Minutes of the Interagency Autism Coordinating Committee (IACC) Meeting on July 15, 2009
The Interagency Autism Coordinating Committee (IACC, also referred to as "the committee") convened on July 15, 2009, from 8:30 a.m. to 3:00 p.m., in the Polaris Suite of the Ronald Reagan building in N.W., Washington, D.C. During the morning session, the IACC met with with the National Vaccine Advisory Committee (NVAC) Vaccine Safety Working Group.
In accordance with Public Law 92-463, the meeting was open to the public. Thomas R. Insel, M.D., Director, National Institute of Mental Health, chaired the meeting.
Interagency Autism Coordinating Committee (IACC) Members:
Committee Members Present at the Meeting: 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; Duane F. Alexander, M.D., Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Ellen W. Blackwell, M.S.W., Centers for Medicare & Medicaid Services (CMS); Judith Cooper, Ph.D. (representing James F. Battey), National Institute on Deafness and Other Communication Disorders (NIDCD); Lee Grossman, Autism Society of America; Gail R. Houle, Ph.D., U.S. Department of Education (ED); Larke N. Huang, Ph.D., Substance Abuse and Mental Health Services Administration (via teleconference); Story C. Landis, Ph.D., National Institute of Neurological Disorders and Stroke (NINDS); Cindy Lawler, Ph.D., National Institute of Environmental Health Sciences (NIEHS); Christine M. McKee, J.D.; Lyn Redwood, R.N., M.S.N., Coalition for SafeMinds; Alison Tepper-Singer, M.B.A., Autism Science Foundation; Edwin Trevathan, M.D., M.P.H., Centers for Disease Control and Prevention (CDC); Peter van Dyck, M.D., M.P.H., Health Resources and Services Administration (HRSA).
National Vaccine Advisory Committee (NVAC) Vaccine Safety Working Group Members:
Guthrie Birkhead, M.D., M.P.H., NVAC Chair; Bruce Gellin, M.D., M.P.H., NVAC Executive Secretary; Tawny Buck, Working Group Co-Chair; Marie McCormick, M.D., Sc.D., Working Group Co-Chair, Andrew Pavia, M.D., Working Group Co-Chair; Robert Beck, J.D.; Chris Carlson, Ph.D.; Vicky Debold, Ph.D., RN; Cornelia Dekker, M.D.; Mark Feinberg, M.D.; Lance Gordon, Ph.D.; James Mason, M.D.; Gerald Medoff, M.D.; Trish Parnell; William Raub, Ph.D., Daniel Salmon, Ph.D., National Vaccine Policy Office Staff Member.
Call to Order and Opening Remarks
Dr. Thomas Insel welcomed the group of IACC and NVAC members to the meeting. The participants introduced themselves and Dr. Insel provided some introductory comments regarding the mission and work of the IACC. Dr. Insel explained the IACC's Congressional mandate, under the Combating Autism Act of 2006, to create a strategic plan for ASD research. The plan is divided into six questions that relate to the needs of families affected by ASD and includes specific long-term and short-term objectives. While drafting the plan, the need for more intervention research and an increased focus on adults with ASD emerged as themes, Dr. Insel said. Contributors to the plan also cited a need for more environmental risk factor research. Within environmental risk factors, the question of vaccine research divided the IACC and the public. Some felt that the research had conclusively shown that vaccines were not linked to autism and no further studies needed to be done. Others felt that, while much research had been done, fundamental questions about the vulnerability of specific subpopulations and autism subtypes still needed to be addressed. A third group acknowledged that vaccines were not likely contributors to autism, but felt that more science was needed to allay public concerns.
Dr. Insel said that the IACC had initially decided to include objectives on vaccine research in their strategic plan. These objectives called for a study to determine the feasibility of research comparing outcomes in vaccinated and unvaccinated children, as well as developing cellular and animal studies to investigate potential mechanisms by which physiological responses to vaccines could contribute to ASD. However after more discussion, the committee decided that additional information was needed from an expert source before they could call for specific vaccine-related objectives in the plan. Acknowledging that the IACC does not include the needed expertise on vaccine safety issues, the committee voted to move the vaccine objectives to the "What Do We Need" section and worked to convene with the National Vaccine Advisory Committee (NVAC).
Joint Meeting of the Interagency Autism Coordinating Committee and the National Vaccine Advisory Group
Recent Activities and Future Direction of NVAC Safety Working Group
Dr. Bruce Gellin, Director of NVAC's National Vaccine Program Office, had spoken with the IACC earlier in the year to inform them about his office and its duties. He said that the NVPO was in the process of updating the National Vaccine Plan, which had been drafted during the mid-1990s.The NVPO is working with the Institute of Medicine to review the plan and its five broad goals.
