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Interagency Autism Coordinating Committee Strategic Plan for Autism Spectrum Disorder Research – 2013 Update

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Question 1: When Should I Be Concerned?

Introduction

Aspirational Goal: Children at risk for ASD will be identified through reliable methods before ASD behavioral characteristics fully manifest.

When originally framed, Question 1 was directed toward identifying at-risk children by the age of 24 months to facilitate the greatest chance of successful early intervention. Scientific advances since then have shown that, in infants at high genetic risk for ASD due to having an older sibling with autism, symptoms of autism begin to emerge as young as 6 months of age in those who later develop ASD. These new findings suggest that it may someday be possible to screen for children at risk for ASD before the emergence of the full symptoms of autism and early enough to facilitate even more effective intervention. While recent findings have demonstrated this early screening potential in high-risk infant siblings, future challenges include determining whether the same potential for very early identification can be extended to other high risk populations (e.g., very low birth-weight infants) and/or to the general population.

Many of the advances in the screening and diagnosis area have been in development and refinement of screening tests. Moving forward, more attention needs to focus on innovations in diagnostic tools. There also remains a great need for the development of efficient and cost effective screeners for use in children below 18 months of age, as well as more efficient methods of deploying developmental and ASD screening in community settings, including evaluation of effective parent-professional communication strategies for coping with concerns, referrals, follow-up evaluations for services and diagnosis, and linkage to appropriate services and supports. In addition, the development of culturally sensitive diagnostic tools that can be more easily used in both clinical and research settings is urgently needed. Finally, there has been a growing awareness of the need for better tools to diagnose adolescents and adults on the autism spectrum and to provide meaningful assessments of functioning--an issue that is captured in an objective in Question 6 of the IACC Strategic Plan, but may involve adaptation of tools that are currently used to diagnose children.

Progress Toward the Strategic Plan Objectives

The 2011-2012 IACC ASD Research Portfolio Analysis reviewed projects funded by both government agencies and private foundations from 2008-2012. From 2008-2012, the total funding devoted to projects that address Question 1 was $187 million, and if just the years since the publication of the first IACC Strategic Plan in 2009 are considered, the funding for Question 1 related projects was $158 million. On average for each year from 2009-2012, the funding levels for this Question were 35 percent higher than the 2008 level ($29 million) that preceded publication of the IACC Strategic Plan. Also in years 2009-2012, 11 percent of the funding for this Question supported core/other research projects outside of the research gaps covered by the nine objectives in Question 1.

Of the nine specific objectives under Question 1, four objectives addressing development of screening and diagnostic tools, identification of risk biomarkers, and a workshop on ethical issues, met or exceeded the recommended budget and fulfilled the recommended number of projects. Three objectives, concerning determining the utility of genetic tests and developing measures of heterogeneity and symptom severity, partially met the recommended budget and had a number of projects underway. One objective, on understanding the reasons for disparities in screening and diagnosis, was far below the recommended budget and number of projects. The remaining objective, on studies to understand if early diagnosis leads to early intervention and better outcomes, did not have any dedicated funding or projects, though some aspects of this research topic are covered in projects that are categorized elsewhere, such as a project in Question 4 on early intervention (that was preceded by early diagnosis) that also partially addresses the issue of outcomes.

Progress in the Field

Over the past 5 years, progress has been made toward developing tools and practices for more effective screening and diagnosis. New research suggests that existing screening tools, such as the Modified Checklist for Autism in Toddlers (in particular, the new M-CHAT-revised with follow-up interview (M-CHAT-R/F), which is not yet in widespread use)1, 2 and the Infant-Toddler Checklist,3 can be effectively used by pediatricians and other community providers. The M-CHAT-R/F shows promise as a screen for communication and developmental delays and as an ASD screen with the follow-up interview between 18 – 36 months of age. The Infant-Toddler Checklist shows promise as a broadband screen for communication impairments that can identify children with autism between 12 and 24 months and has practical value as the basis of a 5-minute screen during the 1-year well-baby check-up.4 New research suggests that with repeated screening at the ages of 6, 12, and 18 months, it might be possible to identify as many as 95 percent of children with ASD by the age of 24 months. While this represents a remarkable scientific advance, validation and translation of this potential into reality in the general population and in community settings remains an enormous gap.

