Minutes of the Interagency Autism Coordinating Committee (IACC) Subcommittee for Planning the Annual Strategic Plan Updating Process Conference Call and Webinar on October 6, 2010
The Subcommittee for Planning the Annual Strategic Plan Updating Process met on Wednesday, October 6, 2010, from 9:00 a.m. to 12:00 p.m. at the Neuroscience Center in Rockville, Maryland.
Subcommittee Members and OARC Staff Participating in the Teleconference:
Thomas R. Insel, M.D., IACC Chair, National Institute of Mental Health (NIMH); Della Hann, Ph.D., Executive Secretary, Office of Autism Research Coordination (OARC), NIMH; Susan Daniels, Ph.D., Office of Autism Research Coordination (OARC), NIMH; Coleen Boyle, Ph.D., Centers for Disease Control and Prevention (CDC); Geraldine Dawson, Ph.D., Autism Speaks; Jennifer Johnson, Ed.D., (representing Ms. Sharon Lewis), Administration for Children and Families; Walter Koroshetz, M.D., National Institute of Neurological Disorders and Stroke (NINDS); Ari Ne'eman, Autistic Self Advocacy Network (attended by phone); Lyn Redwood, R.N., M.S.N., Coalition of SafeMinds; Alison Singer, M.B.A., Autism Science Foundation; Marjorie Solomon, Ph.D., M.B.A., University of California, Davis (attended by phone)
Welcome and Approval of the Minutes
Dr. Thomas Insel welcomed the committee members and introduced Dr. Colleen Boyle, who has replaced Dr. Ed Trevathan as the representative from the Centers for Disease Control and Prevention. Dr. Susan Daniels reviewed the contents of the participants' binders and the group then voted to accept the minutes of the previous subcommittee meeting on September 21, 2010, with one correction.
Discussion of the Strategic Plan Update
Dr. Insel expressed his surprise at the number of edits and new objectives the subcommittee members had proposed for the 2011 update of the Strategic Plan for ASD Research. It was his understanding that the group had agreed to avoid major rewrites in order to track progress on the existing objectives. Any revisions would be based on major scientific breakthroughs, he said, noting that no transformative findings had occurred during the year. He cautioned that an ever-changing plan would be of no use in priority setting for the research field. Ms. Ellen Blackwell had sent an email voicing similar surprise at the extensive revisions.
Mr. Ne'eman said that while he saw the benefit of holding the plan constant, the new healthcare legislation had major implications for ASD services research. Ms. Blackwell agreed, saying that some of these issues would be addressed at the Services Workshop on November 8, 2010. Dr. Walter Koroshetz put forward two options – update the existing prose or leave the plan as is and add any additional material to the end of each chapter. This will make it apparent how the plan has evolved over time and what progress is being made. Mr. Ne'eman said that he liked the idea of adding an end section on progress with a justification for new objectives but also wanted revisions to the existing language. Ms. Lyn Redwood commented on the awkwardness of updating the "What do we know?" section as an addendum and noted that members of the public responding to the Request for Information had commented on the question rather than scientific breakthroughs. Dr. Koroshetz noted that revisions to the text could result in a lengthy wordsmithing process and missing out on the opportunity to assess the plan and highlight new additions. Dr. Dawson said that much work had gone into the initial framing of the plan and that any new objectives should stem from the addition of new members or events in the past year. She said that there had been three areas of progress made in 2010: research jump-started by stimulus funds, the effort to move intervention approaches into the community, and advances in bioinformatics and infrastructure.
Ms. Alison Singer said she liked the idea of adding a "What have we learned" section to the end of each question. This would allow the IACC to track progress by keeping the existing objectives in place. Dr. Dawson said that the Autism Speaks strategic plan has a similar section on its annual accomplishments. Reviewing the ASD research funding data from the 2009 Portfolio Analysis, Ms. Singer voiced her concern that much of the funding was going to work unrelated to plan objectives. Mr. Ne'eman said that the plan should increase focus on comparative effectiveness research and long-term services and supports. He advocated making edits to the existing prose and adding a new section on recent developments. Dr. Koroshetz was asked to further explain his proposal and he described adding sections to the end of each chapter that identified new areas of opportunity and remaining research gaps. Including this information in a new section would draw added attention, he noted.
