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

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Question 4: Which Treatments and Interventions Will Help?

Introduction

Aspirational Goal: Interventions will be developed that are effective for reducing both core and associated symptoms, for building adaptive skills, and for maximizing quality of life and health for people with ASD.

A review of the state of the science in 2009 noted that many treatments were in use, but little rigorous evidence existed to support their safety or efficacy.1 At that point, the Committee identified intervention research needs from two quite different approaches. One approach, dependent on progress in the basic and translational research areas covered under Questions 2 and 3, called for novel, targeted interventions based on an understanding of the molecular mechanisms of ASD. The other approach, related to the applied research and real-world deployment of tools and services covered in Questions 5 and 6, called for rigorous studies to test the efficacy and safety of interventions that were already in wide use, including behavioral and complementary medicine approaches.

Question 4 in the 2009 IACC Strategic Plan included six objectives, with an additional six objectives (including some with multiple parts) added in the revisions in 2010 and 2011. Altogether, the most recent version of the IACC Strategic Plan recommended a wide range of studies under Question 4, including 19 randomized clinical trials, 20 model system studies to identify treatment targets, and one workshop. The total recommended budget was $283 million across all 12 objectives.

Progress Toward Strategic Plan Objectives

The 2011-2012 IACC Portfolio Analysis reviews ASD projects funded by both government agencies and private organizations from 2008 to 2012. Based on this analysis, the cumulative investment in projects categorized in Question 4 from 2008 to 2012 was $309 million. Focusing on 2009 to 2012, the period after publishing the 2009 IACC Strategic Plan, the total investment was $255 million. This means that on average, the yearly investment in the research area targeted by Question 4 during this period was 18 percent higher than in 2008 ($54 million). It is important to note that from 2009 to 2012, roughly 90 percent of the investments assigned to Question 4 aligned with one of the 12 objectives, which address gap areas in the portfolio, and about 10 percent of the objectives address core/other activities that were not specific to any objective and may represent emerging areas of research not yet captured by the IACC Strategic Plan objectives.

Because most clinical trials require several years for completion, the snapshot of 2012 may be helpful for assessing the current cross-agency portfolio of activities relating to treatments and interventions for ASD. There were 269 projects funded in 2012 at a cost of $64 million, with 240 projects distributed among each of the 12 objectives and 29 projects ($3.9 million) assigned to core/other activities, thus demonstrating the broad range of research currently taking place in this area.

The research portfolio related to four of the objectives was considered to have met the recommended budget and number of projects, including those that called for randomized controlled trials (RCTs) addressing co-occurring conditions, development of model systems, early intervention trials, and studies on interventions for non-verbal/minimally verbal individuals. Eight objectives partially met their recommended number of projects and/or budgets. These objectives included testing safety and efficacy of interventions, investigating biological signatures, health promotion, medication trials, interventions to prevent recurrence in siblings, medications to treat co-occurring conditions, community studies evaluating intervention effectiveness, and a workshop on clinical subtypes and treatment personalization (with regard to the last objective, it was deemed only partially met because the relevant workshops and activities that took place were not exclusively focused on the topic mentioned in the objective, though some of the activities incorporate not only meetings/discussion, but also implementation of projects). 

As noted above, there were 269 active projects in 2012 that were responsive to Question 4, with the large number of studies reflecting the wide variety of research into treatments and interventions for ASD. Despite the numerous avenues currently being pursued, however, many funded psychosocial, behavioral, medication and other biomedical intervention trials are being conducted with small budgets, suggesting that these projects are under-powered to provide the needed evidence for efficacy or safety. It is important to note that some of these projects are exploratory, and thus are appropriately funded with smaller budgets as an initial step, prior to larger scale investment if the strategies yield promising results. Additionally, the absence of therapeutic targets or consensus outcome measures makes interpretation of positive or negative results difficult, although as this field matures and the research moves forward, this problem is likely to resolve.

Again, reflecting the very early stage of intervention development for ASD, nearly one-third of the funding aligned with Question 4 was invested in one objective: the standardization and validation of model systems (such as cellular and animal models) to identify molecular targets or circuits for treatment development. Several objectives that address the assessment of current treatments received less investment. In particular, testing the safety and efficacy of widely-used treatments ($1.3 million in 2012) and studies of interventions for either secondary conditions ($1 million in 2012) or co-occurring conditions (less than $1 million in 2012) received relatively little investment, indicating a need to increase work in these areas. In developing the IACC Strategic Plan, the Committee emphasized the need for research to develop treatments for those most severely disabled by ASD, including those who are minimally verbal. Encouragingly, examination of the research portfolio showed strong growth in research on minimally verbal ASD, reflecting the interest of the research community in seeking to develop new approaches to help this population. Continued investment in this area will be vital to progress.

Overall, there has been considerable activity on Question 4 since the launch of the IACC Strategic Plan in 2009. While the overall financial investment roughly matches and, in many areas exceeds, the recommendations put forth in the IACC Strategic Plan, it is too early to assess the impact of these investments. Although clinical trials of pharmacological interventions for core symptoms of ASD are now underway, they require several years for completion, analysis, and reporting, resulting in very few published findings to date.2 Preclinical studies, which have a shorter delivery time have, however, yielded some remarkable insights, especially on mice with mutations that model syndromic forms of ASD, such as Fragile X or Rett Syndrome.3, 4 In affected mice, experimental treatments reverse the syndrome both in development and in adulthood.5 While these studies give hope, the relationship of syndromic autism (ASD caused by known genetic syndromes) to idiopathic autism (autism of unknown cause) is not clear. Furthermore, in many areas of neuroscience, efficacy of treatments in mice has not translated into efficacy of treatments in human patients. In summary, while there have been significant advances in the areas of genetics and neurobiological studies, the advances have not yet been translated into a full pipeline of molecular, cellular, and systems targets for interventions. The recent interest of pharmaceutical companies in investing in autism has been an encouraging development, as partnerships between government, nonprofit organizations and pharmaceutical companies will be essential to filling the pipeline toward development of new pharmacotherapies for ASD.