The clinical reality is that currently only about 20 percent of children with ASD are being identified early (by 3 years of age).5 Barriers to the broader deployment of advanced screening and diagnostic tools include cost and the expertise required to administer the tests. Also, repeat screenings at 6 month intervals beginning at 6 months of age are not being done in practice, despite demonstrated efficacy of such screenings in at-risk infants.6 In addition, it appears that children who are identified in early screens are not always being referred for diagnosis and early intervention, even though there is now strong evidence to suggest the benefit of early intervention.7–9 Thus, we need to better understand the barriers that are preventing caregivers from seeking a diagnostic evaluation after a child fails an autism screen and to identify strategies that will help caregivers navigate the pathway from screening to diagnosis to entry into early intervention. Until this gap between screening and intervention is closed, the potential impact of ASD screening on improving outcomes for individuals with ASD will not be realized.

More needs to be done to raise awareness in the practitioner community of the current capabilities and benefits of early, repeated screenings, early diagnosis, and early intervention. Although not within the scope of a research plan, the severe lack of capacity of professionals to conduct screening and diagnosis and to provide services and supports remains a major stumbling block. Currently, in the United States, over 1 percent of children are estimated to have an ASD and about 15 percent of children are identified with developmental disorders throughout childhood. Although not all developmental disorders are identifiable in the first 3 years of life, research indicates that only an estimated 2.8 percent of infants and toddlers receive early intervention services, suggesting that many children who need early intervention services are not receiving them.10 More complete data are needed to estimate the population and characteristics of children with ASD and other developmental delays that are likely to need early intervention services so that early identification leads to timely evaluation and access to services and supports.

Some progress has been made in understanding the prevalence of ASD in diverse communities, with recent results now suggesting that what initially appeared to be lower prevalence of ASD in some minority populations may instead be a reflection of less effective diagnosis of ASD in those communities.11, 12 There is still a gap, however, in understanding the reasons for disparities in access to screening, diagnosis, referral, and early intervention services. While this issue was targeted by the IACC in the 2009 IACC Strategic Plan, much more work is needed to address this gap, and it should remain the subject of intense focus.

An area of groundbreaking research for Question 1 has been the detection of ASD risk in high risk infants (infant siblings) as young as 6 months of age. Among infant siblings, differences in the development of white-matter tracts have been observed in 6-month-olds who are later diagnosed with ASD.13 A similar population of high risk infants has also been shown to have significant delays in postural development, including slower emergence and mastery of advanced postures such as sitting and, later, standing.14 Additionally, differences in the developmental trajectories of visual attention to social stimuli were identified as a marker of those infant siblings who later developed ASD. Eye tracking technology that gives children a choice between looking at moving geometric patterns or human faces was found to reliably distinguish children with ASD, who prefer to look at the geometric images, as young as 14 months of age.15 A decline in a child's visual attention to the eyes of others during social interactions when he/she is 2 to 6 months of age is another biomarker of infants who are later diagnosed with ASD.16 These exciting results suggest new potential screening tools based on eye tracking technology, which, like other existing tools, must now be validated in other high risk populations and in the general population. If proven efficacious, these tools must be modified for broader use in order to be beneficial to the wider community.

