Mechanistic understanding in clinical practice: complementing evidence-based medicine with personalized medicine.

In the last century, medicine has undergone an unprecedented wave of radical changes. From the implementation of surgery up to the development of single gene-targeted therapies, clinical decision making has become increasingly complex to handle. Today, this complexity needs to be rethought in the light of two emerging paradigms: evidence-based medicine ( EBM) and personalized medicine ( P- Med). The new availability of diverse sources of scientific evidence raises significant issues concerning how clinicians will compare, evaluate and orient their decisions in front of a rapidly growing plethora of therapies, procedures, medical technologies and drugs. In this paper, we compare the background visions behind these two paradigms, evaluating their respective relevance for present and future clinical decision making. In particular, we argue that EBM and P- Med are driven by two diverse modes of reasoning about 'evidence making' in medicine. EBM is grounded on statistical notions and epidemiological data, generally gathered through systematic meta-reviews of randomized controlled trials; P- Med, instead, is grounded on mechanistic explanations of molecular interactions, metabolic pathways and biomarkers. While both paradigms are epistemically sound, we argue that they cannot, and should not, be hybridized into a unique model. Rather, they ought to represent two compatible, but alternative ways of informing the clinical practice. Hence, we conclude that clinicians may expect to see their responsibility increasing as they will deal with diverse, but equally compelling, ways of reasoning and deciding about which intervention will qualify as the 'best one' in each individual case. [ABSTRACT FROM AUTHOR]