The original IACC Strategic Plan, launched in 2009, was structured around only six Questions. In 2010, the IACC recognized that grouping the topics of research infrastructure, workforce, and ASD surveillance into a separate chapter would highlight these issues that are critically important to research success and help the Committee track investments and evaluate progress in this area in the same organized, rigorous manner that is used in the rest of the IACC Strategic Plan. Over the past 5 years, a total of $158 million dollars has been invested in building and maintaining the ASD research infrastructure to support needed research and surveillance efforts. Many of the original infrastructure needs identified in 2009 have been accomplished, but continued investment is critical in order to develop, maintain, and build on these valuable new resources. 

Progress Toward the Strategic Plan Objectives

The IACC ASD Research Portfolio Analyses reviewed projects funded by both government agencies and private foundations from 2008-2012. From 2009-2012, the total funding devoted to projects pertaining to Question 7 was $158 million. On average for each year from 2010-2012, the funding levels for this Question were doubled from the 2009 level ($16 million) and the number of funded projects was also more than twice as high. Additionally, in years 2009-2012, 27 percent of the total funding went toward core/other research projects that were not aligned with the research gaps covered by the 16 objectives in Question 7.

Of the 16 specific objectives within Question 7, 8 objectives addressing basic and clinical data sharing and dissemination, workforce expansion, and model-systems resources met or exceeded the recommended budget and fulfilled the recommended number of projects. Four objectives, concerning documenting the services available in each state, expanding biobanks, and expanding surveillance infrastructure partially met the recommended budget and had a number of projects underway. Four more objectives did not have any funding or projects. Two of these objectives, focused on a needs assessment for database linkage and a funding mechanism for rapid replication of research results, remain a high priority. The objective concerning development of a web tool for prevalence estimates was fulfilled through several projects that encompassed multiple conditions including autism; the intended goal was achieved, although it was done outside the autism portfolio. The intent of the objective to disseminate best practices in service provision through the publication of "Promising Practices" papers was not completed; this goal may have been superseded by other types of best practice dissemination methods (e.g., web pages, tool kits, presentations at conferences), so the objective in its current form was not viewed by the Committee as a high priority to continue.

Infrastructure

Over the past 5 years there has been a significant rise in data sharing among researchers, increased availability of biological samples, expanded surveillance efforts, substantial investment in building the ASD research workforce and major improvement in dissemination of research results to the community.

Databases have been developed to house and provide researchers with access to valuable research data collected from those affected by autism as well as neurotypical subjects. In addition, in 2011 the NIH Office of Autism Research Coordination (OARC) developed and launched a new database, the IACC Portfolio Analysis Web Tool, that gathers data on federal and non-profit supported ASD research-related projects together into one place, enabling broad public access to detailed information about these projects, as well as searching, sorting and graphics to facilitate further analysis and monitoring of progress over time.

The Interactive Autism Network (IAN), developed by the Kennedy Krieger Institute, is a tool designed to match scientists with research subjects to enhance the pace of research. The IAN network has also greatly facilitated rapid research on issues of symptom severity and intervention. For example, in 2011 when concerns about the impacts of autistic wandering behavior were brought to the IACC's attention through a public presentation at an IACC meeting, members of the IACC and other organizations were able to work with the IAN network within a period of 3 months to launch and complete a study involving over 1,200 children utilizing the IAN database. Results of the study indicated that almost 50 percent of children with ASD had wandered.¹ In conjunction with this rapid study, a new International Classification of Diseases (ICD-9) code to track autistic wandering in health records was almost immediately implemented and the American Academy of Pediatrics (AAP) issued new guidelines that included wandering in patient-family anticipatory guidance, alerting parents of children with ASD to the prevalence of wandering so that they could take preventive measures.²

The National Database for Autism Research (NDAR), funded by the NIH, is a rich resource that includes genomic data and imaging studies as well as other types of data for use in ASD research. NDAR has become the standard data repository for the ASD research community. In January 2010, the NIH began including an expectation for data sharing in most of its awards, requiring that human subject data be deposited in a broadly accessible database. In 2012, 81 percent of NIH-funded human subjects grants were contributing data to NDAR. NDAR also supports data sharing from other funders of autism research including the Autism Science Foundation, the Centers for Disease Control and Prevention (CDC), the Department of Defense, and the State of New Jersey. NDAR has also now linked to IAN and the Autism Speaks supported Autism Genetic Resource Exchange (AGRE)  and Autism Tissue Program (ATP),  enabling researchers to access data in those repositories.

