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Epidemiologia E Prevenzione 2015To identify those studies in which economic analysis of predictive genetic and pharmacogenetic testing programs have been carried out. Since the Italian National... (Review)
Review
OBJECTIVES
To identify those studies in which economic analysis of predictive genetic and pharmacogenetic testing programs have been carried out. Since the Italian National Prevention Plan 2014-2018 foresees the implementation of genetic testing for inherited breast cancer, special attention was given to the cost-effectiveness of BRCA1/2 testing programs.
METHODS
A systematic review of primary economic evaluations (EEs) of predictive genetic and pharmacogenetic testing programs and an overview of previously published systematic reviews of economic evaluations (ERs) was performed.
RESULTS
Overall 128 EEs and 11 ERs were identified. The methodological quality of both EEs and ERs was good on average. Both predictive genetic and pharmacogenetic testing programs were mainly concerned with oncological diseases. Seventeen percent of genetic testing programs are cost-saving, while a further 44% of cost/QALY ratios fall under the commonly used threshold of €37,000 per QALY. For BRCA1/2 testing, only cascade genetic screening programs, targeted to close relatives of carriers, show clear evidence of cost-effectiveness.
CONCLUSION
Despite some limitations, EEs and ERs are powerful tools that provide indications to policy-makers on which genetic testing programs might be introduced into health care systems and public health practice.
Topics: Breast Neoplasms; Cost-Benefit Analysis; Delivery of Health Care; Early Detection of Cancer; Female; Genes, BRCA1; Genes, BRCA2; Genetic Diseases, Inborn; Genetic Predisposition to Disease; Genetic Testing; Global Health; Health Care Costs; Humans; Insurance, Health, Reimbursement; Life Expectancy; Ovarian Neoplasms; Pharmacogenomic Testing; Quality-Adjusted Life Years
PubMed: 26499415
DOI: No ID Found -
American Journal of Health-system... Dec 2016Both regulatory science and clinical practice rely on best available scientific data to guide decision-making. However, changes in clinical practice may be driven by... (Review)
Review
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.
Topics: Clinical Decision-Making; Genetic Testing; Humans; Pharmacogenetics; Pharmacogenomic Testing; United States; United States Food and Drug Administration
PubMed: 27864207
DOI: 10.2146/ajhp160476 -
Medical Principles and Practice :... 2017Personalized management of cardiovascular disorders (CVD), also referred to as personalized or precision cardiology in accordance with general principles of personalized... (Review)
Review
Personalized management of cardiovascular disorders (CVD), also referred to as personalized or precision cardiology in accordance with general principles of personalized medicine, is selection of the best treatment for an individual patient. It involves the integration of various "omics" technologies such as genomics and proteomics as well as other new technologies such as nanobiotechnology. Molecular diagnostics and biomarkers are important for linking diagnosis with therapy and monitoring therapy. Because CVD involve perturbations of large complex biological networks, a systems biology approach to CVD risk stratification may be used for improving risk-estimating algorithms, and modeling of personalized benefit of treatment may be helpful for guiding the choice of intervention. Bioinformatics tools are helpful in analyzing and integrating large amounts of data from various sources. Personalized therapy is considered during drug development, including methods of targeted drug delivery and clinical trials. Individualized recommendations consider multiple factors - genetic as well as epigenetic - for patients' risk of heart disease. Examples of personalized treatment are those of chronic myocardial ischemia, heart failure, and hypertension. Similar approaches can be used for the management of atrial fibrillation and hypercholesterolemia, as well as the use of anticoagulants. Personalized management includes pharmacotherapy, surgery, lifestyle modifications, and combinations thereof. Further progress in understanding the pathomechanism of complex cardiovascular diseases and identification of causative factors at the individual patient level will provide opportunities for the development of personalized cardiology. Application of principles of personalized medicine will improve the care of the patients with CVD.