Dr. Andrew Pavia then reported on the recent activities and future directions of the NVAC Vaccine Safety Working Group. He had started as the sole chair, but currently co-chaired the position with two others, Ms. Tawny Buck and Dr. Marie McCormick. The Working Group developed a two-fold mission: to help in the creation, review and vetting of a five-year (or longer) research agenda by the Immunization Safety Office (ISO) at the CDC; and to advise on content and research gaps. The Working Group was also asked to prioritize research areas and to identify scientific barriers to implementing the research agenda.
Dr. Pavia then described the area expertise of the group and the process by which the ISO research agenda was drafted. The Working Group subdivided into four groups which drafted initial comments and recommendations that were reviewed internally. A group of stakeholders was then invited to help determine prioritization criteria. At the same time, an extensive public engagement process was ongoing, orchestrated by the Keystone Institute. Three town hall-style meetings were held to get public input from families in Birmingham, AL; Ashland, OR; and Indianapolis, IN. The Oregon site was chosen because of the high proportion of "vaccine-hesitant" families – those who chose to opt out of vaccination or vaccinate on an alternate schedule, generally spacing out immunizations over a longer period of time.
Once a draft had been written, a broader stakeholder meeting was held in Washington, D.C., and a Request for Information (RFI) was put out for written public comments. (An earlier RFI had been released soliciting comments on the existing CDC-ISO report.) After engaging the public, the Working Group redrafted the report and presented it to the full NVAC in June 2009, where it received unanimous support from the committee.
Dr. Pavia then highlighted the elements of the report on the ISO agenda that pertain to autism spectrum disorders. The public engagement process identified substantial concern related to thimerosal, particularly with regard to ASD, Dr. Pavia reported. He said that the NVAC is convinced by the many epidemiological studies that have demonstrated that thimerosal in vaccines is not associated with ASD in the general population. This is a broad statement without regard to specific subgroups or additional areas for future research, he said. The NVAC noted that a small and specific subset of the general population, such as those with mitochondrial dysfunction, may be at elevated risk of reduced neurological functioning, possibly including developing ASD subsequent to vaccination. Individuals with regressive autism are of particular interest.
Dr. Pavia said that while vaccination almost certainly does not account for the recent rise in ASD diagnoses in the population as a whole, public concern regarding vaccines and autism, taken with the prevalence and severity of ASD, warrant additional study in well-defined subpopulations.
He said that that the broad question of whether vaccines caused the significant increase in the prevalence of autism is a settled question of science. But he stated that there are areas where the science needs to be pushed further to look at specific subgroups and specific biologically-driven hypotheses.
IACC and NVAC Discussion: Feasibility and Design Issues Regarding Epidemiological Studies of Vaccinated, Unvaccinated, and Alternatively Vaccinated Populations
Dr. Pavia said that the NVAC had discussed the feasibility of comparing outcomes in children who are unvaccinated with those who are fully vaccinated or vaccinated according to an alternate schedule. He said that there was not full consensus on the issue but that previous discussions on the topic in other venues had lacked the scientific rigor and discipline needed to accurately discern feasibility.
In its report, the NVAC recommended that a feasibility study be undertaken by an independent organization such as the Institute of Medicine that would bring together scientists of the highest academic credentials. The committee recommended "establishing an ad hoc committee with broad methodologic design and ethical expertise to consider the strengths and weaknesses, ethical issues, and feasibility; including timelines and the cost of various study designs." This process should be open and transparent. The final recommendation from the report was to assess the ability to include biomarkers of immunity and metabolic dysfunction outcomes, including autism, among other disorders.
Dr. Pavia stated that, in order to take advantage of the investment, efforts to determine feasibility and/or carry out the vaccinated vs. unvaccinated study should not focus on a single predetermined outcome like autism, but rather look at a range of possible outcomes. Dr. Pavia summarized that the NVAC has now reviewed the CDC agenda and the CDC is making changes based on the NVAC's recommendations and the appointment of a new Director. The NVAC is in the process of reviewing the current Federal vaccine safety system and developing a white paper to recommend changes to the system infrastructure, reduce adverse events when possible, and improve public confidence in vaccine safety. The goal is to update the system using current scientific capabilities.
After their morning meeting with the IACC, the NVAC planned to hold five panel discussions to help develop the white paper on the Federal vaccine safety system. The panels will address implementing principles and policy alternatives; overcoming gaps in the current system; meeting the needs of the public, health care professionals, and public health professionals; integrating lessons from other safety arenas; and enhancing adoption and implementation of the NVAC white paper.
