Consistency of Association

A consistent association requires that the association be found regularly in a variety of studies, for example, in more than one study population and with different study methods. However, consistency alone is not sufficient evidence of an association. The committee considered findings that were consistent in direction among studies of different designs to be supportive of an association. It did not require exactly the same magnitude of association in different populations to conclude that there was a consistent association. A consistent association could occur when the results of most studies were positive and the variations in measured effects were within the range expected on the basis of sampling error, selection bias, and confounding.

Thus, for a health effect to be considered associated with deployment there had to be corroboration, that is, replication of findings among studies and populations. The degree to which an effect could be consistently reproduced gave the committee confidence that they were observing a true effect.

Specificity of Association

Specificity of association is the degree to which exposure to a given stressor predicts a particular outcome. A positive finding is more convincing of causality when the association between the exposure and the health effect is specific to one or both than when the association is nonspecific to the exposure and the health effect. The committee recognized, however, that one-to-one specificity is not to be expected, given the multifactorial etiology of many of the health effects under examination.

Biologic Plausibility

Biologic plausibility reflects knowledge of the biologic mechanism(s) by which an agent could lead to a health outcome. That knowledge comes through mechanism-of-action or other studies in pharmacology, physiology, and other fields—typically in studies of animals. A biologically plausible mechanism may not be known when an association is first documented. Biologic plausibility was required by the committee only in drawing a conclusion of “sufficient evidence of a causal association” (see below); for the other categories of association, it was not necessary to demonstrate a biologically plausible mechanism.

CATEGORIES OF ASSOCIATION

The committee attempted to express its judgment about the available data as clearly and precisely as possible. The committee agreed to use the categories of association that have been established and used by previous Committees on Gulf War and Health and other Institute of Medicine (IOM) committees that have evaluated vaccine safety, effects of herbicides used in Vietnam, and indoor pollutants related to asthma (IOM 2000, 2003, 2005, 2006, 2007). These categories of association have gained wide acceptance over more than a decade by Congress, government agencies (particularly the Department of Veterans Affairs [VA]), researchers, and veterans groups.

The five categories below describe different levels of association and sound a recurring theme: the validity of an association is likely to vary to the extent to which common sources of error—chance variation and bias, including confounding—could be ruled out as the reason for



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