The Autism Treatment Network and Autism Intervention Research Network on Physical Health were established in 2008 with goals of improving understanding of the medical aspects of autism spectrum disorders. Over the past decade, the combined network has conducted >2 dozen clinical studies, established clinical pathways for best practice, developed tool kits for professionals and families to support better care, and disseminated these works through numerous presentations at scientific meetings and publications in medical journals. As the joint network enters its second decade continuing this work, it is undergoing a transformation to increase these activities and accelerate their incorporation into clinical care at the primary care and specialty care levels. In this article, we describe the past accomplishments and present activities. We also outline planned undertakings such as the establishment of the Autism Learning Health Network, the increasing role of family members as co-producers of the work of the network, the growth of clinical trials activities with funding from foundations and industry, and expansion of work with primary care practices and autism specialty centers. We also discuss the challenges of supporting network activities and potential solutions to sustain the network.

The Autism Treatment Network (ATN) started in 2005 as a group of clinical investigators with a strong interest in families’ concerns surrounding medical aspects of autism spectrum disorders (ASDs). With support from Autism Speaks, the network expanded in 2008 and obtained funding from the Health Resources and Services Administration to become the Autism Intervention Research Network on Physical Health (AIR-P). This combined ATN-AIR-P network has been active for the past decade developing a portfolio of clinical and research initiatives to advance our understanding of and care delivery to individuals with ASD.

When the ATN was formed, there was much controversy surrounding whether the co-occurring medical conditions reported by families and some clinicians were truly more frequent than in the general population and whether they were unique to autism. In an attempt to help resolve these issues, 1 of the first joint network activities was the establishment of a registry of children and adolescents receiving care at ATN-AIR-P sites.1  Each child enrolled in the registry was well described by a battery of evaluations including medical, cognitive, and behavioral measures. The measures were agreed on by all sites to not only collect research data but to establish best practice clinical care. The presence of medical conditions other than autism was documented, and a better picture of co-occurring medical problems has emerged. This work has led others to examine these issues and eventually confirmed that there are more gastrointestinal (GI) problems, sleep problems, and epilepsy and immune concerns in children with ASD compared with the general population.26 

As evidence accumulated regarding medical aspects of ASD, clinicians and families faced the dilemma of how to best approach these problems. Clinicians conducted systematic reviews to determine what treatments work best. In some cases, practice pathways were developed, tested, and eventually published for dissemination. Two of these in particular dispelled common myths surrounding GI issues (specifically, constipation) and sleep-onset insomnia.7,8 

ATN Registry data identified sleep-onset insomnia as the most common sleep-associated problem among children and adolescents with autism. The prevalence of this condition and need for clinicians to provide better management led to the development of a practice pathway for sleep problems.7  These problems are usually treated with behavioral interventions to improve overall sleep hygiene in typically developing children, and this is generally effective.9  ATN-AIR-P investigators demonstrated that behavioral treatments are also effective in children with ASD in the majority of cases.10  A total 65% of parents who were taught these interventions responded “strongly agree” when asked if they had seen improvement in sleep habits. When evaluating a parent teaching intervention using these behavioral techniques, they found either group or individual parent training by a trained sleep professional is associated with improvements in sleep. Parent sleep education was also associated with improved aspects of child behavior (including repetitive behavior, a core symptom of ASD), pediatric quality of life, and parenting sense of competence.10  A tool kit of behavioral strategies for families to implement was developed and made available online; it has been downloaded >25 000 times.

ATN Registry data also revealed that constipation was the most common GI concern and that it is often overlooked and undertreated.11  Again, the high prevalence of this condition led to the development of a practice pathway.7  The efficacy of this practice pathway was tested along with interventions to promote family-clinician communication, and its utility has been demonstrated.12  In this study, ATN-AIR-P investigators found that collaborative goal-setting increased family engagement and improved treatment adherence. This led to better parent monitoring by diary, and weekly calls with the clinic staff kept treatment modifications up to date and assured progress toward goals. Through this approach, 85% of families reported improvement.

