Welcome and Introductions
Alan Guttmacher, MDCC Chair
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), National Institutes of Health (NIH)
Conflict of Interest Statement, General Info
Glen Nuckolls, MDCC Executive Secretary
National Institute of Neurological Disorders and Stroke (NINDS), NIH
Reports from Federal Agencies
The National Institutes of Health
National Institute of Neurological Disorders and Stroke
Walter Koroshetz, Director, NINDS
National Heart, Lung and Blood Institute/Parent Project Muscular
Dystrophy (NHLBI/PPMD) Workshop on Dystrophic Cardiomyopathy
Jon Kaltman, Program Director, NHLBI
Tiina Urv, Program Director, NICHD
Department of Defense
The Duchenne Muscular Dystrophy Research Program, Congressionally
Directed Medical Research Programs
Marielena McGuire, Program Manager, CDMRP
Food and Drug Administration
Office of New Drugs, Center for Drug Evaluation and Research
Devanand Jillapalli, Medical Officer
Social Security Administration
Office of Disability Policy
Melissa Spencer, Acting Deputy Associate Commissioner
Health Resources and Services Admin (HRSA)
Maternal and Child Health Bureau, Division of Services for Children with
Special Health Needs
Joan Scott, Chief, Genetic Services Branch
Department of Education
Office of Special Education and Rehabilitative Services
Sue Swenson, Deputy Assistant Secretary
Discussion of the Draft 2015 Action Plan for the Muscular Dystrophies
Introduction to the Draft Action Plan
MDCC Member Comments on the Draft Action Plan
Parent Project Muscular Dystrophy
Muscular Dystrophy Association
Public Comments on the Draft Action Plan
Myotonic Dystrophy Foundation
Summary of responses from Request for Information
Open Discussion of the Draft Action Plan
Alan E. Guttmacher, Chair
Implementation of Care Guidelines
Progress on Care Guidelines for Muscular Dystrophies
Natalie Street, CDC
Care Guidelines for CMD
Anne Rutkowski, CureCMD
PPMD Clinic Certification Program
Kathi Kinnett, PPMD
MDA Clinic Program
Valerie Cwik, MDA
Open discussion of Care Guidelines and Implementation
Alan E. Guttmacher, Chair
Public Comment Period
Alan E. Guttmacher, Chair
The Interagency Muscular Dystrophy Coordinating Committee (MDCC) was convened on March 17, 2015 at the Natcher Conference Center in Bethesda, MD. Dr. Alan Guttmacher, Director of the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD), served as the Chairperson and Dr. Glen Nuckolls, Program Director, National Institute of Neurological Disorders and Stroke (NINDS) served as Executive Secretary. The entire meeting was held in open session, and was in accordance with Public Law 92-463.
Call to Order and Opening Remarks
Dr. Alan Guttmacher called the meeting to order and proceeded with introductions of those in attendance and those participating by phone. An overview of the agenda was then presented.
Dr. Glen Nuckolls provided an overview of how membership on the MDCC is determined and an update on the status of new members mandated by the re-authorization of the MD-CARE Act in 2014 (including representatives from the Social Security Administration (SSA), Administration for Community Living (ACL), the Department of Education (DoEd), and one additional public member). The MDCC is currently waiting on approval of these nominations by the Department of Health and Human Services. The MDCC is governed by the policies of the Federal Advisory Committee Act (FACA), and thus all MDCC members were required to disclose any conflicts of interest.
Reports from Federal Agencies
Dr. Walter Koroshetz, Acting Director of NINDS, started off the report from Federal members of the MDCC with an overview of NIH and specifically NINDS support for muscular dystrophy (MD) research. Dr. Koroshetz provided specific examples of how past NINDS investments have contributed to advances in MD research and also provided an overview of how NINDS supports research across the spectrum from basic studies to clinical trials. The presentation concluded with an overview of the BRAIN Initiative, and how these research investments may have particular relevance to those MDs with neurodevelopmental or neurological components.
Dr. Jonathan Kaltman, Program Director, National Heart, Lung, and Blood Institute (NHLBI), provided a summary of the recent “Contemporary Cardiac Issues in Duchenne Muscular Dystrophy (DMD)” that was co-sponsored by Parent Project Muscular Dystrophy (PPMD). With a goal of identifying knowledge gaps in natural history, diagnosis, and treatment in DMD, the workshop brought together experts in basic and clinical research to regulatory policies and patient advocates. The discussion topics covered a wide range of topics with several recommendations for refining care and research being presented. An executive summary of the workshop can be found here. There was some interest following the presentation on NHLBI support for research on other dystrophies, and Dr. Guttmacher commented that this could be the topic of a future MDCC meeting.
