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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.

The implementation of pharmacogenomics (PGx) has come a long way since the dawn of utilizing pharmacogenomic data in clinical patient care. However, the potential benefits of sharing PGx results have yet to be explored. In this paper, we explore the willingness of patients to share PGx results, as well as the inclusion of family medication history in identifying potential family members for pharmacogenomics cascade testing (PhaCT). The genetic similarities in families allow for identifying potential gene variants prior to official preemptive testing. Once a candidate patient is determined, PhaCT can be initiated. PhaCT recognizes that further cascade testing throughout a family can serve to improve precision medicine. In order to make PhaCT feasible, we propose a novel shareable HIPAA-compliant informatics platform that will enable patients to manage not only their own test results and medications but also those of their family members. The informatics platform will be an external genomics system with capabilities to integrate with patients' electronic health records. Patients will be given the tools to provide information to and work with clinicians in identifying family members for PhaCT through this platform. Offering patients the tools to share PGx results with their family members for preemptive testing could be the key to empowering patients. Clinicians can utilize PhaCT to potentially improve medication adherence, which may consequently help to distribute the burden of health management between patients, family members, providers, and payers.

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.

Interindividual variability in drug efficacy and toxicity is a major challenge in clinical practice. Variations in drug pharmacokinetics (PKs) and pharmacodynamics (PDs) can be, in part, explained by polymorphic variants in genes encoding drug metabolizing enzymes and transporters (absorption, distribution, metabolism, and excretion) or in genes encoding drug receptors. Pharmacogenomics (PGx) has allowed the identification of predictive biomarkers of drug PKs and PDs and the current knowledge of genome-disease and genome-drug interactions offers the opportunity to optimize tailored drug therapy. High-throughput PGx genotyping, from targeted to more comprehensive strategies, allows the identification of PK/PD genotypes to be developed as clinical predictive biomarkers. However, a biomarker needs a robust process of validation followed by clinical-grade assay development and must comply to stringent regulatory guidelines. We here discuss the methodological challenges and the emerging technological tools in PGx biomarker discovery and validation, at the crossroad among molecular genetics, bioinformatics, and clinical medicine., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Pharmacogenomics (PGx) testing, which aims to identify the genes that affect our responses to drugs, has been favoured by healthcare professionals as a means of maximising drug efficacy and improving the safety and cost-effectiveness of healthcare. Support from the public is needed to determine the successful development of this technology and its implementation in society. Therefore, the objective of this paper was to analyse factors that influence stakeholders' intentions to adopt pharmacogenomic testing in Malaysia. A validated instrument was administered through face-to-face interviews with a total of 421 adult respondents who were stratified according to 2 stakeholder groups: healthcare providers (n = 221) and patients/family members (n = 200). The data were then analysed using SPSS® version 24 software and the advanced multivariate statistical approach of Partial Least Square (PLS) path modelling in order to analyse the complex relationships among variables. Results of the studies indicated that the Malaysian stakeholders had a high amount of trust in the key players (mean score of 5.31), perceived high benefits (mean score of 5.53) and claimed to have high intentions of adopting PGx (mean score of 5.39). The majority of the predictors have significant direct relationships with the intention to adopt PGx, with the exception of moral concerns. Perceived benefits appeared to be the most important direct predictor of the intention to adopt PGx testing (ß = 0.371, P < 0.001) followed by trust in the key players (ß = 0.312, P < 0.001), engagement (ß = 0.272, P < 0.001) and religiosity (ß = 0.133, P < 0.01). In addition, perceived risks also had a direct negative association with the intention to adopt PGx (ß = -0.096, P < 0.05). At the same time, the perceived benefits also served as a mediator for all the other factors except risk. The results provide insights into the multidimensional nature of the determinants of the intention to adopt PGx testing in Malaysia. Although the results showed that the stakeholders in Malaysia were very positive towards PGx testing, they were also cautious about it. The predictors identified in this study can serve as indicators for social acceptance of PGx testing to facilitate the clinical research and implementation of PGx.

