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The application of pharmacogenomics could meaningfully contribute toward medicines optimization within primary care. This review identified 13 studies describing eight implementation models utilizing a multi-gene pharmacogenomic panel within a primary care or community setting. These were small feasibility studies (n <200). They demonstrated importance and feasibility of pre-test counseling, the role of the pharmacist, data integration into the electronic medical record and point-of-care clinical decision support systems (CDSS). Findings were considered alongside existing primary care prescribing practices and implementation frameworks to demonstrate how issues may be addressed by existing nationalized healthcare and primary care infrastructure. Development of point-of-care CDSS should be prioritized; establishing clinical leadership, education programs, defining practitioner roles and responsibilities and addressing commissioning issues will also be crucial.

Several healthcare organizations across Minnesota have developed formal pharmacogenomic (PGx) clinical programs to increase drug safety and effectiveness. Healthcare professional and student education is strong and there are multiple opportunities in the state for learners to gain workforce skills and develop advanced competency in PGx. Implementation planning is occurring at several organizations and others have incorporated structured utilization of PGx into routine workflows. Laboratory-based and translational PGx research in Minnesota has driven important discoveries in several therapeutic areas. This article reviews the state of PGx activities in Minnesota including educational programs, research, national consortia involvement, technology, clinical implementation and utilization and reimbursement, and outlines the challenges and opportunities in equitable implementation of these advances.

Pharmacogenetics represents a major driver of precision medicine, promising individualized drug selection and dosing. Traditionally, pharmacogenetic profiling has been performed using targeted genotyping that focuses on common/known variants. Recently, whole-genome sequencing (WGS) is emerging as a more comprehensive short-read next-generation sequencing approach, enabling both gene diagnostics and pharmacogenetic profiling, including rare/novel variants, in a single assay. Using the example of the pharmacogene CYP2D6 , we demonstrate the potential of WGS-based pharmacogenetic profiling as well as emphasize the limitations of short-read next-generation sequencing. In the near future, we envision a shift toward long-read sequencing as the predominant method for gene diagnostics and pharmacogenetic profiling, providing unprecedented data quality and improving patient care.

Aim: To assess the impact of sociodemographic factors and beliefs about medicines on the uptake of pharmacogenomic testing in older adults in a public healthcare system. Materials & methods: Data are based on a sample of 347 primary care older adults. Results: Most respondents (90%) were willing to provide a saliva sample and 47% were willing to pay for it. Increased age (odds ratio: 0.91; p = 0.04) and negative beliefs about the harmfulness of medicines (odds ratio: 0.68; p = 0.02) were associated with a decreased willingness to provide a sample. Lower education (less than university, odds ratio: 0.54; p = 0.04) was associated with a decreased willingness to pay. Conclusion: Education and beliefs about medicines are important factors in the acceptability of pharmacogenomic testing in older adults.

Pharmacogenomics test coverage and reimbursement are major obstacles to clinical uptake. Several early adopter programs have been successfully initiated through dedicated investments by federal and institutional research funding. As a result of research endeavors, evidence has grown sufficiently to support development of pharmacogenomics guidelines. However, clinical uptake is still limited. Third-party payer support plays an important role in increasing adoption, which to date has been limited to reactive single-gene testing. Access to and interest in direct-to-consumer genetic testing are driving demand for increasing healthcare providers and third-party awareness of this burgeoning field. Pharmacogenomics implementation models developed by early adopters promise to expand patient access and options, as testing continues to increase due to growing consumer interest and falling test prices.

This narrative review describes implementation, current status and perspectives of a pharmacogenomic (PGx) program at the Brazilian National Cancer Institute (INCA), targeting the cancer chemotherapeutic drugs - fluoropyrimidines, irinotecan and thiopurines. This initiative, designed as a research project, was supported by a grant from the Brazilian Ministry of Health. A dedicated task force developed standard operational procedures from recruitment of patients to creating PGx reports with dosing recommendations, which were successfully applied to test 100 gastrointestinal cancer INCA outpatients and 162 acute lymphoblastic leukemia pediatric patients from INCA and seven other hospitals. The program has been subsequently expanded to include gastrointestinal cancer patients from three additional cancer treatment centers. We anticipate implementation of routine pre-emptive PGx testing at INCA but acknowledge challenges associated with this transition, such as continuous financing support, availability of trained personnel, adoption of the PGx-informed prescription by the clinical staff and, ultimately, evidence of cost-effectiveness.

Aim: CYP2C19 and multigene pharmacogenomics (PGx) testing on medications beyond antiplatelet therapy in a real-world cohort of PCI patients that underwent CYP2C19 and multigene pharmacogenomics (PGx) testing on medications beyond antiplatelet therapy in a real-world cohort of PCI patients that underwent CYP2C19 testing. Methodology & results: Multiple medications with actionable PGx recommendations, including proton pump inhibitors, antidepressants and opioids, were commonly prescribed. Approximately 50% received a CYP2C19 metabolized medication beyond clopidogrel and 7% met criteria for a CYP2C19 genotype-guided intervention. A simulation analysis projected that 17.5 PGx-guided medication interventions per 100 PCI patients could have been made if multigene PGx results were available. Conclusion: This suggests that CYP2C19 and multigene PGx results could be used to optimize medication prescribing beyond antiplatelet therapy in PCI patients.