After Dr. Pavia finished his presentation, Dr. Raub asked to what extent the research needs in the strategic plan were being handed down from the government, versus being initiated by the scientific community. Dr. Insel said that a recent portfolio analysis of ASD research helped answer this question. By mapping current research funding to the goals outlined in the strategic plan, the IACC was able to determine gaps. This was concurrent with $60 million in American Recovery and Reinvestment Act (ARRA) funds becoming available for autism research. Dr. Gellin said that the NVAC used the CDC draft plan as a starting point and then convened a range of experts to organize and frame the scientific agenda. In some cases, issues had been highlighted but research questions or hypotheses had not been formulated, he said. Dr. Chris Carlson and Dr. McCormick said that the ISO agenda had items that extended beyond traditional epidemiology and ventured into questions of basic science. The NVAC felt that the ISO was not equipped to carry out this basic science research, so they were tasked with deciding who would be most appropriate.
Dr. Gordon explained that the ISO is an office within the CDC, which is not equipped with laboratory facilities. It is necessary to partner with agencies like the NIH to carry out this work. Dr. Birkhead said that the committee had considered the National Children's Study (NCS) as a vehicle for carrying out the feasibility study for the proposed comparison of vaccinated and unvaccinated cohorts. He asked if the IACC had considered using the NCS, as well. Dr. Duane Alexander said that issues of vaccine safety and vaccination in relation to developmental disorders had been included in the agenda for the NCS. He said that while they anticipated gathering prospective data on immunization, the current plan does not include examining physician records because it would be too costly, adding at least an additional $15 million.
Dr. Alexander cautioned that even with a group of 100,000 children, there may not be a sufficiently large population of unvaccinated children or specific autism subgroups. He estimated that a study of 100,000 children would yield about 10,000 children who have received limited or no vaccinations, or those that have been immunized on an alternate schedule. So while the question of studying outcomes related to vaccines will be addressed in the NCS, it will not be to the fullest scale possible for more detailed evaluation.
Dr. Gutherie Birkhead stated that other options exist outside of examining physician records, including immunization registries available in some states. Dr. Daniel Salmon said that a small group with representatives from the NCS, FDA, and CDC was examining the current study plan and considering additional approaches.
Dr. Insel asked whether looking at an enriched sample would improve feasibility. For example, examining a small Canadian sample of younger siblings of children with ASD showed that 56 percent of the siblings were unimmunized or received partial vaccine schedules. If a sample such as this could be increased ten-fold, would it provide useful information about the relationship of vaccines to a host of health outcomes in a subsample with potential genetic vulnerability?
Dr. Pavia said that such an approach had been discussed and had merits, although it fell outside the scope of the ISO agenda, so is not mentioned in their report. Dr. Carlson said that study self-selection would be a challenge to overcome. A study could likely show a potentially inaccurate association between incomplete vaccination and autism because many of the children who are not vaccinated have older siblings with ASD, making them more likely to develop the disorder. (Younger siblings have a 10 percent recurrence risk for ASD.) Dr. Insel said that there were several potential problems with a study of younger siblings – it would not be a randomized sample; these children would have a greater risk of developing ASD; and there may be fundamental differences in families where more than one child is affected (multiplex families). Dr. Insel asked whether a cohort of 2,000 infants with autistic siblings would be meaningful to study for other families of autistic children, or whether such a sample could be helpful in understanding the larger public health impact of unvaccinated children. Dr. Feinberg said that the ethical issues would be very complex, noting that an observational study where parents have self-selected not to immunize is vastly different from a study where participants are recruited and counseled on the risks and benefits of refusing immunizations. Because vaccines are known to prevent potentially deadly diseases, the ethics of enabling people to not get the recommended vaccines is problematic, he said.
Dr. Insel asked if the NVAC felt that small observational studies such as the Canadian baby siblings study would be helpful or just create more confusion. Dr. Birkhead said he would be concerned with the generalizability of a study that only had 2,000 participants. Dr. Carlson said they were grappling with whether to invest major resources when a perfect study may be impossible. Dr. Pavia noted that the scientific community approaches observational studies in areas outside of vaccine research differently. They acknowledge that there are unavoidable biases and do not place weight on any single study. However, when studying vaccine safety, researchers may be hesitant to conduct important studies because of the risk that results will be misinterpreted as stand-alone pieces, when results should be looked at in the context of many other studies. In considering the baby siblings study, Dr. Pavia said they should not shy away simply because it will not "tell the whole story."
Ms. Lyn Redwood recommended using the vaccine safety data set previously reviewed to look for links between thimerosal and autism. She said that an NIEHS report had recommended examining the set for vaccine-related outcomes.
Mr. Lee Grossman asked the NVAC if they could comment on the time frame for suggested studies and what should be told to families in the interim. Dr. Birkhead estimated that the feasibility study for the vaccinated/unvaccinated outcomes study could be conducted in a year. He said that currently the CDC tried to allay public concern over vaccines with written materials.
