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Review                                                                                                                                                       Open Access

## A Systematic Review of Social Communication and Interaction Interventions for Patients with Autism Spectrum Disorder

Tatja Hirvikoski 1,2 , Ulf Jonsson 1 , Linda Halldner 1,3,4 , Aiko Lundequist 1 , Elles de Schipper 1 , Viviann Nordin 1,5 , Sven Bölte 1,4

1 Center of Neurodevelopmental Disorders (KIND), Pediatric Neuropsychiatry Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; 2 Habilitation & Health, Stockholm County Council, Stockholm, Sweden; 3 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 4 Center for Psychiatry Research, Child and Adolescent Psychiatry, Stockholm County Council, Stockholm, Sweden; 5 Sachs' Children and Youth Hospital, Stockholm, Sweden

*Corresponding author: Sven.bolte@ki.se

## Abstract

Background : Autism spectrum disorder (ASD) is currently not curable, but it may be malleable to varying degrees in response to different interventions to improve outcomes.

Objective: We conducted a systematic review of interventions aimed at ameliorating social communication impairments in patients  with  ASD.  This  study  was  registered  in  the  International  Prospective  Register  of  Systematic  Reviews  (no. CRD42013003780).

Methods : We focused on the ASD interventions that are frequently applied in Swedish clincial practice to address ASD. To ensure stakeholder involvement, we also conducted two surveys with three  major Swedish ASD interest organizations to assess perceived research priorities for ASD treatment. With the use of this rationale for selection, Early Intensive Behavioral Intervention [EIBI], Treatment and Education of Autistic and Related Communication Handicapped Children [TEACCH], social  skills  training  groups,  and  interventions  that  involved  significant  others  were  reviewed.  A  bibliographic  search  was conducted  via  five  databases:  Medline,  PubMed,  PsycInfo,  CINAHL,  and  ERIC.  Identified  articles  were  screened  for relevance by two independent reviewers, who also assessed the risk of bias in randomized controlled trials using systematic checklists.

Results : A total of 7264 citations were identified as being published before February 2013, and 109 studies (18 of EIBI, 18 of social skills training, 4 of TEACCH, and 69 of interventions involving significant others) were included in the analysis. The included studies provided some support for the positive effects of each of the interventions; this is especially true if the most recently  published  research  (March  2013  through  August  2015)  is  considered,  and  a  crude  updated  search  for  relevant randomized controlled trials was performed. The interventions that involve the significant others of individuals with ASD form a heterogenous area of treatment strategies that require subcategorization for future review.

Conclusions : These findings provide preliminary support for treatments that are commonly used in clinical practice for the treatment of ASD in Sweden. However, larger and more rigorously designed and controlled studies are still needed before definitive conclusions regarding their effects can be made.

Key words : Autism spectrum disorder; pervasive developmental disorder; treatment; intervention; therapy; review.

## Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V)  as  involving  either  current  or historical deficits in social communication and interaction across multiple contexts; it also includes restricted and repetitive patterns, interests, or activities as manifested by at least two prototypically inflexible  behaviors.  An  internationally  increasingly accepted prevalence estimate for ASD  among school-aged children is approximately 1%  (1), although  some  more  recent  studies  have  reported figures  that  are  substantially  higher  (2),  and  the percentage  of  diagnosed  cases  among  adolescents between the ages of 13 and 17 years in Stockholm County, Sweden, reached 2.6% in 2011 (3). Males are affected three to four times more often than females, and  comorbidity  with  other  neurodevelopmental disorders and other psychiatric or neurological disorders  is  the  rule  rather  than  the  exception  (4). ASD is a brain-based disorder of complex origin that is  currently  not  considered curable, although many have claimed that certain developmental, educational, psychological, pharmacological, and complementary  and  alternative  interventions  have resulted in improvements or even cured this condition (5,6).

Recent  systematic  reviews  of  some  behavioral interventions for individuals with ASD have demonstrated  low  to  moderate  evidence  for  the improvement of ASD symptoms as well as cognitive or  adaptive  functioning;  these  have  included  early behavioral  intervention  and  social  skills  and  social cognition  training  (7-11).  Systematic  reviews  are deemed the gold standard for evaluating evidence in clinical science. The method summarizes the existing scientific knowledge in terms of randomized controlled trials (RCTs), which may serve as a basis for the making of political decisions that affect future clinical services development and prioritization. Systematic reviews describe the availability of highquality  studies  for  certain  interventions,  but  they should not be confused with immediate or absolute recommendations  by  clinicians for the use (or ceasing  of  use)  of  certain  techniques  in  clinical practice.  They  are  not  intended  and  are  equally unable to assess the actual quality of regional clinical services, so their findings should therefore be interpreted  with  prudence  (12).  In  addition,  many systematic reviews of interventions for patients with ASD have focused on efficacy rather than effectiveness  and  directed  relatively  little  attention toward implementability (13).

The aim of this study was to conduct a systematic review  of  ASD  interventions  that  are  aimed  at ameliorating social communication impairments. As compared with earlier systematic reviews, this work not only incorporates the current state of science but also addresses health care practices as well as societal and social network issues, which accounts for several aspects  of  the  generalizability  and  applicability  of intervention  methods.  In  addition  to  providing  an update on intervention techniques covered by prior studies-particularly Early Intensive Behavioral Intervention  (EIBI),  Treatment  and  Education  of Autistic  and  Related  Communication  Handicapped Children (TEACCH), and social skills training-this article also covers interventions that involve significant  others,  which  are  assessed  here  for  the first time. The choice of intervention techniques to be reviewed was based on those commonly applied during the clinical treatment of individuals with ASD in  Swedish  child  and  adolescent  psychiatry  and habilitation services. We also addressed those interventions  deemed  important  by  stakeholders, such as those that involve the relatives of the affected individual. We will first briefly and generally describe the different interventions reviewed as well as their objectives, concepts, and target groups. This will be followed by a discussion of the selection process and then the actual systematic literature review for each of the four study areas selected.

## Reviewed social communication and interaction interventions for autism spectrum disorder

Early Intensive Behavioral Intervention . EIBI is currently one of the most widely used and accepted treatments for infants and young children with ASD. It involves several  typical  components:  a  1:1  trainer-to-child ratio, intense intervention of 20 to 40 hours per week for up to 4 years, and discrete trial training in home or  preschool  settings.  Discrete  trial  training  is  a teaching method in which learning units are simplified  and  structured:  a  skill  is  not  taught  as  a whole but rather broken down and then conveyed one step at a time. Normally, the method is carried out or supervised by personnel who are certified in applied behavior analysis (14). This type of analysis seeks  to  develop  appropriate  behavior  repertoires and to decrease or reduce inappropriate behaviors by employing the following methods: 1) positive reinforcement, such as praise, a token, or a favorite activity;  2)  shaping,  which  involves  reinforcing  the individual  for  exhibiting  behavior  that  approaches the target behavior or goal; 3) fading, which reduces the individual's dependence on the trainer for help; 4)  prompting,  which  includes  providing  cues  as  to the performance of an appropriate behavior; and 5) maintenance  strategies,  which  help  to  ensure  the generalization of the learned behavior and  the avoidance of inappropriate behaviors (e.g., analyzing and  manipulating  the  antecedents  that  trigger  the behavior, ignoring the behavior, providing undesired or unpleasant consequences). Possible variables that affect EIBI outcomes may be the treatment provider (e.g., parent, clinician, teacher), the treatment intensity and duration, the quality of the supervision and the intervention settings,  and  the  allegiance  to the method (15).

Treatment and Education of Autistic and Related Communication  Handicapped  Children. TEACCH is an educational program that was developed during the 1960s at the University of North Carolina (16). It is broadly used by organizations that provide services for  individuals  with  ASD  and  their  families  to improve the affected subject's functioning at home (or in a group home) and in the classroom. TEACCH acknowledges  that  ASD  is  a  disorder  of  neural development that affects both cognitive and emotional development, and it tries to identify ways to facilitate everyday activities with the use of visual information  processing,  visual  clarity  and  frugality, and the reduction of distractibility. The latter aims to compensate  for  attention  deficits;  difficulty  with organizing  ideas,  materials,  and  activities;  poor  use and understanding of verbal and non-verbal language in social interactions; and difficulty with generalization  processes.  TEACCH  suggests  that individuals with ASD benefit from a highly structured  teaching  approach  that  provides  routine and  predictability  (17).  This  so-called  'structured teaching'  builds  on  several  principles,  such  as  the individualized  assessment  of  communication,  selfcare,  vocational,  and  leisure  time  skills.  Specific instruments  such  as  the  Psychoeducational  Profile (18) are used to identify the patient's strengths and interests  to  facilitate  learning  processes,  and  family involvement  is  assessed  to  facilitate  the  generalization  of  skills.  Major  components  of  structured teaching  include  the  organization  of  the  physical environment  by  visual  cues  (space  is  adapted  for specific  activities  [e.g.,  colored  areas  for  play]),  the sequential organization of activities (visual schedules show  activities  for  the  day),  the  introduction  of routines  (increasing  predictable  events),  and  the organization of tasks and materials (activity materials are  located  in  the  places  where  activities  are  being carried out).

Social skills training. This intervention approach attempts to teach children with ASD the skills they need to engage in social interaction and communication  to  create  opportunities  for  social contact, to behave in socially expected ways, to build social  relationships,  and  to  increase  the  likelihood that  they  will  experience  social  interaction  as  both meaningful and enjoyable (19). Social skills training is usually conducted in a group setting, and it typically involves  rather  high-functioning  individuals  with ASD  in  a  structured  lesson  format.  For  young children, the training may focus on simple acts such as offering a greeting, joining a peer in playing with a toy, or sharing a preferred object. For older individuals,  the  training  commonly  involves  the acquisition of social rules, social cognition exercises, perspective and turn taking, and the avoidance of and coping with conflicts. Social skills training is generally designed  for  individuals  who  are  6  years  old  and older.  Groups  range  in  size  to  include  up  to  eight participants, with one to three trainers.  Many manualized training programs involve weekly sessions of 60 to 90 minutes that occur over a period of 12 weeks or more. Targeted skills are modeled in different ways (e.g., role playing, group discussion), and group members are welcome to suggest topics of individual relevance.

Interventions involving significant others . These  interventions included a range of partly different interventions that are offered to parents and other relatives. They all aim to support the relatives or to improve the relatives' capacities to better understand and nurture their family members with ASD. These interventions include everything from  providing information about the diagnosis and treatment options  to  more  complex  education  about  certain intervention techniques. This is surely an area that is under development. Carrying out a classical systematic  review  is  compromised  as  a  result  of heterogeneity  of  both  the  interventions  and  the target groups (20,21).

## Methods

## Protocol and registration

This study was conducted on behalf of the National Board of Health and Welfare, Sweden and registered in the International Prospective Register of SystematicReviews (crd.york.ac.uk/NIHR\_PRO-SPERO/; no. CRD42013003780).

The selection of target interventions was based on three criteria: 1) the availability of scientific evidence; 2)  current  applicability  to  Swedish  clinical  practice and recommendation by regional clinical guidelines; and 3) the values, preferences, needs, and attitudes put forth by interest organizations and stakeholders in Sweden. We first selected three treatment methods for  systematic  review  on  the  basis  of  the  first  two criteria:  EIBI,  TEACCH,  and  social  skills  group training. In August 2012, before the current review and database searches were conducted, we assessed the  viewpoints  of stakeholders  regarding  the  focus and  objectives  of  the  project  and  the  selection  of interventions to review. Three major Swedish interest organizations participated in this survey: The Autism  and  Asperger  Association  (Autism-  and Aspergerförbundet; www.autism.se); The  Attention National Association (Riksförbundet Attention; www.attention-riks.se);  and  the  Organized  Aspies (Organiserade  Aspergare;  www.aspergare.org).  The survey results indicated a strong preference for the inclusion  of  interventions  that  involved  significant others.