The clinical research agenda is also very much a work in progress. The development of Autism Speaks' Autism Treatment Network (ATN) This link exits the Interagency Autism Coordinating Committee Web site and the entry of industry into this area are both promising changes, providing potential venues and support for future trials. While in 2008, only six clinical trials for ASD were listed in ClinicalTrials.gov, currently there are 92 ASD intervention trials recruiting subjects in the United States, including pharmacological studies to address core symptoms.

Recent developments in clinical trials on the use of the naturally occurring hormone oxytocin to address social impairments have yielded promising results. In an initial pilot RCT funded by Autism Speaks, researchers administered oxytocin nasal spray or a placebo to 25 children and teens twice a day for 2 months.6 The children who received oxytocin showed greater improvement in social behaviors compared to those who received the inactive nasal spray. Preliminary results from a larger, follow-on, NIH-funded clinical trial have demonstrated that a single spray of intranasal oxytocin can normalize brain function when performing social tasks, suggesting that oxytocin may be able to enhance social function in children.7 Further research on the efficacy of oxytocin therapy alone and in combination with behavioral therapy will be important areas for future study.

In addition to research on treating core symptoms, other efforts are providing insights into managing the symptoms associated with co-occurring conditions such as attention deficit hyperactivity disorder (ADHD),8–10 epilepsy,8, 9, 11, 12 and disturbances in sleep,13–17 immunity,18, 19 metabolism,20–24 and gastrointestinal (GI) function.25–28 Reflecting the growing focus on co-occurring conditions, in 2012, the Health Resources and Services Administration (HRSA) funded the Autism Intervention Research Network for Physical Health (AIR-P) and the ATN published empirically-validated physician guidelines for the assessment and treatment of GI, sleep, and ADHD symptoms in children with ASD.17, 27–34 In addition, the American Academy of Pediatrics (AAP) This link exits the Interagency Autism Coordinating Committee Web site  published guidelines for treatments of core symptoms, associated symptoms, and the use of complementary and alternative treatments.35

Several clinical trials of behavioral interventions were completed in the last 5 years with some notable successes. These early behavioral intervention trials demonstrated efficacy for significantly improving cognitive, language, and social abilities, as well as adaptive behavior, and have indicated that the improvements seen are maintained over time.36–41 For example, the Early Start Denver Model (ESDM) This link exits the Interagency Autism Coordinating Committee Web site has been shown to be effective in improving cognitive, language, social, and adaptive behaviors as well as in reducing the severity of ASD diagnosis.36, 41 In order to facilitate translation of the ESDM to the community, ongoing effort is focusing on alternate delivery of the intervention, such as through telehealth, community group settings, and parent-delivered approaches.37, 41 Another recent trial of a low intensity and brief intervention called JASPER (Joint Attention Symbolic Play Engagement and Regulation) This link exits the Interagency Autism Coordinating Committee Web site demonstrated significant improvement compared with community treatment.38 The relatively lower intensity of the intervention suggests that JASPER could be widely implemented.

Progress also is being made in educational intervention research. A recent comparative study of LEAP (Learning Experiences and Alternative Program for Preschoolers and their Parents), TEACCH (Treatment and Education of Autistic and Related Communication Handicapped Children), and non-model specific special education intervention approaches showed that in high-quality special education classrooms, all approaches were effective in improving symptom severity, as well as social, behavioral, and communication skills.42 The study found that the quality of the classroom, rather than the specific intervention method, was the most important indicator of how much the child's symptoms improved. Future work on educational intervention approaches will be important not only to develop effective strategies, but also to learn which approaches will work best in specific subsets of children or in particular settings.

As progress on the development of interventions continues, research into biomarkers remains a high priority, and is vital to success in this field. First, identification of molecular and behavioral biomarkers of ASD would help to stratify the population so that treatments could be targeted to those who are most likely to benefit. For example, while as many as 50 percent of children will respond well to behavioral interventions, there is still a lack of biomarkers that can accurately predict response and help match individuals with appropriate treatments.

Additionally, biomarkers are essential as key indicators to establish when therapies are working. Biomarkers showing treatment response can be used to help researchers determine the best age and the best dose (in the case of behavioral interventions, low versus high intensity) at which to deliver therapy to achieve the maximum benefit in terms of brain and behavioral development of children with ASD. Along these lines, a recent study demonstrated that early intensive behavioral intervention correlated with positive change in EEG activity that was associated with improvements in social behavior, providing the first demonstration of a physiological biomarker to indicate the effect of a behavioral treatment.43

Additional biomarkers of treatment success are needed. Until it becomes possible to biologically measure treatment response, negative results from pharmacological and behavioral interventions will be difficult to interpret and positive results may not definitely indicate the requisite dose or duration of treatment. In addition to an improved ability to measure the initial response to treatments, there is also a need for longitudinal studies to evaluate the long-term outcomes of treatments and interventions, including measures of quality of life.44 In summary, autism treatment research remains a young field that shows promise, and the focus must now be on identification of consensus outcome measures (including biomarkers) that are both robust and sensitive to change.

A wide range of treatments with varying degrees of evidence to support them are widely used for ASD. The "practice to research" approach, in which information on interventions that are already in use is collected from large health care systems, registries, from clinical networks such as the ATN, and through virtual, self-reporting networks such as the Interactive Autism Network (IAN), This link exits the Interagency Autism Coordinating Committee Web site could prove useful for assessing current interventions in real-world settings. If fully developed for ASD, the practice to research approach promises to be a fruitful strategy for collecting data on treatment effectiveness, leading more quickly to randomizedclinical trials.

