Summary Minutes - December 4-5, 2017

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 4-5, 2017

Introductions

The 55th meeting of the NABMRR was called to order at 9:00 a.m. Board members introduced themselves, followed by brief introductions from NIH staff and other visitors. Minutes from the previous meeting of May 1-2, 2017, were unanimously approved. Future Board meetings will be May 7-8, 2018, December 3-4, 2018, and May 6-7, 2019.

Members Present:

Members Absent:

Sureyya Dikmen

Ad Hoc Members Present:

Ex-Officio Members Absent:

Ex Officio Members Absent:

Teresa Brininger, DOD

NICHD Staff and Visitors:

NICHD Director’s Report

Diana W. Bianchi, M.D., NICHD Director, provided the following update.

Legislative Update

The government was operating on a continuing resolution, which would continue through December 8 and was expected to be extended. Because of the budget uncertainty, some grants that the National Advisory Child Health and Human Development Council approved at its September meeting would be withheld until the fiscal year (FY) 2018 budget is passed.

NICHD is implementing several portions of the 21st Century Cures Act, including medical rehabilitation research, research on pregnant women and lactating women, inclusion of children in research, and the Next Generation Researchers Initiative. The NCMRR had already fulfilled another Cures Act requirement by publishing the NIH Research Plan on Rehabilitation.

As a requirement of the Cures Act, the NICHD formed the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) to identify research needs in the areas of pregnancy and lactation, particularly related to medication safety. There is very little research available on medications that pregnant women and lactating women can use. The lack of data leaves women with hard choices about whether to take their medications during pregnancy and lactation or to go without. An NICHD literature review indicated that the few studies on pregnant women and medications centered on hypertension, preterm labor, and labor pain. There is little research on medications related to many other conditions, including anxiety, depression, and alcohol and cocaine abuse. There are also very few studies on the transfer of drugs to breast milk.

NICHD took part in NIH’s Inclusion Across the Lifespan workshop in June. The workshop focused on the challenges and barriers of including children (younger than 18 years) and older adults (65 years and older) in clinical trials. The workshop identified strategies to produce more age-inclusive clinical trials. NICHD focused on including children and people with physical and developmental disabilities in NIH-funded research.

In preparation for the meeting, NICHD staff reviewed the literature and found that 65 percent of NIH-funded studies planned to include children (defined as people younger than age 21), but only half of those planned to include children who were younger than 18. Further, in 60 percent of NIH phase III clinical trial grants that planned to include children, the researchers did not plan to analyze the results by age. And 25 percent of the studies planning to include children under 18 did not include them in the conclusion of the study. NIH Director Francis Collins, M.D., Ph.D., will issue recommendations based on the workshop findings.

Vision Update: Partnerships

NICHD is developing stronger partnerships across the NIH, including with the National Human Genome Research Institute (NHGRI), the National Institute on Drug Abuse (NIDA), the Office of the Director’s Environmental Influences on Child Health Outcomes (ECHO), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute on Aging (NIA), the National Institute of Allergy and Infectious Diseases (NIAID), the NIH Clinical Center, and the All of Us Research Program.

NICHD and the NHGRI held a meeting in May to address the research gaps in prenatal, perinatal, and neonatal genomics; to explore genomic technology and its implementation; and to explore the ethical and social implications of work in this field. NICHD will also cohost a workshop to identify gap areas for future funding.

ECHO and NICHD will address the opioid crisis as it relates to pregnant women and their newborns through a new program, Advancing Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW). There is an increased prevalence of opioid use during pregnancy, leading to a fivefold increase in neonatal opioid withdrawal syndrome. In 2012, nearly 22,000 infants were born with the syndrome. There are many questions that research could help answer, such as whether it is better to treat the infant in the intensive care unit, in a special setting, or at home. There is also increased interest in medically supervised withdrawal during pregnancy, but it is not clear whether this approach is safe for the pregnant woman and her fetus. ACT NOW is a partnership involving the Neonatal Research Network Centers and the Institutional Development Award (IDeA) States Pediatric Clinical Trials Network. The Pediatric Clinical Trial Network sites are in states with a higher prevalence of opioid misuse. The partnership will develop a protocol to treat infants who have been exposed to opioids.

NICHD and the NIDDK will coordinate efforts to address the epidemic of childhood obesity. At the current rate, 60 percent of the U.S. population could be obese by the time they are 35 years old. This will have implications for medical rehabilitation, including an increased need for knee replacements. The Institutes will determine the gaps in knowledge and opportunities for shared initiatives.

A similar effort is under way with the NIA to expand the trans-NIH strategy for research in Down syndrome. The effort will build on the Down Syndrome Consortium’s work. NIH provides $27 million to Down syndrome research, most of it from NIA and NICHD. NICHD and the NIA are also exploring the possibility of developing public-private partnerships to expand the pool of funding. The biology of those with Down syndrome is unique; they have a much lower incidence of solid tumors, but they often develop Alzheimer’s disease. There is opportunity to learn from their biology and to apply it to other conditions.

NICHD and the NIAID are partnering to ensure that mothers, children, and adolescents are included in future clinical networks involving existing and emerging infectious agents. This activity is part of an effort to improve how to respond to infectious diseases in pregnant women. More than 5,000 pregnant women are already enrolled in the Zika in Infants and Pregnancy study in sites in the United States, including Puerto Rico.

NICHD is identifying opportunities for intramural basic and clinical research collaborations at the Clinical Center. Currently, children younger than 3 years old and pregnant women cannot participate in clinical protocols at the Clinical Center because subspecialists who can provide critical care to these populations are not available. Dr. Bianchi has been appointed to the Clinical Center’s Governance Board, where she will serve as an advocate to include pregnant women, children, and people with developmental disabilities in the Clinical Center’s work.

Council

At the January Council meeting, members will review the portfolio involving people with disabilities, including developmental disabilities. The Council will also hear a presentation from a patient as part of its Voice of the Patient series. The patient speakers’ experiences are related to research presented at the Council.

Dr. Bianchi has recently met with members of the Congressional Black Caucus and the Women’s Congressional Policy Institute. Dr. Bianchi was also among those who met with the Acting Secretary of HHS Eric Hargan.

Training Update

An analysis of NICHD-funded physician scholars who received either an institutional K award (a K12) or an individual K award (a K08 or a K23) found that physician-scholars (those with an M.D. only) who received individual K awards were more likely to apply for and to receive an independent NIH grant later. This analysis will soon appear in JAMA Pediatrics. This finding has resulted in a policy change to provide more individual awards than institutional awards. It is not clear why those who receive an individual K award are more successful, but one possibility is that the individual K award provides experience with independently writing a grant application.

Data and Specimen Hub (DASH)

DASH is a centralized resource for researchers to store and access de-identified data from studies supported by the NICHD. DASH now contains data from 53 studies covering 22 topics. Many studies also link to biospecimens. NICHD is working to make the biospecimens available to researchers. There are now 11,300 users, and the number is growing. There have been 68 data requests so far. Ninety percent of the users are from the United States; the remaining 10 percent are from low- and middle-income countries. A study of the progress of normal labor, which has been downloaded 35 times, is one of the most frequently accessed. DASH gives fellows and junior faculty an opportunity to conduct a study without having to recruit participants.

Strategic Plan

NICHD is beginning its strategic planning process, which will include input from internal and external stakeholders. As part of the process, NICHD will look to see whether networks have changed clinical practice and whether patents have been issued as a result of NICHD-funded studies. NCMRR has already completed its strategic plan, so it will not be included in the overall plan.

Discussion

A Board member asked whether Dr. Bianchi had looked at rehabilitation separately within the K01 (Mentored Research Scientist Career Development Award) and the K12 (Clinical Scientist Institutional Career Development Program Award). NCMRR Director Alison Cernich, Ph.D., said that NCMRR had done that analysis and found that those who received an individual K award do better than those who receive the K12. This suggests that it may be more fruitful to use the individual K awards, but that is something that the Board must discuss. Dr. Bianchi emphasized that the NICHD is reallocating, not decreasing, the training funds. This shift is meant to fund those with the best chance of becoming independent investigators.