To date, NDAR has facilitated the sharing of data on 70,000 research subjects with much more expected in the next 24 months. Also, the rich "omics" (genomics, proteomics, transcriptomics, metabolomics, etc.) and imaging datasets have been de-identified and protected in the computational cloud, enabling an unprecedented array of resources, techniques and computational software to be used collaboratively by the research community. The results of such efforts along with categorization of data into common concepts like IQ, language and executive function enable users to query and pull down data from across multiple sources and disciplines, maximizing the utility of the data and driving scientific discovery. NDAR data have been cited in publications, and access requests have been substantial. Over 300 researchers at 75 laboratories from 10 countries applied for and were granted access to NDAR in 2013. 

Aggregated data in NDAR, among its federated partners and the labs sharing data are available to the general public (see NDAR Query).³ NDAR now supports harmonized receipt of all human subjects research data, including clinical, imaging, genomics, proteomics, electroencephalogram (EEG), eye tracking, and task- based functional magnetic resonance imaging (fMRI) data. Figure 1 provides a summary of the shared research subjects data now available in NDAR. The NIMH Repository and Genomics Resource (NIMH-RGR)  is another key resource that has played an important role in supporting research by providing access to biological samples from more than 150,000 well- characterized, high quality patient and control samples from a wide-range of mental disorders, including autism. The number of samples in the NIMH Genomics Repository has increased to more than 27,000, many with extensive phenotype/genotype information. The NIMH repository has also started collecting induced pluripotent stem cell (iPS) lines and fibroblasts. In terms of DNA, this represents a two-fold increase since 2008.

In addition to genomics and cell line samples, brain tissue is another critically important resource needed to further autism research. Unfortunately, brain tissue samples have actually declined in number during the past 5 years due to a freezer malfunction in 2012 that resulted in the loss of more than half of the existing samples from the largest autism brain repository in the United States. The brains lost have not yet been replaced in terms of numbers, and it may take several years to fully recover. In 2013, only nine new ASD brains were added to existing repositories. Despite these challenges and setbacks, there is a concerted effort both publicly and privately to increase the number of brain tissue samples. In 2013, NIH launched a new NIH Neurobiobank initiative. This repository will collect and standardize brain tissue samples for research on ASD as well as other brain disorders. The initiative includes a publication to increase awareness of brain donation, "Why Brain Donation? A Legacy of Hope." (PDF - 946 KB) In addition, a group of private funders including the Autism Science Foundation, Autism Speaks,  the Nancy Lurie Marks Family Foundation,  and the Simons Foundation,  recently launched the AutismBrainNet,  a multi-site effort to increase the numbers of ASD-specific brain samples. Their efforts will also include an ASD-specific outreach and education plan to encourage tissue donation. 

Launch of NDAR Increases Number of Subjects Whose Data are Shared

Figure 1. In 2009, essentially all human subjects data being shared within the autism research community were contained in two separate databases—the Autism Speaks AGRE and ATP data repositories—and totaled approximately 4,000 subjects. In 2009, NDAR was collecting data, but its data sharing capabilities were not launched until 2010. Since the launch, NDAR has continued to both collect and make data available to researchers. By 2013, the total number of research participants for whom data were available for study through NDAR had dramatically increased, with data now available for 70,000 subjects. This includes data collected by NDAR as well as the AGRE and ATP datasets, all of which are now available through NDAR. In addition, by 2013 a wide variety of data types was available, with many subjects in the databases having multiple data types available. Examples of the kinds of data shared through NDAR include imaging data, genomes, proteomes, clinical data, and exposures data.

