Strategies to Improve the Clinical Outcomes for Direct-to-Consumer Pharmacogenomic Tests.
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ABSTRACT:
SUBMITTER: Tafazoli A
PROVIDER: S-EPMC7999840 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug safety, helping to improve drug efficacy or reduce the risk of toxicity. Despite its clinical relevance, the implementation of PGx testing in paediatric practice to date has been variable and limited. As with most paediatric pharmacological studies, there are well-recognised barriers to obtaining high-quality PGx evidence, particularly when patient numbers may be small, and off-label or unlicensed prescribing remains widespread. Furthermore, trials enrolling small numbers of children can rarely, in isolation, provide sufficient PGx evidence to change clinical practice, so extrapolation from larger PGx studies in adult patients, where scientifically sound, is essential. This review paper discusses the relevance of PGx to paediatrics and considers implementation strategies from a child health perspective. Examples are provided from Canada, the Netherlands and the UK, with consideration of the different healthcare systems and their distinct approaches to implementation, followed by future recommendations based on these cumulative experiences. Improving the evidence base demonstrating the clinical utility and cost-effectiveness of paediatric PGx testing will be critical to drive implementation forwards. International, interdisciplinary collaborations will enhance paediatric data collation, interpretation and evidence curation, while also supporting dedicated paediatric PGx educational initiatives. PGx consortia and paediatric clinical research networks will continue to play a central role in the streamlined development of effective PGx implementation strategies to help optimise paediatric pharmacotherapy.
| S-EPMC9544158 | biostudies-literature
Project description:BackgroundClinical laboratory tests are now being prescribed and made directly available to consumers through retail outlets in the USA. Concerns with these test have been raised regarding the uncertainty of testing methods used in these venues and a lack of open, scientific validation of the technical accuracy and clinical equivalency of results obtained through these services.MethodsWe conducted a cohort study of 60 healthy adults to compare the uncertainty and accuracy in 22 common clinical lab tests between one company offering blood tests obtained from finger prick (Theranos) and 2 major clinical testing services that require standard venipuncture draws (Quest and LabCorp). Samples were collected in Phoenix, Arizona, at an ambulatory clinic and at retail outlets with point-of-care services.ResultsTheranos flagged tests outside their normal range 1.6× more often than other testing services (P < 0.0001). Of the 22 lab measurements evaluated, 15 (68%) showed significant interservice variability (P < 0.002). We found nonequivalent lipid panel test results between Theranos and other clinical services. Variability in testing services, sample collection times, and subjects markedly influenced lab results.ConclusionWhile laboratory practice standards exist to control this variability, the disparities between testing services we observed could potentially alter clinical interpretation and health care utilization. Greater transparency and evaluation of testing technologies would increase their utility in personalized health management.FundingThis work was supported by the Icahn Institute for Genomics and Multiscale Biology, a gift from the Harris Family Charitable Foundation (to J.T. Dudley), and grants from the NIH (R01 DK098242 and U54 CA189201, to J.T. Dudley, and R01 AG046170 and U01 AI111598, to E.E. Schadt).
| S-EPMC4855945 | biostudies-literature
Project description:Although at first relatively disinterested in race, modern genomic research has increasingly turned attention to racial variations. We examine a prominent example of this focus-direct-to-consumer racial admixture tests-and ask how information about the methods and results of these tests in news media may affect beliefs in racial differences. The reification hypothesis proposes that by emphasizing a genetic basis for race, thereby reifying race as a biological reality, the tests increase beliefs that whites and blacks are essentially different. The challenge hypothesis suggests that by describing differences between racial groups as continua rather than sharp demarcations, the results produced by admixture tests break down racial categories and reduce beliefs in racial differences. A nationally representative survey experiment (N = 526) provided clear support for the reification hypothesis. The results suggest that an unintended consequence of the genomic revolution may be to reinvigorate age-old beliefs in essential racial differences.
| S-EPMC4392852 | biostudies-literature
Project description:Pharmacogenomic (PGx) testing is gaining recognition from physicians, pharmacists and patients as a tool for evidence-based medication management. However, seemingly similar PGx testing panels (and PGx-based decision support tools) can diverge in their technological specifications, as well as the genetic factors that determine test specificity and sensitivity, and hence offer different values for users. Reluctance to embrace PGx testing is often the result of unfamiliarity with PGx technology, a lack of knowledge about the availability of curated guidelines/evidence for drug dosing recommendations, and an absence of wide-spread institutional implementation efforts and educational support. Demystifying an often confusing and variable PGx marketplace can lead to greater acceptance of PGx as a standard-of-care practice that improves drug outcomes and provides a lifetime value for patients. Here, we highlight the key underlying factors of a PGx test that should be considered, and discuss the current progress of PGx implementation.