At the molecular level, there has been significant progress in identifying genetic differences in ASD. Mutations associated with genetic risk for ASD can now be identified in about 30 percent of individuals diagnosed with ASD.17–23 This increase in the capability to link cases of ASD with specific genetic markers has risen substantially over the past 5 years, and further progress is anticipated. In order for these genetic markers to be useful from a screening perspective, they too will need to be validated in general populations. Such an advance could also help address the issue of adult diagnosis. It is noteworthy that the overwhelming majority of screening and diagnostic tools currently under development are designed for and are being tested in infants and children, but there is a scarcity of tools that can be used effectively in adults. More effort needs to be focused on developing, adapting, and validating screening and diagnostic tools for use across the lifespan.

Advances in capabilities to detect ASD early create a variety of legal, ethical, and social concerns, and the IACC Strategic Plan update of 2011 recommended that a workshop be held to address these issues. The NIH, the Autistic Self Advocacy Network, and Autism Speaks all held workshops that either directly or partially addressed this topic, fulfilling the original IACC Strategic Plan objective. Still, continued attention to this topic is warranted as the legal, ethical, and social implications of ASD screening will continue to evolve in response to changing technologies.

In 2013, the Diagnostic and Statistical Manual of Mental Disorders (DSM) This link exits the Interagency Autism Coordinating Committee Web site was revised for the release of its fifth edition, consolidating previous ASD diagnoses together into a single "autism spectrum disorder" category.24, 25 The new criteria in DSM-5 raised potential concerns in parts of the autism community that some people who would have previously met the criteria for diagnosis (and potentially benefitted from ASD-specific services) may no longer be diagnosed under the new criteria. Some studies have been conducted to better understand the potential implications of the change in diagnostic criteria,26–28 but more research will be needed to further assess the reliability and validity of DSM-5 ASD criteria, and to understand the impact of these new criteria on diagnosis, prevalence estimates, and access to services. In addition, diagnostic instruments must be adapted to accommodate the new criteria.

Progress Toward the Aspirational Goal:
Children at Risk for ASD Will Be Identified Through Reliable Methods Before ASD Behavioral Characteristics Fully Manifest.

Within the past 5 years, tools and technologies have emerged that have the potential capability to detect children at risk for ASD before the full manifestation of behavioral symptoms, which is the aspirational goal of this Question. The challenges that remain are to develop practical, cost effective tools that will be broadly accessible; validate and adapt these tools for use in a variety of diverse populations; support the development of the needed provider workforce; and deploy these tools so that this capability becomes a clinical reality across communities. Additionally, the link between screening and referral to intervention remains weak, but must be strengthened for the realization of the aspirational goal. Even when early screening takes place and at-risk children are identified in clinical and community settings, almost half the children are not progressing through the system to diagnosis and early intervention and face major roadblocks in the ultimate goal of accessing needed services and supports as early as possible. Future work should focus on identifying and removing the cultural and logistical impediments that may be preventing families and providers from following up on screening results that have identified a child with increased risk for ASD.

In the area of continued screening tool development, there is a need for increased investigation of risk factors in the 0-12 month age group. Currently there is no combination of genetic and behavioral markers in this age group that are reliable indicators of ASD risk. Also, the focus of the search for biomarkers has been on behavior and genetics, but this focus needs to be broadened to include a number of physiologic markers as well (e.g., sleep, autonomic measures, and neurological, metabolic/microbiome, immune, and gastrointestinal (GI) function measures). In addition, in the period prior to the development of language skills, biomarkers such as early motor tone, posture, symmetry, visual attention, and joint attention should be explored further. To improve accuracy of identification, emphasis should be placed on both direct observation and parent report.

In order to increase community usefulness of established tools, more investment is needed for community-based studies with larger sample sizes that will increase knowledge of disparities among various groups in access to screening and in applicability of screening tools. New technologies such as portable device applications (apps), electronic health records (EHRs), and video tasks will also be important for the development of innovative screening methods and screeners that could be used for diagnosis in children and adults. Finally, rigorous validation of existing tools is necessary so the community will know which ones are reliable in which populations.