## Eligibility criteria

For  studies  of  EIBI,  TEACCH,  and  social  skills  group training

Participants. Children and adolescents (≤18 years old)  diagnosed  with  autism,  Asperger  syndrome, atypical autism, or pervasive developmental disorders not otherwise specified according to DSMIV, DSM-IV-TR, or International Statistical Classification of  Diseases  and  Related  Health  Problems,  10th  Revision, criteria; studies of adult populations (>18 years old) were excluded

Interventions. TEACCH,  EIBI,  and  social  skills group training

Comparators. Any comparators

Outcome measures. Primary  outcomes: Social  communication/interaction skills at the time point when the study or treatment is terminated and long-term follow up

Secondary outcomes: Adaptive behaviors; core symptoms of ASD; symptoms of comorbid conditions;  cognitive  development;  quality  of  life; caregiver burden; parental stress, parental knowledge of ASD

Study design. RCTs and observational studies with comparison groups; case studies were excluded

For studies of interventions involving significant others

Participants. Family members (i.e., parents, grandparents,  siblings, or caregivers  in  a  home setting) of individuals with any kind  of  ASD diagnosis, as described previously

Interventions. Any  interventions  involving  significant others

Comparator. As described previously

Outcome measures. As described previously

Study design. RCTs and observational studies with or  without  comparison  groups;  case  studies  were

excluded

## Information sources

Electronic  searches  were  conducted  using  Medical Subject  Headings  (MeSH)  and  relevant  text  word terms. Five databases (Medline, PubMed, PsycINFO, CINAHL, and ERIC) were searched up to February 15, 2013. The search was performed by an information specialist at the University Library of Karolinska Institutet. For studies published between February 2013 and August 2015, we only added an unsystematic crude update search that was conducted via PubMed. These results are added at the end of the Results section and discussed in the Conclusion section.

## Search strategy

We  used search terms relevant for the study interventions  and  population.  Search  results  were limited to original studies from 1990 or later and to those  written  in  English,  Danish,  Norwegian,  or Swedish.  Animal  studies  and case studies  were excluded. For a detailed description of search terms, see Appendix 1.

## Study selection

For  studies  of  EIBI,  TEACCH,  and  social  skills  group training

Two reviewers independently screened the titles and abstracts identified by the search strategy. Studies of potential relevance were grouped according to intervention and then screened a second time by two reviewers. If it was deemed necessary at this stage, the  full  text  of  the  article  was  obtained,  and  two reviewers  then  independently  assessed  the  text  to determine inclusion. Any disagreements were resolved by discussions between the reviewers. Reference lists and systematic reviews were screened for additional studies of relevance.

## For studies of interventions involving significant others

As  a  result  of  the  heterogeneity  of  the  identified studies  in  this  area  and  to  enable  a  descriptive synthesis, the search results for studies of interventions involving significant others were divided  by  two  researchers  (TH  and  AL)  into  two major subcategories: interventions involving parents and interventions involving significant others other than  parents.  The  interventions  were  then  further subclassified into several content-valid subcategories on  the  basis  of  the  target  group/receiver  of  the intervention (type of relative) and the primary focus of the treatment: either the relative receives treatment (e.g., parents learn how to cope with stress) or  the  relative  conducts  treatment  (e.g.,  parents support their children in the development of social skills).

## Data collection process

From each included RCT with a moderate or low risk of bias (as discussed later in this article), data were extracted and inserted into a table by one reviewer. A second  reviewer  then  audited  the  data  extraction. Any disagreements were resolved by discussion.

## Data items

Information about the following topics was extracted from the  included  RCTs:  1)  participants  (e.g.,  age, diagnosis);  2)  treatment;  3)  type  of  comparator;  4) relevant outcome measures; and 5) adverse events or deterioration.

## Risk of bias in individual studies

Two  reviewers  independently  assessed  the  risk  of bias of the selected RCTs with the use of checklists developed by the Swedish Council on Health Technology  Assessment.  The  risk  of  bias  is  the systematic tendency that any aspect of the study may make the estimated treatment effect deviate from its true value (i.e., the extent to which the results of an included  trial  can  be  believed).  The  checklist  for RCTs is very similar to the Cochrane Collaboration's tool for assessing the risk of bias (22), and it includes 31 items to consider related to randomization (methods and outcomes; 3 items); treatment (blinding,  compliance,  therapists,  and  confounding variables;  5  items);  assessment  (blinding,  reliability, validity, timing, and analysis; 9 items); dropout (size, balance, covariates, and analysis; 5 items); reporting bias (protocol, primary/secondary outcome, adverse events,  and  assessment;  6  items);  and  conflicts  of interest (3 items). A rating of low, moderate, or high risk of bias was given to each category of items and then combined into a global rating for the trial. The risk  of  bias  was  not  assessed  for  observational  or quasi-experimental studies or for those studies involving significant others.

## Methods  of  analysis  for  social  communication interventions

Initially,  a  quantitative  synthesis  of  RCTs  (using RevMan 5 software) related to each of the research questions was planned. If quantitative synthesis was not  meaningful  or  possible,  a  descriptive  synthesis was  performed.  For  observational  or  quasi-experimental  studies,  only  a  descriptive  synthesis  was planned. If systematic reviews of high quality were available from previous studies of the areas examined, they were used as resources for consistency checks and cross-validation.

## Results

## Early Intensive Behavioral Intervention

A total of 161 studies of potential relevance for EIBI were  identified  by  the  literature  search;  18  studies remained after screening by two reviewers (AL and LH).  There were 17 observational studies that included  control  groups  and  1  RCT,  which  was conducted  in  the  United  States  (23).  The  RCT included 28 children, of which 15 were in the EIBI group; the boys-to-girls ratio was 12:3 in the intervention  group  and  11:2  in  the  control  group. The children in the EIBI group received a mean of 30  hours  of  treatment  per  week  for  two  to  three years;  the  control  group  had  supervised  parental training  twice  a  week  for  a  total  of  five  hours  per week, training with parents for five hours per week, and education in a special class for ten to 15 hours per  week  for  three  to  nine  months.  The  outcome measures  are  presented  in  Table  1.  There  were  no significant differences between groups before treatment  with  regard  to  outcome  variables.  After treatment, there were statistically significant differences in intelligence as measured by the Stanford-Binet  Intelligence  Scales,  in  visuospatial abilities as measured by the Merrill-Palmer Scales of Development, and in verbal ability according to the Reynell Developmental Language Scales between the EIBI group and the control group. However, there was a certain risk for bias, because the groups were not comparable with regard to the interval between completed treatment and follow-up measurement.

Of  the  17  non-randomized  studies  with  control groups that were identified, 4 were from the United Kingdom (24-27), 4 were from the United States (2831),  two  were  from  Italy  (32,33),  two  were  from Israel  (34,35),  one  was  from  Canada  (36),  one  was from Sweden (37), one was from Norway (38), one was  from  Norway  and  Sweden  (39),  and  one  was from Norway and the United States (40). Two of the non-randomized studies with control groups (25,27) examined the same sample, with the later study being a  2-year  follow-up  study  of  the  intervention.  One more study  with  a  control  group  from  the  United Kingdom was identified, but the intervention consisted of  more than EIBI, and the control and intervention groups differed only by the intensity of the same treatment interventions (41), so it was not further considered.

All  non-randomized  studies  reported  improvements in different areas at the group level for both children who underwent EIBI treatment and control children.  Of  these,  13  studies  showed  superior improvement for the EIBI groups in some outcome measures as compared with the control groups (2330,32,36-38,40).  Outcome  measures  varied  among studies, with most studies applying several outcome measures. Results showed relative improvements in intelligence quotient (10 studies), adaptive behavior (10 studies), language and communication (7 studies), symptom  reduction  (6  studies),  and  the  need  for school  assistance  (1  study).  Results  also  demonstrated  changes  in  diagnostic  status  (1  study)  and personality and other behaviors (2 studies). Many of these studies had relatively small sample sizes.

One  study  with  relatively large study groups showed no difference in outcomes between the EIBI group (n = 45) and the control group (n = 33) after intervention  (35).  The  control  group  in  this  trial received  'individualized  eclectic  treatment'  of  the same magnitude as and parallel to the EIBI group. In the  other  study  that  did  not  demonstrate  better outcomes  after  high-intensity  EIBI  treatment,  the control group received low-intensity EIBI treatment (37). However, in this design, the study groups were not comparable, the study lacked both the control of what  was  actually  administered  and  the  quantity (number of hours) of the treatment, and the health care professionals were not comprehensively trained in EIBI techniques.

During the two years of follow up by Kovshoff and colleagues  (29),  the  group  differences  that  were initially observed ultimately disappeared (27). Alternatively,  McEachin  and  colleagues  (30),  who studied the long-term outcomes of a previous study (42),  found  persistent  effects  in  the  intervention group as compared with a non-randomized comparison group.

## Treatment and Education of Autistic and Related Communication Handicapped Children

Thirty-six studies of potential relevance to TEACCH were found in our literature search. After screening (by AL and ES), four studies remained, whereas 32 studies  were  excluded:  11  studies  with  irrelevant research questions, nine observational studies without comparison  groups, five reviews, three studies with adult participants, one case study, and one study of an intervention other than TEACCH.

TABLE 1. Randomized controlled trials of EIBI (until 2/2013)

| Publication     | Risk of bias   | Participants        | Participants            | Intervention   | Intervention                | Outcome measures               | Main results Mean post-treatment (Standard deviation)   | Main results Mean post-treatment (Standard deviation)   |
|-----------------|----------------|---------------------|-------------------------|----------------|-----------------------------|--------------------------------|---------------------------------------------------------|---------------------------------------------------------|
| Name Year       |                | Study group         | Comparison group        | Study group    | Comparison group            |                                | Study group                                             | Comparison group                                        |
| Country         |                |                     |                         |                |                             |                                |                                                         |                                                         |
| Smith, 2000 USA | High- modera   | n=15 Clinical       | n=13 Clinical ASD       | EIBI 30 h/week | two parental                | Stanford-Binet: IQ             | 66.5 (24.1)                                             | 49.7 (19.7)*                                            |
|                 | te             | ASD diagnosis (n=8) | diagnosis (n=7) PDD-NOS | during 2-3     | training sessions 5 h/week& | Marill -Palmer: Visuo- spatial | 64.3 (18.7)                                             | 49.2 (21.4)*                                            |
|                 |                | PDD-NOS (n=7)       | (n=6)                   | years          | Special education           | Reynell: Language              | 87.4 (46.2)                                             | 61.3 (31.9)*                                            |
|                 |                | Age                 | Age 35.77 (5.37) months |                | 10-15 h/ week               | Vineland: communication        | 67.87 (30.08)                                           | 60.77 (17.26)                                           |
|                 |                | 36.07 (6.05)        |                         |                | during 3-9                  | DLS                            | 62.3 (25.8)                                             | 63.0 (17.0)                                             |
|                 |                | months              | Follow up Age           |                | months                      | Socialization                  | 66.3 (24.8)                                             | 68.9 (16.9)                                             |
|                 |                | Follow up Age 94.07 | 92.23(17.24) months     |                |                             | CBCL                           |                                                         |                                                         |
|                 |                | (1.17)              |                         |                |                             | Internalizing - Parent         | 59.3 (10.3)                                             | 60.2 (7.8)                                              |
|                 |                | months              |                         |                |                             | - Teacher                      | 61.9 (7.0)                                              | 55.0 (4.4)                                              |
|                 |                |                     |                         |                |                             | Somatic complaints - Parent    | 56.1 (8.2)                                              | 56.1 (8.2)                                              |
|                 |                |                     |                         |                |                             | - Teacher                      | 52.3 (5.0)                                              | 54.9 (8.5)                                              |
|                 |                |                     |                         |                |                             | Anxious/Depressed - Parent     | 52.2 (5.2)                                              | 59.7 (11.6)                                             |
|                 |                |                     |                         |                |                             | - Teacher                      | 54.2 (5.3)                                              | 54.6 (4.1)                                              |
|                 |                |                     |                         |                |                             | Social problem - Parent        | 60.1 (13.5)                                             | 64.3 (11.4)                                             |
|                 |                |                     |                         |                |                             | - Teacher                      | 59.8 (9.6)                                              | 57.4 (8.0)                                              |
|                 |                |                     |                         |                |                             | Thought problem - Parent       | 67.1 (10.8)                                             | 64.5 (12.7)                                             |
|                 |                |                     |                         |                |                             | - Teacher                      | 64.7 (13.6)                                             | 62.6 (7.6)                                              |
|                 |                |                     |                         |                |                             | Attention problem - Parent     | 64.8 (10.3)                                             | 67.5 (4.2)                                              |
|                 |                |                     |                         |                |                             | - Teacher                      | 64.9 (12.8)                                             | 61.6 (9.3)                                              |
|                 |                |                     |                         |                |                             | - Parent Teacher               | 54.7 (9.2) 53.4 (12.8)                                  | 54.0 (5.1) 61.6 (9.3)                                   |
|                 |                |                     |                         |                |                             | - Aggressive behav.            |                                                         |                                                         |
|                 |                |                     |                         |                |                             | - Parent Teacher               | 56.1 (9.1)                                              | 59.7 (10.4)                                             |
|                 |                |                     |                         |                |                             | -                              | 60.0 (10.8)                                             | 55.7 (5.6)                                              |