Other clinical practice parameters for attention-deficit/hyperactivity disorder and irritable and/or aggressive behavior were developed and targeted primary care providers (PCPs) in an effort to empower these clinicians and improve access for families,.13,14  The combined network has produced 5 practice pathways and conducted another 3 systematic reviews to help identify areas in need of additional research such as telehealth, screening and diagnosis of ASD, and anxiety.8,10,15,16 

The network has embarked on studies to describe clinical status and validate commonly used but unproven treatments. The nutritional status of children, that is, supplement receipt or lack thereof, was studied to determine if these children were at risk for under- or overexposure to vitamins and other nutrients.17,18  These studies revealed that children with ASD and matched controls consumed similar amounts of nutrients from food. Only children with ASD aged 4 to 8 years consumed significantly less energy, vitamins A and C, and the mineral zinc; those 9 to 11 years consumed less phosphorous. In other nutrition research protocols, we have studied iron status and its relationship to sleep issues; we have also studied metabolic concerns such as creatine deficiency syndrome and bone mineral density.1922  A variety of novel treatments have been trialed through Autism Speaks and AIR-P funding. Network investigators have studied electronic toilet training alarms, iron supplements for restless sleep, and use of metformin to reduce weight gain associated with use of atypical antipsychotic medications,.23,24  Three network studies were recognized among the 20 most influential publications of 2017 compiled by the Interagency Autism Coordinating Committee.2527  One in particular, a randomized, placebo-controlled trial of metformin for the treatment of overweight induced by antipsychotic medication,27  found that individuals diagnosed with ASD taking atypical antipsychotic medications can use metformin to decrease weight gain from these medications. A long-term (1 year) open-label extension study provided further confirmation for the effectiveness of this approach and has received significant attention for consideration as part of standard management of this problem.

A partial compilation of network studies and their findings appear in Table 1.

