader (mean age range at diagnosis
from nearly 5 years to 8 years) than that in PACT because
autism is typically diagnosed earlier (at around age
5 years26) in the UK than in south Asia.27 Children had a
developmental assessment by a specialist as part of a
baseline assessment to ensure that their developmental
age was equivalent to older than 12 months.
We excluded children with a twin with autism, a
non-verbal age equivalent to 12 months or younger on
the Vineland Adaptive Behaviour Scales (VABS), epilepsy
with seizures in the previous 6 months, severe hearing or
visual impairment in a parent or the child, or a parent
with a severe psychiatric disorder requiring treatment.
www.thelancet.com/psychiatry Published online December 15, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00388-0
Articles
The study was approved by the University of Liverpool
Research Ethics Committee, local ethical committees in
Goa (Sangath) and Rawalpindi (Human Development
Research Foundation), and by the Indian Council of
Medical Research. At least one parent of each child
provided written informed consent.
Randomisation and masking
After informed consent was obtained and baseline
assessments were completed, children were given a For more on PASS see
sequential identification number and randomly allocated http://hdrfoundation.org/docs/
training/PASS_Manual_web-
via computer to the PASS (plus treatment as usual) 2015.pdf
group or treatment-as-usual alone group in a 1:1 ratio by
an independent statistician at the Manchester Academic
Health Sciences Clinical Trials Unit, UK, who informed
the clinical sites. Allocation was done with probabilistic
minimisation, controlling for treatment centre (Goa or
Rawalpindi), age (<6 years or ≥6 years), and functional
impairment (VABS composite score <65 or ≥65).
Assessors and supervising research staff were masked to
treatment allocation; however, treatment allocation could
not be masked from families and therapists.
Strict separation was maintained between assessment
and clinical data; assessors and therapists were located
and supervised separately at both sites. To avoid the effects
of familiarity, materials and location for assessment of
children were different from those for the interventions.
Assessors assessed baseline and endpoints using
anonymised videotapes, unaware of the case details,
assessment timepoint (ie, baseline or endpoint), and
treatment status. Because many participants were unlikely
to be familiar with video recording, two additional video-
recorded sessions per participant were included in the
treatment-as-usual group so that families could become
accustomed to being filmed and to avoid any possible
measurement error because of unfamiliarity with the
procedure.
Procedures
The intervention consisted of one-to-one clinic or home
sessions between the health worker and the parent with For M-CHAT see
the child present. The aim of the intervention was, first, http://www.m-chat.org
to increase parental synchronous response to the child’s
communication and reduce over-directive parental
responses by working with the parent and using video-
feedback methods to address parent–child interaction.
Second, further incremental development of the child’s
communication was helped by promotion of a range of
strategies such as action routines, familiar repetitive
language, and pauses. PASS was thus staged and
specifically manualised to represent the developmental
progression of early social communication skills. As we
mentioned previously, the age of presentation of autism
in the subcontinent tends to be later than in Europe and
North America,27 hence we raised the upper age of
inclusion to 9 years. The intervention did not require any
specific adaptations to make it relevant to older children;
3
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it has been used successfully in children of this age group
in the UK with pre-language and early language stages of
development. Feasibility and case series information
obtained during the formative phase showed that PASS
was feasible and appropriate for children up to 9 years of
age, particularly with the more severely affected children
in south Asia.
For training and supervision in intervention and
research assessments, we used a cascaded procedure
(described in this report and in detail elsewhere).24 The
UK team (CA, CT, and JG) trained and supervised local
specialists (AM, GD, and VV) who then trained and
supervised the local staff (implementation specialists).
The UK team also continued to provide online support as
necessary during the trial. At each site there were separate
local experts for research and intervention who trained
and supervised the local assessors and the health workers,
respectively. In keeping with the task-shifting model, the
implementation therapists had a college-level education,
but no previous experience of delivering mental health
