Browsing by Author "Ong, Henry H."

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    Design and Rationale of GUARDD-US: A pragmatic, randomized trial of genetic testing for APOL1 and pharmacogenomic predictors of antihypertensive efficacy in patients with hypertension
    (Elsevier, 2022) Eadon, Michael T.; Cavanaugh, Kerri L.; Orlando, Lori A.; Christian, David; Chakraborty, Hrishikesh; Steen-Burrell, Kady-Ann; Merrill, Peter; Seo, Janet; Hauser, Diane; Singh, Rajbir; Maynor Beasley, Cherry; Fuloria, Jyotsna; Kitzman, Heather; Parker, Alexander S.; Ramos, Michelle; Ong, Henry H.; Elwood, Erica N.; Lynch, Sheryl E.; Clermont, Sabrina; Cicali, Emily J.; Starostik, Petr; Pratt, Victoria M.; Nguyen, Khoa A.; Rosenman, Marc B.; Calman, Neil S.; Robinson, Mimsie; Nadkarni, Girish N.; Madden, Ebony B.; Kucher, Natalie; Volpi, Simona; Dexter, Paul R.; Skaar, Todd C.; Johnson, Julie A.; Cooper-DeHoff, Rhonda M.; Horowitz, Carol R.; GUARDD-US Investigators; Medicine, School of Medicine
    Rationale and objective: APOL1 risk alleles are associated with increased cardiovascular and chronic kidney disease (CKD) risk. It is unknown whether knowledge of APOL1 risk status motivates patients and providers to attain recommended blood pressure (BP) targets to reduce cardiovascular disease. Study design: Multicenter, pragmatic, randomized controlled clinical trial. Setting and participants: 6650 individuals with African ancestry and hypertension from 13 health systems. Intervention: APOL1 genotyping with clinical decision support (CDS) results are returned to participants and providers immediately (intervention) or at 6 months (control). A subset of participants are re-randomized to pharmacogenomic testing for relevant antihypertensive medications (pharmacogenomic sub-study). CDS alerts encourage appropriate CKD screening and antihypertensive agent use. Outcomes: Blood pressure and surveys are assessed at baseline, 3 and 6 months. The primary outcome is change in systolic BP from enrollment to 3 months in individuals with two APOL1 risk alleles. Secondary outcomes include new diagnoses of CKD, systolic blood pressure at 6 months, diastolic BP, and survey results. The pharmacogenomic sub-study will evaluate the relationship of pharmacogenomic genotype and change in systolic BP between baseline and 3 months. Results: To date, the trial has enrolled 3423 participants. Conclusions: The effect of patient and provider knowledge of APOL1 genotype on systolic blood pressure has not been well-studied. GUARDD-US addresses whether blood pressure improves when patients and providers have this information. GUARDD-US provides a CDS framework for primary care and specialty clinics to incorporate APOL1 genetic risk and pharmacogenomic prescribing in the electronic health record.
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    Evaluating the extent of reusability of CYP2C19 genotype data among patients genotyped for antiplatelet therapy selection
    (Nature, 2020-11) Beitelshees, Amber L.; Stevenson, James M.; El Rouby, Nihal; Dillon, Chrisly; Empey, Philip E.; Fielstein, Elliot M.; Johnson, Julie A.; Limdi, Nita A.; Ong, Henry H.; Franchi, Francesco; Angiolillo, Dominick P.; Peterson, Joshua F.; Rosenman, Marc B.; Skaar, Todd C.; Tuteja, Sony; Cavallari, Larisa H.; Medicine, School of Medicine
    Purpose Genotype-guided antiplatelet therapy is increasingly being incorporated into clinical care. The purpose of this study is to determine the extent to which patients initially genotyped for CYP2C19 to guide antiplatelet therapy were prescribed additional medications affected by CYP2C19. Methods We assembled a cohort of patients from eight sites performing CYP2C19 genotyping to inform antiplatelet therapy. Medication orders were evaluated from time of genotyping through one year. The primary endpoint was the proportion of patients prescribed two or more CYP2C19 substrates. Secondary endpoints were the proportion of patients with a drug–genotype interaction and time to receiving a CYP2C19 substrate. Results Nine thousand one hundred ninety-one genotyped patients (17% nonwhite) with a mean age of 68 ± 3 years were evaluated; 4701 (51%) of patients received two or more CYP2C19 substrates and 3835 (42%) of patients had a drug–genotype interaction. The average time between genotyping and CYP2C19 substrate other than antiplatelet therapy was 25 ± 10 days. Conclusions More than half of patients genotyped in the setting of CYP2C19-guided antiplatelet therapy received another medication impacted by CYP2C19 in the following year. Given that genotype is stable for a patient’s lifetime, this finding has implications for cost effectiveness, patient care, and treatment outcomes beyond the indication for which it was originally performed.
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    Opportunity for Genotype-Guided Prescribing Among Adult Patients in 11 US Health Systems.
    (Wiley, 2021-07) Hicks, J. Kevin; El Rouby, Nihal; Ong, Henry H.; Schildcrout, Jonathan S.; Ramsey, Laura B.; Shi, Yaping; Anne Tang, Leigh; Aquilante, Christina L.; Beitelshees, Amber L.; Blake, Kathryn V.; Cimino, James J.; Davis, Brittney H.; Empey, Philip E.; Kao, David P.; Lemkin, Daniel L.; Limdi, Nita A.; P Lipori, Gloria; Rosenman, Marc B.; Skaar, Todd C.; Teal, Evgenia; Tuteja, Sony; Wiley, Laura K.; Williams, Helen; Winterstein, Almut G.; Van Driest, Sara L.; Cavallari, Larisa H.; Peterson, Josh F.
