Cognitive Rehabilitation Therapy for Traumatic Brain Injury: Evaluating the Evidence

To complete its task (see Box S-1 for the Statement of Task), the IOM formed an ad hoc committee of experts from a range of disciplines including neurology, psychology, psychiatry, rehabilitation medicine, neuropsychology, neuropharmacology, nursing, speech-language pathology, epidemiology and neurocognitive study design, and disability and long-term care. The committee developed a strategy for reviewing the evidence, including a comprehensive review of the literature on CRT for TBI. After reviewing the statement of task and meeting with a representative from the Department of Defense to clarify intent, the committee interpreted its charge as assessing the state of the evidence. The committee acknowledges the goal of evidence assessments is to inform policy, upon which clinical practice guidelines are developed. Those at the Department of Defense are the only ones in position to make policy judgments for the Military Health System. After extensive deliberation, the committee determined it was beyond its charge to interpret its assessment of the evidence with respect to policy recommendations or clinical practice guidelines.

In addition to reviewing the literature, the committee heard from experts in the fields of cognitive rehabilitation research and practice, investigators of major research studies of traumatic brain injury in military and civilian settings, and advocates for the role of families and communities in providing ongoing support to injured members of the military and veterans. The committee also received statements from stakeholders from various organizations and members of the public. Over the course of the study, the committee met six times, engaged the public through two workshops, and participated in a number of ongoing activities organized by working groups. The committee did not complete an independent assessment of the treatment of TBI by cognitive rehabilitation within the MHS (Subtask 5). This exclusion was due to constrained resources, including a lack of access to available data and time limitations.

In broad terms, a TBI is an injury to the head or brain caused by externally inflicted trauma. DoD defines TBI as a “traumatically induced structural injury and/or physiological disruption of brain functions as a result of an external force.” TBI may be caused by a bump, blow, or jolt to the head, by acceleration or deceleration forces without impact, or by penetration to the head that disrupts the normal function of the brain (CDC 2011b; Katz 1997; VA/DoD 2009a). The events that lead to TBI vary by population. Among civilians, motor vehicle accidents are the leading cause of TBI-related deaths; among young children and older adults, falls are a major cause of TBI (CDC 2010); and among soldiers and veterans, the most common source of TBI is a blast (i.e., BINT), followed by falls, motor vehicle accidents, and lastly, assault (DVBIC 2009). Chapter 2 provides a more complete description of TBI, including mechanisms of injury and classification schemes, which may aid in short- and long-term prognosis.

Across time, incidence of TBI has risen among the military population as an all-volunteer force has been engaged in the longest war (OEF) in U.S. history, and service members are exposed to longer and more frequent deployments. While in-theater, service members are increasingly attacked by more explosive weaponry. Approximately 22 percent of wounded soldiers from OEF/OIF theaters experienced wounds to the head, face, or neck (Okie 2005). From 2000 to 2010, the number of military service members diagnosed with TBI has nearly tripled (DVBIC 2011). Mild TBI, also called concussion, often goes underreported since period of unconsciousness may be negligible and medical attention may not be sought. Therefore the actual annual incidence of TBI is thought to be higher than currently estimated.

TBI is a major public health concern for civilians as well as members of the military. Each year, an estimated 1.7 million individuals in the United States sustain a TBI (CDC 2010). Of those, approximately 52,000 individuals die each year from their injuries. According to the U.S. Centers for Disease Control and Prevention (CDC), each year an estimated 124,626 people with TBI experience long-term impairment or disability from their injury (CDC 2011a).

Determining the appropriate method and timing of treatment for an individual with TBI depends on a number of factors, including severity of injury, stage in recovery, and premorbid, comorbid, and environmental conditions, unique to every individual. The focus of treatment changes as a patient progresses from the acute, immediate phase after injury to more chronic, long-term stages of recovery. In the acute phase, treatment may primarily focus on increasing the patient’s chances of survival while reducing the long-term impact of the sustained injury or injuries (Meyer et al. 2010). Though effects of TBI often coincide shortly after injury, long-lasting effects of TBI do not always appear immediately after injury; likewise, the acute-stage impairments may recover with or without treatment and rehabilitation (Lovell et al. 2003). (Also known as spontaneous recovery, this type of recovery can occur at any time and is difficult to predict or control for in research.) In the chronic stage of recovery, the goals of rehabilitation are functional recovery of long-lasting physical, cognitive, and emotional impairments.

