Ten Years of Experience Support Pharmacogenetic Testing to Guide Individualized Drug Therapy.
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ABSTRACT:
SUBMITTER: Pena-Martin MC
PROVIDER: S-EPMC8779486 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There is growing interest in utilizing pharmacogenetic (PGx) testing to guide antidepressant use, but there is lack of clarity on how to implement testing into clinical practice. We administered two surveys at 17 sites that had implemented or were in the process of implementing PGx testing for antidepressants. Survey 1 collected data on the process and logistics of testing. Survey 2 asked sites to rank the importance of Consolidated Framework for Implementation Research (CFIR) constructs using best-worst scaling choice experiments. Of the 17 sites, 13 had implemented testing and four were in the planning stage. Thirteen offered testing in the outpatient setting, and nine in both outpatient/inpatient settings. PGx tests were mainly ordered by psychiatry (92%) and primary care (69%) providers. CYP2C19 and CYP2D6 were the most commonly tested genes. The justification for antidepressants selected for PGx guidance was based on Clinical Pharmacogenetics Implementation Consortium guidelines (94%) and US Food and Drug Administration (FDA; 75.6%) guidance. Both institutional (53%) and commercial laboratories (53%) were used for testing. Sites varied on the methods for returning results to providers and patients. Sites were consistent in ranking CFIR constructs and identified patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and the identification of champions as most important for implementation. Sites deployed similar implementation strategies and measured similar outcomes. The process of implementing PGx testing to guide antidepressant therapy varied across sites, but key drivers for successful implementation were similar and may help guide other institutions interested in providing PGx-guided pharmacotherapy for antidepressant management.
| S-EPMC8841452 | biostudies-literature
Project description:ObjectiveThis study assessed pharmacist experiences with delivering pharmacogenetic (PGx) testing in independent community pharmacies.MethodsWe conducted a cluster randomized trial of independent community pharmacies in North Carolina randomized to provide either PGx testing as a standalone service or integrated into medication therapy management (MTM) services. Surveys and pharmacist data about the delivery of PGx testing were collected. Semi-structured interviews were also conducted.ResultsA total of 36 pharmacists participated in the study from 22 pharmacies. Sixteen pharmacists completed the pre-study and post-study surveys, and four pharmacists completed the semi-structured interviews. Thirty-one percent (11/36) of pharmacists had had some education in personalized medicine or PGx prior to the study. The only outcome that differed by study arm was the use of educational resources, with significantly higher utilization in the PGx testing only arm (p=0.007). Overall, compared to the pre-study assessment, pharmacists' knowledge about PGx significantly improved post-study (p=0.018). In the post-study survey, almost all pharmacists indicated that they felt qualified/able to provide PGx testing at their pharmacy. While 75% of pharmacists indicated that they may continue to provide PGx testing at their pharmacy after the study, the major concerns were lack of reimbursement for PGx counseling and consultation given the necessary time required.ConclusionOur findings demonstrated a positive experience with delivering PGx testing in the community pharmacy setting with little difference in pharmacists' experiences in providing PGx testing with or without MTM. Pharmacists were confident in their ability to provide PGx testing and were interested in continuing to offer testing, though sustained delivery may be challenged by lack of prescribing provider engagement and reimbursement.
| S-EPMC8289463 | biostudies-literature
Project description: Not available
| S-EPMC10479465 | biostudies-literature
Project description:BackgroundIn polypharmacy patients, medication therapy management (MTM) services provide a comprehensive review of current medications and future treatment goals. Pharmacogenetics (PGx) may further optimize the identification of potential drug therapy problems (DTPs); however, the clinical utility of PGx information with a clinical decision support tool (CDST) in an MTM setting in identifying DTPs has not been systematically assessed.ObjectiveTo assess the clinical utility of an MTM service enhanced by pharmacogenetic test results and a clinical decision support tool.MethodsThis study was a post hoc analysis of the data obtained from an open-label, randomized, observational trial. Polypharmacy patients eligible for MTM service were randomly assigned to 3 intervention arms: standard MTM (SMTM), MTM incorporating CDST (CMTM), and CMTM further enhanced by PGx test results of CYP450 and VKORC1 enzymes (PGxMTM). Allocation for this post hoc analysis was based on patient adherence to the research protocol and completion of a PGx test. The number of DTPs per patient was compared across the 3 arms using analysis of variance. In addition, the frequency of serious DTPs as a categorical variable (grade 3 or above vs. lower grade) was compared across the 3 arms between PGx driven and non-PGx driven DTP recommendations. Statistical significance was tested using the chi-square test. The level of agreement between the DTP seriousness and the acceptance made by prescribers was presented as Cohen's kappa coefficient.ResultsNumbers of patients after cohort reallocation based on completion of PGx testing were 104, 180, and 58 for the SMTM, CMTM, and PGxMTM arms, respectively. On average, 3.08 DTPs were identified for each patient, which was