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 1-2, 2014
Dr. Richard Shields, Board Chair, called the 49th meeting of the NABMRR to order at 9:00 am.
Future Board meetings will be: May 4-5, 2015; December 7-8, 2015, and May 2-3, 2016
|Anthony Delitto||Sureyya Dikman||Todd Kuiken|
Ex-Officio Members Present:
|Tim Brindle, VA
Daofen Chen, NINDS
|Alan Guttmacher, NICHD
Lyndon Joseph, NIA
|Ralph Nitkin, NICHD
John Tschida, NIDRR
Ex-Officio Members Absent:
|Ted A. Conway, NSF
Martin Gould, NCD
Roger Miller, NIDCD
|Lynn Padgett, NCI
James Panagis, NIAMS
|Michael Swanson, CDC
Lois Tully, NINR
NICHD Staff and Visitors:
|Ruth Brannon, NIDRR
Josephine Briggs, NCCAM
Leighton Chan, NIHCC
Peter Como, FDA
Theresa Cruz, NICHD
Robyn Ellerbe, APTA
Rosemarie Filart, Penn St
Craig Fisher, APA
Tinera Fobbs, NICHD
Michael Hoffman, FDA
Stuart Hoffman, VA
Lyn Jakeman, NINDS
Rusti Johnson, NICHD
|Lisa Kaeser, NICHD
Partap Khalsa, NCCAM
Naomi Kleitman, CHNFdn
Audrey Kusiak, VA
Susan Lin, AOTA
Karin Lohman, NCCAM
Michael Marge, NICHD
Mary Ellen Michel, NICHD
Maria Nurminskaya, CSR
Jo Pelham, CSR
Vivek Pinto, FDA
Lou Quatrano, NICHD
Mary Rogers, NIBIB
|Devjani Saha, FDA
Sarah Savoy, Assn Rehab Nurses
Brian Schultz, VA
Carol Sheredos, NICHD
Cathy Spong, NICHD
Katie Stout, MRMC
Nichole Stout, NIH CC
Sue Swenson, ED/OSERS
Nancy White, APTA
Cheri Wiggs, NEI
Bill Winfrey, CDR Fdn
The newest Board members (Amy Bastian, Joseph Hidler, Kevin Means, Randy Nudo, and Michelle Camicia) introduced themselves, followed by briefer introductions from the rest of the Board, NIH staff, and other visitors. Minutes from the previous meeting, May 2014, were approved.
Report of the Acting NCMRR Director
Dr. Ralph Nitkin, Acting Director of the NCMRR, provided the following updates. Dr. Nancy Shinowara has retired. A strong supporter of rehabilitation research for more than 2 decades, she first served as an NIH review officer and, since 2003, as the director of the Spinal Cord and Musculoskeletal Disorders and Assistive Devices Program in the NCMRR.
After reviewing over 28,000 clinical trials, the Australian Physiotherapy Evidence Database named the Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial as one of the top physiotherapy trials of the past 15 years. The trial, jointly funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the NCMRR, demonstrated that constraint-induced stroke therapy produced significant improvements in arm motor function.
The White House Summit on Improved Health and Fitness for Children with Disabilities was held on October 6–7. Researchers, advocates, parents, and consumers attended the summit, which was sponsored by the President's Council on Fitness, Sports, and Nutrition. The first day highlighted the I Can Do It, You Can Do It! Program, while the second day focused on research finding and opportunities.
The NCMRR continued conversations with the Food and Drug Administration (FDA). The FDA made a presentation to the Board at the May 2014 meeting on the medical device approval process. This was followed by a visit to the FDA by a dozen representatives from the NCMRR and other NIH colleagues in November, 2014, to discuss goals, regulatory procedures, research frontiers, and collaborative opportunities. NIH representatives also attended an FDA workshop on November 21, Brain-Computer Interface Devices for Patients with Paralysis and Amputation.
