Dr. Thomas Strax, Board Chair, called the 27th meeting of the National Advisory Board on Medical Rehabilitation Research to order at 8:40 a.m. Current Board members and visitors introduced themselves. Minutes of the previous meeting were approved.
Dr. Strax highlighted the summit on Access to Assistive Technologies, which was sponsored by the Foundation for Physical Medicine and Rehabilitation and the American Academy of Physical Medicine and Rehabilitation November 20, 2002. The final report can be accessed at http://www.foundationforpmr.org/NEW/programs.html.
December 8-9, 2003May 6-7, 2004December 2-3, 2004
Dr. Michael Weinrich indicated that the National Institutes of Health (NIH) has received its appropriation, which included a generous increase. However, in future years the increases may be somewhat smaller. If so, the NIH would have to constrain new initiatives in order to maintain a reasonable payline for investigator-initiated proposals. Dr. Weinrich highlighted an upcoming conference on Physical Disabilities through the Lifespan, which will take place on the NIH campus July 21-22, 2003. This is a broad federal collaboration, lead by the NCMRR, to identify gaps in scientific knowledge about the special problems of aging for individuals with disabilities and to inform public policy on issues related to aging and disability. For further information go to: http://physicaldisabilities.iqsolutions.com/.
He added that the NCMRR is building a clinical trials network for the study of traumatic brain injury. Dr. Beth Ansel had solicited successful applications from eight clinical sites and one data-coordinating center. She is working with the steering committee to develop standards for recruitment, treatment, outcomes, and data structure and analysis. The network will soon be considering specific clinical research proposals.
The NCMRR recently added a new program person, Dr. Nancy Shinowara. She has extensive experience in the review of small business engineering grants, and will take on a program of Spinal Cord and Musculoskeletal Disorders and Assistive Devices. The titles of other NCMRR programs will be adjusted accordingly.
The NCMRR has several research initiatives that are in various stages of review or funding. Pharmacological Approaches to Enhance Neuromodulation in Rehabilitation got a significant response, and the NCMRR is working with the National Institute of Neurological Disorders and Stroke (NINDS) to fund several interesting studies that use drugs to enhance rehabilitative approaches. A solicitation on the Molecular and Cellular Basis of Contractures for Design of Therapeutic Interventions had a more limited response, but the NCMRR will fund three interesting applications and will continue to promote research to treat this disabling condition in muscles and joints. The new Pediatric Critical Care and Rehabilitation Program launched two successful initiatives to support research on respiratory function in children: Pilot Clinical Trials in the Epidemiology, Prevention and Treatment of Respiratory Failure in Children and Clinical Trial Planning Grants to Guide and Improve Timing, Intensity, Duration and Outcomes of Pediatric Critical Care and Rehabilitation Therapeutic Interventions in Childhood Cardiopulmonary Arrest; both initiatives resulted in the funding of several clinical research proposals. The NCMRR has an upcoming initiative on the Biomechanical Modeling of Movement. Overall, the NCMRR will continue to work with the clinical and basic research community to increase the number of applications in medical rehabilitation. Dr. Weinrich reminded the Advisory Board that about 80% of NIH funds go to investigator-initiated proposals rather than those developed in response to specific research initiatives.
Because of its broad expertise, the Advisory Board is sometimes called on to provide an additional level of review for certain NCMRR research initiatives. With several initiatives already underway, the NCMRR had only a single initiative to discuss at this meeting. Brief background material was distributed to Board members prior to the meeting. As head of the NICHD Division of Scientific Review, Dr. Robert Stretch presided over this process.
Dr. Weinrich presented a Request for Applications (RFA) to solicit collaborative and multidisciplinary research to examine the relationship between disability and family welfare. This initiative would promote a comprehensive and responsive analysis of current data sets to support the efforts of public policy makers who are trying to support the needs of individuals and families coping with disability. Currently disability and family welfare data are filled with gaps and inconsistent analytical standards. Within the research community, studies of disability and family welfare cross a large number of disciplines so diverse in their research approaches and needs that communication and collaborations across fields are difficult and translation into policy is nearly impossible. The Advisory Board was supportive, but felt that the initiative should not be limited to just secondary analysis of current data sets; it should support the development of new data sets as well. The initiative will also have relevance to development of healthcare policy at the state level and the work of healthcare providers.