New technologies, including devices to serve as social prosthetics (to provide social feedback or information) or tools for communication assistance, are exciting opportunities for the next generation of interventions in ASD. For example, the National Science Foundation (NSF) currently funds a project to develop a robot designed to act as a social therapy tool, providing an opportunity for individuals with ASD to practice social interactions in a safe and comfortable way without the complexities that are found in human interactions. New technologies are also being used to improve communication abilities of those people with ASD who are minimally verbal. In the future, devices will likely be used in combination with behavioral interventions and medications to create personalized treatments. The combinations of devices, behavioral interventions, and medications will be a profound challenge for research design and regulatory approval, but may prove most useful for children and adults with complex needs.

Along with progress in developing interventions for ASD, there will continue to be a need for access to reliable information about interventions that can be accessed by providers and families considering intervention choices. Encouragingly, the past 5 years have seen the publication of several systematic reviews of interventions as well as the launch of new tools, such as a publicly accessible "Interventions, Treatments and Therapies for Autism" database that provides lay-friendly information about autism interventions (supported by Research Autism in the United Kingdom).45–47

Progress Toward Aspirational Goal

Interventions that are effective for reducing both core and associated symptoms, for building adaptive skills, and for maximizing quality of life and health for people with ASD, will likely need a stronger foundation from the preceding IACC Strategic Plan questions; in particular, information about the stratification of ASD into subtypes (so that interventions can be tailored) and a deeper understanding of the biology of ASD (so that interventions can be effective). While in the past, serendipitous findings based on clinical observation have led to treatments for neuropsychiatric disorders without a deep understanding of the underlying biology, it is anticipated that investment in understanding the mechanisms underlying ASD will facilitate the development of the next generation of treatments. In addition, continued improvement of behavioral, educational and technological interventions will be important. Early intervention to restore a normal developmental trajectory must remain a high priority.

There are now several medications that are being tested in RCTs that are expected to be completed in 2014 or 2015. However, to date, progress on reducing core symptoms has been most evident with early behavioral interventions. The efficacy of these treatments is powerful evidence that ASD core symptoms can be treated, even if medications or devices which might be more rapid and more accessible have yet to be developed. Looking forward, future clinical trials will need to assess quality of life measures as well as reducing symptoms. In addition, effort should be made to scale up interventions that are effective in lab settings so that they may serve the broader community.

Progress has also been made in the development of treatments for several co-occurring conditions, and this continues to be an important avenue of ASD research. Associated conditions and symptoms such as epilepsy, ADHD, anxiety and depression are already being treated effectively, with both medications and behavioral interventions, although more work to improve these approaches and explore the combination of medical and behavioral approaches is needed. Recent guidelines on the management of co-occurring conditions such as sleep disturbances, ADHD, and gastrointestinal (GI) issues are a clear sign of progress for families and providers,17, 27–30, 32–34 with the hope that more evidence-based guidelines will be developed in the future.

Future efforts will need to address the needs of the ASD population across the lifespan. Much of the effort to develop treatments to date has focused on children, yet based on the larger proportion of life that is spent in adulthood, it is possible that the number of adults with ASD may be much larger than the number of children with ASD. Future studies must include development of treatments and interventions for individuals of all ages, including adults and adolescents, as well as children. In addition, treatments must address the needs of the entire spectrum of needs, including those who are minimally verbal individuals and those with intellectual disabilities. Furthermore, interventions must be tailored to the needs of individuals from diverse communities in a manner that is culturally responsive, and parents need to have access to high quality sources of information about available interventions.

While the field of ASD intervention has made important strides in the past 5 years, the need for a wider variety of effective intervention options to meet varying needs remains an outstanding goal. Partnerships between government and private organizations and involvement of families and individuals affected by ASD in research will be essential as the community continues to work toward the aspirational goal of developing interventions that will help all people with ASD to build adaptive skills and maximize quality of life and health.


Question 4 Cumulative Funding Table

IACC Strategic Plan Objectives 2008 2009 2010 2011 2012 Total
Support at least three randomized controlled trials that address co-occurring medical conditions associated with ASD by 2010.

IACC Recommended Budget: $13,400,000 over 3 years
4.2
$4,583,171
5 projects

4.S.A
$4,733,841
6 projects

4.S.A
$3,787,700
4 projects

4.S.A
$1,826,542
4 projects

4.S.A
$2,174,124
3 projects

$17,105,378
4.S.A. Funding: The recommended budget for this objective was met.

Progress: More than three projects were funded, including trials of sleep, anxiety, seizure and gastrointestinal (GI) interventions, meeting the objective. Additional work will be needed in the future to fully address these conditions.

Remaining Gaps, Needs, and Opportunities: Sleep issues, anxiety, hyperactivity and GI issues are key co-occurring medical conditions in patients with ASD.   Although there is much more known today about sleep initiation than what was understood 5 years ago, there is little understanding of what interventions/treatments are effective for sleep maintenance or night awakening.  There is not much known concerning anxiety treatments for those with ASD, and challenges exist regarding the adaptation of anxiety treatments from outside ASD patient groups.  Research into interventions for hyperactivity may be transferred from populations outside of those with ASD (i.e., ADHD).  Though there has been an increased awareness of gastrointestinal difficulties and common symptoms among people with ASD, little is known about the etiology of autism-related GI issues.  More research on the etiology of GI issues will be needed to develop appropriate treatments/interventions.
 
Standardize and validate at least 20 model systems (e.g., cellular and/or animal) that replicate features of ASD and will allow identification of specific molecular targets or neural circuits amenable to existing or new interventions by 2012.

