National Advisory Board on Medical Rehabilitation Research (NABMRR)
National Center for Medical Rehabilitation Research (NCMRR)
Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NICHD)
December 2-3, 2019
Edelle C. Field-Fote
Stephanie C. DeLuca
Robyn Watson Ellerbe
Arthur W. English
Thubi H.A. Kolobe
Albert C. Lo
Craig M. McDonald
Eric Jon Perreault
David J. Reinkensmeyer
Elizabeth R. Skidmore
Ex-Officio Members Present:
Alison Cernich, NICHD
Theresa Cruz, NICHD
Mary F. Lovley, OSERS
Ralph Nitkin, NICHD
Lana Shekim, NIDCD
Chuck Washabaugh NIA
Ex-Officio Members Absent:
Daofen Chen, NINDS
Jerome L. Fleg, NHLBI
Lyndon Joseph, NIA
James Whitehead, NIDILRR
Erik Wolf, DoD
NICHD Staff and Visitors:
Joseph Bonner, NICHD
Timothy Brindle, VA
Scott Campbell, AOTF
Tinera Fobbs, NICHD
Jennifer Jackson, NICHD
Lisa Kaeser, NICHD
Susan Marden, NICHD
Clay Mash, NICHD
Joe Nahra, DRRC
Alexis Pierce, PPSV
Rodney Rivera, NICHD
Christie Rogers, NICHD
Karen Siegel, VA
Erin Spaniol, OD
JoAnn Thierry, CDC
Biao Tian, CSR
Lois Tully, NINR
Welcome, Introduction of New Members, and Approval of Minutes
Chair Dr. Field-Fote called the meeting to order at 9:00 a.m. Members of the Board introduced themselves, followed by brief introductions from NIH staff and other visitors. Dr. Field-Fote welcomed newly nominated Board members: Abiodun Akinwuntan, Ph.D., M.P.H., M.B.A.; Stephanie DeLuca, Ph.D., M.A.; Albert Lo, M.D., Ph.D.; and Eric Perreault, Ph.D., M.S. Minutes from the previous meeting of May 2019 were unanimously approved. The Board will meet May 4–5, 2020; December 7–8, 2020; and May 3–4, 2021.
NCMRR Director’s Report
Theresa Cruz, Ph.D., Acting Director, NCMRR, NICHD
Alison Cernich, Ph.D., ABPP-CN, former NCMRR director, was recently appointed the deputy director of NICHD. Dr. Cruz is now NCMRR’s acting director.
Clay Mash, Ph.D., formerly from NICHD’s Division of Intramural Research Section on Child and Family Research, is now an NCMRR program analyst.
Updates on Trans-NIH Initiatives
The NIH HEAL (Helping to End Addiction Long-term℠) Initiative. This initiative will improve the treatments of opioid misuse and addiction and enhance pain management, with the latter goal relying on rehabilitation medicine. For example, rehabilitation is important for HEAL’s Back Pain Consortium (BACPAC) Research Program, managed by Chuck Washabaugh, Ph.D., from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Many rehabilitation researchers receive funding through the NIH HEAL InitiativeSM. NCMRR staff are involved in HEAL working groups and Requests for Application (RFA) planning.
The Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative. The initiative’s director designee is John Ngai, Ph.D., from the University of California, Berkeley. The BRAIN Initiative has various transdisciplinary funding opportunities; see https://braininitiative.nih.gov/funding/funding-opportunities. Dr. Cruz and her team will present an update about the BRAIN Initiative’s clinical trials at the Multi-Council Working Group meeting on January 31, 2020, which NIH will videocast and archive at https://videocast.nih.gov/.
The All of Us Research Program. Currently at more than 200,000 participants, the program’s goal is to recruit and study 1 million participants from across the United States. NCMRR is working with All of Us to ensure it recruits people from the disability community, enhances accessibility for participants with disabilities (e.g., by providing accessible recruitment centers), and works with the program’s disability community partner, the American Association on Health and Disability. All of Us also accepted an NCMRR-nominated researcher to participate in the alpha testing of the Research Hub, which will host participant data the research community can access.
Sound Health. This initiative, previously known as Music and the Mind, is a collaboration between NIH, the National Symphony Orchestra, and the National Endowment for the Arts. Sound Health has awarded $20 million in grants, including for rehabilitation research projects. For more information, go to https://www.nih.gov/research-training/medical-research-initiatives/sound-health.
NCMRR Funding Opportunities and Initiatives
RFA-HD-20-004: Medical Rehabilitation Research Resource (P2C Clinical Trial Optional)
This RFA is a partnership between NICHD, National Center for Complementary and Integrative Health (NCCIH), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Biomedical Imaging and Bioengineering, National Institute on Deafness and Other Communication Disorders, and National Institute for Nursing Research. Applications were reviewed in November, and a funding plan is being drafted for the January National Advisory Child Health and Human Development Council (NACHHD) meeting.
RFA-HD-20-005: Research Project Grants in Pediatric Rehabilitation (R01 Clinical Trial Optional)
Applications were reviewed in October, and a funding plan is being drafted for the January NACHHD meeting.
PAR-20-042: NCMRR Early Career Research Award (R03 Clinical Trial Optional)
This award is a reissue of the PAR-18-211. Unlike typical R03 funding, which is $50,000 direct costs per year for 2 years, this program would support grants for up to $100,000 direct costs per year, allowing clinical researchers to collect pilot data and then be more competitive for an R01 grant. This award defines “early career researcher” as someone within 7 years of their final degree. R03-awarded investigators would still retain their early-stage investigator eligibility when applying for an R01. NCMRR is currently funding 20 R03 investigators and hopes to fund more once Congress passes a budget. The annual application due dates for this initiative are March 30, 2020; March 30, 2021; and March 30, 2022.
Rehabilitation Common Data Elements
NCMRR is collaborating with NINDS on this data launch. An initial meeting occurred at the American Congress of Rehabilitation Medicine’s annual conference. Noelle Carlozzi, Ph.D., and former Board member Allen Heinemann, Ph.D., are chairing the launch group.
Action Item: Board members who are interested in working on the Rehabilitation Common Data Elements should contact Dr. Cruz at firstname.lastname@example.org.
Limb Loss and Preservation Registry
This collaboration between NIH and the U.S. Department of Defense (DoD) provides information about people who have lost a limb, including the cause of their limb loss, surgeries received, and devices used. Mayo Clinic is leading a pilot for the registry with three sites in early 2020. There are also the Limb Loss Common Data Elements, an interagency collaboration among NIH, the U.S. Food and Drug Administration, the Centers for Medicare & Medicaid Services (CMS), and other agencies to standardize limb loss and prosthetic data elements for research purposes. A request for public input and a webinar will be held in June 2020, and the finalized data elements will be shared through the National Library of Medicine.
Rehabilitation Research Funding in NCMRR and across NIH
Within NICHD, NCMRR represents 6.7 percent of the NICHD extramural budget. Center funding has steadily increased over the years, to $73 million for fiscal year (FY) 2019. Funding of rehabilitation research projects across NIH was $450 million in FY 2013 and is now at almost $700 million in FY 2019. This demonstrates that rehabilitation research connects to several other institutes and centers (ICs) across NIH and that NCMRR’s efforts at coordinating these activities are strongly leveraged.