care. The health workers received training for 10 days that
included classroom instructions, role playing, and
observations in resource rooms, followed by initial
supervised practice-based learning on non-trial cases.
The training covered basic child development and autism,
109 children assessed for eligibility
(44 Goa, India, and 65 Rawalpindi,
Pakistan)
44 excluded (14 Goa and 30 Rawalpindi)
24 did not meet inclusion criteria (3 Goa and 21 Rawalpindi)
9 declined to participate (1 Goa and 8 Rawalpindi)
4 met exclusion criteria (Goa)
7 other reasons
3 migrated out of Goa
4 could not be contacted (3 Goa and 1 Rawalpindi)
65 children randomly allocated
(30 Goa and 35 Rawalpindi)
33 allocated to treatment-as-usual group 32 allocated to PASS group (15 Goa and 17 Rawalpindi)
(15 Goa and 18 Rawalpindi) 26 received PASS (12 Goa and 14 Rawalpindi)
6 discontinued PASS after ≤3 sessions (3 Goa
and 3 Rawalpindi)
1 intervention not relevant (Goa)
3 pursued other services (2 Goa and 1 Rawalpindi)
2 moved to another country or city (Rawalpindi)
3 lost to follow-up (Rawalpindi) 3 lost to follow-up (Rawalpindi)
1 pursued other services 1 pursued other services
2 moved to another country or city 2 moved to another country or city
30 intention-to-treat analysis 29 intention-to-treat analysis
(15 Goa and 15 Rawalpindi) (15 Goa and 14 Rawalpindi)
Figure: Trial profile
PASS=parent-mediated intervention for autism spectrum disorder in south Asia.
4 www.thelancet.com/psychiatry Published online December 15, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00388-0
alongside PASS theory and practice. The health workers
had to achieve a prespecified level of competency to
proceed to work in the trial phase. One-to-one supervision
was done at the two sites until the non-specialist health
workers achieved a predetermined level of measured
competence on a standardised assessment. Group
supervision continued during the trial within local sites
by the site specialists. All trial therapy sessions were video
recorded. During the intervention, the health workers
were supported with semistructured scripts to help them
communicate the goals of the programme to parents and
individualise the programme. They had group supervision
with the local specialist to discuss progress and any
necessary tailoring of the intervention. Adherence of the
implementation therapist to the model during the trial
was assessed by therapy experts from Manchester, UK
(CT and CA), who rated videos of 10% (36 of 360) of
treatment sessions, randomly selected across health
workers and stages of PASS and used the same fidelity
coding procedure as in PACT.14
The intervention was delivered in the participating
parents’ language of choice (Urdu in Pakistan, and
English [n=5], Konkani [n=6], Marathi [n=1], Marathi and
Konkani mixed [n=1], and English and Konkani mixed
[n=1] in India). All written information and questionnaire
instruments were translated and used in these preferred
languages.24 All sessions in India were delivered in the
home, and all those in Pakistan in the clinic. An important
principle in the adaptation process was to have flexibility
in the location of delivery of the intervention, to take into
account structure of health systems, cultural norms,
therapist safety issues, and family preference. In India,
parents appreciated the convenience of home delivery; in
Pakistan, families were used to attending a clinical setting
and hence this was the location of choice. No family
transportation costs were covered by the study. Families
attended 1-h sessions every 2 weeks for 6 months
(12 sessions). The initial home visit from the non-
specialist health worker, supported by the supervisor,
explored parents’ beliefs about the nature and origin of
autism and other factors that might affect engagement,
including individual learning styles of the target parent.24
At each session, a videotape of the parent and child was
made and watched and discussed in detail with the
parents in terms of progress since the last session, fidelity
to treatment goals, and planning of the next steps. Parents
were asked to spend 30 min a day between clinic sessions
practising predefined strategies at home and were
encouraged to keep a daily record of their achievements.
The pace of work was individualised to the parent and
family’s specific needs and progress and interim goals
were attained before moving to the next stage.
Families in both groups of the trial continued with
treatment as usual as provided by their local facilities. In
the experimental group, PASS was delivered separately
from, and in addition to, treatment as usual. Recognising
that carers seek advice and care from a variety of health,
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education, and traditional services,28 we used a Client assessed using the Patient Health Questionnaire, a nine-
Services Receipt Inventory29 to measure the type of item instrument widely used for this purpose and