| S-EPMC6133969 | biostudies-literature
Project description:ObjectiveTo explore the implications of direct-to-consumer pharmacogenomic testing for community pharmacy practice.SummaryIn 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.ConclusionCommunity 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.
| S-EPMC7229642 | biostudies-literature
Project description:Despite the potential to improve patient outcomes, the application of pharmacogenomics (PGx) is yet to be routine. A growing number of PGx implementers are leaning toward using combinatorial PGx (CPGx) tests (i.e., multigene tests) that are reusable over patients' lifetimes. However, selecting a single best available CPGx test is challenging owing to many patient- and population-specific factors, including variant frequency differences across ethnic groups. The primary objective of this study was to evaluate the detection rate of currently available CPGx tests based on the cytochrome P450 (CYP) gene variants they target. The detection rate was defined as the percentage of a given population with an "altered metabolizer" genotype predicted phenotype, where a CPGx test targeted both gene variants a prospective diplotypes. A potential genotype predicted phenotype was considered an altered metabolizer when it resulted in medication therapy modification based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Targeted variant CPGx tests found in the Genetic Testing Registry (GTR), gene selection information, and diplotype frequency data from the Pharmacogenomics Knowledge Base (PharmGKB) were used to determine the detection rate of each CPGx test. Our results indicated that the detection rate of CPGx tests covering CYP2C19, CYP2C9, CYP2D6, and CYP2B6 show significant variation across ethnic groups. Specifically, the Sub-Saharan Africans have 63.9% and 77.9% average detection rates for CYP2B6 and CYP2C19 assays analyzed, respectively. In addition, East Asians (EAs) have an average detection rate of 55.1% for CYP2C9 assays. Therefore, the patient's ethnic background should be carefully considered in selecting CPGx tests.
| S-EPMC8506148 | biostudies-literature
Project description:PURPOSE:There is increasing demand from the public for direct-to-consumer (DTC) genetic tests, and the US Food and Drug Administration limits the type of health-related claims DTC tests can market. Some DTC companies provide raw genotyping data to customers if requested, and these raw data may include variants occurring in genes recommended by the American College of Medical Genetics and Genomics to be reported as incidental/secondary findings. The purpose of this study was to review the outcome of requests for clinical confirmation of DTC results that were received by our laboratory and to analyze variant classification concordance. METHODS:We identified 49 patient samples received for further testing that had previously identified genetic variants reported in DTC raw data. For each case identified, information pertaining to the outcome of clinical confirmation testing as well as classification of the DTC variant was collected and analyzed. RESULTS:Our analyses indicated that 40% of variants in a variety of genes reported in DTC raw data were false positives. In addition, some variants designated with the "increased risk" classification in DTC raw data or by a third-party interpretation service were classified as benign at Ambry Genetics as well as several other clinical laboratories, and are noted to be common variants in publicly available population frequency databases. CONCLUSION:Our results demonstrate the importance of confirming DTC raw data variants in a clinical laboratory that is well versed in both complex variant detection and classification.
| S-EPMC6301953 | biostudies-literature
Project description:Genetic/genomic profiling at a single-patient level is expected to provide critical information for determining inter-individual drug toxicity and potential efficacy in cancer therapy. A better definition of cancer subtypes at a molecular level, may correspondingly complement such pharmacogenetic and pharmacogenomic approaches, for more effective personalized treatments. Current pharmacogenetic/pharmacogenomic strategies are largely based on the identification of known polymorphisms, thus limiting the discovery of novel or rarer genetic variants. Recent improvements in cost and throughput of next generation sequencing (NGS) are now making whole-genome profiling a plausible alternative for clinical procedures. Beyond classical pharmacogenetic/pharmacogenomic traits for drug metabolism, NGS screening programs of cancer genomes may lead to the identification of novel cancer-driving mutations. These may not only constitute novel therapeutic targets, but also effector determinants for metabolic pathways linked to drug metabolism. An additional advantage is that cancer NGS profiling is now leading to discovering targetable mutations, e.g., in glioblastomas and pancreatic cancers, which were originally discovered in other tumor types, thus allowing for effective repurposing of active drugs already on the market.