IACC Recommended Budget: $75,000,000 over 5 years
4.5
$15,879,827
42 projects

4.S.B
$20,162,709
70 projects

4.S.B
$23,229,501
92 projects

4.S.B
$21,606,118
89 projects

4.S.B
$21,232,514
94 projects

$102,110,669
4.S.B. Funding: The recommended budget was met. Significantly more than the recommended minimum budget was allocated to projects specific to this objective.

Progress: More than 90 projects were supported to develop animal models.

Remaining Gaps, Needs, and Opportunities: Planning Group members discussed whether the amount of investment in this area is appropriate when compared to investments in clinical trials and other later stage studies. Invited experts suggested that the current stage of scientific research in ASD requires pre-clinical research to identify targets from animal and cellular models.  Similar to cancer treatment development pathways, which spanned 20-30 years, research in ASD must invest in model systems to understand the fundamental biology from which translation to the clinic can be built.   The translational validity of research in non-human animals cannot be determined until human trials are conducted, thus the need for rapid progress to clinical studies in humans is important.
 
Test safety and efficacy of at least five widely used interventions (e.g., nutrition, medications, assisted technologies, sensory integration, medical procedures) that have not been rigorously studied for use in ASD by 2012.

IACC Recommended Budget: $27,800,000 over 5 years
4.6
$641,285
8 projects

4.S.C
$3,252,941
29 projects

4.S.C
$1,509,745
18 projects

4.S.C
$2,254,724
18 projects

4.S.C
$1,288,226
17 projects

$8,946,921
4.S.C. Funding: The recommended budget was partially met.

Progress: Several projects were funded in this area, but more work is needed, as this is an area of significant public interest.

Remaining Gaps, Needs, and Opportunities: Experts discussed the best balance between developing new treatments and testing current treatments that lack evidence, especially when funds are limited and conclusive clinical trials are expensive.  The group noted that interventions for minimally verbal children are needed; some projects on assistive communication technologies, robotics and speech processing technology to assist with social communication training are funded, but more are needed.  There are other projects related to minimally verbal autism in objective 4.S.G. Small pilot studies on nutritional therapies (i.e., GFCF diet studies) have been conducted with inconclusive outcomes, demonstrating the necessity for further exploration of nutritional interventions.  Future emphasis on scientific investment in sensory integration and assisted technologies is needed.
 
Complete two multi-site randomized controlled trials of comprehensive early intervention that address core symptoms, family functioning and community involvement by 2013.

IACC Recommended Budget: $16,700,000 over 5 years
4.7
$4,236,869
5 projects

4.S.D
$7,540,613
9 projects

4.S.D
$10,306,148
18 projects

4.S.D
$11,156,647
20 projects

4.S.D
$8,848,130
21 projects

$42,088,407
4.S.D. Funding: The recommended budget was met. Significantly more than the recommended minimum budget was allocated to projects specific to this objective.

Progress: In 2011 and 2012, ~20 trials were supported, including a mix of trial sizes. 

Remaining Gaps, Needs, and Opportunities: There is a need for both small, pilot studies and larger, robustly powered studies in this area.  Several larger studies in the past few years (e.g., Early Start Denver Model) have emerged, but most studies in this area are generally smaller than in other fields of medicine and therefore lack the power to be informative if negative or definitive if positive.  This objective also cites "family functioning" and "community living," which may have significant overlap with objectives in Questions 5 and 6 of the Strategic Plan.
 
Convene a workshop to advance the understanding of clinical subtypes and treatment personalization (i.e., what are the core symptoms to target for treatment studies) by 2011.

IACC Recommended Budget: $50,000
* This objective was partially completed in 2011
N/A

4.S.E
$0
0 projects

4.S.E
$0
0 projects

4.S.E*
$26,000
1 project

4.S.E*
$0
0 projects

$26,000
4.S.E. Funding: The recommended budget was partially met, but was not put toward a single dedicated workshop.

Progress: Two workshops and other activities that have partially addressed this issue have taken place, but to date there has not been a dedicated workshop on this issue, so this objective is marked "yellow."

Remaining Gaps, Needs, and Opportunities: Autism Speaks held two relevant workshops. The first, that took place on January 2011, "Outcome Measures for Clinical Trials with Individuals with ASD: Challenges and Opportunities," was focused on developing strategies for advancing clinical trials of medications for ASD core and associated symptoms.  The second, "Translational Medicine Research in ASD: Challenges and Opportunities," that also took place in January 2011 focused on the basic science needed to discover and develop new treatments. Biomarkers and treatment personalization were among the topics discussed in both workshops.  The EU-AIMS public-private consortium in Europe is working toward "developing and validating translational approaches for the advancement of novel therapies to treat ASD."  Identification of biomarkers of subtypes of ASD and personalization of interventions are within the consortium's goals.  Joint meetings between EU-AIMS and the Foundation for NIH Biomarkers Consortium, another recently-formed consortium around biomarkers and personalized treatments, are ongoing to determine the opportunities for collaboration on identifying surrogate markers for ASD treatment studies.  Thus, while a dedicated workshop on clinical subtypes has not taken place, some of the present activities are discussing and implementing projects related to this topic. 
 
Launch randomized controlled trials of interventions including biological signatures and other measures to predict response, and monitor quality of life and functional outcomes in each of the following groups:
  • Five trials in infants and toddlers by 2013.

    IACC Recommended Budget: $30,000,000 over 5 years (revised in 2010)
  • Three trials in school-aged children and/or adolescents by 2013.

    IACC Recommended Budget: $18,000,000 over 5 years (revised in 2010)
  • Three trials in adults by 2014.

    IACC Recommended Budget: $18,000,000 over 5 years

Total IACC Recommended Budget: $66,000,000 over 5 years

4.3 & 4.4
$12,109,516
16 projects & 30 projects

4.S.F
$9,791,270
42 projects

4.S.F
$7,575,212
30 projects

4.S.F
$5,445,599
23 projects


4.S.F
$6,255,438
21 projects


$41,177,035
4.S.F. Funding: The recommended budget was partially met.