A Board member noted that some conditions, such as obesity and opioid addiction, are the result of an individual’s choices. Other conditions are biological and beyond the individual’s control. He asked whether those categories are treated any differently when funding decisions are made.

Dr. Bianchi said that question should be addressed during the strategic planning process. For the most part, the studies that are funded are those that receive the best scores from the study sections. Another question for the planning process is whether to fund across a wide range of science or to prioritize some areas. Individual program officers can boost a highly scored application that just missed the payline in order to move more grant funding into priority areas.

Next Generation Researchers Initiative

Della Hann, Ph.D., NICHD, discussed the Next Generation Researchers Initiative, which focuses on helping new investigators reach independence earlier in their careers. Because of the highly competitive funding environment, more of the grant money is going to established investigators and the number of early career investigators has been declining. The 21st Century Cures Act calls on the NIH to promote opportunities for early career investigators to become independent more quickly.

NIH will prioritize funding for 200 additional early stage investigators (ESIs) in FY 2017 compared to FY 2016. ESI investigators are those who are within 10 years of their terminal degree or postgraduate clinical training but who have not successfully competed for a substantial NIH independent research award.

NIH will also prioritize funding for 200 more early established investigators (EEI) in FY 2017 compared to FY 2016. EEI investigators are those who are within 10 years of receiving their first substantial independent R01, but who are at risk of losing all NIH research support if they are not funded in the current year. NIH is still working on the EEI definition, but the spirit of the definition is to assist those who may lose their laboratories if they are unable to receive additional funding.

Dr. Hann said that the Initiative began when the fiscal year was already under way, and the NIH is still gathering data for FY 2017. But so far, NICHD alone has funded an additional 38 ESIs and an additional 51 EEIs.

Discussion

A Board member asked whether an ESI is any investigator who has not yet received NIH funding. Dr. Hann said that ESIs are those who have neither received an independent NIH grant, nor a major grant from another agency.

A Board member asked whether the 10-year time frame could be extended because of a break for child-rearing. Dr. Hann said that waivers of the time frame are possible for child-rearing and a variety of other reasons.

Clinical Trials Policy Update

Meredith Temple-O’Connor, Ph.D., NICHD, discussed changes to NIH policies in human subjects research. She noted that researchers should read the new and broader NIH definition of a clinical trial. NIH made these changes to enhance the efficiency of human subject trials, increase NIH accountability, make the research more transparent, and increase timely reporting of research results.

All research involving human participants will use new forms to collect human subjects’ information, use a single institutional review board (IRB) for multisite studies, and require certificates of confidentiality for all research that uses identifiable and sensitive information. There would be clinical trial-specific funding opportunity announcements (FOAs), new review criteria, and expanded registration and results reporting in ClinicalTrials.gov.

NIH has a new form containing four questions; if investigators answer “yes” to all four questions, their study meets the definition of a clinical trial. The four questions are:

• Does your study involve one or more human subjects?
• Does your study prospectively assign human subjects to interventions?
• Does your study evaluate the effect of interventions on the human subjects?
• Does your study have a health-related biomedical or behavioral outcome?

As of January 25, 2018, investigators who are conducting a clinical trial must respond to a clinical trial-specific FOA. Investigators must also address timelines and milestones to ensure timeliness in completing and reporting the results, and must register and report all clinical trials in ClinicalTrials.gov.

Those who are applying for grants with a due date on or after January 25, 2018, must complete the new Human Subjects and Clinical Trial Information form, which consolidates all human subjects and clinical trial questions that had previously appeared on multiple forms into a single form. The form uses structured data fields and presents key information to reviewers and staff in a consistent format that aligns with ClinicalTrials.gov. The new form is available at https://grants.nih.gov/policy/clinical-trials/new-human-subject-clinical-trial-info-form.htm.

New registration and reporting requirements for NIH-funded clinical trials went into effect in January 2017 to ensure that information about clinical trials and their results are made available to the public in a timely manner.

Multisite human subjects research studies will require a single IRB for grant and contract applications due on or after January 25, 2018. The single IRB is not applicable to career development (K awards), research training (T awards), or fellowships (F awards). International studies are not subject to the single IRB unless two or more domestic sites are included in the study. There are also some further exceptions; for example, studies involving Native Americans may require review by aTtribal IRB. Other exceptions may be added as needed. Dr. Temple-O’Connor referenced https://grants.nih.gov/policy/clinical-trials/single-irb-policy-multi-site-research.htm for more information.

NIH also updated the Certificates of Confidentiality policy. Certificates will now be issued automatically for any NIH-funded project using identifiable sensitive information that was active as of December 13, 2016, or later. This eliminates the need for NIH-funded investigators to apply for a Certificate of Confidentiality. Dr. Temple-O’Connor referred Board members to https://grants.nih.gov/policy/humansubjects.htm for more information.
Other resources that Dr. Temple-O’Connor provided included clinical trial requirements for grants and contracts (https://grants.nih.gov/policy/clinical-trials.htm) and training resources (https://grants.nih.gov/policy/clinical-trials/training-resources.htm).

Discussion

Dr. Cernich said that the NCMRR had the second highest number of clinical trials within NICHD, including the SBIR and STTR awards. NCMRR Deputy Director Ralph M. Nitkin, Ph.D., said that there could be a period of adjustment as program officers, study sections, and applicants become accustomed to using the new FOAs.

Dr. Nitkin asked who would be responsible for registering a trial being conducted by a trainee. Dr. Temple-O’Connor said that she would get back to Dr. Nitkin with a more complete answer.

A Board member said that junior investigators who are applying for their first independent award for a small mechanistic study that involves prospective randomization are concerned about calling their study a clinical trial because they believe the study section may review them poorly compared to a large phase III clinical trial. There is a need to educate the junior investigators and the study section members. Dr. Temple-O’Connor said that any study that meets the four criteria will be considered a clinical trial. NIH has begun educating the reviewers about the new review criteria. The studies will continue to be grouped by the type of science, but additional experts such as statisticians and trialists may need to be added to the review sections. She will relay the Board’s concern about this issue to the Center for Scientific Review.

A Board member, noting that there is a parallel between the information on the new form and the ClinicalTrials.gov form, asked whether the two systems will “talk to each other.” Dr. Temple-O’Connor said that the NIH expects to develop that functionality, but it is not currently available.

A Board member commented that the single IRB has worked well in the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) study. However, the single IRB requires additional resources and investigators need guidance as to how to support and budget for it.

NIH Research Plan on Rehabilitation

Drs. Alison Cernich and Jennifer Jackson, Ph.D., NCMRR, presented a draft proposal for tracking progress on the NIH Research Plan on Rehabilitation. The draft had already been reviewed by a subcommittee of the Board and by the Trans-NIH Medical Rehabilitation Coordinating Committee (MRCC). Dr. Cernich asked Board members to comment on whether they thought the approach was tracking the right data.

The baseline data was from the FY 2015 portfolio. The analysis uses the Research, Condition, and Disease Categorization (RCDC) system, with two caveats: it contains the physical rehabilitation category, but does not contain intramural projects. The analysis returned 1,370 projects totaling $476 million.

Each project was categorized into two tiers. Tier 1 is based on a keyword approach for six categories within the research plan as follows:

1. Rehabilitation Across the Lifespan
2. Community and Family
3. Technology Use and Development
4. Research Design and Methodology
5. Translational Science
6. Research Capacity and Infrastructure

Tier 2 defines the phase of research for the project including basic (cells, tissues, etc.), disease-related basic (humans or animals), or applied translational or clinical (which includes an intervention).

