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Suggested Citation:"1 Introduction." National Academies of Sciences, Engineering, and Medicine. 2022. Traumatic Brain Injury: A Roadmap for Accelerating Progress. Washington, DC: The National Academies Press. doi: 10.17226/25394.

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1

Introduction

Despite significant advances achieved over the past 60 years in addressing the problem of traumatic injury, injury remains today an important cause of death and disability, by one estimate posing a burden of death and disability second only to that of cancer and just slightly greater than that of heart disease (Moses et al., 2015). Reflecting the magnitude of this burden, prior reports of the National Academies of Sciences, Engineering, and Medicine and others have addressed injury prevention and trauma care (see Box 1-1). Yet, funding directed at research on injury is not yet commensurate with the magnitude of the problem (see Figure 1-1).

Traumatic brain injury (TBI), defined in Box 1-2 and the focus of this report, represents only one type of accidental or deliberate injury. However, TBI was diagnosed in approximately 2 percent of the total emergency department (ED) visits, hospitalizations, and deaths in the United States in 2013 (Taylor et al., 2017), and half of military Veterans have reported a lifetime history of experiencing at least one TBI (Shura et al., 2019). TBI has been reported to contribute to 30 percent of injury-related deaths in a U.S. study (Taylor et al., 2017) and to 41 percent of years of life lost to premature death in a study of 16 European countries (Majdan et al., 2017). TBI thus represents a significant component of overall injury, providing an important opportunity to improve health and well-being if prevention, care, and recovery can be advanced.

STUDY CONTEXT

Every community and every segment of the population is affected by TBI. TBI affects civilian and military populations and occurs in both rural and urban settings. Causes as diverse as falls, sports injuries, vehicle collisions, intimate partner violence, and military incidents can result in such injuries across a spectrum of severity and among every age group, from babies and children, to adults, to the elderly.¹Chapters 2 and 3 present a detailed look at the scope and burden of TBI.

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¹ Symptoms consistent with experiencing a TBI have also been reported after incidents among U.S. staff in Cuba, China, and other locations, and it has been suggested that these injures may be caused by radiofrequency energy. This report does not focus on such cases. (For a recent assessment, see NASEM, 2020.)

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Suggested Citation:"1 Introduction." National Academies of Sciences, Engineering, and Medicine. 2022. Traumatic Brain Injury: A Roadmap for Accelerating Progress. Washington, DC: The National Academies Press. doi: 10.17226/25394.

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BOX 1-1 PRIOR REPORTS ON INJURY PREVENTION AND TRAUMA CARE

Assessment of the challenges posed by traumatic brain injuries and opportunities for improving care and research to address these challenges builds on a history of engagement in injury prevention and care that stretches back decades (see the figure below).

Selected prior reports on injury control and trauma care.

SOURCE: NASEM, 2016.

The 1966 report Accidental Death and Disability: The Neglected Disease of Modern Society (NAS and NRC, 1966) called injury a “neglected epidemic” that was “the leading cause of death in the first half of life’s span” (NAS and NRC, 1966, p. 5). The committee responsible for that report recommended improved awareness and treatment of trauma and called for establishing trauma registries, expanding support for trauma research, and establishing a national institute of trauma to serve as a coordinated focus of trauma-related activity. The first edition of Optimal Hospital Resources for Care of the Seriously Injured was published in 1976 (ACS, 1976) and has since become an important guide for trauma centers. Two decades later, Injury in America: A Continuing Public Health Problem (NRC and IOM, 1985) reported that improvements in trauma care had been achieved but that injuries remained the “leading cause of death up to the age of 44 … [and] cause the loss of more working years of life than all forms of cancer and heart disease combined” (NRC and IOM, 1985, p. 1). The report identified the need for additional research on biomedical mechanisms of injury and on optimal injury management but noted that research on injury and injury control was “disproportionately low and discontinuous, in comparison with that for cancer, heart disease, and other major health problems” (NRC and IOM, 1985, p. 2). The attention to trauma resulting from these and other reports led to a new era of emphasis on the problem in public health, including the establishment of a center at the Centers for Disease Control and Prevention (CDC) focused on injury prevention and control. In 1992, the Defense and Veterans Head Injury Program, now known as the Traumatic Brain Injury Center of Excellence, was established. And in 2005, the Department of Veterans Affairs designated a network for rehabilitation after polytrauma, establishing its Polytrauma System of Care.

