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Pharmacogenomics Apr 2021Despite the expansion of pharmacogenetics (PGx), the views of pediatric patients remain unknown. This study explores adolescents' understanding and perceptions of PGx...
Despite the expansion of pharmacogenetics (PGx), the views of pediatric patients remain unknown. This study explores adolescents' understanding and perceptions of PGx testing. Adolescents who had PGx testing were interviewed and their electronic health records were reviewed. Adolescents accurately described reason for testing and most felt the results impacted their current and future care. None perceived risks to securing future employment or insurance. All felt PGx would benefit their peers. Adolescents understand the reasons for PGx and perceive testing to be useful, low risk and applicable to peers. Findings from this study advocate for the inclusion of adolescents in shared decision-making regarding testing and for active engagement in the discussion of results.
Topics: Adolescent; Attitude; Child; Electronic Health Records; Employment; Female; Humans; Insurance, Health; Male; Pharmacogenomic Testing; Young Adult
PubMed: 33849282
DOI: 10.2217/pgs-2020-0177 -
Mayo Clinic Proceedings Jan 2017Recent technological advances have radically changed genetic testing from an expensive and burdensome undertaking to a rapid and less costly option for many purposes.... (Review)
Review
Recent technological advances have radically changed genetic testing from an expensive and burdensome undertaking to a rapid and less costly option for many purposes. The utility of "next-generation" sequencing has been found to establish the diagnosis for hundreds of genetic disorders, to assess pharmacogenomic variants, and to identify treatable targets within malignant neoplasms. The ready availability of genomic information has led to the question of whether there would be clinical benefit of sequencing the genome of individuals who are not seeking a diagnosis, that is, genomic screening in generally healthy people, to provide anticipatory insights for their health care. Little research has been conducted in this area. We examine the considerable unresolved scientific and ethical issues encountered when considering whole-genome sequencing of healthy people.
Topics: Gene Expression Profiling; Genetic Predisposition to Disease; Genome, Human; Humans; Pharmacogenomic Testing; Precision Medicine; Sequence Analysis, DNA
PubMed: 28062062
DOI: 10.1016/j.mayocp.2016.10.019 -
British Journal of Clinical Pharmacology Mar 2021Pre-emptive pharmacogenomic (PGx) testing is potentially an efficient approach to improve drug safety and efficacy but the target population to test is unclear.
BACKGROUND
Pre-emptive pharmacogenomic (PGx) testing is potentially an efficient approach to improve drug safety and efficacy but the target population to test is unclear.
OBJECTIVES
We aim to describe the prescription pattern of PGx drugs among adult medical outpatients.
METHODS
We estimated the 5-year cumulative incidence (CI) for receiving three groups of PGx drugs using competing risks analysis: (i) all PGx drugs, (ii) PGx drugs with guidelines and (iii) PGx drugs with serious clinical effects. Comparisons of CIs were also done by patient characteristics using Gray's test.
RESULTS
The 5-year CIs of receiving any new PGx drug, PGx drug with guidelines and serious clinical effects were 42.6%, 37.3% and 13.7%, respectively. The 5-year CI of receiving any new PGx drug was higher for patients >40 years old (43.6% vs ≤40 years old 36.0%, P < 2.2 × 10 ), Malays and Indians (50.3% and 49.8% vs Chinese 31.1%, P < 2.2 × 10 ), those who attended one of the following four specialties at the index visit compared to other specialties (infectious diseases [46.2% vs 42.6%, P = 2.9 × 10 ], psychiatry [48.3% vs 42.3%, P = 7.4 × 10 ], renal [49.8% vs 40.9%, P < 2.2 × 10 ], and rheumatology and immunology [54.8% vs 41.7%, P < 2.2 × 10 ]) and those prescribed ≥5 drugs at index visit (51.7% vs 0-4 drugs 41.7%, P < 2.2 × 10 ).
CONCLUSIONS
Medical outpatients have a substantial probability of benefiting from pre-emptive PGx testing and this is higher in certain subgroups of patients.