Dr. Tiina Urv, Program Director, NICHD, provided an update and background on policy issues surrounding newborn screening for neuromuscular disorders. Newborn screening for the MDs is of considerable interest to the community, and is currently at the stage of being considered for the Recommended Uniform Screening Panel by the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children. Dr. Urv also presented a recent change to legislation as part of the Newborn Screening Saves Lives Reauthorization Act of 2014, which would require informed consent for any federally funded research on dried blood spots used for newborn screening. This change is likely to have significant implications for researchers who have previously conducted studies on excess anonymized, dried blood spots. Going forward however, informed consent will be required in order for any samples containing DNA (including dried blood spots) to be used for federally supported research.
Dr. Marielena McGuire, Program Manager, Congressionally Directed Medical Research Program (CDMRP), presented an overview of the DMD Research Program at the Department of Defense. Applications to the DMD Research Program go through a two-tier review process with priorities determined each year by an integration panel. The focus of the program is on trying to expedite the process of moving therapies to patients, with a large component of the program aimed at translational research with additional funding going towards training, clinical care, and quality of life research.
Dr. Devanand Jillapalli, Medical Officer, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration (FDA), discussed several recent MD-related activities at the FDA. The FDA is currently considering draft guidance submitted by PPMD which was received in June 2014. FDA along with NIH is hosting a workshop on Measuring Dystrophin in Dystrophinopathy Patients and Interpreting the data. FDA is participating in the upcoming Second Facioscapulohumeral Muscular Dystrophy (FSHD) Clinical Trial Preparedness workshop to reassess the current state of developing relevant clinical outcome measures, biomarkers and surrogate outcome measures for future FSHD trials. Dr. Jillapalli concluded his presentation with an overview of FDA resources available for patients, patient advocacy groups and research community: Office of Orphan Products Development, Critical Path Innovation Meeting, Rare Disease Program, and Professional Affairs and Stakeholder Engagement.
Ms. Melissa Spencer, Deputy Associate Commissioner, Office of Disability Policy, Social Security Administration (SSA) gave an introduction and overview of the SSA Disability Program. The mission of the Office of Disability Policy is to empower individuals with a disability and minimize financial hardship consistent with the principles of the SSA. Ms. Spencer provided an over of specific programs at SSA, the definition of disability used to determine eligibility, and the process for evaluating claims made. Medical status, ability to work, and income status are all factors in the decision making process. Some rare diseases are included on a list of compassionate allowances where diagnosis automatically qualifies one for disability programs from the SSA. Several in attendance were interested in following-up with the SSA on why some MDs are included in the compassionate allowance list and others are not currently.
Ms. Joan Scott, Chief, Genetic Services Branch, Maternal Child health Bureau, Health Resources and Services Administration (HRSA) provided an overview of where HRSA fits in the health care development and delivery pipeline, as well as services HRSA provides relevant to the MD community. HRSA focuses on clinical care and healthcare systems, especially for individuals who are vulnerable or underinsured. Most of HRSA’s programs are disease-agnostic, which includes medical homes, transitional care policies, and health information centers. HRSA also has a Genetic Services Branch which aims to increase individual’s access to genetic services. This branch also provides support for new born screening policy implementation at the federal and state levels.
Ms. Sue Swenson, Acting Assistant Secretary, Office of Special Education and Rehabilitative Services, Department of Education, presented some of the many resources and services provided by the Department of Education (DoEd) for children and young adults with disabilities. Many of the programs and services DoEd provides are contingent on how states define disability, and it is important to note that DoEd services are based only on the function of a child, not the diagnosis. DoEd participates in early screening and intervention programs as well as college and career-readiness programs. Transition into adult life and vocational rehabilitation are also areas of major emphasis.
Discussion of the Draft 2015 Action Plan for the Muscular Dystrophies
Dr. Nuckolls gave a brief history of the MDCC Action Plan and an overview of the process for developing the draft 2015 Plan. Through specific examples of research progress, Dr. Nuckolls illustrated how the field has changed since the last action plan was approved in 2005. These advances have led to new and expanded topics in the 2015 draft as well as the retirement or de-emphasis of others. Overall, the action plan contains a broad range of research objectives and goals for reducing the disease burden of MD that extends well beyond the mission of NIH or any one organization. The action plan is perhaps best viewed not as a roadmap, but as a topographical map, allowing each organization to decide what path to take in addressing the recommendations proposed.