Dr. Pavia said that studies of children with mitochondrial disorders were in the planning stages and that reanalysis of existing data sets could be accomplished in a timely manner.
Dr. Insel said that members of the IACC may struggle with the recommendation that the question of feasibility for the vaccinated/unvaccinated study be "booted" to another committee, such as the Institute of Medicine. He asked if it would be beneficial to release a Request for Proposals (RFP) to see whether a well-designed study could be proposed.
Dr. Story Landis said that going forward with a pilot sibling study looking at a host of outcomes seemed like a proactive next step, even if the study had inherent selection flaws. Dr. Insel added that he felt that spending another year in panels discussing feasibility would not address the urgency felt by parents currently grappling with immunizing siblings of their autistic children. Dr. James Mason said he understood the urgent quest for answers but cautioned that conducting a poorly-designed study with misleading results would be worse than no study at all. He recommended convening an expert panel as rapidly as possible with epidemiologists, geneticists, and statisticians to ensure a well-designed study if it were to go forward.
Dr. Carlson said that it would be possible for an investigator-initiated study to be funded and would not require a committee's actions. Dr. William Raub supported the idea of issuing an RFP, calling it a wonderful, pragmatic tool with relatively low risk. In the worst case scenario, no high-quality proposals are received.
Mr. Grossman said that the CDC should be transparent with the public about any new studies in order to allay fears from parents who ask "why now?" Ms. Buck, mother of a vaccine-injured child, reminded the IACC that the Vaccine Safety Working Group is looking at a host of adverse events, autism only being one of many.
Ms. Redwood said that she felt it was the responsibility of the IACC to add vaccine initiates into the strategic plan. She noted that the CDC does not have the laboratory capacity to conduct mechanistic studies and should not be the lead on these studies.
Dr. Pavia said that basic science questions and mechanistic questions could not be answered by researchers at CDC and would fall to the NIH and its network of investigators. The white paper will address the agenda for studying mechanisms of vaccine injury and how to achieve coordination between agencies, he said.
Dr. Mark Feinberg returned to Mr. Grossman's point about public outreach and emphasized that the overall safety and benefits of vaccinations should be reinforced. The available scientific evidence suggests that there is no association between vaccines and autism in the general population. Dr. Carlson said that a siblings study would be more valuable if the number of exposures was broadened instead of focusing on a single endpoint.
Dr. Vicky Debold said that the public would question what was meant by the "general population." She cautioned that a clear explanation would be very important. She asked if there was an open RFA or RFP at NIAID on vaccine safety. Dr. Insel said that NIAID had a program announcement (PA) open, but that means they are soliciting investigator proposals but without a specific set-aside budget committed to that effort. Grants applications received under PAs compete with investigator-initiated grant applications for funding.
Dr. Alexander said in response to Dr. Carlson's comment that the National Children's Study was an example of a study looking at hundreds of variables and influences, in addition to vaccines.
Dr. Insel explained to Dr. Debold that RFAs and RFPs, which have money specifically assigned to them, would be opened to generate interest if nothing came from a program announcement.
Dr. Cornelia Dekker informed the committee that some of their investigators were trying to take advantage of the vaccine safety program announcement. Dr. McCormick added that the committee should consider how to standardize information on outcomes and adverse events. The group then heard comment from members of the public.
Dr. Geraldine Dawson, Chief Science Officer at Autism Speaks, explained the organization has concluded that there is no compelling evidence for a connection between thimerosal or MMR and autism, particularly in terms of the increases in the general population. However, Autism Speaks feels that more research should go into investigating genetic- or immune-vulnerable subgroups. The organization currently sits on the autism advisory panel for the National Children's Study. By not collecting medical records, the study is limited in examining vaccine risk and other potential risk factors. Therefore, the panel is going to recommend an adjunct study that includes the collection of medical records. Dr. Dawson said that Autism Speaks had conducted a study to determine the feasibility of using the large cohort of baby siblings in their consortium for a vaccine outcomes study. They concluded that the study would be underpowered and did not invest more money, but have contributed funding to two Autism Centers of Excellence network studies of baby siblings.
Ms. Singer asked if clinicians involved in the baby siblings research consortium had been consulted on the ethics and practicality of collecting prospective data. Dr. Dawson said that one of their subgroups on the National Children's Study was looking specifically at ethical issues and they had discussed how to best conduct risk communication.
Dr. Insel said that the 3,700 baby siblings between the research consortium groups and additional studies may provide study opportunities that that IACC can revisit.
