from peer-reviewed publications. In the case of an as intensively studied agent as asbestos, however, the committee considered that the findings of most studies would be published. It is possible that only statistically significant or particularly notable results on nonrespiratory endpoints would be included in the published reports on the cohort studies, and this could lead to reporting bias for cancers at the designated sites.

Once germane studies have been identified, they may undergo evaluation so that they can be classified according to the quality of the evidence that they provide. They may be evaluated systematically according to a standardized protocol and placed into tiers on the basis of their quality. In a systematic review, results of studies may be qualitatively evaluated and subjected to an overall judgment; additionally, data may be combined to derive a quantitative summary and to explore variation in results among studies. Analyzing aggregated summaries of studies is often referred to as meta-analysis; on occasion, data from studies are obtained at the level of individual participants and jointly analyzed, an approach sometimes referred to as pooled analysis. Statistical approaches for quantitative meta-analysis have been developed (Petitti 2000), as well as methods for detecting publication bias in meta-analyses (Peters et al. 2006).

Guidelines for causal inference have long been used; perhaps the best-known are those offered in the first report of the US surgeon general on smoking and health (HEW 1964):

  • The consistency of the association.

  • The strength of the association.

  • The specificity of the association.

  • The temporal relationship of the association.

  • The coherence of the association.

The guidelines provide principles for interpreting epidemiologic evidence in a context set by biologic plausibility and the coherence of different lines of evidence. This committee has used such criteria in meeting its charge.

Specificity refers to a unique exposure-disease relationship, which is characteristic of diseases caused by infectious organisms. The concept has also been applied for investigating the contribution of physical and chemical agents to disease (Weiss 2002). The association of asbestos with mesothelioma constitutes one of the few examples of a high degree of specificity for a toxic agent and cancer risk, but the committee gave minimal weight to the criterion of specificity because the cancer sites under consideration have multiple causes and more will likely be identified.

From the outset, the committee recognized that asbestos fibers are known to be carcinogenic and that its conclusions with regard to the cancers specified in its charge would rest heavily on the epidemiologic evi-



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