A National Trauma Care System: Integrating Military and Civilian Trauma Systems to Achieve Zero Preventable Deaths After Injury (NASEM, 2016) emphasized lessons learned by military and civilian trauma systems and again highlighted the enormous societal burden of traumatic injury, the dramatic contributions it makes to years of life lost before age 75, and its contributions to almost half of all deaths under age 46. The report argued for the value of integrating these two systems to achieve the best possible care, highlighting practices, such as coordinated handoffs, that had contributed to reductions in military trauma deaths. The report stimulated further efforts to strengthen the U.S. trauma care system, including the 2018 launch of the National Trauma Research Action Plan (Bulger et al., 2018).

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Suggested Citation:"1 Introduction." National Academies of Sciences, Engineering, and Medicine. 2022. Traumatic Brain Injury: A Roadmap for Accelerating Progress. Washington, DC: The National Academies Press. doi: 10.17226/25394.

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**FIGURE 1-1** Relationship between NIH disease-specific research funding and burden of disease for selected conditions. Injury is shown on the right side of the figure and below the line, indicating that it poses a high burden but with less-than-predicted levels of research support.
SOURCE: Moses et al., 2015. Reproduced with permission from the *Journal of the American Medical Association*. © 2015 American Medical Association. All rights reserved.

BOX 1-2 DEFINITION OF TBI USED IN THIS REPORT

As defined by the initiative on Common Data Elements (CDE) for Research on Traumatic Brain Injury and Psychological Health, a traumatic brain injury is “an alteration in brain function, or other evidence of brain pathology, caused by an external force“ (Menon et al., 2010, p. 1638). The CDE definition of TBI is both concise and inclusive, encompassing any external force that leads to brain tissue damage of any severity level and resultant disruption in the normal function of the brain. The brain injury can result from an impact, from rotational forces (e.g., angular acceleration or deceleration of the head), or from a pressure wave, and the injury can be blunt or penetrating. Because this study looks broadly across all types of TBI in all military and civilian populations, the CDE definition is the one used as the basis for this report.

It should be noted that different communities addressing TBI have developed operational definitions focused on the signs and symptoms most relevant to their particular foci, including loss of consciousness or alteration of mental state and other postinjury elements. A number of TBI definitions are collected in Appendix B of the report Evaluation of the Disability Determination Process for Traumatic Brain Injury in Veterans (NASEM, 2019). Some definitions focus on how individuals experiencing a TBI can be identified, especially at the point of injury (e.g., DoD, 2012, 2015; French et al., 2008; McCrory et al., 2017). Others address injuries for which the injured person can be considered for disability adjudication and compensation (VA, 2015) or for payment of claims against health benefit plans. Still others provide guidance for clinical practice or inclusion criteria for clinical studies (APA, 2013; Giza et al., 2013; Malec et al., 2007). Although this report uses the encompassing CDE definition, such operational definitions remain valuable to the sectors of the TBI field for which they were developed.

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Just as the many causes of TBI and the people who experience it are diverse, so, too, are the physiological, cognitive, and behavioral changes that can occur following injury. An impact to the head, brain acceleration and deceleration, and the potential for the brain to shift internally and hit the opposite side of the skull can create bruising, damage the blood–brain barrier and blood vessels, and stretch or shear neurons and other cell types in the brain. These forces can lead to bleeding and swelling, as well as to a host of cellular and molecular events that lead to further damage, including disruption of neurotransmitter and ion flows in brain synapses, alterations in metabolism, and inflammatory responses. Although many people who experience a TBI have minor symptoms that resolve over hours or days, others experience alterations or loss of consciousness and have prolonged symptoms such as headaches, dizziness, vision and speech disturbances, agitation, cognitive dysfunction, and other long-term effects. One study found that even among those who had experienced an injury considered a mild TBI, 53 percent reported continued impairment a year later (Nelson et al., 2019). Headache is one of the most common symptoms after TBI (Lucas, 2015); however, experiencing one or more TBIs has also been connected to increased risk of developing anxiety, anger, depression, substance use disorders, and dementia, and to suicide and reduced life expectancy (Graham and Sharp, 2019; Harrison-Felix et al., 2015; Juengst et al., 2017; Madsen et al., 2018; Neumann et al., 2017; Shura et al., 2019). Table 1-1 lists examples of consequences that may arise after TBI.