Note. DLS = Developmental Language Scales; CBCL = Child Behavior Checklist

There  were  two  RCTs  (43,44)  (Table  2)  and  two quasi-experimental  studies  with  matched  controls (45,46): two of these studies were conducted in the United  States  (44,45),  one  was  performed  in  Italy (46), and one took place in China (43). Each of the four included studies was deemed to be of low quality and to have a high risk for bias.

In the first  RCT,  Tsang  and  colleagues  (43) evaluated  the  usefulness  of  TEACCH  for  Chinese preschool children between the ages of three and five years with autism. The experimental group (n = 18) received  full-time  center-based  TEACCH  training, whereas the control group (n = 16) received types of training  other  than  TEACCH.  The  experimental group  demonstrated  motor  skills  as  rated  by  the Psychoeducational Profile, Revised (PEP-R). Alternatively, the control group showed more progress than the experimental group in social Note . CPEP-R = Psycho Educational Profile-Revised Chinese version; HKBABS = Hong Kong Based Adaptive Behavior Scale (Chinese adaptation of Vineland Adaptive Behavior Scales); MPSMT = Merrill-Palmer Scale of Mental Tests; MSEL = Mullen Scales of Early Learning; SIB-R = Scales of Independent BehaviorRevised; PSI = Parent Stress Index-3 rd  edition social  adaptive  functioning  as  indicated  by  higher scores  on  the  Daily  Living  and  Adaptive  Behavior Composite scales of the Hong Kong Based Adaptive Behavior  Scale  (i.e.,  adjusted  Vineland  Adaptive Behavior Scales). Cognitive functioning as measured by the Merrill-Palmer Scales of Development did not improve in either of the two groups.

TABLE 2. Randomized controlled trials of TEACCH (until 2/2013)

| Publication                                                   | Risk of bias   | Participants                                                     | Participants            | Intervention                                                                                                                                                                              | Intervention                                                        | Outcome measures                                                                                                                                                                                      | Main results Mean post-treatment (Standard deviation)                                                                                                                                                                                                                                                    | Main results Mean post-treatment (Standard deviation)                                                                                                                                                                                                                                                  |
|---------------------------------------------------------------|----------------|------------------------------------------------------------------|-------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Name Year Country                                             |                | Study group                                                      | Comparison group        | Study group                                                                                                                                                                               | Comparison group                                                    |                                                                                                                                                                                                       | Study group                                                                                                                                                                                                                                                                                              | Comparison group                                                                                                                                                                                                                                                                                       |
| Tsang, Shek, Lam, Tang& Cheung 2007 China                     | High           | Clinical ASD- diagnosis according to DSM- IV; Age: 3-5 yrs; n=18 | As in study group; n=16 | Full time center- based TEACCH training: structured physical set-up and tasks organization with use of schedule, visual support and Independent Work System (IWS); 12 months, 7 h per day | Treatment as usual; non- TEACCH classroom set- up and teaching mode | Tests : Psycho Educational Profile-Revised Chinese version; Merril-Palmer Scale of Mental Tests; Hong Kong Based Adaptive Behavioral Scales (Chinese adaptation of Vineland Adaptive Behavior Scales) | Adjusted means corrected for pretest and covariates CPEP-R: Perception 10.067 (SD .693) Fine Motor 11.091 (SD .729) Gross Motor 15.425 (SD .915) Other subscales ns HKBABS: Daily Living Skills 54.951 (SD 2.309) Sum of Domains 253.425 (SD 7.881) Other subscales ns Merril-Palmer : 48.106 (SD 2.233) | Adjusted means corrected for pretest and covariates CPEP-R: Perception 7.300 (SD .740) Fine Motor 8.522 (SD .778) Gross Motor 11.522 (SD .978) Other subscales ns HKBABS: Daily Living Skills 69.680 (SD 2.473) Sum of Domains 284.771 (SD 8.513) Other subscales ns Merril-Palmer : 51.505 (SD 2.387) |
| Welterlin, Turner-Brown, Harris, Mesibov & Delmolino 2012 USA | High           | Clinical autism- diagnosis; Age: 2-3 yrs; n=10                   | As in study group; n=10 | Home TEACCHing Program: training parents to work with child on cognitive, fine motor and language skills; 12 weekly sessions of 1.5h                                                      | Wait-list                                                           | Tests : Mullen Scales of Early Learning; Scales of Independent Behavior- Revised; Parent self- report: Parent Stress Index-3rd edition                                                                | MSEL : 63.7 (SD 17.4) SIB-R - social interaction : 18.4 (SD 7.3) SIB-R - language comprehension : 12.0 (SD 4.7) SIB-R - language expression : 16.2 (SD 7.1) PSI : 242.4 (SD 41.5)                                                                                                                        | MSEL : 58.1 (SD 25.0) SIB-R - social interaction : 16.0 (SD 5.0) SIB-R - language comprehension : 10.9 (SD 4.8) SIB-R - language expression : 14.2 (SD 7.1) PSI : 256.2 (SD 70.0)                                                                                                                      |

In  the  other  RCT,  Welterlin  and  colleagues  (44) evaluated  the  effect  of  a  TEACCH-based  home training  program  on  children  with  ASD  and  their parents. Parents were trained to support their children  in  the  areas  of  cognitive,  fine  motor,  and language skills. Twenty  families were randomly assigned  to  the  treatment  group  or  the  waiting  list group. The results suggested that participation in the home training program led to improvements in the children's independence and in the parents' ability to structure the children's learning environment and to effectively prompt their children in teaching situations.  However,  group  comparisons  did  not reveal significant differences in child developmental outcomes (Mullen Scales of Early Learning), adaptive behavior (Scales of Independent Behavior, Revised), or parent stress (Parenting Stress Index,  Third Edition).

In the non-randomized study with a control group (45), parents were trained to implement TEACCH at home in the treatment group; members of both the treatment and the control groups were enrolled in a regular day treatment program. Twenty-two children between the ages of two and six years were assigned non-randomly to the treatment or the control groups (n = 11 in each group). The results demonstrated that children in the treatment group improved significantly more than those in the control group on the PEP-R subscales of imitation, fine motor, gross motor, and non-verbal conceptual skills as well as on their  overall  PEP-R  scores.  Correlations  between pretreatment scores and total change scores indicated that subjects with mild ASD and good language skills benefited the most.

Panerai and colleagues (46) compared two educational  treatments  in  schools:  the  TEACCH program and the integration program for individuals with  disabilities  that  is  commonly  used  in  Italian schools.  Two  groups  of  children  with  ASD-an experimental group (n = 8) and a control group (n = 8)-were matched by gender (all males) and diagnosis  (ASD  and  severe  intellectual  disability combined). The mean chronological age was 9 years. The  authors  found  improvements  on  the  PEP-R scales (test items were scored as 'passing,' 'emerging,'  and  'failing,'  depending  on  specific scoring  criteria)  for  all  'passing'  categories  except that  of fine  motor skills, but  this  was  not  the  case with the 'emerging' categories. The analysis of the results from the Vineland Adaptive Behavior Scales did not yield improvements in communication and interpersonal  relationships.  The  authors  concluded that the TEACCH program was more effective than the treatment applied to the control group.

## Social skills training

During  the  first  screening  of  abstracts  (by  UJ  and VN), 204 unique citations of potential relevance for social skills training were identified. A total of 186 of these  reports  were  excluded:  57  case  studies;  30 observational studies without comparison groups; 76 studies with irrelevant research questions; eight studies  of  other  interventions;  three  studies  with adult participants; six study protocols; and 6 reviews. The  remaining  reports-11  RCTs  and  seven  nonrandomized studies with comparison groups-were included. A recent systematic review of high quality that included five of the 11 RCTs was identified (11).

The systematic review by Reichow and colleagues searched  the  literature  up  to  December  2011  and included five RCTs  of  social skills training as compared with a waitlisted control group. All five of these trials were conducted in the United States. The sample sizes of all included trials were relatively small and ranged from 18 to 76 participants (Table 3). In total,  196 participants were included in the studies. The participants were children between the ages of 7 and  12  years,  with  the  exception  of  one  trial  that included adolescents between the ages of 13 and 17 years  (47).  To  some  extent,  the  outcome  measures differed between the trials: 4 trials measured social competency (47-50), and 2 trials measured friendship quality (48,51). The social skills groups improved in overall  social  competence  (effect  size  =  0.47;  95% confidence  interval,  0.16  to  0.78)  and  friendship quality (effect size = 0.41; 95% confidence interval, 0.02 to 0.81), but there was no effect on emotional recognition  and  understanding  of  idioms.  Overall, the quality of evidence was rated as low. Given the nature of the intervention and the selected outcome measures, the authors concluded that the risk of bias was high.

Our search identified two additional trials of comparable interventions (52,53), which were published  after  the  final  search  in  the  review  by Reichow  and  colleagues  (11).  In  a  trial  from  the United  States  (52),  a  total  of  35  children  were randomized to social skills group training or to being waitlisted. The  intervention consisted of group sessions  5  days  a  week  for  5  weeks.  A  number  of outcome measures were used to assess improvements in social competency and social communication, and the effects were comparable to the effects observed in previous trials. DeRosier and colleagues  (53)  compared  a  social  skills  training intervention specifically designed to address multiple social skill areas for children between the ages of 8 and  12  years  with  high-functioning  ASD  with  a similar intervention developed for typically developing children; 55 children were included in the study, and the results indicated that the specifically designed  intervention  had  better  effects  on  social skills.  We  have  determined that  these  trials  do  not change  the  conclusions  drawn  in  the  review  by Reichow and colleagues.

An additional  four  RCTs  of  social  skills  training were identified, but the interventions differed substantially from the ones included in the Cochrane review. Beaumont and Sofronoff (54) tested a 7-week program  that included computer games, group sessions,  parent  training,  and  information  being given  to  teachers.  A  total  of  49  children  were randomized to either the intervention group or being waitlisted. Parent and teacher ratings indicated that children  who  received  the  intervention  had  more improved  social  skills  and  that  the  effects  were maintained  at  a  5-month  follow-up  appointment. The remaining 3 trials were assessed as having a high risk of bias factors, such as a small sample size and baseline  differences  between  the  intervention  and control  groups.  One  of  these  trials  evaluated  a training  program  for  theory  of  mind  (55),  one compared two forms of skills training programs (56), and one studied the effect of a multimodal intervention for social skills and anxiety (57).

