Minutes of the Interagency Autism Coordinating Committee (IACC) Subcommittee for Basic and Translational Research Conference Call on March 6, 2013
The Interagency Autism Coordinating Committee's (IACC) Subcommittee for Basic and Translational Research (BTR) convened a conference call on Tuesday, March 6, 2013, from 2:00 p.m. to 4:33 p.m.
In accordance with Public Law 92-463, the meeting was open to the public. Dr. Thomas Insel, Co-Chair, and Dr. Geraldine Dawson, Co-Chair, presided.
Thomas Insel, M.D., Chair, IACC, National Institute of Mental Health (NIMH); Geraldine Dawson, Ph.D., Co-Chair, BTR Subcommittee, Autism Speaks; Susan Daniels, Ph.D., Executive Secretary, IACC, NIMH; Anshu Batra, M.D., Our Special Kids; Linda Birnbaum, Ph.D., National Institute of Environmental Health Sciences (NIEHS); Coleen Boyle, Ph.D., M.S., Hyg., Centers for Disease Control and Prevention (CDC); Noah Britton, M.A., Bunker Hill Community College; Matthew Carey, Ph.D., Left Brain Right Brain; Dennis Choi, M.D., Ph.D., State University of New York at Stony Brook; Jan Crandy, Nevada State Autism Treatment Assistance Program; Tiffany Farchione, M.D., Food and Drug Administration (FDA); Donna Kimbark, Ph.D., U.S. Department of Defense (DoD); Walter Koroshetz, M.D., National Institute of Neurological Disorders and Stroke (NINDS); Lyn Redwood, R.N., M.S.N., Coalition for SafeMinds; Scott Robertson, M.H.C.I., The Autistic Self Advocacy Network (ASAN); Alison Tepper Singer, M.B.A., Autism Science Foundation
Roll Call and Opening Remarks
Dr. Susan Daniels welcomed BTR Subcommittee members, IACC members, and members of the public listening to the call. Dr. Thomas Insel responded to a question from Dr. Geraldine Dawson on sequestration by saying that little has changed within the IACC and NIH. He said they were operating on a continuing resolution budget and have been since October 1, 2012; this would continue until March 27, 2013, the date by which a new budget would be needed. Dr. Daniels called the roll.
Dr. Insel said that this call was a followup to a discussion held at the last IACC meeting. The Committee agreed that much of the work of the IACC could be done by the BTR Subcommittee and the Services Research and Policy (SRP) Subcommittee. He said that the goal of this meeting was to identify and prioritize important topics and projects.
Approval of Draft Minutes for November 26, 2012
There was an unanimous motion to approve the minutes of the November 26, 2012 meeting, with two revisions (one from Ms. Lyn Redwood and one from Dr. Anshu Batra).
Discussion of BTR Subcommittee Plans for 2013
Dr. Insel said that during the last meeting, the BTR Subcommittee had identified three areas of focus. One was to develop recommendations around social communication disorder (SCD) – a new diagnosis in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 1 The BTR Subcommittee wanted to ensure that those who receive this diagnosis would not be excluded from access to services. In addition, more research is needed to understand what SCD is and how it relates to autism spectrum disorder (ASD). The second focus area was to develop ideas for updating the Strategic Plan. The Subcommittee discussed the possibilities of identifying urgent objectives and objectives with barriers or little progress. The third area was the development of a statement from the Committee about the medical research needs of people with autism, including those with limited communication abilities.
Dr. Dawson added that issues regarding the evidence base, research, and insurance were also important areas that the IACC should consider. She also noted that efforts often have been unsuccessful to ensure insurance coverage for certain practices or to have practices legitimately recognized as empirically supported. Dr. Dawson said that there were huge research gaps for adult interventions. Dr. Walter Koroshetz mentioned the hierarchy of the evidence base, including efficacy (placebo-controlled randomized trials and reproducibility) and real-world effectiveness. Dr. Dawson said that there were few effectiveness trials for autism treatments and even fewer large randomized controlled trials.
Dr. Insel pointed out that often there was insufficient rigor in many of the studies. There was also a lack of standard outcome measures to allow comparison across trials. Dr. Batra suggested that with regard to building the evidence base, there should be an emphasis on developing reliable, physiologic, nonqualitative measures for diagnosis. Perhaps these could eventually become tools for monitoring the efficacy, strengths, and weaknesses of treatment interventions. Dr. Insel noted that Committee members also have expressed concerns about the effects of diagnostic changes in DSM-5.
