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 7-8, 2009
Dr. Joy Hammel, Board Chair, called the 39th meeting of the NABMRR to order at 8:30 am. Minutes from the previous meeting were approved.
May 3-4, 2010December 6-7, 2010May 5-6, 2011
The meeting opened with brief introductions of Board Members and guests. Four new members of the board were welcomed: George Kraft, M.D., M.S., University of Washington; Denise Tate, Ph.D., University of Michigan; Pam Duncan, P.T., Ph.D., FAPTA, FAHA, Duke University; and J. Michael Dean, M.D., M.B.A., University of Utah.
Given the recent changes in NICHD leadership, Deputy Director Dr. Yvonne Maddox delivered the NICHD Director’s Report.
Fiscal year 2009 ended on September 30, 2009 with an NICHD budget of $1.294 billion, which funded 451 new and continuing grants. As of yet, fiscal year 2010 has no appropriation; however the expected budget is $1.313 billion. [President Obama has since signed the 2010 appropriation for the NICHD for $1.329 billion.] NICHD leadership expressed great concern about the anticipated pay line for new research grants, which will probably fall in the range of the 8-9 percentile. The Institute has to support a relatively large number of ongoing grants, which make up the noncompeting base. In the absence of an official appropriation, the NICHD will start with a more conservative pay line at the 6 percentile. However paylines for the Small Business Innovation Research (SBIR) and Small Business Technology Transfer Research (STTR) programs are expected to improve.
In February, President Obama signed the American Recovery and Reinvestment Act (ARRA), which appropriated $8 billion to the extramural programs of the NIH. The NICHD received $330 million, 60% of which was awarded to Research Project Grants (RPGs), including truncated two-year R01 grants, R21 and R03 grants, Challenge grants (RC1) and Grand Opportunity (GO) grants (RC2). In addition, $30 million was provided to existing grants in the form of administrative supplements and support for summer students. Because the NCMRR does not use the Center mechanisms commonly used elsewhere in the NICHD, some supplemental funds were allotted to the R24 Medical Rehabilitation Research Resource Program. Although the majority of ARRA money has been disbursed for 2009 and extending into 2010, there are still some ARRA funds reserved for new opportunities in 2010. There will be a re-competition for GO grants under the RC4 mechanism (Director’s Opportunities grants in the five thematic areas identified by NIH Director Dr. Francis Collins). The RC4 mechanism would allow for upfront money distribution of 2010 funds to be used over a two-year period.
In other NIH news, Dr. Francis Collins was appointed as the new NIH Director starting in the summer of 2009. His vision for the future of the NIH includes support for translation of therapies from the bench to the bedside and comparative effectiveness research, which aligns especially well with NICHD and NCMRR priorities.
The NICHD has also undergone changes in leadership. In September, Dr. Duane Alexander, who had lead the NICHD for 23 years, moved to the Fogerty International Center as senior scientific advisor in maternal and child health, which is part of the Global Health Initiative outlined by the US State Department. Dr. Susan Shurin, Deputy Director of NHLBI, was initially appointed acting director of the NICHD and served for two months until she was called back to the NHLBI to serve as acting director there upon the retirement of Elizabeth Nabel. On December 1, Dr. Alan Guttmacher was appointed acting director of the NICHD. He is a pediatrician by training with research interests in the genomics. Dr. Guttmacher was the former acting director of NHGRI and before that senior clinical advisor to the NHGRI director.
Dr. Guttmacher provided his own welcome to the Board and briefly answered questions about his vision for the institute. He discussed his commitment to medical rehabilitation and the disability community, stressing his belief that the institute is a good fit for the NCMRR.
