extensive literature searches. The VAO list has been supplemented over time in response to developments in the literature.

The information used by the committee was developed through a comprehensive search of relevant data bases. Public and commercial data bases covering biological, medical, toxicological, chemical, historical, and regulatory information were examined. The majority of these data bases were bibliographic, providing citations to scientific literature. Committee staff examined the reference lists of major review articles, books, and reports for relevant citations. Reference lists of individual articles were also scanned for pertinent citations. Search engines were used to scan for information posted on the Internet. Literature identification continued through September 30, 2000. The input received both in written and oral form from veterans and other interested persons at public hearings and in written submissions served as a valuable source of additional information.

This third biennial update concentrates on evaluating the evidence published following the completion of work on Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (IOM, 1994), Veterans and Agent Orange: Update 1996 (IOM, 1996), Veterans and Agent Orange: Update 1998 (IOM, 1999), and Veterans and Agent Orange: Herbicide/Dioxin Exposure and Type 2 Diabetes (IOM, 2000). For each health outcome, the new evidence is reviewed in detail. Conclusions are based on the totality of accumulated evidence, not just on recently published studies. In other words, new evidence is not interpreted alone but is put in the context of evidence addressed in previous reports.

The committee’s judgments have both quantitative and qualitative aspects; they reflect both the evidence examined and the approach taken to evaluate it. In VAO, the committee delineated how it approached its task so that readers would be able to assess and interpret the committee’s findings. By offering this information, the committee wished to make the report useful to those seeking to update its conclusions as new information was obtained. The committees responsible for subsequent reports have adopted the original committee’s approach.

The remainder of this chapter delineates the primary considerations underlying the evaluation process. A more complete description of methodological issues may be found in Chapter 5 of VAO and in Chapter 4 of Update 1996 and Update 1998.

Is Herbicide Exposure Statistically Associated with the Health Outcome?

The committee necessarily focused on a pragmatic question: What is the nature of the relevant evidence for or against a statistical association between exposure and the health outcome? The evidentiary base that the committee found to be most helpful derived from epidemiologic studies of populations—that is, investigations in which large groups of people are studied to determine the association between the occurrence of particular diseases and exposure to the substances at issue. To determine whether an association exists, epidemiologists

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