BOX 5-1

Five Categories Used by IOM to Classify Associations (IOM 2003)

Sufficient Evidence of a Causal Relationship


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 sufficient evidence of an association (below) and satisfies several of the guidelines used to assess causality: strength of association, dose-response relationship, consistency of association, biologic plausibility, and a temporal relationship.


Sufficient Evidence of an Association


Evidence from available studies is sufficient to conclude that there is a positive association. A consistent positive association has been observed between exposure to a specific agent and a specific health outcome in human studies in which chance and bias, including confounding, could be ruled out with reasonable confidence. For example, several high-quality studies report consistent positive associations, and the studies are sufficiently free of bias, including adequate control for confounding.


Limited/Suggestive Evidence of an Association


Evidence from available studies suggests an association between exposure to a specific agent and a specific health outcome in human studies, but the body of evidence is limited by the inability to rule out chance and bias, including confounding, with confidence. For example, at least one high-quality study reports a positive association that is sufficiently free of bias, including adequate control for confounding. Other corroborating studies provide support for the association, but they were not sufficiently free of bias, including confounding. Alternatively, several studies of less quality show consistent positive associations, and the results are probably not due to bias, including confounding.


Inadequate/Insufficient Evidence to Determine Whether an Association Exists


Evidence from available studies is of insufficient quantity, quality, or consistency to permit a conclusion regarding the existence of an association between exposure to a specific agent and a specific health outcome in humans.


Limited/Suggestive Evidence of No Association


Evidence from well-conducted studies is consistent in not showing a positive association between exposure to a specific agent and a specific health outcome after exposure of any magnitude. A conclusion of no association is inevitably limited to the conditions, magnitudes of exposure, and length of observation in the available studies. The possibility of a very small increase in risk after exposure studied cannot be excluded.

categorizations are still valid or should be changed. Each health-outcome section below brief summarizes the evidence as described in the 2003 IOM report, reviews the new evidence, and presents conclusions drawn from the totality of the epidemiologic evidence. Appendix E presents tables of details on each of the new studies. Whenever possible, the committee evaluated the associations between TCE or PCE and the end points and reported findings specifically on those solvents. If a study addressed solvent mixtures, the evidence was examined and a category of association was determined with the default presumption that there was not information specifically on TCE or PCE. The committee expands on IOM’s approach in Chapter 7 by explicitly considering how the toxicologic evidence presented in Chapter 4 adds to the weight of evidence in characterizing health risks related to the TCE and PCE.



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