The largest part of NCMRR funding (73 percent) is for research projects (i.e., R01, R03, R21), which is consistent with the distribution of funding in other ICs. While ICs are required to spend 3.5 percent of their extramural funds on Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants, NCMRR is more active in these areas, using 8 percent of its funding for these mechanisms. The center had been providing as much as 20 percent of its funding for these grants but believes 8 percent is a more appropriate commitment to SBIR/STTR grants and aligns well with NCMRR’s strategic goals. NCMRR also maintains a strong commitment to training and career development (11 percent of funding), in contrast the broader parts of NICHD and NIH in general (typically 5-6 percent of funding).
Meetings and Workshops
NCMRR is involved with international efforts for global rehabilitation and assistive technology. Dr. Cernich attended a World Health Organization meeting about the Rehabilitation 2030 plan, which includes rehabilitation interventions that can be delivered by nonprofessionals, which will be useful for low- to middle-income countries, and a rehabilitation research agenda. NCMRR is also partnering with the United States Agency for International Development to support the Global Partnership for Assistive Technology. The initiative recently published its research goals.
In September, NCCIH hosted the Neurocircuitry of Force-Based Manipulations workshop, which brought together basic and clinical researchers to inform each other of their work and identify gaps and barriers in the research field. A draft report from this workshop is currently moving through the approval process.
The Pathways to Prevention workshop, supported by NCMRR, NINDS, and the Office of Disease Prevention, is March 30–31, 2020. The workshop will inform physical activity guidelines for wheelchair users and is an interagency collaboration between NIH, the U.S. Department of Veterans Affairs, the Centers for Disease Control and Prevention, the National Institute on Disability, Independent Living, and Rehabilitation Research, and DoD.
The Rehabilitation Research Conference will be held October 15–16, 2020, at NIH’s Natcher Conference Center.
Outreach and Resources
NICHD wants to be more proactive about reaching out to community through social media.
Action Item: NCMRR-funded researchers should contact NCMRR about publicizing their research.
Dr. Cruz reminded the Board about NCMRR’s K12 career-development networks; R25 grantsmanship programs, physiatrist training program, and other workshops; and the P2C infrastructure centers.
Dr. Cernich thanked Dr. Cruz for her leadership as NCMRR’s acting director. She also thanked the NCMRR staff and NIH colleagues for their help during this transition.
One Board member asked about the status of the NIH FY 2020 budget and the continuing resolution (CR). Dr. Cruz indicated that the CR funds NIH through December 20, but NIH will update the community as they learn more. Dr. Cernich said the uncertainty of the budget affects the ability to pay for grants and forecast funding for future years. Lisa Kaeser, J.D., said that NICHD is planning for different scenarios, such as passing of a short-term CR until February or March, a yearlong CR, or a shutdown, but NICHD will keep its grant applicants up to date.
Liaison to NICHD Advisory Council Update
Kenneth Ottenbacher, Ph.D., OTR, Professor and Director, Division of Rehabilitation Sciences, The University of Texas Medical Branch
Dr. Ottenbacher, the Board’s NACHHD liaison, reported on the September 2019 meeting.
Dr. Bianchi’s report highlighted a Science article about the impact that Francis Collins, M.D., Ph.D., has had as NIH director and provided updates about several NICHD initiatives. The meeting focused mostly on the newly released NICHD Strategic Plan 2020, which will guide NICHD’s research activities for the next 5 years. The plan outlines NICHD’s new mission and vision statements and addresses five broad research themes with cross-cutting issues. The plan highlights NICHD’s current research goals and objectives, as well as the institute’s aspirational goals for future research activities (discussed in more depth later in this Board meeting).
Additional presentations included reports from the directors of NICHD’s Divisions of Extramural and Intramural Research; an overview of genetic research and its role in understanding human fertility, followed by a tour of NIH’s zebrafish facility; a discussion about whether NICHD should implement the Outstanding Investigator Award (R35) mechanism; a presentation from new NCCIH director Helene Langevin, M.D., C.M.; and a presentation about the impact of rare pediatric diseases with a “Voice of the Participant” perspective from a mother who had two young children who died from an unknown genetic disorder. More detailed information about the meeting can be at https://www.nichd.nih.gov/about/advisory/council/archive/201910.
Dr. Bianchi said that the “Voice of the Participant” session was very powerful and emotional. As a result of the session, the family was able to connect with investigators who are researching rare disorders and other families who are advocating for this research.
Update on the NIH HEAL Initiative
Rebecca G. Baker, Ph.D., Director, NIH HEAL Initiative, NIH
Dr. Baker said that the United States is currently dealing with two public health crises: an increase in opioid addiction, misuse, and overdose deaths, and the rise in the number of adults who are dealing with chronic pain. The NIH HEAL Initiative is a response to these crises. Congress awarded $500 million per year for this trans-NIH effort, and the initiative spent more than $945 million in the first year to fund more than 400 awards through 40 funding opportunity announcements (FOAs) in 41 states. There are 12 NIH ICs leading 26 HEAL research programs, with more than 20 collaborating ICs and offices. The research programs and their funded projects range from prevention research, basic and transitional research, clinical trials in pain and addiction, and implementation science studies.
The initiative’s two main goals are to improve treatments for misuse and addiction and to enhance pain management. Dr. Baker provided an overview of the six research focus areas, indicated the research programs within each focus, and highlighted specific programs within each focus areas. More information about these focus areas and research programs can be found at https://heal.nih.gov/research.
Novel Medication Options for Opioid Use Disorder (OUD) and Overdose
- Focusing Medication Development to Prevent and Treat OUD and Overdose
Studies in this program will focus on expanding therapeutic options for opioid addiction and overdose (e.g., user-friendly formulations of existing medications, long-duration or more powerful overdose treatments, new targets for treating OUD).
- Immunotherapies for Opioids to Prevent Relapse and Overdose
The use of vaccines and immunotherapies against opioids can help prevent relapse and overdose in populations at the highest risk for opioid addiction and misuse.
Enhanced Outcomes for Infants and Children Exposed to Opioids
- HEALthy Brain and Child Development Study
- Advancing Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW)
ACT NOW will identify effective screening tools and interventions for managing neonatal opioid withdrawal syndrome and perform a longitudinal cohort study to understand the medical, neurodevelopmental, behavioral, and social outcomes of children exposed to opioids in utero.
New Strategies to Prevent and Treat Opioid Addiction
- Preventing At-Risk Adolescents Transitioning into Adulthood from Developing OUD
- Sleep Dysfunction as a Core Feature of OUD and Recovery
- Prevention of Progression to Moderate or Severe OUD
- Optimizing the Duration, Retention, and Discontinuation of Medication Treatment for OUD
- Optimizing Collaborative Care for People with OUD and Mental Health Conditions
Translation of Research to Practice for the Treatment of Opioid Addiction
- Enhancing the National Drug Abuse Treatment Clinical Trials Network to Address Opioids
- Behavioral Research to Improve Medication-Based Treatment
- Justice Community Opioid Innovation Network (JCOIN)
JCOIN will find effective interventions for OUD in justice populations through partnerships with justice systems and community-based treatment providers. JCOIN will perform a national survey of addiction treatment delivery systems within the justice system and research the effectiveness and adoption of new medications, prevention and treatment interventions, and technologies.
