Amy L Kaufman1, Jared Spitz2, Michael Jacobs2, Matthew Sorrentino3, Shennin Yuen2, Keith Danahey4, Donald Saner4, Teri E Klein5, Russ B Altman6, Mark J Ratain7, Peter H O'Donnell8. 1. Pritzker School of Medicine, The University of Chicago, Chicago, IL. 2. Center for Personalized Therapeutics, The University of Chicago, Chicago, IL. 3. Department of Medicine, The University of Chicago, Chicago, IL. 4. Center for Research Informatics, The University of Chicago, Chicago, IL. 5. Department of Genetics, Stanford University, Palo Alto, CA. 6. Department of Genetics, Stanford University, Palo Alto, CA; Department of Bioengineering, Stanford University, Palo Alto, CA; Department of Medicine, Stanford University, Palo Alto, CA. 7. Center for Personalized Therapeutics, The University of Chicago, Chicago, IL; Department of Medicine, The University of Chicago, Chicago, IL; Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL. 8. Center for Personalized Therapeutics, The University of Chicago, Chicago, IL; Department of Medicine, The University of Chicago, Chicago, IL; Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL. Electronic address: podonnel@medicine.bsd.uchicago.edu.
Abstract
OBJECTIVE: To comprehensively assess the pharmacogenomic evidence of routinely used drugs for clinical utility. METHODS: Between January 2, 2011, and May 31, 2013, we assessed 71 drugs by identifying all drug/genetic variant combinations with published clinical pharmacogenomic evidence. Literature supporting each drug/variant pair was assessed for study design and methods, outcomes, statistical significance, and clinical relevance. Proposed clinical summaries were formally scored using a modified AGREE (Appraisal of Guidelines for Research and Evaluation) II instrument, including recommendation for or against guideline implementation. RESULTS: Positive pharmacogenomic findings were identified for 51 of 71 cardiovascular drugs (71.8%), representing 884 unique drug/variant pairs from 597 publications. After analysis for quality and clinical relevance, 92 drug/variant pairs were proposed for translation into clinical summaries, encompassing 23 drugs (32.4% of drugs reviewed). All were recommended for clinical implementation using AGREE II, with mean ± SD overall quality scores of 5.18±0.91 (of 7.0; range, 3.67-7.0). Drug guidelines had highest mean ± SD scores in AGREE II domain 1 (Scope) (91.9±6.1 of 100) and moderate but still robust mean ± SD scores in domain 3 (Rigor) (73.1±11.1), domain 4 (Clarity) (67.8±12.5), and domain 5 (Applicability) (65.8±10.0). Clopidogrel (CYP2C19), metoprolol (CYP2D6), simvastatin (rs4149056), dabigatran (rs2244613), hydralazine (rs1799983, rs1799998), and warfarin (CYP2C9/VKORC1) were distinguished by the highest scores. Seven of the 9 most commonly prescribed drugs warranted translation guidelines summarizing clinical pharmacogenomic information. CONCLUSION: Considerable clinically actionable pharmacogenomic information for cardiovascular drugs exists, supporting the idea that consideration of such information when prescribing is warranted.
OBJECTIVE: To comprehensively assess the pharmacogenomic evidence of routinely used drugs for clinical utility. METHODS: Between January 2, 2011, and May 31, 2013, we assessed 71 drugs by identifying all drug/genetic variant combinations with published clinical pharmacogenomic evidence. Literature supporting each drug/variant pair was assessed for study design and methods, outcomes, statistical significance, and clinical relevance. Proposed clinical summaries were formally scored using a modified AGREE (Appraisal of Guidelines for Research and Evaluation) II instrument, including recommendation for or against guideline implementation. RESULTS: Positive pharmacogenomic findings were identified for 51 of 71 cardiovascular drugs (71.8%), representing 884 unique drug/variant pairs from 597 publications. After analysis for quality and clinical relevance, 92 drug/variant pairs were proposed for translation into clinical summaries, encompassing 23 drugs (32.4% of drugs reviewed). All were recommended for clinical implementation using AGREE II, with mean ± SD overall quality scores of 5.18±0.91 (of 7.0; range, 3.67-7.0). Drug guidelines had highest mean ± SD scores in AGREE II domain 1 (Scope) (91.9±6.1 of 100) and moderate but still robust mean ± SD scores in domain 3 (Rigor) (73.1±11.1), domain 4 (Clarity) (67.8±12.5), and domain 5 (Applicability) (65.8±10.0). Clopidogrel (CYP2C19), metoprolol (CYP2D6), simvastatin (rs4149056), dabigatran (rs2244613), hydralazine (rs1799983, rs1799998), and warfarin (CYP2C9/VKORC1) were distinguished by the highest scores. Seven of the 9 most commonly prescribed drugs warranted translation guidelines summarizing clinical pharmacogenomic information. CONCLUSION: Considerable clinically actionable pharmacogenomic information for cardiovascular drugs exists, supporting the idea that consideration of such information when prescribing is warranted.
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