Dr. Yvonne Maddox, Deputy Director of the NICHD, substituted for Dr. Duane Alexander who was away on travel. As former acting director of the NCMRR, Dr. Maddox has been pleased to see NCMRR support grow from about $37 million in fiscal year 2000 to about $62 million in the current fiscal year.
The current NIH budget for fiscal year (FY) 2003 is $27 billion, an increase of 15.7% over the FY2002 level, although some of these new funds are targeted to biodefense and terrorism research. FY2003 represents the final year of the five-year commitment to double the NIH budget. However, during this time the NICHD never quite got the same level of increases as the rest of the NIH. In FY2003, the NICHD will get $1.2 billion, an increase of 8.6% over FY2002 levels. The new NIH Director, Dr. Elias Zerhouni has had several meetings with the extramural community and advocacy groups. He is particularly interested in translating research results into community practice.
Dr. Maddox provided some background on the ambitious National Children's Study, which aims to determine the fetal antecedents of adult disease. The focus of this study will be a national cohort of 100,000 babies (and their families), studied over the 21 years of adolescence. The study will examine biomedical, environmental and psychosocial factors that contribute to birth defects, injury, and disease. Prior to the recruitment of this prospective cohort, study planners will develop methodology from across several research disciplines and consider appropriate outcome measures. Congress mandated this study and designated the NICHD as the lead agency, but has yet to provide specific funding. The NICHD will contribute about $6.5 million in the current year, but is seeking additional support from the National Institute for Environmental Health and Safety, Department of Education, Centers for Disease Control and Prevention, the Administration for Children, Youth, and Families, and other federal and private agencies in order to meet the projected costs of about $26 million in 2004 and $800 million in 2005.
Dr. Maddox discussed the new NIH roadmap developed by Dr. Zerhouni, which includes specific working groups in the following areas: building blocks for biology, biological pathways and networks, regenerative medicine, structural biology, bioinformatics and computational biology, molecular libraries, nanotechnology, molecular imaging, multidisciplinary research teams, public-private partnerships, high-risk research, translational research, integrated clinical research networks, and clinical research workforce training. Initiatives in health services research and partnerships with the pharmaceutical industry will have special relevance for the NCMRR. According to Dr. Zerhouni, the NIH will renew its focus on health and well-being, rather than being thought of as the "National Institutes of Diseases". Another priority will be continued support for clinicians who are considering careers in research.
To orient the Advisory Board on the new NCMRR program in pediatric critical care and its connection to broader rehabilitation issues, Drs. Murray Pollack and Patrick Kochanek made a presentation about this clinical specialty and the children that it serves.
Dr. Pollack indicated that pediatric critical care is a relatively new field. The first intensive care units (ICUs) appeared in the 1950s, but pediatric-specific units (i.e., PICUs) did not appear until 1967. Although pediatric critical care initially competed with the more mature fields of pediatrics and neonatology, it is now a well-integrated specialty with an increasing scope of care and corresponding scientific base. In 2001, there were 413 PICUs with strong representation in community hospital settings. In the mid 1980s when pediatric critical care initially arose as a separate medical specialty, the mortality rate in childhood critical illnesses was 30-40%; currently mortality rates in PICUs are down to about 3-6%. There are significant links between pediatric critical care and rehabilitation, because children generally enter PICUs with moderate to severe disability or with traumatic conditions that result in significant disability.
Pediatric critical care is a multidisciplinary field with an increasing academic focus. Currently about 994 doctors are board certified in pediatric critical care medicine, with another few hundred contributing to pediatric care from allied fields. About 75% of these intensivists are involved in academic medicine. The field is heavily influenced by adult medicine, but it is distinct from neonatology. Although it is becoming increasingly popular in pediatric departments, the specialty of critical care is more focused on child physiology and multi-system integration than on development and cognitive issues.
