REPORTS Rehabilitation at the National Institutes of Health: Moving the Field Forward (Executive Summary)

Walter R. Frontera, Jonathan F. Bean, Diane Damiano, Linda Ehrlich-Jones, Melanie Fried-Oken, Alan Jette, Ranu Jung, Rick L. Lieber, James F. Malec, Michael J. Mueller, Kenneth J. Ottenbacher, Keith E. Tansey, Aiko Thompson

Approximately 53 million Americans live with a disability. For decades, the National Institutes of Health (NIH) has been conducting and supporting research to discover new ways to minimize disability and enhance the quality of life of people with disabilities. After the passage of the Americans With Disabilities Act, NIH established the Walter R. Frontera, MD, PhD, Department of Physical Medicine and Rehabilitation, Vanderbilt University Medical Center, Nashville, TN, and National Center for Medical Rehabilitation Research, with the goal of developing and implementing a rehabil- Department of Physical Medicine, Rehabilitation and Sports Medicine, itation research agenda. Currently, 17 institutes and centers at NIH invest more than $500 million per year in University of Puerto Rico School of Medicine, San Juan, PR. Address rehabilitation research. Recently, the director of NIH, Francis Collins, appointed a Blue Ribbon Panel to evaluate correspondence to Walter R. Frontera, MD, PhD, Vanderbilt University the status of rehabilitation research across institutes and centers. As a follow-up to the work of that panel, NIH School of Medicine, Vanderbilt University Medical Center, 2201 Children’s Way, Suite 1318, Nashville, TN 37212; [email protected]. recently organized a conference, “Rehabilitation Research at NIH: Moving the Field Forward.” This report is a summary of the discussions and proposals that will help guide rehabilitation research at NIH in the near future. Jonathan F. Bean, MD, MS, MPH, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, and New Frontera, W. R., Bean, J. F., Damiano, D., Ehrlich-Jones, L., Fried-Oken, M., Jette, A., Jung, R., Lieber, R. L., Malec, J. F., & England GRECC, VA Boston Healthcare System, Boston, MA. Mueller, M. J. (2017). Reports—Rehabilitation research at the National Institutes of Health: Moving the field forward Diane Damiano, PT, PhD, Department of Rehabilitation Medicine, (executive summary). American Journal of Occupational Therapy, 71, 7103320010. https://doi.org/10.5014/ajot.2017.713003 Clinical Center, National Institutes of Health, Bethesda, MD.

Linda Ehrlich-Jones, PhD, RN, Department of Physical Medicine and Rehabilitation, Northwestern Feinberg Medical School and Rehabilitation Institute of Chicago, Chicago, IL. pproximately 53 million Americans live with a disability. For decades, the ANational Institutes of Health (NIH) has been conducting and supporting Melanie Fried-Oken, PhD, CCC/Sp, Departments of , Pediatrics, BME, ENT, Oregon Health and Science University, Portland. research to discover new ways to minimize disability and enhance the quality of

Alan Jette, PT, PhD, Health and Disability Research Institute, School of Public life of people with disabilities. After the passage of the American With Disabilities Health, Boston University, Boston, MA. Act, the NIH established the National Center for Medical Rehabilitation Research

Ranu Jung, PhD, Department of Biomedical Engineering, Florida with the goal of developing and implementing a rehabilitation research agenda. International University, Miami. Currently, a total of 17 institutes and centers at NIH invest more than $500 million Rick L. Lieber, PhD, Department of Physical Medicine and Rehabilitation, per year in rehabilitation research. Recently, the director of NIH, Dr. Francis Northwestern Feinberg Medical School and Rehabilitation Institute of Chicago, Chicago, IL. Collins, appointed a Blue Ribbon Panel to evaluate the status of rehabilitation research across institutes and centers. As a follow-up to the work of that panel, NIH James F. Malec, PhD, ABPP-Cn, Rp, Department of Physical Medicine and Rehabilitation, Indiana University School of Medicine and Rehabilitation recently organized a conference under the title “Rehabilitation Research at NIH: Hospital of Indiana, Indianapolis. Moving the Field Forward.” This report is a summary of the discussions and Michael J. Mueller, PT, PhD, Program in and proposals that will help guide rehabilitation research at NIH in the near future. Department of Radiology, Washington University School of Medicine, St. Louis, MO. The conference took place at the NIH Campus on May 25 and 26, 2016. It was cosponsored by the Eunice Kennedy Shriver National Institute of Child Kenneth J. Ottenbacher, PhD, OTR, Division of Rehabilitation Sciences, School of Health Professions, University of Texas Medical Branch, Galveston. Health and Human Development, the National Institute of Biomedical Imaging

Keith E. Tansey, MD, PhD, Methodist Rehabilitation Center, University of and Bioengineering, the National Institute of Neurological Diseases and Stroke, Mississippi Medical Center, Jackson Veterans Administration Medical Center, the National Institute of Nursing Research, the National Institute on Deafness Jackson, MS. and Other Communication Disorders, the National Center for Complementary Aiko Thompson, PhD, Department of Health Science and Research, and Integrative Health, and the Office of Disease Prevention. The main ob- College of Health Professions, Medical University of South Carolina, Charleston. jectives of the conference were to (1) discuss the current NIH portfolio in