Two coders from the NCMRR coded the portfolio of each Institute/Center (IC), and each IC validated the coding for their portfolio. Dr. Jackson summarized the findings of the portfolio analysis. Sixty-five percent of the projects are research projects (R awards), 14 percent were other research-related projects, 7 percent were research centers, 6 percent were small business, 5 percent were individual training projects, and 3 percent fell under the category of other. The National Institute of Neurological Disorders and Stroke (NINDS) had the greatest number of projects, followed by the National Institute on Deafness and Other Communication Disorders (NIDCD) and NICHD. Twenty four of the 27 ICs had at least one rehabilitation project.

Dr. Jackson showed the funding data broken out by IC and by RCDC category. Most of the funding fell under “clinical research,” followed by “neurosciences,” “behavioral and social science,” “bioengineering,” and “brain disorders.”

Dr. Bianchi asked about the large number of rehabilitation projects within NIDCD. Dr. Cernich said that the majority of the NIDCD portfolio involves rehabilitation following receipt of a cochlear implant or a hearing aid. NIDCD also conducts many of the projects on treatment of aphasia.

A Board member asked whether deep brain stimulation is considered rehabilitation. Dr. Cernich said that it is not, but if deep brain stimulation is used to understand motor pathways as related to plasticity and function, it can fit the rehabilitation definition. She also noted that rehabilitation is broadly defined at NIH. Given that the analysis has already begun, they should not try to change the RCDC category, but this could be revisited in 4 years, when the NCMRR writes a new strategic plan.

Dr. Jackson showed a graph of the number of grants per IC and topic. The graph confirms that the ICs are funding rehabilitation projects in the expected areas. For example, the National Cancer Institute (NCI) funds many cancer rehabilitation studies, while NIDCD funds many sound perception and processing rehabilitation studies. Dr. Cernich said that NCMRR funds the preponderance of prosthetics, orthotics, and mobility projects.

The research category analysis showed that about one-third of all projects and funding are in the research design and methodology category. Translational science and technology use and development were the next largest categories. Very few of the projects fall into the community and family category.

About one-half of all the projects were applied clinical trials and about one-quarter were disease-related basic research. Dr. Jackson also went through how the projects fell within the six categories of the rehabilitation plan (rehabilitation across the lifespan, community and family, technology use and development, research design and methodology, translational science, and research capacity and infrastructure) and how the primary and secondary aims were paired within those categories. For example, projects with research design and methodology as a primary aim often had a secondary aim of rehabilitation across the lifespan.

The most common funding mechanisms for clinical trials was the R01. Clinical trials had higher levels of funding.

This was the NCMRR’s first effort at coding the NIH rehabilitation portfolio. Dr. Jackson said that she is working to develop an automated coding algorithm to reduce the amount of work the analysis took. It will take a number of years to perfect the algorithm.

Dr. Cernich said that the purpose of the analysis was to identify what type of rehabilitation projects were being funded and to identify gaps in the research. An annual reanalysis of the portfolio will help determine whether the research community is responding to the strategic plan.

NCMRR has been issuing a rehabilitation update through its listserv every two weeks. The update  includes funding opportunities for NIH and other federal agencies and partners and highlights upcoming meetings and other NIH news.

Dr. Cernich displayed a graphic showing the impact that NIH rehabilitation grants have had, as measured by how often a publication from the research was cited in clinical practice guidelines. Most of the impact involved human subjects research. She noted that the Board should consider whether NCMRR should try to have more of an impact on molecular/cellular or animal research.

Dr. Cernich also explained that the most common professions applying for funding included physicians, psychologists, engineers, neuroscientists, and physiologist. She also provided information about which professions tend to collaborate on projects, but these results are preliminary because this model is still being validated. Once it is validated, the information may be used to promote new collaborations as a way to spur innovation.

Discussion

A Board member asked about the impact of rehabilitation projects on clinical practice guidelines. Dr. Cernich said that it may not be possible to assess the impact that publications have on policy. It may be possible to measure whether publications are associated with patents or with clearance from the Food and Drug Administration.

A Board member asked how much of an impact the NCMRR’s investment in research has on the other ICs. Dr. Cernich said that rehabilitation has increased $50 million in less than 4 years and is projected to increase another $20 million this year. The data are expected to show which areas of rehabilitation research need more investment.

A Board member asked about the investment that NIDCD has been making in rehabilitation research and whether there was a demand for that research. Dr. Cernich said that it was, and that most of the grants were investigator initiated. However, the next research analysis could look at how many grants are funded through FOAs versus parent announcements. That could help answer the question of how much is the community driving where the money is spent versus how much the NIH is driving it.

A Board member noted that the analysis contained a number of phase III clinical trials and a much larger number of studies that were classified as clinical research but not NIH-defined phase III clinical trials. He asked whether it would be possible to receive a further breakdown of the clinical trials category, such as to determine whether the studies classified as clinical research but not phase III clinical trials clinical studies were underpowered. NIH has said it would no longer fund underpowered clinical trials. Dr. Jackson said that those were the only two categories that were available. To break them down further would require manually looking at those 810 studies. Dr. Temple-O’Connor said that part of the reason for changing the definition of clinical trial and requiring the new form is to get more information on the clinical trials. This new approach will provide a more detailed data analysis.

A Board member asked whether some of this information such as the collaboration categories could be more easily obtained in the future. Dr. Cernich said that the next time will be easier because some of the work can build on what has already occurred. For example, the Office of Portfolio Analysis (OPA) makes “recipe cards” to do some of the search in a more automated way. Drs. Cernich and Jackson may also have the opportunity to present their work at the OPA’s annual conference to get feedback on their process. Also, Dr. Jackson is working to develop an algorithm to automate more of the process.

Agenda for May 2018 Board Meeting

The Board held a working lunch to develop topics that they would want to explore at future meetings. Board members made the following suggestions:

• Combination therapies
• Further updates on clinical trials from Dr. Temple-O’Connor
• Challenges being faced with the single IRB (Local IRBs may be unwilling to give up their authority)
• NIH policy and the Molecular Transducers of Physical Activity in Humans Consortium (MoTrPAC)
• Implementation of pragmatic trials, including developing new requests for applications (RFAs), additional training needs for conducting pragmatic trials effectively, and guidance for peer reviewers, who may devalue pragmatic trials
• Common data elements (CDEs), which would allow investigators to more easily combine data from different studies: Dr. Nitkin mentioned a recent Board discussion about CDEs. Dr. Cernich said that the NIH does not require CDEs because investigators have argued that they stifle innovation. The NINDS and the NCI use them, but they are not in wide use across the NIH. Those are factors to consider when deciding whether the Board would want to have this on a future agenda.
• Research in the area of family and community, which the portfolio analysis identified as a gap: Dr. Cernich noted that the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) does a lot of research in family and community, and that the NCMRR should avoid duplicating their research. Randy Nudo, Ph.D., University of Kansas Medical Center, suggested concentrating the research on infrastructure in this area. Dr. Nitkin said that there were no responses when the NCMRR solicited research in that area. Dr. Cernich said that they had a similar experience with a pragmatic trial solicitation in rehabilitation.
• Defining rehabilitation: Dr. Cernich noted that the 21st Century Cures Act had a definition, although it was broad. There was a definition in the research plan that meshed well with the RCDC.
• Health economics: Investigators should understand market strategy and know whether their device, for example, would be reimbursable. NIA has conducted training in health economics research and an NIA staffer could be invited to discuss that program with the Board.
• Dissemination of research findings: Board members inquired whether there were initiatives that they could support to help disseminate findings. Dr. Cernich said that NCMRR could help facilitate those interactions. She also said that Board members should keep their professional organizations informed.
• Spreading the word about funding initiatives: This discussion could include barriers to reaching the people who could help expand rehabilitation research. Dr. Nitkin explained that how NIH publicized special initiatives, which often have a very short turnaround time, was a factor. He added that a second issue is the tension between running a clinical department and setting aside time for clinical research. Dr. Cernich suggested bringing together a panel from the professional societies to discuss the issue. Board members would be asked to help plan the panel.
• Barriers that prevent physicians from responding to RFAs: These may include third party payments, time constraints, administrative barriers, lack of human resources, etc. The panel could also discuss how to encourage more pragmatic trials. Michelle Camicia, MSN, BSN, RN, Kaiser Foundation Rehabilitation Center, noted that there were some successful models to integrate basic researchers and clinicians into a research project.
• Team science efforts at the NIH, such as a collaborative project between an engineer and a physician to make the electronic health record (EHR) more efficient and user-friendly for physicians
• Functional outcomes that will be useful to basic and clinical researchers and who is collecting them
• Person-generated health data such as wearable technologies as a way to assess the health of people with disabilities: Members noted that a simple translation of Fitbit data may not be useful to this population. Issues also include how to integrate the data into the EHR and into clinical trials.
• Data elements that the All of Us Research Program should capture that are specific to people with disabilities
• Scalability of monitoring to allow for application to merging technologies to diverse populations

Dr. Cernich said that the May meeting could include discussion about the trends and gaps related to the research plan and future steps. Board members should send additional ideas for future agenda items to Dr. Nitkin or Gregory Hicks, PT, Ph.D., University of Delaware.