A range of different outcome measures was used in the trials. One questionnaire, the Social Responsiveness Scale (58), was used in five studies. another questionnaire, the Social Skills Rating system for Parents (59), was used in three studies. in only one of the 11 RCTs were both of these questionnaires used. In addition, three of the studies that used the Social Responsiveness Scales had Note. ADI-R = The Autism Diagnostic Interview-Revised; ASC = Adapted Skill-streaming Checklist; ADOS = The Autism Diagnostic Observation Schedule; ALQ = Achieved Learning Questionnaire; ASD = Autism Spectrum Disorders; BASC-2PRS = Behavior Assessment For Children; BDI = Beck Depression Inventory; CASI-Anx = Child and Adolescent Symptom Inventory-4 ASD Anxiety; CASL = Comprehensive Assessment of Spoken Language; CDI = The Children's Depression Inventory; CGI-I = Clinical Global Impressions - Improvement scale; CSBQ = The Children´s Social Behavior Questionnaire; DANVA-2 = Diagnostic Analysis of Nonverbal Accuracy-2; DD-CGAS = Developmental Disabilities Children's Global Assessment Scale; ERSSQ = Emotion Regulation and Social Skills Questionnaire; FQS = Friendship Qualities Scale IQ = Intelligence quotient; LEAS-C = The levels of Emotional Awareness Scale for Children; n = Number of patients; N/A = Not applicable; PARS = Pediatric Anxiety Rating Scale; PEI: The Pupil Evaluation Inventory; PHS = Piers-Harris Self-Concept Scale; QPQ = The Quality of Play; SCI = Social Competence Inventory; SD = Standard deviation; SIOS = Social Interaction Observation System; SKA = Skill-streaming Knowledge Assessment; SRS = Social Responsiveness Scale; SSQ-P = Social Skills Questionnaire - Parent; SSQ-T = Social Skills Questionnaire - Teacher; SSRS-P = Social Skills Rating System - Parent; SSRS-T = Social Skills Rating System - Teacher; TASSK = Test of Adolescent Social Skills Knowledge; TOPS = Test of Problem Solving comparable participant groups but different training programs.

TABLE 3. Randomized controlled trials of social skills training (until 2/2013)

| Publication                            | Risk of bias   | Participants                                                                                                                              | Participants                                                            | Intervention                                                                                                                                                                                             | Intervention                                                                                                              | Outcome measures                                                                                                                                  | Main results Mean pre- and post-treatment                                 | Main results Mean pre- and post-treatment                                 |
|----------------------------------------|----------------|-------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------|---------------------------------------------------------------------------|
| Name Year                              |                | Study group                                                                                                                               | Comparison group                                                        | Study group                                                                                                                                                                                              | Comparison group                                                                                                          |                                                                                                                                                   | (Standard Study group                                                     | deviation) Comparison group                                               |
| Country Beaumont et al. 2008 Australia | Moderate       | Clinical ASD- diagnosis confirmed by parent questionnaires IQ>85 Age: 7½-11 years; n=26 Attrition: N/A                                    | As in study group; n=23 Attrition: N/A                                  | A multi-component social skills intervention; computer game + small group sessions + parent training sessions + teacher handouts; introduction + 7 weekly sessions; follow-up 6 weeks and 5 months post- | Wait-list                                                                                                                 | Tests : Emotion recognition measure; James and the Maths test; Dylan is being teased Parent questionnaires : SSQ-P, ERSSQ Teacher questionnaire : | SSQ-P : Pre 25.30 (7.43) Post 38.8 (SD 9.84)                              | SSQ-P: Pre 23.16 (SD 9.05) Post 25.11 (SD 7.91)                           |
| Begeer et al. 2011 The Netherlands     | High           | Clinical ASD- diagnosis confirmed by parent questionnarires IQ>70; Age: 8-13 years; n=20; Attrition: 1                                    | As in study group; n=20; Attrition: 3                                   | treatment 'The Theory of Mind training'; 16 weekly group sessions + parent program                                                                                                                       | Wait-list                                                                                                                 | SSQ-T Tests : Theory of Mind test; LEAS-C Self-reported empathy : The index of empathy for children and adolescents Parent questionnaire :        | Theory of mind test total score: Pre 50.89 (SD 5.31) Post 58.21 (SD 4.00) | Theory of mind test total score: Pre 54.00 (SD 5.93) Post 58.00 (SD 5.78) |
| DeRosier et al. 2011 USA               | Moderate       | Prior ASD- diagnosis confirmed by parent questionnaires IQ>85; Age: 8-12 years; n=27; Attrition: 3                                        | As in study group; n=28; Attrition: 2                                   | 'The Social Skills Group Intervention - High Functioning Autism' (development of original program); 15 weekly group sessions + parent program                                                            | 'The Social Skills Group Intervention' (original program for children with typical development); 10 weekly group sessions | CSBQ Self-report : Social Dissatisfaction Questionnaire Parent questionnaires : SRS, ALQ Parent and child report : Social Self- efficacy Scale    | SRS - communication (individual change scores): -0.38 (SD 1.07)           | SRS - communication (individual change scores): 0.50 (SD 0.78)            |
| Frankel et al. 2010 USA                | Moderate       | ASD (according to ADI-R + ADOS)+ verbal IQ>60 + basic level of communication and play Age: mean 103.2 months (SD 15.2) n=40; Attrition: 5 | As in study group; Age: mean 101.5 months (SD 15.0); n=36; Attrition: 3 | 'Parent-assisted Children's Friendship Training'; 12 weekly sessions for children and parents separately + homework assignment                                                                           | Wait-list                                                                                                                 | Self-reports : The Loneliness Scale; PHS Parent questionnaires : QPQ; SSRS-P Teacher questionnaire : PEI                                          | SSRS-P ( Self- control): Pre 10.2 (SD=3.4) Post 12.2 (SD 2.9)             | SSRS-P ( Self- control): Pre 9.0 (SD 3.9) Post 10.1 (SD 3.7)              |
| Koenig et al. 2010 USA                 | Moderate       | Prior ASD- diagnosis confirmed by ADOS parent questionnaires IQ>70; Age: 8-11 years; n=25;                                                | As in study group; n=19; Attrition: 1                                   | Training based on social learning and behavior theory; 16 weekly group sessions; peer tutors included                                                                                                    | Wait-list                                                                                                                 | Blinded rating: CGI-I Parent questionnaire : SCI                                                                                                  | Post-treatment much or very much improved on the CGI-I: 16/23             | Post-treatment much or very much improved on the CGI-I: 0/18              |
| Laugeson et al. 2009 USA               | Moderate       | Attrition: 2 Prior ASD- diagnosis IQ>70; Age: 13-17 years; n=17; Attrition: 3                                                             | As in study group; n=16; Attrition: 0                                   | 'Program for the Education and Enrichment of Relational Skills' (the UCLA PEERS program adapted for teens); 12 weekly group sessions for teens and parents separately + homework                         | Wait-list                                                                                                                 | Self-report : TASSK; QPQ; FQS Parent questionnaires : QPQ; SSRS-P Teacher questionnaire: SSRS-T                                                   | SSRS-P: Pre 80.2 (SD 8.8) Post 89.7 (SD 12.1)                             | SSRS-P: Pre 77.9 (SD 12.1) Post 79.8 (SD 11.7)                            |

| Publication             | Risk of bias   | Participants                                                                                                                            | Participants                                                                | Intervention                                                                                                                                  | Intervention                                                                               | Outcome measures                                                                                                                                                       | Main results Mean pre- and post-treatment (Standard deviation)                                                                   | Main results Mean pre- and post-treatment (Standard deviation)                                                                   |
|-------------------------|----------------|-----------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------|
| Lerner& Mikami 2012 USA | High           | Study group 1: Prior diagnosis of high-functioning ASD confirmed by parent questionnaires Age: mean 10.86 (SD 1.68); n=7 Attrition: N/A | Study group 2: As for group 1 Age: mean 11.33 (SD 1.63); n=6 Attrition: N/A | Study group 1: 'Sociodramatic Affective Relational Intervention (SDARI)' (use of games targeting specific social goals); 4 weekly sessions    | Study group 2: 'Skill-streaming' (training steps of social interaction); 4 weekly sessions | Blinded observation : SIOS; Socio- metrics Parent questionnaires : SRS, SSRS-P Teacher questionnaire: SSRS-T                                                           | SRS (parent): Pre 76.57 (SD 10.74) Post 75.57 (SD 13.05)                                                                         | SRS (parent): Pre 82.17 (SD 10.68) Post 76.17 (SD 9.56)                                                                          |
| Lopata et al. 2010 USA  | Moderate       | Prior diagnosis of high-functioning ASD + IQ>70; Age: 7-12 years; n=18 Attrition: N/A                                                   | As in study group; n=18 Attrition: N/A                                      | Intervention according to 'Skill- streaming': summer camp, 5 weeks, 5 days per week + weekly parent training                                  | Wait-list                                                                                  | Tests : SKA; DANVA-2 Child Faces; CASL, Idiomatic Language subtest Parent questionnaires : SRS; ASC; BASC-2- PRS - social skills and withdrawal Staff questionnaires : | SRS (parent): Pre 79.94 (SD 11.02) Post 73.67 (SD 11.42)                                                                         | SRS (parent): Pre 81.12 (SD 13.78) Post 82.53 (SD 13.77)                                                                         |
| Solomon et al. 2004 USA | High           | Prior ASD- diagnosis confirmed by ADI- R and ADOS IQ>75; Age: 8-12 years; n=9 Attrition: N/A                                            | As in study group; n=9 Attrition: N/A                                       | 'The Social Adjustment Enhancement Curriculum'; 20 weekly group sessions + psychoeducational parent groups                                    | Wait-list                                                                                  | ASC, SRS; BASC-2 Tests : DANVA-2-AF; DANVA-2-CF; Strange Stories Task; Faux Pas Stories Task; TOPS-Elementary Revised Self-report : CDI Parent questionnaire : BDI     | DANVA-total faces (expression recognition) Age 8-10: Pre 23.8 (SD 1.3) Post 26.6 (SD 1.5) Age 10-12: Pre 22.5 (SD 2.9) Post 24.8 | DANVA-total faces (expression recognition) Age 8-10: Pre 24.8 (SD 3.1) Post 24.0 (SD 2.3) Age 10-12: Pre 25.2 (SD 3.3) Post 23.6 |
| Thomeer et al. 2012 USA | Moderate       | Prior ASD- diagnosis confirmed by ADI- R IQ>70; Age: 7-12 years; n=17 Attrition: N/A                                                    | As in study group; n=18; Attrition: N/A                                     | Intervention according to 'Skill- streaming': summer camp, 5 weeks, 5 days per week + weekly parent training                                  | Wait-list                                                                                  | Tests : SKA; DANVA-2 CF; CASL, Idiomatic Language subtest Parent questionnaires : ASC; SRS; BASC-2- PRS Teacher questionnaire : BASC-2-TRS                             | (SD 3.4) SRS (parent): Pre 83.24 (SD 17.27) Post 75.24 (SD 13.54)                                                                | (SD 3.3) SRS (parent): Pre 83.06 (SD 12.61) Post 84.29 (SD 13.84)                                                                |
| White et al. 2013 USA   | High           | ASD-diagnosis supported by ADOS and ADI-R + verbal IQ>70 Met criteria for anxiety disorder Age: 12-17 years; n=15; Attrition: 2         | As in study group; n=15; Attrition: 3                                       | 'Multimodal Anxiety and Social Skill Intervention (MASSI)'; 14 weeks with group social skills training + individual therapy + parent coaching | Wait-list                                                                                  | ASC, SRS; BASC-2 Blinded rating: PARS; CGI-I; DD- CGAS Parent questionnaires : SRS; CASI-Anx                                                                           | SRS (parent): Pre 88.87 (SD 12.32) Post 74.33 (SD 12.63)                                                                         | SRS (parent): Pre 85.73 (SD 14.14) Post 84.80 (SD 12.18)                                                                         |

The  studies  included  few  blinded  or  objective measurements. The Diagnostic Analysis of Nonverbal Accuracy (60), which measures an individual's  ability  to  recognize  facial  expressions, was used in two studies (50,51). In 2 other studies, the  improvement  subscale  of  the  Clinical  Global Impressions Scale (61) was used by blinded investigators (49,57). Four of the trials were determined to have a high risk of bias, mainly as a result of uncertainties related to missing information (51,55-57).  For  the  remaining  seven  trials,  the  risk was assessed as moderate.