Progress: The investment in projects under this objective is making good progress toward the recommended amount, with more than 20 projects funded in 2011 and 2012.

Remaining Gaps, Needs, and Opportunities: Current projects in this area are restricted to small pilot studies, which are essential to establishing a foundation prior to expansion to larger scale work.  Thus, increased investment in this area is important.   It should be noted that most RCTs in the future will incorporate some aspect of biological signatures (thus potentially presenting a challenge to future coding of projects).
 
Support at least five studies on interventions for nonverbal individuals with ASD by 2012. Such studies may include:
  • Projects examining service-provision models that enhance access to augmentative and alternative communication (AAC) supports in both classroom and adult service-provision settings, such as residential service-provision and the impact of such access on quality of life, communication, and behavior;
  • Studies of novel treatment approaches that facilitate communication skills in individuals who are nonverbal, including the components of effective AAC approaches for specific subpopulations of people with ASD; and
  • Studies assessing access and use of AAC for children and adults with ASD who have limited or partially limited speech and the impact on functional outcomes and quality of life.
IACC Recommended Budget: $3,000,000 over 2 years
N/A

N/A

4.S.G
$1,907,721
11 projects

4.S.G
$2,830,851
13 projects

4.S.G
$4,841,831
16 projects

$9,580,403
4.S.G. Funding: The recommended budget was met. Significantly more than the recommended minimum budget was allocated to projects specific to this objective.

Progress: Between 11 and 16 studies were funded annually in the years 2010-2012, but results will not be available for at least two years.

Remaining Gaps, Needs, and Opportunities: The field of research on non-verbal patients with ASD is growing, yet still requires significant work and future investment.  ASD research has historically concentrated on verbal individuals and adults, which highlights the need for increased research on minimally verbal populations.
 
Support at least two studies that focus on research on health promotion and prevention of secondary conditions in people with ASD by 2012. Secondary conditions of interest include weight issues and obesity, injury, and co-occurring psychiatric and medical conditions.

IACC Recommended Budget: $5,000,000 over 3 years
N/A

N/A

4.S.H
$225,877
2 projects

4.S.H
$222,265
1 project

4.S.H
$956,827
4 projects

$1,404,969
4.S.H. Funding: The recommended budget was partially met.

Progress: A small number of projects, but more than the recommended minimum, were funded, but further work is needed to address some of the specific issues described in the objective.

Remaining Gaps, Needs, and Opportunities: Overlap in interpretation between "co-occurring" and "secondary" conditions presents a challenge in evaluating this objective.  There is likely overlap between projects that may fit this objective and those in 4.S.A.  Areas of health promotion and disease prevention should be emphasized in this objective, as those are distinct from issues mentioned in other objectives in this Question.  It was noted that 4.S.H's emphasis on prevention and health promotion may also overlap with 5.S.D and 5.L.D on "health and safety and mortality" issues.
 
Complete at least three randomized controlled trials on medications targeting core symptoms in people with ASD of all ages by 2014.

IACC Recommended Budget: $22,200,000 over 5 years
4.8
$1,380,376
12 projects

4.L.A
$1,168,146
10 projects

4.L.A
$1,924,932
11 projects

4.L.A
$1,527,858
12 projects

4.L.A
$3,713,783
14 projects

$9,715,095
4.L.A. Funding: The recommended budget was partially met.

Progress: 10-14 studies have been funded, which is more than the minimum recommended, and momentum within the pre-clinical phases of this objective is currently building. It should be noted, however, in that many of these studies are small trials or pilot studies. 

Remaining Gaps, Needs, and Opportunities: Though there is little evidence that CNS drug development in animals will translate to humans, either in terms of toxicity or efficacy, there is still a need for investment in well-established animal model studies to identify promising molecular, cellular, or systems targets before mounting randomized clinical trials in humans. However, existing drugs for other indications may be adapted to ASD without extensive pre-clinical work, and there is also evidence for proof of concept studies for ASD (particularly those addressing core symptoms).  It is also critically important to develop appropriate outcome measures for use in trials.
 
Develop interventions for siblings of people with ASD with the goal of reducing the risk of recurrence by at least 30% by 2014.

IACC Recommended Budget: $6,700,000 over 5 years
4.9
$14,256
1 project

4.L.B
$132,263
2 projects

4.L.B
$307,349
3 projects

4.L.B
$14,256
2 projects

4.L.B
$362,987
2 projects

$831,111
4.L.B. Funding: The recommended budget was not met; the funding allocated to projects specific to this objective falls far short of the recommendation.

Progress: Only a small number of projects has been funded, and the intent of the objective has not been met to date. Research on siblings is still at an early stage, and the results, just beginning to be published, will inform future progress.

Remaining Gaps, Needs, and Opportunities:  Results from studies within this objective will emerge in the near future.  Greater understanding of the mechanisms underlying sibling development of ASD will be key before any targeted early interventions may be developed for this population.
 
Conduct at least one study to evaluate the safety and effectiveness of medications commonly used in the treatment of co-occurring conditions or specific behavioral issues in people with ASD by 2015.

IACC Recommended Budget: $10,000,000 over 5 years
N/A

4.L.C
$1,061,222
7 projects

4.L.C
$2,302,240
7 projects

4.L.C
$2,834,887
8 projects

4.L.C
$277,072
3 projects

$6,475,421
4.L.C. Funding: The recommended budget was partially met. 

Progress: A small number (3-7) of studies of pharmacological interventions for co-occurring conditions was funded. There exist many studies examining drugs that are in active use for ADHD that are now being adapted to ADHD-ASD patient groups.