Closing Discussion with NVAC
Dr. Gellin asked the IACC how they would like to proceed. Ms. Singer said that consulting an independent committee that could carefully consider feasibility and ethical issues and would be worth the extra time spent. Dr. Alexander said that he had long been a proponent of conducting a feasibility study through the IOM or other group. He said that the expert panel should address shortcomings of the vaccine safety evaluation system, in addition to autism.
Dr. Ed Trevathan said that the vaccine-autism link is a critically important issue but that there is a price to be paid if studies are done in haste and incorrectly. He acknowledged that there is a need to move as quickly as possible and recommended the IOM as the best choice for convening a panel.
Ms. Redwood said that primate studies could be used to move forward quickly to examine mechanism. Dr. Insel closed the meeting by summarizing that the NVAC has an important and broad agenda, of which autism is a small piece. NVAC and IACC have agreed that the next step is to convene a panel to address the question of feasibility for an epidemiological study of outcomes in vaccinated and unvaccinated children. Dr. Insel said that he hoped to be able to look to NVAC again for suggestions about the science and offered the help of the IACC while the NVAC reviewed the broad vaccine safety system. He thanked the NVAC for their collaboration and the morning session adjourned.
After completing the morning session with the National Vaccine Advisory Committee, the IACC convened to discuss committee matters. Dr. Alice Kau presented an overview of the Autism Centers of Excellence, a trans-NIH collaboration on autism research that includes the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute on Deafness and Other Communication Disorders (NIDCD), the National Institute of Environmental Health Sciences (NIEHS), the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS).
The ACE program is a consolidation of two previous programs, the Collaborative Programs of Excellence in Autism (CPEA) and Studies to Advance Autism Research and Treatment (STAART). The program is comprised of research centers and networks; research centers foster collaborations between teams of specialists who share the same facility so that they can address a particular research problem in depth; ACE networks consist of researchers at many facilities in locations throughout the country who work together on a similar research topic.
Dr. Kau explained that ACE centers and networks are required to share their data using the National Database for Autism Research (NDAR). Sites must submit their data twice yearly, even as a study is ongoing, and report common measures for subjects that include IQ, medical history, and other assessments. Dr. Kau listed the principle investigators (PIs) and site locations of the six centers and five networks funded by NICHD. Dr. Nancy Minshew's center at the University of Pittsburgh focuses on information processing and learning. Dr. Susan Bookheimer at UCLA focuses on the core communication deficits of ASD. Dr. Ami Klin, PI at the Yale ACE center, focuses on brain behavioral and molecular studies, in addition to identifying biomarkers for early diagnosis. Dr. Brian King from the University of Washington center investigates risk and protective factors for ASD. Dr. Eric Courchesne's center at UC-San Diego focuses on identifying early brain development and other physical characteristics that may predispose children to develop autism.
Dr. Kau then described the ACE networks supported by NICHD and their topic areas. Dr. Joe Piven focuses on early brain development of infant siblings of autistic children. Dr. Dan Geschwind is identifying autism risk genes. Dr. Diane Chugani's studies currently focus on the safety and feasibility of conducting psychopharmacology trials for children younger than six years old. Dr. Sally Rogers is comparing an intensive behavioral treatment with standard community-based interventions. Dr. Craig Newschaffer's network is conducting a longitudinal investigation of early autism risk, focused on genetic and environmental risk factors.
Presentation on Autism Center of Excellence (ACE) Research by Edwin Cook , M.D. – ACE center, University of Illinois at Chicago
Dr. Edwin Cook described the work his center conducts investigating insistence on sameness, a common characteristic of ASD, and the elevated blood serotonin levels found in some individuals with ASD. Dr. Cook's center is based out of the University of Illinois-Chicago and includes the Vanderbilt University and the University of Chicago. The center's administrative core relies on the Midwest Autism Consortium to improve communication among researchers and facilitate recruitment efforts. The center sends its blood samples to the NIMH Genetics Repository and shares blood for platelet and genetic studies of other approved researchers. Dr. Cook described the various projects being conducted at the center, which include studies of genetic data and the analysis of imaging and neurocognitive data to understand insistence on sameness. The center is also studying the genetic basis for the different neurochemical subtypes related to increased serotonin levels. Dr. Cook described how the centers submit their data to NDAR and how the database could help to answer questions for families affected by ASD in the future.
Presentation on the National Database for Autism Research (NDAR) by Michael Huerta, Ph.D.
Dr. Mike Huerta, NDAR Director, NIMH, spoke to the committee about the value of NDAR to ASD research. NDAR is supported by NIMH, NINDS, NICHD, NIEHS, and the NIH Center for Information Technology. The database facilitates capturing and analyzing high volumes of data and allows researchers to visualize and organize their data in new ways. The database accepts genetic and genomic data, required common measures, clinical assessment measures, and imaging data. In addition, NDAR accepts information about particular datasets, such as methodology details, and importantly can be expanded to include new data types that may be developed in the future.
