Explore the vast range of titles available.

Introduction: Pharmacogenetics (PGx) has the potential to improve health outcomes but cost of testing is a barrier for equitable access. Reimbursement by insurance providers may lessen the financial burden for patients, but the extent to which PGx claims are covered in clinical practice has not been well-characterized in the literature. Methods: A retrospective analysis of outpatient claims submitted to payers for PGx tests from 1/1/2019 through 12/31/2021 was performed. A reimbursement rate was calculated and compared across specific test types (e.g., single genes, panel), payers, indication, and the year the claim was submitted. Results: A total of 1,039 outpatient claims for PGx testing were analyzed. The overall reimbursement rate was 46% and ranged from 36%–48% across payers. PGx panels were reimbursed at a significantly higher rate than single gene tests (74% vs. 43%, p < 0.001). Discussion: Reimbursement of claims for PGx testing is variable based on the test type, indication, year the claim was submitted, number of diagnosis codes submitted, and number of unique diagnosis codes submitted. Due to the highly variable nature of reimbursement, cost and affordability should be discussed with each patient.

Purpose To evaluate the frequency and clinical impact of switches in antiplatelet therapy following implementation of CYP2C19 genotyping after percutaneous coronary intervention (PCI). Methods The frequency of escalation (clopidogrel switched to prasugrel/ticagrelor) and de-escalation (prasugrel/ticagrelor switched to clopidogrel) was evaluated in 1063 PCI patients who underwent CYP2C19 genotyping. Risk of major adverse cardiovascular or cerebrovascular (MACCE) and bleeding events over one year was evaluated. Results Antiplatelet therapy switches were common (19%), with escalation (101/115: 88%) and de-escalation (77/84: 92%) occurring predominantly in patients with and without a CYP2C19 nonfunctional allele, respectively. Nonfunctional allele carriers initiated and continued on clopidogrel had a significantly higher risk of experiencing either a MACCE or bleeding event compared with those escalated to prasugrel/ticagrelor (52 vs. 19 events/100 patient-years; adjusted hazard ratio [HR] 2.89 [1.44–6.13], p  = 0.003). Patients without a nonfunctional allele de-escalated to clopidogrel had no difference in risk compared with those initiated and continued on prasugrel/ticagrelor (21 vs. 19 events/100 patient-years; adjusted HR 1.13 [0.51–2.34], p  = 0.751). Conclusion CYP2C19 -guided escalation and de-escalation is common in a real-world setting. Continuation of clopidogrel in nonfunctional allele carriers is associated with adverse outcomes. De-escalation to clopidogrel in patients without a nonfunctional allele appears safe and warrants prospective study.

Previous findings suggest that medically underserved patients are prescribed medications with pharmacogenetic (PGx) guidelines at a high frequency. Thus, underserved patients may especially benefit from PGx testing, but little evidence exists regarding the effect of testing in this population. This pilot study aimed to generate key feasibility data and explore clinical outcomes of PGx implementation in underserved populations. Black and Latino patients were recruited from an outpatient clinic and underwent PGx testing. Feasibility measures included enrollment metrics and actionable genotype frequencies. The primary clinical outcome was patient medication treatment satisfaction 6 months after testing. Implementation outcomes included the number of healthcare provider encounters and medication changes within the 6‐month follow‐up. Effectiveness outcomes included medication adherence, patient‐perceived test value, and time spent discussing medications with providers. Ninety‐nine patients completed the study. Proton‐pump inhibitors were the most frequent PGx drug class prescribed at baseline (61%) followed by nonsteroidal anti‐inflammatory drugs (36%). Patients with an actionable genotype constituted 96% of the population, whereas 28% had an actionable genotype related to their PGx drug. Patient treatment satisfaction significantly increased over the 6 months after PGx testing. In addition, medication adherence and the number of provider encounters significantly increased over the study period. In a pilot study, preemptive PGx testing was feasible in primary care clinics, improved patient treatment satisfaction and adherence, and increased the number of provider encounters in medically underserved patients. Future clinical trials are warranted to assess the long‐term effects of PGx testing in a larger diverse patient population.