Ms. Redwood said that the area of medical comorbidities also needed urgent attention from the IACC to help improve the health of autistic children and adults. These medical issues included sensory issues, pain, gastrointestinal issues, and immune-system dysfunction. She noted that many physicians are hesitant to treat these conditions in individuals with autism because there are no guidelines. Ms. Redwood said that the Strategic Plan included an objective to hold a workshop that would advance the understanding of clinical subtypes and treatment personalization, but that to date, no agency or organization had held such a workshop. She said that this kind of workshop would allow the Committee to invite and learn from experts on medical comorbidities. In addition, she said that the workshop could also be an opportunity to identify effective treatments and develop practice guidelines.
Ms. Jan Crandy asked whether a guideline or a protocol for the diagnosis of ASD in children could be developed. Dr. Dawson noted that the American Academy of Pediatrics has a clinician toolkit, 2 including a brief summary of a medical workup for a child with autism. The American Academy of Neurology was developing similar guidelines.
Ms. Redwood said that underlying medical conditions often were missed because autistic children, especially nonverbal children, might not be able to communicate with the physician. She said that once these children were treated for their medical conditions, self-injurious behavior often was reduced or eliminated.
Mr. Scott Robertson asked whether such a workshop could include a discussion of the interactions between autistic individuals and the health care system, in terms of understanding medical issues. He said that some autistic adults also had trouble explaining how pain was experienced differently; health care providers might not easily understand this. Mr. Robertson also noted that there was a lack of peer-reviewed literature on pain and sensory issues and how these affected quality of life.
Dr. Dawson said that as a part of the focus on medical comorbidities, whether that took shape in a written document of the Committee, a discussion or a section of the IACC Strategic Plan, should target the adult population. She mentioned that there were new research data published on the kinds of transition services that adolescents receive as they move into adulthood (from pediatric to adult care) suggesting that only 14 percent of young people with ASD had a conversation with their physician – as they left pediatrics – about how their insurance might change or how they would find a provider. Adult health care, Dr. Dawson said, remains a huge gap for adults.
Mr. Robertson said that the Autistic Self Advocacy Network (ASAN) was creating policy briefs on people with developmental disabilities – including autistic individuals – and their interaction with the health care system. The briefs also would cover the transition from pediatrics to adult health care and how this transition could be a problem for those with intellectual developmental disabilities in general. He also mentioned that ASAN has a multiyear grant from NIMH, in partnership with the Academic Autistic Spectrum Partnership in Research and Education, to develop a toolkit and resources to help autistic adults communicate with the health care system.
Dr. Insel asked whether this subject could be framed as a research issue; the task would be to define the science gaps that should be a focus for future research projects. Dr. Dawson expressed concern about the effective dissemination of information, so that best practices were used. She also cited a number of targeted research issues. These included understanding the increased mortality rate for adults with autism (approximately six times greater than that of the general population), strategies that could be used to prevent sudden unexpected death in epilepsy (a contributor to mortality), and pain and its influence on medical care.
Ms. Alison Singer noted that the improvement of the safety of health care delivery should be another targeted research issue. Dr. Insel said that this sounded like items related to comorbidity and medical care – or autism within a broader health care framework.
Dr. Insel noted that the SRP Subcommittee was also scheduled to meet the same week. The SRP Subcommittee's initial task would be to develop a letter that would address issues of coverage in the context of the Affordable Care Act and essential benefits. However, the SRP Subcommittee's discussion would likely address many issues that were being discussed in the current BTR Subcommittee discussion.
Dr. Insel asked if there were any other research topics that the BTR Subcommittee should consider that may not be represented in the current IACC Strategic Plan or that might have not been part of the broader scientific discussion surrounding autism.
Dr. Koroshetz noted that progress has been held back by the lack of common data elements. He asked whether this was an issue that the IACC could address. Dr. Insel asked what has been done to standardize outcome measures for clinical trials (psychosocial or biomedical) and whether there was a set of best practices for demonstrating change in ASD. Dr Dawson mentioned that a series of comprehensive review was being conducted by a public-private partnership involving nonprofits, academia, pharmaceutical companies and FDA that would soon be publishing three papers regarding outcome measures for social communication, repetitive behaviors and anxiety, and that there has been progress through efforts such as NDAR, but that further work is needed. Dr. Dawson suggested that someone from the outcome measures working groups could present to the IACC. Dr. Insel asked if it had been valuable having the FDA involved in the process, and Dr. Dawson responded that yes, it had been very helpful, and that FDA was working on qualifying clinical endpoints that could be standardized for use in trials. She said that FDA was also considering whether autism should be included in a breakthrough designation to allow a faster approval process if there are no safety concerns and the drug would address urgent unmet medical needs. Mr. Scott Robertson asked if there has been consideration of sensory measurements that could be used as endpoints, and Dr. Dawson responded that thought that had not been developed so far, it was an important area.
