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tional epidemiology). Here, however, we review all three approaches: basic science, observational epidemiology, and intervention studies. Rather than review each approach with the aim of examining a preponderance of evidence, this report considers the pattern of evidence across the different areas of scientific study. The pattern of evidence analysis, described in detail by Cordray (1986) and discussed below, has been used in an earlier National Research Council report (1995); it is particularly useful when considering causal inferences across different fields of study.


Basic Sciences

From the perspective of basic sciences, studies are designed and performed to isolate discrete events that are carefully engineered to deliver a set of exposures characterized by replicable frequency, dose, and duration. These exposures are applied to isolated anatomical and physiological systems (e.g., muscles, nerves) that are then measured for anatomical damage or adverse biochemical changes. For example, the question of the extent to which repetitive lifting is related to back disorder can be examined with the assistance of an apparatus that applies a repeatable frequency, dose, and duration of a load to a cadaver or relevant animal models; then biological measures, such as tissue biopsy for measurement of biochemical changes consistent with damage, can be obtained. The results from this type of study provide data on basic mechanisms to show, for example, whether repetitive compression similar to that involved during lifting is associated with tissue damage, and the extent to which damage can be identified as following these discrete events. In the laboratory context, the goal is to isolate events of exposure and outcome to the greatest degree possible, by precise and refined measurement and by controlling extraneous environmental conditions (e.g., temperature, humidity).

The results provide confidence in drawing inferences on whether tissue damage follows application of exposure, but these inferences are tempered by several factors. First, isolation of human tissue for study (such as a particular muscle or group of muscles) may demonstrate damage, but it may remain unclear whether the load applied in the experiment is similar to that experienced by humans. There are studies that report precise physiological abnormalities but no correlation with symptoms or function of the person being studied. These fine measurements may be trivial, or they may represent an early disease process that will become manifest only later. Second, the complexity of the human biological system includes compensatory mechanisms that are excluded in studies that focus on the isolation of mechanisms. For example, some combination of muscle

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