The NICHD and the NINDS cosponsored a workshop on State-of-the-Science and Treatment Decisions in Cerebral Palsy (CP) on November 12–13, 2014. The workshop considered the evidence base for various treatment options for children with CP. CP is rather heterogeneous with respect to prenatal and perinatal etiologies, motor deficits, and secondary conditions. The focus of the workshop was on which treatments work for which children, and what health-care options are available later in life. Discussions are continuing among the NINDS, the NICHD, clinical researchers, and advocates to consider treatment and outcome registries and perhaps a follow-up conference focusing on neuroplasticity and translational research.
Dr. Nitkin presented a list of meetings NCMRR staff had attended over the past year. Although the administrative travel budget is tight, staff works hard to attend appropriate rehabilitation meetings. Board members were encouraged to alert NCMRR staff of important meetings that might come up in their domains.
NCMRR staff will participate in a meeting with the U.S. Department of Veterans Affairs (VA) and Department of Defense (DOD) to review the Clinical and Rehabilitative Medicine Research Program portfolios. Among other projects, the VA and DOD portfolios includes projects on neurological and musculoskeletal injury rehabilitation, prosthetics, and orthotics.
Dr. Nitkin indicated that fiscal year 2014 was a year of change for the NCMRR, which now has a set-aside budget equivalent to 6.5 percent of the NICHD extramural budget. This set-aside budget has given the NCMRR increased flexibility to incentivize, develop, and cofund projects with other NIH Institutes and Centers (ICs). The NCMRR has reinvigorated the Trans-NIH Rehabilitation Coordinating Committee and increased interest in the Rehabilitation Research Infrastructure Network, which is coming up for renewal in 2015.
In fiscal year 2014, the NCMRR had about $67 million to fund rehabilitation research and training and career development. Within any given year, most of the funding is already committed to ongoing, multi-year grants, but in 2014 about $25.4 million was available for new grants and was targeted as follows: $11 million for the Small Business Innovation Research (SBIR) and the Small Business Technology Transfer (STTR) programs; $1.6 million for new training and career development awards; and $12.7 million for new investigator-initiated research grants. About 19 percent of available 2014 NCMRR budget was directed toward cofunding projects with other ICs or to fund meritorious grants that are just beyond the NICHD pay line. NCMRR cofunds included research projects at the NINDS, the National Institute of Biomedical Imaging and Bioengineering, the National Institute on Deafness and Other Communication Disorders (NIDCD), and even other Branches within the NICHD.
The Rehabilitation Research Infrastructure Networks provides access to range of key expertise and technology that is especially relevant to new rehabilitation researchers. Investigators can go to the experts in these networks to take courses or webinars, ask questions, develop collaborations, or even run samples. The network provide expertise across the gamut, including genomics, muscle physiology and function, bioengineering and robotics, outcomes, health services research, and technology transfer. This program, which is coming up for competitive renewal shortly, will continue to provide access to state-of-the art research techniques and approaches. The Request for Applications (RFA) should be published in early 2015, with about 60 days for prospective centers to prepare applications. In the meantime, a Notice of Intent was published, to alert investigators to the renewal of this important program. With the renewal, the NCMRR and other rehabilitation colleagues at the NIH are particularly interested in expanding into the following domains: clinical trial design, engineering and the environment, individualized medicine and dynamic reassessment, and applied behavioral supports for rehabilitation research and healthy outcomes. Dr. Nitkin also highlighted NIH funding of the Mobilize Center (Scott Delp), which provides expertise on big data that is particularly relevant to CP, gait, and obesity research. Board members should help spread the word on all these excellent research resources.
Other recent funding opportunities involving the NCMRR include RFAs on peripheral blood biomarkers of chronic traumatic brain injury (TBI) in humans, rehabilitation robotic technology, and orthotics to promote healthy development as well as program announcements on pregnancy in women with disabilities, technologies for healthy independent living, and smart and connected health.