The prevalence of TBI and the toll it can exact on those who experience it and their families make it an important area of investigation, although the vast heterogeneity of the condition makes assessment of TBI care and research particularly challenging. TBI is not a single type of injury with a single trajectory. Data from the Department of Defense indicate that more than 80 percent of TBIs are classified as “mild,” approximately 10–11 percent as “moderate,” and roughly 2 percent as “severe” or resulting from a penetrating head wound.² Based on data from the Centers for Disease Control and Prevention (CDC), an unknown percentage of people do not seek or receive initial medical care after a potential TBI (CDC,

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² Information on TBI worldwide totals for the period 2000–2020 Q4, available online at DoD TBI Worldwide Numbers. https://health.mil/About-MHS/OASDHA/Defense-Health-Agency/Research-and-Development/Traumatic-Brain-Injury-Center-of-Excellence/DoD-TBI-Worldwide-Numbers (accessed October 4, 2021).

TABLE 1-1 Examples of Physical, Cognitive, and Behavioral Challenges Experienced After TBI

Physical	Cognitive	Behavioral
Headache	Difficulty concentrating	Depression
Movement problems	Memory problems	Anxiety
Impaired or blurred vision	Reduced attention span	Agitation
Difficulties with speech or swallowing	Difficulty with problem solving	Reduced impulse control
Dizziness and balance problems	Confusion	Increased anger or irritability
Seizures	Increased risk of Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative disorders
Fatigue
Pain
Sleep problems

NOTE: This list is intended to illustrate symptoms that can develop after TBI and is not intended to be exhaustive or to represent the experiences of all people who experience such an injury.

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Suggested Citation:"1 Introduction." National Academies of Sciences, Engineering, and Medicine. 2022. Traumatic Brain Injury: A Roadmap for Accelerating Progress. Washington, DC: The National Academies Press. doi: 10.17226/25394.

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2015), while among those seeking care, the CDC data show that 86 percent of those who received initial care were treated and released from the ED (indicating a generally less serious injury), 12 percent were hospitalized and subsequently discharged, and 2 percent died.³Chapters 2 and 3 further explore who experiences TBI and what personal and social burdens the condition poses.

Patients with TBIs across the spectrum of severity may enter the medical system through multiple points, ranging from emergency medical services in the field, to presentation to an athletic trainer in a training room, to evaluation in a primary care setting. This breadth of entry points to clinical care for TBI, along with the variety of care providers potentially involved, presents challenges both to the medical system and to patients and families as they navigate care and recovery.

Differing mechanisms and severity of injury may also result in vastly different clinical courses. Adult patients sustaining moderate or severe TBI, such as from a motor vehicle crash, may find themselves transported by emergency medical services to the ED of a trauma center, with subsequent admission to the intensive care unit of the hospital, perhaps after urgent surgical intervention. This may be followed by an inpatient hospital stay and subsequent inpatient and outpatient rehabilitation, potentially over the course of months or even years. In contrast, a pediatric patient sustaining a mild TBI as the result of participation in a sport, such as soccer, may be evaluated immediately by school athletic personnel and referred to a sports medicine physician for evaluation, with management and oversight of return to learning and sports over the course of a few weeks. The many types of TBI and the many types of people who experience it thus contribute to a maze of clinical paths along which TBI patients may travel, making standardization of care for the optimization of outcomes challenging.

Areas for Improvement

Improving TBI care and research will require addressing essential components across the full spectrum of prevention, treatment, and recovery while recognizing and building on patient and community experiences. These components include the following:

Understanding the scope and causes of TBI and the experiences of those who are faced with or at risk of injury. At the core of any process of improvement in TBI care and research are the needs and participation of those who experience these injuries. Care and research also need to be connected to population-level surveillance to gain insights on the scope of the problem and aid in designing prevention approaches.
Developing, deploying, and improving prevention strategies. The most effective way to improve outcomes of TBI is to prevent people from experiencing such an injury in the first place. Although primary injury prevention is not the focus of this report, the committee emphasizes its importance in any comprehensive framework for understanding and improving the overall TBI system.
Identifying everyone who has experienced a TBI and needs care. To this end, accurate and timely screening and diagnosis are required.
Providing high-quality care to those who have experienced one or more TBIs and facilitating the most successful recovery achievable for that person. Care elements include sufficient access to care and appropriate treatment capacity, provision of the most effective care possible according to current medical understanding and best practices, and delivery of coordinated care. A multidisciplinary response to TBI is

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³ See https://www.cohenveteransbioscience.org/traumatic-brain-injury (accessed December 1, 2021).