Dr. Patrick Kochanek discussed some of the disease processes associated with pediatric critical care and their potential link to rehabilitative issues. Critically ill children (e.g., brain injured, cardiopulmonary arrest, septic shock) often require extensive medical care and long-term follow-up. In addition, a high percentage of children treated in PICUs are those with developmental disabilities. Within clinical departments, there are increasing alliances between pediatric critical care and physical medicine and rehabilitation (PM&R) specialists.
Pediatric traumatic brain injury (TBI) occurs once every 15 seconds, with about 10-15% classified as severe resulting in one death every 12 minutes. Brain-injured children in the 5 to 15 year-old range tend to do better than adults, but those younger than 5 years old do worse. Moreover, about 20% of the cases of child abuse are associated with inflicted neurotrauma. The NIH has tried to develop guidelines for the management of severe TBI in infants and children, but there are remarkably few trials or targeted therapies, and it is difficult to assess outcome in pediatric cases. One strategy involves the analysis cerebral spinal fluid to identify molecular and biochemical markers of brain injury that are predictive of outcome. A possible treatment strategy for TBI involves hypothermia, which is thought to block secondary degenerative processes and decreases lipid peroxidation, although it is unclear what effect it has on inflammation.
Cardiac arrest is another major condition treated in pediatric critical care units, and a cause of major morbidity and mortality in children. Survival rates are only about 16%, and the overwhelming majority of survivors have poor neurologic outcomes and permanent disability. Cardiac arrest has a much worse outcome in children than in adults, because in children it usually results as a secondary complication of respiratory failure, so by the time the heart stops significant anoxic insult has already occurred. Clinical trials in adults suggest that hypothermia may provide some therapeutic benefit, but this has not been adequately tested in children.
Septic shock occurs in about 43,000 children per year, with a 10% mortality rate. Possible treatments involve administration of alpha-thrombotic agents (e.g., activated Protein C) and aggressive plasma exchange. However, in surviving children, reduced flow states may result in amputations and other secondary complications. Ultimately, more clinical and basic research is needed to look at the long-term impact of PICU treatments and their connection to morbidity and disability in childhood.
To continue a discussion from the previous Advisory Board meeting, the NCMRR invited the directors of the four regional research networks to make brief presentations on their respective programs and offer insights into research support and the development of infrastructure. The regional research networks were originally developed in response to an Advisory Board initiative to build research infrastructure in medical rehabilitation. In 2000, the NICHD committed almost $4 million per year to support four, geographically distinct networks to enhance research capacity through scientific cores, information technology, and networking activities. Soon the NICHD must consider whether this program should be renewed and in what format.
Dr. Marjorie Anderson presented on the western network, RehabNet-West; for more information go to http://rehabnetwest.washington.edu. Major activities of this network include consulting (especially in statistics), workshops, communication, and pilot research projects, which has resulted in several research applications from the western region that were submitted to the NIH and other funding agencies. Dr. Anderson also alluded to some of the scientific and administrative challenges of running a research network. Support activities do not lead to academic advancement for those running the network cores, and the grant has only limited benefit to the home institutions. The large geographic focus limits the amount of direct interactions with the research cores. Supporting subcontracts to fund activities and pilot projects at other institutions is an administrative headache. Dr. Anderson suggested that in the future, research networks should concentrate their scientific strengths without the overt burden of broad geographic representation. She added that the NCMRR could provide more flexibility with administrative procedures (e.g., subcontracts). She also recommended support of mini-sabbaticals and protected time, especially for clinical researchers.
Dr. James Blackman presented on the southern network, Enhancing Rehabilitation Research in the South (ERRIS), detailed at http://erris.med.virginia.edu. ERRIS has focused on improving the quantity and quality of new proposals from the southern region, with specific expertise on the quantification of disablement and neuropsychology. One approach is to bring in successful researchers from other fields to mentor prospective rehabilitation researchers, and to promote interactions through the use of Web site clearinghouses and videoconferencing. In addition, ERRIS supported an intensive weeklong workshop on grantsmanship, which will be repeated again in early 2004. The network has had significant impact on participating investigators as well as on their home institutions.