Dr. Nitkin also raised the issue of how much the NCMRR should be prioritize funding research in areas that already overlap with the NCMRR and other NIH Institutes. For example, should the NCMRR fund a project with the National Institute on Aging about impairments that focuses primarily on people who are elderly but not especially disabled? What about studies of sensory disorders (with the National Eye Institute or with the NIDCD) or cancer rehabilitation (with the National Cancer Institute) or cardiovascular rehabilitation (with the National Heart, Lung, and Blood Institute)?
The Board pointed out that the NCMRR has limited funding and a unique mission to fund rehabilitation research; they noted that its mission should weigh into the decision. On the other hand, it may be possible to interest more investigators in rehabilitation research by cofunding research projects that start in allied fields. Moreover, it is important to fund some boundary areas as a way to diversify the portfolio and to expand rehabilitation research. The Board suggested that the NCMRR could cofund a study on, for example, healthy elderly people but require that the study include elderly people with disabilities. A suggestion was made to create a plan that would help guide these funding decisions as they arise.
FDA Regulatory Process For Medical Devices
Dr. Shields introduced this session by noting that there is a growing relationship between the FDA and the NCMRR. This session was a continuation of the conversations between the FDA, the NCMRR, and the Board. Dr. Vivek Pinto, a lead reviewer for the FDA Division of Neurological and Physical Medicine Devices, reminded Board members about the presentation on the medical devices submission pathways and the FDA classification system at the May 2014 Board meeting. Dr. Pinto reviewed the different regulatory pathways, including 510(k), De Novo, and Premarket Approval (PMA). The higher the risk associated with a particular device, the more regulatory requirements involved. The 510(k) regulatory pathway is used for devices that are very similar to already approved devices but that have been modified in a way that does not affect safety (e.g., a modified manual wheelchair). The 510(k) review determines whether the sponsor has established substantial equivalence to a legally marketed predicate (already approved) device.
The De Novo and PMA pathways are for new or existing devices to be used in a novel manner. The De Novo pathway is for low- or moderate-risk devices, while the PMA pathway is for high-risk devices. The PMA pathway usually requires clinical data to support safety and effectiveness. DeNovo and PMA reviews seek to determine whether the sponsor has provided adequate evidence to support safety and effectiveness.
Dr. Pinto gave examples of new intended uses and new questions raised during the regulatory process. He then defined the differences among the terms "indication for use," "modified indication for use," "intended use," and "new intended use," and gave examples of how those concepts affect the FDA approval process.
Dr. Devjani Saha, also an FDA lead reviewer, detailed key issues that must be addressed in FDA applications, including labeling, sterilization, biocompatibility, software, emissions and electrical safety, performance testing, and shelf life. The section on labeling may include the device label, indications for use, clinical and technical manuals, package labeling, and promotional material. If a device has components that need sterilization, the applicant must include refer to a validated sterilization method and the particular sterilant used, and the probability of sterilization failure must be low. Shelf life is considered in terms of the integrity of the packaging to withstand the stresses of shipping and handling and protecting the device over its shelf life. Different types of tests are needed to assess biocompatibility, depending on, among other things, the duration of the contact with the patient and the degree of invasiveness.
The device software also must be documented. This would include not only software but also firmware and relevant hardware. The extent of documentation depends on the level of risk associated with a potential software failure. Electromagnetic components and electrical safety documentation must include, among other things, documentation of whether the new device could interfere with other devices or vice versa.
The FDA has its own regulatory science testing laboratory that helps reviewers establish the kind of testing required of the applicant. Private companies may also do the testing, but the FDA cannot endorse one company over another. If an applicant wants an opinion on whether proposed testing would be adequate, FDA staff can provide them with advice on the protocols before they begin. If necessary, the FDA has the ability to review tests or give the product to the scientific center for follow-up testing.
The 510(k) has a 60-day review period, but applicants must be told within 15 days whether they have included everything required in their application. If there are deficiencies, the applicant is given an additional 6 months to respond. However, PMA and investigational device exemption pathways take longer. Some companies submit their applications without prior communication, and they may need the 6 months to complete the applications. However companies that communicate with FDA prior to submission are more aware of FDA expectations at the time they apply.
