Opinion ID: 1919140
Heading Depth: 1
Heading Rank: 15

Heading: Determining General Causation

Text: While important, a positive association presents only one piece of the causation puzzle. Once an association has been found between exposure to an agent and development of a disease, researchers consider whether the association reflects a true cause-effect relationship. [66] As noted, [e]pidemiologists use causation to mean that an increase in the incidence of disease among the exposed subjects would not have occurred had they not been exposed to the agent. [67] But determining causation differs from the objective inquiry into relative risk. An assessment of a causal relationship is not a scientific methodology as that term is used to describe logic (like a syllogism) and analytic methods. Instead, it involves subjective judgment. Experts consider several factors under different sets of criteria that can point to causation. Relative risk presents only one factor that they consider [68] : Drawing causal inferences after finding an association and considering [causation] factors requires judgment and searching analysis, based on biology, of why a factor or factors may be absent despite a causal relationship, and vice-versa. While the drawing of causal inferences is informed by scientific expertise, it is not a determination that is made by using scientific methodology. [69] For example, government agencies and some experts use a weight-of-the-evidence methodology. That methodology comprehensively analyzes the data from different scientific fields, primarily animal tests and epidemiological studies, to assess carcinogenic risks. [70] As Justice Stevens has noted, it cannot be intrinsically `unscientific' for experienced professionals to arrive at a conclusion by weighing all available scientific evidence when the Environmental Protection Agency uses this methodology to assess risks. [71] But no generally agreed-upon method exists for determining how much weight to apply to particular types of studies. [72] Alternatively, the Reference Manual sets out the Bradford Hill factors that epidemiologists consider to assess general causation. The U.S. Surgeon General first suggested these criteria in 1964; in 1965, Sir Austin Bradford Hill expanded on them. [73] The factors include (1) temporal relationship, (2) strength of the association, (3) dose-response relationship, (4) replication of the findings, (5) biological plausibility, (6) consideration of alternative explanations, (7) cessation of exposure, (8) specificity of the association, and (9) consistency with other knowledge. [74] The Reference Manual explains that one or more causation factors may be absent even when a true causal relationship exists. [75] In addition, experts emphasize that [s]ince causal actions of exposures are neither observable nor provable, a subjective element is present in judging whether, for a given exposure, such an action exists. As a result, scientists may differ both in terms of interpretation of available evidence in support of criteria used to aid causal inference, and in relative weight assigned to each criteria. [76] Here, we comment only on the factors that could raise questions on remand.