Report to Congress: Toward Successful Recovery from Traumatic Brain Injury

Sixty-two percent of the American public fears losing their mental capacity.

Ninety-six percent of the American public thinks it is important to invest in research to prevent, treat and cure disabilities.

— Research!America - Non-profit organization for medical research

Executive Summary

On October 13-16, 2005 over sixty top neuroscientists and physicians from across the United States and from twelve nations, along with representatives from the National Institutes of Health (NIH), National Institute on Disability and Rehabilitation Research (NIDRR), and the Centers for Disease Control and Prevention (CDC), joined family members to review the current state of science in brain injury research and recovery.

The meeting was convened under the auspices of the National Brain Injury Research, Treatment and Training Foundation and Conemaugh Health System in collaboration with the International Brain Injury Association, the Brain Injury Association of America, the Neurotrauma Committee of the World Health Organization, Academia Neurotraumatologica Multidisciplinaria, Coalition for Brain Injury Research, Defense and Veterans Brain Injury Center, and the Neurotrauma Foundation.

The purpose for the meeting was to review the progress or lack of progress in brain injury research and recovery since the congressionally mandated NIH Consensus conference held in 1998.

What emerged was a very bleak conclusion. Little has been accomplished to substantially improve recovery from Traumatic Brain Injury (TBI). While the numbers of survivors of TBI have increased significantly, the cost of care continues to rise.

Facts

According to the Centers for Disease Control and Prevention (CDC)

• There is no cure for TBI
• TBI is a major global health and socioeconomic problem
• In the U.S., 1.6 million TBIs occur each year
• 51,000 U.S. citizens die each year from TBI
• 235,000 hospitalizations occur each year from TBI
• 1,224,000 emergency room visits resulting from TBI
• 124,000 Americans each year sustain a TBI resulting in long-term or lifelong disability
• TBI is the leading cause of death and disability among young adults
• TBI accounts for more years of life lost than cancer and cardiovascular disease combined
• TBI IS THE SIGNATURE INJURY OF THE WAR IN IRAQ AND AFGHANISTAN

Critical Issues

• $60 billion per year in lifetime costs for TBI care
• 55 million Americans are living with TBI
• U.S. federal dollars allocated per person per year
  - AIDS- $12,111.18
  - Breast Cancer- $295.00
  - TBI- $2.25

Action Needed From Congress

1. $100 million request to jump-start research leading to recovery from TBI.

2. Shift from rat research to translational research aimed at improving human outcomes and recovery.

3. Creation of seven Centers of Excellence in TBI Research established by the National Institute of Neurological Disorders and Stroke at NIH to lead in research for recovery from TBI.

RECOMMENDATION: Provide an additional $47 million to National Institute of Neurological Disorders and Stroke (NINDS) to fund these research, clinical and training Centers of Excellence.

4. Expansion of the TBI Model Systems sponsored by NIDRR within the U.S. Department of Education. The goals of the TBI Models Systems at NIDRR should be expanded to focus on end points of improved outcomes and successful recovery including those with more moderate to mild TBI.

RECOMMENDATION: Provide an additional $30 million to expand the number of TBI Model Systems programs and to fund this research, clinical and training initiatives.

5. Funding of a dedicated national center for developing new and updating existing scientifically determined guidelines for the care and management of patients with TBI.

Scientific guidelines for the management of severe head injury have resulted in lower mortality, improved outcomes, shortened length of stay in the ICU and hospital and lower patient costs.

The National Center will also support electronic medical record development.

The Center should be established through the National Centers for Medical Rehabilitation and Research (NCMRR) at the National Institute of Child Health and Human Development of NIH.

RECOMMENDATION: Provide an additional $18 million to establish the National Center for Guidelines in TBI and to fund research, clinical and training initiatives.

6. There is a great need to track, report and analyze the prevalence, causes, costs and burden of TBI in the United States. It is recommended that the Injury Center at the Centers for Disease Control and Injury Prevention receive the necessary resources to conduct this important public health research which is used by every Federal, State and local public health agency to plan budgets and allocate resources.

RECOMMENDATION: Provide the Injury Center at CDC an additional $5 million to fund these research, clinical and training initiatives.

The overall recommendations are to provide an additional aggregate $100 million per year for five years to fund TBI research, clinical and training initiatives. This represents less than 1% of the total annual societal costs of TBI. Without Congressional action, more lives will be lost, costs will continue to escalate and families will be devastated.

NOTE: While the Conemaugh report did not address Department of Defense appropriations for treatment of soldiers with head trauma and scientific research in Traumatic Brain Injury, the Conemaugh group recognizes and supports the work of the Defense and Veterans Brain Injury Center and supports their request for an annual operating budget of $20 million dollars.