Dr. Peter G. Como, another member of the FDA review team, talked about research, development, and validation of medical devices for TBI regulatory perspectives. He focused on the clinical aspects of the regulatory process, using the example of a device related to TBI. However, he pointed out that the FDA has cleared only one TBI diagnostic device. The process began in 2009 in the pre-submission stage, which helped the company understand the requirements that they would have to meet to get the device to market.
The risk level for neurodiagnostic devices is usually rated low or moderate and can be cleared via the 510(k) pathway as long as a similar device has already been cleared through the De Novo pathway. An implantable neurotherapeutic device would require approval through the investigational device exemption or the PMA pathway. When deciding which regulatory pathway a TBI device must take, the FDA takes into account the study design, the population, and the vulnerability of the population using the device. Among the clinical study considerations that FDA takes into account are how the normative database was constructed, whether it accounted for comorbid conditions that can affect performance, which professionals will use the device, and whether the skill needed to use the device is consistent with the person's training. Dr. Como also detailed other issues regarding diagnostic medical devices for TBI, such as the absence of a gold standard for the diagnosis of TBI or concussion; he also noted that TBI is a clinical diagnosis, not one that can be made using only a medical device.
The Board discussed what pathway a device that measures the impact of hits to helmets would have to go through for approval. The FDA reviewer indicated that it would depend on whether the device meets the definition of a medical device and on its intended use. The applicant can request that the FDA determine whether a product meets the definition of a medical device. For example, if a device provides diagnostic information, the applicant may be required to submit an application to the FDA.
The Board asked about a potential gray area involving the development of computer-based neuropsychological test batteries that may be marketed as a diagnostic device. The reviewers explained that FDA does not regulate paper-and-pencil tests but is developing guidance for regulation of computer-assisted assessments; they have not yet finalized that guidance.
The FDA Office of Compliance responds to inquiries regarding products that make claims about diagnosis that are not supported. That office receives many inquiries and prioritizes them based on the possible harm that the device could cause. In such a case, the FDA could take a range of actions, including seizure of the device.
The FDA representatives made some final points about regulatory processes. A product becomes a medical device at the time it is commercialized; the FDA is not mandated to test medical devices but will sometimes test devices at the request of an FDA reviewer. The reference group for a diagnostic device should reflect the makeup of the U.S. population, unless the device is intended only for a certain subpopulation. And the normative database must have appropriate clinical data so that if, for example, a device will be used with individuals 18 to 80 years old, then the database should be representative of people of all backgrounds in that age group.
Because of its expertise, the Board is periodically called on to provide an additional level of review for specific NCMRR initiatives. Ms. Josephine Pelham of the NIH Center for Scientific Review (CSR) stepped in to lead concept clearance for a potential NCMRR RFA for Secondary Analysis of Existing Data in TBI. A brief overview of this proposal had been circulated to the Board prior to the meeting. The RFA would solicit small grant applications to support secondary analysis related to long-term function after TBI.
Dr. Mary Ellen Michel, director of the Traumatic Brain Injury and Stroke Rehabilitation Program at the NCMRR, provided some further background. She indicated that efforts have been underway with the Department of Defense and the NINDS to create a large database with common data elements (CDEs). The intent is to provide access to the large databases such as the Federal Interagency Traumatic Brain Injury Research (FITBIR) informatics system and the Citicoline Brain Injury Treatment Trial (COBRIT). The goal is to provide investigators with an opportunity to conduct secondary analyses of TBI databases in order to enhance the design of new studies for TBI rehabilitation. Many of the relevant studies are clinical trials and most of the data have been collected within the last 5 to 7 years during which time many issues about CDEs, data standards, and database development have already been considered. Thus, it is expected that the data would be accessible and of high quality, but it will be necessary to actually delve into these data to verify that this is true. One problem is that much of the data has been anonymized, which could affect its usefulness for follow-up studies. Although the original investigators may have the necessary identifiers, it would require more collaboration to get that information and match it with the appropriate outcome data.