NIMH Repository and Genomics Resource (NIMH-RGR) Sample Summary 2008-2013

Phenotypic Category	Number of subjects with DNA/LCL/CPL1 samples	Number of subjects with samples and phenotypic2 data in distribution3 (% non-caucasian4)	Number of total affected cases in distribution (independent cases5)	Number of Multiplex families (Trios)	Number of subjects with fibroblast lines (iPSC6) in distribution
Autism (2013)	28,288	15,676 (17%)	6,278 (4,222)	1,553 (3,387)	21 (25)
Autism (2012)	27,240	14,628 (17%)	5,938 (3,906)	1,530 (3,179)	0 (0)
Autism (2011)	25,890	9,822 (24%)	4,252 (2,479)	1,431 (1,860)	0 (0)
Autism (2010)	23,421	8,601 (20%)	3,842 (2,128)	1,386 (1,630)	0 (0)
Autism (2009)	19,824	6,434 (19%)	3,001 (1,598)	1,125 (1,209)	0 (0)
Autism (2008)	14,887	6,434 (19%)	3,001 (1,598)	1,125 (1,209)	0 (0)

Table 7. Summary of sample number and type for Autism specific samples included in the NIMH Genomics Repository.¹ LCL, Lymphoblastoid Cell Line; CPL, Cryopreserved Lymphoblasts ² Phenotypic data includes clinical interviews, DIGS (Diagnostics Interview for Genetics Studies) & DSM variables.  Samples include unaffected family members.³ Distributions are NIMH sample collections with phenotypic data available for distribution to authorized investigators.⁴ Non-Caucasians include Black, Hispanic, American Indian and Asian.⁵ Subjects are unrelated.⁶ Induced pluripotent stem cell lines produced by NIMH Genomics Repository Stem Cell facility.

Surveillance

Updated estimates published in 2012 from the CDC's Autism and Developmental Disability Monitoring Network (ADDM) indicate that 1 in 88 children has been identified with ASD, based on an average taken across multiple ADDM network study sites across the United States.⁴ The ADDM network, which uses a methodology based on review of health and education records, has been the CDC's primary United States surveillance initiative. It currently includes 12 sites, and data are now available over multiple years, which enables researchers to examine prevalence trends as well as characteristics that are changing in the population and average age at diagnosis. The ADDM infrastructure has laid the foundation to expand surveillance to younger children in six ADDM sites. In addition, ADDM investigators have initiated data linkage and analytic projects to better understand characteristics of the population of children with identified ASD. These include evaluations of perinatal characteristics, parental age, medication use, participation in the juvenile justice system, hazardous air pollutant exposures, phenotypic characteristics, and changes in prevalence over time, among others. The ADDM Network has established a system to provide updated ASD prevalence estimates and has enabled a better understanding of the needs of the community. In addition to ADDM, the National Survey of Children's Health (NSCH),  using telephone survey methodology, reported ASD prevalence estimates that were consistent with ADDM estimates.⁵ The 2009-2010 National Survey of Children with Special Healthcare Needs infrastructure was used for the 2010 follow-up study, "Survey of Pathways to Diagnosis and Services," to better understand how children with ASD are identified and treated.⁶ A workshop was held in 2011 to summarize the state of the science and needs in evaluating trends in ASD prevalence.⁷

There are also many private organizations, and groups outside the United States monitoring prevalence and service data. Autism Speaks has supported a population-based screening effort at an ADDM Network site to evaluate how many children with ASD are potentially being missed by current ascertainment methods. Autism Speaks has also initiated the Global Autism Public Health Initiative (GAPH)  to support awareness and epidemiologic studies of ASD in sites around the world. There have also been efforts in the United Kingdom to examine the prevalence of ASD. A study in children using a comprehensive diagnostic assessment method found a prevalence of 1.16 in 100, and a study in adults using a population based survey and diagnostic assessment approach found a similar prevalence of .98 in 100.^8–10 In South Korea, a population based study that used diagnostic assessments found a prevalence of 1 in 38, and that two-thirds of cases of ASD identified were unrecognized and untreated, highlighting a need for improved screening, diagnosis and services.¹¹

There is increasing international focus on surveillance of prevalence and services. In 2012, the United Nations (UN) General Assembly  unanimously passed a resolution, "Addressing the Socioeconomic Needs of Individuals, Families and Societies Affected by Autism Spectrum Disorders, Developmental Disorders and Associated Disabilities,"  calling on governments around the world to monitor and report as well as improve access to healthcare, education, training, and intervention programs for persons with ASD and other developmental disabilities.¹² In 2013, the executive board of the World Health Assembly, governing body of the World Health Organization (WHO),  adopted a complementary resolution, "Comprehensive and Coordinated Efforts for the Management of Autism Spectrum Disorders."¹³ (PDF - 45 KB) These resolutions indicate growing commitment to address ASD on a global level.