- HEALing Communities Study
The HEALing Communities Study is one of the largest NIH HEAL Initiative research programs and will involve a partnership with the Substance Abuse and Mental Health Services Administration. The goal of this multisite study is to reduce opioid overdose deaths by 40 percent over 3 years in 67 urban and rural communities in four states with high rates of opioid overdose (Ohio, New York, Massachusetts, and Kentucky). The study will test the effectiveness of coordinated systems of care to increase the number of individuals receiving OUD medications, increase the distribution of naloxone, and reduce high-risk opioid prescribing in various community settings, including healthcare (e.g., primary care, emergency departments, inpatient hospitals, behavioral healthcare), criminal justice (e.g., jails, prisons, parole and probation systems, drug courts), and community organizations (e.g., families, schools, first responders, police and fire departments, faith-based organizations, housing entities, employment offices). The study results will be shared on the NIH HEAL Initiative website in real time, allowing communities to find interventions and practices that fit their needs.
Preclinical and Translational Research in Pain Management
- Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain
- Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions
- Preclinical Screening Platform for Pain
- Translating Discoveries into Effective Devices to Treat Pain
An example study from this research project is using an implantable peripheral nerve stimulator for managing phantom limb pain in people with amputations.
- Development of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and OUD
- Optimizing Non-Addictive Therapies to Treat Pain
Clinical Research in Pain Management
- Early Phase Pain Investigation Clinical Network (EPPIC-Net)
EPPIC-Net will focus on developing novel small molecules, biologics, and devices to treat a variety of pain conditions. This research will involve partnerships between academia, which has characterized pain conditions, and industry, which has many therapeutics that have not been tested for specific pain conditions. EPPIC-Net will also train new clinical investigators and incorporate newly identified biomarkers from other NIH HEAL Initiative programs into clinical trials.
- BACPAC Research Program
BACPAC’s goal is to understand chronic low back pain through basic, translational, and clinical research. Examples of BACPAC research projects include combining pharmacotherapy and behavioral therapy to treat back pain; characterizing the clinical, biological, behavioral, and biomechanical contributors to back pain; and using biosensing systems and digital health platforms to understand back pain and track treatment outcomes.
- Pain Management Effectiveness Research Network (ERN)
ERN will focus on Phase 3 effectiveness research and nonpharmacological therapy research for a broad array of pain conditions. These studies will allow healthcare providers to stop relying strongly on opioids to treat pain. An example study is testing the efficacy of a behavioral treatment for chronic pain for people who receive prescriptions for buprenorphine.
- Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM)
PRISM will leverage NIH’s previously established infrastructure and investments in pragmatic research and healthcare systems to test nonpharmacological strategies for pain management in real-world settings. For example, NIH will collaborate with CMS to consider Medicare coverage for these potential treatments. Other PRISM projects include testing electronic health record (EHR)-embedded, evidence-based nonpharmacological interventions for perioperative pain management and using transcutaneous electrical nerve stimulation with physical therapy to treat fibromyalgia.
- Integrated Approach to Pain and Opioid Use in Hemodialysis Patients
- Acute to Chronic Pain Signatures Program
The NIH HEAL Initiative is implementing various strategies to ensure these research investments result in meaningful change to opioid misuse and pain management. These strategies include continually engaging research participants, patients, and stakeholders; publicly sharing data through a Public Access and Data Sharing Plan to make primary data and publications immediately available; harmonizing measures so secondary investigators can review the data and conduct their own research; and securing a platform for HEAL data submissions from the basic, preclinical, and clinical research programs.
A Board member asked whether the NIH HEAL Initiative could track the number of rehabilitation-focused projects. Dr. Cruz said all the HEAL projects will be categorized in the NIH RePORTER, which has a category for rehabilitation. Dr. Cernich said the FOAs could also provide information about which research programs are rehabilitation-focused. Dr. Baker said that while there may not be explicit plans for rehabilitation research, as in multisite research programs, there may be a future need for rehabilitation research projects.
Dr. Bianchi said the research community should publicize the number of HEAL-funded rehabilitation projects, because the initiative will fund more projects as it grows. Dr. Baker said the NIH HEAL Initiative strives to be transparent, so researchers can search the website for projects funded by the initiative. Importantly, the initiative is not funding many pharmacological treatment projects, but rather multimodal, nonpharmacological, and integrated approaches to pain management where rehabilitation research can contribute significantly.
Another Board member asked whether there were any efforts to connect basic, translational, and clinical research efforts across the research focus areas and research programs. Dr. Baker said the initiative is working to build connections among all the initiative researchers, such as through an annual investigator meeting.
A Board member asked about the prevalence of the opioid crisis in other countries and whether there were similar research efforts in those countries. Dr. Baker said it was believed the United States had the worst overdose and addiction problems associated with overreliance on prescription drugs, but recent work indicates other countries are dealing with increased rates of heroin and fentanyl use. There are also OUD treatment research efforts in Europe and Canada. The National Academies of Science, Engineering, and Medicine’s recently released Medications for Opioid Use Disorder Save Lives report highlights some international data about OUD. Dr. Bianchi said Canada is also dealing with an opioid crisis. Recently, directors from the Canadian Institutes of Health Research (CIHR) visited NIH, and the incoming director for the CIHR Institute of Human Development, Child and Youth Health expressed an interest in collaborating with the NIH HEAL Initiative.
A Board member said many states are receiving large settlements from opioid pharmaceutical companies and asked whether NIH is working with states to determine how to use these funds. Dr. Baker said NIH is not part of the settlement process, because the NIH HEAL Initiative does not want settlement-funded treatment efforts to affect the outcome of their research trials, particularly in the HEALing Communities Study; however, as the number of these cases increase, states may reach out to NIH and the initiative for their input about how to spend their settlement funds.
NICHD Director’s Report
Diana Bianchi, M.D., Director, NICHD
NCMRR Director Search
In acknowledging Dr. Cernich’s recent appointment as NICHD’s deputy director, Dr. Bianchi said her new role may seem like a loss for NCMRR, but her skills and expertise at the director level will increase the emphasis on rehabilitation research at NICHD. The Board recognized and congratulated Dr. Cernich for this achievement. Dr. Bianchi said Dr. Cruz has generously taken the position of acting NCMRR director. Dr. Cruz has been at NCMRR for 10 years and has strong rehabilitation experience. The Board recognized and thanked Dr. Cruz for her work as acting director.
There is currently a search for a new NCMRR director. The deadline to apply for the NCMRR director position is January 3. There is a search committee that will review applications, invite candidates to interview, conduct reference checks, and create a short list of candidates for Dr. Bianchi to review. Dr. Bianchi and other members of NICHD leadership will interview these candidates and send an appointment recommendation to Dr. Collins for approval. The goal is to put a new director in place by April 2020. Board members are welcome to recommend NCMRR director candidates to the search committee.
NICHD Strategic Plan Release and Implementation
The NICHD Strategic Plan 2020 represents a tremendous amount of work from both internal staff and external stakeholders. This is NICHD’s first strategic plan since 2000. NICHD has a $1.5 million budget, so a strategic plan helps to align resources with the institute’s priorities. The development of the strategic plan began with the NACHHD Council and then involved engagement with the public, a strategic plan working group, and a 2-day workshop. Eventually, there were 270 ideas for research themes, and internal staff evaluated and prioritized these ideas into 5 research themes.
