CASyM winter school of Systems Medicine took place between March 29th and April 1st 2017 in Ljubljana, Slovenia and is entitled »The 3rd SysBioMed hands-on tutorial: Systems Medicine Approaches in Personalized Medicine«
Implementing enabling tools for preemptive pharmacogenomics testing within the Ubiquitous Pharmacogenomics Project: The Slovenian Experience
Vita Dolžan1,Katja Goričar1,Sara Redenšek1,Tanja Blagus1,for Ubiquitous Pharmacogenomics Consortium2
1Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.,2Leiden University Medical Center, Leiden, The Netherlands
Introduction: Evidence showing that pre-emptive pharmacogenomic testing can lead to improved patient treatment outcomes is accumulating, however it is limited to single drug-genes pairs. The aim of the first year of the Horizon2020 project »Ubiquitous Pharmacogenomics (U-PGx): Making actionable pharmacogenomic data and effective treatment optimization accessible to every European citizen« (http://upgx.eu/) was to develop the enabling tools to support a clinical study on clinical utility of preemptive pharmacogenomic testing for a panel of pharmacogenes and to implement them in seven European countries, including Slovenia. Methods: The following tools were identified as necessary to support a clinical study on preemptive pharmacogenetics testing: 1. A panel of drug – pharmacogene pairs with major influence on interpatient variability in drug response; 2. Evidence based guidelines on how to use genetic test results in specific drug, gene and genotype/phenotype; 3. The infrastructure and methodology for prospective genotyping for selected pharmacogenes; 4. ICT tools to make genotyping data and recommendations available to the physician at the time of prescription of the drug. Results: Ad 1. The analysis of the existing data performed by the U-PGx Consortium1 showed that actionable prescribing of over 50 drugs is most strongly linked to 12 pharmacogenes (www.pharmgkb.org/cpic/pairs); Ad 2. The Dutch Pharmacogenetics Working Group (DPWG; https://www.pharmgkb.org/page/dpwg) has already developed guidelines for 56 drugs and 12 genes to support treatment decisions in patient with genotype at risk. Translation into Slovenian language was provided; Ad 3. Real-time PCR fluorescence-based endpoint genotyping (KASPar) was chosen as the genotyping method and SNPline (LCG Group) genotyping system was set up at the Pharmacogenetics Laboratory. The respective KASPar assays were designed and validated by Biologis and LCG Group, respectively and introduced and tested at the Pharmacogenetics Laboratory; Ad 4. The ICT tools developed by the University of Vienna and Biologis were implemented at the Pharmacogenetics Laboratory to enable the transfer of anonymised genotyping data to Biologis server, where automated genotype calling, linking with the personalized treatment guidelines and report generation takes place. The system supports submission of electronic and printed reports to the physician, printing of the safe code card for the patient and inclusion of genotype data into patients’ electronic medical record. At present, only first two options will be implemented within the clinical study in Slovenia. Conclusion: Within the first year of the U-PGx project we have successfully implemented the tools and infrastructure that will enable us to carry out the clinical study on preemptive pharmacogenomics testing to quantify the collective clinical utility of a panel of PGx-markers.
References: 1. van der Wouden, C.H., et al., (2017) Clin Pharmacol Ther, 101(3):341-358.
2006 - University of Ljubljana, Faculty of Medicine, Center for Functional Genomics and Bio-chips.