Health disparities are another area of high interest within the field of surveillance. ADDM Network study results initially showed autism prevalence in some minority groups was lower than in in whites, but more recent data have begun to close the gaps with prevalence in minorities and whites becoming more similar, suggesting that the difference is not in actual prevalence but instead may reflect differences in diagnosis (e.g, later diagnosis, missed diagnosis, etc. in minority communities).^4,14–16 More research is needed to better understand the role of cultural issues, access to services and other issues in this phenomenon.

ASD is also being studied in immigrant populations to learn more about ASD in diverse populations. In 2013, results from a study of ASD prevalence among diverse populations of children in Minneapolis, Minnesota, collaboratively supported by CDC, NIH, Autism Speaks, and the Association of University Centers on Disabilities (AUCD),  showed that while Somali children had a similar prevalence of autism to white children and a higher prevalence than in non-Somali black children or Hispanic children, that the prevalence of intellectual disability among children with ASD was much higher in Somalis.¹⁷ Additional studies will be needed to understand the reasons for these differences. A study by Swedish researchers investigated the relationship between parental immigration status and risk of ASD, taking into consideration the importance of region of origin, timing of immigration and autism subtypes.¹⁸ They found that children of immigrant parents were at increased risk of ASD with intellectual disability, especially when parents immigrated from countries with a low human development index. That risk was also higher when immigration occurred around pregnancy, but elucidation of the reasons for these differences will require further research.

Despite efforts to track the age of diagnosis and increased capability to diagnose ASD earlier, the average age of diagnosis in the United States has remained relatively constant. The proportion of children being diagnosed earlier has improved, however, with ADDM data indicating that the proportion of children diagnosed by age 3 increased from 12 percent in 2002 to 18 percent in 2008.⁴ In addition, due to changes in diagnostic criteria and greater community awareness, more cases are being identified when they were initially missed. As the prevalence of ASD has increased, a greater number of children have been identified with ASD — specifically those with ASD without intellectual disability and, as mentioned earlier, among racial and ethnic minority groups. Children without intellectual disability or with fewer ASD characteristics tend to be identified at later ages. Thus, while more children are being identified, much work needs to be done to identify children with ASD and other developmental delays earlier and more equitably so that all of those in need of services can be connected to appropriate services and supports as early as possible.

The surveillance infrastructure may present opportunities for more in-depth data collection related to services, treatment, and co-occurring conditions to complement data currently collected and identify opportunities for improving diagnosis and treatment of children with ASD. A future challenge to the accuracy of trends in prevalence may result from the implementation of the new DSM-5 diagnostic criteria for ASD. Because ADDM has collected detailed descriptions of the clinical findings for each child, the system is poised to evaluate how prevalence estimates may be influenced by these updated criteria.

Future efforts must focus on encouraging more families from diverse backgrounds to participate in ASD research, join registries, and donate biological samples. Also, as the ability to collect and link data grows, it is crucial to pay greater attention to issues of privacy, security and ethical use of data. 

Progress Toward the Aspirational Goal

Progress toward the Question 7 aspirational goal to "develop and support infrastructure and surveillance systems that advance the speed, efficacy and dissemination of ASD research" has been rapid over the past 5 years. As demonstrated by the above tables, the numbers of shared subjects and samples have doubled at minimum, and in some cases increased by orders of magnitude. This increase in the availability of resources advances the speed and efficacy of ASD research. The sharing of these resources through initiatives such as NDAR, IAN, and AGRE demonstrate effective dissemination of resources, and fuel the cycle of increased research speed and efficacy. In terms of research infrastructure, the aspirational goal will be met as long as current support is continued and current momentum is maintained.