TABLE 1

Sample of Completed Network Studies

Study NameStudy Description and/or FindingsPublication References
Bone Accrual Rates in Boys With ASD Confirmed decreased bone accrual in boys with ASD Neumeyer et al22  
Bone Mineral Density in Children With ASD Confirmed decreased bone mineral density in children with ASD Neumeyer et al22,28  
Communication Deficits and the Motor System in ASD: Dissecting Patterns of Association and Dissociation Between Them Examined potential differences in the contributions of fine versus gross motor skills to autistic profiles Mody et al29  
Development of a Manualized Wireless Moisture Alarm Intervention for Toilet Training Children With Autism Intervention research examining smartphone application to facilitate toilet training; revealed effectiveness Mruzek et al23  
Development of a Parent-Based Sleep Education Program for Children WITH ASD Provided sleep education to parents of children with ASD to determine if an individual or group format was more effective in improving sleep and aspects of daytime behavior and family functioning; revealed effectiveness of both approaches Malow et al10  
Diet and Nutrition in Children With ASDs Examined dietary intake of children with ASD, including the use of supplements; revealed that most common micronutrient deficits were not corrected by supplements and supplementation led to excess vitamin A, folate, and zinc intake across the sample Stewart et al18  
ECHO Autism Training and dissemination project promoting teleconsultation and telementoring to clinicians in underserved areas Sohl et al30  
Evaluating the Impact of Emergency Department Services for Children and Adolescents With ASD Examined experiences of emergency department care from the perspectives of families in which a child has ASD Nicholas et al31  
Overweight and Obesity in ASD: Prevalence, Correlates, and Predictors of Weight Changes Over Time Reviewed the prevalence and factors associated with overweight and obesity Zuckerman et al32  
Hill et al33  
Prevalence of Creatine Deficiency Syndromes and Genetic Variability in Creatine Metabolism in Children With ASD: A Pilot Study The goal of the study was to ascertain the prevalence of creatine deficiency syndromes in children with ASD Schulze et al20  
Cameron et al34  
Relationship Between Gastrointestinal Disorders and Stress Reactivity, Immunity, and Blood Serotonin in ASD Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically developing individuals, particularly stress-responsive cytokines including tumor necrosis factor α and interleukin 6. Ferguson et al35  
Relationship Between Subtypes of Restricted and Repetitive Behaviors and Sleep Disturbance in ASD Examined the association of 2 types of restricted and repetitive behaviors, repetitive sensory motor and insistence on sameness, with sleep problems in children with ASD Hundley et al36  
Sleep Problems in Children With ASD: Examining the Role of Anxiety and Sensory Over-Responsivity Findings suggest that sensory over-responsivity and anxiety may be related to the development and maintenance of sleep problems in children with ASD. Mazurek and Petroski37  
The Autism Impact Measure (AIM): A New Tool to Measure Treatment Outcome in ASD The goal of the project was to develop a clinical tool to broadly assess the outcome in ASD. Kanne et al38  
Treatment of Overweight Induced by Antipsychotic Medication in Young People With ASD Excessive wt gain is a common problem in patients treated with antipsychotic medications; an effective method to reduce this is needed. Anagnostou et al24  
Handen et al27  
Comparison of DSM-IV-TR and DSM-5 Diagnostic Criteria for Autism The study examined effects of change in criteria on diagnosis of children referred for evaluation of possible ASD. Mazurek et al25  
Study NameStudy Description and/or FindingsPublication References
Bone Accrual Rates in Boys With ASD Confirmed decreased bone accrual in boys with ASD Neumeyer et al22  
Bone Mineral Density in Children With ASD Confirmed decreased bone mineral density in children with ASD Neumeyer et al22,28  
Communication Deficits and the Motor System in ASD: Dissecting Patterns of Association and Dissociation Between Them Examined potential differences in the contributions of fine versus gross motor skills to autistic profiles Mody et al29  
Development of a Manualized Wireless Moisture Alarm Intervention for Toilet Training Children With Autism Intervention research examining smartphone application to facilitate toilet training; revealed effectiveness Mruzek et al23  
Development of a Parent-Based Sleep Education Program for Children WITH ASD Provided sleep education to parents of children with ASD to determine if an individual or group format was more effective in improving sleep and aspects of daytime behavior and family functioning; revealed effectiveness of both approaches Malow et al10  
Diet and Nutrition in Children With ASDs Examined dietary intake of children with ASD, including the use of supplements; revealed that most common micronutrient deficits were not corrected by supplements and supplementation led to excess vitamin A, folate, and zinc intake across the sample Stewart et al18  
ECHO Autism Training and dissemination project promoting teleconsultation and telementoring to clinicians in underserved areas Sohl et al30  
Evaluating the Impact of Emergency Department Services for Children and Adolescents With ASD Examined experiences of emergency department care from the perspectives of families in which a child has ASD Nicholas et al31  
Overweight and Obesity in ASD: Prevalence, Correlates, and Predictors of Weight Changes Over Time Reviewed the prevalence and factors associated with overweight and obesity Zuckerman et al32  
Hill et al33  
Prevalence of Creatine Deficiency Syndromes and Genetic Variability in Creatine Metabolism in Children With ASD: A Pilot Study The goal of the study was to ascertain the prevalence of creatine deficiency syndromes in children with ASD Schulze et al20  
Cameron et al34  
Relationship Between Gastrointestinal Disorders and Stress Reactivity, Immunity, and Blood Serotonin in ASD Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically developing individuals, particularly stress-responsive cytokines including tumor necrosis factor α and interleukin 6. Ferguson et al35  
Relationship Between Subtypes of Restricted and Repetitive Behaviors and Sleep Disturbance in ASD Examined the association of 2 types of restricted and repetitive behaviors, repetitive sensory motor and insistence on sameness, with sleep problems in children with ASD Hundley et al36  
Sleep Problems in Children With ASD: Examining the Role of Anxiety and Sensory Over-Responsivity Findings suggest that sensory over-responsivity and anxiety may be related to the development and maintenance of sleep problems in children with ASD. Mazurek and Petroski37  
The Autism Impact Measure (AIM): A New Tool to Measure Treatment Outcome in ASD The goal of the project was to develop a clinical tool to broadly assess the outcome in ASD. Kanne et al38  
Treatment of Overweight Induced by Antipsychotic Medication in Young People With ASD Excessive wt gain is a common problem in patients treated with antipsychotic medications; an effective method to reduce this is needed. Anagnostou et al24  
Handen et al27  
Comparison of DSM-IV-TR and DSM-5 Diagnostic Criteria for Autism The study examined effects of change in criteria on diagnosis of children referred for evaluation of possible ASD. Mazurek et al25  