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often required. No single medical specialty or care provider has the clear lead role in TBI.

Developing a research system capable of supporting improved understanding of TBI and the development of treatments and other interventions that can improve outcomes and address identified gaps and needs for persons with TBI and their families.
Creating processes for feedback, learning, and improvement within the TBI system. Such processes are part of establishing an interconnected, learning health care system for TBI.

The overall TBI ecosystem also encompasses networks beyond health care and research. It includes the related systems that administer and finance health care, accredit care facilities, and provide regulatory approval and oversight of products and therapies. It also intersects with the wide range of community organizations and institutions in which people return to learning, work, and play after experiencing a TBI, including the education system, work environments, professional and amateur sports associations, the criminal justice system, and others. In short, TBI affects a cross section of society and can touch nearly all health care and community institutions. And it involves more than biomedical factors, encompassing social, psychological, and ecological dimensions that significantly affect care and long-term outcomes (see further discussion in Chapters 2 and 3). The present report cannot delve into these many networks and intersections in detail, but emphasizes that TBI needs to be situated within this bigger picture.

Recent TBI Efforts

Efforts by military and civilian federal agencies, foundations, clinicians and researchers, and patient and family advocacy organizations over decades have focused attention on TBI and raised awareness of the needs and challenges it poses. In 2019, for example, federal agencies provided more than $300 million for TBI research.⁴ A variety of efforts to better understand TBI and its management are highlighted in Table 1-2; these and other developments are summarized in Appendix A. Additional efforts and networks address related issues in emergency medical services and trauma care, mental health, and other topics.

These various programs have generated valuable longitudinal data on the recovery trajectories of those who experience TBI, increased researchers’ and clinicians’ understanding of the pathophysiology of brain injuries, and resulted in such successes as a Food and Drug Administration (FDA)–approved blood-based biomarker to help identify concussion (see FDA, 2018).

Collectively, the knowledge gained represents an important base of information for analyzing both areas of progress and areas in which more widespread implementation of best practices or the acquisition of new knowledge can improve care and outcomes for those who experience TBI. Federal agencies involved in the decade-long National Research Action Plan (NRAP) on posttraumatic stress disorder, mental health conditions, and TBI, established in 2013, are looking ahead to next steps. The Brain Trauma Blueprint is designed to foster public–private collaboration around TBI research needs to advance precision medicine, and the Department of Defense (DoD) is moving forward with its Warfighter Brain Health Strategy. Now is the time to advance military and civilian TBI research and care, and this report is intended to contribute to those strategic planning efforts.

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⁴ Based on a search for traumatic brain injury or TBI in the federal RePORTER database, available at https://federalreporter.nih.gov (accessed August 25, 2021). See also Appendix A for further information on federal support for TBI research.

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TABLE 1-2 Selected TBI Research Efforts

