agent and disease is the exception in large populations (IOM 1994b). The committee evaluated the data and based its conclusions on the strength and coherence of the data in the selected epidemiologic studies that met its inclusion criteria.


The committee’s next step, after securing the full text of about 800 epidemiologic studies, was to determine which studies would be included in the review as primary or support studies. For a study to be included in the committee’s review, it had to meet these criteria: methodologic rigor, identification of class or agent, specificity of health outcome, an exposure assessment, and in some cases an exposure-free interval. Studies that met the committee’s criteria are referred to as primary studies. For relevance to the Gulf War veterans, the committee focused on long-term health outcomes that persist after exposure ceases.

Methodologic Rigor

The study had to be a published in a peer-reviewed journal, had to include details of its methodology, had to include a control or reference group, had to have the statistical power to detect effects, and had to include reasonable adjustment for confounders. Case studies and case series were generally excluded from the committee’s consideration (see Appendix C).

Identification of Class or Agent

The study had to identify fuels, combustion products, or propellants as specified in the legislation. Because it is more difficult to draw conclusions on specific agents in studies of multiple chemical exposures, studies of this type were not considered primary. If agents were not specifically identified, the study would have been included if it was of an occupation that involved a fuel or combustion product exposure similar to veterans’ presumed exposures in the Persian Gulf.

Specificity of Outcome

The study had to specify a distinct outcome rather than a nonspecific group of health outcomes. Studies of broad disease categories (for example, diseases of the nervous system) were not considered as primary studies. Lack of specificity occurs primarily in mortality studies that examine all-cause mortality (such as deaths from all nervous system diseases) as opposed to cause-specific mortality (such as from Parkinson’s disease). All-cause mortality studies were excluded unless they analyzed specific health outcomes.

Exposure Assessment and Exposure-free Interval for Reversible Effects

The committee preferred studies that had an independent assessment of exposure rather than self-reported exposure. For example, studies that used assessment by an industrial hygienist or with a job-exposure matrix (JEM) were weighted more heavily by the committee.

To be relevant to Gulf War veterans, a study had to examine long-term rather than short-term outcomes. For some outcomes (for example, dermatologic, neurologic, and respiratory), long-term effects can be determined only after an exposure-free interval of weeks to months

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