Next-generation sequencing (NGS) has enabled the discovery of a multitude of novel and mostly rare variants in pharmacogenes that may alter a patient's therapeutic response to drugs. In addition to single nucleotide variants, structural variation affecting the number of copies of whole genes or parts of genes can be detected. While current guidelines concerning clinical implementation mostly act upon well-documented, common single nucleotide variants to guide dosing or drug selection, in silico and large-scale functional assessment of rare variant effects on protein function are at the forefront of pharmacogenetic research to facilitate their clinical integration. Here, we discuss the role of NGS in variant discovery, paving the way for more comprehensive genotype-guided pharmacotherapy that can translate to improved clinical care.

Aim: To investigate the current state of TPMT testing at a single-academic medical center. Methods: Single-center, retrospective chart review for patients newly prescribed a thiopurine. Data collection and evaluation included the prevalence and timing of TPMT testing, correct dosage adjustment if applicable, and incidence of myelosuppression. Results: 121 patients (71%) received TPMT testing. Out of the tested patients, 110 (90.9%) were designated as wild-type with normal metabolism. Dosing modification was appropriate in applicable patients. In unadjusted analysis, there was a lower incidence of myelosuppression among patients who were tested versus those who were not (16.5 vs 36.7%). Conclusion: Based on the study results, TPMT testing opportunities exist for nearly 30% of patients. Testing may reduce the incidence of myelosuppression.

Aims:  Patients' use of and experience with pharmacogenetic (PGx) testing may be impacted by several factors including patient and provider knowledge, health status, and perceived understanding of results.  Materials & Methods:  We conducted an online survey of individuals who had subscribed to a newsletter service offered by a US commercial PGx testing company, Genelex.  Results:  We find that about half of respondents that had PGx testing reviewed one or more of the lab's web-pages, 43% believed they understood the test results very well, but 40% did not know or could not recall whether their provider had changed their prescription based on the test result.  Conclusions:  There was limited use of the laboratory's online resources by respondents undergoing PGx testing. Increased awareness of the website may improve understanding of test results and facilitate discussions with providers about medication changes.

Despite the significant advances achieved in pediatric acute lymphocytic leukemia (ALL) treatment, adverse side effects of drugs remain a challenging issue. Numerous ALL pharmacogenomic studies have been conducted to elucidate the predisposing genetic factors for their development. Plausible pharmacogenomic data are available for the osteonecrosis associated with glucocorticoids, the neurotoxicity associated with vincristine and the cardiotoxicity related to anthracyclines. However, these data have not been fully translated into the clinic due to several limitations, most importantly the lack of reliable evidence. The most robust pharmacogenomics data are those for thiopurines and methotrexate use, with evidence-based preemptive testing recommendations for the former. Pharmacogenomics has a significant potential utility in pediatric ALL treatment regimens. In this review, gaps and limitations in this field are emphasized, which may provide a useful guide for future research design.

CYP2D6 is one of the most studied enzymes in the field of pharmacogenetics. The CYP2D6 gene is highly polymorphic with over 100 catalogued star (*) alleles, and clinical CYP2D6 testing is increasingly accessible and supported by practice guidelines. However, the degree of variation at the CYP2D6 locus and homology with its pseudogenes make interrogating CYP2D6 by short-read sequencing challenging. Moreover, accurate prediction of CYP2D6 metabolizer status necessitates analysis of duplicated alleles when an increased copy number is detected. These challenges have recently been overcome by long-read CYP2D6 sequencing; however, such platforms are not widely available. This review highlights the genomic complexities of CYP2D6, current sequencing methods and the evolution of CYP2D6 from allele discovery to clinical pharmacogenetic testing.

Aim: This study aims to assess the attitudes and opinions of clinicians practicing in psychiatry toward pharmacogenomic testing, and in so doing elicits possible barriers and risks to employ this technology in patient care., Materials & Methods: Doctors and pharmacists presently practicing in psychiatry were invited to participate in an anonymous web-based survey. Besides information on participant characteristics and experience in psychiatry, specific themes on pharmacogenomics including self-assessed competency, perceived usefulness in clinical situations, perceived risks and preferred mode of education were evaluated., Results: A total of 81% of respondents believed that pharmacogenomic testing would be useful for identifying suitable treatments and 71% believed that pharmacogenomic testing would be useful for medication intolerance. However, only 46.4% felt competent to order these tests. There were significant differences in responses for gender, doctors versus pharmacists and seniority in position. A total of 94.3% of respondents were concerned about costs and 84.5% were concerned about the lack of clear guidelines on its use. A total of 98.5% of respondents were keen on learning more about the applicability of pharmacogenomics, and the most preferred format of education was a lecture (44.5%)., Conclusion: Most clinicians acknowledge the potential of pharmacogenomic testing in clinical practice. However, concerns with regard to its cost-effectiveness and the lack of clear guidelines are possible barriers to its clinical implementation.