True realization of the aspirational goal is dependent on progress on the other Questions of the IACC Strategic Plan. While all the Questions are interrelated, the success of screening and diagnosis in terms of its benefit for those identified will depend most heavily on the development and deployment of effective interventions (Question 4) and services (Question 5) that address the needs of the whole spectrum, including those with mild or moderate levels of disability. In addition, while the aspirational goal of Question 1 focuses on early diagnosis in children, there is also a need to greatly strengthen efforts to develop and adapt diagnostic tools for use in adult populations, addressed in Question 6 of the IACC Strategic Plan, in order to enhance the potential to reduce disability and improve quality of life across the lifespan.


Question 1 Cumulative Funding Table

IACC Strategic Plan Objectives 2008 2009 2010 2011 2012 Total
Develop, with existing tools, at least one efficient diagnostic instrument (i.e., briefer, less time intensive) that is valid in diverse populations for use in large-scale studies by 2011.

IACC Recommended Budget: $5,300,000 over 2 years
1.1
$75,000
2 projects

1.S.A
$4,728,120
15 projects

1.S.A
$4,963,192
15 projects

1.S.A
$2,387,955
8 projects

1.S.A
$2,214,544
8 projects

$14,368,811
1.S.A. Funding: The recommended budget was met. Significantly more than the recommended minimum budget was allocated to projects specific to this objective.

Progress: Though several projects are underway to develop efficient screeners and diagnostic tools, the overarching aim of this objective has not yet been achieved.

Remaining Gaps, Needs, and Opportunities: In addition to efficiency, emphasis should be placed on developing cost-effective, performance-based tools, and on validating these across diverse populations. Recent RFAs issued by NIMH and Autism Speaks that focus on parental engagement and early access to care could result in projects that address this objective. Currently, many screening tools exist, and these tools in many cases can be adapted for broader uses, but improved diagnostic tools remain an outstanding need.
 
Validate and improve the sensitivity and specificity of new or existing screening and diagnostic tools, including comparative studies of general developmental screening versus autism-specific screening tools, in both high-risk and population-based samples, including those from resource-poor international settings and those that are diverse in terms of age, socio-economic status, race, ethnicity, gender, characteristics of ASD, and general level of functioning by 2012.

IACC Recommended Budget: $5,400,000 over 3 years
1.2
$1,246,922
8 projects

1.S.B
$3,973,711
11 projects

1.S.B
$2,443,557
11 projects

1.S.B
$970,284
9 projects

1.S.B
$2,126,824
12 projects

$10,761,298
1.S.B. Funding: The recommended budget was met. Significantly more than the recommended minimum budget was allocated to projects specific to this objective.

Progress: Efforts to validate screening tools in diverse populations have begun, including ACF and CDC-funded work with a general developmental screener in Native American populations. More efforts are needed, however, to cover other diverse populations.

Remaining Gaps, Needs, and Opportunities: There is a need for more comparative studies between general developmental screeners and autism-specific tools. Remaining needs in this area are promotion of family engagement and follow-through, training of intervention and primary care providers and family members, and development of free and validated diagnostic tools for international communities.
 
Conduct at least three studies to identify reasons for the health disparities in accessing early screening and diagnosis services, including identification of barriers to implementation of and access to screening, diagnosis, referral, and early intervention services among diverse populations, as defined by socioeconomic status, race, ethnicity, and gender of the child, by 2012.

IACC Recommended Budget: $2,000,000 over 2 years
N/A

1.S.C
$139,072
1 project

1.S.C
$0
0 projects

1.S.C
$28,000
1 project

1.S.C
$629,521
3 projects

$796,593
1.S.C. Funding: The recommended budget was partially met.

Progress: The projects supported are only a beginning and more needs to be done to address this objective.