The NICHD Strategic Plan research themes are: understanding the molecular, cellular, and structural basis of development; promoting gynecologic, andrologic, and reproductive health; setting the foundation for healthy pregnancies and lifelong wellness; improving child and adolescent health and the transition to adulthood; and advancing safe and effective therapeutics and devices for pregnant and lactating women, children, and people with disabilities. While these themes are broad, the plan outlines specific priorities under each that cover the many interests of NICHD researchers.
The strategic plan’s cross-cutting themes are global health, health disparities, prevention, nutrition, and infectious disease. The strategic plan’s aspirational goals are: advancing the ability to regenerate human limbs; personalizing medicine for children; diagnosing, treating, and curing endometriosis; predicting pregnancies at risk for fetal loss; advancing and applying knowledge of the fetomaternal immune relationship; improving care of premature infants; exploring risks of technology and media exposure in the developing brain; synthesizing and personalizing human milk; building connections between atypical neurodevelopment and risk of neurodegeneration; and training investigators in artificial intelligence.
The 21st Century Cures Act, enacted in 2016, requires each IC to have a strategic plan that follows a common template. One aspect of the template is outlining how the plan will be implemented through scientific stewardship, management, and accountability. The strategic plan’s scientific stewardship goals are: promoting an inclusive scientific workforce that fosters research training; facilitating data sharing and access to biospecimens; partnering to enhance science; setting research priorities; aligning resources to support science; improving clinical trial oversight and management; monitoring and evaluating programs; and facilitating transparency and communication. The management and accountability goals are: promoting workforce development and balance; ensuring infrastructure innovation; improving administrative efficacy; and advancing enterprise risk management.
To implement the strategic plan, NICHD is using a phased approach for making progress toward each objective within the research themes. Some objectives are more long-term, whereas others need to be completed immediately (e.g., information technology support systems). There will also be set goals that can be measured objectively to demonstrate NICHD’s impact on the field (e.g., track productivity and the number of diverse investigators). These implementation processes need to be flexible, due to changing national health priorities and advances in technology.
NIH’s Division of Program Coordination, Planning, and Strategic Initiatives’ Office of Evaluation, Performance, and Reporting, which is within the Office of the Director (OD), is developing a strategic plan tracking system. This system was developed for the OD, but NICHD will be the first institute to use the system for institute-specific tracking. This system will allow NICHD to track the progress of the strategic plan and provide transparency to leadership, including NABMRR. Board members can suggest specific metrics to be included in the system and reported to the Board.
Trans-NIH Pediatric Research Consortium (N-PeRC)
N-PeRC is an effort to harmonize and coordinate child health research efforts across 27 ICs. The consortium has several goals, including creating a working group on transition to adult healthcare, expanding the pediatric research workforce, creating shared pediatric data resources, increasing the number of study section reviewers with child health expertise, and regularly reviewing and discussing existing trans-NIH initiatives that have pediatric components, such as the NIH HEAL Initiative.
N-PeRC has established a transition to adult healthcare working group, which is important for children with chronic health issues (e.g., cerebral palsy). Its members are conducting a portfolio analysis of research in this area and planning a workshop to address transitions across conditions for fall 2020. The working group will likely create RFAs and FOAs based on this research and workshop, and its members also identified research gaps for the transition to adult healthcare, including measures of successful transitions and evaluations of interventions.
Toward the goal of expanding the pediatric workforce, N-PeRC found that NIH spends more than $280 million toward funding career development and training awards for pediatric researchers. The largest contributors toward this funding include NICHD (15 percent); the National Heart, Lung, and Blood Institute (NHLBI) (14 percent); National Institute of General Medical Sciences (12 percent); National Institute of Diabetes and Digestive and Kidney Diseases (12 percent); and National Institute on Minority Health and Health Disparities (10 percent). These percentages correlate with each IC’s budget for pediatric research, except for the National Institute of Dental and Craniofacial Research, which devotes 25 percent of its budget to pediatric research. Another N-PeRC working group will examine and promote awareness of pediatric research training opportunities.
For shared pediatric data resources, N-PeRC is exploring options to combine pediatric data from across the ICs into a shared platform. These datasets include NICHD’s Data and Specimen Hub (DASH), the Gabriella Miller Kids First Pediatric Research Program, the National Cancer Institute’s Childhood Cancer Data Initiative, and the INvestigation of Co-occurring Conditions across the Lifespan to Understand Down SyndromE project. This effort will involve harmonizing the data, establishing common data elements, collecting participant consent, and addressing data security.
Maternal Morbidity and Mortality
Every day in the United States, two women die from complications connected to childbirth, and 60 percent of these deaths are preventable. Studies indicate that African American, American Indian, Alaska Native, and older women are at higher risk for maternal mortality. These complications can occur at different points in pregnancy and up to 1 year postpartum. Many of these pregnancy-related deaths are due to cardiovascular conditions, bleeding, hypertension, infection, or postpartum cardiomyopathy.
The incidence of peripartum and postpartum maternal stroke is increasing. The risk factors for maternal stroke include underlying hypertensive disorders, race and ethnicity, preexisting heart disease, advanced maternal age, cesarean section, infections, and migraine. In Theme 3 of the NICHD Strategic Plan, the objectives include characterizing pre-pregnancy and pregnancy factors that increase risk of adverse maternal conditions, developing strategies to improve prevention and response to these complications, and extending studies into the “fourth trimester,” or postpartum period, which has been inadequately studied.
PregSource® and the All of Us Research Program
PregSource® is a free website that crowdsources information from pregnant women about their pregnancy experiences, including sleep, nausea, exercise, weight, and medications. Recruitment for PregSource® has been low, but there is a recent effort to have the All of Us Research Program encourage its pregnant participants to enroll in PregSource®. The goal is to increase PregSource® enrollment and link maternal and child EHR data. All of Us plans to begin enrolling children into the program in 2020.
Draft NIH Data Sharing Policy
NIH wants to promote efficient data management and share these data with the public. Every 2 years, NIH releases Requests for Information (RFIs) for the research community to contribute to the draft NIH Data Sharing Policy. The rehabilitation research community is encouraged to share their priorities for data management and sharing through the RFI. Responses must be submitted by January 10.
Congress implemented a CR through December 20, and hopefully will pass an FY 2020 budget before the end of the year. NIH was not affected by the previous government shutdown but will be affected if the government shuts down at the end of the year.
Along with filling the NCMRR director position, NICHD is hiring a Pregnancy and Perinatology Branch chief as well as program officers for the following branches: Child Development and Behavior, Intellectual and Developmental Disabilities, Obstetric and Pediatric Pharmacology and Therapeutics, Pediatric Trauma and Critical Illness, and Pregnancy and Perinatology. More information about these jobs is available at https://www.nichd.nih.gov/about/jobs.
In response to a question from the Board, Dr. Bianchi said the template for the NICHD Strategic Plan is the template required by law and will be used for other ICs’ strategic plans. To fulfill the scientific stewardship, management, and accountability aspects of the strategic plan, NICHD is using the OD’s tracking system. If that tracking effort is successful, other ICs may use this system. Dr. Cernich added the system will allow NICHD to track deadlines for specific tasks and look at strategic management.