NCMRR Director’s Report

Dr. Cernich provided a snapshot of ongoing activities, including continued collaboration with the MRCC. The MRCC recently received a collaboration award from the NICHD Director.

The Office of Disease Prevention accepted the NCMRR proposal for a Pathways to Prevention Initiative. Joseph Bonner, Ph.D., put together the initiative in partnership with the NINDS on the state of preventive medicine for wheelchair users. The effort includes a systematic review for assistive devices.

21st Century Cures Act

The 21st Century Cures Act contains a section entitled “Improving Medical Rehabilitation Research at the National Institutes of Health.” NCMRR had already complied with most of the requirements of that section; it published its research plan and the MRCC and NABMRR are in place. NCMRR is reviewing its portfolio to coordinate with other ICs and to prevent duplication.

Trans-NIH Initiatives

NCMRR staff is involved in the following trans-NIH initiatives:

• Dr. Cernich is the NICHD representative to the All of Us Research Program’s Liaisons Committee. She has advocated for the inclusion of people with disabilities including the need to provide a proxy consent.
• Dr. Cernich and Theresa Cruz, Ph.D., are helping to shape the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative FOAs related to human trials.
• Dr. Cernich is on the safety committee of the MoTrPAC, which is examining the effects of physical activity at the molecular level.
• Dr. Cruz in involved with the Common Fund’s Stimulating Peripheral Activity to Relieve Conditions, a project that is looking at ways to use the peripheral nervous system to impact end organs.

With NINDS, NCMRR cohosted the Optimizing the Investment in Medical Devices for Rehabilitation workshop. The workshop included participants from a variety of government agencies, scientists, industry, payer organizations, and venture capitalists. The federal partners will write and publish the proceedings. NIDLRR organized round tables following the workshop. Many factors influence device research. Planning must take into account the entire life cycle of device development. Participants had very different perspectives on how to develop devices.

Interagency Collaboration

Among the interagency collaborations, NCMRR has entered into a partnership with the Department of Defense (DoD) to fund a limb loss registry.

NCMRR participates in partnership calls with a variety of other agencies, including the Centers for Disease Control and Prevention (CDC), NIDLRR, and HHS. Among other activities, the NCMRR participates in review panels for other agencies, such as DoD, the Department of Veterans Affairs (VA), and the NIDILRR. NCMRR is involved in review of portfolios of other agencies including DoD.

Dr. Cernich is involved in a program of the World Health Organization, Rehabilitation 2030. The aim of the program is to enhance rehabilitation research across the globe and to ensure that medical rehabilitation is reimbursed as a medical service. The program will focus on assistive products. Dr. Cernich and representatives of the Fogarty International Center and the NIDCD will attend a follow-up meeting in January to develop the research agenda.

Active FOAs

Active FOAs include an early career research initiative (R03), which has received a big response. There is also an R01 to address sleep disorders in the context of medical rehabilitation and an R25 related to NICHD research education programs. NCMRR also joined with other ICs on various projects, including an R61/R33 project with the National heart, Lung, and Blood Institute (NHLBI) to increase the use of cardiovascular rehabilitation in traditional and community settings and a P41 with the National Institute of Biomedical Imaging and Bioengineering to train researchers in the use of technology.

Other Initiatives

The K12 program awards will provide training and career development for physical and occupational therapists, training for clinicians in neurorehabilitation, and rehabilitation engineering career development.

NCMRR is still under a hiring freeze and has been unable to replace Mary Ellen Michel, Ph.D., who retired. The Center currently has four health science administrators, one program analyst, one program support specialist, and an administrative assistant. It is not known when the hiring freeze will end.

Dr. Cernich has begun distributing a newsletter to highlight changes in clinical trials and other policies affecting grantees and to disseminate network resources, meetings, and pilot funding opportunities. There are 900 subscribers.

Rehabilitation funding at NIH increased by $100 million between FY 2012 and FY 2017, with current funding at about $550 million. Funding for NCMRR is a set percentage of the NICHD budget. About 61 percent of the NCMRR research budget goes to research projects, 16 percent to small business projects, 12 percent to training and career development, and 10 percent to multicomponent projects. NCMRR invests more heavily in small business projects than other ICs do. Although this amount is related to product development, Dr. Cernich asked whether the Center may be investing too much in that area. Most of the NCMRR research project funding is through the R01 awards. The small business projects are primarily funded by R44 awards. Multicomponent projects are primarily funded using the P2C awards.

Dr. Cernich also presented a snapshot of NCMRR investments by both category and dollar amounts. Pediatrics has been the most highly funded, although an individual who is 18 years old meets the definition of a child. There was discussion about better defining pediatrics. Other major funded areas included prosthetics, robotics, and pain. Conditions that are funded included stroke, traumatic brain injury, spinal cord injury, cerebral palsy, and amputation.

Discussion

An attendee asked whether there was overlap in the robotics and prosthetics category and the gait category. Dr. Cernich said that there is often overlap, but a project would be categorized into one or the other of those categories, not both.

Update on NCMRR Concept Clearances

Drs. Theresa Cruz and Jennifer Jackson, NCMRR, discussed the types of FOAs and the FOA process as a lead-in to a discussion of how the NCMRR can use its FOAs to respond to the rehabilitation community’s needs.

FOA types include RFAs and program announcements. RFAs have funding attached to them and must go through concept clearance. Program announcements (Pas) include the PAR and the PAS announcements. A PAR has special receipt, referral, or review considerations. The PAS is a general program announcement that has set aside funds.

The FOA process for RFAs begins with the generation of an idea and goes through operational planning and concept clearance. The RFA then is written and published, applications are received and reviewed, and awards are made. The process takes about 18 months to 2 years.

Dr. Cruz sketched out the process in further detail, using the example of an RFA involving orthotics for healthy development in pediatric populations. There were 13 applications, and five awards were made for a total of $1 million. Three years later, Dr. Cruz found that none of the five projects had gone on to phase II (although one project may go to phase II in the future) and there were no new products produced. Was this RFA a success? What should be the next step? Should the NCMRR reissue the FOA, adapt the FOA to use another mechanism, or do nothing?

Dr. Cruz used a second example of an RFA that was developed as the result of a workshop on personal motion technologies for healthy independent living. NCMRR developed an RFA to look at ways to help people age at home. The PAR was issued in 2011, but not enough applications came in to justify a review meeting. The PAR was reissued in 2014, and the NCMRR received 23 applications, 4 of which were funded.

A third example began with a general PA from the Office of Behavioral and Social Sciences Research (OBSSR), using the R21 mechanism. The OBSSR issued the PA because the research was related to multisensory processing, which falls within the domain of many ICs. When the 2-year R21 came to an end, it was unclear which IC should handle a subsequent R01. The ICs opted to issue an R01 PA that the program officers across ICs would oversee.

Over the past 5 years, NCMRR has been involved in 54 FOAs (RFAs, PARs, and PAs). The NCMRR was the primary IC for some but secondary in others. The FOAs are evidence of NCMRR’s broad partnerships across NIH.