The American Journal of Occupational Therapy 7103320010p1 rehabilitation research, (2) highlight advances in reha- primary and rehabilitative care providers focused on bilitation research supported by NIH, and (3) provide an prevention of mobility decline among older adults. Pre- opportunity for scientists and the general public to com- vention of adverse health outcomes represents a new ment on gaps in knowledge, opportunities for training, and conceptual role for rehabilitative care. Research priorities infrastructure needs. The program included a total of 13 include determining the optimal content and design of expert panels, four remarks by NIH leaders, a consumer preventative rehabilitative care; the potential benefits for keynote, a town hall, a poster session, and the use of social patients, families, and health care organizations; and the media to disseminate information in real time. The fol- cost–benefit of such approaches to care. lowing is a summary of the discussion, and the subheadings (TBI) was used as a case ex- correspond to the titles of the expert panels. ample to discuss the need for further research on ways to integrate pediatric rehabilitation into the broader frame- Rehabilitation Across the Lifespan work of child development. TBI is currently viewed as a discrete event with time-limited consequences while evi- (Moderator: Alan Jette, PhD, Boston University; panelists: dence from the TBI Model Systems suggests lifelong Andrea Cheville, MD, Mayo Clinic; Jonathan Bean, MD, physical and cognitive consequences. Long-term pediatric Boston University; Shari Wade, PhD, Cincinnati Children’s studies are lacking, but existing evidence suggests long-term Hospital Medical Center) effects on educational attainment and vocational and social The theme of this session was moving rehabilitation in- success. However, after the postacute recovery phase, terventions from a traditional “one-and-done” isolated children with TBI receive little ongoing rehabilitation. TBI- model of care to one where rehabilitation interventions are related problems that emerge with shifting developmental integrated into the mainstream of health care. The speakers demands may go unrecognized or be inaccurately charac- addressed integrated care approaches in cancer care, pri- terized. Families and schools constitute powerful contexts mary care, and pediatric rehabilitation. for ongoing rehabilitation and later habilitation. How Barriers to integrating function-directed care into the families function and interact with the child exerts a comprehensive management of progressive diseases, par- powerful influence on the recovery trajectory. Interventions ticularly those with a heavy treatment burden, were iden- need to be developmentally tailored and address the current tified. Cancer was used an exemplar of the simultaneously developmental and neural context. Challenges remain in dynamic and insidious nature of disablement in chronic framing rehabilitation/habilitation as an ongoing process illness. Collaborative care approaches, including telecare, with tune-ups at various developmental stages rather than validatedforpainanddepressionmanagement,were a one-and-done model. A better understanding of adult considered a promising means to proactively and patient- outcome metrics (e.g., education and employment) and centrically address cancer-related disablement. Current long-term burden (disability and life quality) is needed. To research in cancer rehabilitation suggests that challenges reduce heterogeneity and improve prediction, research is revolve around issues such as patient selection and timing, needed to better categorize the initial injury/insult along when and how to intervene, limitations of linear impairment- with better understanding of effects on neurodevelopment to-disability models (with multiple mild impairments and how this relates to long-term functional outcomes. the norm), and competition with disease-modifying ther- Multicenter consortia are urgently needed to support larger apies. Although functional limitations are prevalent (seen scale outcome studies and provide an infrastructure to link in 65% of all cancer patients), rehabilitation intervention school and medical data as well as study interventions and remains underused. In contrast to ischemic and traumatic management practices more efficiently. injuries, rehabilitation interventions in patients with cancer are less prescriptive, more negotiable, and subject to patient Technology in Rehabilitation: From preferences. Current care delivery overwhelmingly emphasizes primary disease management. Cutaneous to Implanted Another presentation focused on limitations with (Moderator: Ranu Jung, PhD, Florida International Uni- mobility tasks, such as walking, rising from a chair, or versity; panelists: Leigh Hochberg, MD, PhD, Harvard climbing stairs, as a signal condition identifying older adult University; Reggie Edgerton, PhD, University of California, primary care patients at an increased risk for disability, Los Angeles; Joseph Rizzo, MD, Harvard University; Mario morbidity, and death. It was discussed how rehabilitative Svirsky, PhD, New York University) care can play a critical role with older adult primary care Innovation and advances in engineering and computing patients by developing integrated care paradigms between are having a ubiquitous impact on health and well-being.

7103320010p2 May/June 2017, Volume 71, Number 3 The purpose of this panel was to discuss the challenges and tandem with technology development would be highly opportunities for developing technologies that interface beneficial. This in itself raises new challenges. with the nervous system at an appropriate level, are user Several of the technological interventions could re- centric and responsive to the ability of the user and their quire extensive development, and the underlying science life span, and could provide new neuroscience insights to of rehabilitation may be insufficient to support the use of inform rehabilitation science. The panel also discussed the these technologies for larger scale human use. It is essential importance of having appropriate assessment methodol- that early development of neurotechnologies, including ogies and comprehensive engagement with regulatory, in- the scientific studies that provide the evidence, are con- dustry, and clinical partners. The moderator and panelists ducted with close consultation of the regulatory bodies, brought to the discussion their experience as neuroscien- such as the Food and Drug Administration. Safety and tists, biomedical engineers, and clinical practitioners, some reliability in small early-feasibility trials need to be con- with personal experience of moving neurotechnology from sidered. In this context, the panel suggested that for se- the laboratory to human studies. Using examples from quential improvements in technology, a modular design engineering of cochlear and visual prosthetic devices and be used. In addition, giving the participant at least some brain, spinal cord, and peripheral nerve interfaces, they control over use of the technology as needed was con- discussed the role of technology in scientific discovery and sidered important. This requires the development of a recovery and restoration of missing or lost function. regulatory acceptance pathway. The overall span of the technology that can influ- There was considerable discussion on the design of ence rehabilitation is broad: from assistive devices, re- study protocols with small numbers of enrolled partici- habilitation robotics, and implanted neuroprostheses to pants. Each participant’s own abilities with turning on or augmented connectivity between people and devices, use shutting off the device could be used as an internal control of virtual reality environments for training, and use of for device evaluation, thereby formalizing and extending mobile health and telehealth platforms for deployment of the value of small studies. The lack of commercial support rehabilitative therapies. The panel discussions focused on for conducting small-sample studies with the associated implanted neuroprostheses. Advances in neurotechnology legal and regulatory requirements indicates that govern- will allow better access to information about the living ment funding support for technology development and system at multiple scales, from cellular to behavioral. Im- early-feasibility trials is paramount for translation of the proved understanding of the endogenous activity patterns neurotechnologies from the laboratory to the clinic. of neural activity could help guide the design of neuro- A key outcome from the panel discussion was that prostheses that can more precisely influence and modify the implanted neurotechnologies offer a “precision medicine” neural activity to initiate and sustain long-term beneficial approach to rehabilitation. They target specific neural neuroplasticity leading to repair or recovery. Design, de- populations. The stimulation paradigms could be com- velopment, and deployment of the neuroprostheses that bined with other treatments, especially cell therapies, to form biohybrid systems with the living body have many maximize function. This ability for precision deployment challenges. could be further tailored to take advantage of the genetic A major challenge in the deployment of neuroprostheses makeup of the recipient to make it a personalized, adaptive that affect recovery is to make the neuroprostheses adaptive approach to rehabilitation. and patient centric. The scheduling (timing) for introducing rehabilitation technology to patients after a traumatic event is very important. In addition, whether all of the capabilities Mechanisms and Markers of Activity for the neurotechnology shouldbeintroducedimmediately and Function or in a controlled sequential manner after deployment has to be considered. For example, after a bilateral sequential Exercise, Plasticity, and Mechanism: How Is Rehabilitation Happening? implantation of cochlear implants, should they be deployed sequentially or together? To restore function after incom- (Moderator: Keith Tansey, MD, PhD, Methodist Rehabilitation plete spinal cord injury (SCI), should epidural stimulation Center; panelists: Rick Lieber, PhD, Rehabilitation Institute of be conducted in parallel with or before treadmill training? Chicago; Stephen Seliger, MD, University of Maryland; James Recovery of function is very patient specific and may Blumenthal, PhD, ) confound assessment of the effectiveness of different neural Rehabilitation interventions are applied to various patient stimulation paradigm interventions. To design appropriate populations with diverse physiological profiles over ex- rehabilitation therapies, conduction of scientific studies in tended periods with relatively little evidence regarding

