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The Journal of Allergy and Clinical... Sep 2020
Topics: Allergy and Immunology; Biomarkers; Cytochrome P-450 Enzyme System; HLA Antigens; Humans; Pharmacogenomic Testing; Practice Patterns, Physicians'; Precision Medicine
PubMed: 32533972
DOI: 10.1016/j.jaci.2020.05.050 -
Genes Aug 2020Drug development (target identification, advancing drug leads to candidates for preclinical and clinical studies) can be facilitated by genetic and genomic knowledge.... (Review)
Review
Drug development (target identification, advancing drug leads to candidates for preclinical and clinical studies) can be facilitated by genetic and genomic knowledge. Here, we review the contribution of population genomics to target identification, the value of bulk and single cell gene expression analysis for understanding the biological relevance of a drug target, and genome-wide CRISPR editing for the prioritization of drug targets. In genomics, we discuss the different scope of genome-wide association studies using genotyping arrays, versus exome and whole genome sequencing. In transcriptomics, we discuss the information from drug perturbation and the selection of biomarkers. For CRISPR screens, we discuss target discovery, mechanism of action and the concept of gene to drug mapping. Harnessing genetic support increases the probability of drug developability and approval.
Topics: Animals; CRISPR-Cas Systems; Drug Development; Gene Editing; Gene Expression Profiling; Genome-Wide Association Study; Genomics; Genotype; Humans; Pharmacogenomic Testing; Single-Cell Analysis; Transcriptome; Whole Genome Sequencing
PubMed: 32824125
DOI: 10.3390/genes11080942 -
The Pharmacogenomics Journal Oct 2017Pharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene-drug associations have been discovered, but PGx-guided treatment... (Review)
Review
Pharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene-drug associations have been discovered, but PGx-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health-care. We reviewed economic evaluations for PGx associations listed in the US Food and Drug Administration (FDA) Table of Pharmacogenomic Biomarkers in Drug Labeling. We determined the proportion of evaluations that found PGx-guided treatment to be cost-effective or dominant over the alternative strategies, and estimated the impact on this proportion of removing the cost of genetic testing. Of the 137 PGx associations in the FDA table, 44 economic evaluations, relating to 10 drugs, were identified. Of these evaluations, 57% drew conclusions in favour of PGx testing, of which 30% were cost-effective and 27% were dominant (cost-saving). If genetic information was freely available, 75% of economic evaluations would support PGx-guided treatment, of which 25% would be cost-effective and 50% would be dominant. Thus, PGx-guided treatment can be a cost-effective and even a cost-saving strategy. Having genetic information readily available in the clinical health record is a realistic future prospect, and would make more genetic tests economically worthwhile.
Topics: Cost-Benefit Analysis; Economics, Pharmaceutical; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; United States; United States Food and Drug Administration
PubMed: 28607506
DOI: 10.1038/tpj.2017.21 -
Archives of Pathology & Laboratory... May 2016-Precision medicine is the promise of individualized therapy and management of patients based on their personal biology. There are now multiple global initiatives to... (Review)
Review
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.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Clinical Trials as Topic; Gastrointestinal Neoplasms; Gastrointestinal Tract; Health Policy; Humans; Molecular Sequence Data; Molecular Targeted Therapy; Mutation; Neoplasm Proteins; Pathology, Clinical; Pharmacogenomic Testing; Precision Medicine; Prognosis; Quality of Health Care; Research Design
PubMed: 27128302
DOI: 10.5858/arpa.2015-0317-RA -
Internal Medicine Journal Jul 2022Despite healthcare professionals (HCP) endorsing the clinical utility of pharmacogenomics testing, use in clinical practice is limited.
BACKGROUND
Despite healthcare professionals (HCP) endorsing the clinical utility of pharmacogenomics testing, use in clinical practice is limited.
AIMS
To assess HCP' perceptions of pharmacogenomic testing and identify barriers to implementation.
METHODS
HCP involved in prescribing decisions at three hospitals in Sydney, Australia, were invited to participate. The online survey assessed perceptions of pharmacogenomic testing, including: (i) demographic and practice variables; (ii) use, knowledge and confidence; (iii) perceived benefits; (iv) barriers to implementation; and (v) operational and/or system changes and personnel required to implement on site.
RESULTS
HCP were predominantly medical practitioners (75/107) and pharmacists (25/107). HCP perceived pharmacogenomic testing was beneficial to identify reasons for drug intolerance (85/95) and risk of side-effects (86/95). Although testing was considered relevant to their practice (79/100), few HCP (23/100) reported past or intended future use (26/100). Few HCP reported confidence in their ability to identify indications for pharmacogenomic testing (14/107), order tests (19/106) and communicate results with patients (16/107). Lack of clinical practice guidelines (62/79) and knowledge (54/77) were identified as major barriers to implementation of pharmacogenomics. Comprehensive reimbursement for testing and clinical practice guidelines, alongside models-of-care involving multidisciplinary teams and local clinical champions were suggested as strategies to facilitate implementation of pharmacogenomic testing into practice.
CONCLUSIONS
Pharmacogenomic testing was considered important to guide drug selection and dosing decisions. However, limited knowledge, low confidence and an absence of guidelines impede the use of pharmacogenomic testing. Establishment of local resources including multidisciplinary models-of-care was suggested to facilitate implementation of pharmacogenomics.
Topics: Australia; Hospitals; Humans; Perception; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 35191159
DOI: 10.1111/imj.15719 -
Clinical and Translational Science Mar 2024Pharmacogenomics has the potential to inform drug dosing and selection, reduce adverse events, and improve medication efficacy; however, provider knowledge of...
