Dataset Information

Implementation of preemptive DNA sequence-based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study.

ABSTRACT:

Purpose

The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping.

Methods

Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response-related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug-gene pairs, were deposited preemptively in the Mayo electronic health record.

Results

For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping.

Conclusion

Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources.

SUBMITTER: Wang L

PROVIDER: S-EPMC9272414 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Implementation of preemptive DNA sequence-based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study.

Wang Liewei L Scherer Steven E SE Bielinski Suzette J SJ Muzny Donna M DM Jones Leila A LA Black John Logan JL Moyer Ann M AM Giri Jyothsna J Sharp Richard R RR Matey Eric T ET Wright Jessica A JA Oyen Lance J LJ Nicholson Wayne T WT Wiepert Mathieu M Sullard Terri T Curry Timothy B TB Rohrer Vitek Carolyn R CR McAllister Tammy M TM St Sauver Jennifer L JL Caraballo Pedro J PJ Lazaridis Konstantinos N KN Venner Eric E Qin Xiang X Hu Jianhong J Kovar Christie L CL Korchina Viktoriya V Walker Kimberly K Doddapaneni HarshaVardhan H Wu Tsung-Jung TJ Raj Ritika R Denson Shawn S Liu Wen W Chandanavelli Gauthami G Zhang Lan L Wang Qiaoyan Q Kalra Divya D Karow Mary Beth MB Harris Kimberley J KJ Sicotte Hugues H Peterson Sandra E SE Barthel Amy E AE Moore Brenda E BE Skierka Jennifer M JM Kluge Michelle L ML Kotzer Katrina E KE Kloke Karen K Vander Pol Jessica M JM Marker Heather H Sutton Joseph A JA Kekic Adrijana A Ebenhoh Ashley A Bierle Dennis M DM Schuh Michael J MJ Grilli Christopher C Erickson Sara S Umbreit Audrey A Ward Leah L Crosby Sheena S Nelson Eric A EA Levey Sharon S Elliott Michelle M Peters Steve G SG Pereira Naveen N Frye Mark M Shamoun Fadi F Goetz Matthew P MP Kullo Iftikhar J IJ Wermers Robert R Anderson Jan A JA Formea Christine M CM El Melik Razan M RM Zeuli John D JD Herges Joseph R JR Krieger Carrie A CA Hoel Robert W RW Taraba Jodi L JL St Thomas Scott R SR Absah Imad I Bernard Matthew E ME Fink Stephanie R SR Gossard Andrea A Grubbs Pamela L PL Jacobson Therese M TM Takahashi Paul P Zehe Sharon C SC Buckles Susan S Bumgardner Michelle M Gallagher Colette C Fee-Schroeder Kelliann K Nicholas Nichole R NR Powers Melody L ML Ragab Ahmed K AK Richardson Darcy M DM Stai Anthony A Wilson Jaymi J Pacyna Joel E JE Olson Janet E JE Sutton Erica J EJ Beck Annika T AT Horrow Caroline C Kalari Krishna R KR Larson Nicholas B NB Liu Hongfang H Wang Liwei L Lopes Guilherme S GS Borah Bijan J BJ Freimuth Robert R RR Zhu Ye Y Jacobson Debra J DJ Hathcock Matthew A MA Armasu Sebastian M SM McGree Michaela E ME Jiang Ruoxiang R Koep Tyler H TH Ross Jason L JL Hilden Matthew G MG Bosse Kathleen K Ramey Bronwyn B Searcy Isabelle I Boerwinkle Eric E Gibbs Richard A RA Weinshilboum Richard M RM

Genetics in medicine : official journal of the American College of Medical Genetics 20220321 5

<h4>Purpose</h4>The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, ...[more]

PMID: 35331649

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Project description:BackgroundPharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention.MethodsWe report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder.FindingsWe show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively).InterpretationWhile only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare.FundingEuropean Union Horizon 2020.

Project description:BackgroundElimination of wasteful diagnostic testing will improve value for the United States health care system.ObjectiveDesign and implement a multimodal intervention to improve evidence-based ordering of cardiac biomarkers for the diagnosis of acute coronary syndrome (ACS).DesignInterrupted times series.SubjectsA total of 60,494 adult inpatient admissions from January 2009 through July 2011 (pre-intervention) and 24,341 admissions from November 2011 through October 2012 (post-intervention) at an academic medical center in Baltimore, Maryland.InterventionMultimodal intervention introduced August through October 2011 that included dissemination of an institutional guideline and changes to the computerized provider order entry system.Main measuresThe primary outcome was percentage of patients with guideline-concordant ordering of cardiac biomarkers, defined as three or fewer troponin tests and zero CK-MB tests in patients without a diagnosis of ACS. Secondary outcomes included counts of tests ordered per patient, incidence of diagnosis of ACS, and estimated change in charges for cardiac biomarker tests in the post-intervention period.Key resultsTwelve months following the intervention, we estimated that guideline-concordant ordering of cardiac biomarkers increased from 57.1 % to 95.5 %, an absolute increase of 38.4 % (95 % CI, 36.4 % to 40.4 %). We estimated that the intervention led to a 66 % reduction in the number of tests ordered, and a $1.25 million decrease in charges over the first year. At 12 months, there was an estimated absolute increase in incidence of primary diagnosis of ACS of 0.3 % (95 % CI, 0.0 % to 0.5 %) compared with the expected baseline rate.ConclusionsWe implemented a multimodal intervention that significantly increased guideline-concordant ordering of cardiac biomarker testing, leading to substantial reductions in tests ordered without impacting diagnostic yield. A trial of this approach at other institutions and for other diagnostic tests is warranted and if successful, would represent a framework for eliminating wasteful diagnostic testing.

Dataset Information

Implementation of preemptive DNA sequence-based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study.

Purpose

Methods

Results

Conclusion

Publications

Implementation of preemptive DNA sequence-based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study.

Similar Datasets

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