In this narrative, we evaluate the role of pharmacogenetics in psychiatry from a pragmatic clinical perspective and address current barriers of clinical implementation of pharmacogenetics. Pharmacogenetics has been successfully implemented to improve drug therapy in several clinical areas, but not psychiatry. Yet, psychotropics account for more than one-third of the drugs for which pharmacogenetic guidelines are available and drug therapy in mental disorders is suboptimal with insufficient effectiveness and frequent adverse events. The limited application of pharmacogenetics in psychiatry is influenced by several factors; e.g. the complexity of psychotropic drug metabolism, possibly impeding the clinical understanding of the benefits of pharmacogenetics. Also, recommendations for most psychotropics classify pharmacogenetic testing only as (potentially) beneficial, not as essential, possibly because life-threatening adverse events are often not involved in these drug-gene interactions. Implementing pharmacogenetics in psychiatry could improve the current practice of time-consuming switching of therapies causing undue delays associated with worse outcomes. We expect pharmacogenetics in psychiatry to expedite with panel-based genotyping, including clinically relevant variants, which will address the complex enzymatic metabolism of psychotropic drugs. Until then, we stress that available pharmacogenetic testing should be seen as an integrated companion, not a competitor, in current clinical psychiatric care., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Large sample sizes are often required to detect statistically significant associations between pharmacogenetic markers and treatment response. Meta-analysis may be performed to synthesize data from several studies, increasing sample size and, consequently, power to detect significant genetic effects. However, performing robust synthesis of data from pharmacogenetic studies is often challenging because of poor reporting of key data in study reports. There is currently no guideline for the reporting of pharmacogenetic studies that has been developed using a widely accepted robust methodology. The objective of this project was to develop the STrengthening the Reporting Of Pharmacogenetic Studies (STROPS) guideline., Methods and Findings: We established a preliminary checklist of reporting items to be considered for inclusion in the guideline. We invited representatives of key stakeholder groups to participate in a 2-round Delphi survey. A total of 52 individuals participated in both rounds of the survey, scoring items with regards to their importance for inclusion in the STROPS guideline. We then held a consensus meeting, at which 8 individuals considered the results of the Delphi survey and voted on whether each item ought to be included in the final guideline. The STROPS guideline consists of 54 items and is accompanied by an explanation and elaboration document. The guideline contains items that are particularly important in the field of pharmacogenetics, such as the drug regimen of interest and whether adherence to treatment was accounted for in the conducted analyses. The guideline also requires that outcomes be clearly defined and justified, because in pharmacogenetic studies, there may be a greater number of possible outcomes than in other types of study (for example, disease-gene association studies). A limitation of this project is that our consensus meeting involved a small number of individuals, the majority of whom are based in the United Kingdom., Conclusions: Our aim is for the STROPS guideline to improve the transparency of reporting of pharmacogenetic studies and also to facilitate the conduct of high-quality systematic reviews and meta-analyses. We encourage authors to adhere to the STROPS guideline when publishing pharmacogenetic studies., Competing Interests: The authors have declared that no competing interests exist.

SWEDEGENE is a Swedish nation-wide sample collection established to facilitate studies of clinical and genetic risk factors for adverse drug reactions (ADRs). Most cases are recruited among patients reported to the ADR registry at the Swedish Medical Products Agency by health-care professionals. Clinical data are collected both from medical and laboratory records and through interviews using standardized questionnaires. Genome-wide scans and whole-genome sequencing are done, and association studies are conducted using mainly controls from the Swedish TwinGene biobank with data on diagnoses and prescribed drugs. SWEDEGENE was established in 2008 and currently contains DNA and information from about 2550 adults who have experienced specific ADRs, and from 580 drug exposed controls. Results from genome-wide association studies have now been published, and data from whole-genome sequencing are being analyzed. SWEDEGENE has the potential to offer a new means of developing individualized and safe drug therapy through patient pre-treatment screening.