In a discussion with the acting NICHD Director, the Board asked for the Institute to increase its commitment to rehabilitation research and the activities of the NCMRR. They described the importance of understanding how people interact with their environment, and the special need collaborate with other federal agencies in areas such as transportation, employment, and environmental resources. The Board was particularly concerned about NIH support for the training of new and early-stage investigators, especially with dwindling numbers of physician scientists. Dr Guttmacher indicated that the NICHD has tried to respond with targeted career-development networks and differential pay lines for new investigators. The Board described the difficulty of doing “comparative effectiveness” research in rehabilitation because of the lack of sufficient understanding of the trajectories of recovery. The Board also discussed data sharing and synergies because of the potential overlap in rehabilitation and geriatric issues. At the other end of the continuum, the pediatric critical care program within the NCMRR could provide a link to younger populations.
Drs. Leighton Chan, Beth Rasch, and Diane Damiano described the rehabilitation services and research performed at the NIH Clinical Center (CC). The Clinical Center is part of the intramural programs of the NIH, which represents 10-13% of the overall NIH budget. All researchers and projects in the intramural program undergo periodic review every four years. In addition, the CC supports a large and unique patient base. The Rehabilitation Medicine Department, with nearly one hundred members, provides physical, occupational, recreational, and speech therapy for the patients in the CC, functional assessments for research protocols, and independent research projects.
Dr. Chan, a physiatrist, is currently the principal investigator for a traumatic brain injury study performed in conjunction with the Department of Defense to understand the progression of biological and neurological factors in traumatic brain injury. The study focuses on both civilian and Armed Forces’ populations.
Dr. Beth Rasch, an epidemiologist and statistician, described collaborations with the Social Security Administration (SSA) and Kaiser Permanente of Northern California. One such study seeks to understand, and ultimately improve, the decision-making process by which denied applications for disability are overturned in order to reduce the time that people with disabilities remain without benefits. She is working with Kaiser Permanente to assess stroke patients from acute treatment, through initial hospitalization, inpatient, outpatient, and day rehabilitation. Kaiser Permanente provides a unique opportunity to examine the continuum of care for the stroke patients.
Dr. Diane Damiano, a physical therapist, is the director of the Functional Applied Biomechanics laboratory, which contains a real-time dynamic gait lab, virtual reality technology combined with an instrumented splitbelt treadmill, wireless electromyography, a ZeroG overhead harness, a BalanceMaster, an ultrasound machine, and rehabilitation robotics. She discussed a study with Dr. Fran Sheehan-Gavelli to use technologies adapted from cardiac imaging to study the structure and function of lower-limb joints during movement. Her colleague, Dr. Hyung Park, is developing robotics for to promote tele-rehabilitation. Dr. Damiano is using elliptical training devices to improve gait in children with cerebral palsy. The CC provides her with special opportunities for collaboration, such as one study where neuroscientists are examining mechanisms of neural plasticity associated with motor training.
The Board was excited the potential for the NCMRR to collaborate with the CC, and also encouraged the NCMRR to see opportunities to collaborate with other NIH Institutes as well as other federal agencies to tackle larger, more complex problems. The Board also expressed the need to coordinate efforts in outcome measurement research to better serve the disability community.
As part of the periodic strategic planning processes within the Institute, the NCMRR is charged with preparing a report for the NICHD Advisory Council, which would be presented in September 2010. The report is to be a prospective discussion of future research opportunities. The planning process will begin with the NCMRR Advisory Board, which has the appropriate expertise and perspective to highlight some of the public health issues and scientific areas ripe for advancement in the field of medical rehabilitation. To facilitate such deliberations, the Board and visitors were divided into three parallel breakout groups: (1) translational studies in basic research and applied engineering, (2) health and participation outcomes with context, and (3) clinical opportunities and needs, which were developed with the Board in the weeks prior to the actual meeting. Each group was given a few hours to meet and then report their discussion back to entire Board:
One key issue is the development of appropriate outcome measures. Moving patients away from facility-based care is a goal of continued care, but uniform measurement of rehabilitation outcomes in the home is a challenge. Current technologies are disparate and, as a result, the outcome measures are disparate. Therefore, the group identified novel technology to measure functional outcomes at home as a key future research topic. This knowledge is particularly important given that the window of plasticity for rehabilitation, while unknown, is likely beyond the time of inpatient rehabilitation. By monitoring what a patient actually does at home and in the community, clinicians may better understand and intervene in the trajectory of disability to both increase recovery and prevent secondary conditions. In conjunction with the need for measurements of function at home is the goal to create more home and community-based rehabilitation opportunities to promote continued post-acute recovery. The goal is to encourage rehabilitation outside the hospital environment.
