considered several important issues, including the quality of the study; its relevance; issues of error, bias, and confounding; the diverse nature of the evidence; and the study population.

The committee classified the evidence for association between exposure to a specific agent and a health outcome into one of five previously established categories. The categories closely resemble those used by several IOM committees that evaluated vaccine safety (IOM, 1991, 1994a), herbicides used in Vietnam (IOM, 1994b, 1996, 1999), and indoor pollutants related to asthma (IOM, 2000). Although the categories imply a statistical association, the committee had sufficient epidemiologic evidence to examine statistical associations for only one of the agents under study (i.e., depleted uranium); the epidemiologic evidence for the other agents examined (i.e., sarin, pyridostigmine bromide, and anthrax and botulinum toxoid vaccines) was very limited. Thus, the committee based its conclusions on the strength and the coherence of the data in the available studies. In many cases, these data distinguished differences between transient and long-term health outcomes related to the dose of the agent. Based on the literature, it became incumbent on the committee to similarly specify the differences between dose levels and the nature of the health outcomes. This approach led the committee to reach conclusions about long- and short-term health effects, as well as health outcomes related to the dose of the putative agents. The final conclusions represent the committee’s collective judgment. The committee endeavored to express its judgments as clearly and precisely as the available data allowed. The committee used the established categories of association from previous IOM studies, because they have gained wide acceptance for more than a decade by Congress, government agencies, researchers, and veteran groups.

  • Sufficient Evidence of a Causal Relationship. Evidence is sufficient to conclude that a causal relationship exists between the exposure to a specific agent and a health outcome in humans. The evidence fulfills the criteria for sufficient evidence of an association (below) and satisfies several of the criteria used to assess causality: strength of association, dose–response relationship,1 consistency of association, temporal relationship, specificity of association, and biological plausibility.

  • Sufficient Evidence of an Association. Evidence is sufficient to conclude that there is a positive association. That is, a positive association has been observed between an exposure to a specific agent and a health outcome in human studies in which chance, bias, and confounding could be ruled out with reasonable confidence.

  • Limited/Suggestive Evidence of an Association. Evidence is suggestive of an association between exposure to a specific agent and a health outcome in

1  

A dose–response relationship refers to the finding of a greater health effect (response) with higher doses of an agent.



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