Aim: To survey the general public about whole genome sequencing interest, including pharmacogenomic testing, and to identify information important for sequencing decisions. Patients & methods: An online survey of 901 members of the general public in an eastern Canadian province. Results: Interest in whole genome sequencing, including pharmacogenomic testing, was high with few differences among demographic variables. Issues identified as very important to sequencing decisions included familial implications of testing, whether treatment was available for conditions tested and knowing who could access genomic information. Most respondents would value support when interpreting sequencing results. Conclusion: Findings reveal the kind of information and support users of sequencing services would value and could inform the implementation of sequencing into care in ways that accord with public preferences and needs.

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 genotyping is used to guide antiplatelet therapy after percutaneous coronary intervention (PCI). This study evaluated the potential impact of 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.

Purpose of Review: Childhood asthma is a heterogeneous inflammatory disease comprising different phenotypes and endotypes and, particularly in its severe forms, has a large impact on the quality-of-life of patients and caregivers. The application of advanced omics technologies provides useful insights into underlying asthma endotypes and may provide potential clinical biomarkers to guide treatment and move towards a precision medicine approach., Recent Findings: The current article addresses how novel omics approaches have shaped our current understanding of childhood asthma and highlights recent findings from (pharmaco)genomics, epigenomics, transcriptomics, and metabolomics studies on childhood asthma and their potential clinical implications to guide treatment in severe asthmatics., Summary: Until now, omics studies have largely expanded our view on asthma heterogeneity, helped understand cellular processes underlying asthma, and brought us closer towards identifying (bio)markers that will allow the prediction of treatment responsiveness and disease progression. There is a clinical need for biomarkers that will guide treatment at the individual level, particularly in the field of biologicals. The integration of multiomics data together with clinical data could be the next promising step towards development individual risk prediction models to guide treatment. However, this requires large-scale collaboration in a multidisciplinary setting.

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.

Purpose: A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers., Methods: We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption. Data were collected on testing approaches, return of results procedures, applications of genotype results, challenges faced, and lessons learned., Results: Among early adopters, CYP2D6 testing was most commonly ordered to assist with opioid and antidepressant prescribing. Key differences among programs included test ordering and genotyping approaches, result reporting, and clinical decision support. However, all sites tested for copy-number variation and nine common variants, and reported results in the medical record. Most sites provided automatic consultation and had designated personnel to assist with genotype-informed therapy recommendations. Primary challenges were related to stakeholder support, CYP2D6 gene complexity, phenotype assignment, and sustainability., Conclusion: There are specific challenges unique to CYP2D6 testing given the complexity of the gene and its relevance to multiple medications. Consensus lessons learned may guide those interested in pursuing similar clinical pharmacogenetic programs.

Objective: To explore the implications of direct-to-consumer pharmacogenomic testing for community pharmacy practice., Summary: In October 2018, the U.S. Food and Drug Administration provided approval for direct-to-consumer genetic testing company, 23andMe (Mountain View, CA), to return select pharmacogenomic test results to their customers. Given the community pharmacist's high accessibility to the public and in-depth knowledge of pharmacology, and the availability of direct-to-consumer genetic testing kits at pharmacies, it is likely that patients will present their pharmacogenomic test results to their pharmacists and expect them to incorporate those results into their care. It is important, therefore, that community pharmacists are aware of the clinical implications of these results, know where to turn for evidence-based clinical pharmacogenomics information, and be mindful of the need for confirmatory testing before changing therapy., Conclusion: Community pharmacists are at the frontlines of health care, and as such will be at the frontlines of direct-to-consumer pharmacogenomic testing. In the near future, it is likely that community pharmacists will need to counsel patients on the interpretation and appropriate use of direct-to-consumer pharmacogenomic test results., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Introduction : Over the last decade, the spread of next-generation sequencing technology along with the rising cost in health management in national health systems has led to widespread use/abuse of pharmacogenetic tests (PGx) in the practice of many clinical disciplines. However, given their clinical significance, it is important to standardize these tests for having an interaction with the clinical analysis laboratory (CAL), in which a PGx service can meet these requirements. Areas covered : A diagnostic test must meet the criteria of reproducibility and validity for its utility in the clinical routine. This present review mainly describes the utility of introducing PGx tests in the CAL routine to produce correct results useful for setting up personalized drug treatments. Expert opinion : With a PGx service, CALs can provide the right tool to help clinicians to make better choices about different categories of drugs and their dosage and to manage the economic impact both in hospital-based settings and in National Health Services, throughout electronic health records. Advances in PGx also allow a new approach for pharmaceutical companies in order to improve drug development and clinical trials. As a result, CALs can achieve a powerful source of epidemiological, clinical, and research findings from PGx tests.