NCMRR has had good success rates with the RFAs, but the PAs and the PARs have been less successful in attracting applications; 22 FOAs received no applications at all. It is not known why the field did not respond to those FOAs.

Dr. Cruz asked the Board members to provide input on the following questions:

• Would the successful RFA applications have been successful coming through a parent announcement?
• Would investigators show interest in a particular topic without an FOA or dedicated funding? Did the NCMRR spur the work, and did it continue?
• Is the NCMRR not getting the word out? Are investigators given enough time to respond?
• Is signing on to a wide breadth of FOAs the best use of resources or is a targeted approach better?

A Board member said that companies can respond much faster to a FOA than academic institutions. Dr. Cruz agreed and added that investigators who are able to meet a quick turnaround time for an application are those who would have applied for an R01 without the FOA. Other ways to use a short turnaround time but to bring new investigators to the field is to use challenge grants or prize competitions. NCMRR may pursue those approaches. A Board member said that, particularly with the small business grants, phase I is the startup, which the company has already completed. Phase II is the new phase I. Dr. Cruz agreed.

A Board member said that it might be helpful to inform the community of the concept clearances as a way to alert investigators that an RFA may be coming. Dr. Cruz said that the Board members could help by notifying their colleagues of any new concepts that are cleared. She added that the NCMRR has very few RFAs.

Dr. Cernich will determine whether the concept clearances could be noted in the newsletter. She also said that the NCMRR has signed on to many projects as a way to alert rehabilitation researchers that rehabilitation projects are included, but asked if it was an effective approach.

A Board member said that it would be helpful to email new announcements to investigators who are currently funded. Dr. Cernich said that she would add all of the NCMRR-funded investigators to the listserv and disseminate new announcements that way.

A Board member suggested that the NCMRR publish a notice of intent to alert interested investigators. Dr. Cruz said that is a possibility and that it is clear that investigators should be given more time to respond to an FOA. She reiterated that 22 FOAs drew zero applications. One question is whether it is worth the effort to tag as many projects as possible as rehabilitation, given the amount of effort and poor response.

A Board member asked about the FOAs that drew no applications and whether there were any themes. Dr. Cruz said that they were FOAs that had not been written by NCMRR. The FOAs included studies on surgery disparities, dissemination and implementation trials, and pragmatic trials. Dr. Cernich said that some investigators have asked her to include rehabilitation on dissemination and implementation trials. NCMRR added rehabilitation language to one announcement and sent it to several investigators interested in the trials but received no rehabilitation-related applications. A Board member said that this is a new area for rehabilitation scientists and suggested continuing the announcement through more rounds. Dr. Cernich said that she would publish reminders about these announcements in the listserv. Dr. Nitkin said that the ideal would be for a rehabilitation scientist to team up with a specialist in another field to apply for a grant. However, those applications are not always as highly rated, because the ideas may be novel.

A Board member said that he agreed that the problem could be a lack of communication or that the goals of the funding announcement might not fit with the goals of the investigators. It may also be that the scale of a particular project is too big for some investigators. Advocates within the study sections may be needed to remind people that the new ideas may be deserving of higher scores. Dr. Cruz said that NCMRR staff discusses the review with the Center for Scientific Review ahead of time to get the best review possible.

A Board member said that the NCMRR has to be more patient with new areas, such as pragmatic trials. One problem is that applicants fear that their application will not have a chance of being funded. Dr. Cernich said that there have been many areas of research that have received no applications, including health disparities and multiscale modeling. Dr. Nitkin said that Board members should encourage colleagues who are reluctant to apply.

A Board member said that it is not unusual or unexpected for a phase I small business grant to not proceed to a phase II. When companies receive phase I money, they are testing a product’s feasibility. If the project is not feasible for some reason, the company will drop it. Another Board member said that a company that finds a product is feasible in phase I is unlikely to apply for phase II funding through the NIH, because the process takes too long. Those companies will seek further funding elsewhere.

Dr. Cruz said that she understood the Board to be saying that the NCMRR should continue with some types of announcements that received no applications but drop others. The other side of the coin is when to stop funding areas that receive a lot of applications. Those areas may have been given enough of a boost that funding should be shifted elsewhere.

An attendee suggested finding more ways of using the newsletter to bring attention to the announcements, such as highlighting successful applicants in the newsletter. Dr. Cernich said that she would do that and will publish a list of active announcements.

A Board member suggested converting a small business announcement to an R01 to see whether the additional funding attracts more applications. Investigators may be more able to justify spending their time on an application for a larger grant.

Dr. Cruz told the Board that the Patient-Centered Outcomes Research Institute has asked for investigators to send them applications.

Dr. Cernich asked whether the NCMRR should consider offering challenge or prize grants. An example of a challenge grant would be to ask for proposals for building a modular pediatric wheelchair that could “grow” with the child to reduce the expense connected with buying a series of new wheelchairs. The Board did not express opposition to the proposal.

The All of Us Research Program: The Precision Medicine Initiative (PMI)

Stephanie Devaney, Ph.D., NIH Office of the Director, said that precision medicine is an emerging approach for treating and preventing disease that takes into account individual variability in lifestyle, environment, and genes. The All of Us Research Program provides an opportunity to scale up that approach.

The All of Us Research Program is part of the PMI, a cross-government effort, as is PMI for Oncology, an effort led by NCI.

The program’s mission is to involve 1 million participants in the program for decades; accelerate health research and enable individualized prevention, treatment, and care; and deliver the largest and richest dataset that will be safe and accessible.

Congress passed the 21st Century Cures Act in 2016, authorizing the PMI for $1.455 billion over 10 years. The Act emphasizes diversity, data sharing, and privacy.
The program is guided by the PMI Privacy and Trust Principles. All data are encrypted and de-identified. The Cures Act also strengthened the certificates of confidentiality, prohibiting investigators from handing over data and making the data inadmissible in court.

To ensure diversity, the research program is developing a national network of health care provider organizations (HPOs) with incentives to reach and enlist a diverse population in the program. The program also allows individuals to enlist themselves online as direct volunteers. It is building a network of partners to help extend the reach of the program and build relationships in key communities and has also developed plans to reach special populations, such as children, American Indians, Alaska Natives, and people who are incarcerated, are decisionally impaired, or have low health literacy.

The program’s major components are a Data and Research Center, biobank, participant center, participant technology systems center, HPOs, and the communications and engagement team.

Participants must sign a consent (paper or eConsent), complete three surveys, and provide their physical measurements, such as height, weight, heart rate, and hip circumference, and biospecimens (blood and urine). Participants have access to their data through their participant portal or by making a request in writing. Over time, the research program will collect additional data, such as Medicare claims data and medication data from the participant’s pharmacy.

The program will return information to participants, who can receive their own data, ongoing study updates, aggregated results for all participants, and scientific findings.

Another of the program’s principles is to make the data widely accessible to citizen scientists, students, and researchers. The data will have a tiered access and will require a “passport” for access to each tier. The data cannot be downloaded. Those who use the data must say publicly what they are working on. The most secure data are the controlled tier, which will require that the individual have registered level access and have an institutional signing official.

The program will hold a workshop in March to identify research priorities. The planning committee includes leaders from across the NIH. Attendees will be asked to plan the research program’s scientific near-, mid-, and long-term strategies. The program will also gather input from the public. Dr. Devaney showed the scientific framework for the workshop that included nine health conditions and seven themes that cut across the health conditions.

The program is now in beta phase and has more than 7,000 participants enrolled through more than 60 sites. The plan is to have the national launch in the spring.

Discussion

A Board member asked how participants who do not have digital access will receive their results. Dr. Devaney said that the program has been working on the return of information for a variety of groups, including people who do not have digital access and people with physical disabilities. These methods must be approved by the IRB. The program is also working through a plan to return genomics information to participants.

Dr. Devaney said that she was unsure whether any of the community partners were linked with people with disabilities, but if the community partners prove to be a successful model for engagement, the research program will fund more of them. Dr. Cernich said that she would send Dr. Devaney suggestions for linking to the disability community. Dr. Cernich also encouraged Board members to monitor the All of Us website for funding announcements and to encourage disability-related organizations to apply.