| S-EPMC8992635 | biostudies-literature
Project description:ImportanceAnticoagulation management services (AMSs; ie, warfarin clinics) have evolved to include patients treated with direct oral anticoagulants (DOACs), but it is unknown whether DOAC therapy management services improve outcomes for patients with atrial fibrillation (AF).ObjectiveTo compare outcomes associated with 3 DOAC care models for preventing adverse anticoagulation-related outcomes among patients with AF.Design, setting, and participantsThis retrospective cohort study included 44 746 adult patients with a diagnosis of AF who initiated oral anticoagulation (DOAC or warfarin) between August 1, 2016, and December 31, 2019, in 3 Kaiser Permanente (KP) regions. Statistical analysis was conducted from August 2021 through May 2023.ExposuresEach KP region used an AMS to manage warfarin but used distinct approaches to DOAC care: (1) usual care (UC) by the prescribing clinician, (2) UC plus an automated population management tool (PMT), or (3) pharmacist-managed AMS care. Propensity scores and inverse probability of treatment weights (IPTWs) were estimated. Direct oral anticoagulant care models were first indirectly compared using warfarin as a common comparator within each region and then directly compared across regions.Main outcomes and measuresPatients were followed up until the first occurrence of an outcome (composite of thromboembolic stroke, intracranial hemorrhage, other major bleeding, or death), discontinuation of KP membership, or December 31, 2020.ResultsOverall, 44 746 patients were included: 6182 in the UC care model (3297 DOAC; 2885 warfarin), 33 625 in the UC plus PMT care model (21 891 DOAC; 11 734 warfarin), and 4939 in the AMS care model (2089 DOAC; 2850 warfarin). Baseline characteristics (mean [SD] age, 73.1 [10.6] years, 56.1% male, 67.2% non-Hispanic White, median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, female sex] score of 3 [IQR, 2-5]) were well balanced after IPTW. Over a median follow-up of 2 years, patients who received the UC plus PMT or AMS care model did not have significantly better outcomes than those who received UC. The incidence rate of the composite outcome was 5.4% per year for DOAC and 9.1% per year for warfarin for those in the UC group, 6.1% per year for DOAC and 10.5% per year for those in the UC plus PMT group, and 5.1% per year for DOAC and 8.0% per year for those in the AMS group. The IPTW-adjusted hazard ratios (HRs) for the composite outcome comparing DOAC vs warfarin were 0.91 (95% CI, 0.79-1.05) in the UC group, 0.85 (95% CI, 0.79-0.90) in the UC plus PMT group, and 0.84 (95% CI, 0.72-0.99) in the AMS group (P = .62 for heterogeneity across care models). When directly comparing patients receiving DOAC, the IPTW-adjusted HR was 1.06 (95% CI, 0.85-1.34) for the UC plus PMT group vs the UC group and 0.85 (95% CI, 0.71-1.02) for the AMS group vs the UC group.Conclusions and relevanceThis cohort study did not find appreciably better outcomes for patients receiving DOAC who were managed by either a UC plus PMT or AMS care model compared with UC.
| S-EPMC10326649 | biostudies-literature
Project description:The genomic inter-individual heterogeneity remains a significant challenge for both clinical decision-making and the design of clinical trials. Although next-generation sequencing (NGS) is increasingly implemented in drug development and clinical trials, translation of the obtained genomic information into actionable clinical advice lags behind. Major reasons are the paucity of sufficiently powered trials that can quantify the added value of pharmacogenetic testing, and the considerable pharmacogenetic complexity with millions of rare variants with unclear functional consequences. The resulting uncertainty is reflected in inconsistencies of pharmacogenomic drug labels in Europe and the United States. In this review, we discuss how the knowledge gap for bridging pharmacogenomics into the clinics can be reduced. First, emerging methods that allow the high-throughput experimental characterization of pharmacogenomic variants combined with novel computational tools hold promise to improve the accuracy of drug response predictions. Second, tapping of large biobanks of therapeutic drug monitoring data allows to conduct high-powered retrospective studies that can validate the clinical importance of genetic variants, which are currently incompletely characterized. Combined, we are confident that these methods will improve the accuracy of drug response predictions and will narrow the gap between variant identification and its utilization for clinical decision-support.
| S-EPMC7057970 | biostudies-literature