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.

Purpose: Preemptive pharmacogenetic testing aims to optimize medication use by having genetic information at the point of prescribing. Payers' decisions influence implementation of this technology. We investigated US payers' knowledge, awareness, and perspectives on preemptive pharmacogenetic testing., Methods: A qualitative study was conducted using semistructured interviews. Participants were screened for eligibility through an online survey. A blended inductive and deductive approach was used to analyze the transcripts. Two authors conducted an iterative reading process to code and categorize the data., Results: Medical or pharmacy directors from 14 payer organizations covering 122 million US lives were interviewed. Three concept domains and ten dimensions were developed. Key findings include clinical utility concerns and limited exposure to preemptive germ-line testing, continued preference for outcomes from randomized controlled trials, interest in guideline development, importance of demonstrating an impact on clinical decision making, concerns of downstream costs and benefit predictability, and the impact of public stakeholders such as the Food and Drug Administration and Centers for Medicare and Medicaid Services., Conclusion: Both barriers and potential facilitators exist to developing cohesive reimbursement policy for pharmacogenetics, and there are unique challenges for the preemptive testing model. Prospective outcome studies, more precisely defining target populations, and predictive economic models are important considerations for future research.

Aim: To evaluate factors influencing cardiologists' perspectives about pharmacogenomic (PGx) testing in clinical practice., Patients & Methods: Semistructured interviews with practicing cardiologists were qualitatively analyzed to identify common themes., Results: Five themes were identified among 16 cardiologists from four specialties (n = 5 general cardiology, n = 3 electrophysiology, n = 2 adult congenital and n = 6 heart failure/transplant): cardiologists' knowledge and needs, perceived clinical validity and utility of PGx testing, dissemination and management of PGx results, patient-related considerations and incidental findings., Conclusion: Lack of evidence was considered by many cardiologists to be a major barrier hindering the use of PGx testing. However, they would consider adopting PGx if they were provided additional education, ongoing support and evidence supporting the clinical utility of PGx testing in cardiovascular medicine.

The field of pharmacogenomics is an area of great potential for near-term human health impacts from the big genomic data revolution. Pharmacogenomics research momentum is building with numerous hypotheses currently being investigated through the integration of molecular profiles of different cell lines and large genomic data sets containing information on cellular and human responses to therapies. Additionally, the results of previous pharmacogenetic research efforts have been formulated into clinical guidelines that are beginning to impact how healthcare is conducted on the level of the individual patient. This trend will only continue with the recent release of new datasets containing linked genotype and electronic medical record data. This review discusses key resources available for pharmacogenomics and pharmacogenetics research and highlights recent work within the field.

High throughput sequencing has opened up new clinical opportunities moving towards a medicine of precision. Oncology, infectious diseases or human genomics, many applications have been developed in recent years. The introduction of a third generation of nanopore-based sequencing technology, addressing some of the weaknesses of the previous generation, heralds a new revolution. Portability, real time, long reads and marginal investment costs, these promising new technologies point to a new shift of paradigm. What are the perspectives opened up by nanopores for clinical applications?, (© 2018 médecine/sciences – Inserm.)

