title: Alternatives to Rothman's approach for assessing synergism (or antagonism) in cohort studies.
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.
mesh_terms: D004813:Epidemiology; D006801:Humans; D008962:Models, Theoretical; D011336:Probability