RT Journal Article
T1 Generating evidence for precision medicine: considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study.
A1 van der Wouden, Cathelijne H
A1 Bohringer, Stefan
A1 Cecchin, Erika
A1 Cheung, Ka-Chun
A1 Davila-Fajardo, Cristina Lucía
A1 Deneer, Vera H M
A1 Dolžan, Vita
A1 Ingelman-Sundberg, Magnus
A1 Jonsson, Siv
A1 Karlsson, Mats O
A1 Kriek, Marjolein
A1 Mitropoulou, Christina
A1 Patrinos, George P
A1 Pirmohamed, Munir
A1 Rial-Sebbag, Emmanuelle
A1 Samwald, Matthias
A1 Schwab, Matthias
A1 Steinberger, Daniela
A1 Stingl, Julia
A1 Sunder-Plassmann, Gere
A1 Toffoli, Giuseppe
A1 Turner, Richard M
A1 van Rhenen, Mandy H
A1 van Zwet, Erik
A1 Swen, Jesse J
A1 Guchelaar, Henk-Jan
A1 Ubiquitous Pharmacogenomics Consortium, 
AB Pharmacogenetic panel-based testing represents a new model for precision medicine. A sufficiently powered prospective study assessing the (cost-)effectiveness of a panel-based pharmacogenomics approach to guide pharmacotherapy is lacking. Therefore, the Ubiquitous Pharmacogenomics Consortium initiated the PREemptive Pharmacogenomic testing for prevention of Adverse drug Reactions (PREPARE) study. Here, we provide an overview of considerations made to mitigate multiple methodological challenges that emerged during the design. An evaluation of considerations made when designing the PREPARE study across six domains: study aims and design, primary endpoint definition and collection of adverse drug events, inclusion and exclusion criteria, target population, pharmacogenomics intervention strategy, and statistical analyses. Challenges and respective solutions included: (1) defining and operationalizing a composite primary endpoint enabling measurement of the anticipated effect, by including only severe, causal, and drug genotype-associated adverse drug reactions; (2) avoiding overrepresentation of frequently prescribed drugs within the patient sample while maintaining external validity, by capping drugs of enrolment; (3) designing the pharmacogenomics intervention strategy to be applicable across ethnicities and healthcare settings; and (4) designing a statistical analysis plan to avoid dilution of effect by initially excluding patients without a gene-drug interaction in a gatekeeping analysis. Our design considerations will enable quantification of the collective clinical utility of a panel of pharmacogenomics-markers within one trial as a proof-of-concept for pharmacogenomics-guided pharmacotherapy across multiple actionable gene-drug interactions. These considerations may prove useful to other investigators aiming to generate evidence for precision medicine.
PB Lippincott Williams & Wilkins
YR 2020
FD 2020/03/02
LK http://hdl.handle.net/10668/15406
UL http://hdl.handle.net/10668/15406
LA en
NO van der Wouden CH, Böhringer S, Cecchin E, Cheung KC, Dávila-Fajardo CL, Deneer VHM, eta al, Generating evidence for precision medicine: considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study. Pharmacogenet Genomics. 2020 Aug;30(6):131-144.
NO We would like to thank the Scientific Advisory Board(Prof. Russ Altman, Prof. Michel Eichelbaum, DavidHaerry, Prof. Mark Ratain, Prof. Mary Relling, and Prof.Dan Roden) for their insights in the development of thestudy protocol and statistical analysis plan.The research leading to these results has receivedfunding from the European Community’s Horizon2020 Programme under grant agreement No. 668353(Ubiquitous Pharmacogenomics). M.S. is in part supported by the Robert Bosch Stiftung, Stuttgart, Germany
DS RISalud
RD Apr 7, 2025