IACC Strategic Plan Update Question 3 (Risk Factors) Planning Group Conference Call Announcement - October 30, 2013

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Topic	Topic Description
Date:	Wednesday, October 30, 2013
Time:	2:00 p.m. to 4:00 p.m. Eastern
Agenda:	The planning group for Question 3 (Risk Factors) will discuss updates for the IACC Strategic Plan.
Place:	No in-person meeting; conference call only
Conference Call:	Dial: (888) 790-3086 Access code: 4051939
Materials:	Meeting materials
Contact Person:	Ms. Lina Perez Office of Autism Research Coordination National Institute of Mental Health, NIH 6001 Executive Boulevard, NSC, Room 6182A Rockville, Maryland 20852 Phone: (301) 443-6040 E-mail: IACCPublicInquiries@mail.nih.gov
Please Note:	The conference call will be open to the public in listen-only mode. Members of the public who participate using the conference call phone number will be able to listen to the meeting but will not be heard. If you experience any technical problems with the conference call, please e-mail HelpDeskIACC@gmail.com or call the IACC Technical Support Help Line at 415-652-8023. Accommodations Statement: The meeting will be open to the public via conference call. Individuals who participate by using this electronic service and who need special assistance such as captioning or other reasonable accommodations should submit a request to the Contact Person listed on this notice at least 3 days prior to the meeting. Schedule subject to change.

No in-person meeting; conference call only. The materials for the meeting can be found here.

Time	Event
2:00 p.m.	Roll Call and Opening Remarks Susan Daniels, Ph.D. Acting Director, Office of Autism Research Coordination, National Institute of Mental Health Executive Secretary, IACC
2:15 p.m.	Discussion of Question 3 IACC Portfolio Analysis Documents and Strategic Plan Progress Reference Documents: 5-Year Strategic Plan Status Chart for Question 3 (Cumulative Funding) Distribution of funding across IACC Strategic Plan (Pie charts for 2008-2012) by Question Subcategory Pie Charts for Question 3 (2010-2012) Full project listings for Question 3 - 2011-2012 (2008-2010 project lists can be accessed from cumulative funding table via links to the Web Tool) Summary sheet for each question Discussion Questions: What progress has been made toward achieving Strategic Plan goals in terms of funding of Strategic Plan objective areas in the past 5 years? Which objectives have been partially or fully accomplished based on information available from the Portfolio Analysis documents? Which objectives received little or no funding, and why? What conclusions can be made about progress on Question 3 based on this funding information?
3:30 p.m.	Planning Group Discussion of Strategic Plan Update Process
3:45 p.m.	Wrap-up and Next Steps
4:00 p.m.	Adjournment

Roll Call and Opening Remarks
Discussion of Question 3 IACC Portfolio Analysis Documents and Strategic Plan Progress

The Interagency Autism Coordinating Committee (IACC) Subcommittee for Basic and Translational Research Strategic Plan Question 3 Planning Group, convened a conference call on Wednesday, October 30, 2013, from 2:07 p.m. to 4:10 p.m.

In accordance with Public Law 92-463, the meeting was open to the public. Susan Daniels, Ph.D., Executive Secretary, IACC, presided.

Participants:

Susan Daniels, Ph.D., Executive Secretary, IACC, Office of Autism Research Coordination (OARC), (NIMH); Matthew Carey, Ph.D., Left Brain Right Brain; Cindy Lawler, Ph.D., National Institute of Environmental Health Sciences (NIEHS) (representing Linda Birnbaum, Ph.D.); Lyn Redwood, R.N., M.S.N., Coalition for SafeMinds

Roll Call and Opening Remarks

Dr. Susan Daniels welcomed the Planning Group and members of the public and called roll. She said that this Group was charged with the update for Question 3 of the IACC Strategic Plan (What Caused This to Happen and Can It Be Prevented?). Dr. Daniels noted that the goal of this call of the Planning Group was to evaluate the status of the Question 3 objectives, by reviewing the funding and project information documents prepared by the Office of Autism Research Coordination (OARC). In the second conference call, external subject matter experts would be invited to work with the Planning Group to qualitatively assess the scientific progress made on Question 7 objectives and to identify research gaps.

