Generating evidence for precision medicine: considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study
Pharmacogenetics and Genomics, vol. 30, pp. 131–144
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors 26
-
Leiden University Medical Center
Affiliation as printed
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center
Leiden University Medical Center, Leiden Network for Personalised Therapeutics
-
Leiden University Medical Center
Affiliation as printed
Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
-
Centro di Riferimento Oncologico
Affiliation as printed
Experimental and Clinical Pharmacology, Experimental and Clinical Pharmacology; Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Aviano, Italy
Experimental and Clinical Pharmacology, Experimental and Clinical Pharmacology
-
Royal Dutch Pharmacists Association
Affiliation as printed
Medicine Information Centre, Royal Dutch Pharmacists Association (KNMP), The Hague, The Netherlands
-
Instituto de Investigación Biosanitaria de Granada
Affiliation as printed
Department of Clinical Pharmacy, San Cecilio University Hospital, Instituto de investigación biosanitaria de Granada, ibs.Granada, Granada, Spain
-
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Clinical Pharmacy, Division of Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
-
Affiliation as printed
Pharmacogenetics Laboratory, Faculty of Medicine, Institute of Biochemistry, University of Ljubljana, Slovenia
-
Affiliation as printed
Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm
-
Affiliation as printed
Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm
-
Affiliation as printed
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
-
Leiden University Medical Center
Affiliation as printed
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
-
Affiliation as printed
The Golden Helix Foundation, London, UK
-
Affiliation as printed
Department of Pharmacy, University of Patras, School of Health Sciences, University Campus, Rion, Patras, Greece
-
University of Liverpool · Royal Liverpool University Hospital
Affiliation as printed
Department of Molecular and Clinical Pharmacology, University of Liverpool, and Royal Liverpool University Hospital, Liverpool, UK
-
Université Toulouse III - Paul Sabatier · Inserm · Université de Toulouse
Affiliation as printed
UMR 1027 Inserm and Université de Toulouse III Paul Sabatier, Toulouse, France
-
Affiliation as printed
Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria
-
Universitätsklinikum Tübingen · Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology · University of Tübingen
Affiliation as printed
Department of Clinical Pharmacology, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany and University of Tübingen
Department of Clinical Pharmacology, University Hospital Tübingen
Department of Pharmacy and Biochemistry, University of Tübingen, Tübingen
-
Justus-Liebig-Universität Gießen
Affiliation as printed
Institute of Human Genetics, Justus Liebig University Giessen
bio.logis Center for Human Genetics, Frankfurt am Main
-
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute of Clinical Pharmacology, University Hospital of RWTH Aachen, Aachen, Germany
-
Affiliation as printed
Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Venna, Vienna, Austria
-
Centro di Riferimento Oncologico
Affiliation as printed
Experimental and Clinical Pharmacology, Experimental and Clinical Pharmacology; Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Aviano, Italy
Experimental and Clinical Pharmacology, Experimental and Clinical Pharmacology
-
University of Liverpool · Royal Liverpool University Hospital
Affiliation as printed
Department of Molecular and Clinical Pharmacology, University of Liverpool, and Royal Liverpool University Hospital, Liverpool, UK
-
Royal Dutch Pharmacists Association
Affiliation as printed
Medicine Information Centre, Royal Dutch Pharmacists Association (KNMP), The Hague, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
-
Leiden University Medical Center
Affiliation as printed
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center
Leiden University Medical Center, Leiden Network for Personalised Therapeutics
-
Henk‐Jan Guchelaar corresponding Aachen Department of Clinical Pharmacy and Toxicology to Henk-Jan Guchelaar Department of Clinical Pharmacy and Toxicology
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center
Leiden University Medical Center, Leiden Network for Personalised Therapeutics
fax: +31 071 526 6980
to Henk-Jan Guchelaar, PharmD, PhD, Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, P.O. Box 9600, NL 2300 RC Leiden, The Netherlands, Tel: +31 071 526 2790
Cited by 44 stored of 44
No patents citing this paper on Lens.org (checked 2026-10-06).