nearly identical across all 3 arms. Blinded clinical pharmacists considered seriousness (grade 3 or 4) in 31% of the PGx-related DTPs in comparison with 4.9% of the non-PGx DTPs (P < 0.001). The more serious (i.e., grade 3 or above) DTP recommendations were more likely to be accepted by prescribers with the odds ratios of 1.95 (P = 0.05) and 2.39 (P = 0.15), when the analysis was performed for all DTPs and DTPs from the PGxMTM arm only, respectively.ConclusionsMTM enhanced by PGx testing and the clinical decision support tool did not increase the number of DTPs identified. However, PGx testing and the decision support software helps pharmacists determine more serious DTPs, and resulting subsequent recommendations were more readily accepted by a prescriber. Future study of the patient safety outcomes and overall health care costs associated with the utility of the decision support is warranted.DisclosuresNo funding was received for conducting the post hoc analysis presented in this study. Magness is employed by Magellan Health, which received funding from Genelex for costs to administrate the medication management program. The open-label randomized trial was sponsored by Genelex (Clinicaltrials.gov ID number NCT02428660). PGx tests were provided and laboratory analysis was performed by Genelex. Valerie Baron is an employee of YouScript, which created the clinical decision support tool used in this study and formerly was part of Genelex. The other authors have nothing to disclose.
| S-EPMC10397798 | biostudies-literature
Project description:UNLABELLED: The advantages of sonographic examination are well known, but its main disadvantage is that it might lead to overdiagnosis, which might cause overtreatment. Variations in the incidence of developmental dysplasia of the hip are well known. We ascertained the incidence of neonatal sonographic developmental dysplasia of the hip without considering the development of those joints during followup. All 45,497 neonates (90,994 hips) born in our institute between January 1992 and December 2001 were examined clinically and sonographically during the first 48 hours of life. Sonography was performed according to Graf's method, which considers mild hip sonographic abnormalities as Type IIa. We evaluated the different severity type incidence pattern and its influence on the total incidence during and between the investigated years. According to our study, sonographic Type IIa has major effects on the incidence of overall developmental dysplasia of the hip with a correlation coefficient of 0.95, whereas more severe sonographic abnormalities show relatively stable incidence patterns. LEVEL OF EVIDENCE: Level I, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
| S-EPMC2504674 | biostudies-other
Project description:It is anticipated that as the range of drugs for which pharmacogenetic testing becomes available expands, primary care physicians (PCPs) will become major users of these tests. To assess their training, familiarity, and attitudes toward pharmacogenetic testing in order to identify barriers to uptake that may be addressed at this early stage of test use, we conducted a national survey of a sample of PCPs. Respondents were mostly white (79%), based primarily in community-based primary care (81%) and almost evenly divided between family medicine and internal medicine. The majority of respondents had heard of PGx testing and anticipated that these tests are or would soon become a valuable tool to inform drug response. However, only a minority of respondents (13%) indicated they felt comfortable ordering PGx tests and almost a quarter reported not having any education about pharmacogenetics. Our results indicate that primary care practitioners envision a major role for themselves in the delivery of PGx testing but recognize their lack of adequate knowledge and experience about these tests. Development of effective tools for guiding PCPs in the use of PGx tests should be a high priority.
| S-EPMC3440554 | biostudies-literature
Project description:Current pharmacogenetic studies have obtained many genetic models that can predict the therapeutic efficacy of anticancer drugs. Although some of these models are of crucial importance and have been used in clinical practice, these very valuable models have not been well adopted into cancer research to promote the development of cancer therapies due to the lack of integration and standards for the existing data of the pharmacogenetic studies. For this purpose, we built a resource investigating genetic model of drug response (iGMDR), which integrates the models from in vitro and in vivo pharmacogenetic studies with different omics data from a variety of technical systems. In this study, we introduced a standardized process for all integrations, and described how users can utilize these models to gain insights into cancer. iGMDR is freely accessible at https://igmdr.modellab.cn.
| S-EPMC7646137 | biostudies-literature
Project description:In 2014, we established a pharmacogenetics unit with the intention of facilitating the integration of pharmacogenetic testing into clinical practice. This unit was centered around two main ideas: i) individualization of clinical recommendations, and ii) preemptive genotyping in risk populations. Our unit is based on the design and validation of a single nucleotide polymorphism (SNP) microarray, which has allowed testing of 180 SNPs associated with drug response (PharmArray), and clinical consultation regarding the results. Herein, we report our experience in integrating pharmacogenetic testing into our hospital and we present the results of the 2,539 pharmacogenetic consultation requests received over the past 3 years in our unit. The results demonstrate the feasibility of implementing pharmacogenetic testing in clinical practice within a national health system.