Dr. Koroshetz asked if clinical endpoints would be a good topic for an IACC workshop, and Dr. Insel asked the group if the topic was ready for more workshops following what had already been done. Dr. Insel reminded the Subcommittee that time was limited because the IACC's authorization would end in 2014. He said that improving clinical trials by standardizing measures could be helpful. Dr. Dawson said that this line of thinking dovetailed nicely with evidence-based treatments and the need to build the evidence base for treatments.
The group continued to discuss whether some type of project could focus on improving outcome measures, improving or standardizing clinical trials overall to ensure that useful results were obtained that could further support the evidence base, or standardizing language for use in electronic medical records. Dr. Anshu Batra asked if consideration could be given to development of tools or a toolkit for helping clinicians diagnose autism and monitor the effectiveness of treatments in individual patients. Dr. Boyle asked if DSM-5 severity measures could be operationalized into outcome measures, and Dr. Dawson said that this could be done, but it would take much more research to accomplish. Mr. Robertson asked if there was any thought about developing better quality of life outcome measures. Dr. Dawson said that the FDA has emphasized that outcome measures need to have meaning from a functional context – how they affect lives. Dr. Insel commented that although there has been much innovation in this area, it has not been translated to the clinical trials arena. He noted that the IACC could potentially bring the appropriate groups together for a discussion to help develop guidelines to improve the quality of outcomes in psychosocial or biomedical trials.
Dr. Insel summarized the topics that had been mentioned in the day's discussion so far: (1) the implications of the new DSM-5 definitions of ASD and SCD; (3) the need to identify unmet research needs related to medical needs and comorbidities associated with autism, including those that affect adults; (4) the need to improve the quality of clinical trials, including the use of common data elements and outcome measures; (5) the need for a repository of research evidence to inform payers so that effective treatments can be covered by insurance and brought into practice more widely; (6) the need for development of a clinical toolkit for diagnosis and response monitoring. Dr. Dawson said that in addition to these important areas, that concerns about environmental risk factors for autism remain for many in the community, and further research on relevant topics like epigenetics and work to help community members interpret the risk associated with environmental factors that have been identified to date would be valuable. After summarizing the topics that had been discussed, the group moved on to discuss the upcoming update of the IACC Strategic Plan.
Strategic Plan Update
Ms. Alison Singer opened the discussion by saying that though the IACC had now issued several IACC Strategic Plan updates, the group had not to date gone through the objectives to prioritize them. Ms. Redwood agreed that this was important, but that in order to o this, one would first need to spend time understanding what had been accomplished under the Strategic Plan, which objectives had been met, and deciding whether or not emphasis on various objective areas should continue. Dr. Insel agreed that it would be important to determine what has been learned, what has been accomplished, and whether priorities have changed since the writing of the Plan. Ms. Redwood suggested that the Strategic Plan objectives should be evaluated in terms of how they have improved the lives of people with autism and their families. There was a discussion about whether this evaluation would occur along with prioritization or whether the prioritization should emerge from the evaluation.
Ms. Redwood asked whether they could look at cumulative funding for each objective. Dr. Daniels said that the data could be prepared in that format, but explained some of the challenges in interpreting cumulative data, given that the number and focus of the Strategic Plan objectives have changed over time. Subcommittee members discussed the process that would be involved, including steps that would need to be taken before setting priorities. The group discussed developing a two-tiered strategy to determine which objectives had been completed and then including subject matter experts and community stakeholders to provide expertise and perspectives on what has been accomplished in terms of the science and what should be prioritized in the future. Dr. Daniels explained that much of the quantitative work of determining how many projects had been funded per objective had already been done by OARC through the Portfolio Analysis, but that the qualitative assessment of how well the projects had achieved the objectives In terms of knowledge gained, etc. and what outcomes/impacts had resulted would need to be done by the Committee and any external experts invited to join the process. The group proposed developing a group to do a pilot study on one Question of the Strategic Plan to help determine a reasonable process for doing a 5-year review of the Strategic Plan.
Dr. Insel said that it would be a good idea to have the group provide feedback on what needed to be done, what a reasonable process would be, how to get the necessary information, who should be included, what the timeframe should be, and whether in-person meetings would be necessary. Dr. Coleen Boyle volunteered to be a part of the pilot and proposed that they look at Question 1 on screening and diagnosis. She said she did not think that this task would require a full meeting; a 2- to 3-hour conference call would be adequate. It would be important to identify the process and the deliverables. In addition to Dr. Boyle, Dr. Batra, Ms. Redwood, Dr. Matthew Carey, and Dr. Dawson agreed to participate in the pilot.