Discussion of Question 3 IACC Portfolio Analysis Documents and Strategic Plan Progress

Dr. Daniels reviewed these materials, prepared by OARC, all of which are available on the IACC website. The materials included: a Compiled Objective Chart for Question 3 (2008 to 2012), an IACC Strategic Plan Funding Summary Sheet for Question 3, Project Lists for Question 3 from the IACC Portfolio Analyses (2008-2012), subcategory pie charts by year, and Strategic Plan pie charts by question and year. Projects were coded to Strategic Plan objectives in the Compiled Objective Chart. Dr. Daniels explained that a recommended budget had been provided for each objective in the IACC Strategic Plan in accordance with the Combating Autism Act in order to provide guidance to the agencies regarding how much it might cost to implement objectives developed by the Committee. Each objective was categorized using a "stoplight" approach: a red highlight indicated that zero projects and zero funding were associated with the Strategic Plan objective in a given year or across all 5 years.; a yellow highlight indicated that some projects related to the Strategic Plan objective had been funded, but the funding amount was less than the IACC recommended budget; and green indicated that the recommended budget for the Strategic Plan objective had been met. Dr. Daniels noted that the IACC Portfolio Analysis data provided for 2011 and 2012 were still draft data as the final report had not yet been published, but that the data would be finalized soon and were not expected to significantly change.

Dr. Daniels also explained that for on objectives where projects were listed but no funding was indicated, that the projects may either have received all of their funding in a lump sum in the first year with no increments in following years, or that projects could be in a no cost extension, where the project continues, but is only using funds that were allocated in a previous year (no new funding was provided in that year). She also noted that there was a subcategory of objectives called "Other," which included research projects and funding that did not map to specific Question 3 objectives, and that this represented projects that were not associated with the gap areas identified in the objectives, but instead represented other types of core projects funded by agencies and organizations.

Dr. Daniels suggested that the Group review each of the objectives to determine what has been accomplished, what gaps remain, and any barriers. (Refer to the Compiled Objective Chart for Question 3, PDF – 166 KB)

3.S.A Coordinate and implement the inclusion of approximately 20,000 subjects for genome-wide association studies, as well as a sample of 1,200 for sequencing studies to examine more than 50 candidate genes by 2011. Studies should investigate factors contributing to phenotypic variation across individuals who share an identified genetic variant and stratify subjects according to behavioral, cognitive, and clinical features. The overall recommended budget has been partially met. Ms. Lyn Redwood suggested examining the projects in detail to determine how many participants have been enrolled. She said across individuals who share an identified genetic variant. She asked how those individuals are stratified. She said that this part of the objective had not been achieved yet. Dr. Daniels reminded the Group that the purpose of this call was to focus on funding and the number of projects, not outcomes. Ms. Redwood said that they were moving in the right direction but more work was needed. Dr. Cindy Lawler said that she believed that demographic/phenotypic information was typically included in genetic variant studies. However, she noted that she had not had a chance to review the projects in detail.

3.S.B Within the highest-priority categories of exposures for ASD, identify and standardize at least three measures for identifying markers of environmental exposure in biospecimens by 2011. The overall recommended budget has been partially met. Dr. Lawler said that this is a problematic objective. It does address a gap, but the gap is not limited to autism. Therefore it is difficult to quantify progress in exposure assessment in autism. In fact, the priority exposures have not been identified yet. Projects have been funded and progress is being made in this area, but it's not necessarily specific to autism. Dr. Daniels said that part of their charge during the call was to identify research gaps and to identify possible barriers. She said that in the case of this objective, there might be projects and funding that were not captured in the Portfolio Analyses because many of the projects addressing this area are not specific to autism. Ms. Redwood questioned whether some of these projects (primarily from 2008) should be in this category, based on the titles. Perhaps NIEHS could provide more information. Dr. Lawler cited the example of NIEHS investment in the development of reliable measures of the endocrine disruptor bisphenol A (BPA). She said that it is crucial to be able to reliably measure environmental exposures, but that research on measuring BPA will help advance exposure measurement science that can be applied across a variety of fields, including autism, but that these projects will not be captured in the Portfolio Analysis because they are not specific to autism. This research, however, is needed to advance the objective. BPA is an endocrine disruptor that could be relevant to autism. She noted that work is going on about how to better measure these types of exposures.