The American Journal of Occupational Therapy 7103320010p3 how which interventions are doing what in whom. Pa- develop appropriate interventions. We may need to develop tients with neurological problems need to be characterized better assessment tools (imaging for instance) to understand better so that we can identify and analyze responders versus these issues. We may also need to connect previously un- nonresponders. Monitoring tools to ensure that rehabil- connected areas of medicine (chronic disease states and itation interventions are proceeding toward more normal their neurological impact for instance) to make a wider physiology over time are also needed. impact with our interventions. Finally, we should part- Neurological plasticity after injury can be both adaptive ner psychological interventions with rehabilitation in- and maladaptive, and we need to work to gain the former terventions to have a greater impact overall on human while limiting the latter. Similarly, skeletal muscle plas- health. ticity is important in injury and rehabilitation, but classic Access to the Lived Environment measures rarely capture the functionally relevant properties of skeletal muscle. Most plasticity studies focus on muscle (Moderator: Melanie Fried-Oken, PhD, Oregon Health & active properties such as force generation and fatigue and Science University; panelists: Cole Galloway, PhD, Uni- less so on problems involving passive mechanical properties versity of Delaware; Maureen Schmitter-Edgecombe, PhD, due to contracture or fibrosis. New areas of investigation in Washington State University; James Coughlan, PhD, the field include extracellular matrix structure and function Smith–Kettlewell Eye Research Institute) and the development of new imaging methods that would This panel presented and discussed evidence that assistive permit mesoscale quantitative measures of muscle perfor- technologies (ATs) provide functional tools to ensure that mance that are objective and clinically relevant. individuals experience their greatest level of functional Older adults with chronic kidney disease have im- independence in daily life. Based on the International paired neurocognitive function, physical performance, and Classification of Functioning, Disability and Health (ICF ) aerobic capacity. Research has been done on the mecha- of the World Health Organization, AT is a facilitator for nisms associating kidney disease with physical and cognitive activities and participation for individuals who experience impairment. Exercise training improves neurocognitive disability and chronic health conditions. The technolo- function and protects against cognitive decline in chronic gies being developed, discussed, and tested by this panel renal disease patients. are often mainstream technologies available to the general Finally, patients undergoing cardiac rehabilitation public that are adapted to meet functional needs and benefit from stress management. The Enhancing Cardiac provide access to daily environments. Devices such as off- Rehabilitation With Stress Management Training trial the-shelf toy racecars that can provide mobility to chil- shows the beneficial effects of combining stress manage- dren with physical impairments, environmental controls ment training with standard exercise-based cardiac re- with infrared sensors to support or assess older adults habilitation in terms of stress levels, coronary heart disease with dementia who are aging in place, and application biomarkers, and clinical outcomes. These findings should software for touch tablets and mobile phones that guide be disseminated, and cardiac rehabilitation programs in- travelers with visual impairments at traffic intersections cluding stress management should be made more acces- were discussed and demonstrated through multimedia sible to patients with coronary heart disease. presentations. The major issues identified and questions raised in The panel discussed three common themes and a this session for further consideration going forward were number of challenges to the design, testing, and imple- as follows: We have to address diverse populations (phy- mentation of ATs, including the following: siologically) in rehabilitation, even within a given diag- 1. Participatory action research is a critical element of nosis. We also need to address our lack of mechanistic rehabilitation research. Individuals with disabilities understanding of interventions, in preclinical and clini- must be included in all stages of hypothesis testing cal scenarios, which makes predicting responders versus and analysis to ensure content validity. Participatory nonresponders difficult and makes translation from ani- action research is sensitive to group as well as individ- mal model to human problematic as well. The idea of ual differences (e.g., cultural, ethnic, lifestyle diversity) tracking progression during an intervention was intro- and leads to people having increased control over their duced: Are we generating more normal biology/function lives. or developing “work-arounds” in rehabilitation? The ques- 2. The utility of AT for value added to end users and tion was raised as to whether we are measuring the right professionals must become a priority for rehabilitation biological markers in our systems, the ones that are actually science. Utility measures such as task performance critical to the pathophysiology/impaired function, so as to (e.g., efficiency and effectiveness of task completion),

