Personalized Medicine

In this thesis we investigated the use of pharmacogenetics throughout different phases of drug research as well as in day-to-day use in the post-marketing phase. Pharmacogenetic research studies the contribution of genetic variation to inter-individual variability in response to medication. The aim is to optimize drug response for an individual patient by using his genetic profile in treatment decisions. We showed the potential benefit of adaptive trial designs for situations in which there is evidence of effect modification by a genomic marker. This enables researchers to learn about the effect of the genetic variability on drug response and to immediately use this information for the remainder of the study. Furthermore, we showed that not only single polymorphisms but also gene-gene interactions seem valuable in predicting statin response. In psychiatric practice, we demonstrated that the presence of aberrant drug metabolism predicted by CYP2D6 and CYP2C19 impacts the consumption of care for patients using antidepressants and antipsychotics. Currently, only a small number of pharmacogenetic tests are routinely used in clinical practice. We hope this thesis contributes to the wider use of pharmacogenetic testing.

Results

• Personalized Medicine: Pharmacogenetic Testing in Drug Development and Clinical Practice (thesis)
• Van der Baan FH, Klungel OH, Egberts AC, Leufkens HG, Grobbee DE, Roes KC, et al. Pharmacogenetics in randomized controlled trials: considerations for trial design. In: Pharmacogenomics, 2011; 12(10): 1485-92. (journal publication)
• Van der Baan FH, Bernabe RD, Bredenoord AL, Gregoor JG, Meynen G, Knol MJ, et al. Consent in psychiatric biobanks for pharmacogenetic research. In: Int J Neuropsychopharmacol, 2012: 1-6. (journal publication)
• Van der Baan FH, Knol MJ, Klungel OH, Egberts AC, Grobbee DE, Roes KC. Potential of adaptive clinical trial designs in pharmacogenetic research. In: Pharmacogenomics, 2012; 13(5): 571-8. (journal publication)
• Van der Baan FH, Knol MJ, Maitland-van der Zee AH, Regieli JJ, Van Iperen EP, Egberts AC, et al. Added value of pharmacogenetic testing in predicting statin response: results from the REGRESS trial. In: Pharmacogenomics J, 2012. (journal publication)