Ms. Redwood said that she did not think that they were making progress in this area, based on the information available to the Planning Group. Dr. Lawler responded that the language of the objective does not allow for better assessment of progress. Better wording might ask about applying improvements in environmental assessments to human studies. Dr. Lawler said that she felt uncomfortable saying that there had been no progress on this objective. Dr. Daniels summarized that progress is being on the science of measuring exposures but work is needed to translate it to autism and to be adopted by autism community. Dr. Daniels suggested that this be included in the text. Ms. Redwood asked Dr. Lawler if she could share some information about this research.

3.S.C Initiate efforts to expand existing large case-control and other studies to enhance capabilities for targeted gene-environment research by 2011. The overall recommended budget has been partially met. However, the number of projects is small. Ms. Redwood said that they are moving in the right direction. She said that she had concerns about work being done in other countries because environment exposures abroad may not be relevant to the United States. Ms. Redwood said that the funding may not be adequate when compared with other objectives. Dr. Lawler noted that the aim of this objective was to expand existing larger case-control and other studies – and there are a limited number of these studies available to expand. So this objective is about capitalizing on existing studies. She said that good progress has been made on this objective. However, work needs to be continued.

3.S.D Enhance existing case-control studies to enroll racially and ethnically diverse populations affected by ASD by 2011. The overall recommended budget has been partially met. Ms. Redwood said that they really had not met the funding recommendation. Dr. Daniels pointed out that projects might have been coded to other questions/objectives but also might be relevant to other objectives. OARC was asked to determine if the Autism Center of Excellence (ACE) at the University of California at Los Angeles (UCLA) was funded in 2012. Dr. Lawler said that it did not seem that they had met the objective. Ms. Redwood said that it's unclear if the projects are on models of enrollment or are actively enrolling patients. They were curious if there were studies at the UCLA ACE that were enrolling racially and ethnically diverse populations. Dr. Daniels asked if they could think of potential barriers to this objective. She said that this could be a topic for the next call. Dr. Lawler said that there may be efforts as part of existing studies to include diverse populations, but these would not be captured in this objective because the primary aim of the studies would be captured elsewhere.

3.S.E Support at least two studies to determine if there are subpopulations that are more susceptible to environmental exposures (e.g., immune challenges related to infections, vaccinations, or underlying autoimmune problems) by 2012. The overall recommended budget has been partially met. Ms. Redwood said that the funded projects were on target, but that in her opinion, there were not enough of them. This objective required two studies and there were 33. She noted a trend toward decreased funding in later years. Dr. Daniels said that NIH had received additional funding from the American Recovery and Reinvestment Act of 2009 (ARRA) in 2008-2009, and that the higher funding levels in those years this might be a factor in causing the appearance of a decline. Ms. Redwood asked whether any studies addressed vaccinations. There were two studies in 2009 on vaccination – one on regression (Robert L. Davis, M.D., Principal Investigator) and one on immune and physiologic response in children with autism following immune challenge (at the University of California at Davis [Judy Van de Water, Ph.D., Principal Investigator]). Dr. Catherine Rice said that she would look at the project lists more closely to identify any other vaccine studies. The Group agreed that additional research work was needed. Dr. Lawler noted that it was likely that some of these studies made use of existing cohorts and might have been less expensive than projected for this reason. This might contribute to the cost/funding difference.