Pharmacogenomics has the potential to inform drug dosing and selection, reduce adverse events, and improve medication efficacy; however, provider knowledge of pharmacogenomic testing varies across provider types and specialties. Given that many actionable pharmacogenomic genes are implicated in cardiovascular medication response variability, this study aimed to evaluate cardiology providers' knowledge and attitudes on implementing clinical pharmacogenomic testing. Sixty-one providers responded to an online survey, including pharmacists (46%), physicians (31%), genetic counselors (15%), and nurses (8%). Most respondents (94%) reported previous genetics education; however, only 52% felt their genetics education prepared them to order a clinical pharmacogenomic test. In addition, most respondents (66%) were familiar with pharmacogenomics, with genetic counselors being most likely to be familiar (p < 0.001). Only 15% of respondents had previously ordered a clinical pharmacogenomic test and a total of 36% indicated they are likely to order a pharmacogenomic test in the future; however, the vast majority of respondents (89%) were interested in pharmacogenomic testing being incorporated into diagnostic cardiovascular genetic tests. Moreover, 84% of providers preferred pharmacogenomic panel testing compared to 16% who preferred single gene testing. Half of the providers reported being comfortable discussing pharmacogenomic results with their patients, but the majority (60%) expressed discomfort with the logistics of test ordering. Reported barriers to implementation included uncertainty about the clinical utility and difficulty choosing an appropriate test. Taken together, cardiology providers have moderate familiarity with pharmacogenomics and limited experience with test ordering; however, they are interested in incorporating pharmacogenomics into diagnostic genetic tests and ordering pharmacogenomic panels.
Topics: Humans; Pharmacogenomic Testing; Cardiovascular System; Genetic Testing; Pharmacists; Pharmacogenetics
PubMed: 38421234
DOI: 10.1111/cts.13737 -
Pharmacogenomics Sep 2016We aimed to understand consent practices for pharmacogenetic (PGx) testing. (Review)
Review
AIM
We aimed to understand consent practices for pharmacogenetic (PGx) testing.
METHODS
We conducted a literature review and analysis of consent forms from clinical laboratories offering PGx testing.
RESULTS
Our review of the literature shows a lack of consensus about the need for and type of informed consent for PGx testing. We identified 35 companies offering PGx testing and were able to confirm consent practices for 22 of those. We found a range of variability in the consent practices regarding the consent approach and information disclosed.
CONCLUSION
Variability in the consent practices among laboratories offering PGx testing mirrors the ambiguous practices and recommendations reported in the literature. Establishing a minimal set of information to be disclosed to patients may help address the disparities in consent practice.
Topics: Humans; Informed Consent; Pharmacogenomic Testing
PubMed: 27533720
DOI: 10.2217/pgs-2016-0039 -
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 -
Romanian Journal of Internal Medicine =... Jun 2020Pharmacogenomics describes the link between the genetic code and variations in drug response or adverse effects. It is rapidly gaining in both interest and... (Review)
Review
Pharmacogenomics describes the link between the genetic code and variations in drug response or adverse effects. It is rapidly gaining in both interest and accessibility. The knowledge of the gene-drug pairing for a wide range of medications will allow the clinician to select drugs with the best efficacy, appropriate dose and lowest likelihood of serious side effects. In order to apply this knowledge, practitioners need to be familiar with the basic principles of pharmacodynamics and pharmacokinetics and how these relate to drug response. Once these are understood, so can be the genetic variations that lead to different phenotypes. Our review explains these concepts and uses examples of commonly prescribed medications and their gene pairings. At the present time, the Food and Drug Administration (FDA) guidelines remain sparse in regards to pharmacogenomic testing but, despite this, direct-to-consumer testing is widely available. In this context, we detail how to interpret a pharmacogenomic report, we review the indications for testing, as well as its limitations. This information is a step ahead towards invidualized medicine, in the hope that tailoring medications and doses to an individual's genetic make-up will predict a safe and effective response.
Topics: Cytochrome P-450 Enzyme System; HLA Antigens; Humans; Liver-Specific Organic Anion Transporter 1; Methyltransferases; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Practice Guidelines as Topic
PubMed: 32074077
DOI: 10.2478/rjim-2020-0001 -
Transplant International : Official... Mar 2018Treatment of acute rejection (AR) following kidney transplantation has improved in recent years, but there are still limitations to successful outcomes. This review... (Review)
Review
Treatment of acute rejection (AR) following kidney transplantation has improved in recent years, but there are still limitations to successful outcomes. This review article covers literature in regard to recipient and donor genetics of AR kidney and secondarily of liver allografts. Many candidate gene and some genome-wide association studies (GWASs) have been conducted for AR in kidney transplantation. Genetic associations with AR in kidney and liver are mostly weak, and in most cases, the associations have not been reproducible. A limitation in the study of AR is the lack of sufficiently large populations that account for population stratification to study the AR phenotype which in this era occurs in <10% of transplants. Furthermore, the AR phenotype has been difficult to define and the definitions of classifications have evolved over time. Literature related to the pharmacogenomics of tacrolimus is robust and has been validated in many studies. Associations between gene expression and AR are emerging as markers of outcomes and AR classification. In the future, combinations of pretransplant genotype for AR risk prediction, genotype-based immune suppressant dosing, and pharmacogenomic markers to select AR maintenance or treatment and expression markers from biopsies may provide valuable clinical tools for guiding treatment.
Topics: Gene Expression Profiling; Graft Rejection; Humans; Kidney Transplantation; Pharmacogenomic Testing; Polymorphism, Single Nucleotide
PubMed: 29030886
DOI: 10.1111/tri.13084