service and total time in hours of use in both groups in previously validated in the Goa site in all local languages.30
the 6 months before the assessments of the endpoints. All outcome measures were translated and culturally
The questionnaire has been used in India and Pakistan.29 adapted with the standard method31 in a process that is
described in detail elsewhere.24
Outcomes
The primary outcome was the quality of parent–child Statistical analysis
interaction on the Dyadic Communication Measure The results of PACT showed a treatment effect on the
for Autism.14 A session was video recorded during primary parent–child interaction outcome (an effect
naturalistic play in a standard research (non-treatment) size of 1·37 for parental synchrony and 0·5 for child
setting, consisting of 8 min of coded interaction between communication initiation at 6 months).7 On the basis of
parent and child after a 4 min warm-up phase, using a these effect sizes, we calculated that a sample size of 60
standard set of age-appropriate toys adapted for the (30 participants in the intervention group and 30 in the
culture (eg, everyday stainless steel kitchen utensils that non-intervention group) was sufficient to give 90%
could be used as stacking toys).24 The researcher doing power to detect an effect size of 0·85 on dyadic
the coding was masked to group status, assessment interaction using a two-sample t test with a 0·05
point, and a-priori hypothesis, on three prespecified two-sided significance level, 80% power to detect an
variables coded independently of each other: the effect size of 0∙75, and 70% power to detect an effect
proportion of parental communications with the child size of 0∙65. We allowed for 10% attrition.
that were synchronous (utterances that acknowledged, Using a prespecified analysis plan, we assessed
confirmed, or reinforced the child’s focus, play, actions, primary and secondary endpoints at 8 months. The
thoughts, or intentions); the proportion of the child’s feasibility and acceptability of the implementation of
communications with the parent that were initiations PASS are shown with summary statistics. Treatment
(as opposed to responses to the parent); and the effects were analysed on an intention-to-treat basis. The
proportion of time spent in mutual shared attention (ie, primary outcome—change in parent–child social
episodes in which each person shared thoughts, communication—was analysed with linear regression
feelings, experiences, objects, or the attention focus of (ANCOVA), with covariation in the baseline
the other person). Maternal synchrony and child
initiations, measured as event counts, can occur during Treatment-as- PASS group
or outside periods of mutual shared attention, a duration usual group (n=33) (n=32)
measure, and thus are distinct in the coding scheme. Site
Coding with Dyadic Communication Measure for Goa, India 15 (45%) 15 (47%)
Autism was done by two assessors per site after training Rawalpindi, Pakistan 18 (55%) 17 (53%)
to full reliability with UK trainers (KL and CT) in a Sex
similar cascade model to the treatment. A random Male 27 (82%) 26 (81%)
sample of 14 (20%) of 70 session clips was double coded Female 6 (18%) 6 (19%)
at each site and checked by a UK trainer (KL). Inter-rater Age (months) 66·67 (23·60) 63·72 (21·86)
reliability showed intraclass correlations of 0·9 (India) <6 years 19 (58%) 21 (66%)
and 0·92 (Pakistan) for parental synchrony, 0·58 and ≥6 years 14 (42%) 11 (34%)
0·84 for child initiations (the result for India was VABS adaptive behaviour
affected by a single case outlier, removal of which standard score
increased the intraclass correlation to 0∙90), and 0·98 <65 19 (58%) 19 (59%)
and 0·98 for mutual shared attention. ≥65 14 (42%) 13 (41%)
Secondary outcomes were parent-report of child Father’s education
adaptation and language, recorded on the VABS (a Non-graduate 16 (48%) 22 (69%)
standard interview measure of child adaptive functioning Graduate 16 (48%) 9 (28%)
that has been used by different cultures); parent-report of Missing 1 (3%) 1 (3%)
child language use, recorded using the MacArthur VABS adaptive behaviour
Communicative Development Inventory (raw scores standard score
from the form for infants); and verbal and non-verbal Goa, India 57·27 (9·76) 59·60 (10·01)
aspects of the child’s social communication, assessed Rawalpindi, Pakistan 68·39 (9·17) 65·12 (13·54)
using the Communication and Symbolic Behavior Scales
Data are number (%) or mean (SD). PASS=parent-mediated intervention for autism
Developmental Profile (questionnaire to record social spectrum disorder in south Asia. VABS=Vineland Adaptive Behaviour Scales.
composite raw scores for carers). All these assessment
measures are widely used in general autism research. Table 1: Baseline demographics and clinical measures in patients with
autism spectrum disorder
Other endpoints were maternal depressive symptoms,