Introduction
On October 13-16, 2005, in Johnstown, PA, an international symposium was held in conjunction with the Conemaugh Health System, the John P. Murtha Neuroscience and Pain Institute and the National Brain Injury Research, Treatment and Training Foundation, in association with the Brain Injury Association of America, along with other leading associations and societies involved with TBI. Over 60 neuroscientists from 12 countries and major research centers gathered to review current research in traumatic brain injury (TBI) and develop a consensus document on research issues and priorities. Four levels of research in TBI were the focus of the discussion including: basic science, acute intervention, neurorehabilitation, and improving quality of life. Each working group was charged with reviewing current research, discussing and prioritizing future research directions, identifying critical issues that impede research in brain injury, and establishing a research agenda that will drive research over the next five years, leading to significantly improved outcomes and quality of life for individuals with brain injury.

Background
Traumatic brain injury constitutes a major global health and socioeconomic problem (Bazzoli, et al., 1995). At least 10 million TBIs, serious enough to result in death or hospitalization, occur annually, and an estimated 57 million people worldwide have experienced one or more TBIs (Murray and Lopez, 1996). In the United States, an average of 1.4 million TBIs occur each year, resulting in 50,000 deaths, 235,000 hospitalizations, and 1.1 million emergency department visits (Thurman, et al., 1999). These numbers, however, underestimate the true burden of TBI since the number of persons with TBI who receive little or no care is not known, and unfortunately, there is no standardized registration of TBI throughout the United States or shared databases.

Children, older adolescents, and adults aged 75 years or older are more likely to sustain a TBI than persons in other age groups (Langlois, et al., 2004). It is the leading cause of death and disability among young adults, accounting for a quarter to a third of trauma deaths and for a much larger proportion of those with life long disability (Bulger, et al., 2002). TBI accounts for more potential years of life lost than cancer and cardiovascular disease combined (Thurman, et al., 1999). TBI is an increasing concern among rescue workers and survivors of terrorism-related assaults worldwide, including the 911 attacks (Center for Disease Control and Prevention, 2002a, 2002b), and among military personnel serving in Iraq and Afghanistan (Okie, 2005; Scott, et al., 2005), where blasts are the leading cause of TBI (Defense and Veterans Brain Injury Center, 2005). The leading causes of TBI are, motor vehicle crashes, struck by or against events, and assaults, respectively, and the World Health Organization has projected that by the year 2020 automobile accidents will rank as the third leading cause of global burden of disease and injury, second only to ischemic heart disease and major depression (Langlois, et al., 2004).

Not only does TBI lead to great personal suffering and family disruption but it poses a significant burden to society with direct and indirect costs being estimated at over $6 billion per year (Finkelstein, et al., 2006). TBI is the most significant cause of death and disability in trauma. Compared to other injuries, it results in the greatest loss of productivity; more than 14 times the loss associated with spinal cord injury (Finkelstein, et al., 2006). The lifetime costs of TBI in the U.S., including lost productivity, total an estimated $60 billion annually (Finkelstein, et al., 2006).

TBI is a complex disease entity, which includes a vastly heterogeneous spectrum of pathology ranging from focal to diffuse neural injury and neurophysiological cascades. The primary insult occurring at the moment of accident initiates a complex sequence of events leading to secondary brain injury, which may be exacerbated by systemic insults such as hypoxia and/or hypotension (Cooper, 1985; Hovda and Feeney, 1992). The concept of secondary injury provides opportunities for treatment aimed at preventing and limiting this damage.

Research has greatly advanced our understanding and treatment of TBI. International scientific groups have collaborated on TBI assessment and intervention. Guidelines for the treatment and acute management of TBI have been developed (Bullock, et al., 1996). Bench research has elucidated our understanding of the complex pathphysiologic mechanisms occurring in TBI and this research has led to the development of various therapies with neuroprotective potential to reduce secondary injury. Rehabilitation centers throughout the United States are focusing on early intensive rehabilitation, and very recently, a disease specific Quality of Life scale has been introduced by the United States and European investigators (Tazopou, 2005).