    The value of utilizing a multigene pharmacogenetic panel to tailor pharmacotherapy is contingent on the prevalence of prescribed medications with an actionable pharmacogenetic association. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has categorized over 35 gene-drug pairs as "level A," for which there is sufficiently strong evidence to recommend that genetic information be used to guide drug prescribing. The opportunity to use genetic information to tailor pharmacotherapy among adult patients was determined by elucidating the exposure to CPIC level A drugs among 11 Implementing Genomics In Practice Network (IGNITE)-affiliated health systems across the US. Inpatient and/or outpatient electronic-prescribing data were collected between January 1, 2011 and December 31, 2016 for patients ≥ 18 years of age who had at least one medical encounter that was eligible for drug prescribing in a calendar year. A median of ~ 7.2 million adult patients was available for assessment of drug prescribing per year. From 2011 to 2016, the annual estimated prevalence of exposure to at least one CPIC level A drug prescribed to unique patients ranged between 15,719 (95% confidence interval (CI): 15,658-15,781) in 2011 to 17,335 (CI: 17,283-17,386) in 2016 per 100,000 patients. The estimated annual exposure to at least 2 drugs was above 7,200 per 100,000 patients in most years of the study, reaching an apex of 7,660 (CI: 7,632-7,687) per 100,000 patients in 2014. An estimated 4,748 per 100,000 prescribing events were potentially eligible for a genotype-guided intervention. Results from this study show that a significant portion of adults treated at medical institutions across the United States is exposed to medications for which genetic information, if available, should be used to guide prescribing.
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    Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients
    (American Medical Association, 2020-12) Ramsey, Laura B.; Ong, Henry H.; Schildcrout, Jonathan S.; Shi, Yaping; Tang, Leigh Anne; Hicks, J. Kevin; El Rouby, Nihal; Cavallari, Larisa H.; Tuteja, Sony; Aquilante, Christina L.; Beitelshees, Amber L.; Lemkin, Daniel L.; Blake, Kathryn V.; Williams, Helen; Cimino, James J.; Davis, Brittney H.; Limdi, Nita A.; Empey, Philip E.; Horvat, Christopher M.; Kao, David P.; Lipori, Gloria P.; Rosenman, Marc B.; Skaar, Todd C.; Teal, Evgenia; Winterstein, Almut G.; Obeng, Aniwaa Owusu; Salyakina, Daria; Gupta, Apeksha; Gruber, Joshua; McCafferty-Fernandez, Jennifer; Bishop, Jeffrey R.; Rivers, Zach; Benner, Ashley; Tamraz, Bani; Long-Boyle, Janel; Peterson, Josh F.; Van Driest, Sara L.; Pediatrics, School of Medicine
    Importance: Genotype-guided prescribing in pediatrics could prevent adverse drug reactions and improve therapeutic response. Clinical pharmacogenetic implementation guidelines are available for many medications commonly prescribed to children. Frequencies of medication prescription and actionable genotypes (genotypes where a prescribing change may be indicated) inform the potential value of pharmacogenetic implementation. Objective: To assess potential opportunities for genotype-guided prescribing in pediatric populations among multiple health systems by examining the prevalence of prescriptions for each drug with the highest level of evidence (Clinical Pharmacogenetics Implementation Consortium level A) and estimating the prevalence of potential actionable prescribing decisions. Design, setting, and participants: This serial cross-sectional study of prescribing prevalences in 16 health systems included electronic health records data from pediatric inpatient and outpatient encounters from January 1, 2011, to December 31, 2017. The health systems included academic medical centers with free-standing children's hospitals and community hospitals that were part of an adult health care system. Participants included approximately 2.9 million patients younger than 21 years observed per year. Data were analyzed from June 5, 2018, to April 14, 2020. Exposures: Prescription of 38 level A medications based on electronic health records. Main outcomes and measures: Annual prevalence of level A medication prescribing and estimated actionable exposures, calculated by combining estimated site-year prevalences across sites with each site weighted equally. Results: Data from approximately 2.9 million pediatric patients (median age, 8 [interquartile range, 2-16] years; 50.7% female, 62.3% White) were analyzed for a typical calendar year. The annual prescribing prevalence of at least 1 level A drug ranged from 7987 to 10 629 per 100 000 patients with increasing trends from 2011 to 2014. The most prescribed level A drug was the antiemetic ondansetron (annual prevalence of exposure, 8107 [95% CI, 8077-8137] per 100 000 children). Among commonly prescribed opioids, annual prevalence per 100 000 patients was 295 (95% CI, 273-317) for tramadol, 571 (95% CI, 557-586) for codeine, and 2116 (95% CI, 2097-2135) for oxycodone. The antidepressants citalopram, escitalopram, and amitriptyline were also commonly prescribed (annual prevalence, approximately 250 per 100 000 patients for each). Estimated prevalences of actionable exposures were highest for oxycodone and ondansetron (>300 per 100 000 patients annually). CYP2D6 and CYP2C19 substrates were more frequently prescribed than medications influenced by other genes. Conclusions and relevance: These findings suggest that opportunities for pharmacogenetic implementation among pediatric patients in the US are abundant. As expected, the greatest opportunity exists with implementing CYP2D6 and CYP2C19 pharmacogenetic guidance for commonly prescribed antiemetics, analgesics, and antidepressants.