Dr. William Zev Rymer discussed the midwestern regional network, Center for the Advancement of Research in Neurorehabilitation (CARN), which is further described at http://marvin.smpp.nwu.edu. In addition to increasing research capacity throughout the midwestern region, CARN provides particular expertise in neurorehabilitation and engineering. It also supports small development and feasibility grants to nurture young investigators. New projects are chosen through a competitive peer-review process that provides direct feedback to prospective researchers. CARN has also been able to take advantage of NICHD initiatives in health disparities to support additional rehabilitation projects. Dr. Rymer agreed that research networks should be primarily theme-based rather than regionally focused. While activities related to grantsmanship and training are helpful, perhaps they could be nationally coordinated across all the NCMRR networks. He agreed with Dr. Anderson that the administration of subcontracts to support pilot projects and research collaborations is a pain, but probably not avoidable.
Dr. John Whyte discussed the Northeast Cognitive Rehabilitation Research Network (NCRRN), which is described at http://www.ncrrn.org . NCRRN took a more thematic focus, building on their particular strengths in brain injury, cognitive rehabilitation, and brain imaging. The network sought to develop promising technologies and export them regionally to potential clinical researchers. It also built up a brain injury patient database that currently serves 15 research projects, and supported the use of functional magnetic resonance imaging (fMRI) to clarify mechanisms of impairment and treatment response. Last spring, the network convened a small workshop to explore methodological issues in cognitive rehabilitation and published the findings on the Web. The network is interested in promoting junior investigators and building a comprehensive program of effectiveness trials. Dr. Whyte agreed that the NCMRR networks should have thematic rather than geographic responsibilities, with some flexibility for each network to develop their particular theme. He supported the emphasis on capacity building, along with the integration of established investigators from allied fields.
The Advisory Board was greatly impressed with the progress of the regional research networks in the first three years of operation. The networks provided major resources for rehabilitation scientists and for NICHD research in general. The Advisory Board generally agreed on the need to shift from regionally based to thematically based centers, but with a focus on conceptual domains rather than specific patient diagnoses or disabling conditions. To establish these themes, the NCMRR should convene expert panels to discuss research needs and opportunities throughout medical rehabilitation. The Advisory Board discussed the relative merits of capacity building, career development, and support of patient registries. However, they cautioned the NCMRR not to stack the resources in favor of established lines of investigation at the expense of supporting emerging opportunities and new investigators coming to rehabilitation from other fields. The Board recommended that the NCMRR continue to support long-distance mentoring and collaborative efforts to promote research activities beyond the traditional rehabilitation centers. The Board added that the NCMRR should leverage NIH funding to draw out institutional and other local support and resources. Within the field of medical rehabilitation, there is a still a need for capacity building and integration. There is a lack of real research experience at the senior level and several rehabilitation departments function in relative isolation.
Before retiring from the Advisory Board, Dr. Marjorie Anderson was asked to share some of her neuroscience knowledge in the form of a brief review of her research activities at the University of Washington. For several years, she has been interested in how the brain controls movement, particular in the context of disorders such as Parkinson disease. She has collaborated on a series of studies to eavesdrop on neural activity in the brain by implanting electrodes just prior to brain surgery in humans or in related studies in animal models. Neuroanatomical and electrophysiological studies provide insight into the functional circuitry of the brain, and help develop hypotheses about motor control in normal circumstances and the deficiencies associated with specific disease states. Dr. Anderson allowed the Board to "listen in" to neurons in the basal ganglia, an area of the brain that has a key role in regulation of movement (e.g., inhibiting unwanted movements or enabling desired ones). The neurons of the globus pallidus are tonically active, and their high level of activity may explain why they are so sensitive to metabolic insults and carbon monoxide poisoning. If neurons in this region are temporarily suppressed by the drug muscimol, excessive "drifting" of hand movements results with an overall slowing of purposeful function. Substantia nigra neurons are the dopamine-containing cells that degenerate in Parkinson disease, resulting in characteristic movement disorders and even cognitive deficits. Understanding the complex circuitry of this brain region and the responses to chronic alterations in activity and long-term drug treatments (e.g., DOPA treatment for Parkinson) are essential in the design of rational therapies to limit functional decline and reduce secondary symptoms in movement disorders.