7103320010p4 May/June 2017, Volume 71, Number 3 user satisfaction, and quality of life must become stan- with specialized therapists” with the goal to increase pa- dard. It is challenging to measure value because the tient participation in rehabilitation and social activities. user population is extremely heterogeneous in terms The outcomes of patients receiving physical therapy of needs, abilities, and preferences. Researchers must at home for activity-limiting pain, total hip or knee re- determine whether it is better to assess utility for a placements, and implantable cardiac devices show some narrow population who is most likely to benefit from improvement over time. Family caregivers play a critical AT or for a broad population, where only a subset role in supporting older adults and family members with of individuals is likely to benefit. The variability of user a chronic disease or disability. Intervention strategies that population and task conditions can make it very hard are aimed at supporting family caregivers and reducing and/or costly to get good statistics on utility. Although caregiver burden with an emphasis on technology-based statistical success is easier to obtain under controlled interventions are needed to facilitate improved outcomes laboratory conditions, the laboratory conditions do in people with disabilities. The end goal of incorporating not translate to real-world conditions. Measurement the home, the family, and the community is greater in- of user satisfaction (or dissatisfaction) and quality of dependence and providing opportunities for people with life, constructs that are often used for outcomes, has disabilities to actively contribute to their community. challenges as well. Strategies that help individuals to self-manage their dis- 3. AT must be scaled, in terms of sustainability and ability can lead to achievement or maintenance of positive accessibility, to the population. As technology is rap- outcomes. The challenges experienced by caregivers of idly advancing, we must try to get at the back end of it individuals with disabilities need further attention. even as it gets more complex. For example, as infrared Gaps and opportunities for future research include sensors became wireless, laboratories and smart homes examination of the impact of sociodemographic influ- needed to adjust so that our tools are sustainable. For ences, including geography, socioeconomic status, edu- the biggest impact, one goal in technology research cation, and language/culture, on rehabilitation success. and development must include keeping products In addition, development of self-management strategies and services affordable so they can be accessed by that can be implemented in community settings to help the population who needs them. Likewise, we must individuals better understand and manage their disability increase awareness and benefits of ATs for the general and achieve or maintain positive quality of life and in- public. The AT must meet the environmental and dependence are necessary areas of future research. personal demands of the end users while protecting privacy and maintaining confidentiality and security Understanding the Context: Environmental of personal information. Impacts in Rehabilitation Individuals, Families, and Community (Moderator: Michael Mueller, PhD, Washington University (Moderator: Linda Ehrlich-Jones, PhD, Rehabilitation School of Medicine; panelists: James Burke, MD, University Institute of Chicago; panelists: Christopher Murtaugh, PhD, of Michigan; Amanda Botticello, PhD, MPH, Kessler Visiting Nurse Service of New York; George Alexopoulos, Foundation; Patrick Kitzman, PhD, University of Kentucky) MD, Cornell University; Sara Czaja, PhD, University of The purpose of this session was to consider how envi- Miami Miller School of Medicine) ronmental factors influence outcomes in rehabilitation. Rehabilitation interventions incorporating the home, the The “environment” is an important, modifiable, and family, and the community promote active engagement understudied element in the ICF framework. of patients, family, and community members to achieve An example was provided of patients with diabetes increased quality of life for people with disabilities. Psy- and peripheral neuropathy that illustrated how a con- chosocial interventions aimed at reducing poststroke de- ceptual framework had been used to help direct inter- pression and stress rely on five integrated components: (1) ventions at the environmental level (casting, footwear, offer patients an action-oriented “new perspective” about community screening, and education) to reduce the rate recovery; (2) provide an “adherence enhancement struc- of lower-extremity amputation. Other, more complex ture”; (3) offer a “problem-solving structure” to the pa- models are being developed to illustrate ways in which race tient focusing on problems, valued by the patient, and and socioeconomic factors may interact with contextual pertinent to daily function; (4) help the patient’s family factors such as caregiver support, transportation, neigh- “reengineer its goals, involvement, and plans” to accom- borhood environment, and social network to limit access modate the patient’s disability; and (5) “coordinate care to rehabilitation. Some drivers of racial differences in

The American Journal of Occupational Therapy 7103320010p5 poststroke disability are modifiable, and we should con- Lynn Snyder-Mackler, PT, ScD, University of Delaware; sider stroke survivor– and family-level strategies to reduce Catherine Lang, PhD, Washington University; Susan Horn, disability and decrease disparities. PhD, University of Utah) There are links between community context and long- This symposium examined phases, options, and challenges term outcomes for people with SCI. Community char- in advancing a line of rehabilitation research. Methodol- acteristics such as socioeconomic disadvantage, resource ogies for addressing challenges were explored, as well as for deprivation, segregation, and physical inaccessibility likely incorporating mechanisms, defining dose, and examining threaten the physical, psychological, and social func- the effectiveness of standard rehabilitation procedures. tioning gains achieved during rehabilitation. Neighbor- Traditional phases in a line of research include idea hood socioeconomic factors affect health and well-being generation, natural history and/or animal models, early over and above personal characteristics. For example, human testing for safety and feasibility, efficacy trials, and employment rates for SCI are poor, with rural rates the effectiveness trials. This sequence may be most informative lowest, followed by suburban rates, and urban rates the if viewed as iterative and recursive rather than linear. highest. The best prospects for employment and com- Designs such as the randomized controlled trial (RCT) munity participation are for those people with SCI and offer strong internal validity. However, some aspects of the high socioeconomic status in urban environments. The RCT, for example, participant and researcher blinding and challenge of providing rehabilitation services to people development of a viable control condition, may be difficult with SCI in rural settings was highlighted with a de- to implement in rehabilitation research. Other designs, scription of a specific program targeting rural Kentucky, such as large-scale observational or practice-based evidence a state at the bottom of several U.S. health outcome measures. trials, may offer stronger external validity. Balancing in- The Kentucky Appalachian Rural Rehabilitation Network ternal and external validity is critical to encourage timely is working to overcome these barriers and encourages a translation into practice. Other considerations and chal- bidirectional flow of information, providing clear benefits lenges in advancing rehabilitation research include het- for the community, being accountable, and providing long- erogeneity of participants and interventions (which are term commitment (i.e., sustainability) to the community. typically individualized in practice), fidelity assurance, All presentations and discussion highlighted the fact dosing, consideration of nonspecific factors as moderators that interactions between environment and outcomes are as opposed to confounders of treatment effect, and the highly complex and vary according to location, socio- precision of measurement tools used to assess outcomes economic level, race, age, and disability. Understanding that are not directly observable and must be assessed by these complex relationships will require further refinement observer or participant rating. of conceptual models and a variety of research approaches Investigating the underlying mechanisms of action to understand outcomes and devise policy to enhance in high-quality clinical trials and observational quasi- outcomes. Big data sets are useful, and the net of these data experimental studies within rehabilitation research is achiev- sets needs to be spread even further to capture common ablebutfraughtwithobstaclesthatdonotoccurintypical concerns across wide geographic areas. Consistent with clinical drug trials. Unlike the delivery of an active med- other sessions, there is a need for common outcome mea- ication or placebo, rehabilitation interventions are typically sures but also for qualitative studies to better understand multimodal and involve active participation of both the these themes at an individual level. patient and the clinicians. Thus, ensuring fidelity, that is, Finally, another important theme was the need for defining the intervention(s), ensuring that the intervention(s) ongoing support for people with chronic disabilities. are reliably applied and defining the active component(s), Longitudinal research is needed to determine how dis- is particularly challenging in studies of rehabilitation. Use ability affects people in their environment over time. of fidelity metrics, ideally completed by more than one Intervention should not be “one and done” but should observer, addresses this challenge. In rehabilitation research, dynamically meet the ongoing and changing needs of outcomes are often complex, occur across the ICF domains, people with chronic health problems. and include patient-reported as well as performance-based and instrumented outcomes. Consequently, strategic se- Effective Pathways to Evidence lection and pretrial testing of precision outcome metrics and control conditions are critical. for Rehabilitation It is also critical to consider dosing in rehabilitation (Moderator: James Malec, PhD, Indiana University School trials to not waste resources and to eventually improve of Medicine/Rehabilitation Hospital of Indiana; panelists: outcomes. In rehabilitation, dose is an interaction of multiple

