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American Journal of Health-system... Dec 2016The operational elements essential for establishing an inpatient pharmacogenetic service are reviewed, and the role of the pharmacist in the provision of genotype-guided... (Review)
Review
PURPOSE
The operational elements essential for establishing an inpatient pharmacogenetic service are reviewed, and the role of the pharmacist in the provision of genotype-guided drug therapy in pharmacogenetics programs at three institutions is highlighted.
SUMMARY
Pharmacists are well positioned to assume important roles in facilitating the clinical use of genetic information to optimize drug therapy given their expertise in clinical pharmacology and therapeutics. Pharmacists have assumed important roles in implementing inpatient pharmacogenetics programs. This includes programs designed to incorporate genetic test results to optimize antiplatelet drug selection after percutaneous coronary intervention and personalize warfarin dosing. Pharmacist involvement occurs on many levels, including championing and leading pharmacogenetics implementation efforts, establishing clinical processes to support genotype-guided therapy, assisting the clinical staff with interpreting genetic test results and applying them to prescribing decisions, and educating other healthcare providers and patients on genomic medicine. The three inpatient pharmacogenetics programs described use reactive versus preemptive genotyping, the most feasible approach under the current third-party payment structure. All three sites also follow Clinical Pharmacogenetics Implementation Consortium guidelines for drug therapy recommendations based on genetic test results.
CONCLUSION
With the clinical emergence of pharmacogenetics into the inpatient setting, it is important that pharmacists caring for hospitalized patients are well prepared to serve as experts in interpreting and applying genetic test results to guide drug therapy decisions. Since genetic test results may not be available until after patient discharge, pharmacists practicing in the ambulatory care setting should also be prepared to assist with genotype-guided drug therapy as part of transitions in care.
Topics: Genotype; Hospitalization; Humans; Patient Care Team; Pharmacogenetics; Pharmacy Service, Hospital; Professional Role; Program Development
PubMed: 27864202
DOI: 10.2146/ajhp150946 -
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 -
Cold Spring Harbor Perspectives in... Feb 2019Inherited genetic variations in pharmacogenetic loci are widely acknowledged as important determinants of phenotypic differences in drug response, and may be actionable... (Review)
Review
Inherited genetic variations in pharmacogenetic loci are widely acknowledged as important determinants of phenotypic differences in drug response, and may be actionable in the clinic. However, recent studies suggest that a considerable number of novel rare variants in pharmacogenes likely contribute to a still unexplained fraction of the observed interindividual variability. Next-generation sequencing (NGS) represents a rapid, relatively inexpensive, large-scale DNA sequencing technology with potential relevance as a comprehensive pharmacogenetic genotyping platform to identify genetic variation related to drug therapy. However, many obstacles remain before the clinical use of NGS-based test results, including technical challenges, functional interpretation, and strict requirements for diagnostic tests. Advanced computational analyses, high-throughput screening methodologies, and generation of shared resources with cell-based and clinical information will facilitate the integration of NGS data into candidate genotyping approaches, likely enhancing future drug phenotype predictions in patients.
Topics: Computational Biology; Genetic Variation; High-Throughput Nucleotide Sequencing; High-Throughput Screening Assays; Humans; Pharmacogenetics; Phenotype; Sequence Analysis, DNA
PubMed: 29844222
DOI: 10.1101/cshperspect.a033027 -
BMC Health Services Research Oct 2021Pharmacogenetics targets genetic variations that influence drug response. It is relatively a new science that has not been vastly employed in most developing countries...
BACKGROUND
Pharmacogenetics targets genetic variations that influence drug response. It is relatively a new science that has not been vastly employed in most developing countries including Syria. Therefore we aimed at evaluating the depth of knowledge in pharmacogenetics and the attitude towards it amongst Syrian pharmacists and physicians.
METHODS
We carried out an internet-based questionnaire consisted of 26 questions, sent through specialized websites and private groups with a large number of pharmacists and physicians members. The survey was available online for a period of 1 month.
RESULTS
The total number of respondents was 154, mostly female pharmacists. Our statistical analysis showed a strong positive association between profession (in favour of pharmacists) and pharmacogenetics knowledge p = 0.049; however, no correlation with experience p = 0.811 was found. A significant difference was reported between the knowledge of pharmacists and physicians p = 0.001 concerning drugs that need pharmacogenetics testing before being prescribed. The majority of respondents had no information about applying genetic tests in Syria before prescribing medications nor did they possess the knowledge regarding drugs that show differential responses in patients according to their unique genotypes. In our study, the percentage knowledge assessment score was low in general (mean ± Standard deviation, SD) (46% ± 13.9%). The majority of the respondents agreed that pharmacists should provide counselling to patients on the subject of pharmacogenetics. Respondents' opinions varied concerning making pharmacogenetics learning a priority.
CONCLUSION
Lack of pharmacogenetics knowledge was found amongst respondents in general. Our findings raise concerns about the lack of awareness amongst physicians, which may hinder the implementation of this crucial field in Syria. We suggest an emphasis on the role of education, training, and conducting genotyping research on the Syrian population.