NDAR also allows laboratories to collaborate on the same research question. ACE investigators and those funded by the ARRA are required to submit their data to NDAR. Researchers can link to other ASD data resources such as the NIH pediatric MRI data repository and can privately share data with a select group of others using NDAR. Ultimately, NDAR can help transform ASD research across multiple data types and disciplines, Dr. Huerta said.
Ms. Singer asked whether supplemental funding mechanisms could be put in place to encourage privately-funded researchers to contribute their data to NDAR. Dr. Huerta said that ARRA funds had been used to solicit applications and supplement existing NIH grants. Small grants of $5,000 to $6,000 are available to NIH grantees to offset the cost of the labor needed to submit data to NDAR.
Ms. Singer also asked how study results from ACE centers are disseminated and effectively communicated to parents. Specifically, she cited the results of two Citalopram studies, conducted at separate ACE centers, which released conflicting results within a few weeks of one another. Parents had trouble assessing the results and applying them to decisions about their own children, she said.
Dr. Cook, who heads the ACE Center that conducted one of the studies, said that the research did not directly address anxiety disorder or depression and autism. Instead, he would advise parents who have questions regarding their child's medication to look to the SFARI web site discussion or to the authors' statements in the paper itself. Dr. Cook said that communicating complex and nuanced results is difficult and can be misinterpreted as "nothing was learned."
Dr. Lawler said that Ms. Singer brought up a good point -- currently there are no uniform dissemination efforts to communicate ACE study results to the broader scientific and public communities.
Mr. Lee Grossman asked whether researchers outside the NIH were being encouraged to submit data and how that was being done. Dr. Huerta said that an NIH Guide Notice had been issued in March asking researchers to share their data.
Dr. Landis asked whether any non-NIH researchers had submitted data and Dr. Huerta reported that they had not, but that the notice had only been published four months ago and said that some interest had been expressed informally. He said that part of the process was increasing awareness about NDAR so that investigators could build the cost to submit data into their budget.
Dr. Landis asked how much money had been invested into NDAR to date and Dr. Huerta reported that the current budget was $1.06 million for FY2009. In November 2008, NDAR had 29 Global Unique Identifiers (GUIDS), each attached to a research subject. Currently, NDAR contains around 1,200 GUIDs and they expect to have information from about 10,000 additional subjects soon.
Ms. Redwood asked whether historical treatment data could also be included in NDAR. Dr. Huerta said that the database could be expanded to include that data and major data resources could soon be connected. He described the 29 different clinical assessments that are part of the common measures submitted with every subject. This includes several medical history forms that would include treatment information that could be searched.
Mr. Grossman asked if there was a cost to submit information to NDAR and Dr. Huerta clarified that submitting data was free but there was inherent cost in the labor required to prepare and submit the data. Mr. Grossman also asked about "cloud technology" used in the NDAR database. Dr. Huerta explained that cloud computing makes computing cycles available through the Internet while the analyzing software is housed elsewhere. NDAR is not using cloud computing but is developed such that cloud computing can be used in the future.
Ms. Singer said that NDAR needs to reflect a greater sense of urgency and pointed out that the system is still not accessible for researchers to use. Dr. Huerta said that recently he had seen tremendous progress in NDAR and expected 10,000 GUIDs in the next ten months. Currently, there are nine months between the time data is submitted and it is viewable and Dr. Huerta said he would like to shorten that period considerably. Ms. Singer said that funds need to be available for researchers to input their data. Currently, ARRA funds will be put to this end but only on a one-time basis. Dr. Huerta said that interested investigators could contact Lisa Gilotty, Alice Kau, or other program officers to request supplements. However, Dr. Landis said that private funders probably would not know about this option.
Dr. Huerta explained that NDAR is a landmark database because it allows subjects to be tracked and cross-referenced. Because of this feature, duplicate data can be extracted when analyzing across different data sets. Importantly, the individual identity of the subject remains anonymous.
Dr. Gail Houle asked who could gain access to NDAR data and Dr. Huerta responded that researchers at NIH-recognized research institutions are granted access. Dr. Insel said that after ARRA funds were awarded much progress would be made and the NDAR's progress may be rapidly accelerated.
Approval of May 4, 2009 Meeting Minutes
The committee then voted on the May 4, 2009 minutes. Ms. Redwood asked that committee vote counts be included in future minutes and Dr. Insel asked for the wording of a sentence to be changed to sound less pejorative. The minutes were then unanimously approved.