www.thelancet.com/psychiatry Published online December 15, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00388-0 5

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measurement of the outcome, treatment assignment,
and the minimisation variables of the treating centre,
age (<6 years vs ≥6 years), and functional impairment
(VABS ABC score: <65 vs ≥65) as fixed effects. Standard
regression methods were applied for the analysis of the
primary outcome.
The linear regression models allowed analysis of all
available data for primary and secondary outcomes
without imputation, under the assumption that data
were missing at random, conditional on the covariates.
All models were bootstrapped with 250 replications. We
report estimated treatment effects, with their
bootstrapped SEs, and 95% CIs. The statistician was
masked to treatment allocations during the analysis.
The study is registered with ISRCTN, number
ISRCTN79675498.
Role of the funding source
The funder had no role in the design and conduct of the
study, collection, management, analysis, and
interpretation of data, or the preparation, review, or
approval of the manuscript. The corresponding author
had full access to all of the data in the study and had final
responsibility for the decision to submit for publication.
Results
Participants were recruited between Jan 1, and July 20,
2013, in Rawalpindi, and between March 15, and July 30,
2013, in Goa. Assessment at 8 months was completed
between Sept 1, 2013, and March 14, 2014, in Rawalpindi
and between Nov 11, 2013, and March 24, 2014, in Goa.
Of 65 participants, 32 were randomly allocated to the
PASS group and 33 to the treatment-as-usual group
(figure). Six (9%) of 65 participants were lost to follow-
up (figure); this attrition was less than the 10% allowed
for in the study design. The treatment groups were well
matched at baseline for demographic and clinical
variables (table 1).
26 (81%) of 32 participants in the intervention group
completed the 12 sessions of treatment. The
non-specialist therapists achieved high therapist fidelity:
the median number of fidelity items passed per session
was 15 (IQR 14–16) out of 16, and 32 (89%) of 36 sessions
met key fidelity criteria. No adverse events were reported
in the PASS or treatment-as-usual groups.
Analysis of treatment as usual showed some inevitable
between-country differences in background provision,
but importantly for the internal validity of the trial,
within each country, the type and provision of usual
treatment was balanced in the trial groups. In
Rawalpindi, services accessed outside of PASS were
similar in the two trial groups; six (35%) of 17 children in
the PASS group attended a specialist school (median
17∙5 h [range 5–25] per week) and six (35%) attended a
mainstream school (17∙5 h [5–25] per week); in the
treatment-as-usual group, seven (39%) of 18 children
attended specialist schools (20 h [15–25] per week) and
five (28%) attended mainstream schools (25 h [20–30]
per week). In Goa, services for treatment as usual were
also well balanced across the two trial groups. Most
children in both groups in Goa attended specialist or
resourced educational provision (12 [80%] of 15 in the
PASS group and 14 [93%] of 15 in the treatment-as-usual
group), with the remainder attending mainstream
schools. In Goa, some families attended speech and
language therapy outside the school setting and this was
similar in both trial groups: seven (47%) of 15 children in
the PASS group (0∙5 h [range 0–5·0] per week) and
seven (47%) of 15 in the treatment-as-usual group (0∙5 h
[0–1·0] per week). Occupational therapy or physiotherapy
was accessed by one (7%) of 15 children in the PASS
group and three (20%) of 15 children in the treatment-
as-usual group in Goa. At both sites, specialist and
mainstream schools offered largely respite care with
some remedial education, with no notable specific
intervention. Other than occasional one-off consultations