The tremendous personal suffering and tragedy, and the high socioeconomic costs associated with TBI call for immediate and extensive research efforts to increase our understanding of the disease and improve treatments. This can only be accomplished by intensive collaboration, involving multiple disciplines including epidemiology, basic neuroscience research, neurology, neurosurgery, intensive care medicine, general traumatology, rehabilitation medicine, outcome research and other allied health professions. Networking between the organizations involved in TBI research should be promoted and collaboration between academic and scientific centers encouraged. Population based studies are essential to determine the scope of the problem and to further guide prevention programs. Database studies and electronic medical record data sharing programs are important to improve outcomes in brain injury. Basic research should be promoted to help elucidate physiological cascade mechanisms in TBI and related secondary injuries, and to investigate the therapeutic potential of new neuroprotective agents. Some of this work can be performed with in-vitro models, utilizing cell cultures, but clinically relevant in-vivo approaches are important for exploring the more complex effect of injury on tissue perfusion, oxygenation and metabolism (Povlishok, et al., 1992).

Research in the field of genomics and proteomics may shed more light on individual responses to injuries and help to guide the implementation or more individualized treatment methods (Hayes et al., 1992; McCracken et al., 1999; and Shah, 2002). An important focus in basic research is to explore possibilities for repairing the damage caused by TBI by promoting regeneration and plasticity. Europe currently has a distinct advantage over the USA in stem cell research. Stem cell therapy may suggest efficacy in some neurological diseases, but research into its potential use in TBI is still in its infancy. The acute care management of patients with TBI currently follows standardized approaches in which individualized treatment, targeted to the specific needs of individual patients, is largely neglected. A significant research effort is required to determine which mechanisms may be active in different patients at various times and hence become targets for therapy. In the acute care setting, little evidence exists to support any specific treatment modalities, and further research to obtain such evidence is considered a priority. These priorities relate both to non-operative treatment and to surgical management. For example, little doubt exists about the necessity to operate on extracerebral blood accumulations compressing the brain, but considerable debate exists on the desirability to operate on contusions or hemorrhages within the brain.

Despite the many advances in TBI care, we still do not understand why some patients unexpectedly deteriorate and die, and why lesions progress in some patients, but not in others. We may understand more about the pathophysiology of TBI, but do not yet have any specific treatment with proven benefit. Therapies aimed at repairing deficits are only just emerging, and too little attention has been paid to coping with residual impairments. A better understanding of TBI and new therapies will greatly reduce the suffering experienced by both victims and relatives, will improve the quality of life of patients and significant others, and reduce the high costs associated with TBI.

While from the public and legislative perspective, the problem and impact of TBI typically focuses on severe injury, it is equally important to note that moderate and mild TBI have similar, and perhaps greater, personal and societal impact, particularly when considering our recent experience in Iraq with IED blast injuries, many motor vehicle accidents, and sports-related injuries in children adolescents. Seventy-five percent of all TBIs fall in the moderate to mild range with considerable persisting morbidity/dysfunction at six to twelve months post-injury and longer in many cases, which obviously impacts upon their quality of life and that of their loved ones (Sosin, et al., 1996). While United States researchers are making advances in TBI research, there is a GREAT need for substantial funding to make the possibility of successful recovery from brain injury a reality. What is needed is a call to action similar to the call to develop and explore space and to land a man on the moon: a Manhattan type project where scientists across the country join together to work to understand the last great frontier of medical research, the brain/mind connection leading to a cure for brain injury.

Recognizing that TBI remains a significant health care problem with staggering societal and personal costs, the need for continued vigilance and action is obvious. In consideration of this, and in light of current literature and state of practice, the Conemaugh Symposium advanced multiple recommendations to improve and enhance basic science discovery, focus on the clinical care, management, and rehabilitation of traumatically brain injured patients to assure their successful recovery and provide education and training in this vital area of clinical neuroscience. As part of this conference, a position paper on TBI research priorities was drafted with specific recommendations advanced:

The recommendation is to provide an additional aggregate $100 million per year for five years to fund TBI research, clinical, and training initiatives, which represents less than 1% of the total annual societal costs of TBI.

Specific Research Recommendations for Federal Institutes and Centers

Recommendations for National Institute of Neurological Disorders and Stroke (NINDS) Centers of Excellence:

Based upon the recommendations advanced at the Conemaugh Symposium, there was strong support for the creation of up to seven geographically distributed regional Centers of Excellence for the Study and Treatment of TBI. As recommended, each Center should be supported by $5 million in total costs per year for a total funding period of five years. These Centers should be comprehensive and multi-disciplinary involving basic scientists, clinician investigators and other health care providers who would be directly involved in advancing the current scientific and clinical knowledge of TBI, moving basic science discovery to translational investigations in appropriate animal model systems as a prelude to the initiation of targeted clinical trials. The studies ongoing in the Centers should address the full spectrum of TBI ranging from mild through severe. The advanced clinical studies conducted in these Centers should improve upon the standard of care in the field, while also focusing carefully on a continuum of care over the course of the patient’s hospital care to assure optimal recovery. In addition to participating in stateof- the-art basic science and clinical investigations, it is also anticipated that each Center of Excellence will maintain a strong tradition of predoctoral, postdoctoral and fellowship training. Lastly, it is envisioned that each Center will participate in routine data sharing and potential collaborative publications to assure the timely reporting and dissemination of their findings.