Another issue is how to account for multiple environments during clinical trials because environment influences disability. Traditionally, environment has been viewed as a covariate, but it should be measured as an independent factor. Researchers could measure the impact of the environment and possibly manipulate it, or at least acknowledge it as a mediating variable.
Assistive devices, in particular neural prosthetics, were highlighted as a future research area. There are three lines of research that stem from man-machine interactions: (1) the physical interface between the body and the machine (e.g., can tissue engineering or novel biomaterials be used to improve this interface - something like the human cuticle or dental implants?); (2) the extraction and processing of the control signals needed to actuate the devices (e.g., muscle versus nerve signals, implanted versus surface electrodes, fuzzy logic versus muscle synergies); and, (3) adaptations of both the robotic device and the person (e.g., what is the device response? how does the person interact with the machine?). Different people respond differently to the same device, highlighting a behavioral aspect of assistive technologies. This aspect of translation needs more attention because behavioral adoption is a key component. Responses to devices depend, for example, on how people view opportunities, their future, and these devices. In addition to these technical challenges, there is also the hurdle of acceptance by the subjects and rehabilitation culture to adopt technology. To address this concern, the panel identified the need for high functional recovery for device acceptance; a comprehensive support structure for devices should also be part of this deliverable.
The panel discussed the difficulty in conducting clinical trials in rehabilitation medicine and suggested that research into alternative study designs, beyond the randomized controlled trial would be helpful for scientific progress.
Another area for investigation is quantification of the biomechanical factors associated with surgeries, (e.g., tendon transfer and tendon lengthening surgeries in cerebral palsy). Specifically, why do similar surgeries have inconsistent clinical outcomes? This knowledge could guide future surgeries and prevent painful and costly interventions with undesirable outcomes.
The genomics of rehabilitation is a field ripe for exploration. If biomarkers for positive (or negative) responses to specific therapies or drug combinations can be identified, then rehabilitation regiments can be tailored to the individual for greater recovery.
The group highlighted pain (neuropathic and other) as a public health issue to be addressed. Research should address how pain affects participation in studies.
Finally, there is a need to develop means for aerobic exercise in patients with non-responsive autonomic nervous systems. Obesity is a dangerous secondary condition in the disabled population, which may be combated by exercise.
Research on the trajectory of recovery is needed. For example, what happens when issues accumulate for people with long-term disabilities? What factors contribute to an enablement versus a disablement trajectory over time? One scientific opportunity might be the physiological mechanisms that underlie health behaviors.
Disparities are a major public health issue. A smaller proportion of women are admitted for rehabilitation than for men with comparable disabilities or conditions. What are the disparities experienced by people with long-term disabilities? Are they receiving necessary specialized care (e.g., gynecology and other non-rehabilitation services)? People with disabilities experience physical and attitudinal barriers in trying to obtain these services.
The group focused its recommendations on health behavior-change research. Studies should address health behavior changes, the mechanisms underlying these changes, and the factors that influence them. Specifically, many health behavior interventions for the general population are not effective in people with disabilities. Research is needed on the amount of adaptation that people with disabilities need to start exercising, for example, compared to people without disabilities. One scientific opportunity in this area is comparative effectiveness research to determine whether specialized interventions for people with disabilities are more effective than interventions designed for the general population in producing health behavior change. Furthermore, the potential exists for brain reorganization that may affect health behaviors, and these health behaviors could have an impact on societal participation or other broader outcomes. In addition, if people with disabilities do not engage in health behaviors, their risk of secondary conditions (such as obesity or diabetes) increases.
