Heterogeneous treatment effects represent a major issue for medicine as they undermine reliable inference and clinical decision-making. To overcome the issue, the current vision of precision and personalized medicine acknowledges the need to control individual variability in response to treatment. In this paper, we argue that gene-treatment-environment interactions (G × T × E) undermine inferences about individual treatment effects from the results of both genomics-based methodologies—such as genome-wide association studies (GWAS) and genome-wide interaction studies (GWIS)—and randomized controlled trials (RCTs). Then, (...) we argue that N-of-1 trials can be a solution to overcome difficulties in handling individual variability in treatment response. Although this type of trial has been suggested as a promising strategy to assess individual treatment effects, it nonetheless has limitations that limit its use in everyday clinical practice. We analyze the existing variability within the designs of N-of-1 trials in terms of a continuum where each design prioritizes epistemic and pragmatic considerations. We then support wider use of the designs located at the pragmatic end of the explanatory-pragmatic continuum. (shrink)

Justin Biddle and Quill Kukla have introduced the concept of phronetic risk to refer to epistemic risks emerging in activities that either are conditions for empirical reasoning or included in empirical reasoning and that have to be weighted according to different values and interests. In this paper, I show how a phronetic risk arises in research agenda setting. Given the prevalence of noncommunicable diseases associated with diet, there is a need for science-based nutritional public health interventions. However, how the relation (...) between nutrition and health should be studied is a contested matter. I argue that the choice between different approaches of studying nutrition-related disease causation involves considerable phronetic risks that cannot be managed by researchers alone. Funding agencies, non-governmental organisations and science policy decision makers should be considered epistemically relevant actors. (shrink)