Effort	Key Funders	Year(s)	Target Population(s)	Description
Research Consortia, Initiatives, and Networks
Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI)	20 European universities	2013–present	European civilians	Various efforts to study TBI, develop TBI databases, and translate research to policy
Chronic Effects of Neurotrauma Consortium (CENC)	DoD, VA	2013–2019	Military personnel (Veterans)	Study to investigate the long-term effects of mild TBI (mTBI) among military service personnel and Veterans
Collaborative Neuropathology Network Characterizing Outcomes of TBI (CONNECT-TBI)	NINDS, University of Pennsylvania	2020–present	Athletes, military personnel, and civilians	Network to promote the sharing of tissue and datasets
Concussion Assessment, Research and Education Consortium (CARE)	NCAA, DoD	2014–present	Student athletes and cadets	Study to explore concussive injury and recovery
International Initiative for Traumatic Brain Injury Research (InTBIR)	NIH, European Commission, Canadian Institutes of Health Research	2011–2019	Civilians, military personnel, athletes, and pediatric populations	International effort to reduce TBI burden by leveraging and coordinating TBI research
Long-term Impact of Military-relevant Brain Injury Consortium (LIMBIC)	DoD, VA, universities, private research institutions	2019–present	Military (Veterans)	Further research for TBI military personnel and Veterans (newest iteration of CENC)
TBI Endpoint Development Initiative (TED)	DoD, FDA, PPPs	2014–present	Civilians, athletes, military personnel	Efforts to identify/validate measures of TBI and recovery
TBI Model Systems (TBIMS)	NIDILRR, (Administration for Community Living, HHS)	1987–present	Civilian	Longitudinal study of long-term outcomes of individuals with moderate-severe TBI who received inpatient rehabilitation; the network also supports projects aimed at meeting the needs of individuals with TBI
Transforming Research and Clinical Knowledge in TBI (TRACK-TBI)	NIH, DoD, OneMind, NeuroTrauma Sciences LLC, Abbott Laboratories	2009–present	Civilian	Largest-scale initiative to analyze clinical TBI data and TBI outcomes
VA TBMIS Research Program	VA, NIDILRR (HHS)	2008–present	Military service members and Veterans	Longitudinal study of outcomes after inpatient rehabilitation at 5 VA Polytrauma Rehabilitation Centers
Enabling Research Infrastructure
Common Data Elements (CDE)	NIH, HHS	2010–present		Effort to create data standards for TBI clinical research

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Effort	Key Funders	Year(s)	Target Population(s)	Description
Federal Interagency TBI Research Informatics System (FITBIR)	DoD, VA, NIH	2011–present	Military personnel and civilians	Centralized TBI research database
Research Agenda and Priority Setting
Brain Trauma Blueprint	Cohen Veterans Bioscience	2019–present	Military personnel and civilians	Framework for identifying gaps and synthesizing information to advance precision diagnostics and therapeutics, building on a 2019 summit
Congressionally Directed Medical Research Program on TBI and Psychological Health	Congress	2007–present	Military personnel	Support for research in TBI prevention, detection, diagnosis, treatment, and rehabilitation
National Research Action Plan on TBI and PTSD (NRAP)	DoD, VA, HHS	2013–present	Military personnel and civilians	Established by a 2012 executive order to address research and care gaps
Education and Awareness
HEADS UP	CDC	2003–present	Youths and the elderly	Educational initiatives to improve TBI awareness and prevention among youths and the elderly

NOTE: CDC = Centers for Disease Control and Prevention; DoD = Department of Defense; DOE = Department of Energy; FDA = Food and Drug Administration; HHS = Department of Health and Human Services; NCAA = National Collegiate Athletic Association; NFL = National Football League; NIDILRR = National Institute on Disability Independent Living and Rehabilitation Research; NIH = National Institutes of Health; NINDS = National Institute of Neurological Disorders and Stroke; PPP = public–private partnership; TBI = traumatic brain injury; UCSF = University of California, San Francisco; VA = Department of Veterans Affairs.

STUDY PURPOSE, SCOPE, AND APPROACH

Recognizing the importance of and opportunities for improving TBI care and research, DoD’s Combat Casualty Care Research Program asked the National Academies to convene an ad hoc committee of experts to consider the challenges entailed in achieving such improvements and recommending steps that can be taken to overcome those challenges. The committee’s statement of task is present in Box 1-3. The committee quickly realized that no one study could fully address the many networks and intersections outlined above, and so, while emphasizing the importance of situating TBI within that bigger picture, focused on identifying both gaps in and opportunities to advance TBI care and research. The committee also identified prevention as an essential topic, though not covered explicitly in its statement of task, sitting firmly at the beginning of the chain of care. This report represents the committee’s response to its statement of task, documenting its understanding of the many crucial elements that need to form part of an optimized system for TBI care and research and presenting a roadmap for accelerating progress toward achieving that system.

The committee formed to carry out this complex task included 18 members with expertise in basic, translational, and clinical research on TBI; epidemiology; neurotrauma; systems of care for TBI, from acute emergency medicine and trauma care through rehabilitation and community reintegration; neuropsychology and mental health; and health sciences and health care policy. The committee met virtually over the course of the study, holding meetings

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BOX 1-3 STATEMENT OF TASK

An ad hoc committee under the auspices of the National Academies of Sciences, Engineering, and Medicine will gather input from a wide range of public and private experts and stakeholders; examine the current landscape of basic, translational, and clinical traumatic brain injury (TBI) research; and identify gaps and opportunities to accelerate research progress and improve care for those affected by TBI.