Studies presently underway or recently completed address factors associated with general health and wellness. Parent reports of difficulty promoting good dental habits with their children led to the dental health training program currently underway. Data from the registry and other studies have indicated individuals with ASD have an increased risk of overweight and obesity.32,33,39  This led to 2 studies promoting regular exercise for individuals. Physical Exercise to Reduce Anxiety in Underserved Children with ASD examines the feasibility and efficacy of a physical exercise intervention to reduce anxiety in children from underserved families as well as promote physical health. The results will provide critical insight into the feasibility and efficacy of a physical exercise intervention to reduce anxiety in children from underserved families. Such a program will aid in the development of an evidence-based physical exercise intervention tool kit for the treatment of anxiety as well as other behaviors and improvement of physical health in children with ASD from underserved populations.

Parents of a child with ASD are prone to chronic stress, and this can have negative effects on the health and well-being of both the parents and child. Treatments that can reduce stress may have benefits for both the parents and child. ATN-AIR-P investigators have conducted a controlled pilot trial to examine an adapted virtual mind-body group intervention for parents of children with ASD.40  The study yielded positive results for feasibility, acceptability, and preliminary efficacy and may be expanded for additional evaluation.

Over the past few years, the network has also adopted the Extension for Community Healthcare Outcomes (ECHO) technique to encourage more rapid translation of existing knowledge and new findings to community care. ECHO is a collaborative model of medical education and care management that builds capacity by teaching best practices using case-based learning, video technology, and outcome evaluation.30,41  Originally developed to improve care for rural patients with hepatitis, the format is ideally suited for extending the reach of autism specialists into both rural and urban settings. With 14 participants, ECHO Autism started in Missouri in 2015 with funding from AIR-P. AIR-P funding then supported a replication study at 10 additional sites, engaging 148 PCPs across 7 US states. These sites and Missouri make up the ECHO Autism Collaborative. The ATN provided resources for sites in the collaborative to continue their ECHO Autism programs after the replication study ended. To date, 5 sites have relaunched their ECHO Autism programs with 133 new PCPs enrolled. Missouri has also led efforts within the state to use the ECHO model to reduce wait times to an ASD diagnosis. This was done by the ECHO Autism Screening Tool for Autism in Toddlers and Young Children (n = 26) and ECHO Autism Diagnostics (n = 10) collaborative groups. The first of these trained PCPs on the Screening Tool for Autism in Toddlers and Young Children,42  allowing them to make ASD diagnoses for children <4 years of age with the most obvious autism signs. Most recently, the Missouri team has launched ECHO Autism Crisis Care in February 2019 to provide consultation and mentoring regarding acute and urgent situations. ECHO Autism Transition and ECHO Center Development and Support are also currently underway.