Another Board member asked about additional NIH datasets and resources that could be publicized in the research community. Dr. Bianchi said DASH is an excellent resource for clinical research data. NHLBI’s Trans-Omics for Precision Medicine program has genomic data related to heart, lung, blood, and sleep disorders, and there is a trans-NIH Database of Genotypes and Phenotypes.
NCMRR’s Support of Career Development: K12 National Networks
Ralph Nitkin, Ph.D., Deputy Director, NCMRR, NICHD
Dr. Nitkin said NCMRR is committed to training rehabilitation researchers and supporting career development. Compared with other NIH components, NCMRR devotes a higher percentage of its budget to training and career development (11 percent versus 5-6 percent). Within the FY 2019 NCMRR training and career development budget, 30 percent was devoted to institutional career development awards (K12); 25 percent to individual career development awards (K01, K08, K23); and 23 percent to departmental training awards (T32).
As background, NICHD has an unusually large percentage of training and career development funds (38 percent) dedicated to K12 networks, as compared to other ICs (up to 11 percent). This large investment in career development networks reduces the budget for individual K awards, so NICHD reviewed its training priorities. NICHD decided to maintain its commitment to use 6 percent of its budget for funding training and career-development awards, but would realign the programs based on recommendations from the NICHD Training Review, the NIH Biomedical Research Workforce, and the NIH Physician-Scientist Workforce Working Group. Their recommendations were to increase K08 and K23 salary contributions from $75,000 to $100,000, increase success rates for individual career development and K99/R00 awards, and increase relative proportion of funds that go to individual K versus institutional K12 awards.
Unlike some other NICHD programs that support institutional K12 programs, NCMRR has four K12 networks that support physical and occupational therapy doctorates, rehabilitation bioengineers, and neurorehabilitation clinicians, respectively; an earlier NCMRR K12 program provided support for physiatrists. The NCMRR programs provide salary to meritorious scholars for 2 to 3 years, and continued career support (but no further salary) for an additional few years. Despite the strengths of these K12 program, a significant number of scholars never apply for independent research awards. However, K12 scholars who went on to get individual K awards were more likely to apply and later succeed with R award funding. Similar trends were seen throughout NICHD K12 programs, further reinforcing the recommendation to emphasize support of individual K awards over K12 networks.
Based on these data, NCMRR will no longer support the K12 program but continue supporting individual K awards (e.g., K01, K08, K23, K25). Additional career-development funding opportunities from NCMRR include the Early Career Research Program (PAR-20-042), and several Research Education Programs (R25), which support the Training in Grantsmanship for Rehabilitation Research (TIGRR) workshop, the Rehabilitation Medicine Scientist Training Program, and the Team-Based Design in Biomedical Engineering Education (PAR-19-215). Additionally, members of NCMRR staff participate in early-career workshops at national meetings (e.g., American Congress of Rehabilitation Medicine, the Association of Academic Physiatrists, and the American Physical Therapy Association).
One Board member asked about the differences between the R25 and K12 programs. Dr. Nitkin indicated the K12 programs have a much larger budget, including funds for individual scholar salaries. In contrast, the R25 provides up to $150,000 for short courses, summer programs, or educational activities, but no direct support for trainee salaries. Individual K awards provide for up to 5 year’s salary and a small amount for research costs.
Another Board member asked about the K99/R00 Pathways to Independence awards in contrast to other individual K awards. Dr. Nitkin indicated it is difficult to compare these mechanisms, because most of the individual K awards are meant for trainees who have a clinical background but may need more research experience. The K99/R00 awards are open to a broader group of researchers (including more traditional Ph.D.s) and provide only 1 to 2 years of mentored support. Then, if the trainee secures a tenure-track faculty position, they can activate the 3-year R00 phase to support independent research projects. There is an NIH-wide effort to fund more K99/R00 awards to support young investigators moving into academic positions and independent research careers. Dr. Cruz added that eligibility for K99/R00 awards is limited to investigators within 4 years of their terminal degree who do not yet have a tenure-track appointment.
Another Board member asked about NCMRR’s efforts to work with rehabilitation programs and institutions to implement training and career development activities, such as internships. Dr. Cernich reiterated that NCMRR is working to inform the community about the end of NCMRR K12 programs so that academic departments and professional organizations can plan for their own programs and mentor networks to support trainees who are applying for individual K awards and beginning research grants. The larger NICHD will retain some K12 programs, but significantly downsize and reprioritize training and career development into individual award mechanisms.
Another Board member noted the rehabilitation bioengineering K12 scholars showed high rates of applying for and receiving R funding, and NCMRR should consider what worked for that program before eliminating the K12 programs. Dr. Nitkin agreed the K12 programs established strong networks and connections among scholars and mentors. Dr. Cernich agreed some K12 programs worked better than others but emphasized that academic institutions and professional societies need to take on the role of supporting trainee mentorship and promoting careers in research. In that manner, NCMRR could support a broader array of support trainees at lower cost if organizations and academic departments took on a more active role in training.
A Board member asked whether other training funding mechanisms were open to other researchers and mentors, such as nurses. Dr. Nitkin said those mechanisms are open to anyone with an appropriate research background.
Another Board member noted the major benefits of K12 programs were training and support of the mentor networks, more nimble appointment of research scholars, and the creation of an emerging cadre of research scholars. The Board member suggested some of these activities could be supported through small workshops. Dr. Nitkin reiterated NCMRR staff supports such activities and networks at professional meetings.
A Board member asked whether there were other targeted funding mechanisms that were successful for specific clinical fields. But Dr. Nitkin pointed out that support for more targeted and individualized training programs would diminish resources available to the broader research community. Dr. Cernich added that the Board encouraged NCMRR to promote more interdisciplinary science, rather than specialized programs. She also noted there is now a robust group of mentors in rehabilitation research fields. Another Board member added that these mentors would contribute to improved success with individual career-development awards.
A Board member asked about K12 outcomes relating to scholars seeking independent funding from various foundations (e.g., the American Heart Association). Dr. Cernich indicated NCMRR looked for applications to other federal agencies (e.g., U.S. Department of Veterans Affairs (VA), National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR), and National Science Foundation), but could not track applications to independent foundations.
Rehabilitation Research Plan 2018 Data Update
Jennifer Jackson, Ph.D., Health Program Specialist, NCMRR, NICHD
Dr. Jackson provided an overview of the strategy and coding process, the development and validation of the algorithm, the results of the 2018 rehabilitation portfolio analysis, the results of clinical impact and interdisciplinary collaboration analysis, and yearly trends in the 2015–2018 data. These data are still considered a draft until approved by the NIH Office of Financial Management but will be used in the NIH Research Plan on Rehabilitation.