Topics: Biomarkers; Cardiovascular Agents; Cardiovascular Diseases; Cell- and Tissue-Based Therapy; Computational Biology; Genetic Predisposition to Disease; Genomics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Style; Lipids; Myocardial Ischemia; Nanotechnology; Pharmacogenomic Testing; Polymorphism, Single Nucleotide; Precision Medicine; Systems Biology
PubMed: 28898880
DOI: 10.1159/000481403 -
Clinics (Sao Paulo, Brazil) Oct 2018Pharmacogenetics, a major component of individualized or precision medicine, relies on human genetic diversity. The remarkable developments in sequencing technologies... (Review)
Review
Pharmacogenetics, a major component of individualized or precision medicine, relies on human genetic diversity. The remarkable developments in sequencing technologies have revealed that the number of genetic variants modulating drug action is much higher than previously thought and that a true personalized prediction of drug response requires attention to rare mutations (minor allele frequency, MAF<1%) in addition to polymorphisms (MAF>1%) in pharmacogenes. This has major implications for the conceptual development and clinical implementation of pharmacogenetics. Drugs used in cancer treatment have been major targets of pharmacogenetics studies, encompassing both germline polymorphisms and somatic variants in the tumor genome. The present overview, however, has a narrower scope and is focused on germline cancer pharmacogenetics, more specifically, on drug/gene pairs for which pharmacogenetics-informed prescription guidelines have been published by the Clinical Pharmacogenetics Implementation Consortium and/or the Dutch Pharmacogenetic Working Group, namely, thiopurines/TPMT, fluoropyrimidines/UGT1A1, irinotecan/UGT1A1 and tamoxifen/CYP2D6. I begin by reviewing the general principles of pharmacogenetics-informed prescription, pharmacogenetics testing and the perceived barriers to the adoption of routine pharmacogenetics testing in clinical practice. Then, I highlight aspects of the pharmacogenetics testing of the selected drug-gene pairs and finally present pharmacogenetics data from Brazilian studies pertinent to these drug-gene pairs. I conclude with the notion that pharmacogenetics testing has the potential to greatly benefit patients by enabling precision medicine applied to drug therapy, ensuring better efficacy and reducing the risk of adverse effects.
Topics: Brazil; Evidence-Based Medicine; Humans; Mutation; Neoplasms; Pharmacogenomic Testing; Polymorphism, Genetic; Precision Medicine
PubMed: 30328952
DOI: 10.6061/clinics/2018/e565s -
Pharmacogenomics Jul 2019Several high-profile examples of adverse outcomes from medications used in the perioperative setting are well known (e.g., malignant hyperthermia, prolonged apnea,... (Review)
Review
Several high-profile examples of adverse outcomes from medications used in the perioperative setting are well known (e.g., malignant hyperthermia, prolonged apnea, respiratory depression, inadequate analgesia), leading to an increased understanding of genetic susceptibilities underlying these risks. Pharmacogenomic information is increasingly being utilized in certain areas of medicine. Despite this, routine preoperative genetic screening to inform medication risk is not yet standard practice. In this review, we assess the current readiness of pharmacogenomic information for clinical consideration for several common perioperative medications, including description of key pharmacogenes, pharmacokinetic implications and potential clinical outcomes. The goal is to highlight medications for which emerging or considerable pharmacogenomic information exists and identify areas for future potential research.
Topics: Drug-Related Side Effects and Adverse Reactions; Genetic Predisposition to Disease; Genetic Testing; Humans; Perioperative Care; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 31411557
DOI: 10.2217/pgs-2019-0040 -
The Journal of Molecular Diagnostics :... Mar 2022Clinical laboratories offering genome sequencing have the opportunity to return pharmacogenomic findings to patients, providing the added benefit of preemptive testing...
Clinical laboratories offering genome sequencing have the opportunity to return pharmacogenomic findings to patients, providing the added benefit of preemptive testing that could help inform medication selection or dosing throughout the lifespan. Implementation of pharmacogenomic reporting must address several challenges, including inherent limitations in short-read genome sequencing methods, gene and variant selection, standardization of genotype and phenotype nomenclature, and choice of guidelines and drugs to report. An automated pipeline, lmPGX, was developed as an end-to-end solution that produces two versions of a pharmacogenomic report, presenting either Clinical Pharmacogenetics Implementation Consortium or US Food and Drug Administration guidelines for 12 genes. The pipeline was validated for performance using reference samples and pharmacogenetic data from the Genetic Testing Reference Materials Coordination Program. To determine performance and limitations, lmPGX was compared with three additional publicly available pharmacogenomic pipelines. The lmPGX pipeline offers clinical laboratories an opportunity for seamless integration of pharmacogenomic results with genome reporting.
Topics: Genetic Testing; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Phenotype
PubMed: 35041930
DOI: 10.1016/j.jmoldx.2021.12.001 -
Genes Oct 2020Digital health (DH) is the use of digital technologies and data analytics to understand health-related behaviors and enhance personalized clinical care. DH is... (Review)
Review
Digital health (DH) is the use of digital technologies and data analytics to understand health-related behaviors and enhance personalized clinical care. DH is increasingly being used in clinical trials, and an important field that could potentially benefit from incorporating DH into trial design is pharmacogenetics. Prospective pharmacogenetic trials typically compare a standard care arm to a pharmacogenetic-guided therapeutic arm. These trials often require large sample sizes, are challenging to recruit into, lack patient diversity, and can have complicated workflows to deliver therapeutic interventions to both investigators and patients. Importantly, the use of DH technologies could mitigate these challenges and improve pharmacogenetic trial design and operation. Some DH use cases include (1) automatic electronic health record-based patient screening and recruitment; (2) interactive websites for participant engagement; (3) home- and tele-health visits for patient convenience (e.g., samples for lab tests, physical exams, medication administration); (4) healthcare apps to collect patient-reported outcomes, adverse events and concomitant medications, and to deliver therapeutic information to patients; and (5) wearable devices to collect vital signs, electrocardiograms, sleep quality, and other discrete clinical variables. Given that pharmacogenetic trials are inherently challenging to conduct, future pharmacogenetic utility studies should consider implementing DH technologies and trial methodologies into their design and operation.
