Theory and methodology: essential tools that can become dangerous belief systems.

We thank Dr. Karp for his interest [1] in our paper [2]. We agree on some points, but our theoretical description differs from his in ways leading to important divergences for teaching and practice. We also see a danger of overextending abstract theory (with its inevitable and extensive simplifications) into practice [3], especially when the practical questions are causal but the theory applied lacks an explicit, sound longitudinal causal model to address these questions. As we will explain, a defect in the “study base” theory Dr. Karp adopts as a foundational belief system is that it takes as a foundation a parameter affected by baseline risk factors—including exposure when that has effects on follow-up or disease. It consequently leads to biases and misconceptions of the sort documented elsewhere [4, 5] and below, which require a coherent theory of longitudinal causality to address. Our divergence from Dr. Karp thus raises the issue of the role of theory and methods in research, although matching serves to illustrate our points in a familiar epidemiologic context.