In 2014, we established a pharmacogenetics unit with the intention of facilitating the integration of pharmacogenetic testing into clinical practice. This unit was centered around two main ideas: i) individualization of clinical recommendations, and ii) preemptive genotyping in risk populations. Our unit is based on the design and validation of a single nucleotide polymorphism (SNP) microarray, which has allowed testing of 180 SNPs associated with drug response (PharmArray), and clinical consultation regarding the results. Herein, we report our experience in integrating pharmacogenetic testing into our hospital and we present the results of the 2,539 pharmacogenetic consultation requests received over the past 3 years in our unit. The results demonstrate the feasibility of implementing pharmacogenetic testing in clinical practice within a national health system., (© 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objectives: To examine the knowledge, attitudes, and interest of an inner-city population toward pharmacogenetic testing, with the primary objective of identifying facilitators and barriers toward pharmacogenetic testing; and secondary objectives of determining predictors of patient interest in pharmacogenetic testing and how much patients would pay for the test., Methods: Patients were recruited from an Antithrombosis Clinic from March to April 2014. A cross-sectional 19-question survey was administered in person to determine patients' knowledge and awareness of pharmacogenetic testing and collect demographic information. After explaining pharmacogenetics, patients ranked their interest toward the test and answered open-ended questions that elicited facilitators and barriers toward pharmacogenetic testing and elucidated how much patients would pay for testing., Results: A total of 120 patients (mean age 55.0 ± 14.0 years, 39.2% male, 69.2% African American) were surveyed. Facilitators included providing further information about pharmacogenetic testing; elaborating on benefits of testing to predict treatment efficacy; patients' trust in their providers to make correct genotype-guided prescribing decisions; and insurance coverage and test affordability. Barriers to testing included concerns about the negative consequences associated with test results; burden of the testing process; perceived lack of utility among elderly and those whose medications were working; privacy issues; and concerns regarding insurance coverage and test affordability. Women had 4.2 times higher adjusted odds of being interested in pharmacogenetic testing. Almost half (44.4%) of the patients with high interest in the test were willing to pay $20 or more, whereas 76.2% of patients with low interest wanted testing at no cost., Conclusion: This study identified facilitators, such as providing additional pharmacogenetic test information, and barriers, such as perceived negative impact of the results and test utility, as issues to address when engaging an urban, largely minority population in pharmacogenetic testing. Female sex was a predictor of interest toward pharmacogenetic testing. These facilitators and barriers should be taken into consideration as pharmacogenetic testing gains widespread utility among inner-city populations., (© 2017 Pharmacotherapy Publications, Inc.)

Advancing the use of biomarkers and pharmacogenomics has been a key priority area for the U.S. Food and Drug Administration (FDA). The FDA offers prescribing recommendations to manage ~100 gene-drug interactions, and multiple institutions around the United States and abroad have incorporated genomic testing into patient care. However, the penetration of pharmacogenomic testing remains incomplete. In this perspective, we summarize the evidence streams to support the clinical utility of pharmacogenomic testing and its transition into clinical practice., (© 2017 Pharmacotherapy Publications, Inc.)

Aim: To explore primary care physicians' views of the utility and delivery of direct access to pharmacogenomics (PGx) testing in a community health system., Methods: This descriptive study assessed the perspectives of 15 healthcare providers utilizing qualitative individual interviews., Results: Three main themes emerged: perceived value and utility of PGx testing; challenges to implementation in practice; and provider as well as patient needs., Conclusion: While providers in this study viewed benefits of PGx testing as avoiding side effects, titrating doses more quickly, improving shared decision-making and providing psychological reassurance, challenges will need to be addressed such as privacy concerns, cost, insurance coverage and understanding the complexity of PGx test results.