Researchers have been treating people with disabilities as a special group with special outcomes, instead of applying the approaches used in the general population to people with disabilities as well. People with disabilities experience the same public health issues but they often experience these issues differently from the general population. Most of the research on these public health issues excludes people with disabilities, especially people with cognitive disabilities. Therefore, research on obesity, diabetes, and pain in the disabled population is warranted.
Body structure and function factors have traditionally been the focus of research on disabilities. However, environmental factors also influence wellness and heath in this population. The breakout group called for an interactional model that takes into account both kinds of influencing factors in identifying outcomes and developing measurement tools to examine these factors. Interventions could target the environmental factors.
The group identified interactions among genomic, epigenetic, environmental, and behavioral factors on functional outcomes as a key research area. This needs to be considered at two levels: (1) predispositions that might or might not be genetic, and (2) polymorphisms. Perhaps the most important scientific opportunity would be to identify partnerships that exploit the consideration of genetic factors, possibly through joint funding or a mandate in appropriate RFAs to require the encourage the participation of genetic epidemiologists.
A second area of interest is the underlying mechanisms and enhancements of neuroplasticity to improve functional outcomes. In particular, what might be influential modulators and biomarkers? It is clear that experience is necessary to promote plasticity but it appears that the experience must be task specific. The locus and molecular mechanisms underlying reorganization need to be explored. The validity of neuroplasticity principles must be established, especially with respect to learning versus re-learning; differences among motor, sensory, and cognitive plasticity; and declarative versus procedural learning.
An overarching issue is finding ways to maintain the concept of clinical trials but do them in a more efficient way. Many rehabilitative therapies need rigorous testing, such as the 38 multiple sclerosis drugs in the pipeline, but few people and insufficient infrastructure are available to test them. The challenge is finding innovative ways to use technology to promote clinical trials especially with limitations in researchers and time.
A better understanding of the basic science of the genome and epigenetic phenomena would lead to a better understanding of the clinical population and more efficient RCTs. For example, key genomic differences (e.g., polymorphisms) could figure into the entry criteria or serve as covariates for secondary analysis. Stratification by other underlying comorbidities should also be considered in the design of clinical trials.
The group identified the need for parsimonious (simplified) and consensus outcome measures that may be used in combination trials. This will be an important factor in the development integrated treatments across the continuum of care that easily transitions to community-based programs and anticipates the need for sustainability.
One of the major obstacles for patients is fatigue. The field needs a basic understanding of energy production and use and how it relates to disability. A scientific opportunity is to understand the mechanisms of energy production and fatigue in the disabled population and the impact of fatigue on function.
Another research opportunity is to define the role of rehabilitation in predictive health (factors that contribute to the expression of disease). To what extent should rehabilitation interface with initiatives in predictive health, such as preventing strokes? One approach is to examine covariates that contribute to the expression of the disease process and ask what role rehabilitation plays in prevention (i.e., neuroprotection). Understanding how to reap the promise of cellular and molecular strategies to promote neuro-reconstruction should also be considered.
The group also recommended supplements to Clinical and Translational Science Awards (CTSA) to promote the rehabilitative and recovery programs, including training for community-based providers. This could also include direct interactions among researchers and people with disabilities to better understand needs and opportunities.
The Board reconvened to share discussions across the three breakout groups. Several research themes emerged. Namely, there is a need for improved measurements of impairments, activity, function, and participation over time to better understand the progression of disease, secondary conditions, and the role of environmental factors. Further research is needed on caregiver support, home-based strategies, and the effect of stress. In order for these goals to be achieved, a harmonization of the outcome measures reported by researchers will be required, with increased input from people with disabilities and their families. The identification of biomarkers, surrogate measures, and disease phenotypes, especially involving genetic polymorphisms, were other key opportunities identified by the Board. The processes of recovery and plasticity need to be better understood. There is also a need to quantify the compliance and dose-response to therapies and assistive devices. Researchers need to evaluate the theoretical basis and practical effectiveness of the interventions used to improve recovery. Follow-up measures should examine the durability of an outcome and the tipping point of sustainability, as well as the actual impact on participation.