Treatment-as-usual group PASS group Mean difference

Number Mean (SD) Number Mean (SD) Adjusted mean difference Bootstrapped Effect size (95% CI) Number
(95% CI) SE
Proportion of total parent communication acts 0·25 (0·14 to 0·36) 0·057 1·61 (0·90 to 2·32) 59
that were synchronous
Baseline 33 0·236 (0·163) 32 0·201 (0·149)
8 months 30 0·219 (0·170) 29 0·458 (0·264)
Proportion of total child communication acts 0·15 (0·04 to 0·26) 0·054 0·99 (0·29 to 1·68) 59
that were initiations
Baseline 33 0·165 (0·161) 32 0·194 (0·142)
8 months 30 0·176 (0·153) 29 0·337 (0·265)
Proportion of time in mutual shared attention –0·16 (–0·26 to –0·05) 0·054 –0·70 (–1·16 to –0·23) 59
Baseline 33 0·598 (0·243) 32 0·608 (0·205)
8 months 30 0·665 (0·213) 29 0·511 (0·269)

PASS=parent-mediated intervention for autism spectrum disorder in south Asia.

Table 2: Quality of parent–child interaction on the Dyadic Communication Measure for Autism at 8 months (primary outcome)

6 www.thelancet.com/psychiatry Published online December 15, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00388-0

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Treatment-as-usual PASS group Mean difference

group
Number Mean (SD) Number Mean (SD) Adjusted mean difference Bootstrapped Effect size (95% CI) Number
(95% CI) SE
VABS adaptive behaviour composite standard score –0·93 (–3·53 to 1·68) 1·331 –0·08 (–0·31 to 0·15) 59
Baseline 33 63·33 (10·86) 32 62·53 (12·15)
8 months 30 63·67 (10·54) 29 61·76 (12·51)
VABS communication domain standard score 1·33 (–2·37 to 5·03) 1·886 0·10 (–0·17 to 0·36) 59
Baseline 33 60·91 (13·26) 32 59·28 (14·41)
8 months 30 60·73 (13·84) 29 60·28 (13·84)
MCDI receptive subscale V score 0·19 (–0·56 to 0·94) 0·384 0·07 (–0·21 to 0·35) 59
Baseline 33 8·73 (2·49) 32 8·31 (2·83)
8 months 30 9·47 (2·53) 29 9·24 (2·65)
MCDI expressive subscale 0·03 (–0·46 to 0·52) 0·251 0·01 (–0·19 to 0·22) 59
Baseline 33 6·67 (2·30) 32 6·41 (2·51)
8 months 30 6·97 (2·11) 29 6·69 (2·51)
VABS socialisation domain standard score 0·94 (–1·60 to 3·49) 1·298 0·09 (–0·15 to 0·33) 59
Baseline 33 61·58 (10·80) 32 60·63 (10·64)
8 months 30 61·73 (8·07) 29 61·41 (9·02)
PHQ 9 0·95 (–1·38 to 3·27) 1·189 0·27 (–0·40 to 0·94) 59
Baseline 33 2·24 (2·73) 32 3·41 (4·11)
8 months 30 2·17 (4·68) 29 3·83 (5·35)
CSBS total weighted raw score –0·68 (–8·79 to 7·42) 4·135 –0·02 (–0·29 to 0·24) 59
Baseline 33 77·50 (31·18) 32 76·54 (30·35)
8 months 30 96·83 (30·72) 29 92·16 (29·67)
CSBS social composite raw score 0·94 (–2·43 to 4·32) 1·724 0·11 (–0·28 to 0·50) 59
Baseline 33 30·88 (8·15) 32 29·13 (9·10)
8 months 30 36·60 (7·68) 29 35·76 (8·18)