After brief Board discussion, the Board provided unanimous approval for the proposed initiative through a voice vote.
Update From The National Institute On Disability, Independent Living, And Rehabilitation Research (NIDRR)
NIDDR Director John Tschida, M.P.P., said that the NIDRR's mission is to generate knowledge that will allow people with disabilities to take part fully in activities in the community, and, if necessary, to expand opportunities and accommodations for this population. He provided the example of the NIDRR's investment in driverless technology.
The Workforce Investment and Opportunity Act moved the NIDRR from the Department of Education (DOE) to the Administration for Community Living (ACL), which is in the Department of Health and Human Services. The ACL is responsible for increasing access to community supports for older Americans and people with disabilities across the lifespan. The Act also added the term "independent living" to NIDRR's name.
There are many tasks involved in moving NIDRR from the DOE to the HHS; the NIDRR and the ACL continue to work on the transition. During the transition, the NIDRR would continue its regular duties. The fundamental mission of the NIDRR will remain the same, as would its total budget and the types of investments that it makes. NIDRR staff members have already established close working relationships with ACL staff. The ACL has a strong policy and a strong program focus but no research experience and the NIDRR will bring research capacity to the agency. One area of research that will continue to be important is the development of new technology to help people with brain injuries live in the community.
The NIDRR will continue to focus on collaborations through its many interagency agreements and memoranda of understanding. For example, the NIDRR is working with the Federal Communications Commission on cloud technology to allow access and portability for people with disabilities. The NIDRR is also interested in continuing collaborations with the NCMRR, perhaps even opportunities to cofund research. The NIDRR will continue to maintain the rigor of its research program, emphasize research that is relevant to people with disabilities, maintain flexibility in funding opportunities, and engage with its constituents.
In discussion with the Board, Mr. Tschida said that the NIDRR will continue to invest in centers of excellence, which include model systems in spinal cord injury (SCI), brain injury, and burns. The burn model system has leveraged a limited NIDRR investment into larger funding opportunities with the VA. The NIDRR has not had a focus on pediatric brain injury in the past, but would welcome conversations with the NCMRR on doing more.
The NIDRR has a diverse portfolio, including a training component, but needs to make tough choices about where to focus in the future. Its research has had success in some areas; in some others, a little more funding would produce good results. The agency hopes to have multiple stakeholders (including the NCMRR) involved in developing its next 5-year plan. It is important to build capacity by attracting people from allied fields and by increasing the diversity of voices at the table.:
Initiative In Cancer Rehabilitation
Dr. Nicole Stout gave the Board an update on a collaboration initiated by the NIH Clinical Center to promote cancer rehabilitation. More than 70 percent of cancer patients now survive their cancer, but many will have impairments that result from treatment or even the cancer itself. Rehabilitation can mitigate and, in some cases, prevent the negative effects of cancer treatments, but very little work is being done to promote and integrate rehabilitation following cancer diagnosis.
The NIH Clinical Center Rehabilitation Medicine Department has several goals for this initiative, which include elevating practice and research in cancer rehabilitation, convening experts to develop national initiatives in cancer rehabilitation, and working with extramural funding bodies to enhance research in this area. The initiative will convene a consortium of experts in multiple disciplines to promote standards for cancer rehabilitation practice and facilitate collaborations within the NIH and with external partners. The initiative has already engaged the NCMRR and the Livestrong Foundation. Subject-matter experts have been recruited to consider various rehabilitation models for cancer care, screening for impairments, functional outcomes measures, interdisciplinary decision-making, and research opportunities.
The working groups will use a broad definition of cancer rehabilitation, with a lifespan perspective, across care settings, and with the understanding that cancer care puts a heavy burden on the patient as well as the family. The working groups are holding monthly progress webinars and culminating in a cancer rehabilitation conference in June 2015 on the NIH campus to help identify needs and develop collaborations. During the June meeting, the working groups will disseminate their findings and engage the audience to discuss the finding and next steps.