As noted earlier, the ATN began with clinicians concerned with patients and their families’ repeated reports of a variety of recurring medical problems affecting their health. Support from advocacy groups, representing the interests of families, initially helped the network move forward and to inform clinicians to some degree. Although clinical investigators have historically proposed many of our studies, virtually all studies have had the imprint of engaged family members asking health professionals about various symptoms and signs. The ATN-AIR-P has had a family advisory committee (FAC) nearly from inception, with each site having a local FAC and 2 of its members representing the site at the larger network level. Family members review proposed research studies, provide input on study design, and share their ideas for potential research activities. Over the past 4 years, the level of family engagement has been progressing toward that of family members as co-producers of network activities and partners of the clinical teams and not simply as advisors or consultants. Expansion of the FAC has occurred through natural maturation and increased awareness of the network, representing more diverse families and their children with ASD across the United States. Additionally, numerous training opportunities have been made available to families to learn more about autism research, raising a child with autism, and becoming more involved in community activities to improve life outcomes. Current FAC leadership is working both nationally and locally to mentor new FAC members into leadership roles from all sites across the network. The network is also working to expand the FAC membership to include self-advocates from each site. One self-advocate was added during this last year to the FAC with a plan to expand membership at each site in the network in the coming year. More formal processes have been created for the FAC, including a charter, commitment statement, and a formalized honorarium system, to recognize FAC members for their time and dedication with their participation. The network, with input from the FAC leadership team, also developed guidance (FAC Development Guide) to assist local FACs in organizing and improving participation to a level corresponding with ATN leadership goals. The network has also supported national FAC leaders to work directly with local FACs to improve participation and engagement at ATN sites, both virtually and in person. During the last renewal process for the AIR-P network funding in 2015, family members were integral in identifying network priorities and shaping the principal research initiatives undertaken in the present funding period. Family members work with researchers and clinicians on ATN-AIR-P studies, collaborating to ensure translational research that is meaningful to families, patients, and the research community for both the present day and future. In 2019, the ATN-AIR-P will be supporting the funding of 2 FAC leaders to attend an 8-month health care quality improvement methodology course to further their roles as leaders within the network.

After a decade in its current format, the ATN-AIR-P has accomplished a great deal by traditional metrics. The ATN Registry amassed >7000 subjects and has been studied carefully by dozens of investigators. Forty-three ATN-AIR-P studies have been conducted (4 are still in process), with thousands of subjects enrolled in this research. More than 170 presentations at scientific meetings have been delivered, and >130 publications have appeared in scientific journals.

Moving forward, other changes in health care have opened opportunities for new approaches to knowledge acquisition and dissemination as well as implementation of innovative treatments and interventions. The expansion of quality improvement philosophy in health care has led to rapid trials of care delivery approaches. The information that can be found in large electronic health record databases is an underused source and can provide answers to the effectiveness of changes in treatments more rapidly than past controlled trials. This is the advent of learning health networks in which multiple institutions share data and collaborate in testing and implementing new methods of providing interventions. Rather than recruiting subjects meeting specific criteria for a focused research study, learning networks seek to enroll all patients with a certain condition and observe their ongoing care. With this philosophy of learning from every patient and monitoring outcome measures to determine those treatments that work, learning networks can accelerate the testing of new practices. Learning health networks then have the potential to more rapidly translate these new research findings to clinical care than has been customary in the past. The ATN-AIR-P is transforming into such a learning health network.43  By September 2019, the network had already enrolled >1000 children and adolescents with autism and collected >2000 parent-reported outcome measures on problems such as anxiety and attention-deficit/hyperactivity disorder. Among the benefits of this learning network will be better, quicker identification of potential subjects for clinical trials. This transition will provide increased support for the treatment implementation activities of the network, broader dissemination of best practices, and improved infrastructure for autism intervention research endeavors to advance care.44 

Dr Coury conceptualized and designed the study, drafted the initial manuscript, and coordinated and supervised data collection; Drs Murray and Kuhlthau and Ms Fedele, Mr Hess, and Ms Kelly provided edits and content to the original and revised manuscript and assisted with data collection; and all authors reviewed and revised the manuscript, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.

FUNDING: Autism Treatment Network activity was supported by Autism Speaks and cooperative agreement UA3 MC11054 through the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program to Massachusetts General Hospital. This work was conducted through the Autism Speaks Autism Treatment Network.

AIR-P

Autism Intervention Research Network on Physical Health

ASD

autism spectrum disorder

ATN

Autism Treatment Network

ECHO

Extension for Community Healthcare Outcomes

FAC

family advisory committee

GI

gastrointestinal

PCP

primary care provider

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.