Topics: Female; Health Knowledge, Attitudes, Practice; Humans; Male; Pharmacists; Pharmacogenetics; Physicians; Surveys and Questionnaires; Syria
PubMed: 34592972
DOI: 10.1186/s12913-021-07040-9 -
Wiley Interdisciplinary Reviews.... 2010Pharmacogenetics and pharmacogenomics involve the study of the role of inheritance in individual variation in drug response, a phenotype that varies from potentially... (Review)
Review
Pharmacogenetics and pharmacogenomics involve the study of the role of inheritance in individual variation in drug response, a phenotype that varies from potentially life-threatening adverse drug reactions to equally serious lack of therapeutic efficacy. Pharmacogenetics-pharmacogenomics represents a major component of the movement to 'individualized medicine'. Pharmacogenetic studies originally focused on monogenic traits, often involving genetic variation in drug metabolism. However, contemporary studies increasingly involve entire 'pathways' that include both pharmacokinetics (PKs)--factors that influence the concentration of a drug reaching its target(s)--and pharmacodynamics (PDs), factors associated with the drug target(s), as well as genome-wide approaches. The convergence of advances in pharmacogenetics with rapid developments in human genomics has resulted in the evolution of pharmacogenetics into pharmacogenomics. At the same time, studies of drug response are expanding beyond genomics to encompass pharmacotranscriptomics and pharmacometabolomics to become a systems-based discipline. This discipline is also increasingly moving across the 'translational interface' into the clinic and is being incorporated into the drug development process and governmental regulation of that process. The article will provide an overview of the development of pharmacogenetics-pharmacogenomics, the scientific advances that have contributed to the continuing evolution of this discipline, the incorporation of transcriptomic and metabolomic data into attempts to understand and predict variation in drug response phenotypes as well as challenges associated with the 'translation' of this important aspect of biomedical science into the clinic.
Topics: Cytochrome P-450 CYP2D6; Genetic Variation; Genome, Human; Genome-Wide Association Study; Humans; Inactivation, Metabolic; Metabolomics; Methyltransferases; Models, Biological; Pharmacogenetics; Signal Transduction; Systems Biology
PubMed: 20836007
DOI: 10.1002/wsbm.42 -
Blood Reviews Jul 2015Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults accounting for no more than 20% of all cases of acute leukemia. By contrast with the pediatric... (Review)
Review
Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults accounting for no more than 20% of all cases of acute leukemia. By contrast with the pediatric population, in whom significant improvements in long term survival and even cure have been achieved over the last 30years, adult ALL remains a significant challenge. Overall survival in this group remains a relatively poor 20-40%. Modern research has focused on improved pharmacokinetics, novel pharmacogenetics and personalized principles to optimize the efficacy of the treatment while reducing toxicity. Here we review the pharmacogenetics of medications used in the management of patients with ALL, including l-asparaginase, glucocorticoids, 6-mercaptopurine, methotrexate, vincristine and tyrosine kinase inhibitors. Incorporating recent pharmacogenetic data, mainly from pediatric ALL, will provide novel perspective of predicting response and toxicity in both pediatric and adult ALL therapies.
Topics: Female; Humans; Male; Pharmacogenetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 25614322
DOI: 10.1016/j.blre.2015.01.001 -
Pharmacogenomics Nov 2018Despite the introduction of direct acting oral anticoagulants, warfarin remains the most commonly prescribed oral anticoagulant. However, warfarin therapy is plagued by... (Review)
Review
Despite the introduction of direct acting oral anticoagulants, warfarin remains the most commonly prescribed oral anticoagulant. However, warfarin therapy is plagued by the large inter- and intrapatient variability. The variability in dosing fueled research to identify clinical and genetic predictors and develop more accurate dosing algorithms. Observational studies have demonstrated the significant impact of single nucleotide polymorphisms in CYP2C9 and VKORC1 on warfarin dose in patients of European ancestry and African-Americans. This evidence supported the design and conduct of clinical trials to assess whether genotype-guided dosing results in improved anticoagulation control and outcomes. The trial results have shown discordance by race, with pharmacogenetic algorithms improving dose and anticoagulation control among European ancestry patients compared with African-American patients. Herein, we review the evidence from observational and interventional studies, highlight the need for inclusion of minority race groups and propose the need to develop race specific dosing algorithms.
Topics: Anticoagulants; Black People; Dose-Response Relationship, Drug; Genotype; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Warfarin; White People
PubMed: 30345882
DOI: 10.2217/pgs-2018-0146 -
PloS One 2018Pharmacogenetics practice has been successfully implemented in many developed countries to enhance personalized medicine and improve clinical and economic outcomes. An...
BACKGROUND
Pharmacogenetics practice has been successfully implemented in many developed countries to enhance personalized medicine and improve clinical and economic outcomes. An understanding of healthcare providers' knowledge, perceptions, confidence towards pharmacogenetics, and their active enrollment with pharmacogenetic testing is essential for test acceptance and utilization. This study was designed to assess physicians' and pharmacists' knowledge, perceptions, and confidence towards pharmacogenetics, determine the preferred learning format for their future education in pharmacogenetics, and identify the barriers to its application in their practice settings.