Remaining Gaps, Needs, and Opportunities: The studies coded to this objective do not focus on identifying reasons for early screening and diagnosis disparities; instead, they are aimed at developing tools to address these disparities. The progress in this area is poor for autism relative to other disease fields, and the more sophisticated approaches employed in fields such as AIDS prevention should be applied to autism. More work should be done to identify the reasons for disparities and to validate the tools that are being developed. A barrier to progress is the need for qualitative studies and the difficulty in securing funding for such studies.
 
Conduct at least two studies to understand the impact of early diagnosis on choice of intervention and outcomes by 2015.

IACC Recommended Budget: $6,000,000 over 5 years
N/A

1.S.D
$0
0 projects

1.S.D
$0
0 projects

1.S.D
$0
0 projects

1.S.D
$0
0 projects

$0
1.S.D. Funding: There has been no specific funding for this objective.

Progress: No projects that are specifically targeted to this area have been initiated, though there are some projects coded to Question 4 that represent progress on this objective (e.g., Early Start Denver Model studies that study children who were diagnosed early and some of their outcomes following treatment, and studies coded to 4.S.F. that investigate early interventions for toddlers with ASD).

Remaining Gaps, Needs, and Opportunities: The Planning Group felt that the wording of this objective is confusing. Based on transcripts from when this objective originated, it appears that the committee wanted to better understand if early diagnosis led to early intervention, and if so, if that led to better outcomes. Some of the questions that could be asked are whether or not early diagnosis leads to early intervention, and whether or not early diagnosis is always associated with better outcomes when compared to late diagnosis, or if the outcomes depend on the type of early intervention used. In future revisions of the Strategic Plan, the committee may want to refocus this objective.
 
Conduct at least one study to determine the positive predictive value and clinical utility (e.g., prediction of co-occurring conditions, family planning) of chromosomal microarray genetic testing for detecting genetic diagnoses for ASD in a clinical setting by 2012.

IACC Recommended Budget: $9,600,000 over 5 years
N/A

N/A

1.S.E
$2,180,042
3 projects

1.S.E
$690,019
1 project

1.S.E
$1,273,122
4 projects

$4,143,183
1.S.E. Funding: The recommended budget for this objective was partially met.

Progress: Microarray testing is now recommended in AAP guidelines. The utility of this testing is more clear in cases where there is already a concern than for diagnostic use in the general population.

Remaining Gaps, Needs, and Opportunities: There is a need to better understand the relationship of genotype to phenotype, implications of genotype for treatment or medical management options, and to understand the potential impact of microarray testing on providers and families.
 
Convene a workshop to examine the ethical, legal, and social implications of ASD research by 2011. The workshop should define possible approaches for conducting future studies of ethical, legal, and social implications of ASD research, taking into consideration how these types of issues have been approached in related medical conditions.

IACC Recommended Budget: $35,000 over 1 year
*This objective was completed in 2011
N/A

N/A

1.S.F
$0
0 projects

1.S.F*
$71,489
1 project

1.S.F*
$0
0 projects

$71,489
1.S.F. Funding: The recommended budget for this objective was met.

Progress: The objective was accomplished as the committee intended. NIH held a workshop, "The Ethical, Legal and Social Implications of Autism Spectrum Disorder Research," ASAN held a symposium This link exits the Interagency Autism Coordinating Committee Web site of the same title on this topic, and Autism Speaks held a related conference, "Ethics of Communicating Scientific Findings of Autism Risk." This link exits the Interagency Autism Coordinating Committee Web site

Remaining Gaps, Needs, and Opportunities: Although the workshop called for was completed, this area remains of interest due to the ethical concerns that will continue to arise as screening tools progress. Responsible communication of risk and examination of barriers to care and services for positively screened patients are among these concerns. This topic should be revisited continually to address issues that may arise as the field advances. Additional workshops would be one way to continue to work on these issues.
 
Identify behavioral and biological markers that separately, or in combination, accurately identify, before age 2, one or more subtypes of children at risk for developing ASD, and evaluate whether these risk markers or profiles can improve early identification through heightened developmental monitoring and screening by 2014.