7103320010p6 May/June 2017, Volume 71, Number 3 parameters. Explicit studies of dose–response are necessary immunohistochemistry, it has been demonstrated that to determine essential information about active ingredients, satellite cell number (muscle stem cells) is decreased by their biological targets and mechanisms of action, and their about 70% in contractures. This may cause muscle half-lives. As with other elements of high-quality clinical shortening, deranged extracellular matrix, and increased trials, key dosing parameters are best determined through muscle stiffness. Finally, studies of gene expression from pretrial feasibility study. Methods to determine appropriate these muscles revealed altered transcriptional pathways dose include careful quantification of the active ingredient, relative to other models of decreased use such as immo- multiple assessments over the course of the intervention, bilization, SCI, or spaceflight. Thus, muscle contracture multiple groups receiving different doses, and sophisticated represents a dramatic and unique model that must be statistical modeling of data across time (e.g., hierarchical understood mechanistically to develop novel treatment linear modeling, individual growth curve analysis). approaches. Electronic medical records are collecting detailed Studies at the cellular level may explain why SCI patient, treatment, and outcome data now and will do so rehabilitation can be quite effective in some individuals even more in the future. This information can be used to while others show limited improvement. In rodent models determine those interventions that are associated with of contusion, the timing to deliver task-specific training better outcomes for patients with specified sets of char- and cellular factors that are conducive to motor learning acteristics through practice-based evidence study designs. has been determined. These findings suggest that in- Practice-based evidence is an example of an innovative re- flammation in cord regions remote to the injury is a barrier search methodology that addresses many of the challenges to effective rehabilitation. In fact, animal models show to the traditional RCT posed by rehabilitation research. that training delivered early after SCI during high in- This session identified a number of challenges to flammation worsens function, but reducing this inflam- interventional rehabilitation research, including heterogene- mation allows robust locomotor recovery using a brief ity of participants, individualized and complex treatments, training paradigm. The source and genetic profiles of balancing internal and external validity, implementing viable cellular inflammation have been identified, which may control conditions, difficulty blinding participants and re- allow development of biomarkers for rehabilitation. searchers, nonspecific treatment moderators, fidelity assur- New neuroplasticity protocols are being used in hu- ance, and dosing. A greater emphasis on pretrial studies and mans with SCI, and noninvasive electrophysiology can be alternative designs to the traditional RCT offers opportu- used to guide therapeutic interventions. The corticospinal nities to address many of these challenges. tract is an important target for motor recovery after SCI. Noninvasive techniques have been used to develop tailored Central and Peripheral Mechanisms protocols for precise timing of the arrival of descending of Rehabilitation and peripheral volleys at corticospinal synapses of upper- and lower-limb muscles in humans with chronic partial (Moderator: Rick Lieber, PhD, Rehabilitation Institute of paralysis. Voluntary motor output depends on the efficacy Chicago; panelists: D. Michele Basso, PhD, Ohio State of synapses between corticospinal axons and spinal motor University; Monica Perez, PhD, University of Miami; Mike neurons, which can be modulated by precise timing of Boninger, MD, University of Pittsburgh) central and peripheral neuronal spikes. Thus, noninvasive In this session, the mechanisms of plasticity in rehabili- techniques can be used to develop tailored protocols for tation were discussed. The presenters focused on approaches precise timing of the arrival of descending and peripheral to measuring brain, spinal cord, and skeletal muscle func- volleys at corticospinal–spinal motor neuron synapses tion and discussed how rehabilitation and regenerative involved in intrinsic finger muscle function in humans therapies could be applied to improve central and peripheral with chronic incomplete SCI. function. Using electrophysiological measurements by stimu- Human skeletal muscle adapts to contractures that lating different levels of the corticospinal pathway in in- occur secondary to stroke and (CP). Intra- dividual subjects, accurate estimates of the time of arrival operative structural studies of upper-extremity muscles show of action potentials to the muscle have been measured; that sarcomere length increased while serial sarcomere indeed, latencies of electromyographic responses relied on number decreased dramatically. The extracellular matrix the generation of action potentials in motor neurons. The in contractures was deranged (hypertrophic and altered results indicate that arrival of presynaptic volleys before composition) and apparently does not support a functional motor neuron discharge enhances corticospinal trans- stem cell niche. Using both flow-assisted cell sorting and mission and hand voluntary motor output. In contrast, the