Surveillance systems have also progressed over the past 5 years, allowing the tracking of prevalence, age of diagnosis, and other trends over time. As awareness of ASD has grown in the community and diagnostic criteria have broadened, more children have been identified with ASD, especially those without intellectual disability and among racial and ethnic minority groups, who tend to be identified at later ages. Thus, while more children are being identified, advances leading to earlier identification for children across all cultural backgrounds and across the entire spectrum and will be critical to ensure that all of those in need of services can receive them as early as possible. With the surveillance infrastructure now in place, there is an opportunity to use it for more in-depth data collection related to services, treatment, and co-occurring conditions to complement data currently collected and identify opportunities for improving diagnosis and treatment of children with ASD.

The progress toward meeting the goal of dissemination and communication of autism research findings has been significant. Many government and private organizations and groups including Simons Foundation, Autism Speaks, Autism Science Foundation, Interactive Autism Network, NIH and the CDC regularly share lay-audience friendly summaries of recent research findings and new interventions to raise community awareness. Future efforts must focus on encouraging more families from diverse backgrounds to participate in ASD research, join registries, and donate biological samples. Throughout the process of ASD surveillance and infrastructure expansion, it will also be important to maintain focus on ethical issues surrounding the privacy of research participants and security of data. The initial steps toward the aspirational goal to "develop and support infrastructure and surveillance systems that advance the speed, efficacy and dissemination of ASD research" have begun, but continued investment and broader outreach will be needed to ensure that the benefits of ASD research and access to the highest quality interventions, services and supports are attainable for all communities across the United States and around the globe.

Question 7 Cumulative Funding Table

Table 8: Question 7 Cumulative Funding Table, see appendix for a color-coding key and further details.

^* This total reflects all funding for projects aligned to current objectives in the 2011 IACC Strategic Plan and incorporates funding for projects that may have been coded differently in previous versions of the Plan.

^† The totals reflect the funding and projects coded to this Question of the Strategic Plan in the particular year indicated at the top of the column. When reading each column vertically, please note that the projects and funding associated with each objective for the years 2008, 2009, and 2010 may not add up to the total at the bottom of the column; this is due to revisions of the Strategic Plan that caused some objectives to be shifted to other Questions under the Plan. The projects and funding associated with these reclassified objectives are now reflected under the Question in which they appear in the 2011 Strategic Plan.

References

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² American Academy of Pediatrics. Autism: Caring for children with autism spectrum disorders. (2013). CD-ROM

³ National Database for Autism Research. Query.

⁴ Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators & Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders--Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. Morb. Mortal. Wkly. Rep. Surveill. Summ. Wash. DC 2002. 2012 Mar; 61(3):1–19. [PMID: 22456193]

⁵ Van Naarden Braun K, Pettygrove S, Daniels J, Miller L, Nicholas J, Baio J, Schieve L, Kirby RS, Washington A, Brocksen S, Rahbar H, Rice C; Centers for Disease Control and Prevention. Evaluation of a methodology for a collaborative multiple source surveillance network for autism spectrum disorders--Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2002. Morb. Mortal. Wkly. Rep. Surveill. Summ. Wash. DC 2002. 2007 Feb; 56(1):29–40. [PMID: 17287716]

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¹² United Nations General Assembly. Resolution 67/82: Addressing the socioeconomic needs of individuals, families and societies affected by autism spectrum disorders, developmental disorders and associated disabilities. 2012 Dec;

¹³ The World Health Organization, Executive Board. Resolution EB133. R1: Comprehensive and coordinated efforts for the management of autism spectrum disorders. 2013 May;

¹⁴ Autism and Developmental Disabilities Monitoring Network Surveillance Year 2000 Principal Investigators & Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders--autism and developmental disabilities monitoring network, six sites, United States, 2000. Morb. Mortal. Wkly. Rep. Surveill. Summ. Wash. DC 2002. 2007 Feb; 56(1):1–11. [PMID: 17287714]

¹⁵ Autism and Developmental Disabilities Monitoring Network Surveillance Year 2002 Principal Investigators & Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders--autism and developmental disabilities monitoring network, 14 sites, United States, 2002. Morb. Mortal. Wkly. Rep. Surveill. Summ. Wash. DC 2002. 2007 Feb; 56(1):12–28. [PMID: 17287715]

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