Funded NIH projects were categorizing into two tiers. In the first analysis, each project was assigned to primary and secondary themes from the NIH Research Plan on Rehabilitation:
- Rehabilitation across the lifespan
- Community and family
- Technology use and development
- Research design and methodology
- Translational science
- Research capacity and infrastructure
A secondary analysis assigned the projects by type of research:
- Disease-related basic
- Applied (translational or clinical)
The results of the 2018 rehabilitation portfolio analysis included:
- The number of grants and the amount of funding for rehabilitation projects per funding mechanism, per IC, and per NIH Research, Condition, and Disease Categorization (RCDC) term (e.g., projects under the RCDC terms Clinical Research, Neurosciences, and Behavioral and Social Science had the most grants and received the most funding)
- Funding across more than 50 rehabilitation topics and within specific ICs
- A specific focus on rehabilitation-related clinical trials, particularly Phase III trials
- Specific linkages among primary and secondary categories
- The number of publications associated with the 2018 rehabilitation portfolio
- Analyses of the biosketches to determine specialties of the primary investigator (PI) and collaborations among other investigators
- Longitudinal analysis from FY 2015 to FY 2018 for growth of primary research categories, types of research, clinical trials, and Phase III clinical trials
One Board member asked about the use of biosketches for pulling out the PI specialties, and how they dealt with multiple specialties. Dr. Jackson indicated that specialties were determined by text-mining the biosketches, but they often involve different formats. Dr. Cernich added that NIH Office of Portfolio Analysis is working to update and standardize this analysis process.
Another Board member wanted clarification on the definition of “rehabilitation” that was used in these analyses. Dr. Cernich responded that RCDC categories are based on an official, internal NIH working definition of rehabilitation. This definition was developed by consensus among experts at NIH but is not publicly shared because it is still evolving; it also includes subcategories. Dr. Jackson indicated she often defers to the definition of rehabilitation from the 21st Century Cures Act definition, which continues to be used for the development of the NIH Research Plan on Rehabilitation.
A Board member asked whether, based on these analyses, interdisciplinary, multi-specialty grants will be more successful than single-specialty grants. Dr. Cernich said that funding success would depend on the type of project and whether it requires multiple disciplines. Dr. Nitkin asked whether there was a way to analyze the larger pool of applications, especially those that were close to receiving funding. Dr. Jackson indicated that starting in 2018, RCDC has categorized all applications received not just those funded, so this analysis would be possible for 2018 to present.
Rehabilitation Research Conference Subcommittee
Dr. Reinkensmeyer said that the subcommittee is excited about developing a great conference. The conference will be October 15–16, 2020, and will focus on the future of rehabilitation research, the types of new collaborations that are needed, and ways to push for implementation. People with disabilities, especially those who are involved with the research, will be an integral part of the conference. There will also be a focus on the specific themes and topics from the Research Plan on Rehabilitation.
There is a draft agenda, but specific speakers have not yet been invited yet. Dr. Cruz said the subcommittee did not want to invite people who spoke at the previous Rehabilitation Research Conference in May 2016. The potential speakers are funded by a variety of NIH ICs, have a variety of training backgrounds, and have good ethnic/racial and gender representation.
One Board member suggested the inclusion of a session on community and family research. The subcommittee agreed.
Dr. Nitkin asked about the subcommittee’s process for defining the conference agenda. Dr. Reinkensmeyer said the conference will be forward-thinking but also focused on what practices could be implemented soon. The conference will also assess progress toward previously established goals and look ahead to the next 5 years. Dr. Cernich said the conference in 2016 focused on educating the community about rehabilitation research and funding opportunities at different ICs, so the subcommittee decided to focus this upcoming conference on future goals for the rehabilitation field.
Another Board member suggested connecting the research plan and conference planning. Dr. Cruz agreed and indicated the goal is to have the conference inform the research plan, but their planning is moving in parallel. Ideally, themes for the research plan should be on the conference agenda, because input from the conference, either during the town hall or from other polling opportunities, will be integrated into the research plan. The Board member suggested providing conference attendees with a brief outline of the proposed research plan to solicit feedback during the conference, and Dr. Cruz agreed. Dr. Nitkin added the research plan needs to be broad and aspirational, to excite the research community about the topics and goals of the research plan.
A Board member asked about the target date for the actual release of the research plan. Dr. Cruz indicated the plan must be presented to Congress in 2021 and there is an extensive clearance process within NIH prior to that. The Board member said there would be adequate time for public feedback but wondered how this could be integrated with the clearance process. Dr. Cernich said that previously, the full research plan was released for public comment prior to the conference, and the RFI closed before the conference. This time, the RFI could be through the conference, but the timing of the public comment period would depend on how much the group wants to update and change the base plan.
Dr. Nitkin added that implementation and dissemination should be important focuses of the research plan.
After some discussion, the Board agreed there should be an opportunity for feedback about the research plan during the conference, such as the town hall, and have the RFI open at the same time as the conference, to ensure that people who could not attend the conference in person could still provide feedback. The Board also liked the idea of hosting a webinar about the RFI before the conference for additional feedback, similar to the webinar for the 2016 research plan. Dr. Cernich said that by the May Board meeting, there should be a more concrete timeline for the research plan and RFI so the community can prepare their responses.
Dr. Cernich said the conference will also feature a celebration of NCMRR’s 30th anniversary.
One Board member asked about the RFI response rate for the research plan. Dr. Cernich said the 2016 Research Plan on Rehabilitation received 120 comments from the RFI, and a recent RFI about the upcoming research plan received 39 comments. The most recent feedback was positive and had minimal comments about structurally changing the basic priorities of the research plan. The Board member suggested creating a survey for conference attendees to complete before the conference. Dr. Cernich said NIH cannot release surveys, but it could use IdeaScale for crowdsourcing using structured questions.
Another Board member asked about the evolution of NCMRR’s advocacy for rehabilitation research. Dr. Nitkin said NCMRR has always worked to coordinate rehabilitation research across NIH but having their own budget in recent years has increased the center’s ability to influence other ICs and the larger research community.
Rehabilitation Research Plan Subcommittee
Dr. Lutz said the subcommittee has reviewed the RFI comments about the research plan. Overall, the comments were supportive of the current research plan but had suggestions for improved metrics for measuring progress. The plan will keep the same themes, but the subcommittee is working to update the plan’s format and objectives.
A subcommittee member added that they plan to add the data from Dr. Jackson’s recent analyses to the research plan to demonstrate the success of current efforts to expand the rehabilitation research portfolio.
A Board member asked whether the research plan had a required template and plan to track outcomes. Dr. Cernich said there is not a required format, since this is a research plan and not a strategic plan. This research plan outlines the rehabilitation research agenda across NIH and will track metrics such as the growth of the portfolio, known gaps in the research, and the impact on publications, patents, and U.S. Food and Drug Administration (FDA) approvals.
In response to Dr. Nitkin’s question, Dr. Cruz said that the research plan themes will remain the same, but the objectives within each theme will be changing.
Dr. Field-Fote adjourned the first day of the formal Board meeting 4:00 p.m., to provide each of the subcommittees (Conference and Rehabilitation Research Plan) further time to meet.
Pathways to Prevention (P2P) Initiative Update
Joseph Bonner, Ph.D., Health Science Administrator/Program Officer, NCMRR, NICHD
Dr. Bonner said the P2P initiative addresses scientific areas that are underdeveloped and require an unbiased, evidence-based assessment. The upcoming P2P workshop, “Can Physical Activity Improve the Health of Wheelchair Users?” will be held March 30–31, 2020, at Natcher Conference Center on the NIH campus. Registration for the workshop is open and the event will be videocast. The first three rows of the auditorium will be removed to accommodate attendees who use wheelchairs. For more information go to https://prevention.nih.gov/research-priorities/research-needs-and-gaps/pathways-prevention/can-physical-activity-improve-health-wheelchair-users.