Remaining Gaps, Needs, and Opportunities: There currently is much need for greater understanding of drug efficacy in ASD populations.
 
Support at least five community-based studies that assess the effectiveness of interventions and services in broader community settings by 2015. Such studies may include comparative effectiveness research studies that assess the relative effectiveness of:
  • Different and/or combined medical, pharmacological, nutritional, behavioral, service-provision, and parent- or caregiver-implemented treatments;
  • Scalable early intervention programs for implementation in underserved, low-resource, and low-literacy populations; and
  • Studies of widely used community intervention models for which extensive published data are not available.
Outcome measures should include assessment of potential harm as a result of autism treatments, as well as positive outcomes.

IACC Recommended Budget: $37,500,000 over 5 years
N/A

N/A

4.L.D
$8,756,832
32 projects

4.L.D
$6,296,024
32 projects

4.L.D
$10,186,313
45 projects

$25,239,169
4.L.D. Funding: The recommended budget was partially met, and the annualized recommended budget targets were met for all 3 years since the objective was introduced.  Therefore, the funding for this objective is on track.

Progress: 30-45 studies have been supported, which is greater than the recommended minimum of at least five studies.  Considerable work has been done under this objective, but these projects do not cover the full scope of interventions in the community. Comparing the large number of studies to the funding suggests that many small studies are being funded rather than fewer large ones.

Remaining Gaps, Needs, and Opportunities: Emphasis on both the evaluation of interventions in controlled/academic settings prior to community based studies and the translation of interventions to community-based settings is key.  Understanding of "Type 2 Translation," or transfer of research from academic settings to real-world settings is important, considering barriers to transferring academic-based interventions to clinical groups and communities. Investment is still necessary in the academic setting before successful translation to community-based interventions can occur.  For successful T2 translation to underserved communities, cost effectiveness and case coordination or case management is often helpful with uptake.  This objective also overlaps considerably with objectives in Question 5.  It is important to explore which supports are specifically executed at the community level (vs. home, schools, etc.), and to determine how they are best designed.
 
Not specific to any objective (Core/Other Activities) 4.Core/Other Activities
$14,075,905
54 projects

4.Core/Other Activities
$15,560,011
59 projects

4.Core/Other Activities
$6,290,633
49 projects

4.Core/Other Activities
$4,777,350
37 projects

4.Core/Other Activities
$3,862,655
29 projects

$44,566,554
Total funding for Question 4 $53,968,973
178 projects

$63,403,014
234 projects

$68,123,890
277 projects

$60,819,121
260 projects

$63,999,900
269 projects

$309,267,132*

Table 4: Question 4 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

1 Rossignol DA. Novel and emerging treatments for autism spectrum disorders: a systematic review. Ann. Clin. Psychiatry Off. J. Am. Acad. Clin. Psychiatr. 2009 Dec; 21(4):213–236. [PMID: 19917212]

2 Berry-Kravis EM, Hessl D, Rathmell B, Zarevics P, Cherubini M, Walton-Bowen K,Mu Y, Nguyen DV, Gonzalez-Heydrich J, Wang PP, Carpenter RL, Bear MF, Hagerman RJ. Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with Fragile X syndrome: a randomized, controlled, phase 2 trial. Sci. Transl. Med. 2012 Sep; 4(152):152ra127. [PMID: 22993294]

3 Udagawa T, Farny NG, Jakovcevski M, Kaphzan H, Alarcon JM, Anilkumar S,Ivshina M, Hurt JA, Nagaoka K, Nalavadi VC, Lorenz LJ, Bassell GJ, Akbarian S,Chattarji S, Klann E, Richter JD. Genetic and acute CPEB1 depletion ameliorate Fragile X pathophysiology. Nat. Med. 2013 Nov; 19(11):1473–1477. [PMID: 24141422]

4 Buchovecky CM, Turley SD, Brown HM, Kyle SM, McDonald JG, Liu B, Pieper AA,Huang W, Katz DM, Russell DW, Shendure J, Justice MJ. A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome. Nat. Genet. 2013 Sep; 45(9):1013–1020. [PMID: 23892605]

5 Rotschafer SE, Trujillo MS, Dansie LE, Ethell IM, Razak KA. Minocycline treatment reverses ultrasonic vocalization production deficit in a mouse model of Fragile X Syndrome. Brain Res. 2012 Feb; 14397–14. [PMID: 22265702]

6 Autism Speaks. Res. Launch Study Oxytocin Nasal Spray. This link exits the Interagency Autism Coordinating Committee Web site

7 Gordon I, Vander Wyk BC, Bennett RH, Cordeaux C, Lucas MV, Eilbott JA,Zagoory-Sharon O, Leckman JF, Feldman R, Pelphrey KA. Oxytocin enhances brain function in children with autism. Proc. Natl. Acad. Sci. 2013 Dec; 110(52):20953–20958. [PMID: 24297883]

8 Aman MG, Van Bourgondien ME, Wolford PL, Sarphare G. Psychotropic and anticonvulsant drugs in subjects with autism: prevalence and patterns of use. J. Am. Acad. Child Adolesc. Psychiatry. 1995 Dec; 34(12):1672–1681. [PMID: 8543539]

9 Coury DL, Anagnostou E, Manning-Courtney P, Reynolds A, Cole L, McCoy R,Whitaker A, Perrin JM. Use of psychotropic medication in children and adolescents with autism spectrum disorders. Pediatrics. 2012 Nov; 130 Suppl 2S69–76. [PMID: 23118256]

10 Golubchik P, Sever J, Weizman A. Reboxetine treatment for autistic spectrum disorder of pediatric patients with depressive and inattentive/hyperactive symptoms: an open-label trial. Clin. Neuropharmacol. 2013 Apr; 36(2):37–41. [PMID: 23503544]

