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Preemptive Genotyping for Personalized Medicine: Design of the Right Drug, Right Dose, Right Time—Using Genomic Data to Individualize Treatment Protocol



      To report the design and implementation of the Right Drug, Right Dose, Right Time—Using Genomic Data to Individualize Treatment protocol that was developed to test the concept that prescribers can deliver genome-guided therapy at the point of care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated into the electronic medical record (EMR).

      Patients and Methods

      We used a multivariate prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR.


      The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for International Classification of Diseases, Ninth Revision codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance.


      This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice.

      Abbreviations and Acronyms:

      CAB (Community Advisory Board), CAP (College of American Pathologists), CDS (clinical decision support), CGSL (Clinical Genome Sequencing Laboratory), CLIA (Clinical Laboratory Improvement Amendments), eMERGE (Electronic Medical Record and Genomics), EMR (electronic medical record), FDA (Food and Drug Administration), NGS (next-generation sequencing), PGL (Personalized Genomics Laboratory), PGRN (Pharmacogenomics Research Network), PGx (pharmacogenomics), RIGHT (The Right Drug, Right Dose, Right Time—Using Genomic Data to Individualize Treatment)
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