One factor that contributed to the development of this P2P workshop about wheelchair users was the U.S. Department of Health and Human Services’ Physical Activity Guidelines for Americans from 2018. The report did not show strong evidence of the benefits of the physical activity recommendations to reduce disease burden for wheelchair users. Additionally, the National Academies of Science, Engineering, and Medicine’s report, The Promise of Assistive Technology to Enhance Activity and Work Participation, predicts the number of wheelchair users will quadruple between 2005 and 2030. The report notes that the right wheelchair can improve workforce participation and highlights a lack of data regarding wheelchair use, both in the literature and through datasets.
The NIH Office of Disease Prevention (ODP) requires proposals to be supported by at least two ICs; this P2P initiative is supported by NCMRR and NINDS. The P2P initiative involves a systematic evidence review performed by one of the Agency for Healthcare Research and Quality’s Evidence-Based Practice Centers. The center that performs the review remains confidential until release of the draft evidence review. The initiative also involves a 1.5-day workshop. The review and workshop processes run in parallel. ODP also appoints an independent panel, which will be chaired by Thomas LaVeist, Ph.D., to evaluate the systematic review and the workshop outcomes and prepare a report with action items for consideration by the federal partners, which include NIH, VA, Centers for Disease Control and Prevention, NIDILRR, and the U.S. Department of Defense.
The initiative will assess a wheelchair user population limited to people with spinal cord injury (SCI), multiple sclerosis (MS), and cerebral palsy (CP). “Physical activity” is defined as any gross motor activity that increases energy expenditure. The goals of the P2P initiative are to inform the future clinical practice guidelines for wheelchair users, identify research gaps, inform future research, and create a synergistic action plan with the federal partners.
The evidence review and the workshop are based on four key questions:
- What is the evidence base on physical activity interventions to prevent obesity, diabetes, and cardiovascular conditions, including evidence on harms of the interventions in people with MS, CP, or SCI who are at risk for or currently using a wheeled mobility device?
- What are the benefits and harms of physical activity interventions (e.g., type and amount of activity) for people who are at risk for or currently using a wheeled mobility device?
- What are the patient factors (e.g., cause of wheelchair use, age) that may affect the benefits and harms of physical activity in patients who are at risk for or currently using a wheeled mobility device?
- What methodological weaknesses or gaps are there in the evidence to determine the benefits and harms of physical activity in patients who are at risk for or currently using a wheeled mobility device?
Dr. Bonner reviewed the P2P workshop agenda. Sessions focused on the key questions involve a summary of the findings based on systematic evidence review and presentations from experts in the field. The systematic evidence review will be posted for public comment in early 2020, the workshop will be March 30–31, the independent panel report will be released in spring 2020, and then the federal partners will meet to discuss the action items from the panel report in the summer or fall of 2020.
One Board member asked whether people with a congenital injury or spina bifida would be included in the review. Dr. Bonner said these populations were not excluded, but they did not meet the criteria to be included in the review. The workshop will cover any population of wheelchair users, but the scope of the evidence review had to be narrowed.
Another Board member asked how many P2P topics are in review and whether there were other potential P2P topics NCMRR could pursue. Dr. Bonner said NCMRR is not planning any P2P topics at this time. There are usually two P2P topics publicly announced per year, but it is it a competitive selection process because it is funded by the OD.
Teaming with Participants to Improve the Validity and Rigor of Rehabilitation Research
Jennifer Stevens-Lapsley, PT, Ph.D., Director, Rehabilitation Sciences Ph.D. Program, MOVE Lab, University of Colorado School of Medicine, VA Eastern Colorado Health Care System
Rob Wudlick, Project Director, Research, University of Minnesota Medical School
Dr. Stevens-Lapsley and Mr. Wudlick discussed the need to include advocates and people with disabilities in the research process to address the disconnect between the goals of academic research and the needs of the clinical community. Participants could also include anyone who influences clinical care, including patients, payers, providers, and policymakers.
It can take between 17 and 25 years to translate original research into clinical practice, depending on the time it takes to receive funding, collect pilot data, and conduct the study. One potential solution to speed up this timeline and enhance translation is to include participants from the beginning and throughout the research process, including developing protocols, writing grant applications, conducting pilot testing and research, interpreting data, and publishing and disseminating research.
The benefits of including participants are a better generation of ideas, validation of research concepts and strategies that benefit consumers, diverse viewpoints that enhance funding opportunities, improved understanding of consumers (e.g., different needs for quadriplegics versus paraplegics), and the advantage of specific participants’ skills (e.g., engineers, doctors, lawyers). FDA recently released a draft guidance, Patient Engagement in the Design and Conduct of Medical Device Clinical Investigations, which identified other benefits of participant engagement, including faster participant recruitment and study completion, greater participant commitment, better study compliance, and outcomes relevant to consumers. For more information, see https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-engagement-design-and-conduct-medical-device-clinical-investigations.
While there is a cost associated with engaging these participants, there should be a priority to invest in these participants at the beginning of the project so research has better long-term impacts.
Dr. Stevens-Lapsley and Mr. Wudlick provided recommendations, based on their experiences, on how to engage with participants effectively:
- Reimburse and formally recognize participants as consultants if they provide valuable contributions.
- Formally engage and integrate participants in the research team, rather than inviting them for a one-time meeting.
- Avoid tokenism in which participants are checkmarks rather than meaningful contributors for processes such as peer review of publications or grant applications and meetings about device development.
- Locate potential participants through patient-representation organizations, patient online chat and community forums (e.g., Facebook groups), community gathering places (e.g., adaptive fitness centers), local clinicians, and social media, as well as past or current participants.
- Adjust to participant needs by making visits convenient (e.g., providing travel or parking vouchers, carpools), eliminating transportation barriers (e.g., hosting virtual meetings, visiting participants’ homes), providing accessible materials (e.g., larger font, voice amplifiers), and fostering participation affiliation (e.g., producing newsletters or study updates).
- Use formal participant networks (e.g., the Older Veteran Engagement Team), focus groups, and surveys to engage participants with research studies.
- Consider participant diversity, such as ethnic and racial representation, health beliefs and life priorities, socioeconomic barriers, gender and sex, barriers to physically accessing materials, health literacy, and education.
- Inform participants of the results or publications associated with a clinical trial, even if the results are released years after their participation.
- Continue engaging with participants after the completion of the study, to get feedback about the study process.
- Use participants to help disseminate study findings through their advocacy groups and networks and as representatives at research conferences.
Additionally, NIH could track and reward investigators for including diverse participants in the research process through grant review funding and a section in grants that notes diverse recruitment efforts. There are some K awards and administrative supplements for individuals with disabilities.
The Board discussed the importance of informing participants at the beginning of a study about when they should expect to receive study results, that they cannot receive any results before the completion of the study, and the scientific rigor required to prevent participant bias that could influence study outcomes. The Board also discussed using a layperson summary to explain the results to study participants.
One Board member asked whether participation in unsuccessful SCI research studies would affect participants’ willingness to participate in other studies. Mr. Wudlick said there are many failed SCI studies, but researchers who study interventions that continually fail can cause frustration and distrust among participants.