Background The CYP2C19 nonfunctional genotype reduces clopidogrel effectiveness after percutaneous coronary intervention (PCI). Following clinical implementation of CYP2C19 genotyping at University Florida (UF) Health Shands Hospital in 2012, where genotype results are available approximately 3 days after PCI, testing was expanded to UF Health Jacksonville in 2016 utilizing a rapid genotyping approach. We describe metrics with this latter implementation. Methods Patients at UF Health Jacksonville undergoing left heart catheterization with intent to undergo PCI were targeted for genotyping using the Spartan RX™ system. Testing metrics and provider acceptance of testing and response to genotype results were examined, as was antiplatelet therapy over the 6 months following genotyping. Results In the first year, 931 patients, including 392/505 (78%) total patients undergoing PCI, were genotyped. The median genotype test turnaround time was 96 min. Genotype results were available for 388 (99%) PCI patients prior to discharge. Of 336 genotyped PCI patients alive at discharge and not enrolled in an antiplatelet therapy trial, 1/6 (17%) poor metabolizers (PMs, with two nonfunctional alleles), 38/93 (41%) intermediate metabolizers (IMs, with one nonfunctional allele), and 119/237 (50%) patients without a nonfunctional allele were prescribed clopidogrel (p = 0.110). Clopidogrel use was higher among non-ACS versus ACS patients (78.6% vs. 42.2%, p < 0.001). Six months later, among patients with follow-up data, clopidogrel was prescribed in 0/4 (0%) PMs, 33/65 (51%) IMs, and 115/182 (63%) patients without a nonfunctional allele (p = 0.008 across groups; p = 0.020 for PMs versus those without a nonfunctional allele). Conclusion These data demonstrate that rapid genotyping is clinically feasible at a high volume cardiac catheterization facility and allows informed chronic antiplatelet prescribing, with lower clopidogrel use in PMs at 6 months. Trial registration ClinicalTrials.gov Identifier: NCT02724319; registered March 31, 2016; https://www.clinicaltrials.gov/ct2/show/NCT02724319?term=angiolillo&rank=7

Over the past decade, pharmacogenetic testing has emerged in clinical practice to guide selected cardiovascular therapies. The most common implementation in practice is CYP2C19 genotyping to predict clopidogrel response and assist in selecting antiplatelet therapy after percutaneous coronary intervention. Additional examples include genotyping to guide warfarin dosing and statin prescribing. Increasing evidence exists on outcomes with genotype-guided cardiovascular therapies from multiple randomized controlled trials and observational studies. Pharmacogenetic evidence is accumulating for additional cardiovascular medications. However, data for many of these medications are not yet sufficient to support the use of genotyping for drug prescribing. Ultimately, pharmacogenetics might provide a means to individualize drug regimens for complex diseases such as heart failure, in which the treatment armamentarium includes a growing list of medications shown to reduce morbidity and mortality. However, sophisticated analytical approaches are likely to be necessary to dissect the genetic underpinnings of responses to drug combinations. In this Review, we examine the evidence supporting pharmacogenetic testing in cardiovascular medicine, including that available from several clinical trials. In addition, we describe guidelines that support the use of cardiovascular pharmacogenetics, provide examples of clinical implementation of genotype-guided cardiovascular therapies and discuss opportunities for future growth of the field.In this Review, Cavallari and colleagues examine the evidence supporting pharmacogenetic testing in cardiovascular medicine, describe guidelines for the use of cardiovascular pharmacogenetics and provide examples of the clinical implementation of genotype-guided therapies.

Background To realize potential public health benefits from genetic and genomic innovations, understanding how best to implement the innovations into clinical care is important. The objective of this study was to synthesize data on challenges identified by six diverse projects that are part of a National Human Genome Research Institute (NHGRI)-funded network focused on implementing genomics into practice and strategies to overcome these challenges. Methods We used a multiple-case study approach with each project considered as a case and qualitative methods to elicit and describe themes related to implementation challenges and strategies. We describe challenges and strategies in an implementation framework and typology to enable consistent definitions and cross-case comparisons. Strategies were linked to challenges based on expert review and shared themes. Results Three challenges were identified by all six projects, and strategies to address these challenges varied across the projects. One common challenge was to increase the relative priority of integrating genomics within the health system electronic health record (EHR). Four projects used data warehousing techniques to accomplish the integration. The second common challenge was to strengthen clinicians’ knowledge and beliefs about genomic medicine. To overcome this challenge, all projects developed educational materials and conducted meetings and outreach focused on genomic education for clinicians. The third challenge was engaging patients in the genomic medicine projects. Strategies to overcome this challenge included use of mass media to spread the word, actively involving patients in implementation (e.g., a patient advisory board), and preparing patients to be active participants in their healthcare decisions. Conclusions This is the first collaborative evaluation focusing on the description of genomic medicine innovations implemented in multiple real-world clinical settings. Findings suggest that strategies to facilitate integration of genomic data within existing EHRs and educate stakeholders about the value of genomic services are considered important for effective implementation. Future work could build on these findings to evaluate which strategies are optimal under what conditions. This information will be useful for guiding translation of discoveries to clinical care, which, in turn, can provide data to inform continual improvement of genomic innovations and their applications.