3.S.F Initiate studies on at least 10 environmental factors identified in the recommendations from the 2007 IOM report "Autism and the Environment: Challenges and Opportunities for Research" as potential causes of ASD by 2012. The overall recommended budget has been partially met. Dr. Daniels noted that the number of projects tailed off in later years. This may have been due to the completion of earlier studies. Dr. Lawler said that some studies may also have been coded elsewhere, but the funding direction, nevertheless, was concerning. Dr. Daniels said in addition, new objectives may have been added and that some projects originally coded to this objective could have been moved elsewhere. The CHARGE (Childhood Autism Risks from Genetics and the Environment) study was mentioned, but it was noted that this study has been funded continuously, so it was not likely to have contributed to the decline observed. Dr. Daniels also said that three projects from 2011, which had no funding, may have been no-cost extensions. Ms. Redwood noted that the studies in 2008 were essentially baseline studies for the IACC Strategic Plan. Dr. Lawler said that certain CDC studies that were listed in 2008 may have been categorized under other objectives or questions after that time. The Group agreed that this dramatic drop off in funding was very concerning, and they wanted to note this in the text. Perhaps renewed emphasis was needed in the text. OARC will check to see if projects were coded under other objectives/questions.

3.S.G Convene a workshop that explores the usefulness of bioinformatics approaches to identify environmental risks for ASD by 2011. The overall recommended budget was met. The workshop was held in 2011 at NIEHS. Dr. Lawler was involved in the workshop and said that it the workshop fulfilled the objective. Ms. Redwood asked about if there was a summary of the meeting outcomes. Dr. Lawler said that there was a report (PDF – 189 KB) from the workshop and that she would share it with IACC members.

3.S.H Support at least three studies of special populations or use existing databases to inform our understanding of environmental risk factors for ASD in pregnancy and the early postnatal period by 2012. Such studies could include: comparisons of populations differing in geography, gender, ethnic background, exposure history (e.g., prematurity, maternal infection, nutritional deficiencies, toxins), and migration patterns; and comparisons of phenotype (e.g., cytokine profiles), in children with and without a history of autistic regression, adverse events following immunization (such as fever and seizures), and mitochondrial impairment. These studies may also include comparisons of phenotype between children with regressive ASD and their siblings. Emphasis on environmental factors that influence prenatal and early postnatal development is particularly of high priority. Epidemiological studies should pay special attention to include racially and ethnically diverse populations. The overall recommended budget has been partially met. There have been 32 projects and 3 were expected. Ms. Redwood said that the recommended number of studies/budget is a "floor" value, and more studies still are needed. She also asked about the International Collaboration for Autism Registry Epidemiology (iCARE). She noted that the proposed investigation locations included Scandinavia (Denmark, Sweden, Finland and Norway), Australia and Israel. Dr. Lawler said that this effort (now based at Mt. Sinai) was originally funded by Autism Speaks and subsequently received an NIH ACE Network grant award. The researchers will analyze records and biospecimens from 20,000 cases of ASD from 7 countries. The effort has received a number of different awards to different countries, but they're all part of the same project, she said. The Group agreed that good progress is being made on this objective, but it needs to be maintained.

3.S.I Support at least two studies that examine potential differences in the microbiome of individuals with ASD versus comparison groups by 2012. The overall recommended budget has been partially met. Dr. Lawler said that they have made a good start, but that more investment in this area was needed. She noted that sequencing is very expensive. Given that, smaller pilot studies may have been funded to save money. They agreed to include this in the text, as a reason for possible gaps. These studies need to be more fully developed. Dr. Daniels asked if the NIH Human Microbiome project might be relevant. They agreed to follow up on this during the next call. The Group agreed that progress is being made, but the studies are small. Larger and more extensive studies are needed, but the cost of sequencing may be a barrier.

3.S.J Support at least three studies that focus on the role of epigenetics in the etiology of ASD, including studies that include assays to measure DNA methylations and histone modifications and those exploring how exposures may act on maternal or paternal genomes via epigenetic mechanisms to alter gene expression, by 2012. The overall recommended budget has been partially met. The Group agreed that this objective is on track, but that funding needs to continue at the same level. The Group also agreed that the number of projects appeared to be adequate. They concluded that progress on this objective is strong, but should be maintained.

