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Philosophical Transactions of the Royal... Aug 2005Over the last two decades, identification of polymorphisms that influence human diseases has begun to have an impact on the provision of medical care. The promise of... (Review)
Review
Over the last two decades, identification of polymorphisms that influence human diseases has begun to have an impact on the provision of medical care. The promise of genetics lies in its ability to provide insights into an individual's susceptibility to disease, the likely nature of the disease and the most appropriate therapy. For much of its history, pharmacogenetics (PGx-the use of genetic information to impact drug choice) has been limited to comparatively simple phenotypes such as plasma drug levels. Progress in genetics technologies has broadened the scope of PGx efficacy and safety studies that can be implemented, impacting on a broad spectrum of drug discovery and development activities. Recent PGx data show the ability of this approach to generate information that can be applied to dose selection, efficacy determination and safety issues. This in turn will lead to significant opportunities to affect both the approach to clinical development and the probability of success--the latter being an important aspect for pharmaceutical companies and for the patients who will benefit from these new medicines.
Topics: Clinical Trials as Topic; Drug Delivery Systems; Drug Design; Humans; Pharmacogenetics; Pharmacokinetics; Polymorphism, Genetic
PubMed: 16096107
DOI: 10.1098/rstb.2005.1688 -
Journal of the American Academy of... Jun 2021AACAP's recent policy statement on Clinical Use of Pharmacogenetic Tests in Prescribing Psychotropic Medications for Children and Adolescents recommends that "clinicians...
AACAP's recent policy statement on Clinical Use of Pharmacogenetic Tests in Prescribing Psychotropic Medications for Children and Adolescents recommends that "clinicians avoid using pharmacogenetic testing to select psychotropic medications in children and adolescents." We agree that there are limitations to the nascent evidence base for using pharmacogenetics, especially in combinatorial form (eg, test results that bin medications based on multiple genes). However, all-or-nothing recommendations fail to recognize the nuance and context of this testing and contrast with the AACAP Facts for Families on pharmacogenetic testing. Moreover, pharmacogenetic testing may inform dosing for antidepressants that are commonly used in child and adolescent psychiatry (eg, sertraline, escitalopram, citalopram, fluvoxamine) as well as the tolerability of some psychotropic medications. With this in mind, we wish to remind the AACAP community of the accumulating evidence and to highlight important principles of pharmacogenetic testing in youths. Specifically: 1) pharmacogenetic testing is not always performed by commercial companies and is not always combinatorial; 2) dosing recommendations or assessment of risk for severe hypersensitivity reactions are based on pharmacogenetics in the Food and Drug Administration (FDA)-approved product inserts for several medications commonly prescribed to children (eg, citalopram, aripiprazole, atomoxetine, carbamazepine, oxcarbazepine at www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling); 3) expert consensus guidelines for dosing or identifying hypersensitivity risk for these drugs are available from the National Institutes of Health (NIH)-supported Clinical Pharmacogenetics Implementation Consortium (CPIC, www.cpicpgx.org/), which provides transparent, regularly updated, and evidence-based evaluations of pharmacogenetic data; and 4) randomized trials are not required for clinical dose adjustments; for example, dose adjustments because of decreased hepatic function or concomitant interacting medications are based on pharmacokinetic data, similar to many pharmacokinetic gene-based recommendations from CPIC.
Topics: Adolescent; Antidepressive Agents; Child; Humans; Pharmacogenetics; Pharmacogenomic Testing; Psychopharmacology; Psychotropic Drugs
PubMed: 32860906
DOI: 10.1016/j.jaac.2020.08.006 -
BMC Medical Genetics May 2015Pharmacogenetics is a rapidly growing field that aims to identify the genes that influence drug response. This science can be used as a powerful tool to tailor drug...
BACKGROUND
Pharmacogenetics is a rapidly growing field that aims to identify the genes that influence drug response. This science can be used as a powerful tool to tailor drug treatment to the genetic makeup of individuals. The present study explores the coverage of the topic of pharmacogenetics and its potential benefit in personalised medicine by the UK newsprint media.
METHODS
The LexisNexis database was used to identify and retrieve full text articles from the 10 highest circulation national daily newspapers and their Sunday equivalents in the UK. Content analysis of newspaper articles which referenced pharmacogenetic testing was carried out. A second researcher coded a random sample (21%) of newspaper articles to establish the inter-rater reliability of coding.