Board members discussed a range of issues related to cancer rehabilitation, including how to integrate patients into a continuum of care. This is an important issue, because although exercise can change overall survival rates, individuals who have undergone cancer treatment maybe at increased safety risk (e.g., cardiotoxicity) during therapeutic treatments. Are there sufficient rehabilitation specialists who are trained to work with people with cancer? At what point should cancer rehabilitation be introduced? Insurance may not pay for a rehabilitation exercise program that is run through a private gym. It is also necessary to consider how rehabilitation might help treat cancer-related chronic pain. There are also health disparities to consider, with some groups having a disproportionate share of cancer diagnoses and a greater likelihood of having pain. There is a need to educate payers about the benefits of cancer rehabilitation and to develop a more knowledgeable health-care workforce.
Report Of The NICHD Director
Dr. Alan Guttmacher thanked Board members for their service and reassured them that the NICHD takes seriously the advice that they give. His update began with personnel changes at NIH. Dr. Story Landis retired as Director of the NINDS. Pat White retired as NIH associate director for legislative analysis to lead a new advocacy effort in support of the NIH. Dr. Don Lindberg, the Director of the National Library of Medicine (NLM), will be retiring in March. The NLM has established PubMed Commons as a forum to comment in real time about scientific publications that appear in PubMed.
The NIH has been involved in the federal response to Ebola. The NIH treated a patient who contracted the disease. The National Institute of Allergy and Infectious Diseases helped to provide information about Ebola and developed diagnostics to detect the virus, therapeutics to treat the illness, and a vaccine to prevent infection that is now being tested in a Phase I clinical trial.
Dr. Guttmacher indicated that Dr. Eric Betzig, who won the Nobel Prize in Chemistry, began his initial research in the NICHD laboratory of Dr. Jennifer Lippincott-Schwartz.
A working group of the Advisory Committee to the Director (ACD) is evaluating the NIH Intramural Research Program and will present its report at the December 11–12 ACD meeting. The NIH hired Dr. Hannah Valantine as the first Chief Officer for Scientific Workforce Diversity. The NIH National Diversity Consortium is working to diversify the biomedical workforce, with three new diversity initiatives: Building Infrastructure Leading to Diversity, the National Research Mentoring Network, and the Coordination and Evaluation Center. This effort is a high priority for the NIH.
Dr. Cathy Spong is the new Deputy Director of the NICHD and Dr. Caroline Signore has moved up to be the Acting Director of Extramural Research. A search for a permanent Director of Extramural Research was ongoing. The search for a permanent NCMRR Director is still underway but should be completed soon.
The National Children's Study (NCS) was part of the Children's Health Act of 2000 and aimed to better understand the environmental influences on children's health. But the Institute of Medicine had some concerns about the study's design, and the NIH has put the main study on hold to determine the best path forward. An ACD was been assembled to answer some key questions about the study, including whether it is still feasible to carry it out, especially given the current budget situation. The working group will present their findings to the NIH Director at the regularly scheduled ACD meeting December 11–12.
The TBI bill that reauthorizes federal prevention, surveillance, and registry programs related to TBI has been signed into law. There is some uncertainty regarding how the federal government will be funded after December 11. No matter what happens, the NCMRR will continue to receive 6.5 percent of the NICHD extramural budget.
Summary Of Day 1 Discussions
Dr. Shields, Board Chair, provided a recap of discussion from the previous day. The recommendations of the Blue Ribbon Panel are being implemented under the leadership of Dr. Nitkin. The NCMRR, with a guaranteed budget equivalent to 6.5 percent of the NICHD extramural budget, has coordinated rehabilitation efforts across the NIH. The Panel also endorsed the renewal of the Rehabilitation Research Infrastructure Network and its potential expansion into new research domains, which can be shared with researchers, and looks forward to publication of that funding opportunity.
Board members acknowledged that the NCMRR has made significant progress in the past 18 months. They thanked Dr. Nitkin for his leadership in making those changes and in bringing the Blue Ribbon Panel recommendations to fruition. The Board also thanked NCMRR staff and said that it was important to keep building on that considerable progress.
