ABSTRACT
B. Wilffert,a J. J. Swen,b H. Mulder,c R. H. N. van Schaik,d
M. Nijenhuis,e L. Grandia,e A. H. Maitland-van der Zee,f
G. A. Rongen,g T. Schalekamp,f J. van derWeide,h A. de Boer,f
Evidence-based medicine applies guidelines developed on the basis
of consensus from randomized clinical trials (RCTs), observational
studies, and spontaneously reported adverse events. These RCTs are
performed in carefully selected patient populations studied under
strongly regulated conditions. It often is a challenge to translate
the results of RCTs to a specific patient in the real world. In RCTs
often (young) people having one particular disease are selected.
In daily clinical practice a significant part of the patients consists
of elderly individuals often having multiple morbidities. For the
majority of these patients still no evidence-based drug treatment
is yet available. Therefore in these situations there seems to be a
need for a more mechanism-based approach toward drug therapy
personalized for the individual patient to be able to work evidence
based. In this context evidence-based medicine could be defined
as efficacy that has been demonstrated on hard endpoints, like mortality, hospitalization, and costs of health care. Mechanism-based medicine can be defined as efficacy that has been demonstrated on intermediate endpoints, like drug plasma concentration or disease activity as reflected by biomarkers. In mechanism-based medicine it is already common practice to adjust drug dose to age and liver
and renal function, to the disease, and/or, more specifically, to
the disease activity. Pharmacogenetics-the study of variations in
deoxyribonucleic acid (DNA) sequence as related to drug response
(EMEA/CHMP/ICH/437986/2006)—is trying to obtain its position
among the multitude of factors affecting drug exposure and
response. These factors can be discriminated in:
