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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 -
Journal of Pediatric... 2022Pharmacogenetic (PGx) testing, a component of personalized medicine, aims to ensure treatment efficacy while reducing side effects and symptoms. Before this testing...
Pharmacogenetic (PGx) testing, a component of personalized medicine, aims to ensure treatment efficacy while reducing side effects and symptoms. Before this testing becomes routine in the pediatric oncology population, nurses need to understand the knowledge and concerns of providers, patients, and family members with regard to the timing, extent, interpretation, and incorporation of PGx testing. As part of a comprehensive PGx study (larger study) for children diagnosed with cancer, we surveyed providers and caregivers of children with cancer about their knowledge of and comfort with PGx testing. Caregivers who declined to participate in the larger PGx study were also asked to participate in the survey. Chi-square tests and a two-sample -test were used to compare variables. One hundred and two participants from the larger PGx study and 12 families who refused (response rate of 77% and 54%, respectively) as well as 29 providers (88%) completed surveys. Families not on the study were less interested in and comfortable with PGx results. Both groups were concerned about health or life insurance discrimination and payment. Providers would like support in ordering PGx testing and interpreting PGx. Providers remain wary of most PGx testing, uncomfortable with interpreting and applying the results. Families are interested in the possibilities of personalized prescribing while worried about who has access to their child's genetic information. Further education on relevant tests for providers, including nurses, and the testing process for families, including details on privacy and sharing of genetic information, appear necessary.
Topics: Child; Genetic Testing; Humans; Medical Oncology; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 35467433
DOI: 10.1177/10434542211055999 -
Journal of Medical Genetics Jan 2023Population databases could help patients with cancer and providers better understand current pharmacogenomic prescribing and testing practices. This retrospective... (Observational Study)
Observational Study
Population databases could help patients with cancer and providers better understand current pharmacogenomic prescribing and testing practices. This retrospective observational study analysed patients with cancer, drugs with pharmacogenomic evidence and related genetic testing in the National Institutes of Health database. Most patients with cancer (19 633 (88.3%) vs 2590 (11.7%)) received ≥1 drug and 36 (0.2%) received genetic testing, with a significant association between receiving ≥1 drug and age group (p<0.001), but not sex (p=0.612), race (p=0.232) or ethnicity (p=0.971). Drugs with pharmacogenomic evidence-but not genetic testing-were common for patients with cancer, reflecting key gaps preventing precision medicine from becoming standard of care.
Topics: Humans; Precision Medicine; Pharmacogenomic Testing; Population Health; Pharmacogenetics; Neoplasms
PubMed: 34872990
DOI: 10.1136/jmedgenet-2021-108112 -
Personalized Medicine Nov 2022To elicit preferences for pharmacogenomic (PGx) testing in polypharmacy patients. A face-to-face discrete choice experiment survey was designed and administered to...
To elicit preferences for pharmacogenomic (PGx) testing in polypharmacy patients. A face-to-face discrete choice experiment survey was designed and administered to adult polypharmacy patients recruited at a local retail pharmacy in Albuquerque (NM, USA). A total of 128 eligible polypharmacy patients completed the discrete choice experiment survey and significantly preferred a PGx test with lower cost, better confidentiality and higher certainty of identifying best medication/dose and side effects and one that can be used to advocate for their treatment needs (all p < 0.01). This is the first study eliciting preferences for PGx testing among polypharmacy patients. The study found most polypharmacy patients were willing to take a PGx test and their preferences were mostly influenced by test cost.
Topics: Adult; Humans; Pharmacogenomic Testing; Polypharmacy; Pharmacogenetics; Drug-Related Side Effects and Adverse Reactions; Confidentiality
PubMed: 36317592
DOI: 10.2217/pme-2022-0056 -
Clinical and Translational Science Jul 2022Actionable drug-gene pairs relevant to depression treatment include CYP2D6 and CYP2C19 with specific antidepressants. While clinical use of pharmacogenetic testing is...