PASS=parent-mediated intervention for autism spectrum disorder in south Asia. VABS=Vineland Adaptive Behaviour Scales. MCDI=MacArthur Communicative Development Inventory. PHQ 9=Patient Health
Questionnaire 9. CSBS=Communication and Symbolic Behavior Scales.

Table 3: Secondary outcomes

from family doctors or traditional practitioners, no other
intensive interventions were used during this period at
either site.
For parental synchronous interaction (table 2), the
treatment effect was significant and in favour of the
PASS intervention, with an adjusted mean difference
between the two groups of 0·25 (95% CI 0·14 to 0·36;
effect size 1∙61 [95% CI 0·90 to 2·32]). A positive
treatment effect was also noted for the child’s
communication initiations with the parent; however, for
the outcome of shared attention, the treatment was
negative (table 2). The minimisation variables did not
have significant effects on outcomes (data not shown).
For the secondary outcomes, differences between the
control and intervention groups were not significant
(table 3).
Discussion
Two of three primary outcome components measured
in the parent–child interaction (parent synchrony and
child initiations) were substantially improved by PASS
with large effect sizes (table 2), replicating effects shown
in the UK PACT. These were the same two variables that
in PACT had showed both a positive treatment effect
and a key role in mediation of symptom outcome:
mediation analysis32 showed that the change in
synchrony mediated increased communication
initiations by the child and the change in initiations
mediated change in symptom severity. The effect sizes
for both these outcomes were larger with PASS than
with the PACT intervention (effect size for parental
synchrony 1∙61 in PASS and 1∙22 in PACT, and for
child communication 0∙99 in PASS and 0∙41 in PACT).
In conjunction with the achievement of high therapist
fidelity, these results lend support to the practicality of
using a parent-mediated intervention developed in a UK
context in LMICs. The intervention was based on a
developmental science of autism that has itself largely
been generated within high-income countries; our
finding of similar treatment effects on dyadic interaction
in this trial suggests some universality in the relevance
of these same development processes in autism within
the very different cultural context of south Asia.
The treatment effect of the intervention in the PASS
trial with respect to the third interaction variable (mutual
shared attention) was opposite to that in PACT. The

www.thelancet.com/psychiatry Published online December 15, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00388-0 7

