The committee began its work by overseeing extensive searches of the peer-reviewed medical and scientific literature, including published articles, other peer-reviewed reports, and dissertations. The searches retrieved over 30,000 potentially useful epidemiologic studies, and their titles and abstracts were reviewed. The committee focused its attention on clinical and epidemiologic studies of adults with long-term health effects that resulted from TBI by any mechanism, such as occupational injury, motor-vehicle collision, sports injury, gunshot wound, or other act of violence, including military combat. Studies of patients with TBI due to malignancy, stroke, infection, ischemia, other diseases or disorders of the brain, intoxication, or oxygen deprivation were not considered. The committee did not systematically review studies of young children, the elderly, or brain-injured patients in litigation for compensation claims. Its review excluded case reports, case series with few participants, and studies of acute outcomes that resolved within days to a few months (that is, less than 6 months). The committee did not review general studies of “disability” as a gross measure of morbidity but rather evaluated studies that associated TBI with specific health outcomes.

After its assessment of the 30,000 titles and abstracts, the committee members identified about 1,900 studies for further review. Those studies were objectively evaluated without preconceived ideas about health outcomes or the existence or absence of associations. The committee adopted a policy of using only peer-reviewed published literature or unpublished reports that had undergone rigorous peer review, such as dissertations and some government reports, as the basis of its conclusions. The process of peer review by fellow professionals increases the likelihood of high quality but does not guarantee the validity of a study or the ability to generalize its findings. Accordingly, committee members read each study critically and considered its relevance and quality. They did not collect original data, nor did they perform any secondary data analysis.


Many of the studies reviewed by the committee presented substantial obstacles to determining associations between TBI and long-term health outcomes in that they were beset by limitations that are commonly encountered in epidemiologic studies, including lack of a representative sample, selection bias, lack of control for potential confounding factors, self-reporting of exposure and health outcomes, premorbid status, and outcome misclassification.

Some of the studies reviewed did not specify the time between injury and followup, so the committee could not determine whether the outcome lasted longer than 6 months. Many studies involved populations in rehabilitation centers where subjects might have had multiple injuries that included TBI but the initial TBI might have been due to a stroke or a brain tumor; these studies presented several problems, such as lack of representativeness of the younger veteran population and an inherent selection bias, for example, if they included only people who had health insurance.

Most cohort studies rely on self-reporting of symptoms on questionnaires. Symptom self-reporting potentially introduces reporting or recall bias, which occurs when the group being studied reports what it remembers more frequently than a comparison group does. Reporting bias

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