Actionable drug-gene pairs relevant to depression treatment include CYP2D6 and CYP2C19 with specific antidepressants. While clinical use of pharmacogenetic testing is growing, little is known about pharmacogenetic testing for depression treatment in managed care. We determined the incidence of single-gene CYP2D6 and CYP2C19 testing following a new depression episode among US managed care patients, and described characteristics and antidepressant use of patients receiving tests. We used paid medical and pharmacy claims for patients from commercial health plans in the US. For adult patients with a new depression episode from January 1, 2013 to June 30, 2018, we identified covered claims for single-gene CYP2D6 and CYP2C19 pharmacogenetic tests and antidepressant fills. Fewer than 1% (n = 1795) of the depressed cohort (n = 438,534) received a single-gene CYP2D6 or CYP2C19 test through their insurance within 365 days of their earliest depression episode. The percentage of patients who received a test nearly tripled from 0.2% in 2013 to 0.5% in 2014 before plateauing at 0.4% from 2014 to 2017. Among the patients who received a single-gene CYP2D6 or CYP2C19 test and filled an antidepressant within 365 days of their depression diagnosis, up to 30% may have had their initial antidepressant informed by the test result. Our findings describe the use of antidepressants before and after pharmacogenetic testing, which is clinically relevant as pharmacogenomic testing becomes more common in clinical practice. Our study also emphasizes the need for procedure and billing codes that capture multiple-gene panel tests to be more widely implemented in administrative databases.
Topics: Adult; Antidepressive Agents; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Depression; Humans; Managed Care Programs; Pharmacogenomic Testing
PubMed: 35385214
DOI: 10.1111/cts.13279 -
Translational Psychiatry Oct 2021Pharmacogenomics (PGx) is the study of genetic influences on an individual's response to medications. Improvements in the quality and quantity of PGx research over the... (Review)
Review
Pharmacogenomics (PGx) is the study of genetic influences on an individual's response to medications. Improvements in the quality and quantity of PGx research over the past two decades have enabled the establishment of commercial markets for PGx tests. Nevertheless, PGx testing has yet to be adopted as a routine practice in clinical care. Accordingly, policy regulating the commercialization and reimbursement of PGx testing is in its infancy. Several papers have been published on the topic of challenges, or 'barriers' to clinical adoption of this healthcare innovation. However, many do not include recent evidence from randomized controlled trials, economic utility studies, and qualitative assessments of stakeholder opinions. The present paper revisits the most cited barriers to adoption of PGx testing: evidence for clinical utility, evidence for economic effectiveness, and stakeholder awareness. We consider these barriers in the context of reviewing PGx literature published over the past two decades and emphasize data from commercial PGx testing companies, since they have published the largest datasets. We conclude with a discussion of existing limitations to PGx testing and recommendations for progress.
Topics: Attitude; Pharmacogenetics; Pharmacogenomic Testing; Psychiatry
PubMed: 34615849
DOI: 10.1038/s41398-021-01600-7 -
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 -
Circulation. Genomic and Precision... Jun 2022Statin-associated muscle symptoms (SAMS) are the most frequently reported adverse events for statin therapies. Previous studies have reported an association between the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Statin-associated muscle symptoms (SAMS) are the most frequently reported adverse events for statin therapies. Previous studies have reported an association between the p.Val174Ala missense variant in and SAMS in simvastatin-treated subjects; however, evidence for genetic predictors of SAMS in atorvastatin- or rosuvastatin-treated subjects is currently lacking.
METHODS
ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; n=18 924) was a double-blind, randomized, placebo-controlled study evaluating the efficacy and safety of alirocumab (a PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitor) in acute coronary syndrome patients receiving high-intensity statin therapy. The goal of this pharmacogenomic analysis was to identify genetic variants associated with atorvastatin- and rosuvastatin-mediated SAMS among ODYSSEY OUTCOMES subjects who consented to participate in the genetic study (n=11 880). We performed multi-ancestry exome-wide and genome-wide association studies and gene burden analysis across 2 phenotypes (clinical SAMS [n=10 617] and creatine kinase levels [n=9630]).
RESULTS
A novel genome-wide significant association for an intronic variant (rs6667912) located within (odds ratio [95% CI], 1.39 [1.24-1.55]; =3.71×10) for patients with clinical SAMS (cases=894, controls=9723) was identified. This variant is located ≈30 kb upstream of , a locus associated with severe SAMS. We replicated 2 loci, at and , previously associated with creatine kinase levels during statin treatment. No association was observed between p.Val174Ala (rs4149056) in and SAMS (odds ratio [95% CI], 1.03 [0.90-1.18]; =0.69).
CONCLUSIONS
This study comprises the largest discovery exome-wide and genome-wide association study for atorvastatin- or rosuvastatin-mediated SAMS to date. These novel genetic findings may provide biological/mechanistic insight into this drug-induced toxicity, and help identify at-risk patients before selection of lipid-lowering therapies.