The NCMRR started a dialogue with the Advisory Board challenging them to work within their various organizations and constituencies to increase awareness of medical rehabilitation research at the NIH. The NCMRR wants to be more responsive to the needs of the clinical, professional, and public constituents, while also increasing awareness of research advances and opportunities. In their professional lives, each Advisory Board member connects to multiple constituencies through their professional and personal networks, which provides special opportunities for the NCMRR to accomplish these goals.
Although the NCMRR has the overall mandate to direct medical rehabilitation research within the NIH, relevant research is also supported by other NIH Institutes (e.g., clinical neurology and neuroprosthetics in National Institute of Neurological Disorders and Stroke [NINDS], bioengineering in the new National Institute of Biomedical Imaging and Bioengineering [NIBIB], and musculoskeletal function in National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS]). Likewise, the interests of the rehabilitation community are represented by other federal agencies, several professional organizations (e.g., American Academy of Neurology, American Academy of Physiatry, American Academy of Physical Medicine and Rehabilitation, American Congress of Rehabilitation Medicine, American Occupational Therapy Association, American Physical Therapy Association, American Society for Neurorehabilitation, etc.), and advocacy groups centered on various neurological and musculoskeletal conditions.
The NCMRR is still relatively young and lacks visibility within the NIH and beyond. The Advisory Board suggested some marquee activities to heighten awareness of the medical rehabilitation research, such as newsletters, background publications, high-visibility meetings and consensus conferences. Although the NIH is not involved in advocacy, the Advisory Board suggested that rehabilitation supporters could promote the inclusion of specific congressional "report language" to reaffirm rehabilitation research priorities within the NIH. The NCMRR can provide information on research accomplishments and opportunities to constituency organizations, so that they can more effectively advocate for these research needs. It is important for the NCMRR to publicize its conferences and demonstrate that they are developing "real life solutions for real life problems". This will help to get constituents to view the NCMRR as their home. Although consumers may not completely understand some of the technical issues, they remain supportive of the research enterprise.
The Board noted that foundations and other private agencies develop materials to excite the public. The NCMRR should likewise highlight research findings and the promise of rehabilitative therapies, and demonstrate the wisdom of investing in disability research. The NCMRR should also cultivate relationships with universities and local media to excite teachers and students on rehabilitative approaches (much like current National Science Foundation educational programs). Perhaps advocates within the medical rehabilitation community should link to the Friends of NICHD, a broad coalition of groups that advocate for the broad and diverse interests of the Institute.
The Advisory Board also discussed how the NCMRR develops research initiatives (e.g., potential requests for applications or program announcements). Currently, ideas for initiatives come from consensus conferences, workshops, interactions with the research community, and literature review. The Advisory Board raised the possibility of building on the good will of current and past NCMRR grantees as a form of stakeholder equity. The Advisory Board itself could develop a "marketing" subcommittee to assist the NCMRR in promotional activities (e.g., current research findings, "silver bullet" cures, potential breakthroughs, and research opportunities).
The Advisory Board proposed the formation of a subcommittee to develop an Action Plan that would be presented at the next meeting in December. The following members volunteered to serve on that subcommittee: Gail Gamble, Gerben DeJong, Audrey Holland, Robert Dean, John Whyte, and Meredith Harris, with support of NCMRR staff.