3.S.K Support two studies and a workshop that facilitate the development of vertebrate and invertebrate model systems for the exploration of environmental risks and their interaction with gender and genetic susceptibilities for ASD by 2012. The overall recommended budget has been partially met. Dr. Matthew Carey noted that the funding levels have decreased over time. Ms. Redwood and Dr. Lawler agreed. Even though they have almost met the objective, there is a risk of missing the goal. He said that they need to renew the focus on this objective. It was unclear whether a workshop had occurred. Dr. Daniels noted said that gender issues might be categorized in other questions or objectives. OARC would check on this, and whether there had been a workshop.

3.L.A Conduct a multi-site study of the subsequent pregnancies of 1,000 women with a child with ASD to assess the impact of environmental factors in a period most relevant to the progression of ASD by 2014. The overall recommended budget was met and exceeded. The number of projects is low though. Dr. Daniels noted that the Early Autism Risk Longitudinal Investigation (EARLI) was included in 2012 projects. However, Dr. Lawler said that the EARLI project does not have continued funding at this time. The Group was concerned about this. They agreed that this concern should be expressed in the text of the update. Dr. Daniels said that they could note that the objective had been met through 2011, but was no longer funded. Ms. Redwood asked why the Markers of Autism Risk in Babies – Learning Early Signs (MARBLES ) study was not included. Dr. Daniels said that OARC would check to see where this study had been categorized.

3.L.B Identify genetic risk factors in at least 50% of people with ASD by 2014. The overall recommended budget was met and well exceeded. Ms. Redwood said that while they had exceeded the recommended budget, she did not think that they had made substantial progress in meeting the objective. Dr. Lawler called the objective very ambitious. There have been a number of large studies that have identified a number of genetic risks, but genetic risk factors had not identified in half of individuals with ASD in any of the large samples. Dr. Carey said that the language of this objective differs from others because there is a specified deliverable. They agreed that they could not say that this objective has been met. Ms. Redwood said that it may not be feasible to meet this objective. Dr. Daniels said that the question of feasibility would be something that they should include in the text. It was not clear if this number was even measurable because every time a new genetic factor is found, the percentages of people estimated to be affected change. Progress has been good, but the objective has not been met. Ms. Redwood said that they should focus more on epigenetic risk factors and triggers, not genetics. Dr. Carey disagreed, saying that there are a number of genetic conditions that are related, and have resulted in treatments that have improved quality of life and lifespan

3.L.C Determine the effect of at least five environmental factors on the risk for subtypes of ASD in the prenatal and early postnatal period of development by 2015. The overall recommended budget has been partially met. Dr. Carey said that there is good work being done but only a few projects seem to be more specific. Dr. Lawler said that the objective may not be achievable because of the language of the objective. Most epidemiologic studies look at subgroups. These studies may be included elsewhere. The Group agreed that these studies are good. There might be overlap with objective 3.L.A. Ms. Redwood said that the number of projects are dwindling and this is concerning. Ms. Redwood suggested that this concern of decreasing funding overall in text. Dr. Lawler said there are a number of robust larger studies but is concerned that they may be lacking smaller more innovative studies. Dr. Daniels noted that the current economic climate may have contributed to reduced funding by private funders.

3.L.D Support ancillary studies within one or more large-scale, population-based surveillance and epidemiological studies, including U.S. populations, to collect data on environmental factors during preconception, and during prenatal and early postnatal development, as well as genetic data, that could be pooled (as needed) to analyze targets for potential gene/environment interactions by 2015. The overall recommended budget was met and exceeded. The Group noted that most of the studies are related to CADDRE. This may be concerning. Dr. Lawler noted that there also could be projects categorized under other objectives. Dr. Carey pointed out that funding has been flat over time. Perhaps making use of large ongoing projects may provide a solution to limited funding.