We  identified  a  total  of  seven  non-randomized studies with control groups that evaluated different forms of social skills group training interventions. Of these, 5 were conducted in the United States (62-66), one took place in the United Kingdom (67), and one occurred  in  Australia  (68).  Some  of  the  studies included children (62,63,67,68), whereas others focused on adolescents (64-66).

A study by Kroeger and colleagues compared two kinds  of  social  skills  groups  for  4-  to  6-year-old children with ASD (62). A 3-year retrospective study by  Legoff  and  colleagues  (63)  compared  the  longterm outcomes of children with ASD who participated  in  Lego-based  interactive  playgroups and a matched comparison group who had received comparable non-Lego therapy. A study by Owen and colleagues  (67)  evaluated  Lego  therapy  as  well  as another social skills intervention, the Social Use of Language  Program,  for  6-  to  11-year-old  children with  high-functioning  autism  and  Asperger  syndrome.  Participants  were  matched  and  randomly assigned to one of the interventions and compared with a control group that was not randomly assigned. A pilot study by Castorina and Negri (68) compared social  skills  training  (alone  or  with  a  sibling)  with waitlisting  for  boys  with  Asperger  syndrome  who were between the ages of 8 and 12 years.

A small study by Ozonoff and Miller (64) evaluated the effectiveness of a social skills training program for adolescent boys with high-functioning autism as compared with a no-treatment control group. Another  study  compared  a  parent-assisted  social skills group intervention for high-functioning adolescents  with  ASD  with  a  delayed-treatment control group (65). Finally, another study examined the  effectiveness  of  an  intervention  that  adapted dramatic  training  activities  to  improve  social  skills among  adolescents  with  Asperger  syndrome  and high-functioning ASD diagnoses (66).

The number of included participants was exceptionally small in most studies, with between 5 and 14 participants in the intervention groups. The only  exception  was  the  retrospective  study  of  the Lego-based interactive playgroups (63), which included  60  participants  in  the  intervention  group. Although all 7 studies reported beneficial effects of the interventions, we assessed that the results should be interpreted with caution due to the small sample sizes and the non-randomized design.

## Interventions involving significant others

A  total  of  441  studies  of  potential  relevance  were identified.  After  screening  (by  AL  and  TH),  71 studies remained. We identified the following subclasses of interventions that involved relatives: 1) parent-mediated  treatment  of  children  with  ASD (excluding  EIBI  and  TEACCH;  these  studies  are presented above); 2) support and education for the parents  of  children  with  ASD  (i.e.,  help  for  the parents  themselves);  3)  support  for  parents  while their children are receiving professional treatment; 4) education for parents with the aim of improving their skills related to teaching others about ASD and their children;  5)  sibling-mediated  intervention  for  the individual  with  ASD;  6)  support  for  siblings  of individuals  with  ASD  (i.e.,  support  for  the  siblings themselves);  and  7)  interventions  involving  grandparents.

## Parent-mediated treatment of children with ASD (excluding EIBI)

In this category, the focus was on intervention that aimed at the parent-mediated treatment of the child with ASD rather than at support for the parents. The parent-mediated, communication-focused treatment of  children  with  autism  has  been  studied  in  a multicenter RCT in the United Kingdom called the Preschool  Autism  Communication  Trial  (PACT) (89).  Children  were  assigned  to  PACT (n = 77) or treatment as usual (n = 75). The PACT intervention did not reduce autism symptoms; however, there was a clear benefit for parent-child dyadic social communication.  Sofronoff  and  colleagues  (70,71) evaluated an intervention program aimed at improving parental self-efficacy for the management of problem  behaviors  associated with  Asperger syndrome among children of primary school age. In this research, 51 parents were randomly assigned to different  formats  (i.e.,  a  1-day  workshop  or  six individual sessions) of the parental self-efficacy program  or to a waiting list. Parents in both intervention groups reported fewer problem behaviors  in  children  and  increased  parental  selfefficacy  after  the  interventions  at  both  four  weeks and  three  months  of  follow  up.  In  addition,  22 families participated in an accelerated parental educational program for 12 weeks, and half of them also  participated  in  an  additional  weekly  parent education support group. Results indicated that the addition  of  a  parent  support  group  may  increase parental mastery of teaching techniques as well as the success of accelerated programming (72). In a study by Keen and colleagues (73), families were assigned to a professionally supported intervention that included a workshop and 10 home visits (n = 17) or to a self-directed video-based intervention (n = 22). The professionally supported intervention resulted in greater  development  in  social  communication  and adaptive behavior in children as well as more reduced parenting stress and increased parenting self-efficacy as compared with the self-directed intervention.

Other  studies  within  this  category  were  open studies, most of which were small pilot studies (7492); others were randomized small pilot studies (93) or the further analysis of previously published studies (94,95).

## Support  and  education  for  parents  (i.e.,  help  for  parents themselves)

Interventions  with  primary  outcome  measures  that reflected parental stress, mental health, or parenting style  (i.e.,  with  the  primary  focus  on  parents)  were classified as belonging to this category. In one of the RCTs (96), parents were allocated to either a 20-week manual-based parent education and behavior management intervention (n = 35) or a manual-based parent  education  and  counseling  intervention  (n  = 35).  Both programs  provided improvements  in parental  mental  health  and  adjustment.  In  another RCT (97), 59 families were randomized either to the Stepping Stones Triple P program or to a waiting list. The  results  indicated  significant  improvements  in parenting  styles,  parental  satisfaction,  and  conflicts related to parenting. Additional effects were observed in parental reports of child behavior.

Other  identified  studies  were  small  randomized studies (n ≤ 31 in total) or non-randomized controlled studies that indicated positive effects on family interaction (98), decreased hopelessness and improved  coping  (99),  and  perceived  self-efficacy regarding the care of autistic children (100). Internetbased  parent  support  group  participation  had  no effect  on  parental  well-being,  although  participant satisfaction was high (101).

No effects were observed in response to increased counseling  with  a  pediatric  nurse  practitioner  in conjunction with the diagnostic assessment (102) or to  parent  support  group  participation  on  mental health or quality of life (103); this was possibly related to the small sample sizes.

## Support  and  education  for  parents  while  their  children  are receiving professional treatment

In an  RCT  (104), 35 preschool children were randomized  to  an  intervention  group  or  a  control group. In the intervention group, the child's parents and child care workers received a 12-week intervention  that  consisted  of  lectures  and  on-site consultations  with  day  care  centers.  In  addition, supportive work was undertaken with the children's families.  Control  subjects  received  day  care  alone. The  intervention  was  significantly  superior  to  day care  alone  with  regard  to  its  effects  on  caregivers' knowledge of autism, the perception of control on the part of mothers, and greater parental satisfaction. In  another  RCT,  children  with  ASD  and  serious behavioral problems (n = 124) were randomized to pharmacological treatment alone (risperidone) (105) or pharmacological treatment in combination with a parent  training  program.  The  combined  treatment showed modest additional benefit over pharmacological  treatment  alone.  In  another  RCT, parents  of  preschoolers  with  ASD  and  minimal speech received parent responsiveness training, whereas the children were allocated to a discrete trial or a naturalistic language treatment (106). However, because the parents of all children received the same intervention,  it  was  not  possible  to  distinguish  the specific effects of parent responsiveness training.

A trial of transition planning intervention included training sessions for families in the transition process as  well  as  other  components  that  were  aimed  at facilitating  the  transition  process  of  an  adolescent with ASD from high school to adult life (107). As compared  with  waitlisted  controls,  the  transition intervention  group  showed  improved  student  and family expectations as well as higher levels of  selfdetermination and career decision-making ability.

Other studies within this area were open or nonrandomized studies with promising preliminary effects  on  subjective  stress  and  well-being  after participation in parallel parent support and education programs when the children with ASD were being treated by professionals (90,108-111).

## Parents are educated with the aim of educating and informing others in the networks of their children with ASD

A few open trials have reported positive outcomes in response to educating parents, who in turn educate other people in their children's networks (112,113).

## Sibling-mediated intervention for individuals with ASD

Both children with ASD and their typically developing  siblings  were  reported  to  benefit  from interventions that involved siblings to improve the social skills of the children with ASD (68,114). Both of the studies found were open pilot studies.

## Support for siblings of individuals with ASD (i.e., support for the siblings themselves)

Two  pilot studies with an open study design (115,116)  described  preliminary  positive  effects  of sibling support groups.

## Interventions involving grandparents

A small pilot study with an open study design (117) reported  preliminary  positive  effects  of  involving grandparents in the treatment of their grandchildren with ASD through a joint activity.

## Crude search update on randomized controlled studies of all  interventions  from February 2013 through August 2015

Our crude search update on all examined interventions that were aimed at ameliorating social communication impairments in children and adolescents with ASD yielded a notheworthy recent increase in RCTs. We identified 2 additonal studies of EIBI (118,119), one of TEACCH (120), four of social skills training (121-124), and five of interventions involving significant others related to the parent-mediated treatment of children with ASD (excluding  EIBI)  (125-129).  All  studies  reported findings that were in favor of the respective intervention  method  evaluated,  with  small  to  large effect  sizes;  however,  study  samples  were  mostly small to medium large (i.e., N = 11 to N = 86).

## Discussion

## Early Intensive Behavioral Intervention

Results  of  the  identified  studies  of  EIBI  mostly showed improvements for both the EIBI group and the control group, although the effect for the EIBI group  as  compared  with  the  control  group  ranged from  no  difference  to  better  effect.  However,  we only  found  a  single  RCT  that  compared  the  EIBI method  with  another  (or  no)  intervention.  Nonrandomized  studies  indicate  a  risk  for  systematic differences between the compared groups (e.g., the motivation for treatment). The interventions for the control groups of the described studies varied considerably, and most of the studies offered some kind  of  active  treatment  to  the  control  group.  In several studies, it was not clear exactly which form of EIBI treatment was administered, and the treatment fidelity was not assessed. Most  of the studies included higher proportions of boys than girls. The male-to-female  ratio  also  varied  with  respect  to known gender differences in ASD prevalence, and it was not always reported. Thus, the impact of EIBI on girls with ASD is probably even more uncertain than the effects on boys. All of this can obviously contribute to heterogeneous results from the different  studies.  Furthermore,  the  study  groups were generally small, which may in fact have masked smaller  differences  in  outcome  between  the  EIBI groups and the control groups, considering the vast interindividual differences and the fact that children in general develop and make progress independently of intervention.

A  Cochrane  report  that  evaluated  the  effects  of EIBI  for  children  with  ASD  included  four  nonrandomized  controlled  studies  (all  included  in  this report) as well as an RCT study (10). It concluded that the quality of the evidence is low (as rated by the Grading  of  Recommendations  Assessment,  Development and Evaluation system) when it comes to judging the effects of the EIBI method.

