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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 -
Journal of Personalized Medicine Sep 2022The clinical adoption and implementation of pharmacogenomics (PGx) beyond academic medical centers remains slow, restricting the general population from benefitting from...
The clinical adoption and implementation of pharmacogenomics (PGx) beyond academic medical centers remains slow, restricting the general population from benefitting from this important component of personalized medicine. As an initial step in the statewide initiative of PGx implementation in Minnesota, we engaged community members and assessed attitudes towards PGx testing and acceptability of establishing a secure statewide PGx database for clinical and research use among Minnesota residents. Data was collected from 808 adult attendees at the 2021 Minnesota State Fair through an electronic survey. Eighty-four percent of respondents felt comfortable getting a PGx test for clinical care. Most respondents trusted health professionals (78.2%) and researchers (73.0%) to keep their PGx data private. The majority expressed their support and interest in participating in a statewide PGx database for clinical and research use (64-72%). Higher acceptability of the statewide PGx database was associated with younger age, higher education, higher health literacy, having health insurance, and prior genetic testing. The study sample representing Minnesota residents expressed high acceptability of receiving PGx testing and willingness to participate in PGx data sharing for clinical and research use. Community support and engagement are needed to advance PGx implementation and research on the state scale.
PubMed: 36294754
DOI: 10.3390/jpm12101615 -
Delaware Journal of Public Health Dec 2021Pharmacogenetics allows providers to enhance their treatment decisions for common medications used in certain conditions such as depression, gastroesophageal reflux...
Pharmacogenetics allows providers to enhance their treatment decisions for common medications used in certain conditions such as depression, gastroesophageal reflux disease (GERD), pain, and acute lymphoblastic leukemia. A precision medicine approach combines pharmacogenetics (when appropriate) with other clinical and environmental factors to minimize trial-and-error of treatment. Public awareness of the impact of pharmacogenetics on treatment decisions is growing, and healthcare should be aware of the resources supporting it. Pharmacogenetics may seem daunting, but the accessibility of pharmacogenetic testing has improved with growing availability of evidence-based clinical recommendations, pharmacogenetic tests, clinical decision support resources, insurance coverage, and digestible education materials. As precision medicine and precision public health expands over the next decade, pharmacogenetic testing will continuously grow to be cheaper and part of routine genetic or genomic screenings, and be another common test-like liver or kidney function tests-that can enhance treatment decisions.
PubMed: 35619975
DOI: 10.32481/djph.2021.12.006 -
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 -
Diagnostics (Basel, Switzerland) Jun 2021For many authorized drugs, accumulating scientific evidence supports testing for predictive biomarkers to apply personalized therapy and support preventive measures... (Review)
Review
For many authorized drugs, accumulating scientific evidence supports testing for predictive biomarkers to apply personalized therapy and support preventive measures regarding adverse drug reactions and treatment failure. Here, we review cytogenetic and biochemical genetic testing methods that are available to guide therapy with drugs centrally approved in the European Union (EU). We identified several methods and combinations of techniques registered in the Genetic Testing Registry (GTR), which can be used to guide therapy with drugs for which pharmacogenomic-related information is provided in the European public assessment reports. Although this registry provides information on genetic tests offered worldwide, we identified limitations regarding standard techniques applied in clinical practice and the information on test validity rarely provided in the according sections.
PubMed: 34206978
DOI: 10.3390/diagnostics11071169 -
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