Are there pathophysiologic differences in the illness under study that may lead to a diminished treatment response?
Diseases with a single name may represent conditions with important pathophysiologic differences. These differences can sometimes lead to diminished treatment responses due to 1) divergence in pathogenetic mechanisms or 2) biologic differences in the causative agent. Hypertension in blacks, which has been observed to be relatively responsive to diuretics, and unresponsive to beta-blockers [7], provides an example of the former. This selective response reflects a state of relative volume excess that investigators now theorize may have served protective functions in their hot and arid ancestral environments [8]. Malaria provides an example of a condition that may vary because of biologic differences in the causative agent. Malaria treatment protocols vary depending on drug resistance patterns [9]. In these examples, clinicians should anticipate variation in response to treatment, and should temper hasty conclusions regarding the applicability of trial results.