Clearly, more sound scientific evidence is needed to be able to draw definitive conclusions about the effects  of  EIBI  as  a  treatment  method  for  ASD. Criticism  against  the  EIBI  method  has  been  put forward  from  clinical  researchers,  which  may  also complicate  the  clinical  application  of  the  method. For  example, the effect of EIBI  on  the  core symptoms of ASD has been questioned. The impact of  the  baseline  functioning  of  the  children  on  the intervention effects, the consequences for the children  and  their  families  (e.g.,  distress),  and  the possibility of implementing the method considering its intensity and extensiveness have also been discussed  (23,27).  In  addition,  questions  have  been raised  about  the  costs  associated  with  the  EIBI method,  although  these  may  need  to  be  weighed against lowered future costs if the method is effective (130).

Our survey of three Swedish interest organizations showed inconsistent stakeholder  viewpoints.  While one organization advocates the EIBI method as the treatment method to offer all preschool children with autism or ASD, another association views the EIBI method  as  too  directive  and  less  desirable  as  a treatment  method.  These  differences  in  attitude illustrate  the  importance  of  accurate  information regarding the purpose and contents of the intervention  as  well  as of actively involving  all concerned  individuals  in  the  making  of  decisions about interventions.

## Treatment and Education of Autistic and Related Communication Handicapped Children

Few  studies  have  evaluated  the  effectiveness  of TEACCH. All four of the studies identified in this review (two RCTs  and  two quasi-experimental studies  with  matched  controls)  reported  positive effects on outcome measures for children with ASD, mainly with regard to cognitive, motor, and language skills  and,  to  a  lesser  extent,  to  social  adaptive functioning  and  communication  skills.  However, these studies were of low quality and had a high risk for bias as a result  of  their  unclear  and  nonrandomized procedures for recruitment and assignment  to  a  treatment  or  control  group.  This made it hard to determine whether the participants were  representative  of  the  population.  In  addition, neither  the  participants  nor  the  researchers  were blind  to  the  treatment  condition,  which  may  have created a placebo effect in the participants and a bias in  the  assessment  of  the  treatment  effect  by  the researchers. These and other factors made it difficult to draw any strong conclusions about the reliability of  the  findings  reported  in  these  studies.  More controlled trials are necessary to scientifically establish the effectiveness of TEACCH.

The promotion of a 'culture of autism,' which is a central concept in the TEACCH program and which refers to the specific characteristics that are common among individuals with ASD, has led to the criticism that the TEACCH  method  does  not  facilitate inclusion  but  rather  creates  a  separation  of  autistic and neurotypically developing individuals. According to the creators of the TEACCH method, however, the objective is to facilitate inclusion in addition to respecting  and  promoting  an  individual's  specific skills,  interests,  strengths,  and  needs.  This  is  why increasing the understanding of ASD is an important part of the TEACCH method, which aims to create an  environment  in  which  there  is  space  for  the individual with ASD to function.

Other criticisms that are often heard are that the TEACCH method is too structured, that it focuses too much on task completion, and that it does not leave room for spontaneous interaction and communication. This criticism seems to be supported  by  the  findings  of  the  present  study,  in which  effects  on  cognitive  skills  are  clearer  than those  on  social  and  communication  skills.  Such effects  might  make  the  method  less  suitable  for higher-functioning individuals with ASD.

## Social skills training

A core deficit in individuals with ASD is difficulty with social communication and functioning. Another core feature involves repetitive patterns of behaviors. This latter feature can contribute to social impairment by restricting the child with ASD's range of  interests  as  well  as  his  or  her  opportunities  to collect social experiences. Children with  ASD without  severe  mental  retardation  will  experience more serious social difficulties as could be expected from  cognitive  abilities.  In  this  group  of  children, loneliness  and  isolation  may  give  rise  to  comorbid psychiatric disorders (e.g., depression, anxiety disorders).  Continued  isolation  will  result  in  more obvious social exclusion as children with ASD grow older.  Group  activities  that  involve  both  children with ASD and typically developing children without other  simultaneous  interventions  have  not  been shown to increase social interaction for children with ASD (131).  Therefore,  training  in  social  skills  is  a logical  step  in  the  support  of  children  with  ASD, both at schools and via health care services.

In  summary,  the  RCTs  included  in  this  review provide  some  scientific  support  for  the  positive short-term effect of social skills training delivered in a group format. We judge that our analysis of further trials does not differ from the conclusions drawn by Reichow and colleagues (11): the quality of evidence is low. We also concur with the conclusion of those researchers that there is limited generalizability from the studies because they were mainly conducted in the United States, they mainly focused on children between the ages of 7 and 12 years, and they included participants of average or above-average intelligence.

The  broad  range  of  social  and  communication deficits  that  are  common  to  individuals  with  ASD requires  a  comprehensive  approach.  The  training programs include different amounts of such tactics as direct instruction, modeling, role playing, computer games, behavior feedback, and reinforcement. Parent training and parent and teacher  handouts  are  used.  It  is  not  possible  to conclude  if  any  program  is  better  than  any  other. Only one replication RCT has been published (52); there are no RCTs of the long-term effects of any program.

In the included RCTs, both study and comparison samples were adequately matched on key variables. The  interventions  were  well  described.  A  central factor that confers a high risk of bias ratings for these studies is the small sample sizes that were used. The use of delayed treatment (i.e., placement on a waiting list) was the usual method used for comparison. This might lead to the confounding of results by attention-related factors. Another risk factor for bias is the dependence  on  parent questionnaires as outcome measures. In many programs, the parents are engaged as coworkers as well (e.g., helping with exercises and activities of daily living). When asked, parents reported high satisfaction with the program (132). This is clearly a desirable element of a social skills training program, but it also increases the risk for  biased  assessment.  For  future  studies,  more objective  or  blinded  outcome  measures  should  be used.

## Interventions involving significant others

Family-based interventions have been shown to be effective  for  several  mental  disorders  (133).  The involvement of significant others in assessment and treatment has been found to be of importance for patients  with  ASD  as  well  (134-138),  and  this  was clearly endorsed by the involved interest organizations in the current project. Increased knowledge of ASD may improve significant others' ability  to participate in everyday family life with an autistic relative (137). In this study, interest organizations also stressed the importance of parallel interventions  for  individuals  with  ASD  and  their significant others as well as information about and the involvement of individuals with ASD (adjusted to their developmental phase) in interventions given to significant others. Moreover, a lack of support for parents  who  have  adult  offspring  with  ASD  was highlighted by the interest organizations. Parents of adult offspring with ASD may experience high levels of stress due to their own health problems in addition to the burden of the lifelong care and support of their affected children (139).

Interventions for the significant others of individuals with ASD is a broad and heterogeneous area that is currently under development, and there is an urgent need for further studies that apply stringent research methods (21), with well-defined intervention targets and formats (20). Furthermore, long-term  follow  up  and  generalizability  to  other contexts should be further explored (140). Evidencebased practice and clinical guidelines for these types of interventions were also called for by the interest organizations addressed in the current research. The interest  organizations  further  stressed  the  need  for different kinds of family interventions, depending on the  family  dynamics  and  the  affected  individual's characteristics.  Other  future  challenges  include  the development  of  interventions  that  are  targeted  at specific issues, such as sexuality in adolescents with ASD (141), transitioning to adulthood (107), and the use of new technological possibilities (e.g., internetdelivered interventions) (142).

## Conclusion

This systematic review examined the evidence related to social communication interventions for the treatment of ASD. The present results update and largely confirm previous findings of low to moderate scientific  support  for  several  commonly  applied techniques  in  Swedish  clinical  practice  of  ASD treatment (e.g., EIBI, TEACCH, social skills training),  despite  the  need  for  more  thorough  and large-scale research. Our crude update search found an increased number of RCTs to have taken place in the last two years, especially for social skills training and parent-mediated training methods, thereby indicating  developments  in  the  area  of  increasing study quality and broadening the evidence base for these techniques. Moreover, according to registered trials at ClinicalTrials.gov and Controlled-Trials.com, several large-sized RCTs are currently being conducted (e.g., NCT01854346, I SRCTN94863788).

In this study-for the first time and based on the recommendations of interest organizations and stakeholders-we  explored  the  interventions  that specifically involve the significant others of children and adolescents with ASD. These interventions are heterogeneous in terms of addressees and procedures, thereby making scientific support hard to  judge  and  the  need  for  more  rigorous  research especially apparent. Although  the  current study tackles some of the most frequently used interventions, it covers only a small proportion of the methods claimed by some to be effective or that are used in international clinical practice (143). For many of  these  interventions,  systematic  reviews  will  only serve the purpose of showing that they have never been evaluated in RCTs.

This review suffers from at least two limitations. First, it may already be somewhat obsolete, because only studies  that  occurred  before  the  beginning  of 2013  were  included  in  the  systematic  review.  For studies  that  occurred  from  February  2013  through August 2015, we only added a crude update search. Second,  we  did  not  assess  the  non-randomized studies for quality. There is a large risk of confounding bias in the non-randomized studies, and most of them must be viewed as being of low quality. Moreover, even systematic reviews  show  some limitations,  thus  hampering  their  use  as  a  starting point  for  the  selection  of  scientifically  supported methods  for  evidence-based  practice.  Inevitably, systematic reviews only summarize data from primary  research  studies.  Therefore,  the  results  of these reviews cannot be markedly more informative than the information taken from the original studies directly. Many of the primary studies, while reaching sufficient  internal  validity,  lack  the  characteristics necessary  for  effectiveness  or  generalizability.  For instance,  as  compared  with  clinical  reality,  studies almost never examine combined ('eclectic') interventions or those that are naturalistically integrated into the flow of clinical routine. In addition, studies and systematic reviews often focus on changes in core ASD symptoms as defined in the Diagnostic and Statistical Manual of Mental Disorders or the International  Statistical  Classification  of  Diseases  and Related Health Problems, even though functional adaptation, quality-of-life measures, changes in comorbidity severity, or the perceived stress of the affected  individual  and  his  or  her  relatives  may  be equally  important.  It  should  also  be  noted  that adverse effects are rarely monitored and reported in trials of psychological interventions, precluding riskbenefit analyses (144). Moreover, the quality of the delivery of the respective methods is rarely controlled,  although  frequently  in  published  trials interventions  are  not  administered  by  experienced personnel. To somewhat comply with limitations in external  validity,  in  this  study,  we  introduced  a bottom-up approach when selecting the methods to be included in the review. We addressed the attitudes of the interest organizations, and we also mapped the clinical practices and opportunities in Sweden; both of these were seen as important prerequisites for the implementation  of  intervention  techniques.  This strategy  identified  the  significance  of  interventions that involved significant others, which had not been systematically evaluated previously.

We deem our bottom-up approach to be a strength of this study as compared with previous systematic reviews: it enhanced communication with stakeholders and policy makers, who frequently feel that  scientific  reviews  are  difficult  to  comprehend and that they do not take into account anything other than scientific views. We hope to encourage future intervention research to increasingly include societal perspectives and issues of implementation to maximize  patient  gains  and  the  impact  of  ASD research on clinical practice.

## Acknowledgements

This study was conducted on behalf of the National Board of Health and Welfare, Sweden. Sven Bölte was  supported  by  the  Swedish  Research  Council (grant no. 523-2009-7054).