Comments from MDCC Members
Mr. Brian Denger, Collaborative Program Administrator, Parent Project Muscular Dystrophy (PPMD), described the 2015 Action Plan as an evolution, noting the substantial progress made in DMD for example since the first action plan and enactment of the MD CARE Act. Mr. Denger highlighted PPMD’s role in the process of updating the action plan and made several suggestions for revisions. Among these were recommendations to recognize the role of patients who contributed to the action plan, continued support for basic mechanistic studies into MD pathology, addressing the practice and use of muscle biopsies, and more attention to biomarkers as well as cell and combination therapies.
Dr. Valerie Cwik, EVP & Chief Medical and Scientific Officer, Muscular Dystrophy Association (MDA), focused her remarks on how the MDA will utilize the action plan going forward. Dr. Cwik noted how the action plan fits well with the mission of the MDA and that several MDA programs intersect with the current draft. Dr. Cwik also described how the action plan would be used as the MDA refines its strategic priorities and suggested that a strategy for monitoring progress on the action plan objectives be incorporated into the plan.
Mr. Daniel Perez, Chief Executive Officer, Facioscapulohumeral Muscular Dystrophy Society (FSH Society) began his remarks with an overview of the FSH Society and its investments in research and training. Mr. Perez broke his comments on the action plan down into pros and cons, with overall support for the plan balanced by recommendations for NIH to increase funding for FSHD in institutes with missions relevant to the multisystemic features of FSHD, as well as to capitalize on recent breakthroughs in the understanding of FSHD disease mechanisms.
Dr. Peter Wald, Enterprise Medical Director, USAA, expressed his support for the action plan and provided several recommendations. Dr. Wald noted that the impact of adult onset diseases and their multisystemic features are not sufficiently emphasized in the plan, and also expressed a need to develop better prevalence data. Dr. Wald also expressed an interest in adding recommendations to the plan on the societal impact of MDs, including the economic impact to society.
Dr. Anne Rutkowski, Cure Congenital Muscular Dystrophy (CMD), focused her remarks on two gaps she perceived in the action plan. The first was the lack of a repository for negative results, where researchers could learn from what has failed or been proven wrong. The second was insufficient focus on pulmonary complications in the MDs. Dr. Rutkowski believes the cardiopulmonary objective should be separated into two objectives with pulmonary issues occupying its own objective.
Dr. Julie Bolen, Lead Health Scientist, Centers for Disease Control and Prevention (CDC), framed her remarks around the “Living with Muscular Dystrophy” section of the action plan, as that is the section she contributed to. Dr. Bolen discussed how several CDC services fit within the action plan, and made several recommendations for more emphasis from a public health perspective. These recommendations included quantifying the impact of the MDs on health, employment, and personal and societal economics, as well as ensuring access to coordinated care throughout life especially during the transition from pediatric to adult clinics.
Comments from the Public
Dr. Sharon Hesterlee, Research Director, Myotonic Dystrophy Foundation (MDF), provided a brief introduction to myotonic dystrophy and the MDF as well as comments on how the MDF will use the action plan. Dr. Hesterlee’s comments focused on a need for better prevalence data and more recognition for the multisystemic nature of myotonic dystrophy. Dr. Hesterlee also noted that there was very little input from industry during the drafting of the updated action plan.
Dr. Tom Cheever, Office of Science Policy and Planning, NINDS, summarized comments received from the Request for Information (RFI) on the action plan draft. The most commented on section was the “Living with Muscular Dystrophy” section, followed by the “Clinical Therapy Development” and “Diagnosis, Screening and Biomarkers” sections. Some of the most frequently mentioned themes in the comments were a need to consolidate and ensure access to data repositories, and regulatory issues surrounding approval of combination, cell-based, and exon-skipping therapies. Several other comments focused on a need for increased emphasis on pulmonary issues for people with MD and better ways to determine the pathogenicity of mutations following sequencing.
Open discussion of the action plan followed the commenting period. One of the major topics was how to measure progress on the action plan recommendations. There was significant discussion on what to measure, what is most meaningful to patients and families, and what types of metrics might be the most informative. Several examples were brought up by MDCC members with the positives and negatives of each discussed. Dr. Guttmacher suggested the committee consider forming a working group to examine ways to measure progress on the action plan and then report back to the full MDCC. This idea will be discussed further at future meetings.
