Multi-Institutional Implementation of Clinical Decision Support for APOL1, NAT2, and YEATS4 Genotyping in Antihypertensive Management

(1) Background: Clinical decision support (CDS) is a vitally important adjunct to the implementation of pharmacogenomic-guided prescribing in clinical practice. A novel CDS was sought for the APOL1, NAT2, and YEATS4 genes to guide optimal selection of antihypertensive medications among the African American population cared for at multiple participating institutions in a clinical trial. (2) Methods: The CDS committee, made up of clinical content and CDS experts, developed a framework and contributed to the creation of the CDS using the following guiding principles: 1. medical algorithm consensus; 2. actionability; 3. context-sensitive triggers; 4. workflow integration; 5. feasibility; 6. interpretability; 7. portability; and 8. discrete reporting of lab results. (3) Results: Utilizing the principle of discrete patient laboratory and vital information, a novel CDS for APOL1, NAT2, and YEATS4 was created for use in a multi-institutional trial based on a medical algorithm consensus. The alerts are actionable and easily interpretable, clearly displaying the purpose and recommendations with pertinent laboratory results, vitals and links to ordersets with suggested antihypertensive dosages. Alerts were either triggered immediately once a provider starts to order relevant antihypertensive agents or strategically placed in workflow-appropriate general CDS sections in the electronic health record (EHR). Detailed implementation instructions were shared across institutions to achieve maximum portability. (4) Conclusions: Using sound principles, the created genetic algorithms were applied across multiple institutions. The framework outlined in this study should apply to other disease-gene and pharmacogenomic projects employing CDS.

[1]  S. Waring,et al.  Primary Care Clinicians Attitudes and Knowledge of Pharmacogenetics in a Large, Multi-state, Healthcare System. , 2018, Innovations in pharmacy.

[2]  G. Ginsburg,et al.  Primary care providers' use of pharmacist support for delivery of pharmacogenetic testing. , 2017, Pharmacogenomics.

[3]  J. Peterson,et al.  Clinician Perspectives on Using Pharmacogenomics in Clinical Practice. , 2015, Personalized medicine.

[4]  Marc B Rosenman,et al.  Lessons Learned When Introducing Pharmacogenomic Panel Testing into Clinical Practice. , 2017, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[5]  E. Boerwinkle,et al.  Association of Chromosome 12 locus with antihypertensive response to hydrochlorothiazide may involve differential YEATS4 expression , 2012, The Pharmacogenomics Journal.

[6]  David W. Bates,et al.  Synthesis of Research Paper: Ten Commandments for Effective Clinical Decision Support: Making the Practice of Evidence-based Medicine a Reality , 2003, J. Am. Medical Informatics Assoc..

[7]  Barry I. Freedman,et al.  APOL1 risk variants, race, and progression of chronic kidney disease. , 2013, The New England journal of medicine.

[8]  L. Appel,et al.  Strict blood pressure control associates with decreased mortality risk by APOL1 genotype. , 2017, Kidney international.

[9]  B. Freedman,et al.  The Impact of APOL1 on Chronic Kidney Disease and Hypertension. , 2019, Advances in chronic kidney disease.

[10]  Michael T. Eadon,et al.  Genotype-Guided Hydralazine Therapy , 2020, American Journal of Nephrology.

[11]  P. Suffys,et al.  Different phenotypes of the NAT2 gene influences hydralazine antihypertensive response in patients with resistant hypertension. , 2014, Pharmacogenomics.

[12]  Rennie Negron,et al.  Determining the effects and challenges of incorporating genetic testing into primary care management of hypertensive patients with African ancestry. , 2016, Contemporary clinical trials.

[13]  Giulio Genovese,et al.  APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. , 2011, Journal of the American Society of Nephrology : JASN.

[14]  P. Deloukas,et al.  Integrating Genome-Wide Genetic Variations and Monocyte Expression Data Reveals Trans-Regulated Gene Modules in Humans , 2011, PLoS genetics.

[15]  Ebony B Madden,et al.  Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network , 2018, Genetics in Medicine.

[16]  E. Boerwinkle,et al.  Hypertensive APOL1 risk allele carriers demonstrate greater blood pressure reduction with angiotensin receptor blockade compared to low risk carriers , 2019, PloS one.

[17]  Ebony B Madden,et al.  Establishing the Value of Genomics in Medicine – The IGNITE Pragmatic Trials Network , 2021, Genetics in Medicine.

[18]  M. Fornage,et al.  APOL1 variants associate with increased risk of CKD among African Americans. , 2013, Journal of the American Society of Nephrology : JASN.

[19]  Andre Kushniruk,et al.  A Framework for Usable and Effective Clinical Decision Support: Experience from the iCPR Randomized Clinical Trial , 2015, EGEMS.

[20]  J. Marc Overhage,et al.  Details of a Successful Clinical Decision Support System , 2007, AMIA.

[21]  Janet E Olson,et al.  Integrating Pharmacogenomics into Clinical Practice: Promise vs Reality. , 2016, The American journal of medicine.

[22]  R. Altman,et al.  Implementing Personalized Medicine: Development of a Cost‐Effective Customized Pharmacogenetics Genotyping Array , 2012, Clinical pharmacology and therapeutics.

[23]  R. Freimuth,et al.  Implementing Genomic Clinical Decision Support for Drug‐Based Precision Medicine , 2017, CPT: pharmacometrics & systems pharmacology.

[24]  Randolph A. Miller,et al.  Focus on health information technology, electronic health records and their financial impact: A framework for evaluating the appropriateness of clinical decision support alerts and responses , 2012, J. Am. Medical Informatics Assoc..

[25]  Brooke L. Fridley,et al.  Genomic Association Analysis Suggests Chromosome 12 Locus Influencing Antihypertensive Response to Thiazide Diuretic , 2008, Hypertension.

[26]  C. Winkler,et al.  Genetic Testing for APOL1 Genetic Variants in Clinical Practice: Finally Starting to Arrive. , 2019, Clinical journal of the American Society of Nephrology : CJASN.