The American Journal of Occupational Therapy 7103320010p7 reverse order of volley arrival and sham stimulation does not ify the cellular environment to create permissive learning decrease voluntary motor output and electrophysiological conditions? outcomes. Overall, these findings demonstrate that spike timing–dependent plasticity of residual corticospinal– Bending the Arc of Technology Toward spinal motor neuron synapses provides a mechanism to Rehabilitation and Health improve motor function after SCI. Modulation of re- sidual corticospinal–spinal motor neuron synapses may (Moderator: Aiko Thompson, PhD, Medical University of present a novel therapeutic target for enhancing voluntary South Carolina; panelists: Steve Cramer, MD, University of motor output in motor disorders affecting the cortico- California, Irvine; James Rimmer, PhD, Lakeshore Foundation; spinal tract. Susan Magasi, PhD, University of Illinois at Chicago) The integration of principles and approaches in re- The purpose of this session was to discuss how the in- habilitation science and regenerative medicine may help us tegration of technology into rehabilitation, health care, develop innovative and effective methods that promote the and wellness services can promote better communication restoration of function through tissue regeneration and between health care professionals and patients and thereby repair. The application of rehabilitation protocols in help patients achieve healthy lifestyles and better quality combination with cellular therapeutics for the treatment of of life. injured or diseased tissue enhances transplantation efficacy The use of information and communication tech- and improves functional outcomes. Although it is clear nologies eliminates distance barriers and can make re- that the convergence of rehabilitation approaches with habilitation and health care services available to people regenerative medicine strategies will accelerate the science who have limited access to transportation and other access underlying tissue restoration after injury and disease, col- issues. In recent years, digital health (e.g., telehealth, laborative research efforts across the fields of regenerative telerehabilitation [telerehab], eHealth [health care services medicine and rehabilitation are greatly lacking. An NIH delivered or enhanced through the Internet], and mHealth RePORTER search of active funding using the Boolean [delivery of health care services via mobile communication terms “regenerative medicine” yielded over 2,231 studies. devices]) is becoming a significant part of health care and When we modified this search to include only “physical the health care economy. Digital health funding has been medicine and rehabilitation” and “other health profes- steadily increasing. Tools for developing and imple- sions,” which include physical therapy, occupational ther- menting mobile health care services and research appli- apy, and speech–language pathology departments, a total of cations are becoming more and more available. It is clear only 16 grants was displayed. This is remarkable consider- that the use of information and communication tech- ing that the promotion of tissue healing and regeneration is nology can broaden rehabilitation and health care research a primary goal of many rehabilitation interventions. There opportunities for researchers and service opportunities is, therefore, a great need to expand scientific knowledge, for patients. In this session, the speakers provided three expertise, and methodologies across the domains of re- levels of remote rehabilitation training management: habilitation science and regenerative medicine, with the full management (by health care professions), middle-level ultimate goal of improving the lives of individuals with management, and self-management (by patients). These disabilities. different levels are not mutually exclusive but are har- Gaps in the understanding of mechanisms underlying monious approaches that allow the patient to transition rehabilitation include the following questions: What has from one level of management to another, based on his/her the greatest impact on skeletal muscle strength, the ner- progress in recovery and changes in needs for care and vous system or the biomechanical manipulation of muscle? services. Which stem cell populations can rehabilitation profes- Many patients do not receive enough dose of rehabili- sionals realistically manipulate? How can exercise influence tation therapy after stroke. Telerehab is ideally suited to the stem cell population? How do bioscaffolds interact with maximize the gains from therapy; for instance, telerehab can stem cells? Because the timing of SCI treatment is an increase the duration and intensity of therapy and therefore important factor in good outcomes, how will we be able to contribute to greater functional gains. Pilot studies and clinical translate animal studies into human treatments? What are trials are ongoing (Cramer) on a home-based telerehab the most appropriate strategies for applying regenerative system for patients with stroke. Telerehab also offers the medicine to rehabilitation? Does the cellular state of the option for a holistic approach to patient care, for example, central nervous system dictate the response to rehabili- incorporating education, sensor data collection, and regular tation treatment, or can the right type of exercise mod- structured interactions with therapists.

7103320010p8 May/June 2017, Volume 71, Number 3 Other technologies such as eHealth and mHealth secondary health conditions and provide them with ef- can contribute to health promotion emphasizing self-care fective dose of interventions has yet to be realized. rather than expert care. In furthering the view that digital health technologies can help to overcome existing health Transitions Across the Lifespan care problems (e.g., lack of integration and coordination across different disciplines and accessibility barriers), it was (Moderator: Walter Frontera, MD, PhD, Vanderbilt Uni- suggested that telerehab may prevent well-known post- versity; panelists: Sharon Ramey, PhD, Virginia Polytechnic rehabilitation health decline as the patient transitions Institute and State University; Ellen Giarelli, EdD, RN, MS, from dependence to independence. Preliminary findings CRNP, Drexel University; Eric Lenze, MD, Washington of the ongoing project (Rimmer), “TExT-ME: Telehealth University) Exercise Training for Monitoring and Evaluation of Home- The purpose of this session was to examine current evi- Based Exercise,” show that home-based tele-exercise inter- dence and discuss future research needs in the area of ventions can achieve better participant adherence than rehabilitation across the lifespan with a particular empha- conventional onsite exercise programs, leading to better sis on transitions. Disability has an effect on growth and health benefits. Participants of this tele-exercise program development, transition to adulthood, and aging (particu- reported that the convenience and online interaction with larly disabling medical conditions). At the same time, these a telecoach enhanced their motivation to attend the sessions. processes can influence how individuals adapt to the pres- This telecoaching (i.e., midmanagement) model may ence of disability and the nature of their health care needs. become a precursor to self-management and mHealth for The first presentation focused on the need to increase optimizing recovery in people with neuromuscular the number of implementation science trials to identify disability. approaches and strategies that work best with a high degree On the other hand, the expansion of smartphone use of certainty. Examples of areas in need of this approach and app design is literally placing sophisticated rehabili- include studies on cost–benefit ratio and health dispar- tation interventions in the hands of people with disabil- ities. Rapid high-fidelity science is needed to put research ities. Potential of mRehab applications include symptom into practice more quickly. In a real-world setting, it is monitoring, real-time data capture, real-time access to important to know whether the clinician is familiar with information about navigating the community, social con- the latest evidence and the best way to effectively deliver nectedness through peer-to-peer support, and bidirectional care with high efficiency and consistency. We need to communication. However, there exist barriers to use of understand the barriers and obstacles that prevent research mHealth, such as limited scientific evidence; lack of inte- results from being implemented. In other words, why does gration of multiple perspectives and disciplines into it take so much time and energy to change practice? workflow; concerns over data confidentiality, privacy, and Health care, and specifically rehabilitation for patients security; and lack of provisions for reimbursement. Of with chronic syndromes diagnosed in childhood, in- particular concern for the disability community is how cluding those associated with genetic variants, is best factors at the human–technology interface can impose accomplished when it is begun early in life, as soon as a barriers to use. Accessibility and usability of mRehab in- diagnosis is pending, conceptualized as requiring the in- terventions are essential factors that must be considered tegration of skills, knowledge, and clear intentions of a throughout app development. An iterative interdisciplinary diverse team composed of the patient, health care pro- design process that brings together content, accessibility, viders, family members, and other advocates. Tran- and information technology experts with people with sitioning of any kind can be complicated and is always disabilities can help ensure that the needs and priorities highly personal. Furthermore, lifelong management is of the disability community are met. complex, requires more health care, and is associated with Many patients after acquiring a disability are unable higher costs. Therefore, we must use models that capture to receive the optimal amount of rehabilitation and health sociocultural, environmental, and health variables and care services because of a number of challenging barriers. barriers to identify paths to or loci of success. A fundamental With continuing growth in the use of the Internet and goal is promoting the patient’s skill at self-surveillance and smartphones, the development of digital health applications self-management, including rehabilitation. There are no can significantly broaden rehabilitation and health care tricks, no magic, or failsafe; it is hard work that must be opportunities for patients. The full potential of digital health individualized and supported. technologies to reach a large number of people with dis- Aging is associated with significant emotional, cog- abilities who exhibit a range of physical and psychosocial nitive, and motivational impairments that interfere with