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71. Sofronoff K, Leslie A, Brown W. Parent management training and Asperger  syndrome:  a  randomized  controlled  trial  to  evaluate  a parent based intervention. Autism 2004;8:301-17.
72. Stahmer AC, Gist K. The effects of an accelerated parent education program  on  technique  mastery  and  child  outcome.  J  Pos  Behav Interv 2001;3:75-82.
73. Keen D, Couzens D, Muspratt S, Rodger S. The effects of a parentfocused intervention for children with a recent diagnosis of autism spectrum disorder on parenting stress and competence. Res Autism Spectr Disord 2010;4:229-41.
74. Anan RM, Warner LJ, Mcgillivary JE, Chong IM, Hines SJ. Group Intensive  Family  Training  (GIFT)  for  preschoolers  with  autism spectrum disorders. Beh Interv 2008;23:165-80.
75. Baker-Ericzen  MJ,  Stahmer  AC,  Burns  A.  Child  demographics associated with outcomes in a community-based pivotal response training program. J Pos Beh Interv 2007;9:52-60.
76. Coolican J, Smith IM, Bryson SE. Brief parent training in pivotal response treatment for preschoolers with autism. J Child Psychol Psychiatry 2010;51:1321-30.
77. Donaldson SO, Elder JH, Self EH, Christie MB. Fathers' perceptions of their roles during in-home training for children with autism. J Child Adoles Psychiatr Nurs 2011;24:200-7.
78. Dunn W, Cox J, Foster L, Mische-Lawson L, Tanquary J. Impact of a contextual intervention on child participation and parent competence  among  children  with  autism  spectrum  disorders:  a pretest-posttest repeated-measures  design.  Am  J  Occup  Ther 2012;66:520-8.
79. Elder  JH,  Donaldson  SO,  Kairalla  J,  et  al.  In-home  training  for fathers of children with autism: a follow up study and evaluation of four individual training components. J Child Fam Stud 2011;20:26371.
80. Elder JH, Valcante G, Yarandi H, White D, Elder TH. Evaluating in-home training for fathers of children with autism using singlesubject  experimentation  and  group  analysis  methods.  Nurs  Res 2005;54:22-32.
81. Juneja  M,  Mukherjee  SB,  Sharma  S,  Jain  R,  Das  B,  Sabu  P. Evaluation of a parent-based behavioral intervention program for children with autism in a low-resource setting. J Pediatr Neurosci 2012;7:16-18.
82. Kashinath S, Woods J, Goldstein H. Enhancing generalized teaching strategy use in daily routines by parents of children with autism. J Speech Lang Hear Res 2006;49:466-85.
83. Okuno H, Nagai T, Sakai S, et al. Effectiveness of modified parent training  for  mothers  of  children  with  pervasive  developmental
19. disorder on parental confidence and children's behavior. Brain Dev 2011;33:152-60.
84. Pillay M, Alderson-Day B, Wright B, Williams C, Urwin B. Autism Spectrum  Conditions  -  Enhancing  Nurture  and  Development (ASCEND):  an  evaluation  of  intervention  support  groups  for parents. Clin Child Psychol Psychiatry 2011;16:5-20.
85. Prelock PA, Calhoun J, Morris H, Platt G. Supporting parents to facilitate communication and joint attention in their young children with autism spectrum disorders: two pilot studies. Top Lang Disord 2011;31:210-34.
86. Research Units  on  Pediatric  Psychopharmacology  [RUPP]  autism network. Parent training for children with pervasive developmental disorders: A multi-site feasibility trial. Behav Interv 2007;22:179-99.
87. Robbins FR, Dunlap G. Effects of task difficulty on parent teaching skills and behavior problems of young children with autism. Am J Mental Retard 1992; 96:631-643.
88. Seung H, Ashwell S, Elder J, Valcante G. Verbal communication outcomes in children with  autism  after  in-home  father  training.  J Intellect Disabl Res 2006;50:139-50.
89. Shields J. The NAS EarlyBird Programme: partnership with parents in early intervention. The National Autistic Society. Autism 2001;5:49-56.
90. Solomon M, Ono M, Timmer S, Goodlin-Jones B. The effectiveness of parent--child interaction therapy for families of children on the autism spectrum. J Autism Dev Disord 2008;38:1767-76.
91. Todd  S,  Bromley  J,  Ioannou  K,  et  al.  Using  group-based  parent training  interventions  with  parents  of  children  with  disabilities:  a description  of  process,  content  and  outcomes  in  clinical  practice. Child Adolesc Mental Health 2010;15:171-75.
92. Williams  K,  Wishart  J.  The  Son-Rise  Program  intervention  for autism: an investigation into family experiences. J Intellect Disabl Res 2003;47:291-99.
93. Venker CE, McDuffie A, Ellis Weismer S, Abbeduto L. Increasing verbal  responsiveness  in  parents  of  children  with  autism:a  pilot study. Autism 2012;16:568-85.
94. Aldred  C,  Green  J,  Emsley  R,  McConachie  H.  Brief  report: mediation of treatment effect in a communication intervention for pre-school children with autism. J Autism Dev Disord 2012;42:44754.
95. Whittingham K, Sofronoff K, Sheffield J, Sanders MR. Behavioural family intervention with parents of children with ASD: what do they find useful in the parenting program stepping stones triple P? Res Autism Spectr Disord 2009;3:702-13.
96. Tonge B, Brereton A, Kiomall M, Mackinnon A, King N, Rinehart N.  Effects  on  parental  mental  health  of  an  education  and  skills training  program  for  parents  of  young  children  with  autism:  a randomized controlled trial. J Am Acad Child  Adolesc Psychiatry 2006;45:561-69.
97. Whittingham K,  Sofronoff K,  Sheffield  J,  Sanders  MR.  Stepping stones triple P: an RCT of a parenting program with parents of a child diagnosed with an autism spectrum disorder. J Abnorm Child Psychol 2009;37:469-80.
98. Koegel RL, Bimbela A, Schreibman L. Collateral effects of parent training on family interactions. J Autism Dev Disord 1996;26:34759.
99. Erguner-Tekinalp B, Akkok F. The effects of a coping skills training program  on  the  coping  skills,  hopelessness,  and  stress  levels  of mothers of children with autism. Int J Advance Counsel 2004;26:257-69.
100. Puttahraksa P, Tilokskulchai F, Sitthimongkol Y, Prasopkittikul T, Liknapichitkul D. Empowerment program on promoting perceived

- self-efficacy  in  caregivers  of  autistic  children.  Thai  J  Nurs  Res 2006;10:180-90.
101. Clifford  T,  Minnes  P.  Logging  On:.Evaluating  an  online  support group  for  parents  of  children  with  autism  spectrum  disorders.  J Autism Dev Disord 2013;43:1662-75.
102. Giarelli E, Souders M, Pinto-Martin J, Bloch J, Levy SE. Intervention  pilot  for  parents  of  children  with  autistic  spectrum disorder. Pediatr Nurs 2005;31:389-99.
103. Shu B, Lung F. The effect of support group on the mental health and  quality  of  life  for  mothers  with  autistic  children.  J  Intellect Disabl Res 2005;49:47-53.
104. Jocelyn LJ, Casiro OG, Beattie D, Bow J, Kneisz J. Treatment of children  with  autism:  a  randomized  controlled  trial  to  evaluate  a caregiver-based intervention program in community day-care centers. J Dev Behav Pediatr 1998;19:326-34.
105. Scahill L, McDougle CJ, Aman MG, et al. Effects of risperidone and parent training on adaptive functioning in children with pervasive developmental  disorders  and  serious  behavioral  problems.  J  Am Acad Child Adolesc Psychiatry 2012;51:136-46.
106. Paul  R,  Campbell  D,  Gilbert  K,  Tsiouri  I.  Comparing  spoken language treatments for minimally verbal preschoolers with autism spectrum disorders. J Autism Dev Disord 2013;43:418-31.
107. Hagner D, Kurtz A, Cloutier H, Arakelian C, Brucker DL, May J. Outcomes of a family-centered transition process for students with autism  spectrum  disorders.  Focus  Autism  Other  Dev  Disabl 2012;27:42-50.
108. Fernandes FDM, Amato CaDLH, Balestro JI, Molini-Avejonas DR. Orientation to mothers of children of the autistic spectrum about language and communication. J Soc Bras Fonoaudiol 2011;23:1-7.
109. Perry A, Condillac RA. The TRE-ADD preschool parent training program:  program  evaluation  of  an  innovative  service  delivery model. J Dev Disabl 2010;16:8-16.
110. Schultz  TR,  Stichter  JP,  Herzog MJ,  McGhee  SD,  Lierheimer K. Social  Competence  Intervention  for  Parents  (SCI-P):  comparing outcomes for a parent education program targeting adolescents with ASD. Autism Res Treat Print 2012;681465.
111. Schwartz IS, Sandall SR, McBride BJ, Boulware GL. Project DATA (Developmentally Appropriate Treatment for Autism). An inclusive school-based  approach  to  educating  young  children  with  autism. Topics Early Child Spec Edu 2004;24: 156-68.
112. Bendixen  RM,  Elder  JH,  Donaldson  S,  Kairalla  JA,  Valcante  G, Ferdig  RE.  Effects  of  a  father-based  in-home  intervention  on perceived  stress  and  family  dynamics  in  parents  of  children  with autism. Am J Occup Ther 2011;65:679-87.
113. Symon  JB.  Expanding  Interventions  for  children  with  autism. Parents as trainers. J Pos Behav Interv 2005;7:159-73.
114. Chu CH, Pan CY. The effect of peer- and sibling-assisted aquatic program on interaction behaviors and aquatic skills of children with autism  spectrum  disorders  and  their  peers/siblings.  Res  Autism Spect Disord 2012;6:1211-23.
115. Granat T, Nordgren I, Rein G, Sonnander K. Group intervention for  siblings  of  children  with  disabilities:  a  pilot  study  in  a  clinical setting. Disab Rehab 2012; 34:69-75.
116. Smith T, Perry A. A sibling support group for brothers and sisters of children with autism. J Dev Disabl 2004;11:77-88.
117. Wright SD, D'astous V, Wright CA, Diener ML. Grandparents of grandchildren with autism spectrum disorders (ASD): strengthening relationships through technology activities. Int J Aging Hum Dev 2012;75:169-84.
118. Hardan  AY,  Gengoux  GW,  Berquist  KL,  et  al.  A  randomized controlled trial of pivotal response treatment group for parents of children with autism.J Child Psychol Psychiatry 2015;56:884 -92.
119. Mohammadzaheri  F,  Koegel  LK,  Rezaee  M,  Rafiee SM.  A randomized  clinical  trial  comparison  between  pivotal  response treatment  (PRT)  and  structured  applied  behavior  analysis  (ABA) intervention  for  children  with  autism.  J  Autism  Dev  Disord 2014;44:2769 -77.
120. Ichikawa K, Takahashi Y, Ando M, et al. TEACCH -based group social  skills  training  for  children  with  high -functioning  autism:  a pilot randomized controlled trial. Biopsychosoc Med 2013;7:14.
121. Baghdadli A, Brisot J, Henry V, et al. Social skills improvement in children with high -functioning autism: a pilot randomized controlled trial. Eur Child Adolesc Psychiatry 2013; 22:433 -42.
122. Schohl KA, Van Hecke AV, Carson AM, Dolan B, Karst JS, Stevens SJ. A  replication and  extension of  the  PEERS  intervention: examining effects on social skills and social anxiety in adolescents with autism spectrum disorders. J Autism Dev Disord 44(3): 53245.
123. Yoo HJ, Bahn G, Cho IH, et al. A randomized controlled trial of the Korean  version  of  the  PEERS(®)  parent -assisted social skills training program for teens with ASD. Autism Res 2014;7:145 -61.
124. Laugeson EA, Gantman A, Kapp SK, Orenski K, Ellingsen R. A. Randomized controlled trial to improve social skills in young adults with autism spectrum disorder: The UCLA PEERS(®) program. J Autism Dev Disord 2015 Jun 25. [Epub ahead of print]
125. Kasari C, Gulsrud  A,  Paparella T,  Hellemann  G,  Berry  K. Randomized comparative efficacy study of parent -mediated interventions  for  toddlers  with  autism.  J  Consult  Clin  Psychol 2015;83:554 -63.
126. Wetherby  AM,  Guthrie  W,  Woods  J,  et  al.  Parent -implemented social  intervention  for  toddlers  with  autism:  an  RCT.  Pediatrics 2014;134:1084 -93.
127. Kasari C, Siller M, Huynh LN, et al. Randomized controlled trial of parental  responsiveness  intervention  for  toddlers  at  high  risk  for autism. Infant Behav Dev 2014;37:711 -21.
128. Tellegen CL, Sanders MR. A randomized controlled trial evaluating a  brief  parenting  program  with  childrenwith  autism  spectrum disorders. J Consult Clin Psychol 2014;82:1193 -200.
129. Siller M, Swanson M, Gerber A, Hutman T, Sigman M. A parent -mediated  intervention  that  targets  responsive  parental  behaviors increases attachment behaviors in children with ASD: results from a randomized clinical trial. J Autism Dev Disord 2014;44:1720 -32.
130. Peters-Scheffer N, Didden  R, Korzilius H, Matson  J. Cost comparison of early intensive behavioral intervention and treatment as usual for  children  with  autism  spectrum  disorder  in  The Netherlands. Res Dev Disabl 2012;33:1763-72.
131. McConnell  SR.  Interventions  to  facilitate  social  interaction  for young  children  with  autism:  review  of  available  research  and recommendations for educational intervention and future research. J Autism Dev Disord 2002;32:351-72.
132. White SW, Ollendick T, Albano AM, et al. Randomized controlled trial: multimodal anxiety and social skill intervention for adolescents with autism spectrum disorder. J Autism Dev Disord 2013;43:38294.
133. Kaslow  NJ,  Broth  MR,  Smith  CO,  Collins  MH.  Family-based interventions for child and adolescent disorders. J Marital Fam Ther 2012;38:82-100.
134. Bosa CA. Autism: Psychoeducational intervention. Rev Bras Psiquiatr 2006;28:S47-S53.

