The committee’s first step was to identify the literature it would review. It began its work by overseeing extensive searches of the peer-reviewed medical and scientific literature (Appendix B). It identified epidemiologic studies of persistent health outcomes associated with exposure to hydrazines, red fuming nitric acid, hydrogen sulfide, oil-fire byproducts, and diesel-heater fumes, as directed by PL 105–277 and PL 105–368. At the request of the Department of Veterans Affairs, the committee also identified epidemiologic studies on persistent health outcomes associated with exposure to fuels (for example, jet fuel and gasoline) used during the Gulf War.
The searches retrieved over 33,000 potentially relevant references. All searches were completed early in 2004; relevant studies published later will be reviewed by future IOM committees. After an assessment of the titles and abstracts in the results of the initial searches, the committee focused on some 800 potentially relevant epidemiologic studies for review and evaluation. The committee reviewed epidemiologic studies of fuels and combustion products rather than the numerous components of those agents. Those studies were assessed for evidence of associations between the agents of interest and persistent health outcomes in humans. The committee used its collective judgment in selecting studies thought to reflect the types of exposures that Gulf War veterans might have experienced. Although Gulf War veterans were exposed to multiple complex mixtures, epidemiologic studies are not typically designed to address such types of exposures.
Because only a few studies were related directly to veterans’ exposures, the committee reviewed primarily occupational studies of populations that had been exposed to the agents of interest. Those studies often included people whose exposures had been over a lifetime (such as exposure to air pollution in their communities) or workers employed in particular industries over many years. In contrast, the exposures of veterans in the Persian Gulf were of relatively short duration with varying degrees of intensity. Therefore, the exposures experienced during the Gulf War might only approximate the exposures described in the occupational literature reviewed in this report. The conclusions as to statistical associations based on occupational and other types of studies are meant to serve as a guide to potential health effects associated with specific agents.
The committee adopted a policy of using only peer-reviewed published literature as the basis of its conclusions. Publications that were not peer-reviewed had no evidentiary value for the committee; that is, they were not used as evidence for arriving at conclusions about the degree of association between exposure to a particular agent and adverse health effects. The process of peer review by fellow professionals, which is one of the hallmarks of modern science, ensures high standards of quality but does not guarantee the validity of a study or the ability to generalize results. Accordingly, committee members read each study critically and considered its relevance and quality. In some instances, non-peer-reviewed publications provided background information for the committee and raised issues that required further literature searches. The committee did not collect original data, nor did it perform any secondary data analysis.
With that orientation to the committee’s task, the following sections provide a brief discussion of the value of epidemiologic studies, the committee’s inclusion criteria for review of those studies, considerations in evaluating the evidence or data provided by the studies, and the categories of association that are used to draw conclusions about the strength of the evidence presented in the studies.