11 Cao Z, Hulsizer S, Tassone F, Tang HT, Hagerman RJ, Rogawski MA, Hagerman PJ, Pessah IN. Clustered burst firing in FMR1 premutation hippocampal neurons: amelioration with allopregnanolone. Hum. Mol. Genet. 2012 Jul; 21(13):2923–2935. [PMID: 22466801]

12 Ntsambi-Eba G, Vaz G, Docquier M-A, van Rijckevorsel K, Raftopoulos C. Patients with refractory epilepsy treated using a modified multiple subpial transection technique. Neurosurgery. 2013 Jun; 72(6):890–897; discussion 897–898. [PMID: 23531857]

13 Adkins KW, Molloy C, Weiss SK, Reynolds A, Goldman SE, Burnette C, Clemons T, Fawkes D, Malow BA. Effects of a standardized pamphlet on insomnia in children with autism spectrum disorders. Pediatrics. 2012 Nov; 130 Suppl 2S139–144. [PMID: 23118244]

14 Buckley AW, Sassower K, Rodriguez AJ, Jennison K, Wingert K, Buckley J, Thurm A, Sato S, Swedo S. An Open Label Trial of Donepezil for Enhancement of Rapid Eye Movement Sleep in Young Children with Autism Spectrum Disorders. J. Child Adolesc. Psychopharmacol. 2011 Aug; 21(4):353–357. [PMID: 21851192]

15 Cortesi F, Giannotti F, Sebastiani T, Panunzi S, Valente D. Controlled-release melatonin, singly and combined with cognitive behavioural therapy, for persistent insomnia in children with autism spectrum disorders: a randomized placebo-controlled trial. J. Sleep Res. 2012 Dec; 21(6):700–709. [PMID: 22616853]

16 Malow B, Adkins KW, McGrew SG, Wang L, Goldman SE, Fawkes D, Burnette C. Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes. J. Autism Dev. Disord. 2012 Aug; 42(8):1729–1737; author reply 1738. [PMID: 22160300]

17 Malow BA, Byars K, Johnson K, Weiss S, Bernal P, Goldman SE, Panzer R, Coury DL, Glaze DG; Sleep Committee of the Autism Treatment Network. A practice pathway for the identification, evaluation, and management of insomnia in children and adolescents with autism spectrum disorders. Pediatrics. 2012 Nov; 130 Suppl 2S106–124. [PMID: 23118242]

18 Boris M, Kaiser CC, Goldblatt A, Elice MW, Edelson SM, Adams JB, Feinstein DL. Effect of pioglitazone treatment on behavioral symptoms in autistic children. J. Neuroinflammation. 2007 Jan; 4:3. [PMID: 17207275]

19 Akhondzadeh S, Fallah J, Mohammadi MR, Imani R, Mohammadi M, Salehi B,Ghanizadeh A, Raznahan M, Mohebbi-Rasa S, Rezazadeh SA, Forghani S. Double-blind placebo-controlled trial of pentoxifylline added to risperidone: effects on aberrant behavior in children with autism. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2010 Feb; 34(1):32–36. [PMID: 19772883]

20 Spilioti M, Evangeliou AE, Tramma D, Theodoridou Z, Metaxas S, Michailidi E,Bonti E, Frysira H, Haidopoulou A, Asprangathou D, Tsalkidis AJ, Kardaras P,Wevers RA, Jakobs C, Gibson KM. Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD). Front. Hum. Neurosci. 2013 Dec; 24(7):858. [PMID: 24399946]

21 Novarino G, El-Fishawy P, Kayserili H, Meguid NA, Scott EM, Schroth J, Silhavy JL, Kara M, Khalil RO, Ben-Omran T, Ercan-Sencicek AG, Hashish AF, Sanders SJ, Gupta AR, Hashem HS, Matern D, Gabriel S, Sweetman L, Rahimi Y, Harris RA, State MW, Gleeson JG. Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy. Science. 2012 Oct; 338(6105):394–397. [PMID: 22956686]

22 Celestino-Soper PBS, Violante S, Crawford EL, Luo R, Lionel AC, Delaby E, Cai G, Sadikovic B, Lee K, Lo C, Gao K, Person RE, Moss TJ, German JR, Huang N, Shinawi M, Treadwell-Deering D, Szatmari P, Roberts W, Fernandez B, Schroer RJ, Stevenson RE, Buxbaum JD, Betancur C, Scherer SW, Sanders SJ, Geschwind DH, Sutcliffe JS, Hurles ME, Wanders RJ, Shaw CA, Leal SM, Cook EH Jr, Goin-Kochel RP, Vaz FM, Beaudet AL. A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism. Proc. Natl. Acad. Sci. U. S. A. 2012 May; 109(21):7974–7981. [PMID: 22566635]

23 Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ, Tassone F, Hertz-Picciotto I. Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiol. Camb. Mass. 2011 Jul; 22(4):476–485. [PMID: 21610500]

24 Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tassone F, Hertz-Picciotto I. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Am. J. Clin. Nutr. 2012 Jul; 96(1):80–89. [PMID: 22648721]

25 Buie T. The relationship of autism and gluten. Clin. Ther. 2013 May; 35(5):578–583.[PMID: 23688532]

26 Buie T, Campbell DB, Fuchs GJ 3rd, Furuta GT, Levy J, Vandewater J, Whitaker AH, Atkins D, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinyo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Natowicz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010 Jan; 125 Suppl 1S1–18. [PMID: 20048083]

27 Furuta GT, Williams K, Kooros K, Kaul A, Panzer R, Coury DL, Fuchs G. Management of constipation in children and adolescents with autism spectrum disorders. Pediatrics. 2012 Nov; 130 Suppl 2S98–105. [PMID: 23118260]