The NCMRR may influence the research field in several ways. With regards to training, the field needs a truly transdisciplinary cadre of researchers. Training models must shift to include integration with allied disciplines and broader research domains. The NCMRR might use the Small Business Innovation Research (SBIR) mechanism more effectively to generate testable hypotheses and determine which devices have the greatest impact. Furthermore, basic science findings should translate into evidence-based interventions. As such, the NCMRR Report to Council should be directed not only to the NIH but also a wider audience.
In an effort to coordinate rehabilitation activities across the NIH and promote cooperative funding across relevant Institutes, the Board would like to address the issue of how ‘credit’ for a grant or supplement is assigned to a particular institute with Dr. Alan Guttmacher, Acting Director of the NICHD. Given the unique, multi-disciplinary nature of rehabilitation, as well as the diverse, understudied, and underserved patient populations, the NICHD should push the current model to encourage more co-funding opportunities. Drs. John Chae, George Kraft, and Lynn Gerber volunteered to write up a detailed recommendation on behalf of the Board.
The discussion of effective means for communicating and disseminating the Council Report was tabled in the interest of time. The Board requested this topic be reserved for the May 2010 meeting.
Drs. Enders and Hogan gave a presentation about the contrasting definitions of rural and how it affects the interpretation of demographic data. Rural is often a residual measure of sites defined as ‘not urban.’ Definitions also vary by country and may be based on population, infrastructure, or economic metrics. In general, sub-state geographic units are required to understand ‘rural’ and this designation is important for funding distribution and identification of health professional shortage areas.
The greatest percentages of disabled workers as defined by social security (SSDI) are located in rural counties in Appalachia and the northeast US. In rural areas, children with disabilities typically live in poverty and come from families with disabilities and low levels of education. In contrast, children with disabilities in cities typically live in poverty and come from single parent families in high crime areas.
Dr. Enders suggested the need for a national program to address the needs of children with disabilities. Resources for children with disabilities have been shifted to the schools, whose funding is linked to local property taxes. Therefore, those schools in impoverished areas lack resources to provide necessary services, and there is a limit to the federal funding for children with disabilities in a community. This creates a negative spiral as the communities with the fewest resources have the largest disability burdens.
Dr. Hogan described his work to correlate childhood disability with socio-economic factors. His regression models suggest that disability in children correlates to poverty, but not to the rural versus urban environment.
Information on disability at a national level had been obtained every ten years through the US Census. However, questions about disability have been removed from the 2010 Census, and instead, the American Community Survey will be used to gather such information. Given the rolling approach to this survey, data will be available in one-, three-, and five-year timetables, depending on the population of the community assessed.Given statistics regarding people with disabilities living in rural areas, researchers are encouraged to include this population when conducting studies.
The Board provided feedback to the NCMRR about meeting logistics. They would appreciate early access to the meeting minutes. They would also like a draft of the NCMRR Council Report to be discussed at the May 2010 meeting. They further suggested that a website would be useful for posting content. At the May meeting, the Board would like to discuss improved methods of dissemination of the Council Report, in particular the executive summary. The Board also reiterated that they preferred face-to-face interaction better than the teleconferenced virtual meeting. The Board also liked the increased proportion of discussion versus formal presentations. They requested that Dr. Nitkin present the NCMRR update early in the meeting and have the NICHD Director’s Report later, preferably on the second day.
At the next meeting, the Board would like a review of the effect of the new scoring system on NCMRR grant applications, in particular with regards to training, RFAs and investigator-initiated applications. They also raised the issue of how NIH peer-review evaluates “significance”. The Board considered a presentation from other institutes that collaborate with the NCMRR to promote rehabilitation research, such as the National Institute on Aging. They would also like a presentation of NCMRR research efforts in a particularly relevant topic, such as TBI, pain, autonomic dysfunction, obesity, or fatigue. The Board also discussed future work with other federal agencies, in particular, CMS.
Meeting was officially adjourned at 12:00 pm.