IACC Recommended Budget: $33,300,000 over 5 years
1.3
$2,885,940
14 projects

1.L.A
$16,465,034
43 projects

1.L.A
$13,270,045
45 projects

1.L.A
$12,416,466
43 projects

1.L.A
$12,894,621
40 projects

$57,932,106
1.L.A. Funding: The recommended budget was met. Significantly more than the recommended minimum budget was allocated to projects specific to this objective.

Progress: More than 40 projects have been supported in this area, but most projects are still in the discovery phase. Identifying reliable early biomarkers has been challenging, but some progress has been made. More work is needed to achieve the full intent of the objective.

Remaining Gaps, Needs, and Opportunities:   Remaining research needs include continued discovery of biomarkers, linking biomarkers to treatment response, validation of biomarkers discovered in high risk populations for applicability in the general population, and evaluation of whether these biomarkers translate to improvement in screening and diagnosis real-world settings. There is also a need for biomarkers that are cost-effective.
 
Develop at least five measures of behavioral and/or biological heterogeneity in children or adults with ASD, beyond variation in intellectual disability, that clearly relate to etiology and risk, treatment response and/or outcome by 2015.

IACC Recommended Budget: $71,100,000 over 5 years
1.4
$5,773,203
18 projects

1.L.B
$8,760,010
34 projects

1.L.B
$15,228,060
52 projects

1.L.B
$9,376,400
42 projects

1.L.B
$12,813,396
39 projects

$51,951,069
1.L.B. Funding: The recommended budget was partially met.

Progress: Over 50 projects were supported in this area. While behavioral and/or biological heterogeneity are well covered by existing projects, gaps still exist in relating these measures to etiology and risk, treatment response, and/or outcomes.

Remaining Gaps, Needs, and Opportunities: There was a discussion of whether this objective should be expanded to be compatible with the Research Domain Criteria (RDoC) now being used by NIMH, which focus on functional domains rather than disorder-specific characteristics.
 
Identify and develop measures to assess at least three "continuous dimensions" (i.e., social reciprocity, communication disorders, and repetitive/restrictive behaviors) of ASD symptoms and severity that can be used by practitioners and/or families to assess response to intervention for people with ASD across the lifespan by 2016.

IACC Recommended Budget: $18,500,000 over 5 years
1.5
$912,159
2 projects

1.L.C
$861,069
6 projects

1.L.C
$3,893,622
22 projects

1.L.C
$2,353,440
15 projects

1.L.C
$2,600,028
15 projects

$10,620,318
1.L.C. Funding: The recommended budget was partially met.

Progress: Basic science and clinical aspects of the research are underway, but more work is needed for the studies to be applied for use by practitioners and/or families.

Remaining Gaps, Needs, and Opportunities: There is a need for finer ways to quantify social behavior and detect change in response to successful treatment. There is a need to move toward performance-based measures and away from the checklist approach.
 
Not specific to any objective (Core/Other Activities) 1.Core/Other Activities
$18,229,985
63 projects

1.Core/Other Activities
$9,766,926
37 projects

1.Core/Other Activities
$3,643,562
18 projects

1.Core/Other Activities
$2,310,877
16 projects

1.Core/Other Activities
$2,175,749
13 projects

$36,127,099
Total funding for Question 1 $29,123,209
107 projects
$44,693,942
147 projects
$45,622,080
166 projects
$30,604,930 136 projects $36,727,805
134 projects
$186,771,966

Table 1: Question 1 Cumulative Funding Table, see appendix for a color-coding key and further details.

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Suggested Citation
Interagency Autism Coordinating Committee (IACC). IACC Strategic Plan for Autism Spectrum Disorder (ASD) Research —2013 Update. April 2014. Retrieved from the U.S. Department of Health and Human Services Interagency Autism Coordinating Committee website: http://iacc.hhs.gov/strategic-plan/2013/index.shtml.


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