Your browser doesn't support javascript.
loading
Generating evidence for precision medicine: considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study.
van der Wouden, Cathelijne H; Böhringer, Stefan; Cecchin, Erika; Cheung, Ka-Chun; Dávila-Fajardo, Cristina Lucía; Deneer, Vera H M; Dolzan, Vita; Ingelman-Sundberg, Magnus; Jönsson, Siv; Karlsson, Mats O; Kriek, Marjolein; Mitropoulou, Christina; Patrinos, George P; Pirmohamed, Munir; Rial-Sebbag, Emmanuelle; Samwald, Matthias; Schwab, Matthias; Steinberger, Daniela; Stingl, Julia; Sunder-Plassmann, Gere; Toffoli, Giuseppe; Turner, Richard M; van Rhenen, Mandy H; van Zwet, Erik; Swen, Jesse J; Guchelaar, Henk-Jan.
Affiliation
  • van der Wouden CH; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center.
  • Böhringer S; Leiden University Medical Center, Leiden Network for Personalised Therapeutics.
  • Cecchin E; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
  • Cheung KC; Experimental and Clinical Pharmacology, Experimental and Clinical Pharmacology; Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Aviano, Italy.
  • Dávila-Fajardo CL; Medicine Information Centre, Royal Dutch Pharmacists Association (KNMP), The Hague, The Netherlands.
  • Deneer VHM; Department of Clinical Pharmacy, San Cecilio University Hospital, Instituto de investigación biosanitaria de Granada, ibs.Granada, Granada, Spain.
  • Dolzan V; Department of Clinical Pharmacy, Division of Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Ingelman-Sundberg M; Pharmacogenetics Laboratory, Faculty of Medicine, Institute of Biochemistry, University of Ljubljana, Slovenia.
  • Jönsson S; Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm.
  • Karlsson MO; Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm.
  • Kriek M; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
  • Mitropoulou C; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
  • Patrinos GP; The Golden Helix Foundation, London, UK.
  • Pirmohamed M; Department of Pharmacy, University of Patras, School of Health Sciences, University Campus, Rion, Patras, Greece.
  • Rial-Sebbag E; Department of Molecular and Clinical Pharmacology, University of Liverpool, and Royal Liverpool University Hospital, Liverpool, UK.
  • Samwald M; UMR 1027 Inserm and Université de Toulouse III Paul Sabatier, Toulouse, France.
  • Schwab M; Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
  • Steinberger D; Department of Clinical Pharmacology, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany and University of Tübingen.
  • Stingl J; Department of Clinical Pharmacology, University Hospital Tübingen.
  • Sunder-Plassmann G; Department of Pharmacy and Biochemistry, University of Tübingen, Tübingen.
  • Toffoli G; bio.logis Center for Human Genetics, Frankfurt am Main.
  • Turner RM; Institute of Human Genetics, Justus Liebig University Giessen.
  • van Rhenen MH; Institute of Clinical Pharmacology, University Hospital of RWTH Aachen, Aachen, Germany.
  • van Zwet E; Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Venna, Vienna, Austria.
  • Swen JJ; Experimental and Clinical Pharmacology, Experimental and Clinical Pharmacology; Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, National Cancer Institute, Aviano, Italy.
  • Guchelaar HJ; Department of Molecular and Clinical Pharmacology, University of Liverpool, and Royal Liverpool University Hospital, Liverpool, UK.
Pharmacogenet Genomics ; 30(6): 131-144, 2020 08.
Article de En | MEDLINE | ID: mdl-32317559
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.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Effets secondaires indésirables des médicaments / Médecine de précision / Test pharmacogénomique Type d'étude: Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Limites: Humans Langue: En Journal: Pharmacogenet Genomics Sujet du journal: FARMACOLOGIA / GENETICA MEDICA Année: 2020 Type de document: Article

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Effets secondaires indésirables des médicaments / Médecine de précision / Test pharmacogénomique Type d'étude: Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Limites: Humans Langue: En Journal: Pharmacogenet Genomics Sujet du journal: FARMACOLOGIA / GENETICA MEDICA Année: 2020 Type de document: Article