FIGURE 1. Flowchart of the included studies

Identification

Screening

Eligibility

Included

135. Cappe E, Wolff M, Bobet R, Adrien JL. Quality of life: a key variable to consider in the evaluation of adjustment in parents of children with autism spectrum disorders and in the development of relevant support and assistance programmes. Qual Life Res 2011;20:1279-94.
136. Smith LO, Elder JH. Siblings and family environments of persons with  autism  spectrum disorder:  a  review  of  the  literature.  J  Child Adolesc Psychiatric Nurs 2010;23:189-95.
137. Sullivan  A,  Winograd  G,  Verkuilen  J,  Fish  MC.  Children  on  the autism spectrum: grandmother involvement and family functioning. J Appl Res Intellect Disabl 2012;25:484-94.
138. Tsao LL, Davenport R, Schmiege C. Supporting siblings of children with autism spectrum disorders. Early Child Edu J 2012;40:47-54.
139. Dillenburger K, Mckerr L. "40 Years is an awful long time": Parents caring  for  adult  sons  and  daughters  with  disabilities.  Behav  Soc Issues 2009;18:1-20.

Full-text articles assessed for eligibility

(n = 183)

Studies included in the synthesis

Total: n = 111

Early Intensive Behavioral Intervention: n = 18

<!-- image -->

140. Patterson S, Smith V, Jelen M. Autism spectrum  disorders: information for pediatricians supporting families of young children on the spectrum. Advan Exp Med Biol 2012;724:51-60.
141. Meister C, Norlock D, Honeyman S, Pierce K. Sexuality and autism: a parenting skills enhancement group. Can J Hum Sex 1994;3:28389.
142. Wentz E, Nydén A, Krevers B. Development of an internet-based support and coaching model for adolescents and young adults with ADHD and autism  spectrum disorders:  a  pilot  study.  Eur  Child Adolesc Psychiatry 2012;21:611-22.
143. Howlin  P.  The  effectiveness  of  interventions  for  children  with autism. J Neural Transm Suppl 2005;69:101-19.
144. Jonsson U, Alaie I, Parling T, Arnberg FK. Reporting of harms in randomized  controlled  trials  of  psychological  interventions  for mental  and  behavioral  disorders:  a  review  of  current  practice. Contemp Clin Trials 2014;28:1-8.

Full-text articles

excluded

(n = 72)

## Appendix 1. Search terms

## Medline (OVID)

Early Intensive Behavioral Intervention (EIBI)

1. animals/ not humans/
2. autis*.tw.
3. exp child development disorders, pervasive/
4. asperger*.tw.
5. (PDD or PDDs).tw.
6. (ASD or ASDs).tw.
7. "pervasive develop*".tw.
8. 2 or 3 or 4 or 5 or 6 or 7
9. "eibi".tw.
10. "early intensive behavio*".tw.
11. exp behavior therapy/
12. Early Intervention/
13. Early Medical Intervention/
14. "early intervention*".tw.
15. (child* or infant* or baby or babies or toddler or girl* or boy* or pre*school*).tw.
16. exp child/
17. exp infant/
18. adolescent/
19. 15 or 16 or 17 or 18
20. (behavio* adj1 (analys* or therap* or modification or interven* or lovaas or lovas or communicat*)).tw.
21. ("applied behavio*" adj1 (intervention* or analys*)).tw.
22. 9 or 10 or 14 or 20 or 21
23. 12 or 13
24. 11 and 23
25. 22 or 24
26. 8 and 19 and 25
27. 26 not 1
28. limit 27 to yr="1990 -Current"
29. limit 28 to ((danish or english or norwegian or
30. swedish) and (case reports or journal article))

## Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH)

1. autis*.tw.
2. exp child development disorders, pervasive/
3. asperger*.tw.
4. (PDD or PDDs).tw.
5. (ASD or ASDs).tw.
6. "pervasive develop*".tw.
7. 1 or 2 or 3 or 4 or 5 or 6
8. "Treatment and Education of Autistic".tw.
9. "TEACCH*".tw.
10. "university of north carolina".mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier]
11. 8 or 9 or 10
12. 7 and 11
13. 12 not (animals/ not humans/)

## Social skills training

1. autis*.tw.
2. exp child development disorders, pervasive/
3. asperger*.tw.
4. (PDD or PDDs).tw.
5. (ASD or ASDs).tw.
6. "pervasive develop*".tw.
7. 1 or 2 or 3 or 4 or 5 or 6
8. animals/ not humans/
9. "communication skill*".tw.
10. "human relation*".tw.
11. exp communication disorders/
12. exp social behavior/
13. "train*".tw.
14. "treatment*".tw.
15. "intervention*".tw.
16. "therap*".tw.
17. "educat*".tw.
18. "program*".tw.
19. exp behavior therapy/
20. communication/
21. language/
22. exp verbal behavior/
23. 20 or 21 or 22
24. socialization/
25. interpersonal relations/
26. social participation/
27. (interpersonal adj1 (behavio* or communication* or competenc* or relation* or skill*)).tw.
28. (social adj1 (behavio* or adjustment* or interaction* or communication* or competenc* or relation* or skill*)).tw.
29. 9 or 10 or 11 or 12 or 23 or 24 or 25 or 26 or 27 or 28
30. 13 or 14 or 15 or 16 or 17 or 18 or 19
31. 7 and 29 and 30
32. 31 not 8
33. 32
34. limit 33 to yr="1990 -Current"
35. limit 34 to ((danish or english or norwegian or swedish) and (case reports or journal article))

## Interventions involving significant others

1. animals/ not humans/
2. autis*.tw.
3. exp child development disorders, pervasive/
4. asperger*.tw.
5. (PDD or PDDs).tw.
6. (ASD or ASDs).tw.
7. "pervasive develop*".tw.
8. 2 or 3 or 4 or 5 or 6 or 7
9. exp child/
10. exp infant/
11. adolescent/
12. (child* or infant* or baby or babies or toddler or girl* or boy* or pre*school* or adolescent* or teen*age* or school*).tw.
13. 9 or 10 or 11 or 12
14. exp family/
15. caregivers/
16. (support* or educat* or training* or program* or psychoeduca* or knowledge or intervention* or guidance or supervis*or promot*).tw.
17. ((parent* or care*giver* or family or families or mother* or father* or maternal* or paternal* or network* or "significant other*" or sibling* or group*) adj3 (support* or educat* or training* or program* or

psychoeduca* or knowledge or intervention* or guidance or supervis*or promot*)).tw.

18. 14 or 15
19. 16 and 18
20. 17 or 19
21. 8 and 13 and 20
22. 21 not 1
23. limit 22 to (yr="1990 -Current" and (danish or english or norwegian or swedish) and (case reports or journal article))

## PsycInfo (OVID)

## Early Intensive Behavioral Intervention (EIBI)

1. (autis* or asperger* or pdd or pdds or asd or asds or "pervasive develop*").ab,ti.
2. exp Pervasive Developmental Disorders/
3. exp Early Intervention/
4. exp Behavior Therapy/
5. (eibi or "early intensive behavio*" or "Early Intervention").ab,ti.
6. "early medical intervention".ab,ti.
7. (child* or infant* or baby or babies or toddler or girl* or boy* or pre*school*).ab,ti.
8. (behavio* adj1 (analys* or therap* or modification or interven* or lovaas or lovas or communicat*)).ab,ti.
9. ("applied behavio*" adj1 (intervention* or analys*)).ab,ti.
10. 1 or 2
11. 3 or 4 or 5 or 6 or 8 or 9
12. 7 and 10 and 11
13. limit 12 to (journal article and (danish or english or norwegian or swedish) and yr="1990 -Current")

Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH)

1. TEACCH.mp. [mp=title, abstract, heading word, table of contents, key concepts, original title, tests & measures] 2. "university of north carolina".mp. [mp=title, abstract, heading word, table of contents, key concepts, original title, tests & measures]
3. "Treatment and Education of Autistic".mp. [mp=title, abstract, heading word, table of contents, key concepts, original title, tests & measures]
4. 1 or 3

## Social skills training

1. (autis* or asperger* or pdd or pdds or asd or asds or "pervasive develop*").ab,ti.
2. exp Pervasive Developmental Disorders/
3. communication/ or communication skills/ or communication skills training/ or exp communication barriers/ or exp communication disorders/
4. ("communication skill*" or "human relation*").ab,ti.
5. exp Interpersonal Communication/ or exp Interpersonal Relationships/ or exp Interpersonal Interaction/
6. social behavior/ or social adjustment/ or exp social interaction/ or exp social skills/
7. exp Socialization/
8. exp Intervention/

9. exp Treatment/

10. exp Training/
11. (train* or treatment* or intervention* or therap* or educat* or program*).ab,ti.
12. exp Behavior Therapy/
13. "social participation* ".ab,ti.
14. (interpersonal adj1 (behavio*r* or communication* or competenc* or relation* or skill*)).ab,ti.
15. (social adj1 (behavio*r* or adjustment* or interaction* or communication* or competenc* or relation* or skill*)).ab,ti.
16. 1 or 2
17. 3 or 4 or 5 or 6 or 7 or 13 or 14 or 15
18. 8 or 9 or 10 or 11 or 12
19. 16 and 17 and 18

## Interventions involving significant others

1. (autis* or asperger* or pdd or pdds or asd or asds or "pervasive develop*").ab,ti.
2. exp Pervasive Developmental Disorders/
3. (child* or infant* or baby or babies or toddler or girl* or boy* or pre*school*).ab,ti.
4. (adolescent* or teen*age* or school*).ab,ti.
5. exp Family/
6. exp Caregivers/
7. ((parent* or care*giver* or family or families or mother* or father* or maternal* or paternal* or network* or "significant other*" or sibling* or group*) adj3 (support* or educat* or training* or program* or psychoeduca* or knowledge or intervention* or guidance or supervis*or promot*)).ab,ti.
8. 1 or 2
9. 3 or 4

10. 5 or 6 or 7

11. 8 and 9 and 10
12. limit 11 to (journal article and (danish or english or norwegian or swedish) and yr="1990 -Current")