Dr. Nitkin said it would be interesting to determine whether researchers who integrated participant engagement in their study process had shorter clinical implementation timelines. Dr. Stevens-Lapsley said this analysis could be conducted soon.
Another Board member asked how to engage participants and consumers with more basic or mechanistic studies. Mr. Wudlick said participants could provide a statement of support about how this basic research would apply to their condition. Dr. Stevens-Lapsley said researchers should show clearly the potential translation of these basic mechanistic questions.
Dr. Stevens-Lapsley and Mr. Wudlick said research teams should inform the research and participant communities about negative data, potentially through publications. A Board member added that for negative or failed studies, it is important to remind participants that their role in the study still had many benefits. Mr. Wudlick agreed and said the research team should determine what data from these studies can be used. Another Board member said sharing data with the research community can also be important to help in future studies or as benchmarks for historical and natural history datasets.
Dr. Cernich said that ClinicalTrials.gov is an important resource for the research community. This website will be redesigned to include return of results to study participants and a lay results summary. These features will allow negative studies that cannot be published to still be publicized. Most of the studies listed on the website are not funded by NIH. The website will release an RFI asking for suggestions for the website redesign. Mr. Wudlick said that SciTrials.org also has lay results summaries.
A Board member asked about the best practices for vetting participants with specific expertise. Mr. Wudlick said it is often trial and error, but research teams can share their abstracts or research plans with consumer representative organizations and the disease community. Dr. Stevens-Lapsley said interviews are also helpful for understanding a participant’s intentions and level of engagement.
Another Board member appreciated the points about avoiding tokenism and tracking and rewarding investigators for their inclusion efforts. She suggested training reviewers to identify and reward grants that note efforts to include participants.
A Board member added that research teams should consider how to disengage with participants in a caring manner after a study is over or funding has ended. While the team can maintain contact with these participants or invite them to meetings, it could still be a difficult transition for participants. Mr. Wudlick agreed and said participants can be very passionate about projects, which makes it difficult when these studies end. Teams can prepare participants for these outcomes at the beginning of the study or use participants to disseminate the research.
Mr. Wudlick said people who live with specific conditions have years of unique, valuable, and often underused knowledge of and experience with those conditions.
Scientific Presentation—Precision Medicine in Pediatric Rehabilitation: Optimizing the Functional Potential of Each Child
Craig McDonald, M.D., Professor and Chair, Department of Physical Medicine & Rehabilitation, University of California, Davis
Dr. McDonald presented his research about rapidly progressive childhood-onset diseases such as Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), and the use of precision medicine to optimize treatments for these diseases. Dr. McDonald provided background on the pathophysiology and impairments associated with these conditions, as well as the clinical assessments used to monitor disease progression and precision medicine therapies for these diseases.
DMD is a relatively rare X chromosome–linked disease that affects boys and young men, causing the loss of motor skills, ambulation, and upper limb function and leading to paralysis, respiratory failure, cardiomyopathy, and premature death. DMD is caused by the absence of dystrophin. Current rehabilitation and management options for DMD include glucocorticoids, respiratory treatments, mechanical devices, and cardiac treatments. There is evidence that long-term steroid treatment of DMD patients increases life expectancy, prolongs the time before ambulation loss, and improves performance in various clinical assessments.
Currently, there are molecular genetic exon-skipping therapies (e.g., eteplirsen) that promote the assembly of a shortened, functional dystrophin protein and slow disease progression. Eventually, around 70-80 percent of DMD patients could be treated with exon-skipping therapies. There are also microdystrophin gene therapies that attempt to deliver the critical domains of dystrophin. Early single-dose microdystrophin treatment studies show integration of microdystrophin in muscle cells and improvements in motor performance; however, the treatment’s safety and durability has not yet been proven.
SMA is the most common genetic cause of death in children. The genes survival motor neuron 1 and 2(SMN1 and SMN2) are associated with SMA; SMN1 is the causative gene, and SMN2 modifies the disease’s severity. There are three types of SMA. Type 1, the most severe form of SMA, is caused by two copies of SMN2. Disease onset occurs between birth and the age of 6 months, results in a shortened life expectancy, and requires respiratory support. Type 2 is an intermediate form caused by three copies of SMN2 and develops between the ages of 6 months and 18 months. People with SMA type 2 have a life expectancy of around 20 years and often require motorized wheelchairs and noninvasive ventilation. Type 3 is caused by three or four copies of the SMN2 gene, and the disease manifests between the ages of 18 months and 3 years. People with SMA type 3 have a normal life expectancy and are able to walk but have decreased ambulatory function over time.
Early treatment of SMA is essential to improve outcomes. A recent study showed a single-dose gene replacement therapy that delivers the SMN gene in an adeno-associated virus capsid increases the duration of survival without permanent ventilation and improves motor function. Another gene therapy targets the mRNA of SMN2 to produce a full-length protein and is administered through a fecal transplant. This treatment increases event-free survival and improves long-term motor function. Some SMA patients use Jaco robotic arms to assist them with day-to-day activities.
Dr. Nitkin asked whether the activity-based strategies further enhanced the ability of molecular genetic treatments (e.g., exon-skipping or microgene therapies) to improve motor function. Dr. McDonald said there is some evidence that physical activity improves muscle fibers’ uptake of exon-skipping therapy, but this has not been analyzed with the single-dose therapies. Since these patients still have serious motor impairments, activity-based treatments would be helpful at improving their functional outcomes.
A Board member asked whether there was a level of activity that would damage the muscle fiber. Dr. McDonald said the evidence shows that DMD and SMA patients have better functional outcomes when they are engaged in aerobic physical activities, but high resistance load activities may decrease muscle function and promote damage.
Final Summary and Planning for the Next Meeting
Edelle C. Field-Fote, PT, Ph.D., Chair
Dr. Field-Fote asked the Board members to suggest topics for the next Board meeting in May.
In response to a question from a Board member, Dr. Cernich indicated that the May meeting will include a discussion about the Research Plan on Rehabilitation, but the planning of the Rehabilitation Conference should be mostly finalized by May.
Another Board member said there should be a continued discussion about the K award funding mechanisms, particularly about the benefits and disadvantages for each mechanism, to advise future applicants. Dr. Nitkin agreed and said he could explain how each mechanism affects rehabilitation career trajectories. Dr. Nitkin asked about what relevant data were needed for this discussion and the Board suggested data about the success of different K awardees receiving R01 funding, the time it takes for these awardees to receive R01 funding, and differences between the rehabilitation backgrounds. Dr. Cruz said it may be difficult to define control groups for these analyses, since there are budget and other funding changes each year. Dr. Cernich suggested that Board members read the Office of Extramural Research blog, Open Mike, which tracks R01 funding success based on different factors such as applicant location, sociodemographic factors, and specific policies.
Another Board member asked about having an update of the rehabilitation research portfolio data, and Dr. Cruz said an update would likely be provided at the December 2020 Board meeting.
A Board member requested a presentation with information about loan repayment grants, so investigators could also understand these mechanisms. Dr. Cruz agreed but indicated that NCMRR does not review loan repayment grants. However, members of NIH staff who do review these grants could be invited to present to the Board.
Dr. Field-Fote thanked the Board members for their contributions and said members may be contacted about presenting at the next Board meeting. The meeting was adjourned at 11:46 a.m.