The extent to which pharmacogenomic-guided medication use has been adopted in various health systems is unclear. To assess the uptake of pharmacogenomic-guided medication use, we determined its frequency across our health system, which does not have a structured testing program. Using a multisite clinical data repository, we identified adult patients' first prescribed medications between January 2011 and December 2013 and investigated the frequency of germline and somatic pharmacogenomic testing, by the Pharmacogenomics Knowledgebase level of the US Food and Drug Administration label information. There were 268,262 medication orders for drugs with germline pharmacogenomic testing information in their drug labels. Pharmacogenomic testing was detected for 1.5% (129/8,718) of medication orders with recommended or required testing. Of the 3,817 medication orders associated with somatic pharmacogenomic testing information in their drug labels, 20% (372/1,819) of required tests were detected. The low rates of detectable pharmacogenomic testing suggest that structured testing programs are required to achieve the success of precision medicine., (© 2017 American Society for Clinical Pharmacology and Therapeutics.)

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.

Multiple sclerosis (MS) is a chronic, progressive, disabling disorder characterized by immune-mediated demyelination, inflammation, and neurodegenerative tissue damage in the central nervous system (CNS), associated with frequent exacerbations and remissions of neurologic symptoms and eventual permanent neurologic disability. While there are several MS therapies that are successful in reducing MS relapses, none have been effective in treating all patients. The specific response of an individual patient to any one of the MS therapies remains largely unpredictable, and physicians and patients are forced to use a trial and error approach when deciding on treatment regimens. A priori markers to predict the optimal benefit-to-risk profile of an individual MS patient would greatly facilitate the decision-making process, thereby helping the patient receive the most optimal treatment early on in the disease process. Pharmacogenomic methods evaluate how a person's genetic and genomic makeup affects their response to therapeutics. This review focuses on how pharmacogenomics studies are being used to identify biologically relevant differences in MS treatments and provide characterization of the predictive clinical response patterns. As pharmacogenomics research is dependent on the availability of longitudinal clinical research, studies concerning glatiramer acetate and the interferon beta products which have the majority of published long term data to date are described in detail. These studies have provided considerable insight in the prognostic markers associated with MS disease and potential predictive markers of safety and beneficial response., (Copyright © 2016. Published by Elsevier Ltd.)

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.

Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. Opportunely, several implementation studies and programs have been initiated over recent years. This article presents an overview of these studies and identifies current research gaps. Importantly, one such gap is the undetermined collective clinical utility of implementing a panel of PGx-markers into routine care, because the evidence base is currently limited to specific, individual drug-gene pairs. The Ubiquitous Pharmacogenomics (U-PGx) Consortium, which has been funded by the European Commission's Horizon-2020 program, aims to address this unmet need. In a prospective, block-randomized, controlled clinical study (PREemptive Pharmacogenomic testing for prevention of Adverse drug REactions [PREPARE]), pre-emptive genotyping of a panel of clinically relevant PGx-markers, for which guidelines are available, will be implemented across healthcare institutions in seven European countries. The impact on patient outcomes and cost-effectiveness will be investigated. The program is unique in its multicenter, multigene, multidrug, multi-ethnic, and multihealthcare system approach., (© 2016 American Society for Clinical Pharmacology and Therapeutics.)