One Board member said that there should be more discussion of health services for the people whom the Board represents. Also, there has to be a greater effort to integrate diversity issues into the Board's discussions and help reduce health disparities. One Board member noted that the NCMRR has limited resources and should have a strategic plan that focuses on what is achievable. Another Board member agreed and said that pain, which limits many people with disabilities, should be a priority. Other priorities should include health disparities. These areas of research are now receiving additional attention at NIH, so it may be possible to leverage funds to achieve progress in these areas. As the NCMRR plans for the future, the Board would continue to focus on how to increase the size and quality of the rehabilitation research portfolio, how to bring more scientific disciplines into rehabilitation research, and whether there are ways to refine the ways they do research.
Board members were reminded that rehabilitation research funding can be found across the NIH, but that it does not always contain the word "rehabilitation" in the title. One example is the Mobilize Center, which pairs rehabilitation research with big data experts and receives funding through the NIH Common Fund. The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, supported through the NIH Common Fund, also has implications for people with disabilities.
Transitioning And Translating From The NIH National Center For Complementary And Alternative Medicine (NCCAM)
NCCAM Director Dr. Josephine Briggs indicated that there is a proposal to rename the NCCAM as the National Center for Complementary and Integrative Health, because NCCAM's portfolio is increasingly focusing on health practices that are integrated into medical care (e.g., deep breathing, chiropractic, acupuncture, meditation, yoga, and massage). Pain is an important health issue that NCCAM shares with rehabilitation researchers. Meditation, massage, and yoga are the most common complementary approaches to pain management and are in the NCCAM portfolio. There is currently an epidemic in the abuse of opioid analgesics, but physicians do not have the evidence base or resources to adequately manage use of these drugs. Non-pharmaceutical ways of managing pain have to be developed, but the research base is lacking; clinicians have opinions about what works, but they do not have data.
NCCAM studies complementary approaches that are used by the public, especially in the area of mind-body interactions. Research is needed to find out whether there is a benefit to specific approaches and, if so, how to optimize them. The NCCAM is supporting pragmatic clinical trials to test the value of interventions under real-world conditions. The pragmatic trials would support participation of a wide range of patients, allow them to continue to see their regular health practitioners, but would not support follow-up visits or anything beyond usual compliance. One pragmatic trial concerns the management of chronic pain in primary care. This study takes a team approach to improving patient pain outcomes while managing the use of opioid analgesics. Pain management is one area in which the NCCAM and the NCMRR could collaborate.
The NCMRR might want to consider using pragmatic trials, although they do have limitations. One limitation is that the trials' outcome measures are drawn from electronic health records and patient reports. But the design of the trials encourages provider involvement in research outcomes. This model is a good one for answering certain questions, but more research is needed to identify the type of questions best suited to this approach.
The Board briefly discussed some of the pros and cons of pragmatic trials. A comment was made that the NCMRR should consider pragmatic trial designs when it draws up its next strategic plan; these trials might work well when investigating issues of health care delivery. However, peer review panels are not enthusiastic about pragmatic clinical trial design, so one Board member suggested that the NCMRR should take some initial steps to demonstrate to review panels the utility of this design especially for real-world research issues.
Dr. Partap Khalsa, also of the NCCAM, discussed the challenges associated with back pain research. This is a major clinical issue and the number of people with chronic low back pain is growing. In 2012, the NIH Pain Consortium formed a task force of 16 experts to develop research standards to evaluate chronic low back pain. The task force developed the minimum data-set and published it simultaneously in seven journals in order to reach as many pain researchers as possible. These core data should be included in all studies of low back pain. The task force developed core data by using the NIH Patient Reported Outcomes Measurement Information System, which relies on patient reports of pain intensity and how much it interferes with daily life. Adherence to a standardized minimum dataset would allow comparison across studies. Grant applications coming into the NIH are now required to include these research standards. The NIH is also aware of the need to strengthen approaches to data sharing. In every study requesting more than $1 million annually, investigators must include a data-sharing plan, but there is no way to ensure that the plan is actually implemented.
