research. The committee, however, did not collect original data, nor did it perform any secondary data analysis.

In its evaluation of the peer-reviewed literature, the committee considered several important issues, including the quality and relevance of the studies; issues of error, bias, and confounding; the diverse nature of the evidence and the research; and the disparate populations being studied. Additionally, for many of the agents being studied (e.g., vaccines, PB, sarin) there were few epidemiologic studies, and much of the evidence was in the form of case studies and case reports, forms of publication that often do not provide sufficient evidence upon which to base conclusions about the statistical associations between illnesses and the agents under consideration.

TYPES OF EVIDENCE

The scientific literature on the putative agents varied from agent to agent in the number and type of published studies. For most agents, the epidemiological evidence was sparse. For only one agent was there a solid base of epidemiological studies from which the committee could draw conclusions. The extensive occupational studies of uranium workers provided a statistical foundation from which the committee could assess the strength of the association between uranium and adverse health effects. For the other agents, the committee had to rely primarily on a variety of human studies that had not been designed specifically to study adverse health effects related to the putative agents. Studies of patients with myasthenia gravis, for example, were designed primarily to examine the treatment effectiveness of PB, and had not been designed as robust epidemiologic studies (i.e., they often examined small populations or did not have control groups). The committee, however, adopted a uniform approach for evaluating the varied types of available evidence as reflected in the literature on each of the putative agents.

Animal and Other Nonhuman Studies

Studies of laboratory animals and other nonhuman systems are essential to understanding mechanisms of action, biologic plausibility, and providing information about possible health effects when experimental research in humans is not ethically or practically possible (Cohrssen and Covello, 1989; NRC, 1991). Such studies permit a potentially toxic agent to be introduced under conditions controlled by the researcher—such as dose,3 duration, and route of exposure—to probe health effects on many body systems. Nonhuman studies are also a valuable complement to human studies of genetic susceptibility. While nonhuman

3  

The term dose is used to denote the total amount of the agent to which an organism is exposed. Dose usually implies the “exposure dose” (i.e., the total amount of the agent penetrating [or given] to an organism by a particular route of exposure) (Ballantyne, 1992).



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