28 Hyman SL, Stewart PA, Schmidt B, Cain U, Lemcke N, Foley JT, Peck R, Clemons T, Reynolds A, Johnson C, Handen B, James SJ, Courtney PM, Molloy C, Ng PK. Nutrient intake from food in children with autism. Pediatrics. 2012 Nov; 130 Suppl 2S145–153. [PMID: 23118245]

29 Coury DL, Hyman SL, Cole L, Reynolds AM, Clemons T. Gastrointestinal conditions in children with autism spectrum disorder: developing a research agenda. Pediatrics. 2012 Nov; 130 Suppl 2S160–168. [PMID: 23118247]

30 Lajonchere C, Jones N, Coury DL, Perrin JM. Leadership in health care, research, and quality improvement for children and adolescents with autism spectrum disorders: Autism Treatment Network and Autism Intervention Research Network on Physical Health. Pediatrics. 2012 Nov; 130 Suppl 2S62–68. [PMID: 23118255]

31 Mahajan R et al. Clinical practice pathways for evaluation and medication choice for attention-deficit/hyperactivity disorder symptoms in autism spectrum disorders. Pediatrics. 2012 Nov; 130 Suppl 2S125–138. [PMID: 23118243]

32 Perrin JM et al. Complementary and alternative medicine use in a large pediatric autism sample. Pediatrics. 2012 Nov; 130 Suppl 2S77–82. [PMID: 23118257]

33 Sikora DM, Johnson K, Clemons T, Katz T. The relationship between sleep problems and daytime behavior in children of different ages with autism spectrum disorders. Pediatrics. 2012 Nov; 130(Suppl 2):S83–90. [PMID: 23118258]

34 Sikora DM, Vora P, Coury DL, Rosenberg D. Attention-deficit/hyperactivity disorder symptoms, adaptive functioning, and quality of life in children with autism spectrum disorder. Pediatrics. 2012 Nov; 130 Suppl 2S91–97. [PMID: 23118259]

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

36 Dawson G, Rogers S, Munson J, Smith M, Winter J, Greenson J, Donaldson A,Varley J. Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics. 2010 Jan; 125(1):e17–23. [PMID: 19948568]

37 Eapen V, Crnčec R, Walter A. Clinical outcomes of an early intervention program for preschool children with Autism Spectrum Disorder in a community group setting. BMC Pediatr. 2013 13(1):3. [PMID: 23294523]

38 Goods KS, Ishijima E, Chang Y-C, Kasari C. Preschool based JASPER intervention in minimally verbal children with autism: pilot RCT. J. Autism Dev. Disord. 2013 May; 43(5):1050–1056. [PMID: 22965298]

39 Kasari C, Gulsrud A, Freeman S, Paparella T, Hellemann G. Longitudinal follow-up of children with autism receiving targeted interventions on joint attention and play. J. Am. Acad. Child Adolesc. Psychiatry. 2012 May; 51(5):487–495. [PMID: 22525955]

40 Landa RJ, Holman KC, O'Neill AH, Stuart EA. Intervention targeting development of socially synchronous engagement in toddlers with autism spectrum disorder: a randomized controlled trial. J. Child Psychol. Psychiatry. 2011 Jan; 52(1):13–21. [PMID: 21126245]

41 Rogers SJ, Estes A, Lord C, Vismara L, Winter J, Fitzpatrick A, Guo M, Dawson G. Effects of a brief Early Start Denver model (ESDM)-based parent intervention on toddlers at risk for autism spectrum disorders: a randomized controlled trial. J. Am. Acad. Child Adolesc. Psychiatry. 2012 Oct; 51(10):1052–1065. [PMID: 23021480]

42 Boyd BA, Hume K, McBee MT, Alessandri M, Gutierrez A, Johnson L, Sperry L,Odom SL. Comparative Efficacy of LEAP, TEACCH and Non-Model-Specific Special Education Programs for Preschoolers with Autism Spectrum Disorders. J. Autism Dev. Disord. 2013 Jun; 44(2):366–80. [PMID: 23812661]

43 Dawson G, Jones EJ, Merkle K, Venema K, Lowy R, Faja S, Kamara D, Murias M, Greenson J, Winter J, Smith M, Rogers SJ, Webb SJ. Early behavioral intervention is associated with normalized brain activity in young children with autism. J. Am. Acad. Child Adolesc. Psychiatry. 2012 Nov; 51(11):1150–1159. [PMID: 23101741]

44 Moyal WN, Lord C, Walkup JT. Quality of Life in Children and Adolescents with Autism Spectrum Disorders: What Is Known About the Effects of Pharmacotherapy? Paediatr. Drugs. 2013 Oct 24. [Epub ahead of print] [PMID: 24155138]

45 Maglione MA, Gans D, Das L, Timbie J, Kasari C; Technical Expert Panel; HRSA Autism Intervention Research – Behavioral (AIR-B) Network. Nonmedical interventions for children with ASD: recommended guidelines and further research needs. Pediatrics. 2012 Nov; 130 Suppl 2S169–178. [PMID: 23118248]

46 McPheeters ML, Warren Z, Sathe N, Bruzek JL, Krishnaswami S, Jerome RN, Veenstra-Vanderweele J. A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics. 2011 May; 127(5):e1312–1321. [PMID: 21464191]

47 Warren Z, Veenstra-VanderWeele J, Stone W, Bruzek JL, Nahmias AS, Foss-Feig JH, Jerome RN, Krishnaswami S, Sathe NA, Glasser AM, Surawicz T, McPheeters ML. Therapies for Children With Autism Spectrum Disorders. Comparative Effectiveness Review No. 26. (PDF - 5 MB) (Agency for Healthcare Research and Quality, 2011 Apr).


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All material appearing in this report is in the public domain and may be reproduced or copied. A suggested citation follows.

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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