Dr. Batra said that impact studies often took many years. She asked whether there were any ways to speed the process of designing such studies. Dr. Insel said that NIH had increased the focus on how to get practice into research. He commented that this was one of the ways to accelerate the process. Instead of doing community, participatory-based research at academic health centers, it was more efficient to go where the health care is provided and make that the laboratory. The Committee could invite experts in this area to talk about how this approach might be applied to autism.
Dr. Dawson noted that this related to the topic of developing the evidence base for treatments. She suggested that they invite Laura Esserman, M.D., to talk to the Committee because of her work in creating adaptive clinical trials. Dr. Esserman is a breast cancer surgeon at the University of California at San Francisco. Dr. Insel mentioned the NIH's Health Care Systems Research Collaboratory and its practical trials with electronic health records from large health care systems. It was suggested that the Committee invite Gregory Simon, M.D., of the Group Health Research Institute to talk about these large-scale efforts. Dr. Dawson suggested inviting Paul A. Law, M.D., of the Interactive Autism Network (IAN). Dr. Insel suggested convening a panel for a full Committee meeting to discuss innovations that are now available to accelerate research and the development of treatments.
Dr. Insel returned the group to discussion of tasks at hand, saying that the most important task before the Subcommittee involved the Strategic Plan updates and developing a process for a review of the past 5 years of work for each of the seven questions. Dr. Boyle and Dr. Koroshetz agreed to form a planning group to work on this task using Question 1 as a test question. Dr. Insel said another short-term task would be to plan a panel for the full IACC meeting around innovations. Other topics discussed included medical comorbidities, DSM-5, the quality of clinical trials, the evidence base and how payers are informed, and environmental risk factors. He asked Subcommittee members to think about whether they would like to take on any of these topics or whether they should focus on addressing the Strategic Plan.
Dr. Insel also said that there seemed to be agreement that the Committee should address comorbidities associated with autism and unmet medical needs; this could begin with a panel at an IACC meeting. There was a brief discussion about Centers for Medicare & Medicaid Services (CMS) innovations and experiments; Subcommittee members noted that there were no autism-related applications funded under that initiative.
Dr. Dawson said she would like to develop a strategy for addressing the DSM-5 and SCD issue. This was an area of great concern because of the potential impact that this change in diagnosis could have on access to care. She volunteered to head a planning group to make an informed set of recommendations in this regard. Dr. Boyle said she would participate. Dr. Dawson said that the results of field trials that were in press were consistent with existing field studies, showing that many children who previously had a diagnosis of pervasive developmental disorder not otherwise specified now will have a diagnosis of SCD.
Dr. Insel said that it would be better to act before the May 2013 release of DSM-5 and then to monitor state systems in real time to find out how this change would affect access to care and coverage. He asked those Subcommittee members who might be interested to think through some options to present to the full Committee, so that it might make a recommendation. Dr. Insel noted that, given the pressure on state Medicaid budgets and waiver questions, this would be a significant issue.
Dr. Dawson agreed to head a planning group on DSM-5. Dr. Insel suggested they recruit someone from CMS. He also noted that because the publication was not Web based, it would be more difficult to make changes after May 2013. This made it all the more important that someone monitor the impacts and provided that information to the public.
Several members volunteered to be part of the DSM-5 Planning Group. Dr. Insel said that the DSM-5 Planning Group could report back to the Subcommittee/Committee at the April 9, 2013, IACC meeting to give them a sense of the best options for addressing this issue.
Wrap-Up and Next Steps
Dr. Insel said that during the next BTR Subcommittee meeting, the group would address the issue of clinical trial quality. He asked Dr. Daniels whether it would be possible to plan for a comorbidities panel at the April 19, 2013 IACC meeting. Dr. Daniels commented that many different ideas have come forward – too many for the April 9, 2013 meeting. She said that they should consider prioritizing. Perhaps some topics could be addressed during the July 2013 or October 2013 meetings.
Dr. Insel said that perhaps the topic of comorbidities could be brought forward in April 2013, given the interest of the full Committee. It was noted that the date for the next Subcommittee call had not yet been set. Dr. Boyle said the planning group on the Question 1 progress review would report back to the Subcommittee before the Committee meeting on April 9, 2013.
Dr. Insel adjourned the conference call at 4:33 p.m.
I hereby certify that this meeting summary is accurate and complete.
Thomas Insel, M.D.
Co-Chair, Basic and Translational Research Subcommittee
Geraldine Dawson, Ph.D.
Co-Chair, Basic and Translational Research Subcommittee
1 American Psychiatric Association. 2013. Diagnostic and statistical manual of mental health disorders: DSM-5 (5th ed.). Washington, DC: American Psychiatric Publishing.
2 American Academy of Pediatrics. 2012. Autism: Caring for Children with Autism Spectrum Disorders, A Resource Toolkit for Clinicians (2nd.).