The IOM committee iteratively developed a protocol to address the following questions:

The committee identified 90 studies that met selection criteria. These studies signal there is benefit from some forms of CRT for TBI. However, the evidence for the therapeutic value of CRT is variable across domains and is currently insufficient overall to provide definitive guidance for the development of clinical best practice, particularly with respect to selecting the most effective treatment(s) for a particular patient.

The committee found the insufficiency of the evidence was due to a number of identified limitations in the research designs, commonly seen among studies evaluating rehabilitation strategies, including the heterogeneity and lack of operational definitions of different forms of CRT; small sample sizes; the variety of premorbid conditions, comorbidities, and environmental factors that may moderate the value of a given form of CRT across patients; and the range of outcomes that may be targeted. Some of the studies did not identify injury severity or recovery phase for included participants, or there was a lack of uniformity across studies in defining these criteria. Another limitation is that objective measures sensitive to the cognitive complaints of patients with mild TBI are lacking in many instances and the use of subjective self-report measures as an alternative is problematic when studying treatments that cannot be blinded. Also, studies of subacute treatments require relatively large samples because the ability to gauge the impact of a treatment regimen in individual patients is diminished in the context of rapid and variable natural recovery. Thus, in practice clinicians may defer substantial resource investment in CRT to later stages of TBI when it becomes clear which problems and impairments will persist long term.

The committee focused on studies that used one or several forms of CRT to ameliorate the effects of TBI, and evaluated the outcomes of these studies to determine the short-term, long-term, or patient-centered (i.e., real-world functioning) outcomes, when reported, of the therapies. To determine efficacy, the committee relied on studies that compared the primary CRT treatment to either no treatment or a non-CRT treatment. To determine effectiveness, the committee evaluated studies comparing CRT treatment to another form of CRT. In other words, varying comparators were not considered more or less useful, only that they answer different questions about the value of CRT for TBI.

In an interactive and collaborative process, the committee graded the overall body of evidence for each CRT category (by domain, TBI severity, and recovery phase [for example, CRT interventions for attention deficits in moderate-severe TBI patients in the chronic phase of recovery]). To draw conclusions about treatment efficacy or effectiveness, the committee qualitatively assessed the strength of individual studies, as well as the consistency of treatment effect among studies. The strength of each study was based on an iterative quality assessment, considering study design, size of the sample, reported characteristics of the sample (e.g., injury severity) and treatment (e.g., dosage, frequency, and timing), control for potentially confounding factors, magnitude of the treatment effect, statistical significance of the findings, and the length of follow-up. The committee gave more weight to controlled designs than uncontrolled (e.g., results of RCTs were given more weight than results from pre-post single group designs). Conclusions were not based solely on findings from uncontrolled studies, however the committee included pre-post single group designs and single subject, multiple baseline experiments in the review because uncontrolled studies may include useful information about nascent interventions or lend support to a controlled design with similar results. Where evidence was informative, the committee specifically identifies the treatment mode and cites the one or more studies that led to its conclusion. Box S-2 provides the description of evidence grades used to judge the sufficiency of the evidence. It is important to note that evidence ruled “limited” does not mean the intervention was inadequate; it may simply mean a better-designed or -executed study is necessary to show meaningful short- or long-term treatment effect. In reviewing the evidence regarding the efficacy and effectiveness of CRT, the committee found no studies addressing cognitive deficits in the acute phase of recovery following TBI, few studies addressing cognitive treatment for individuals with mild injuries—of those, only in the chronic phase—and few studies addressing treatment of those with moderate to severe injuries in the subacute phase. The committee did not identify any relevant literature for treatment of visuospatial perception deficits, which are more common after stroke than TBI. Table S-1 summarizes the committee’s conclusions for CRT, reflected in Chapters 7 through 11 in narrative form following detailed descriptions of individual studies.

In its conclusions, the committee separated evidence grades by cognitive domain and multi-modal/comprehensive CRT, further subdividing by reported injury severity, recovery phase, and the treatment approach (i.e., restorative or compensatory). Evidence grades were based on the breadth of literature assessed for each cognitive domain and multimodal/comprehensive CRT; the table does not reflect the grades for individual studies.