Dr. Insel recommended using the reference documents supplied (RFI comments, portfolio analysis, Summary of Advances, etc.) to create this new 1-2 paragraph section describing progress. The addendum would also be used to update older references - for example, newer studies should be cited in Question 4 to support the effectiveness of Applied Behavior Analysis (ABA) therapy. Ms. Redwood stated her concern that the subcommittee was going to disregard the line edits the subcommittee members had put effort into developing. Dr. Insel noted that a template for edits had been sent out and included developing a new section on progress fulfilling objectives. Dr. Dawson stated that the in-line edits that had been made could be collected and incorporated into this new addendum. Mr. Ne'eman said he was concerned that a more limited editing of the plan would not reflect the new representation included on the committee.
The subcommittee then voted on three editing options for the plan: (1) incorporate the line edits to the existing language of the plan, (2) put new material into an addendum section on progress, (3) include both line edits and an added addendum section for each chapter. The subcommittee voted seven to two to incorporate edits into a new section (option 2). Two members voted for option 3.
Dr. Dawson noted that developing an additional section at the end of the chapter ultimately may not be less labor intensive than incorporating line edits. Dr. Koroshetz said that developing the additional addendum section for each chapter was superior because it would provide more focus and accountability. Dr. Insel noted that the addendum would also provide a chance to reflect public comments and track funding through the portfolio analysis. Mr. Ne'eman said that more specific objectives would be needed if the existing plan was not being updated.
Discussion of the Portfolio Analysis
The subcommittee then discussed the portfolio analysis of ASD research funding in 2009. Ms. Redwood said she was concerned with the sizable proportion of funding dedicated to genetic research (17.8 percent of total funding) when other areas had received no funding. Mr. Ne'eman noted that services research and research on adults was underfunded. Dr. Jennifer Johnson said she was struck by the number of projects that were categorized as "other" and wondered whether the plan was missing important areas of research. Dr. Hann said that the committee would receive a full listing of the individual grants shortly and would then be able to determine the nature of these projects. She noted that during the 2010 update, the subcommittee had asked the Office of Autism Research Coordination (OARC) to recategorize some of the grants that they felt had been improperly coded by the funders. As background, Dr. Susan Daniels added that the plan objectives had originally been developed to address gaps in research and were not developed to cover research that was known to already be underway. Dr. Dawson asked whether projects that touch upon multiple areas might be given more than one code. She described how Autism Speaks grappled with categorizing projects that straddle several areas. Ms. Singer asked if OARC could prepare a graphic comparing recommended funding for each objective versus actual funding. Mr. Ne'eman said it would be helpful to see funding broken down by individual agency or organization and Dr. Hann said that the full grant listing would contain that data. Ms. Redwood said that mechanisms should be put in place to encourage researchers to address specific underfunded objectives in the plan. Ms. Singer discussed how to best encourage researchers to pick up projects specified in the plan, noting that they wielded "neither a carrot nor stick" for private funders. Emphasizing the time and consideration that went into creating the plan may be the best method, she said. Dr. Insel noted that NIH had used stimulus funds to release a Request for Applications (RFA) for projects listed in the strategic plan. Dr. Dawson explained that Autism Speaks annually defines targeted research emphasis areas. Proposals must include how the project corresponds to the emphasized research area.
Updates to Question One
Dr. Boyle recommended that the new addendum include references to studies stemming from the ADDM Network and a 2010 study on autism screening in pediatric practices (King, Tandon, Macias, et al., 2010). Dr. Johnson recommended including research on the early signs of autism (Ozonoff, Iosif, Baguio, et al., 2010). Dr. Insel said that Dr. Ami Klin's was doing notable work using eye gaze as an extremely early behavioral indicator for autism (with abnormal patterns detectable at as young as 2 months of age). Dr. Johnson said that the following studies would not impact the plan objectives but should be noted as important advances: research on extremely premature babies (Johnson, Hollis, Kochhar, et al., 2010), research on developmental screening in pediatric practices (King, Tandon, Macias, et al., 2010), and the recommendation on chromosomal microarrays (Miller, Adam, Aradhya, et al., 2010). The studies cited were selected for the 2010 mid-year Summary of Advances in ASD Research.