Topics: Adult; Humans; Outpatients; Pharmacogenetics; Pharmacogenomic Testing; Prescriptions; Psychiatry
PubMed: 32559336
DOI: 10.1111/bcp.14439 -
Genetics in Medicine : Official Journal... Apr 2022Pharmacogenomic testing interrogates germline sequence variants implicated in interindividual drug response variability to infer a drug response phenotype and to guide...
Pharmacogenomic testing interrogates germline sequence variants implicated in interindividual drug response variability to infer a drug response phenotype and to guide medication management for certain drugs. Specifically, discrete aspects of pharmacokinetics, such as drug metabolism, and pharmacodynamics, as well as drug sensitivity, can be predicted by genes that code for proteins involved in these pathways. Pharmacogenomics is unique and differs from inherited disease genetics because the drug response phenotype can be drug-dependent and is often unrecognized until an unexpected drug reaction occurs or a patient fails to respond to a medication. Genes and variants with sufficiently high levels of evidence and consensus may be included in a clinical pharmacogenomic test; however, result interpretation and phenotype prediction can be challenging for some genes and medications. This document provides a resource for laboratories to develop and implement clinical pharmacogenomic testing by summarizing publicly available resources and detailing best practices for pharmacogenomic nomenclature, testing, result interpretation, and reporting.
Topics: Genetics, Medical; Genomics; Humans; Pharmacogenetics; Pharmacogenomic Testing; Phenotype; United States
PubMed: 35177334
DOI: 10.1016/j.gim.2021.12.009 -
Basic & Clinical Pharmacology &... May 2021Predictive biomarkers play an important role in our efforts to individualize pharmacotherapy, and within recent years, a number of different types of assays have been... (Review)
Review
Predictive biomarkers play an important role in our efforts to individualize pharmacotherapy, and within recent years, a number of different types of assays have been introduced. These biomarkers may potentially support the selection and dosage of specific drugs in order to maximize efficacy and minimize adverse reactions in the individual patient. However, in many instances, the scientific and clinical evidence is insufficient to support the prescribing decision. When predictive biomarkers are used to guide pharmacotherapy, it is important to secure that decisions are based on solid clinical evidence. Here, the regulatory authorities, especially the FDA, have been at the forefront in relation to regulate this type of biomarker assay in order to secure patient safety. The approval process for companion diagnostics is an example of this effort, where the scientific validity of the biomarker and assay is in focus. With the approaching implementation of the new IVD Regulation, greater attention will also be paid to analytical and clinical validity of biomarker assays in the EU. For any type of predictive biomarker assay, including pharmacogenetic and tumour profiling tests, the clinical evidence needs to be in place before they are used routinely in the clinic.
Topics: Biological Assay; Biomarkers; Diagnostic Test Approval; European Union; Pharmacogenomic Testing; Precision Medicine; Reagent Kits, Diagnostic; United States; United States Food and Drug Administration
PubMed: 33665955
DOI: 10.1111/bcpt.13578 -
Revista Brasileira de Psiquiatria (Sao... Apr 2020
Topics: Antidepressive Agents; Decision Support Techniques; Depressive Disorder; Humans; Pharmacogenomic Testing; Practice Guidelines as Topic; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 32187320
DOI: 10.1590/1516-4446-2019-0799 -
Genes Oct 2023Pharmacogenomic (PGx) testing to inform antidepressant medication selection and dosing is gaining attention from healthcare professionals, patients, and payors in...
Pharmacogenomic (PGx) testing to inform antidepressant medication selection and dosing is gaining attention from healthcare professionals, patients, and payors in Australia. However, there is often uncertainty regarding which test is most suitable for a particular patient. Here, we identified and evaluated the coverage of and variants in commercial antidepressant PGx testing panels in Victoria, a large and ethnically diverse state of Australia. Test characteristics and star alleles tested for both genes were obtained directly from pathology laboratories offering PGx testing and compared against the Association of Molecular Pathology's recommended minimum (Tier 1) and extended (Tier 2) allele sets. Although all tests covered the minimum recommended alleles for , this was not the case for . This study emphasizes that PGx tests might not be suitable for all individuals in Australia due to the limited range of star alleles assessed. Inadequate haplotype coverage may risk misclassification of an individual's predicted metabolizer phenotype, which has ramifications for depression medication selection and dosage. This study underscores the urgent need for greater standardization in PGx testing and emphasizes the importance of considering genetic ancestry when choosing a PGx testing panel to ensure optimal clinical applicability.