Dr. John Whyte provided an update on the Rehabilitation Medicine Scientist Training Program. In response to the limited supply of physician investigators, the NIH has developed a series of national programs to provide mentored support in a variety of clinical disciplines, such as pediatrics, obstetrics/gynecology, clinical oncology, pediatric neurology, substance abuse, dental medicine, urology, and nursing. Generally, these programs function in conjunction with the corresponding academic professional organizations. These national programs are supported by various NIH institutes through the K12 funding mechanism.
In 1995, the NICHD worked with the Association of Academic Physiatrists to initiate a program for Physical Medicine and Rehabilitation (PM&R) fellows. The initial five-year grant had mixed results, due to relatively few applicants, poorly defined research interests, offers of only two years of mentored support, difficulty in clearing sustained protected research time, and variable productivity among the trainees. Dr. Whyte took over the program in 2001, and instituted a formal pre-application pathway to recruit postgraduate year two (PGY2) and year three (PGY3) PM&R physicians. He involved other senior researchers to create an advisory board and annual mentorship workshop. He promoted earlier interactions between trainees and prospective mentors and got NCMRR to up the commitment to three years of research support. Under the current program, trainees are encouraged to go outside of traditional PM&R departments to seek the specialized training they need to accomplish their clinical research goals. Hopefully, some of this expertise will also filter back to PM&R departments in future years.
Rehabilitation medicine still lacks clear role models and tends to be more focused on patient populations than scientific approaches, but the annual mentoring workshops have been extremely well received. One philosophical issue is the appropriate boundaries of a clinical training program. Should the K12 program support a PM&R trainee who is seeking training in more basic discipline? And what if that fellow goes on to take a position in an academic department outside of PM&R?
The NICHD will have to reevaluate the K12 program in the next few years to determine whether continued support of a specialized training program in rehabilitation is warranted, and if so, whether the support should be restricted to PM&R trainees. Clearly, there is inadequate research mentorship in PM&R departments. This national program has had a significant impact on a select group of trainees and a broader effect on the PM&R departments they serve. While other clinical disciplines beyond PM&R also contribute to rehabilitation medicine, Dr. Whyte indicated that it would be difficult to administer the program across diverse clinical disciplines and the specific leverage within PM&R departments that this program provides to the NCMRR would be diluted out.
The Advisory Board agreed that increasing the research orientation of a clinical field takes time and commitment. Currently, there are direct benefits to PM&R departments: newly trained researchers have increased probability of extramural support and attract researchers and collaborations from other disciplines. Moreover, the K12 program increases the awareness within PM&R departments of the need to support research. There was some sense that diluting a small program to fill a larger research need does not make sense, but the field should do more to support research trainees. Research-trained doctors improve the rehabilitation team, build bridges to related disciplines, and further the goal of translational research.
With the conclusion of this meeting, Thomas Strax finished his one-year term as Chair and John Whyte advanced from the position of Chair-elect to Chair. Thus, nominations were sought for the next Chair-elect. Three excellent nominations were received and after brief discussion and private ballot, Meredith Harris was elected chair-elect by majority vote.
The NCMRR noted its appreciation for the efforts of the following Board members who have completed their terms: Marjorie Anderson, Gloria Eng, and especially Thomas Strax who served as Chair in his final year. The retiring members were presented with special certificates signed by the Director of the NIH. Although Dr. Eng was not able to make the meeting for personal reasons, the other two retiring members shared some personal reflections and thanked their Board colleagues and NCMRR staff for the productive interactions.
Several ideas for future Advisory Board meetings were discussed. The Advisory Board would like to hear about the development of an updated NCMRR research agenda and the progress of the new clinical trial network for traumatic brain injury. Research issues include the role of rehabilitation engineering in the NCMRR, how to define the "active ingredient" in a rehabilitative therapies, and a review of current training programs supported by the NCMRR. The Advisory Board also wanted to continue the discussion of advocacy for NCMRR and rehabilitation policy and legislation in general, with a report from its newly established taskforce. The Board would also like to hear about the research recommendations that result from the NCMRR-sponsored meeting on Physical Disabilities through the Lifespan.
The meeting was adjourned at 11:00 a.m.