METHODS
A cross-sectional survey was conducted using a pretested self-administered questionnaire on a sample of 629 randomly selected physicians and pharmacists. Descriptive and comparative analyses were used in data analysis.
RESULTS
The response rate was 98.1%. Less than one-tenth of respondents were exposed to pharmacogenetics education or training (8.9%), applied pharmacogenetics testing in their practice (9.4%), or provided patient counselling on the results of the pharmacogenetic testing (9.1%), and over 90% of them were physicians. The overall respondents' mean (SD) total knowledge score percentage was low [45.0% (24)] and there was no significant difference between the physicians and pharmacists scores (p>0.05). Only 16.0% of participants indicated that they felt confident in applying pharmacogenetics in their practice settings. Despite these low levels of knowledge and self-confidence, 70.2% of participants expressed overall positive perceptions towards pharmacogenetics and its clinical implications. These positive overall perceptions were found to be significantly more common among pharmacists compared to physicians (p<0.05). The top two perceived barriers facing the implementation of pharmacogenetics in Kuwait were lack of education or training and clinical guidelines.
CONCLUSIONS
These findings highlight important concerns and will aid in the assessment of current pharmacogenetics practice. Also, they will provide further insight in designing future targeted multifaceted interventions to promote the adoption and utilization of pharmacogenetics testing in Kuwait.
Topics: Adult; Attitude of Health Personnel; Cross-Sectional Studies; Female; Genetic Testing; Health Knowledge, Attitudes, Practice; Humans; Kuwait; Male; Pharmacists; Pharmacogenetics; Physicians; Precision Medicine
PubMed: 30183746
DOI: 10.1371/journal.pone.0203033 -
Human Genetics May 2015Understanding the role genes and genetic variants play in clinical treatment response continues to be an active area of research with the goal of common clinical use.... (Review)
Review
Understanding the role genes and genetic variants play in clinical treatment response continues to be an active area of research with the goal of common clinical use. This goal has developed into today's industry of pharmacogenomics, where new drug-gene relationships are discovered and further characterized, published and then curated into national and international resources for use by researchers and clinicians. These efforts have given us insight into what a pharmacogenomic variant is, and how it differs from human disease variants and common polymorphisms. While publications continue to reveal pharmacogenomic relationships between genes and specific classes of drugs, many challenges remain toward the goal of widespread use clinically. First, the clinical guidelines for pharmacogenomic testing are still in their infancy. Second, sequencing technologies are changing rapidly making it somewhat unclear what genetic data will be available to the clinician at the time of care. Finally, what and when to return data to a patient is an area under constant debate. New innovations such as PheWAS approaches and whole genome sequencing studies are enabling a tsunami of new findings. In this review, pharmacogenomic variants, pharmacogenomic resources, interpretation clinical guidelines and challenges, such as WGS approaches, and the impact of pharmacogenomics on drug development and regulatory approval are reviewed.
Topics: Computational Biology; Data Interpretation, Statistical; Databases, Genetic; Databases, Pharmaceutical; Drug Discovery; Genetic Variation; Humans; Pharmacogenetics; Phenotype
PubMed: 25238897
DOI: 10.1007/s00439-014-1484-7 -
BioTechniques Oct 2005Pharmacogenetics and pharmacogenomics are keys to the success of personalized medicine, prescribing drugs based on a patient's individual genetic and biological profile.... (Review)
Review
Pharmacogenetics and pharmacogenomics are keys to the success of personalized medicine, prescribing drugs based on a patient's individual genetic and biological profile. In this review, we will focus on the application of pharmacogenetics and pharmacogenomics in developing monoclonal antibody (MAb) therapeutics in oncology. The significance of pharmacogenomics in MAb therapeutics is highlighted by the association between polymorphisms in Fc receptors and clinical response to anti-CD20 MAb rituximab (Rituxan) or anti-ganglioside GD2 MAb 3F8, as well as the potential link between polymorphisms in HER2 and cardiac toxicity in patients treated with the anti-HER2 MAb trastuzumab (Herceptin). The dependence on gene copy number or expression levels ofHER2 and epidermal growth factor receptor (EGFR) for therapeutic efficacy of trastuzumab and cetuximab (Erbitux), respectively, supports the importance of selecting suitable patient populations based on their pharmacogenetic profile. In addition, a better understanding of target mutation status and biological consequences will benefit MAb development and may guide clinical development and use of these innovative therapeutics. The application of pharmacogenetics and pharmacogenomics in developing MAb therapeutics will be largely dependent on the discovery of novel surrogate biomarkers and identification of disease- and therapeutics-relevant polymorphisms. Challenges and opportunities in biomarker discovery and validation, and in implementing clinical pharmacogenetics and pharmacogenomics in oncology MAb development and clinical practice will also be discussed.
Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents; Humans; Medical Oncology; Neoplasms; Pharmacogenetics; Technology, Pharmaceutical
PubMed: 18957038
DOI: 10.2144/000112043