Update from the Services Subcommittee
Mr. Grossman and Ms. Ellen Blackwell then updated the IACC on the activities of the Services Subcommittee. The subcommittee is sponsoring a town hall meeting at the Autism Society's national conference that will be available through live webcast for remote viewing. Subcommittee members will report on their agency's activities during the opening session and then members of the audience will have the opportunity to make comments on the services sections of the strategic plan, in addition to other comments or questions about services provision, the services subcommittee, etc. Ms. Blackwell said that she hoped the public would take advantage of the rare opportunity to participate with the IACC in real time.
Mr. Grossman reported to the committee on the last meeting of the Services Subcommittee on July 16, 2009. In an effort to keep updated on Federal programs related to autism, Dr. Bonnie Strickland and Dr. Georgina Peacock from HRSA and CDC, respectively, presented on the Learn the Signs. Act Early. program. The subcommittee is making an effort to hear presentations about Federal activities at each meeting. Mr. Grossman said that he was struck by how many teams were engaged in similar activities across the nation and that efforts should be made to connect and collaborate. Speakers on behavioral analysis and other service-related issues will present at the October 23, 2009 meeting of the IACC. Ms. Blackwell added that all Services Subcommittee meetings are open to the public (as are full IACC meetings) and she encouraged the public to participate.
Update from the Subcommittee on the Planning of the Annual Strategic Plan Updating Process
Dr. Insel then updated the committee on the activities of the Subcommittee on the Planning of the Annual Strategic Plan Updating Process. The subcommittee conducted a portfolio analysis of autism research, carried out by the Office of Autism Research Coordination (OARC). The analysis included 19 Federal and private funders who gave information on their present autism research. This information was collected and analyzed to see how it aligned with the strategic plan objectives. Dr. Insel noted that private organizations contributed a large portion of autism funding, with the Simons Foundation and Autism Speaks each contributing over $30 million yearly. In total, about $222 million was spent on autism research in 2008 by the investors included in the analysis; a little more than half of these funds came from NIH.
The research dollars were mapped to the questions in the strategic plan. As expected, funding was meager for services/supports and lifespan research. Much funding went to research on risk factors and interventions, although Dr. Insel expressed surprise that more funding was not being put into interventions research. Dr. Insel led the committee through the figures tracking research investments to the strategic plan objectives. The analysis will help to identify gaps and opportunities when revising the plan for January 2010.
The subcommittee had also decided to issue a Request for Information (RFI), in lieu of a town hall meeting, to gather public input on the existing strategic plan. The RFI will be open for 30 days and will be advertised through different forums, including the IACC twitter account. These public responses will address research gaps, scientific opportunities, and how to prioritize objectives. Responses will be used to inform the IACC Scientific Workshop to be held September 30 – October 1, 2009.
Discussion of Scientific Workshop
The subcommittee decided that the workshop sessions will be divided according to the questions of the strategic plan and conducted over a two-day period. Each panel will consist of researchers, clinicians and personal/family members. Questions five and six ("Where can I turn for services?" and "What does the future hold" will be combined into one panel. Each panel will be led by members of the IACC (later decided to be one Federal and one public member), who will act as liaisons to help the panelists prepare their presentations on the gaps, opportunities, and priorities for their topic area. The panelists will receive the portfolio analysis, information on new funding initiatives, strategic plan, Summary of Advances, RFI results, and comments from the July 24, 2009 town hall meeting on services. The panelists will also be given a list of items that were tabled during the development of the 2009 strategic plan. Dr. Insel added that ARRA funding information would be available for consideration by the time the workshop is held.
Dr. Cindy Lawler said that she was concerned about the small number of panelists if only three individuals sat on each panel. There would be potential for bias and limited scope with such a small number of panelists, she said. Dr. Judith Cooper echoed her concerns, adding that she would like to see more than six individuals representing the scientific community. Ms. Blackwell said that she recommended having more than one IACC member per group acting as liaison. Dr. Lawler asked about involving the chairs from the four-day Scientific Workshop held on January 15-18, 2008. The committee continued to discuss the most appropriate number of panelists and decided to include six individuals on each panel (two researchers, two clinicians, two personal/family members). Ms. Redwood recommended that "clinician" panelists include both clinical researchers and practicing clinicians. Dr. Della Hann asked for committee members to nominate additional panelists and to nominate themselves for liaison positions. The committee agreed to vote on panelists and liaisons by e-mail ballot and discussed the necessity of moving forward quickly to organize the upcoming workshops.
Dr. Lawler asked if the portfolio analysis was available publically and Dr. Hann said that members of the public could request the document by e-mailing IACCPublicInquiries@mail.nih.gov. (Due to 508 compliance issues it currently cannot yet be posted on the Web site; 508 compliance requires that documents be formatted so that they are accessible to people with a range of disabilities and is a labor-intensive process for a table and graph intensive document like the portfolio analysis.)