| S-EPMC5866958 | biostudies-literature
Project description:Background: Awareness about the importance of implementing DPYD pharmacogenetics in clinical practice to prevent severe side effects related to the use of fluoropyrimidines has been raised over the years. Since 2012 at the National Cancer Institute, CRO-Aviano (Italy), a diagnostic DPYD genotyping service was set up. Purpose: This study aims to describe the evolution of DPYD diagnostic activity at our center over the last 10 years as a case example of a successful introduction of pharmacogenetic testing in clinical practice. Methods: Data related to the diagnostic activity of in-and out-patients referred to our service between January 2012 and December 2022 were retrieved from the hospital database. Results: DPYD diagnostic activity at our center has greatly evolved over the years, shifting gradually from a post-toxicity to a pre-treatment approach. Development of pharmacogenetic guidelines by national and international consortia, genotyping, and IT technology evolution have impacted DPYD testing uptake in the clinics. Our participation in a large prospective implementation study (Ubiquitous Pharmacogenomics) increased health practitioners' and patients' awareness of pharmacogenetic matters and provided additional standardized infrastructures for genotyping and reporting. Nationwide test reimbursement together with recommendations by regulatory agencies in Europe and Italy in 2020 definitely changed the clinical practice guidelines of fluoropyrimidines prescription. A dramatic increase in the number of pre-treatment DPYD genotyping and in the coverage of new fluoropyrimidine prescriptions was noticed by the last year of observation (2022). Conclusion: The long path to a successful DPYD testing implementation in the clinical practice of a National Cancer Center in Italy demonstrated that the development of pharmacogenetic guidelines and genotyping infrastructure standardization as well as capillary training and education activity for all the potential stakeholders are fundamental. However, only national health politics of test reimbursement and clear recommendations by drug regulatory agencies will definitely move the field forward.
| S-EPMC10225682 | biostudies-literature
Project description:ImportanceThere are an increasing number of medications with a high level of evidence for pharmacogenetic-guided dosing (PGx drugs). Knowledge of the prevalence of dispensings of PGx drugs and their associated genes may allow hospitals and clinical laboratories to determine which pharmacogenetic tests to implement.ObjectivesTo investigate the prevalence of outpatient dispensings of PGx drugs among Medicaid-insured youths, determine genes most frequently associated with PGx drug dispenses, and describe characteristics of youths who were dispensed at least 1 PGx drug.Design, setting, and participantsThis serial cross-sectional study includes data from 2011 to 2019 among youths aged 0 to 17 years in the Marketscan Medicaid database. Data were analyzed from August to December 2022.Main outcomes and measuresPGx drugs were defined as any medication with level A evidence as determined by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The number of unique youths dispensed each PGx drug in each year was determined. PGx drugs were grouped by their associated genes for which there was CPIC level A evidence to guide dosing, and a dispensing rate (No. of PGx drugs/100 000 youths) was determined for each group for the year 2019. Demographics were compared between youths dispensed at least 1 PGx drug and those not dispensed any PGx drugs.ResultsThe number of Medicaid-insured youths queried ranged by year from 2 078 683 youths in 2011 to 4 641 494 youths in 2017, including 4 126 349 youths (median [IQR] age, 9 [5-13] years; 2 129 926 males [51.6%]) in 2019. The proportion of Medicaid-insured youths dispensed PGx drugs increased from 289 709 youths (13.9%; 95% CI, 13.8%-14.0%) in 2011 to 740 072 youths (17.9%; 95% CI, 17.9%-18.0%) in 2019. Genes associated with the most frequently dispensed medications were CYP2C9, CYP2D6, and CYP2C19 (9197.0 drugs [95% CI, 9167.7-9226.3 drugs], 8731.5 drugs [95% CI, 8702.5-8759.5 drugs], and 3426.8 drugs [95% CI, 3408.1-3443.9 drugs] per 100 000 youths, respectively). There was a higher percentage of youths with at least 1 chronic medical condition among youths dispensed at least 1 PGx drug (510 445 youths [69.0%; 95% CI, 68.8%-69.1%]) than among 3 386 277 youths dispensed no PGx drug (1 381 544 youths [40.8%; 95% CI, 40.7%-40.9%) (P < .001) in 2019.Conclusions and relevanceIn this study, there was an increasing prevalence of dispensings for PGx drugs. This finding suggests that pharmacogenetic testing of specific drug-gene pairs should be considered for frequently prescribed PGx drugs and their implicated genes.
| S-EPMC10865156 | biostudies-literature