Considering the dearth of conclusive evidence identified to date, the committee recommends an investment in research to further develop CRT. As reflected in Table S-1, the evidence provides limited, and in some cases modest, support for the efficacy of CRT interventions. However, the limitations of the evidence do not rule out meaningful benefit. The committee defined limited evidence as “Interpretable results from a single study or mixed results from two or more studies” and modest evidence as “Two or more studies reporting interpretable, informative, and largely similar results” (see Box S-2 for all evidence grades and definitions). The committee emphasizes that conclusions based on the limited evidence regarding the effectiveness of CRT does not indicate that the effectiveness of CRT treatments are “limited”; these the limitations of the evidence do not rule out meaningful benefit. In fact, the committee supports the ongoing clinical application of CRT interventions for individuals with cognitive and behavioral deficits due to TBI. One way policy could reflect the provision of CRT is to facilitate the application of best-supported techniques in TBI patients in the chronic phase (where natural recovery is less of a confound), with the proviso that objectively measurable functional goals are articulated and tracked and that treatment continues only so long as gains are noted.

To acquire more specific, meaningful results from future research the committee has laid out a comprehensive research agenda to overcome challenges in determining efficacy and effectiveness. These recommendations are therefore possible because the evidence review signals some promise. However, to improve future evaluations of efficacy and effectiveness of CRT for TBI, larger sample sizes and volume of data are required, particularly to answer questions about which patients benefit most from which treatment(s). This requires more extensive funding of experimental trials and a commitment to mining clinical practice data in the most rigorous way possible. For such approaches to be most informative, the variables that characterize patient heterogeneity, the outcomes that are used to measure impact of treatment, and the treatments themselves need to be defined and standardized. In addition, more rigorous review of potential harm or adverse events related to specific CRT treatments is necessary.

Nascent efforts at standardization are underway across multiple civilian and military funding agencies. These efforts should take place in collaboration. The National Institutes of Health (NIH) common data element (CDE) initiative, a National Institute on Disability and Rehabilitation Research (NIDRR)–supported center on treatment definition, and several practice-based evidence studies are helping to better characterize TBI patients, treatments, and relevant outcomes. Practice-based evidence studies include the Congressionally Mandated Longitudinal Study on TBI, DVBIC Study on Cognitive Rehabilitation Effectiveness for Mild TBI (SCORE!), Millennium, and TBI Model Systems. These cohorts involve collaborative efforts between DoD and the VA via the Defense and Veterans Brain Injury Center (DVBIC). The committee recognizes the ongoing emphasis from both government agencies to enhance collaboration for TBI and psychological health of service members and veterans through the VA/DoD Joint Executive Council Strategic Plan to integrate health care services (VA/DoD 2009b). This collaboration is especially important in evaluating and maintaining transitions in care and long-term treatment for injured soldiers as they move out of the MHS and into the VA’s health care system, the Veterans Health System.

Because CRT is not a single therapy, questions of efficacy and effectiveness need to be answered for each cognitive domain and by treatment approach. Nevertheless, within a specific cognitive domain, there must be sufficient research and replication for conclusions to be drawn. Standard definitions for intervention type, content, and key ingredients will be critical to developing evidence-based practice standards. The documentation of interventions in practice and more frequent use of manual-based interventions in research will help validate measures of treatment fidelity. For example, while there is evidence from controlled trials that internal memory strategies are useful for improving recall on decontextulized, standard tests of memory, there is limited evidence that these benefits translate into meaningful changes in patients’ everyday memory either for specific tasks/activities or for avoiding memory failures. Therefore, an increased emphasis on functional patient-centered outcomes would allow for a more meaningful translation from cognitive domain to patient functioning.

The committee recommends DoD undertake the following:

The current evidence for CRT does not point a clear path to conclusive findings regarding CRT efficacy or effectiveness in the treatment of TBI-related deficits. The committee thoughtfully considered the challenges it faced throughout the study process. The committee’s recommendations aim to aid the Department of Defense in addressing a significant problem: Members of the military (and civilians) experience high rates of TBI, and TBI often causes significant cognitive, physical, or psychosocial deficits requiring rehabilitation. In light of the lack of conclusive evidence, either because interventions or approaches are new and still being studied, or study designs were flawed, the committee has identified these recommendations as a way forward for the Military Health System.