Purpose: The process and methods used by payers when evaluating coverage of personalized medicine testing are described., Summary: Personalized medicine encompasses a number of diagnostic tools that measure drug metabolism, genetic risk for disease development, and tumor type or markers that can guide oncology treatments. However, whole genome testing, tumor marker testing, and testing for drug metabolism are additional costs to the healthcare system. In order to justify these costs, payers and health technology assessment bodies must evaluate the individual tests or groups of tests on their own merits. In order for a test to be covered by payers, test developers must demonstrate clinical utility as measured by improved outcomes or well-informed decision-making. In the United States, payers generally focus on clinical benefit to individual patients and benefits to the healthcare system. Clinical benefits include improved outcomes. Benefits to the healthcare system are generally considered to be cost offsets, which may be due to reductions in the use of unnecessary interventions or to more efficient use of resources. Provider organizations have been assuming more responsibility and liability for healthcare costs through various risk arrangements, including accountable care organizations and patient-centered medical homes. Diagnostic tests that increase efficiency, reduce unnecessary interventions, and improve outcomes will be chosen by specialists in provider organizations., Conclusion: For personalized medicine approaches to be adopted and covered by health plans, the methods must be shown to be analytically and clinically valid and provide clinical utility at a reasonable level of cost-effectiveness to payers., (Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Clinical trials in psychiatry allow to build the regulatory dossiers for market authorization but also to document the mechanism of action of new drugs, to build pharmacodynamics models, evaluate the treatment effects, propose prognosis, efficacy or tolerability biomarkers and altogether to assess the impact of drugs for patient, caregiver and society. However, clinical trials have shown some limitations. Number of recent dossiers failed to convince the regulators. The clinical and biological heterogeneity of psychiatric disorders, the pharmacokinetic and pharmacodynamics properties of the compounds, the lack of translatable biomarkers possibly explain these difficulties. Several breakthrough options are now available: quantitative system pharmacology analysis of drug effects variability, pharmacometry and pharmacoepidemiology, Big Data analysis, brain modelling. In addition to more classical approaches, these opportunities lead to a paradigm change for clinical trials in psychiatry., (© L’Encéphale, Paris, 2016.)

Purpose: Both regulatory science and clinical practice rely on best available scientific data to guide decision-making. However, changes in clinical practice may be driven by numerous other factors such as cost. In this review, we reexamine noteworthy examples where pharmacogenetic testing information was added to drug labeling to explore how the available evidence, potential public health impact, and predictive utility of each pharmacogenetic biomarker impacts clinical uptake., Summary: Advances in the field of pharmacogenetics have led to new discoveries about the genetic basis for variability in drug response. The Food and Drug Administration recognizes the value of pharmacogenetic testing strategies and has been proactive about incorporating pharmacogenetic information into the labeling of both new drugs and drugs already on the market. Although some examples have readily translated to routine clinical practice, clinical uptake of genetic testing for many drugs has been limited., Conclusion: Both regulatory science and clinical practice rely on data-driven approaches to guide decision making; however, additional factors are also important in clinical practice that do not impact regulatory decision making, and these considerations may result in heterogeneity in clinical uptake of pharmacogenetic testing., (Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

The terms "personalized" or "precision" medicine are being used commonly in some branches of medicine but have yet to be widely adopted in vascular surgery. Despite this, personalized vascular therapy occurs on a daily basis in every vascular specialist's office as we strive to make informed recommendations at the individual patient level. The following is a description of several of the areas where advances in personalized vascular care have been achieved, including custom devices, personalized predictions, pharmacogenetics and surgicogenetics., (© The Author(s) 2016.)

Context: -Precision medicine is the promise of individualized therapy and management of patients based on their personal biology. There are now multiple global initiatives to perform whole-genome sequencing on millions of individuals. In the United States, an early program was the Million Veteran Program, and a more recent proposal in 2015 by the president of the United States is the Precision Medicine Initiative. To implement precision medicine in routine oncology care, genetic variants present in tumors need to be matched with effective clinical therapeutics. When we focus on the current state of precision medicine for gastrointestinal malignancies, it becomes apparent that there is a mixed history of success and failure., Objective: -To present the current state of precision medicine using gastrointestinal oncology as a model. We will present currently available targeted therapeutics, promising new findings in clinical genomic oncology, remaining quality issues in genomic testing, and emerging oncology clinical trial designs., Data Sources: -Review of the literature including clinical genomic studies on gastrointestinal malignancies, clinical oncology trials on therapeutics targeted to molecular alterations, and emerging clinical oncology study designs., Conclusions: -Translating our ability to sequence thousands of genes into meaningful improvements in patient survival will be the challenge for the next decade.