RESULTS
Of the 256 articles captured by the search terms, 96 articles (with pharmacogenetics as a major component) met the study inclusion criteria. The majority of articles over-stated the benefits of pharmacogenetic testing while paying less attention to the associated risks. Overall beneficial effects were mentioned 5.3 times more frequently than risks (pā<ā0.001). The most common illnesses for which pharmacogenetically based personalised medicine was discussed were cancer, cardiovascular disease and CNS diseases. Only 13% of newspaper articles that cited a specific scientific study mentioned this link in the article. There was a positive correlation between the size of the article and both the number of benefits and risks stated (Pā<ā0.01).
CONCLUSION
More comprehensive coverage of the area of personalised medicine within the print media is needed to inform public debate on the inclusion of pharmacogentic testing in routine practice.
Topics: Newspapers as Topic; Pharmacogenetics; Precision Medicine; Public Opinion; Risk
PubMed: 25956914
DOI: 10.1186/s12881-015-0172-3 -
Journal of Managed Care & Specialty... Apr 2015Some have proposed the integration of pharmacogenetic (PGx) testing into medication therapy management (MTM) to enable further refinement of treatments to reduce risk of... (Review)
Review
Some have proposed the integration of pharmacogenetic (PGx) testing into medication therapy management (MTM) to enable further refinement of treatments to reduce risk of adverse responses and improve efficacy. PGx testing involves the analysis of genetic variants associated with therapeutic or adverse response and may be useful in enhancing the ability to identify ineffective and/or harmful drugs or drug combinations. This "enhanced" MTM might also reduce patient concerns about side effects and increase confidence that the medication is effective, addressing 2 key factors that impact patient adherence: concern and necessity. However, the feasibility and effectiveness of the integration of PGx testing into MTM in clinical practice has not yet been determined. In this commentary, we consider some of the challenges to the integration and delivery of PGx testing in MTM services.
Topics: Community Pharmacy Services; Genetic Testing; Humans; Medication Therapy Management; Pharmaceutical Preparations; Pharmacogenetics
PubMed: 25803768
DOI: 10.18553/jmcp.2015.21.4.346 -
Pediatric Research Feb 2022This review evaluates the pediatric evidence for pharmacogenetic associations for drugs that are commonly prescribed by or encountered by pediatric clinicians across... (Review)
Review
This review evaluates the pediatric evidence for pharmacogenetic associations for drugs that are commonly prescribed by or encountered by pediatric clinicians across multiple subspecialties, organized from most to least pediatric evidence. We begin with the pharmacogenetic research that led to the warning of increased risk of death in certain pediatric populations ("ultrarapid metabolizers") who are prescribed codeine after tonsillectomy or adenoidectomy. We review the evidence for genetic testing for thiopurine metabolism, which has become routine in multiple pediatric subspecialties. We discuss the pharmacogenetic research in proton pump inhibitors, for which clinical guidelines have recently been made available. With an increase in the prevalence of behavioral health disorders including attention deficit hyperactivity disorder (ADHD), we review the pharmacogenetic literature on selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, and ADHD medications. We will conclude this section on the current pharmacogenetic data on ondansetron. We also provide our perspective on how to integrate the current research on pharmacogenetics into clinical care and what further research is needed. We discuss how institutions are managing pharmacogenetic test results and implementing them clinically, and how the electronic health record can be leveraged to ensure testing results are available and taken into consideration when prescribing medications. IMPACT: While many reviews of pharmacogenetics literature are available, there are few focused on pediatrics. Pediatricians across subspecialties will become more comfortable with pharmacogenetics terminology, know resources they can use to help inform their prescribing habits for drugs with known pharmacogenetic associations, and understand the limitations of testing and where further research is needed.
Topics: Attention Deficit Disorder with Hyperactivity; Child; Genetic Testing; Humans; Pediatricians; Pharmacogenetics; Selective Serotonin Reuptake Inhibitors
PubMed: 33824446
DOI: 10.1038/s41390-021-01499-2 -
BMC Medicine Aug 2013Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already... (Review)
Review
Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already happening, and will accelerate with developments in personalized medicine. However, its promise has not always translated into improvements in patient care due to the complexities involved. There are also concerns that advice for tests has been reversed, current tests can be costly, there is fragmentation of funding of care, and companies may seek high prices for new targeted drugs. There is a need to integrate current knowledge from a payer's perspective to provide future guidance. Multiple findings including general considerations; influence of pharmacogenomics on response and toxicity of drug therapies; value of biomarker tests; limitations and costs of tests; and potentially high acquisition costs of new targeted therapies help to give guidance on potential ways forward for all stakeholder groups. Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients.