Dr. Dawson presented her proposal for two new objectives, including conducting a study to determine the clinical utility (e.g., prediction of co-morbid conditions, family planning) of chromosomal microarray genetic testing for ASD in a clinical setting and a related study to gauge the attitudes, needs, and concerns of people with ASD and their families around such genetic testing.
After discussion among the subcommittee, the term used by NIH: "ethical, legal, and social issues (ELSI)" was substituted for "attitudes needs, and concerns." Dr. Insel noted that Dr. Gerald Fischbach had been involved with the ELSI initiative at NHGRI. Dr. Koroshetz recommended two studies from the 2009 Summary of Advances for inclusion in the new Question 1 section: research showing that diagnosis is delayed in females (Kogan, Blumberg, Schieve, et al., 2009) and a study showing increased risk for ASD with advanced maternal and paternal age (Grether, Anderson, Croen, et al., 2009). Dr. Insel said that researchers were beginning to look for metabolomic markers and that the committee could create a stake in the field by developing a related objective. Dr. Koroshetz emphasized that it would be critical to validate and replicate the discovery of any potential biomarkers. Dr. Insel said that the FDA was exploring the use of metabolomic markers but that there was a need to standardize measures and replicate results.
Ms. Singer noted that many of the objectives that had migrated from Question 1 to Question 7 had received no funding. Dr. Dawson then discussed her third proposed objective to develop and test one model for autism screening and diagnosis that could be integrated into existing developmental screening practices for underserved/underrepresented communities in the U.S. and abroad.
She said that there was currently no validated model for effective screening and diagnosis. The subcommittee discussed the lack of a rapid screening instrument usable in large-scale studies and agreed that the new addendum should describe what had been accomplished to meet this goal and what gaps still existed. Mr. Ne'eman said that the committee may want to call for a version of the study conducted in the United Kingdom to determine the adult prevalence of ASD. The subcommittee noted that this objective may be better suited for Question 6 or 7. Dr. Insel stated that several papers on disparities in diagnosis had come out but that they largely focused on the detecting the disparities rather than testing solutions.
Dr. Boyle was selected as the lead to draft the addendum with input from Dr. Johnson, Dr. Koroshetz, and Dr. Dawson. Dr. Hann said that she would send a template to follow identifying what has been learned, gap areas, and potential new objectives. She asked that she or Dr. Daniels be copied on all emails discussing the edits. The subcommittee agreed to circulate the edited chapters for all subcommittee members to review before taking the recommendations before the full committee on October 22, 2010.
Updates to Question Two
Reviewing suggested edits to Question 2, Dr. Koroshetz commented that the metabolomics field was moving quickly and Dr. Insel noted that a large metabolomic study of depression had received no investors. He described a recent advance in the field - a biomarker assay had been developed that could be used as an early predictor for type II diabetes. Ms. Redwood recommended intensive study of regression and study of improvement during fever, both of which were discussed at the National Institute of Environmental Health Sciences (NIEHS) workshop on autism and the environment. The subcommittee discussed adding fever to the study of immune markers. Dr. Marjorie Solomon recommended encouraging the use of structural and functional neuroimaging. Ms. Singer noted that this was not a research topic but rather a technique but said that more work was needed to understand adolescent brain development and neurodevelopment throughout the lifespan. The subcommittee discussed how investigating dimensions of social cognition could be incorporated into the plan. The subcommittee discussed advances in discovering epigenetic changes associated with ASD and noted that Dr. Andrew Feinberg had recently published a paper on epigenetic marks that are stable predictors of BMI and diabetes risk (Feinberg, Irizarry, Fradin, et al. 2010).
Dr. Solomon volunteered to serve as the group lead with input from Ms. Redwood, Dr. Koroshetz, and Ms. Singer.