The committee will plan and host a large public workshop that examines the current landscape and explores future opportunities for collaborative action. Workshop attendees will include representatives of federal, state, and local governments; military and Veterans’ health stakeholders; the private sector; the academic community; patient advocacy stakeholders; the clinical community; philanthropic organizations; and traditional TBI research funders, as well as other relevant stakeholders involved in related fields aimed at advancing diagnostic tools, therapeutic trials, and systems of care. Presentations and discussions will address the following topics:

Fostering biomedical research on TBI;
Accelerating translational and clinical research on TBI;
Delivering breakthroughs in TBI treatments; and
Improving TBI systems of clinical care from acute care through rehabilitation.

The study, including the workshop, will address a range of populations affected by TBI and related goals, including improving readiness, retention, return to service, and prevention of long-term sequelae in military populations; and improving return to play and work, and prevention of long-term sequelae in sports participants, older adults who have fallen, individuals affected by traffic/vehicle injuries, and other civilian populations.

Based primarily on the workshop presentations and discussions, supplemented by additional literature review as appropriate, the committee will develop a report, with recommendations, that:

Identifies major barriers and knowledge gaps that are impeding progress in the field;
Highlights opportunities for collaborative action (both intergovernmental and public-private) that could accelerate progress in TBI research and care; and
Provides a roadmap for advancing both research and clinical care that would guide the field over the next decade.

approximately monthly to discuss and analyze the evidence and develop the conclusions and recommendations presented in this report. Evidence was gathered through a literature review, as well as a series of public virtual workshop sessions held in March and April 2021 and public webinars held in May and June 2021, with speakers who generously shared their knowledge and experiences with the committee. See Appendix C for further information on how the committee conducted its work and Appendix D for brief biographies of committee members and staff.

ORGANIZATION OF THE REPORT

Chapter 2 of this report describes the extent of the problems posed by TBI and the experiences and burdens reported by patients and families. Chapter 3 describes how bio-

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logical, psychological, social, and ecological factors affect the experience of and outcomes following TBI, and introduces the care and recovery continuum. Chapter 4 highlights the role of prevention in reducing the numbers of TBIs that occur and explores awareness of and misconceptions about the condition. This information lays the foundation for the committee’s identification of actions that can be taken to make progress in improving TBI care and research.

The report then turns to the patient journey and care pathways following a TBI.

Chapter 5 focuses on the acute phase of care, from the point of injury and prehospital assessment through hospital care and transition to rehabilitation. Chapter 6 addresses the post-acute and longer-term phase of care, emphasizing rehabilitation, recovery to the extent possible, and community reintegration. Each of these chapters lays out the goals and main elements of care provided to a person who has experienced a TBI and identifies a number of remaining clinical gaps and needs for that phase of care.

In Chapter 7, the report examines major gaps, challenges, and opportunities for advancing TBI care and research. The opportunities identified include implementing a new clinical classification system for TBI; using emerging biomarkers as part of an expanded TBI toolkit; learning from and building on existing care systems and networks; increasing patient, family, and stakeholder engagement; and employing additional types of study designs.

Finally, Chapter 8 details the essential elements of an optimized system for accelerating progress in the TBI field, emphasizing the need for a coordinated system capable of more effectively connecting current programs and networks and providing a locus for efforts to advance TBI care and research. This chapter provides the committee’s recommendations for actions that can be taken to help achieve an optimized TBI system and a research agenda for addressing unanswered questions.

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Suggested Citation:"1 Introduction." National Academies of Sciences, Engineering, and Medicine. 2022. Traumatic Brain Injury: A Roadmap for Accelerating Progress. Washington, DC: The National Academies Press. doi: 10.17226/25394.

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Page 26 Cite

Suggested Citation:"1 Introduction." National Academies of Sciences, Engineering, and Medicine. 2022. Traumatic Brain Injury: A Roadmap for Accelerating Progress. Washington, DC: The National Academies Press. doi: 10.17226/25394.

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