ALTERNATIVES TO ROTHMAN'S APPROACH FOR ASSESSING SYNERGISM (OR ANTAGONISM) IN COHORT STUDIES1

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Abstract
K. J. Rothman has explored in some detail the issue of assessing the potential presence of synergism (or antagonism) In data generated from either a cohort or a case-control study. Arguing that the “natural” scale for quantifying the joint effects of two or more factors acting In combination is the probability scale, he has proposed a procedure based on a ratio-type Index for evaluating two-factor interaction in the presence of non-zero background effects. In this paper, the authors review the rationale underlying Rothman's approach for a cohort study. They then present what they maintain Is a simpler and more appropriate test procedure (utilizing a linear contrast of the observed risks) for the additive approximation to his basic probabilistic model of “no Interaction.” A likelihood ratio test based on his original model Is also proposed, as well as a closed form approximation to it. Finally, the assessment of Interaction In cohort studies involving exposure factors measured at more than two levels is addressed.

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