Updates to Question Three
Dr. Dawson reviewed the additional objectives she had proposed for Question 3, explaining that many related to investigating special populations. This included surveying different international populations to identify unique genetic or environmental factors that may affect ASD risk and studies of clinical populations that may have higher rates of ASD (e.g., specific ethnic groups, premature infants, and infants exposed to infection in utero). She also proposed studies to assess bioinformatic tools for use identifying environmental risk factors and studies facilitating the development of vertebrate and invertebrate models of ASD. In addition, she recommended supporting studies that use new technologies like cell phones, passive monitoring, and dermal patches to capture information about real-time environmental exposures. Many of these recommendations came from discussions at the NIEHS meeting on autism and the environment. Dr. Insel said that the draft summary paper of the meeting would be a useful resource.
Dr. Koroshetz noted the importance of focusing on the period during pregnancy and early development. Dr. Insel discussed a recent study citing epigenetic evidence for oxytocin receptor deficiency in ASD (Gregory, Connelly, Towers, et al., 2009). Mr. Ne'eman spoke about the role of social factors in increased ASD diagnosis, citing the 2010 study that found that 48 percent of the increase could be explained by social factors alone (Liu, King, Bearman, 2010). Dr. Insel noted that this still left a significant unexplained increase in ASD.
The subcommittee then discussed another 2010 study led by Dr. Bearman that investigated how social demographic changes affected autism rates (Liu, Zerubavel, Bearman, 2010). Studying concordance in identical twins, the researchers found that the social trend of having children at an older age was contributing to the rate of de novo mutations. This is an example of social change can come together with environmental change and genetics to affect ASD risk, said Dr. Dawson.
Ms. Redwood then reviewed some of her recommendations for the chapter including an objective to initiate studies investigating metabolic pathways perturbations that affect immune function, methylation, and redox homeostasis. Dr. Insel cautioned that evidence of oxidative stress had never been shown to be unique to autism and was present in schizophrenia and other psychiatric disorders. Dr. Koroshetz said that studies of oxidative stress levels needed to be replicated and that the biochemical assays used needed standardization. Dr. Hann noted that NIH rarely funds replication studies and that such work would probably need to be framed differently. Ms. Redwood then reviewed the language she had inserted related to recommendations of the National Vaccine Advisory Committee (NVAC). Mr. Ne'eman asked that ELSI be addressed again in this chapter but others felt that this would be redundant. Dr. Dawson would serve as lead for the revisions to this chapter with input from Dr. Koroshetz, Ms. Redwood, and Dr. Insel.
Updates to Question Four
Dr. Dawson discussed her proposed objectives for Question 4, starting with the recommendation to create funding mechanisms to encourage the use of evidence-based medical treatment protocols. For example, there is a need to develop guidelines on epilepsy and sleep disorder screening after ASD diagnosis. Physicians will increasingly need to make referrals for specialty care, she said. Ms. Redwood said that medical co-morbidities need to be addressed in addition to developing intervention techniques for different clinical subtypes. She also discussed the importance of developing an assessment tool for multiple therapeutic modalities. Dr. Insel noted that the term "effectiveness" should be changed to "efficacy" in one of Dr. Dawson's proposed intervention studies. The subcommittee discussed the need to heavily emphasize the importance of personalized interventions and the necessary subtyping efforts. Dr. Dawson and Ms. Redwood agreed to incorporating the edits into the chapter.
Closing Comments and Adjournment
The subcommittee was unable to review Questions 5, 6, 7 and the Introduction due to time constraints and agreed to schedule a follow-up teleconference. Dr. Insel said that the members would receive a template for developing the addendum and drafts would need to be completed in the following week. With that, the subcommittee was adjourned.
These minutes of the IACC Subcommittee for Planning the Annual Strategic Plan Updating Process were approved by the subcommittee on November 19, 2010.
I hereby certify that this meeting summary is accurate and complete.
Thomas Insel /s/
Thomas Insel, M.D.
Chair, Interagency Autism Coordinating Committee