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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 -
Clinical and Translational Science Jan 2021Many academic institutions are collecting blood samples from patients seeking treatment for coronavirus disease 2019 (COVID-19) to build research biorepositories. It may...
Many academic institutions are collecting blood samples from patients seeking treatment for coronavirus disease 2019 (COVID-19) to build research biorepositories. It may be feasible to extract pharmacogenomic (PGx) information from biorepositories for clinical use. We sought to characterize the potential value of multigene PGx testing among individuals hospitalized with COVID-19 in the United States. We performed a cross-sectional analysis of electronic health records from consecutive individuals hospitalized with COVID-19 at a large, urban academic health system. We characterized medication orders, focusing on medications with actionable PGx guidance related to 14 commonly assayed genes (CYP2C19, CYP2C9, CYP2D6, CYP3A5, DPYD, G6PD, HLA-A, HLA-B, IFNL3, NUDT15, SLCO1B1, TPMT, UGT1A1, and VKORC1). A simulation analysis combined medication data with population phenotype frequencies to estimate how many treatment modifications would be enabled if multigene PGx results were available. Sixty-four unique medications with PGx guidance were ordered at least once in the cohort (n = 1,852, mean age 60.1 years). Nearly nine in 10 individuals (89.7%) had at least one order for a medication with PGx guidance and 427 patients (23.1%) had orders for 4 or more actionable medications. Using a simulation, we estimated that 17 treatment modifications per 100 patients would be enabled if PGx results were available. The genes CYP2D6 and CYP2C19 were responsible for the majority of treatment modifications, and the medications most often affected were ondansetron, oxycodone, and clopidogrel. PGx results would be relevant for nearly all individuals hospitalized with COVID-19 and would provide the opportunity to improve clinical care.
Topics: Adult; Aged; Aged, 80 and over; COVID-19; Cross-Sectional Studies; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Female; Hospitalization; Humans; Male; Middle Aged; Pharmacogenomic Testing; Retrospective Studies; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33085221
DOI: 10.1111/cts.12919 -
Therapie Apr 2017
Topics: Humans; Periodicals as Topic; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 28238399
DOI: 10.1016/j.therap.2017.01.004 -
Pharmacogenomics Jun 2020To perform a meta-analysis of prospective, two-arm studies examining the clinical utility of using the combinatorial pharmacogenomic test, GeneSight Psychotropic, to... (Meta-Analysis)
Meta-Analysis
To perform a meta-analysis of prospective, two-arm studies examining the clinical utility of using the combinatorial pharmacogenomic test, GeneSight Psychotropic, to inform treatment decisions for patients with major depressive disorder (MDD). The pooled mean effect of symptom improvement and pooled relative risk ratio (RR) of response and remission were calculated using a random effect model. Overall, 1556 patients were included from four studies, with outcomes evaluated at week 8 or week 10. Patient outcomes were significantly improved for patients with MDD whose care was guided by the combinatorial pharmacogenomic test results compared with unguided care (symptom improvement Δ = 10.08%, 95% CI: 1.67-18.50; p = 0.019; response RR = 1.40, 95% CI: 1.17-1.67; p < 0.001; remission RR = 1.49, 95% CI: 1.17-1.89; p = 0.001). GeneSight Psychotropic guided care improves outcomes among patients with MDD.
Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; Pharmacogenomic Testing; Prospective Studies; Psychotropic Drugs
PubMed: 32301649
DOI: 10.2217/pgs-2019-0157 -
Pharmacogenomics Aug 2022Pharmacogenetics is the relationship between an individual's genetic variations and their response to pharmacological treatment. We conducted an overview of reviews on... (Review)
Review
Pharmacogenetics is the relationship between an individual's genetic variations and their response to pharmacological treatment. We conducted an overview of reviews on the use of post-treatment pharmacogenetic testing for oncology, based on clinically relevant gene-drug pairs. We conducted a search on Medline, Embase and Cochrane Library, from their inception to 18 June 2020. We selected six eligible systematic reviews. The most studied drug categories were estrogen agonists/antagonists and fluoropyrimidines associated with cytochrome P450 and dihydropyrimidine dehydrogenase genes ( and ), but many studies were classified as being of critically low or low quality. There is a need for more high-quality primary studies and systematic reviews that assess the risk of bias, with consistent definitions of clinical outcomes to consider the benefits of pharmacogenetic testing for oncology.
Topics: Humans; Medical Oncology; Pharmacogenetics; Pharmacogenomic Testing; Systematic Reviews as Topic
PubMed: 36001087
DOI: 10.2217/pgs-2022-0064 -
Pharmacogenomics Feb 2021To assess the impact of sociodemographic factors and beliefs about medicines on the uptake of pharmacogenomic testing in older adults in a public healthcare system....
To assess the impact of sociodemographic factors and beliefs about medicines on the uptake of pharmacogenomic testing in older adults in a public healthcare system. Data are based on a sample of 347 primary care older adults. Most respondents (90%) were willing to provide a saliva sample and 47% were willing to pay for it. Increased age (odds ratio: 0.91; p = 0.04) and negative beliefs about the harmfulness of medicines (odds ratio: 0.68; p = 0.02) were associated with a decreased willingness to provide a sample. Lower education (less than university, odds ratio: 0.54; p = 0.04) was associated with a decreased willingness to pay. Education and beliefs about medicines are important factors in the acceptability of pharmacogenomic testing in older adults.
