Comprehensive targeting: the avenue to a personalized, highly effective, innocuous, and cost-effective medicine of the future

Abstract

Arguably, the current era of “ one-size fits all ” medical strategies is associated with suboptimal efficacy, un necessary toxicity, and wasting of resources in healthcare. Why ? The currently dominating paradigm of medical care, named “ evidence-based medicine ” claims that the ultimate truth for medicine is found in randomized multi-center trials and meta-analyses, in particular those focusing on mortality. The assumption is that statistics describing the average efficacy of a therapy in a large cohort included in a clinical trial will be predictive for the benefit of this therapy in future individual patients and will therefore represent the best therapeutic choice. This will typically include a significant number of individuals at such low risk that harm/benefit and cost/benefit ratios are such that in these, few events are avoided, many side effects are induced, and financial expense is substantial; likewise, those patients with highest risk may not get sufficiently intense therapy to circumvent an adverse clinical course. This neglect of the huge variability in genetic and phenotypic setup in mankind (reflected in genomics, epigenetics, proteomics etc.) which is of major importance for disease course and therapeutic efficacy relegates knowledge about individual variations in the pathophysiology, anatomic presentations and temporal course in a given disease ( “ the art of medicine ” ) to second class information. As the limitations of such a “ one size fits all ” approach are increasingly evident (1) , we need to progress beyond “ evidence-based medicine ” towards a “ knowledge-based medicine ” that embraces a broader view on a patient by giving adequate weight to all knowledge about a patient and his/her disease, integrating cohort information with molecular information about the individual.