In addition to the above exclusions, it should be noted that animal studies had a limited role in the committee’s assessment of association between the putative agent and health outcome. Animal data were used for making assessments of biologic plausibility in support of the human epidemiologic data rather than as part of the weight-of-evidence to determine the likelihood that an exposure to a specific agent might cause a long-term outcome.
The committee did not collect original data or perform any secondary data analysis. It did, however, calculate confidence intervals, when a study did not provide them, on the basis of the number of subjects, the relative risk or odds ratio, or the p value. Confidence intervals calculated by the committee are identified as such in the health-outcome chapters (Chapters 5–9).
The committee adopted a policy of using only published, peer-reviewed literature to draw its conclusions. Although the process of peer review by fellow professionals enhances the likelihood that a study has reached valid conclusions, it does not guarantee it. Accordingly, committee members read each study and considered its relevance and quality. The committee classified the evidence of an association between exposure to a specific agent and a specific health outcome into one of five categories. The categories closely resemble those used by several Institute of Medicine (IOM) committees that have evaluated vaccine safety (IOM, 1991, 1994a), herbicides used in Vietnam (IOM, 1994b, 1996, 1999), and indoor pollutants related to asthma (IOM, 2000). Although the first three categories imply a statistical association, the committee’s conclusions are based on the strength and coherence of the findings in the available studies. The conclusions (Chapters 5–9) represent the committee’s collective judgment.
The committee endeavored to express its judgment as clearly and precisely as the available data allowed, and it used the established categories of association from previous IOM studies because they have gained wide acceptance over more than a decade by Congress, government agencies, researchers, and veterans groups. However, inasmuch as each committee member relied on his or her training, expertise, and judgment, the committee’s conclusions have both quantitative and qualitative aspects. In some cases, committee members were unable to agree on the strength of evidence of an association under review; in such instances, if a consensus conclusion could not be reached, the committee agreed to present both points of view in the text.
The five categories describe different levels of association and sound a recurring theme: the validity of an association is likely to vary with the extent to which the authors reduced common sources of error in making inferences—chance variation, bias, and confounding. Accordingly, the criteria for each category express a degree of confidence based on the extent to which sources of error were reduced.
Evidence from available studies is sufficient to conclude that a causal relationship exists between exposure to a specific agent and a specific health outcome in humans, and the evidence is supported by experimental data. The evidence fulfills the guidelines for