Topics: Humans; Pharmacogenomic Testing; Cytochrome P-450 CYP2D6; Victoria; Cytochrome P-450 CYP2C19; Antidepressive Agents
PubMed: 37895294
DOI: 10.3390/genes14101945 -
Pharmacogenomics Jan 2022Pharmacogenomic testing can indicate which drugs may have limited therapeutic action or lead to adverse effects, hence guiding rational and safe prescribing. However,... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic testing can indicate which drugs may have limited therapeutic action or lead to adverse effects, hence guiding rational and safe prescribing. However, in the UK and other countries, there are still significant barriers to implementation of testing in primary care. This systematic review presents the barriers and enablers to the implementation of pharmacogenomics in primary care setting. MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched through to July 2020 for studies that reported primary qualitative data of primary care professionals and patient views. Following screening, data extraction and quality assessment, data synthesis was undertaken using meta-aggregation based on the theoretical domain's framework (TDF). Confidence in the synthesized findings relating to credibility and dependability was established using CONQual. Eligible papers were categorized into six TDF domains - knowledge; social and professional roles; behavioral regulation; beliefs and consequences; environmental context and resources; and social influences. From 1669 citations, eighteen eligible studies were identified across seven countries, with a sample size of 504 participants including both primary care professionals and patients. From the data, 15 synthesized statements, all with moderate CONQual rating emerged. These categories range from knowledge, awareness among Primary Care Physicians and patients, professional relationships, negative impact of PGx, belief that PGx can reduce adverse drug reactions, clinical evidence, cost-effectiveness, informatics, reporting issues and social issues. Through use of TDF, fifteen synthesized statements provide policymakers with valuable recommendations for the implementation of pharmacogenomics in primary care. In preparation, policymakers need to consider the introduction of effective educational strategies for both PCPs and patients to raise knowledge, awareness, and engagement. The actual introduction of PGx will require reorganization with decision support tools to aid use of PGx in primary care, with a clear delegation of roles and responsibilities between general professionals and pharmacists supplemented by a local pool of experts. Furthermore, policy makers need to address the cost effectiveness of pharmacogenomics and having appropriate infrastructure supporting testing and interpretation including informatic solutions for utilizing pharmacogenomic results.
Topics: Health Services Accessibility; Humans; Pharmacogenomic Testing; Primary Health Care
PubMed: 34911350
DOI: 10.2217/pgs-2021-0131 -
Neurologia May 2022Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly... (Review)
Review
INTRODUCTION
Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly people and their families. Current pharmacological treatment includes acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine; however, only one-third of patients respond to treatment. Genetic factors have been shown to play a role in this inter-individual variability in drug response.
DEVELOPMENT
We review pharmacogenetic reports of AD-modifying drugs, the pharmacogenetic biomarkers included, and the phenotypes evaluated. We also discuss relevant methodological considerations for the design of pharmacogenetic studies into AD. A total of 33 pharmacogenetic reports were found; the majority of these focused on the variability in response to and metabolism of donepezil. Most of the patients included were from Caucasian populations, although some studies also include Korean, Indian, and Brazilian patients. CYP2D6 and APOE are the most frequently studied biomarkers. The associations proposed are controversial.
CONCLUSIONS
Potential pharmacogenetic biomarkers for AD have been identified; however, it is still necessary to conduct further research into other populations and to identify new biomarkers. This information could assist in predicting patient response to these drugs and contribute to better treatment decision-making in a context as complex as ageing.
Topics: Acetylcholinesterase; Aged; Alzheimer Disease; Biomarkers; Donepezil; Humans; Pharmacogenomic Testing
PubMed: 35595404
DOI: 10.1016/j.nrleng.2018.03.022 -
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