A Board member said that important information such as falls and use of assistive devices are often not in an individual’s medical records, but such data would be important information to have. Was there a plan to obtain that information? Dr. Devaney said that the program is working on a list of logic-based surveys so that a particular answer would bring the respondent to a more specific set of questions. She said that falls and use of assistive devices would be a good logic-based item to include.

A Board member asked whether the research program was enrolling children. Dr. Devaney said that the program would begin enrolling children in 2018. Dr. Cernich said that she is working with a committee to develop data elements that would be useful to the research program. She will share the Developmental Milestones tool that was developed by the CDC with Dr. Devaney.

A Board member suggested using the International Classification of Functioning, Disability, and Health to organize some of the information being collected. Dr. Devaney said that could be part of the scientific priority setting.

A Board member suggested having a performance-based test as part of the physical measurements, which provides more information than a self-report. Dr. Devaney agreed and said the research program wants suggestions such as that one.

An attendee asked whether imaging data would be collected as part of the program. Dr. Devaney said that the program hopes to incorporate imaging data in the future.

An attendee suggested measuring grip strength, which correlates with aspects of neural function and activities of daily living.

Use Cases

Dr. Devaney added that the research program is soliciting use cases from the public to help determine studies that would be important to pursue. Dr. Cernich presented two use cases that she had prepared and asked the Board for feedback.

The first use case involved using wearable sensors to record movement. The research question was how science could move beyond single accelerometers or smartphone measures of gross activity to methods capable of characterizing voluntary movements like walking and sitting and involuntary movements, such as tics and tremors. The study would identify what data to collect, how the data could be standardized and analyzed, and how the results could be used. The study would not test a particular sensor but would be a methodological study.

A Board member cautioned that collecting these data without a specific aim may not produce a useful outcome. Dr. Cernich said that the data would likely need to be validated against various diagnoses. Another Board member said that having the data would allow scientists to ask questions about how movement is connected to health, such as whether gait or stride length could predict a fall or fracture. The important thing is to have the data be standardized and validated.

An attendee said that the problem with many sensors is that it is impossible to know what the person was doing when the sensor gives a reading. It may be necessary to do some face-to-face testing first. He also suggested that measuring muscle force would be valuable.

A Board member said that the European Union is setting up a study to measure mobility (for example, walking speed) and its relationship to health outcomes such as activities of daily living.

Dr. Cernich presented a second use case. The research question asked what the characteristics of people who sustain traumatic injury and have optimal recovery are compared with people who do not. This study would provide an opportunity to look at premorbid predictors of an outcome after an injury or onset of a condition. The study could make use of the genomic information that the research program is collecting.

A Board member said that the Patient-Reported Outcomes Measurement Information System (PROMIS) is contained in the latest version of the Epic EHR. Also, Medicare requires the use of G-codes. Dr. Cernich said that those instruments could be tapped to make data available to track functionality.

Dr. Cernich asked Board members to email her any further thoughts about these use cases. She also asked for ideas about how to reach investigators and community members who would want to shape the Research Program or who may want to access the research program data. Dr. Cernich asked whether she should hold webinars as a way to inform the community about the program. Board members agreed that she should. A Board member suggested reaching out to organizations and foundations that serve as the hubs of information for other groups and individuals.

Dr. Cernich asked the Board members to think about how the research program can drive rehabilitation science and to make suggestions. A Board member suggested investigating models that would include family and community influences.

Another Board member added that walking speed is a predictor of health outcomes, but accelerometers do not measure walking speed. Also, arm swing is not a reliable measure of walking in people with disabilities; an accelerometer should be placed on a belt around the hips, not on the wrist. Accelerometers can be used to measure postural sway while standing. Studies should collect raw data, not metrics. And finally, the program should select validated sensors for data collection to ensure data quality. Most consumer devices have not been carefully validated.

Food and Drug Administration (FDA) Pediatric Device Consortium

Eric Chen, MS, FDA, discussed the mission and structure of the Office of Orphan Products Development and provided an overview of the Pediatric Device Consortium.

The Office’s mission is to promote the development of products for the diagnosis and treatment of rare diseases and other orphan conditions involving special populations. This includes the development of pediatric devices, which has lagged behind. FDA wants to get new pediatric devices into use as fast as possible.

Mr. Chen asked Board members to imagine a world where children have access to innovative medical devices at the same time as adults and where the devices are designed and evaluated according to the needs of children and with the appropriate system for industry to innovate in the pediatric medical device market.

The Pediatric Device Consortia Grants Program began in 2007 with the Medical Device Safety and Improvement Act, which established a nonprofit consortium to stimulate pediatric device development. The Consortium offers P50 grants to specialized centers to move devices through the product development life cycle. The program encompasses devices used in all pediatric diseases, not just rare diseases, and was recently reauthorized and extended to 2022.

The statute requires that the program encourage innovation and connect those who have pediatric device ideas with potential manufacturers. The program mentors and manages pediatric device projects through the process, connects innovators and physicians to funding sources, assesses the scientific and medical merit of proposed pediatric devices, provides assistance and advice, and offers regulatory consultation to developers in support of an application for a pediatric device. The statute also requires consortia that receive a grant or contract to coordinate with the NIH’s pediatric device contact point.

For the purpose of pediatric devices, FDA defines pediatric patients as those who are no more than 21 years of age at the time of diagnosis or treatment. There are also pediatric subpopulations, including neonates, infants, children, and adolescents.

Eight consortia currently receive funding under the program. Since 2007, the program has helped fund 900 devices, advised 700 device innovators, and helped bring 18 devices to market. Funding for the program has increased every year. Last year, it was funded at $6 million. As of 2013, the program began putting more of its funding into advising as opposed to funding development.

Among the devices that received help from the consortia are a device using cold and vibration to relieve the pain of needlesticks and intravenous lines, a Geiger pyloric clamp for use in pyloric surgery for infants with congenital hypertrophic pyloric stenosis, and the RhinoGuard, which assists in nasotracheal intubation of children.

There will be a new RFA available soon. The plan is to accept applications and have funding available by September 2018. The grants are available to any domestic nonprofit entity.

Discussion

A Board member asked whether there have been any Class II or Class III medical devices that have gone through the process and, if there have been none, is that because of the higher hurdles for the devices or does it reflect the expertise of the consortium. Mr. Chen said that the Consortium has the expertise, but it takes more effort and more funding to get approval for a Class II or III medical device to market. The Board member said that a 2010 study by AdvaMed found that it costs around $24 million to get a Class II medical device through the FDA approval process. The consortium is working with about 150 devices at any one time. About one quarter of them are Class III devices, and the remainder are Class I or II.

An attendee asked whether, once a device is on the market, the FDA makes any effort to prevent price gouging. Mr. Chen said the FDA does not. However, the innovators do provide some royalties back to the Consortium.

An attendee asked about devices that have component parts, such as devices that have modular capability that can grow with the child. Does the FDA have modular approvals or would the device and each component have to go through the FDA process? Mr. Chen said that there are ways manufacturers can bundle components. The innovating group should request a presubmission meeting with the FDA to ask about bundling versus having the components approved separately.

Dr. Cernich said that Richard Greenwald, Ph.D., is the principal investigator of the New England Pediatric Device Consortium and also oversees the Translation of Rehabilitation Engineering Advances and Technology Center. Having one individual wearing both hats presents a good opportunity for individuals who are developing a pediatric device. A target challenge will soon be issued for pediatric rehabilitation devices through the Pediatric Device Consortium. This is a good opportunity for innovators to move a device through the commercialization process.

A Board member said that there is a need to develop devices for children, who do not have smartphone interfaces for data storage. Also, wearable technologies must be evaluated in young patients and persons with mobility impairments. 