Specific NINDS Research Projects:

• Development and validation of instruments that accurately measure disease specific quality of life in TBI.
  
  Rationale: Unique assessment measures are necessary to TBI because generic health-related QoL measures do not address the sensory, cognitive, and behavior functions unique to TBI. Specific QoL measures will effectively document and gauge the successful recovery of TBI rehabilitation from the point-of-view of the survivors and their families.
• Investigate how QoL measures can be utilized in assessing the cost-effectiveness, cost-benefit, and cost-utility of current service delivery.
  
  Rationale: Currently, treatments are primarily evaluated by objective outcomes, which do not take into account the subjective view of patients and caregivers. Because the ultimate outcome of healthcare interventions are improved quality of life, QoL measures are a crucial endpoint. Additionally, the effectiveness of various therapeutic and social interventions must be assessed utilizing QoL measures.
• Investigate the effects of QoL judgments made by the person with TBI and to what extent they may lack insight into deficits, which may affect QoL.
  
  Rationale: Little is known about whether QoL judgments after TBI are made in the same way as judgments are made by healthy controls. Unless the basis for QoL judgment is understood, the interpretation will remain unclear. Additionally, QoL frame of reference may change or shift with time after injury, and the extent to which patients’ lack of insight into their own deficits cloud their judgment.
• Investigate how QoL measures relate to the existing impairment, disability (activity limitation), and handicap (participation restriction) measures.
  
  Rationale: The World Health Organization’s framework for classification of the disease process is well developed. How QoL relates to the traditional framework established by the WHO has yet to be explored.
• Evaluate pharmacotherapeutic and non-pharmacotherapeutic neurorehabilitation interventions in the context of well-designed, randomized, controlled outcome studies.
  
  Rationale: By examining the effects of medication and non-medication treatment approaches, the best interventions to facilitate recovery and/or lessen neurological impairment can be determined. New medications and combination of medications with other therapeutic interventions show promise for arriving at improved outcomes that can be maintained over the life span of persons with TBI.
• Examine the application of emergent, state-of-the-art technologies. More specifically evaluate the use of electronic, computer, and web-based technologies in facilitation of neural recovery, compensation for impairment, and/or enhancement of functional independence.
  
  Rationale: New advances in computer-based technologies occur at a rapid pace in America today. Opportunities to investigate and apply these new technologies in the most advantageous fashion to improve outcomes need to be explored. By doing so, costs can be reduced and more individuals with TBI can be treated due to the nature and availability/accessibility of these interventions and the decreased need for ongoing professional face-to-face involvement. These technologies should be applied quickly and effectively to the treatment of TBI.

The recommendation is to provide an additional $30 million per year for five years to fund these research, clinical, and training initiatives.

National Center for Medical Rehabilitation and Research (NCMRR)

Based upon the consensus of scientists from the Conemaugh Scientific Symposium on TBI, the priorities for NCMRR were derived. The NCMRR is well positioned to address issues related to the early stages of rehabilitation in TBI. The importance of effectively treating persons with brain injuries immediately following acute care will impact the degree of recovery at all stages in the process of their healing. Comprehensive models of care, involving all aspects of TBI by multidisciplinary teams, are needed to produce optimal outcomes leading to a successful recovery. The effectiveness of treatment models is best measured in the context of clinical trials and the establishment of clinical care path protocols across treatment centers and in collaboration with other federally funded agencies such as NINDS and NIDRR. By doing so, the benefits of cumulative research and outcome studies from all sources can be derived into an overall effective approach that can be disseminated nationally and lead not only to the optimal recovery for persons with TBI, but also minimizing costs of treatment. The scope of the work of NCMRR should also address the range of difficulties, varying from relatively mild problems that often go unrecognized and untreated, to the more obvious problems arising from a severe injury.

Specific NCMRR Research Projects:

• Funding of a dedicated Center for developing new and updating existing guidelines for the care and management of traumatically brain-injured patients.
  