Dr. Lawler said that the committee would be able to gauge the success of the workshop for updating the plan and make changes to the format as needed in the future. She said that in the future, she would also like to get feedback from workshop participants about using and implementing the strategic plan. Dr. Insel agreed that future workshops would provide more information on how well research objectives of the strategic plan were being met. The plan has not yet had the time needed for implementation. The committee can also gauge future progress by tracking the funding source of the discoveries cited in the Summary of Advances, as recommended by Ms. Redwood. Dr. Insel noted that they were running ahead of schedule and asked the committee if they would prefer to continue rather than take the scheduled break.
Summary of Advances Discussion
The committee then began discussing the draft version of the Summary of Advances. Dr. Hann reviewed the methodology for developing the pool of articles from which the committee selected. The NIH Library conducted a search of articles on autism published in peer-reviewed journals during 2008 (e-pubs were excluded). The pool yielded 257 articles, which were then categorized by the OARC according to strategic plan subject area. Members of the committee voted to select articles within the pool and to add, omit, or re-categorize any of the articles. From these selections, the committee chose to include 37 articles in the summary and include the complete list of 257 articles, linked to their PubMed citation, as an appendix to the document. The draft Summary of Advances was written and sent to the IACC for their review.
Ms. Redwood said she had been confused by the various article selection options and felt that the current draft did not reflect all the advances in the year. She was disappointed that work on mitochondrial disorders in autism and Dr. Jill James' work on oxidative stress and increasing glutathione levels with methylcobalamin and folinic acid were not included. She said that the 37 articles did not capture the breadth of research and included a disproportionate number of articles on risk factor. The draft also included an article on umbilical cord clamping that did not relate to autism and an editorial article that did not reflect any new science.
Dr. Insel said that the committee had also discussed and rejected using journal impact factor to select articles. Most importantly the committee must agree on a consistent method to select articles for each annual update of the Summary of Advances, he said. Ms. Singer said that she felt the summary was good but lacked an impact statement for how these advances would improve quality of life for people with ASD and their families. Dr. Insel said that this summary would be viewed as a baseline and future advances could be linked to the strategic plan and evaluated in terms of public health impact.
Ms. McKee said that the selection process was odd with only three public members and three Federal members voting during the initial selection. She also asked that the language describing the differences in the number of articles be rewritten to reflect that the disparity could be the result of less funding going to areas like services and supports, resulting in fewer advances.
Dr. Landis said that the next year's summary could be coupled with a funding diagram. Dr. Insel said that in the future, the document would probably link to funding, new initiatives, and areas of the strategic plan.
Mr. Grossman said he was disappointed that the draft did not reflect the urgency of autism and omitted advances in the applied field. He said that the document should be more expansive and look beyond peer-reviewed journal articles.
Dr. Insel said that there seemed to be low enthusiasm for the document as it stood, but tweaking could be done to add a sense of impact, and it could be sent forward. Dr. Hann said that the 2007 Summary of Advances had been submitted in July 2008, to give a sense of the timeline. Dr. Insel asked the committee whether the document should be tweaked and finalized or should be redrafted. The committee voted nine to three to tweak the document and finalize it, saying that they would decide on a better selection process for next year. Dr. Landis suggested having each committee member select one or two articles that they felt represented important advances. Dr. Insel responded positively to the idea and commented that he had thought of the Summary of Advances as a top 10 list, so including even 37 articles seemed like a large group. Ms. Singer said that fitting each advance into a specific category felt forced and that the document would be better written as a narrative.
Open Session for Public Comment
Dr. Insel noted that committee was still running ahead of schedule and asked to continue on rather than taking a brief break. The committee did not disagree, so then they moved to public comment. Mr. Jim Moody, Director and legal counsel of SafeMinds, called for autism-specific vaccine research to be included in the strategic plan. He said that compensation paid by the Vaccine Injury Compensation Program in cases with a behavioral diagnosis of autism confirmed the link between vaccines and autism. Mr. Moody said that vaccine research was specifically called for in the legislation and the recommendations of the National Vaccine Advisory Safety Working Group had identified crucial gaps in vaccine safety science. He asked that the IACC reinstate the vaccine objectives removed from the strategic plan draft and said they had been removed under the false premise that NIH does not have vaccine safety expertise. He urged that animal projects be started immediately by independent researchers.
Closing Comments and Adjournment
The committee was reminded that the next IACC meeting was scheduled for October 23, 2009 and was then adjourned.
I hereby certify that this meeting summary is accurate and complete.
Thomas Insel, M.D. /s/
Chair, Interagency Autism Coordinating Committee