Another Board member encouraged the FDA to extend guidelines for the use of wearable technologies for children. The validation for sensors in 2- and 3-year-old children, for example, is needed and some of these wearable approaches can be used as clinical trial endpoints for therapeutic trials. The engineers often assume that a smart phone can be used as storage for wearable devices, but most young children do not walk around or wheel throughout their communities with a smart phone in hand or a smart phone strapped to their bodies. The development of devices that can be used in children without smartphone interfaces for storage is important. In addition, wearable technologies need to be evaluated in young patients and persons with mobility impairments. Cardiac and pulmonary rehabilitation research initiatives do not seem to focus on mobility limitation or disability as a barrier or challenge and the extent to which upper versus lower extremity exercise can be effective in cardiac rehabilitation is not as well established. Metabolic syndrome is common in dialed populations. Much of cardiac and pulmonary rehabilitation involves aerobic exercise, which drives mechanisms promoting mitochondrial health and biogenesis. There are emerging nutrition supplement approaches and pharmacologic approaches using small molecule "exercise mimetics" that drive these same pathways that promote health and function. These approaches might help jump start a patient with mobility impairment who has a cardiac or pulmonary disease process. Would nutrition and/or small molecule approaches be of interest in the realm of cardiac and pulmonary rehabilitation? The interest in the Rehabilitation Measures Database collaborating to a greater extent with the NINDS CDE effort is likely to be fruitful. The Rehabilitation Measures Database seems to have a bit of an adult focus at present, with limited pediatric-focused scales included and the integration of additional pediatric rehabilitation measures is a need for the future. 

Update: Interagency Committee on Disability Research (ICDR)

Kristi Hill, Ph.D., NIDILRR, said that the ICDR is charged with promoting coordination and collaboration among federal agencies that are involved in disability, independent living, and rehabilitation research programs. ICDR has focused more independent living than on medical rehabilitation. However, the aim is to integrate all of the work across the agencies.

The ICDR Executive Committee includes statutory representatives from HHS, the Department of Education, the Department of Transportation, the Department of Labor, the VA, the Small Business Administration, the Department of Housing and Urban Development, and DoD. Other agencies that work with ICDR as non-statutory members include the Federal Emergency Management Administration and the Federal Communications Commission.

The ICDR, authorized by the Rehabilitation Act of 1973, is required to develop and execute a government-wide strategic plan. ICDR must also inventory government programs related to rehabilitation and ensure the sharing of information across agencies. The ICDR determines where the gaps and redundancies exist and suggests ways to eliminate the redundancies and fill the gaps.

When working on the government-wide strategic plan, ICDR formed working groups in the areas of health, wellness, and function; assistive technology and universal design; community integration and participation; and education and employment. They spent 4 to 5 months developing goals and objectives.

Earlier this year ICDR produced a draft of the plan that incorporated at least one or two goals from each of the working groups. The plan is being cleared internally. ICDR expects the plan will be the guiding framework for the work of the next few years. After the plan is finalized, ICDR will conduct a second phase to develop more specific collaborative activities.

ICDR is conducting the government-wide inventory with the NIH National Library of Medicine (NLM). The ICDR website contains an events calendar, annual reports, publications, background on the working groups, and other agency information and resources.

Discussion

A Board member asked Dr. Cernich to include the ICDR strategic plan in the newsletter when it is published. Dr. Cernich said that she would do so. She noted that a draft plan had been circulated in an earlier email to Board members. Dr. Cernich said that she has been active in the health and wellness working group and that she and Daofen Chen, Ph.D., NINDS, are working with NLM on the government-wide inventory.

A Board member said that the effort to bring together all the rehabilitation-related agencies under one umbrella is a big effort that will benefit individuals who have disabilities. Dr. Hill said that her efforts were helped by the fact that the NCMRR was developing its strategic plan at the same time.

Enhancing Use of Cardiac and Pulmonary Rehabilitation in Traditional and Community Settings

Jerome Fleg, M.D., NHLBI, and Lyndon Joseph, Ph.D., NIA, led this discussion. Dr. Fleg indicated that two RFAs had been issued to enhance the use of cardiac and pulmonary rehabilitation in traditional and community settings. The RFA was inspired by the Million Hearts initiative.

Dr. Fleg said that about 2 million Americans per year have a coronary event or revascularization procedure, and millions more have a chronic condition for which cardiac rehabilitation is recommended. In 2010, there were 1.5 million emergency room visits for chronic obstructive pulmonary disease (COPD). Many of these patients who would benefit from cardiac or pulmonary rehabilitation do not receive it.

Cardiac and pulmonary rehabilitation is usually conducted by a multidisciplinary team at a center associated with a hospital. The goals of cardiac and pulmonary rehabilitation are to decrease mortality, morbidity, and readmissions; reduce symptom burden; encourage weight management; increase functional capacity; and reduce depression and stress.

Research has shown that cardiac and pulmonary rehabilitation programs are beneficial, although there is more evidence about the benefits of cardiac rehabilitation, because it has been in use for a much longer period of time. Cardiac rehabilitation is associated with a 47 percent reduction in reinfarction, a 26 percent reduction in mortality, and an 18 percent reduction in hospital readmissions.

Pulmonary rehabilitation is associated with a decrease in hospital readmissions, reduced respiratory and all-cause mortality, reduced dyspnea and fatigue, and improved physical capacity. The psychological risk factors of depression, hostility, and anxiety are also markedly reduced with rehabilitation.

Although rehabilitation has been shown to be beneficial and safe, few patients receive it. Only about 20 percent of white people and 8 percent of non-whites receive cardiac rehabilitation. The number of people receiving cardiac rehabilitation is even lower for those who have incomes below $15,000, live in rural areas, or have no rehabilitation program within their county. Pulmonary rehabilitation participation rates are even lower: Less than 4 percent of white people and 3 percent of non-white people receive pulmonary rehabilitation.

One of the biggest barriers to rehabilitation is the lack of referral and encouragement to participate from physicians. Other reasons include limited follow-up and facilitation of enrollment after referral, lack of health care coverage for the rehabilitation, and work or home responsibilities. Medicare will cover up to 36 sessions of cardiac rehabilitation.

The Million Hearts initiative, a program of the American Heart Association and the CDC, advocates for increased participation in cardiac rehabilitation. Million Hearts calls for a number of tactics for increasing participation:

• Targeting for referral older patients, women, minorities, non-English speakers, and people from lower socioeconomic groups and with lower educational attainment
• Expanding the responsibilities of home health nurses, exercise physiologists, physical therapists, and others, to provide home- or community-based cardiac rehabilitation
• Using innovative strategies such as telemedicine and fitness trackers to bring cardiac rehabilitation to more patients
• Reducing barriers to referral and participation, such as patients’ lack of knowledge about the benefits, physicians’ and health systems’ perception of the value of cardiac rehabilitation, and communities’ lack of programs

The NHLBI had some grants for cardiac and pulmonary rehabilitation within its portfolio, but more were needed. The Institute developed an RFA for rehabilitation in traditional and community settings (outside the hospital centers) to test whether that approach could lead to greater use of cardiac and pulmonary rehabilitation and reduce disparities in rehabilitation. The RFA also seeks to develop and test new models of community cardiac and pulmonary rehabilitation and to demonstrate that they lead to patient improvements and are cost effective.

For FY 2018, the RFA offered up to five R01 awards with direct costs of up to $500,000. The NHLBI received 26 applications, 14 of which were cardiac rehabilitation, 8 of which were for pulmonary rehabilitation, and 4 of which included both cardiac and pulmonary rehabilitation.

Dr. Joseph said that the NIA issued an RFA is to elicit applications for strategies to enhance referral, participation, and adherence in cardiac rehabilitation of older adults. The RFA seeks programs that will improve function, independence, and quality of life while reducing disability, future cardiovascular events, readmissions, morbidity, and mortality. The NIA issued the separate RFA in order to focus on the needs of older adults.