Topics: Computational Biology; Humans; Medical Informatics; Pattern Recognition, Automated; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Telemedicine; Wearable Electronic Devices
PubMed: 33114567
DOI: 10.3390/genes11111261 -
Expert Opinion on Drug Metabolism &... Oct 2020β-blockers are among the most widely prescribed of all drugs, used for treatment of a large number of cardiovascular diseases. Herein we evaluate literature pertaining... (Review)
Review
INTRODUCTION
β-blockers are among the most widely prescribed of all drugs, used for treatment of a large number of cardiovascular diseases. Herein we evaluate literature pertaining to pharmacogenetics of β-blocker therapy, provide insight into the robustness of the genetic associations, and determine the appropriateness for translating these genetic associations into clinical practice.
AREAS COVERED
A literature search was conducted using PubMed to collate evidence on associations between , and genetic variation and drug-response outcomes in the presence of β-blocker exposure. Pharmacokinetic, pharmacodynamic, and clinical outcomes studies were included if genotype data and β-blocker exposure were documented.
EXPERT OPINION
Substantial data suggest that specific and genotypes are associated with improved β-blocker efficacy and have potential for use to guide therapy decisions in the clinical setting. While the data do not justify ordering a pharmacogenetic test, if genotype is available in the electronic health record, there may be clinical utility for understanding dosing of β-blockers.
Topics: Adrenergic beta-Antagonists; Cardiovascular Diseases; G-Protein-Coupled Receptor Kinase 5; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Receptors, Adrenergic, beta-1
PubMed: 32726152
DOI: 10.1080/17425255.2020.1803279 -
Journal of Pediatric... 2022Pharmacogenetic (PGx) testing, a component of personalized medicine, aims to ensure treatment efficacy while reducing side effects and symptoms. Before this testing...
Pharmacogenetic (PGx) testing, a component of personalized medicine, aims to ensure treatment efficacy while reducing side effects and symptoms. Before this testing becomes routine in the pediatric oncology population, nurses need to understand the knowledge and concerns of providers, patients, and family members with regard to the timing, extent, interpretation, and incorporation of PGx testing. As part of a comprehensive PGx study (larger study) for children diagnosed with cancer, we surveyed providers and caregivers of children with cancer about their knowledge of and comfort with PGx testing. Caregivers who declined to participate in the larger PGx study were also asked to participate in the survey. Chi-square tests and a two-sample -test were used to compare variables. One hundred and two participants from the larger PGx study and 12 families who refused (response rate of 77% and 54%, respectively) as well as 29 providers (88%) completed surveys. Families not on the study were less interested in and comfortable with PGx results. Both groups were concerned about health or life insurance discrimination and payment. Providers would like support in ordering PGx testing and interpreting PGx. Providers remain wary of most PGx testing, uncomfortable with interpreting and applying the results. Families are interested in the possibilities of personalized prescribing while worried about who has access to their child's genetic information. Further education on relevant tests for providers, including nurses, and the testing process for families, including details on privacy and sharing of genetic information, appear necessary.
Topics: Child; Genetic Testing; Humans; Medical Oncology; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 35467433
DOI: 10.1177/10434542211055999 -
Personalized Medicine Nov 2022To elicit preferences for pharmacogenomic (PGx) testing in polypharmacy patients. A face-to-face discrete choice experiment survey was designed and administered to...
To elicit preferences for pharmacogenomic (PGx) testing in polypharmacy patients. A face-to-face discrete choice experiment survey was designed and administered to adult polypharmacy patients recruited at a local retail pharmacy in Albuquerque (NM, USA). A total of 128 eligible polypharmacy patients completed the discrete choice experiment survey and significantly preferred a PGx test with lower cost, better confidentiality and higher certainty of identifying best medication/dose and side effects and one that can be used to advocate for their treatment needs (all p < 0.01). This is the first study eliciting preferences for PGx testing among polypharmacy patients. The study found most polypharmacy patients were willing to take a PGx test and their preferences were mostly influenced by test cost.
Topics: Adult; Humans; Pharmacogenomic Testing; Polypharmacy; Pharmacogenetics; Drug-Related Side Effects and Adverse Reactions; Confidentiality
PubMed: 36317592
DOI: 10.2217/pme-2022-0056