Implementation of Care Guidelines
Dr. Guttmacher opened this session by noting that the clinical therapy section of the action plan calls for developing, implementing, and monitoring the impact of clinical care guidelines for the MDs. The purpose of this session is to review the status of new clinical care guidelines currently being drafted and to hear from several advocacy groups about their work directed towards the broad implementation of these guidelines.
Dr. Cwik (MDA) provided an overview for how MDA’s Clinical Network is implementing the clinical care guidelines for the MDs. The MDA Clinical Network aims to implement consistent, high quality care across all of its programs. The MDA is also focused on addressing several challenges in clinical care, including geographical restrictions, physician shortages, and variability in care provided. One means of monitoring progress on these challenges is through the MDA’s Neuromuscular Disease Registry, which includes clinician-entered data using NIH common data elements to correlate practice patterns with care guideline implementation and clinical outcomes. Future plans for the MDA Clinical Network include developing a certification process, requirements for clinics to participate in the registry, and efforts to help support clinical trial infrastructure.
Ms. Natalie Street, Health Scientist at the National Center on Birth Defects and Developmental Disabilities at the CDC, presented an update on the CDC’s progress in developing care guidelines and updates for Duchenne as well as other muscular dystrophies. Ms. Street began by giving an overview of how the previous DMD care guidelines were developed and outlined the general process for how the update of these guidelines would be conducted as well as the current status. She also reviewed plans for evaluating the use, feasibility, and accessibility for the updated care guidelines. In addition, the CDC is supporting the American Academy of Neurology (AAN) to develop care guidelines for several other MDs including Limb-girdle/distal, congenital, FSHD, and myotonic dystrophy. Ms. Street concluded by providing an overview of the CDC and AAN plans for disseminating the clinical care guidelines to the community.
Dr. Rutkowski (Cure CMD) presented two major programs related to clinical care that Cure CMD is undertaking: 1) the Congenital Muscle Disease Registry (CMDIR), and 2) a pulmonary surveillance and management survey. The CMDIR is an online patient registry for congenital MDs, myopathy, and myasthenic syndrome, which contains patient reported data and medical records, including biopsy and imaging data. The registry is already proving useful for clinical studies and in examining the prevalence of certain CMDs. A second program highlighted by Dr. Rutkowski was a self-reported survey of pulmonary care management in children with neuromuscular disorders. This survey found that there is significant variability in the pulmonary management of children, although some interventions such as nocturnal non-invasive management are more uniformly prescribed.
Ms. Kathi Kinnett (Senior Vice President for Clinical Care, PPMD) provided an overview of PPMD’s Certified Duchenne Care Center Program (CDCCP) and how it complements the mission of the MDCC. The CDCCP’s mission is to create a clinical network that provides standardized care in line with the CDC clinical care guidelines and specifically address several key discrepancies identified by the guidelines. Ms. Kinnett then went over the application process and how a center is evaluated once certified. Performance metrics from centers are reported publicly and cross-referenced with parent/patient reports on the services provided.
An open discussion session followed where several questions were posed and discussed. One question was what are the implications for insurance coverage and reimbursement once clinical care guidelines are broadly implemented? Other discussion topics included the intersection of personalized medicine and clinical care guidelines, including possible tie-ins with the Personalized Medicine Initiative. Discussion of the importance and policy implications for screening people without active signs of the disease was also brought up in the context of newborn screening issues.
Public Comment Period
A public comment session followed the open discussion session which featured comments from Anne Kennedy, Senior Vice President for Legislation & Public Policy, PPMD. Ms. Kennedy voiced PPMD’s support for the MDCC and encouraged MDCC members to work together on shared goals. She also highlighted several key issues including preclinical work on combination therapies, newborn screening, and hindrances to employment for people with MD.
Dr. Woodie Kessel, Board member for the MDF, also expressed his support for the value of convening so many groups focused on MD via the MDCC. He encouraged the committee to include a strategy for monitoring progress as part of the Action Plan.
Dr. Koroshetz voiced his concern about getting young physicians into the field. He indicated that NINDS would be interested in partnering with other groups to try and leverage resources for clinical training. Other members of the MDCC provided comments that there are several NIH mechanisms to support trainees wishing to enter the field, but that the biggest determinant is the applications received by the NIH. Specific program announcements in the past received very little interest. Dr. Koroshetz noted that patient advocacy and non-governmental groups can have a dramatic effect in getting young investigators interested in the field.
Dr. Guttmacher provided final concluding remarks, noted action items including ideas to monitor progress on the plan, and reminded members of the next MDCC meeting in the fall of 2015.