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reason for this difference was that the changes in the
treatment-as-usual groups in each trial were in opposite
directions (in PACT, mutual shared attention strongly
decreased during the trial, whereas in our study of PASS
it slightly increased); whereas mutual shared attention in
the intervention groups in both trials remained the same
or slightly decreased. Further study is needed to find out
whether the results relate to differences in samples,
parenting style, or treatment as usual between the UK
and south Asia. Cultural issues might play a part; change
in mutual shared attention in the treatment-as-usual
group in south Asia was the only interaction finding that
differed in direction between the two cultures. However,
mutual shared attention generally showed inverse
direction of change to synchrony and communication in
both groups of both trials, and no mediation effect on
outcome in PACT;32 it is therefore a less salient outcome
and the meaning of the effects are less clear than for the
other primary outcome components. Similarly, we did
not detect intervention effects on parent-reported
secondary outcome measures in our trial of PASS, which
does not replicate the findings from the UK trial, in
which a substantial treatment effect on these measures
was shown in favour of PACT. Perhaps PASS was
underpowered to detect the effects of the intervention on
the parent-reported measures, but the findings would
also benefit from further investigation of the sensitivity
of the measures we used (derived from practice in high-
income countries) in the cultural context of south Asia.
The PASS randomised controlled trial is the first in
which substantive assessment of an intervention for
autism spectrum disorder was undertaken in LMICs. We
used an intervention model already evidence tested and
implemented in high-income countries, adapted this
model to the local context for task-shifting using standard
methods,33 and used a task-shifting approach to delivery,
supported by cascaded training and supervision. The
trial had good internal validity, with attrition to follow-up,
for instance, less than allowed for in the design. The
study adds substantially to reports from previous
small studies of parent education or parent-mediated
communication-based strategies.20–22
The task-shifting approach to implementation in
LMICs has been widely advocated as a strategy across
global health and, more specifically, for global mental
health.34 We have shown that a parent-mediated
intervention for early autism delivered by non-specialists
is both feasible and effective in LMICs. The results are
consistent with what our group and others have noted
with other task-shifting interventions in patients with
other mental illness9,34 and could provide a basis for future
scale-up of PASS and similar interventions for
neurodevelopmental disorders in children. Non-specialist
health workers in two countries were able to train to
manual fidelity in a technical psychosocial intervention
for autism, and most importantly sustain this fidelity
throughout the intervention trial. Family adherence to the
8 www.thelancet.com/psychiatry Published online December 15, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00388-0
intervention was also high. The key aspects of this success
are the establishment of a clear supervisory cascade from
specialist trainers in the high-income countries down to
the non-specialists, with support until the local teams
achieved competency, and the local senior specialists
supporting the building and maintenance of competencies
of non-specialists through objective measures.
A limitation for inferring success at scale-up might be
the absence of recruits in this study from remote rural
areas, and that the intervention work was directed and
supervised from academic centres with a highly motivated
team. We do not therefore suggest that it will be without
challenge to achieve such levels of adherence and
outcome in general implementation at scale. Further
research to assess implementation of such interventions
at scale is warranted. As with the UK PACT intervention,
PASS was focused on core problems of a child’s social
communication and did not aim to address specifically
the common mental health comorbidities that often
accompany autism spectrum disorder, such as attention
deficit hyperactivity disorder, sleep problems, or
behavioural difficulties. It will be important to integrate
structured attention for such comorbidities into any
wider intervention programme for scale-up into LMIC
health systems, which usually will not have the resources
needed to deal with them. In another ongoing study, our
group is trialling such an extended package in India,
incorporating into the PASS manual, additional evidence-
based strategies for managing common comorbidities in
the context of autism.
Contributors
AR and JG initiated the study. AR, JG, GD, VP, KL, CA, and CT designed
the study. From the UK, JG led the research coordination, KL led the
research training, and CA and CT led the intervention training. In south
Asia, GD, SUH, and VV led the adaptation of the intervention and
training of non-specialist interveners. Interveners were supervised
directly during the trial by AM, GD, and VV with supervisory support
from CA and CT. In south Asia VV, SUH, PC, AR, and VP supervised
the local research teams, with supervisory support from KL and JG. RE
did the data analysis. GD led the research team in India under VP’s
supervision, SUH led the research team in Pakistan under AR’s
supervision, with JG providing overall direction and advice to both sites.
All authors were involved in interpretation of the data. JG and AR led the
writing of the manuscript with review from all authors. JG and RE had
full access to all the data in the study and take responsibility for the
integrity of the data and the accuracy of the data analysis. VP and JG are
joint senior authors and share equal responsibility for the study with AR.
Declaration of interests
We declare no competing interests.
Acknowledgments
The study was funded by an award from Autism Speaks US. VP is
supported by a Wellcome Trust Senior Research Fellowship in Clinical
Science. We thank colleagues Tony Charman (King’s College, London,
UK) and Mayada Elsabbagh (McGill University, Montréal, QC, Canada)
who provided valuable consultation input at the design stage of the study.
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