Pharmacogenetic (PGx) testing can individualize pharmacotherapy, but many current panels lack inclusivity for diverse populations and are often cost‐prohibitive for medically underserved communities. This study aimed to develop and validate GatorPGx Plus, a low‐cost, preemptive PGx panel tailored for diverse patient populations. Pharmacogenes were selected based on the drug/drug classes potentially influenced by their variants, the clinical severity of drug‐gene interactions, or the strength of guideline recommendations or emerging evidence. Variants within the pharmacogenes were included if their allele frequencies were approximately 1% or greater in any major ancestral population. The panel was validated for accuracy, precision, and analytical sensitivity and applied to 124 participants from an ongoing pharmacogenetic clinical implementation trial. To reduce costs, a high‐throughput platform was chosen, laboratory technician hands‐on time was minimized, and result translation and reporting were automated. The panel comprised tests for 62 variants in 14 genes/gene regions, including a CYP2D6 copy number assay. It demonstrated 100% concordance with reference methods. The average turnaround time between test order and results was 14.3 (±6.4) days. Among the 124 genotyped trial participants (mean age 60 years, 57.3% female), 99% had at least one non‐normal function (less common or higher‐risk) phenotype. The most frequently identified non‐normal function phenotypes were in CYP2C19 (69.4%). CYP2D6 *17, *29, and CYP2C19 *9 were captured at higher frequencies than reported in European populations. GatorPGx Plus is a low per‐test cost, clinically validated, preemptive PGx panel that effectively captures key variants in a mixed‐ancestry population, underscoring its potential clinical utility in diverse, medically underserved populations.

The University of Florida (UF) Health Personalized Medicine Program launched in 2012 with genotyping for clopidogrel response at UF Health Shands Hospital. We have since expanded genotyping to UF Health Jacksonville and established the infrastructure at UF Health to support clinical implementation for five additional gene-drug pairs: -thiopurines, ( )-PEG IFN-α-based regimens, -opioids, -antidepressants and -proton pump inhibitors. We are contributing to the evidence based on outcomes with genotype-guided therapy through pragmatic studies of our clinical implementations. In addition, we have developed a broad array of educational programs for providers, trainees and students that incorporate personal genotype evaluation to enhance participant learning.

The University of Florida Health Precision Medicine Program plays a crucial role in delivering pharmacogenomics (PGx) result notes to providers who request PGx testing. Despite this, there is currently a lack of a formal assessment of provider needs and established best practice design principles to guide the ongoing development of PGx result notes. This study aims to enhance the content and format of the PGx consult note at UF Health by incorporating valuable feedback from healthcare providers. Through in-depth user sessions involving 11 participants, we evaluated the usability of our consult note template. While overall satisfaction with the content was noted, specific sections, including those addressing phenoconversion and the medication list, were identified for revision to enhance clarity based on insightful provider feedback.

Background Population differences in warfarin dosing requirement have been reported; however, unlike the pharmacokinetics (PK) of warfarin, the quantitative influences of pharmacodynamic (PD) factors on the anticoagulation response to warfarin in different ethnic populations are totally unknown. Methods Using population PK/PD analysis, we attempted to identify predictors of S -warfarin clearance [CL(S)] and half maximal effective concentration (EC 50 ) to quantify racial differences in both PK and PD parameters, and to assess the contribution of these parameters to the international normalized ratio (INR) and over-anticoagulation response (INR ≥ 4) in a cohort of 309 White, Asian and African American patients. Results Similar to our previous findings, the median CL(S) was 30% lower in African American patients than Asian and White patients (169 vs. 243 and 234 mL/h, p  < 0.01). EC 50 showed a greater racial difference than CL(S) [1.03, 1.70 and 2.76 μg/mL for Asian, White and African American patients, respectively, p  < 0.01). Significant predictors of INR included demographic/clinical (age, body weight, creatinine clearance and sex) and genotypic ( CYP2C9*3,*8 and VKORC1 −1639G>A ) factors, as well as African American ethnicity. In all three racial groups, genetic predictors of INR appeared to have greater influence than demographic/clinical predictors. Both CL(S) and EC 50 contributed to the over-anticoagulation response to warfarin. Patients having VKORC1 −1639 G>A and/or factors associated with reduced CYP2C9 activity were more likely to have an INR ≥ 4. Conclusions Although there were contrasting racial differences in CL(S) and EC 50 that impacted on the INR, the racial difference in EC 50 was greater than that for CL(S), thus explaining the higher warfarin requirement for African American patients.