The Applicability of N: Ancient Debates and Modern Experimental Design

Medicine has always been characterized by a tension between the particular and the general. A clinician is obligated to treat the individual in front of her, yet she accomplishes this task by applying generalized knowledge that describes an abstract average but not necessarily a specific person. Efforts to systematize this process of moving between the particular and the general have led to the development of randomized controlled trials and large observational studies. Inclusion of tens of thousands of people in such studies, it is argued, will enhance the applicability of the data to more individual circumstances. Yet, as genetic sequencing data have become more widely obtained and used, there has been an increased focus on what has been broadly termed "precision medicine", a highly individualized approach to therapeutics. Moreover, advances in statistical methods have enabled researchers to use N-of-1 study data-traditionally considered too individualized to be broadly applicable-in new ways. This paper contextualizes these apparently modern debates with reference to historical arguments about methods of disease diagnosis and treatment, and earlier physicians' concerns about the tension between the particular and the general that is intrinsic to medical practice.