Topics: Acute Coronary Syndrome; Antigens, CD; Atorvastatin; Cholesterol, LDL; Creatine Kinase; Genome-Wide Association Study; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Membrane Proteins; Muscles; PCSK9 Inhibitors; Pharmacogenomic Testing; Receptors, Immunologic; Rosuvastatin Calcium
PubMed: 35543701
DOI: 10.1161/CIRCGEN.121.003503 -
Clinical and Translational Science Mar 2021Although pharmacogenetic testing is becoming increasingly common across medical subspecialties, a broad range of utilization and implementation exists across pediatric...
Although pharmacogenetic testing is becoming increasingly common across medical subspecialties, a broad range of utilization and implementation exists across pediatric centers. Large pediatric institutions that routinely use pharmacogenetics in their patient care have published their practices and experiences; however, minimal data exist regarding the full spectrum of pharmacogenetic implementation among children's hospitals. The primary objective of this nationwide survey was to characterize the availability, concerns, and barriers to pharmacogenetic testing in children's hospitals in the Children's Hospital Association. Initial responses identifying a contact person were received from 18 institutions. Of those 18 institutions, 14 responses (11 complete and 3 partial) to a more detailed survey regarding pharmacogenetic practices were received. The majority of respondents were from urban institutions (72%) and held a Doctor of Pharmacy degree (67%). Among all respondents, the three primary barriers to implementing pharmacogenetic testing identified were test reimbursement, test cost, and money. Conversely, the three least concerning barriers were potential for genetic discrimination, sharing results with family members, and availability of tests in certified laboratories. Low-use sites rated several barriers significantly higher than the high-use sites, including knowledge of pharmacogenetics (P = 0.03), pharmacogenetic interpretations (P = 0.04), and pharmacogenetic-based changes to therapy (P = 0.03). In spite of decreasing costs of pharmacogenetic testing, financial barriers are one of the main barriers perceived by pediatric institutions attempting clinical implementation. Low-use sites may also benefit from education/outreach in order to reduce perceived barriers to implementation.
Topics: Hospitals, Pediatric; Humans; Pharmacogenomic Testing; Practice Patterns, Physicians'; Reimbursement Mechanisms; United States
PubMed: 33325650
DOI: 10.1111/cts.12931 -
Psychiatria Danubina Sep 2022Quarantine measures with self-isolation of varying duration have been significant psychosocial stressors in the context of the COVID-19 pandemic. The serotonin selective... (Review)
Review
BACKGROUND
Quarantine measures with self-isolation of varying duration have been significant psychosocial stressors in the context of the COVID-19 pandemic. The serotonin selective reuptake inhibitor fluvoxamine has been considered as a prophylaxis against depression in early COVID-19 patients, with additional benefits apparently arising from its antiviral activity. In this narrative review, we draw attention to the body of evidence showing efficacy of fluvoxamine in protecting against depressive disorders in COVID-19 patients, while also attenuating the severity of COVID-19 disease, with a notable reduction in the need for intubation and lower mortality. We consider this potential two-fold action of fluvoxamine in the light of its pharmacogenetic and pharmacological profiles.
SUBJECTS AND METHODS
Full-text publications in English and Russian in Google Scholar, PubMed, NCBI, Web of Science, and E-Library databases were selected by keywords, solitary and in combination (fluvoxamine, COVID-19, depression, anxiety, antidepressants, adverse reactions) for the period from March 01, 2020 to June 06, 2022. We also analyzed the full-text publications in English and Russian language reporting adverse reactions caused by fluvoxamine use for the period from 2012 to 2022.
RESULTS
The literature search yielded 10 papers reporting on the efficacy fluvoxamine in relieving depressive symptoms in COVID-19 patients, and 3 papers on its effect on medical outcome. The preponderance of data indicated a dual therapeutic action of fluvoxamine, and our further literature investigation was informative about drug-drug interactions and genetic factors moderating the antidepressant efficacy of fluvoxamine.
CONCLUSIONS
Patients with COVID-19 seeking psychopharmacological treatment for depressive symptoms must be informed of the benefits and risks of fluvoxamine use. Several lines of findings indicate this agent to possess an additional antiviral action. However, optimal dosage regimens and the trade-off with drug-drug interactions remain unclear. Pharmacogenetic testing may assist in evidence-based optimization of fluvoxamine dosages in the context of COVID-19 infection with comorbid depression.
Topics: Antidepressive Agents; Antiviral Agents; Depression; Fluvoxamine; Humans; Pandemics; Pharmacogenetics; Pharmacogenomic Testing; Serotonin; Selective Serotonin Reuptake Inhibitors; COVID-19 Drug Treatment
PubMed: 36170697
DOI: No ID Found