Topics: Age Factors; Aged; Culture; Female; Follow-Up Studies; Health Expenditures; Health Knowledge, Attitudes, Practice; Humans; Male; Patient Acceptance of Health Care; Pharmacogenomic Testing; Socioeconomic Factors; Surveys and Questionnaires
PubMed: 33601907
DOI: 10.2217/pgs-2020-0077 -
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 -
The American Journal of Psychiatry Jul 2024In this review, the authors update the 2018 position statement of the American Psychiatric Association Council of Research Workgroup on Biomarkers and Novel Treatments... (Review)
Review
OBJECTIVE
In this review, the authors update the 2018 position statement of the American Psychiatric Association Council of Research Workgroup on Biomarkers and Novel Treatments on pharmacogenomic (PGx) tools for treatment selection in depression.
METHODS
The literature was reviewed for new clinical trials and meta-analyses, published from 2017 to 2022, of studies using PGx tools for treatment selection in depression. The blinding and control conditions, as well as primary and secondary outcomes and post hoc analyses, were summarized.
RESULTS
Eleven new clinical trials and five meta-analyses were identified; all studies had primary outcome measures related to speed or efficacy of treatment response. Three trials (27%) demonstrated efficacy on the primary outcome measure with statistical significance; the three studies used different PGx tools; one study was open-label and the other two were small single-blind trials. Five trials (45%) did not detect efficacy with statistical significance on either primary or secondary outcome measures. Only one trial (9%) used adverse events as a primary outcome measure. All studies had significant limitations; for example, none adopted a fully blinded study design, only two studies attempted to blind the treating clinician, and none incorporated measures to estimate the effectiveness of the blinds or the influence of lack of blinding on the study results.
CONCLUSIONS
The addition of these new data do not alter the recommendations of the 2018 report, or the advice of the U.S. Food and Drug Administration, that the evidence does not support the use of currently available combinatorial PGx tools for treatment selection in major depressive disorder. Priority efforts for future studies and the development and testing of effective tools include fully blinded study designs, inclusion of promising genetic variants not currently included in any commercially available tests, and investigation of other uses of pharmacogenomics, such as estimating the likelihood of rare adverse drug effects, rather than increasing the speed or magnitude of drug response.
Topics: Humans; Pharmacogenetics; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder, Major; Depressive Disorder; Pharmacogenomic Testing
PubMed: 38685859
DOI: 10.1176/appi.ajp.20230657 -
Journal of Genetic Counseling Dec 2022Pharmacogenomic (PGx) testing is an increasingly utilized technology that offers the potential for precision drug selection to treat depression. Though PGx-guided...
Pharmacogenomic (PGx) testing is an increasingly utilized technology that offers the potential for precision drug selection to treat depression. Though PGx-guided therapy is associated with increased rates of remission of depression symptoms, for many patients, treatment will not change based on PGx testing results. Lack of consensus guidelines for pre-test counseling may hinder the communication of PGx testing limitations, and patients often have high expectations for test outcomes. To explore this issue, we created and evaluated the impact of a pre-test education video for patients with depression. Individuals in the education group (n = 198) viewed this brief video about PGx testing prior to completing a survey that explored knowledge, perception, and expectations of PGx testing developed using a theoretical framework to measure intention to test. Individuals in the survey-only group (n = 189) completed the same survey but were not provided with any PGx educational materials. Analyses demonstrate efficacy of the video in improving knowledge of PGx. The education group also reported more positive attitudes and greater perceived control over pursuing PGx testing compared to the survey-only group. Further analyses identified significant differences in expectations, attitudes, and intention to pursue PGx testing based on number of previous medication trials. Path analyses identified the best model for predicting PGx testing intention, specifically that social norms and ease of testing have a strong positive association, and knowledge has a strong negative association with patients' intentions to test across the full sample, the education group, and the survey-only group. The findings of this study serve as a foundation for future tailored educational initiatives in the PGx testing space.
Topics: Humans; Pharmacogenomic Testing; Motivation; Pharmacogenetics; Antidepressive Agents; Surveys and Questionnaires
PubMed: 35900228
DOI: 10.1002/jgc4.1612 -
Personalized Medicine Mar 2019To evaluate factors influencing cardiologists' perspectives about pharmacogenomic (PGx) testing in clinical practice.
AIM
To evaluate factors influencing cardiologists' perspectives about pharmacogenomic (PGx) testing in clinical practice.
PATIENTS & METHODS
Semistructured interviews with practicing cardiologists were qualitatively analyzed to identify common themes.
RESULTS
Five themes were identified among 16 cardiologists from four specialties (n = 5 general cardiology, n = 3 electrophysiology, n = 2 adult congenital and n = 6 heart failure/transplant): cardiologists' knowledge and needs, perceived clinical validity and utility of PGx testing, dissemination and management of PGx results, patient-related considerations and incidental findings.
CONCLUSION
Lack of evidence was considered by many cardiologists to be a major barrier hindering the use of PGx testing. However, they would consider adopting PGx if they were provided additional education, ongoing support and evidence supporting the clinical utility of PGx testing in cardiovascular medicine.
Topics: Adult; Attitude of Health Personnel; Cardiologists; Cardiology; Female; Health Knowledge, Attitudes, Practice; Humans; Male; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 30543145
DOI: 10.2217/pme-2018-0099