Older adults have very low participation in cardiac rehabilitation, even though Medicare covers it. Barriers for older patients include fears about their own frailty and vulnerability, lack of knowledge about the benefits of rehabilitation, lack of transportation to a rehabilitation facility, and caregiving responsibilities at home. Other barriers include the duration and number of sessions. Finding patient-centered goals could help improve participation. Giving patients a practical outcome to work toward, such as being able to walk to the store and carry a few bags home, might be more motivating. Reducing the number of medications, if possible, may also help.

The NIA wants clinical trials that will focus on at least one of the barriers for older adults’ participation, such as patient referral or rehabilitation setting. It is encouraging a multidisciplinary approach to include clinical and translational scientists, cardiologists, and geriatricians. The FOA also encourages the use of cutting-edge technology and delivery techniques, especially to underserved areas and patients, to increase adherence; and focusing on the aspects of cardiac rehabilitation related to the needs of older adults, such as the presence of comorbid conditions and polypharmacy.

The NIA issued the RFA in July. The application deadline was November 2017. The NIA received eight applications and hopes to award either one or two R01s for up to $700,000 per year for five years. The review will take place in February 2018.

Discussion

A Board member asked why patients are not referred to cardiac rehabilitation. Dr. Fleg said that he believes that the primary reason is that the physicians do not understand the benefits of a cardiac rehabilitation program. Some institutions have implemented an automated referral system, which has dramatically increased the uptake of cardiac rehabilitation. Another significant factor in nonreferral is the lack of availability of rehabilitation facilities in the community. Dr. Joseph said that it is not clear why physicians do not refer their patients for cardiac rehabilitation, but many physicians may think that prescribing medications will accomplish the same thing.

An attendee asked how these RFAs were able to get so many applications and whether the research would also include policy experts. Dr. Fleg said that groups interested in this research, including Million Hearts, advertised the RFA, which helped improve the response. Dr. Nitkin said that focusing on the psychology of getting patients back on track and to rehabilitation is important.

A Board member said that medical students are not receiving training in rehabilitation. It is important to involve other agencies in training, advertise the need for clinical care and research, and spread the word about available funding.

A Board member said that under-referral is a major problem in rehabilitation. The field is in need of implementation research. Dr. Fleg agreed and said that having rehabilitation in the home or at a community center, as the NHLBI RFA specifies, should increase participation.

A Board member said that the RFAs do not seem to focus on mobility limitation or disability as a barrier or challenge. The extent to which upper versus lower extremity exercise can be effective in cardiac rehab is not as well established. Metabolic syndrome is common in people with disabilities. Much of cardiac rehab and pulmonary rehab involves aerobic exercise which drives mechanisms promoting mitochondrial health and biogenesis. There are emerging nutrition supplement approaches and pharmacologic approaches using small molecule "exercise mimetics" that drive these same pathways that promote health and function. These approaches might help jump start a patient with mobility impairment who has a cardiac or pulmonary disease process. Would nutrition or small molecule approaches be of interest in the realm of cardiac and pulmonary rehab?

Scientific Presentation: The Rehabilitation Measures Database

Allen W. Heinemann, Ph.D., ABPP, Northwestern University, explained that medical professionals often monitor patient progress by using clinical judgment and intuition, not standardized instruments. Professionals cannot know whether a patient has received maximum benefit without standardized measures. Standardized assessments help determine the appropriateness of a treatment plan, identify the patient’s progress, and assist in diagnosis and referrals. In addition, standardized assessments can motivate patients to improve.

Barriers to use of standardized assessments include limited access to research evidence, lack of time, and limited knowledge about how to critique studies. Ways to overcome those barriers include writing research results in a concise and understandable way for clinicians and providing free online resources that are available at the point of care.

Dr. Heinemann and his team set a goal to develop the Rehabilitation Measures Database to promote adoption of standardized outcome measures, using a free web-based searchable database of standardized assessment to help clinicians. The database contains instruments to screen patients, monitor progress, and assess outcomes of physical and cognitive rehabilitation.

The team began by holding focus groups with physical and occupational therapists, speech and language pathologists, psychologists, and nurses to find out what the professionals would want in the database. After analyzing the data, the team set up a website and developed initial summaries of useful instruments. After the website was launched, the team needed to sustain it by monitoring its use, exploring ways to continue to finance it, and developing collaborative relationships to continue its growth.

The Rehabilitation Measures Database contains concise descriptions of instruments and how to administer and interpret them at the point of care. It also contains psychometric information reported by developers and investigators who have used the instrument. The information includes reliability and validity data, measures of clinical utility, and information on how it is administered and scored.

The Database receives more than 100,000 visits per month from users in 195 countries. There are more than 400 instruments available, although some instruments used for multiple populations are counted multiple times. New visitors account for 55 percent of the traffic, while returning visitors account for 45 percent. After the database moved to a new website recently, overall traffic has gone down, but the team expects it to recover.

Dr. Heinemann listed the 20 most-viewed instruments, all of which are relevant to physical therapy. The top five were the Berg balance scale, the timed up and go, the 6-minute walk test, the five times sit to stand test, and the 10-meter walk test.

Initial funding for the database came from the NIDILRR, the Retirement Research Foundation, and the Paralyzed Veterans of America Educational Foundation. The team worked with the Center for Translation of Rehabilitation Engineering Advances and Technology to develop a business model.

One of the American Physical Therapy Association (APTA) Evaluation Database to Guide Effectiveness (EDGE) groups offered funding to develop a mobile app. In 2017, the Feinberg School of Medicine agreed to fund 0.4 of a full-time equivalent to work on the Database.

Physical therapists were the largest group of users, followed by occupational therapists. Other users included recreational therapists, physicians, and psychologists. The types of assessments most often administered were assessments of physical and cognitive function, activities of daily living, and community participation.

The Database team has developed collaborative relationships with faculty in rehabilitation science and nursing programs who assign instrument summaries as class projects. Eight academic programs are collaborating to maintain and expand the Database, but more are needed. The Database has a toolkit that guides contributors in conducting a literature review and writing a summary of an instrument.

The Database has established collaborations with professional associations and with rehabilitation journals. The journals have published instrument summaries designed to be quick-reference guides for clinicians. More than 80 individuals have written instrument summaries.

More collaborators, academic and professional, are needed, and more journal collaborations are needed. The Database must obtain more funding. The team also wants to include more CDEs, including those published by the NINDS.

Discussion

A Board member said that this effort is valuable to rehabilitation researchers because it promotes common outcome measures that enable comparison of results across studies and identification of the best interventions.

A Board member asked whether there is an effort to import data directly into DASH. Dr. Cernich said that it would be more valuable to create CDEs. She suggested discussing that issue at a future meeting.

A Board member said that it would be helpful to have a single database containing resources for outcome measures that could be used across disciplines. Dr. Heinemann said that there are competing interests and demands from different professions, making a common database difficult. The APTA EDGE Task Force wanted to recommend certain instruments for use, and their recommendations are now included.

An attendee said that this is still the early stage of the open data era. One question is how to make these instruments interoperable. She suggested trying to cross-match the NINDS data definitions as one small step toward providing interoperability. Dr. Heinemann said that he would be interested in taking part in that effort.

An attendee asked whether there is a systematic way to update the Database. Dr. Heinemann said that there is not, although the date when an instrument summary was last updated is provided. There is a template and an author toolkit to help individuals who wish to add or update an instrument.

A Board member encouraged a collaboration between the Database and the NINDSCDEs. Also, more pediatric rehabilitation measures are needed in the Database.

Nomination and Vote for Board Chair-Elect

Indira Lanig, M.D., was nominated to serve as the next Board Chair; there were no other nominations from the floor. Dr. Lanig was approved unanimously on a voice vote.

Adjournment

Dr. Cernich asked that members who suggested discussions on specialized topics that would require a consultant to send her nominations.

Dr. Cernich asked that members suggest new candidates for the Board, particularly individuals who have benefitted from rehabilitation research.

Dr. Cernich asked Board members to nominate speakers for the Voice of the Patient portion of the National Advisory Child Health and Human Development Council.

Dr. Nitkin thanked the Board for their work and adjourned the meeting at 11:45 a.m.