  Rationale: Scientific guidelines for the management of severe head injury have resulted in lower mortality, on Disability and Rehabilitation Research (NIDRR), and Centers for Disease Control and Injury Prevention improved outcome, shortened length of stay in the ICU and hospital and lower patient costs. These (CDC), joined family members to review the current state of the science in brain injury research and recovery. Guidelines must be constantly updated and require constant analysis of scientific data, a dedicated staff, and regular national and international conferences, all of which needs to be organized through on agency.
• Institutional and/or government funding through the regional neurotrauma center should be used to assure the Brain Injury Assocation of America, the Neurotrauma Committe of World Health Organization, adequate support for trauma care providers.
  
  Rationale: Given the litigious nature of our society and high cost associated with care of neurotrauma patients, federal support is necessary to have an adequate network of trauma centers. Fewer general surgeons and neurosurgeons are choosing to participate in trauma care, primarily due to the workload and economic realities, and unlike most other surgical diseases, trauma care is extraordinarily intense and stressful. The threat of medical malpractice lawsuits and exorbintant malpractice insurance premiums are also significant disincentives to caring for trauma patients. Federal Tort Reform legislation should be from Traumatic Brain Injury (TBI). While the numbers of survivors of TBI have increased significantly, the passed to remove these economic obstacles from dissuading otherwise interested professionals from caring for trauma patients.

National Center for Medical Rehabilitation and Research (NCMRR)

• Creation and support of a Web-Based Trauma Registration Linked to the Medical Record.
  
  Rationale: There is a critical need for high quality and current clinical trauma patients. Without these data, it is not possible to monitor quality of care in a given region, identify those regions or hospitals providing substandard care, identify best practices, or make effective and timely improvements where needed. In addition, comprehensive and accurate epidemiologic information cannot be obtained without such data. This data collection is also necessary to make progress in clinical trials of new treatments, allowing more rapid accrual of sufficient numbers of patients and assessments of outcome. The most effective method of obtaining current injury data would be through an electronic medical record, with appropriate data elements electronically collected and transferred to an internet-based trauma registry.
• Designation and support of Regional Neurotrauma Centers with outreach telemedicine availablity.
  
  Rationale: Acute treatment of TBI is complex and costly. Regional Neurotrauma Centers are the only cost-effective method of providing this TBI Treatment. The public is unaware that they are more likely than not to live in a state with an underdeveloped or non-existent trauma system. Yet they expect excellent trauma care and consider it as much of a priority as police or fire departments (Congressional Briefing,). These Regional Centers would have the critical mass of expertise and technical support to treat these complex cases and offer training and consultation to outlying community neurosurgeons.

The recommendation is to provide an additional $18 million per year for five years to fund these research, clinical, and training initiatives.

Centers For Disease Control & Injury Prevention (CDC)

The Participants in the Conemaugh Symposium on Traumatic Brain Injury recommend that the Centers for Disease Control & Injury Prevention receive recognition and increased support for the work performed by the Injury Center of CDC to track, report, and analyze the prevalence, causes, costs and burden of TBI in the United States. Collection and analysis of scientific data is critical for state agencies, the scientific community, and for public officials in planning services, determining costs, and allocating resources. Data are also needed in prevention, outcome studies, training and public awareness campaigns.

Specific CDC Research Projects:

• The CDC should be charged with developing a model TBI compatible data collection system for use by all federal agencies involved with TBI data collection.
• CDC data sharing with public and private agencies should be enhanced so that public awareness of TBI is increased and compatible across federal agencies is assured.
• Since the CDC plays a significant role in training first responders and other emergency workers, it is recommended that training in TBI care and diagnosis be included in all future training programs and material.
• CDC public education regarding the causes and prevention of TBI needs to be produced and disseminated utilizing the worldwide web and other media for wide public circulation.
  
  Rationale: The CDC is the premier national organization for epidemiological studies and data collection. The CDC collects and analyzes trauma data, emergency room data including utilization. The work requested for TBI is critical for federal and state health agencies in planning services, allocation of resources and for cost containment. Data sharing currently among federal agencies is compromised due to the different TBI data sets used by the agencies. The development of a model TBI data collection system that can be used by all federal and state agencies would further reduce costs and allow for better planning, coordination and management. Training of first responders and emergency personnel in early management of TBI is critical to the outcome, especially in the event of major disasters and/or terrorist attacks.

The recommendation is to provide an additional $5 million per year for five years to fund these research, clinical, and training initiatives.

The recommendation is to provide an additional aggregate $100 million per year for five years to fund TBI research, clinical, and training initiatives, which represents less than 1% of total annual societal costs of TBI.

Note: While the Conemaugh report did not address Department of Defense appropriations for treatment of soldiers with head trauma and scientific research in Traumatic Brain Injury, the Conemaugh group recognizes and supports the work of the Defense and Veterans Brain Injury Center and supports their request for an annual operating budget of $20 million dollars.

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