The American Journal of Occupational Therapy 7103320010p9 successful rehabilitation interventions. Clinical strategies oping patient-reported outcomes that can evaluate health that focus on patient engagement and therapy intensity outcomes across different patient populations. Efforts can help with behavioral changes that are needed for using these same methods to develop an item bank specific successful rehabilitation. A model of enhanced medical to measuring prosthetic mobility in people with lower- rehabilitation therapy was presented by Dr. Lenze. This limb loss were described. model includes a package of motivational and high- The discussion following the presentations identified a intensity therapy steps that physical and occupational number of issues and challenges. These included a number therapists can take to maximize both patient engagement of general issues such as and therapy intensity. Effort and progress are reinforced • The importance of developing a consolidated infra- during therapy with direct feedback to the patient, and structure, be that through industry partnerships or therapy is linked to goals set by the patient. Older adults academic hubs; receiving therapy from enhanced medical rehabilitation– • Using that infrastructure to develop systems that in- trained therapists had greater engagement in therapy tegrate mHealth, wearables, and patient-reported out- sessions, higher patient active time, and better functional comes in efficient ways so that they complement each recovery compared with patients receiving typical standard- other to optimize assessment and monitoring; of-care therapy. • Developing strategies to incorporate these integrated data elements into measurement systems with which Novel Outcomes in Rehabilitation and patients and clinicians can optimally engage and in- Integration Into Clinical Care teract; and • Integration of the resulting data into the electronic (Moderator: Jonathan Bean, MD, Harvard Medical School; medical record. panelists: Brad Dicianno, MD, University of Pittsburgh; Specific needs that were discussed also included Melissa Morrow, PhD, Mayo Clinic; Brian Hafner, PhD, • Developing standards or best practices for wearable University of Washington) sensor technology akin to what the Patient-Reported The purpose of this session was to examine the clinical and Outcomes Measurement Information System had done scientific relevance of developing novel outcomes in re- for patient-reported outcomes; habilitation and their potential to favorably impact the • Developing strategies for extracting the most impor- changing health care environment. Health care reform tant data from wearable sensors and presenting them and the shifting emphasis on managing health have been in a way that is appropriate for the given stakeholder coupled with exceptional growth and development in (patients, practitioners, payers); and the application of technology and engineering to health • Using these approaches for more optimal management measurement. As the mobile health field and technologies of self-care and thus relieving clinicians of the burden evolve, researchers will continuously be presented with created by interpreting and processing high volumes of challenges in the conceptual design and deployment of data. clinical trials as well as the conduct of clinical care owing to Last, integrated leadership in addressing these concerns the vast array of outcomes measures that can be collected. was viewed as a priority for NIH, especially in cooper- The Interactive Mobile Health and Rehabilitation ation with other relevant agencies such as the Patient- (iMHere) system is an example of a mobile health system Centered Outcomes Research Institute, the Agency for being used to collect ecological momentary assessment Healthcare Research and Quality, and the Veterans outcomes data among patients with spina bifida (Diciano). Health Administration. Furthermore, wearable sensors monitoring different as- pects of health are becoming more widely used in re- Using Data to Drive Discovery habilitation research as a method of capturing real-world outcomes. For example, sensor-based outcomes are being (Moderator: Ken Ottenbacher, PhD, University of Texas used (Morrow) in SCI rehabilitation research, although Medical Branch; panelists: Adrian Hernandez, MD, Duke there are challenges to the integration of big data into University; James Graham, PhD, University of Texas clinical practice. New approaches to outcomes measure- Medical Branch; Jennifer Hicks, PhD, Stanford University) ment have also been applied to the development of The purpose of this session was to examine the use of data patient-reported outcomes. National initiatives, like the as a means to drive discovery. Using data to drive discovery Patient-Reported Outcomes Measurement Information has been a hallmark of scientific investigation since the System, have resulted in rigorous frameworks for devel- 1600s, beginning with the writings of Sir Francis Bacon

