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ASSOCIATION v CAUSATION Helping students recognize the difference between association and causation is fundamental to the scientific process. While this may be a philosophical topic for faculty, it is a vital skill for our students who too often fail to appreciate the difference. In a speech to the Section of Occupational Medicine of the Royal Medical Society in 1965, Sir A. B. Hill summarized his approach to analyzing observations to determine if they “reveal an association between two variables, perfectly clear-cut and beyond what we would care to attribute to the play of chance. What aspects of that association should we especially consider before deciding that the most likely interpretation of it is causation?” Hill’s nine items are as follows: (1) Strength of association Consistency Specificity Temporality Biological gradient (i.e. dose response) Plausibility Coherence Experiment Analogy Hill then notes the importance of the “useful corrective for statisticians to stress, and to teach the need for tests of significance merely to serve as guides to caution before drawing a conclusion, before inflating the particular to the general.” In 2007, Giovannoni and Ebers (2) applied these ideas to an analysis of multiple sclerosis (MS). They concluded that “proving that an association between an environmental factor and MS is causal is complicated and may take years or even decades to achieve. There are several theories to explain how infection may cause MS, some of which are more plausible than others.” The theories include molecular mimicry, persistent infections, direct infection, immune disregulation, and dual infections. There is a great deal of overlap between these theories, and the analysis is confounded by genetic and environmental factors.(2) We intend to construct an exercise initially using environmental data such as sunlight (or latitude) as compared to the incidence of MS on a global scale. Additional comparisons could include infectious disease incidence, HLA distributions, and personal habits such as smoking. It’s clear that there are many other scenarios that could be applied to this sort of analytical approach. We anticipate that the described “association v causation” framework will inspire others to develop additional topics for use at a variety of levels. REFERENCES 1. Hill AB. The environment and disease: association or causation? Proc R Soc Med 1965; 58:295–300. 2. Giovannoni G and G Ebers. Multiple sclerosis: the environment and causation 2007 Curr Opin Neurol 20:261-268.