Topics: Delivery of Health Care; Feasibility Studies; Forecasting; Humans; Patient Care; Pharmacogenetics; Precision Medicine
PubMed: 23941275
DOI: 10.1186/1741-7015-11-179 -
European Journal of Human Genetics :... Dec 2016Pharmacogenomics has been lauded as an important innovation in clinical medicine as a result of advances in genomic science. As one of the cornerstones in precision... (Review)
Review
Pharmacogenomics has been lauded as an important innovation in clinical medicine as a result of advances in genomic science. As one of the cornerstones in precision medicine, the vision to determine the right medication in the right dosage for the right treatment with the use of genetic information has not exactly materialised, and few genetic tests have been implemented as the standard of care in health systems worldwide. Here we review the findings from a SWOT analysis to examine the strengths, weaknesses, opportunities and threats around the role of pharmacogenetics in public health and clinical health care, at the micro, meso and macro levels corresponding to the perspectives of the individuals (scientists, patients and physicians), the health-care institutions and the health systems, respectively.
Topics: Drug Therapy; Genetic Testing; Pharmacogenetics; Precision Medicine; Public Health
PubMed: 27577547
DOI: 10.1038/ejhg.2016.114 -
Drug Metabolism and Personalized Therapy Mar 2016
The role of pharmacogenetics and pharmacogenomics in 21st-century medicine: state of the art and new challenges discussed in the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society (SEFF).
Topics: Delivery of Health Care; Humans; Pharmacogenetics; Precision Medicine; Spain
PubMed: 26641977
DOI: 10.1515/dmpt-2015-0033 -
American Journal of Health-system... Dec 2016Existing pharmacogenomic informatics models, key implementation steps, and emerging resources to facilitate the development of pharmacogenomic clinical decision support... (Review)
Review
PURPOSE
Existing pharmacogenomic informatics models, key implementation steps, and emerging resources to facilitate the development of pharmacogenomic clinical decision support (CDS) are described.
SUMMARY
Pharmacogenomics is an important component of precision medicine. Informatics, especially CDS in the electronic health record (EHR), is a critical tool for the integration of pharmacogenomics into routine patient care. Effective integration of pharmacogenomic CDS into the EHR can address implementation challenges, including the increasing volume of pharmacogenomic clinical knowledge, the enduring nature of pharmacogenomic test results, and the complexity of interpreting results. Both passive and active CDS provide point-of-care information to clinicians that can guide the systematic use of pharmacogenomics to proactively optimize pharmacotherapy. Key considerations for a successful implementation have been identified; these include clinical workflows, identification of alert triggers, and tools to guide interpretation of results. These considerations, along with emerging resources from the Clinical Pharmacogenetics Implementation Consortium and the National Academy of Medicine, are described.
CONCLUSION
The EHR with CDS is essential to curate pharmacogenomic data and disseminate patient-specific information at the point of care. As part of the successful implementation of pharmacogenomics into clinical settings, all relevant clinical recommendations pertaining to gene-drug pairs must be summarized and presented to clinicians in a manner that is seamlessly integrated into the clinical workflow of the EHR. In some situations, ancillary systems and applications outside the EHR may be integrated to augment the capabilities of the EHR.
Topics: Decision Support Systems, Clinical; Electronic Health Records; Humans; Pharmacogenetics; Point-of-Care Systems; Precision Medicine
PubMed: 27864204
DOI: 10.2146/ajhp160030 -
The AAPS Journal May 2016Biotherapeutics (BTs), one of the fastest growing classes of drug molecules, offer several advantages over the traditional small molecule pharmaceuticals because of... (Review)
Review
Biotherapeutics (BTs), one of the fastest growing classes of drug molecules, offer several advantages over the traditional small molecule pharmaceuticals because of their relatively high specificity, low off-target effects, and biocompatible metabolism, in addition to legal and logistic advantages. However, their clinical utility is limited, among other things, by their high immunogenic potential and/or variable therapeutic efficacy in different patient populations. Both of these issues, also commonly experienced with small molecule drugs, have been addressed effectively in a number of cases by the successful application of pharmacogenomic tools and approaches. In this introductory article of the special issue, we review the current state of application of pharmacogenomics to BTs and offer suggestions for further expansion of the field.
Topics: Animals; Biological Products; Biological Therapy; Biopharmaceutics; Humans; Pharmacogenetics; Recombinant Proteins
PubMed: 27007601
DOI: 10.1208/s12248-016-9903-4