A Board member indicated that the Centers for Medicare & Medicaid Services (CMS) does not pay for individuals who are otherwise healthy to go into a rehabilitation hospital following back surgery. Dr. Briggs responded that it is important for the NIH to build an evidence base so that the CMS can make appropriate decisions on payment issues, although these are difficult decisions to make.
Research Talk: Capitalizing On Musculoskeletal Plasticity To Improve Health After SCI
Dr. Shields summarized some of his own research findings on musculoskeletal plasticity among people with SCI. His laboratory looks at how muscle disuse affects the muscles, bones, and overall metabolism. He emphasized that muscles are engaged in cross-talk with nerves and skeleton, and that they should be seen as an integrated system. Skeletal muscle can deteriorate significantly within a year after SCI. Muscle cells develop more fat stores within them, even when the individual's overall body mass index appears to be good. Changes in the muscle cells can lead to insulin sensitivity, insulin resistance, metabolic disease, and obesity. Muscle disuse also results in a very rapid bone loss (about 2 to 3 percent per month), meaning that significant bone mineral density would be lost within 2 years with a very high fracture risk. At the cellular and molecular level, it takes about 1.7 years for a paralyzed soleus muscle to lose oxidative capacity and down-regulate transcription factor PGC1α, which affects the ability of the mitochondria to regenerate.
Dr. Shields' laboratory initiated studies to electrically stimulate the muscles of SCI individuals to help them stand. The patients enjoy standing, and it relieves pressure placed on the skin and risk for sores from being sedentary or bedridden. In one set of experiments, individuals who were bedridden were given a daily 10-minute exercise intervention to train one leg, with the other leg as control. The trained limb did much better than the untrained limb, and there with a six-fold increase in PGC1α, the key mitochondria factor discussed above. Within the muscle, some fast-twitch genes were down-regulated and slow-twitch genes up-regulated with the training. Moreover, regular muscle activity was found to help promote DNA repair.
About 80 percent of patients with SCI are male, but not much is known about potential sex differences in the effects of SCI. However, limited data suggest that male and female muscle changes following SCI are similar, but there may be differences in the time course of these changes.
Epigenetics may provide a means to understand and maintain muscle health in the face of SCI, perhaps by activating genes associated with positive outcomes and silencing genes that cause negative outcomes. As indicated above, regular physical activity activates some of the major transcription factors, including PGC1α, which promotes mitochondrial biogenesis.
New Business And Agenda For Next Meeting
Board members made the following suggestions for the next meeting in May 2015 and beyond:
- Invite a representative of the Patient-Centered Outcomes Research Institute to have a discussion with the board.
- Invite the CSR discuss how changes at in peer review have affected rehabilitation investigators.
- Discuss the metrics used to assess the Rehabilitation Research Infrastructure Network. It is important for the Board to know whether it is getting the most out of this investment.
- Provide more details on how the NCMRR budget is spent, including where grant money is distributed. The discussion could include how the priorities of other NIH ICs compare and synergize with those of the NCMRR. A suggestion was made to do this at the December board meeting.
- Invite nonprofit funders and private-industry members with which the NCMRR might be able to form partnerships to discuss collaborations.
There was a suggestion to have the Board find a way to keep in touch on a more frequent basis. Another Board member asked for more information regarding NCMRR partnerships, including those with other ICs and a different Board member requested a more detailed accounting of NCMRR spending; for example, how much money is being put into TBI or cardiology? This could give the Board an idea of how dispersed NCMRR research funding is. NCMRR staff noted that one difficulty with providing a snapshot of expenditures is that grant money goes primarily to investigator-initiated projects; the NIH is not highly directive with those funds. When an area needs more research, the NIH will issue incentives to stimulate work in the field. The Board also raised the question of whether a larger staff is needed for the NCMRR and whether this would speed up the progress for rehabilitation research.
The meeting was adjourned at 11:48 am.