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The Autism Treatment Network:

Bringing Best Practices to All Children

With Autism

Daniel L. Coury, MD,a,bDonna S. Murray, PhD,c,d,eAngie Fedele, BA,cTom Hess, MA,aAmy Kelly, MBA, MNM,f Karen A. Kuhlthau, PhDg,h

abstract

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.

aDepartment of Pediatrics, Nationwide Childrens Hospital, Columbus, Ohio;bCollege of Medicine, Ohio State University, Columbus, Ohio;cAutism Speaks, New York, New York;dDivision of

Developmental and Behavioral Pediatrics, Cincinnati Children’s Hospital Medical Center, Columbus, Ohio;eDepartment of Pediatrics, College of Medicine, University of Cincinnati, Columbus,

Ohio;fDevereux Advanced Behavioral Health and Family Partners Program, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania;gMassachusetts General Hospital, Boston, Massachusetts; andhHarvard Medical School, Harvard University, Boston, Massachusetts

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 thefinal manuscript as submitted, and agree to be accountable for all aspects of the work.

DOI:https://doi.org/10.1542/2019-1895D Accepted for publication Jan 27, 2020

Address correspondence to Daniel L. Coury, MD, 700 Children’s Drive, LA Suite 5A, Columbus, OH 43205-2664. E-mail: daniel.coury@nationwidechildrens.org PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2020 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE:The authors have indicated they have nofinancial relationships relevant to this article to disclose.

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.

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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.

REGISTRY

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.1Each 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.2–6

MEDICAL ASPECTS OF ASD AND BEST PRACTICES FOR TREATING THEM

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

Sleep Problems

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.7These problems are usually treated with behavioral interventions to improve overall sleep hygiene in typically developing children, and this is generally effective.9ATN-AIR-P investigators demonstrated that behavioral treatments are also effective in children with ASD in the majority of cases.10A 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.10A tool kit of behavioral strategies for families to implement was developed and made available

online; it has been downloaded

.25 000 times.

Constipation

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.7The 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,.13,14The 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

INTERVENTION RESEARCH

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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.19–22A 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,.23,24Three network studies were recognized among the 20 most influential publications of 2017 compiled by the Interagency Autism Coordinating Committee.25–27 One in particular, a randomized, placebo-controlled trial of metformin for the treatment of overweight induced by antipsychotic medication,27found 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 theirfindings appear in Table 1.

CURRENT INITIATIVES

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.40The 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 newfindings 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.30,41Originally 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. Thefirst of these trained PCPs on the Screening Tool for Autism in Toddlers and Young Children,42allowing 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.

NETWORK STRATEGIC PLANNING AND THE ROLE OF FAMILIES

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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

TABLE 1Sample of Completed Network Studies

Study Name Study Description and/or Findings Publication

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 offine 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 factoraand 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.

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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.

THE PATH FORWARD

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 researchfindings 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

ABBREVIATIONS

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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9. van Straten A, van der Zweerde T, Kleiboer A, Cuijpers P, Morin CM, Lancee J. Cognitive and behavioral therapies in the treatment of insomnia: a meta-analysis.Sleep Med Rev. 2018;38:3–16 10. Malow BA, Adkins KW, Reynolds A, et al.

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17. Hyman SL, Stewart PA, Schmidt B, et al. Nutrient intake from food in children

with autism.Pediatrics. 2012;130(suppl 2):S145–S153

18. Stewart PA, Hyman SL, Schmidt BL, et al. Dietary supplementation in children with autism spectrum disorders: common, insufficient, and excessive.

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DOI: 10.1542/2019-1895D

2020;145;S13

Pediatrics

A. Kuhlthau

Daniel L. Coury, Donna S. Murray, Angie Fedele, Tom Hess, Amy Kelly and Karen

Autism

The Autism Treatment Network: Bringing Best Practices to All Children With

Services

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DOI: 10.1542/2019-1895D

2020;145;S13

Pediatrics

A. Kuhlthau

Daniel L. Coury, Donna S. Murray, Angie Fedele, Tom Hess, Amy Kelly and Karen

Autism

The Autism Treatment Network: Bringing Best Practices to All Children With

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Figure

TABLE 1 Sample of Completed Network Studies

References

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