7103320010p10 May/June 2017, Volume 71, Number 3 regarding the modern scientific method. How data have tential to advance rehabilitation science and patient care. been defined and used to generate new knowledge has This session provided an introduction to the emerging evolved dramatically since then. The pace has been par- discipline of data science and its application and impli- ticularly rapid during the past decade. This revolution is cations for rehabilitation research. A better understanding being driven by several factors, including (1) advances in of data science will help rehabilitation clinicians, ad- information technology, (2) the development of sophis- ministrators, and investigators accomplish the confer- ticated data analytics, and (3) the increased availability and ence’s goal of “moving the field forward.” complexity of data. These factors provide opportunities for data integration, exploration, and secondary analysis that Preventing Secondary Disability did not exist even a few years ago. The NIH “Big Data” program, referred to as BD2K (Big Data to Knowledge) (Moderator: Diane Damiano, PhD, PT, NIH Clinical and launched in 2012, is a reflection of the data revolution Center; panelists: Greg Hicks, PhD, University of Delaware; and its impact on biomedical and health care sciences. For Diann Gaalema, PhD, University of Vermont; Sara Mulroy, the fields of rehabilitation medicine and disability sciences PhD, Rancho Los Amigos National Rehabilitation Center) to fully participate in the research opportunities associated This session focused on major issues in prevention of with using data to drive discovery, there is a need to raise secondary disability across four distinct populations. awareness and build research capacity. children with CP, older adults with low back pain, adults Significant opportunities exist for data exploration with SCI, and adults recommended for cardiac rehabili- and analyses in existing administrative and federal data tation programs. Even with this diversity, many similarities sets, including resources supported by the NIH specifically were seen across the presentations. designed for rehabilitation investigators, for example, The scientific basis across populations for addressing Center for Large Data Research and Data Sharing in secondary impairments focuses on the identification of Rehabilitation. In addition, the Mobilize Center, an NIH modifiable factors that, if addressed, would improve BD2K Center of Excellence, is using modern data science outcomes in terms of health and functioning for these tools to integrate and analyze information from wearable individuals. For children with CP, the focus is on physical sensors, research laboratories, and clinics to understand activity throughout the lifespan to preserve and maintain and improve human mobility—for example, to improve optimal muscle and brain functioning. A particular em- treatment of patients with CP. The NIH-funded Na- phasis is the need to intervene very early in life to limit the tional Center for Simulation in Rehabilitation Research development of secondary changes due to the inactivity provides the worldwide rehabilitation research community imposed by the brain lesion. with a common platform for sharing data and models that For older adults with low back pain, trunk muscle describe movement. integrity has been identified as a key modifiable factor in Additional opportunities for discovery exist using large this population that can reduce pain. Interestingly, pain was administrative or public use databases such as Medicare previously thought to be an almost inevitable part of normal claims and assessment files and U.S. Census data (including aging, so much so that older adults were typically excluded data related to the Patient Protection and Affordable Care from studies on low back pain. The patients at highest risk Act and health care reform). There are rapidly emerging for poor outcomes after cardiac surgery are often those opportunities for information sharing and secondary who are least likely to attend rehabilitation programs, which analyses of data from completed studies associated with have been shown to be efficacious in improving outcomes. recent federal data sharing and archiving mandates. The use It is important to identify why these individuals choose not of electronic health records and the creation of large data to attend with the goal of devising strategies to improve networks and a health system collaboratory represent yet their participation. Compliance with rehabilitation or with another opportunity to use clinical data with an emphasis long-term behavioral health changes was a theme that on patient-reported and patient-centered outcomes. Ex- resonated across speakers and with the audience. Efforts amples included the NIH Collaboratory, the National to incentivize patients to participate, while expensive, may Heart, Lung, and Blood Institute’s Heart Failure Clinical reduce health care costs tremendously if successful. Research Network; and PCORnet, the National Patient- Another patient population with secondary disability Centered Clinical Research Network, which includes data is that of people with SCIs with shoulder injuries. Using from more than 100 million people. sophisticated biomechanical analyses, movement patterns Using data to drive discovery is an important and that markedly diminished shoulder pain have been iden- rapidly expanding area of research with enormous po- tified, again showing that research is needed on modifiable

The American Journal of Occupational Therapy 7103320010p11 factors that enable people to remain or increase their ability Through feedback received through the request for to be mobile, whether it is in a wheelchair or walking in the public input, the Medical Rehabilitation Research Co- community. It was emphasized that patients should have ordinating Committee modified the plan to include the greater involvement in our research so we can learn their development of new methods to foster interdisciplinary concerns and challenges and their individual factors that research, placing greater emphasis on health disparities make them more likely to have adverse health outcomes. In and broadening the avenues for development of new some instances, it can be socioeconomic status; in Southern technologies. As a result of the comments, the Medical California, living in a violent neighborhood markedly in- Rehabilitation Research Coordinating committee added creased the chances of having an SCI, [a correlation that] two priority areas and revised and refined other priority presents unique and specific public health challenges in areas. The final plan includes six priority areas: (1) re- addition to the scientific challenges. habilitation across the lifespan, (2) family and community, Future recommendations for research are to better (3) technology use and development, (4) translational engage patients and their needs in research efforts and to science, (5) research design and methodology, and (6) be more open to alternative methodologies besides RCTs research capacity and infrastructure. The plan was to find cost-effective methods to help people maintain intended to be final in June, and a town hall meeting at their health across the lifespan. From a more translational the conference provided the final opportunity for feedback science perspective, we need to know more about mech- to the Medical Rehabilitation Research Coordinating anisms leading to pain across disorders and continue to committee before the plan was published. s explore biomechanical and motor learning/training strat- egies to improve functionality and reduce pain rather than Acknowledgments masking the chronic pain with medication. For children with CP, effective early intervention strategies need more Six Institutes at the National Institutes of Health (NIH) investigation, while the intersection of aging with dis- cosponsored this conference, including the Eunice ability is also a major gap in the literature. Kennedy Shriver National Institute of Child Health and Finally, secondary disability is hardly secondary in cost, Human Development, the National Institute of Nursing duration, and importance to patients. However, because it Research, the National Institute of Biomedical Imaging occurs as a result of a primary injury, these could theo- and Bioengineering, the National Center for Comple- retically all be avoidable, or at least modifiable, and this is mentary and Integrative Health, the National Institute on where rehabilitation research is needed. Deafness and Other Communication Disorders, and the Office of Disease Prevention. Development of an NIH Rehabilitation Financial disclosure statements have been obtained, Research Plan and no conflicts of interest have been reported by the authors or by any individuals in control of the content of (Presenters: Alison Cernich and Lyn Jakeman) this article. This session covered the development of the new NIH Re- This article is being published almost simultaneously habilitation Research Plan. The intent of the plan is to detail in the following six journals: American Journal of Occu- research priorities that are of interest to a large group of the pational Therapy, American Journal of Physical Medicine and institutes and centers in the NIH that invest in rehabilitation Rehabilitation, Archives of Physical Medicine and Rehabili- research. A trans-NIH Medical Rehabilitation Research Co- tation, Neurorehabilitation and Neural Repair, Physical ordinating Committee began development of the plan in Therapy, and Rehabilitation Psychology. 2015. They developed the priorities in the plan in consultation with the National Advisory Board on Medical Rehabilitation Copyright © 2017 by The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Research and the directors of the NIH institutes and centers. Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. NIH published a draft of the plan asking for public comment The work cannot be changed in any way or used commercially without permis- in November of 2015 and revised the plan based on that input. sion from the journal.

7103320010p12 May/June 2017, Volume 71, Number 3