RÉSUMÉ
The University of Florida Health conducted a pragmatic implementation of a pharmacogenetics (PGx) panel-based test to guide medications used for supportive care prescribed to patients undergoing chemotherapy. The implementation was in the context of a pragmatic clinical trial for patients with non-hematologic cancers being treated with chemotherapy. Patients were randomized to either the intervention arm or control arm and received PGx testing immediately or at the end of the study, respectively. Patients completed the MD Anderson Symptom Inventory (MDASI) to assess quality of life (QoL). A total of 150 patients received PGx testing and enrolled in the study. Clinical decision support and implementation infrastructure were developed. While the study was originally planned for 500 patients, we were underpowered in our sample of 150 patients to test differences in the patient-reported MDASI scores. We did observed a high completion rate (92%) of the questionnaires; however, there were few medication changes (n = 6 in the intervention arm) based on PGx test results. Despite this, we learned several lessons through this pragmatic implementation of a PGx panel-based test in an outpatient oncology setting. Most notably, patients were less willing to undergo PGx testing if the cost of the test exceeded $100. In addition, to enhance PGx implementation success, reoccurring provider education is necessary, clinical decision support needs to appear in a more conducive way to fit in with oncologists' workflow, and PGx test results need to be available earlier in treatment planning.
Sujet(s)
Antinéoplasiques , Tumeurs , Test pharmacogénomique , Qualité de vie , Humains , Femelle , Mâle , Adulte d'âge moyen , Tumeurs/traitement médicamenteux , Tumeurs/génétique , Test pharmacogénomique/économie , Test pharmacogénomique/statistiques et données numériques , Adulte , Sujet âgé , Antinéoplasiques/usage thérapeutique , Oncologie médicale/méthodes , Systèmes d'aide à la décision clinique , PharmacogénétiqueRÉSUMÉ
Pharmacogenetic testing could reduce the time to identify a safe and effective medication for depression; however, it is underutilized in practice. Major depression constitutes the most common mental disorder in the US, and while antidepressant therapy can help, the current trial -and error approach can require patients to endure multiple medication trials before finding one that is effective. Tailoring the fit of pharmacogenetic testing with prescribers' needs across a variety of settings could help to establish a generalizable value proposition to improve likelihood of adoption. We conducted a study to explore the value proposition for health systems using pharmacogenetic testing for mental health medications through prescribers' real-world experiences using implementation science concepts and systematic interviews with prescribers and administrators from four health care systems. To identify a value proposition, we organized the themes according to the Triple Aim framework, a leading framework for health care policy which asserts that high-value care should focus on three key metrics: (1) better health care quality and (2) population-level outcomes with (3) reduced per capita costs. Primary care providers whom we interviewed said that they value pharmacogenetic testing because it would provide more information about medications that they can prescribe, expanding their ability to identify medications that best-fit patients and reducing their reliance on referrals to specialists; they said that this capacity would help meet patients' needs for access to mental health care through primary care. At the same time, prescribers expressed differing views about how pharmacogenetic testing can help with quality of care and whether their views about out-of-pocket cost would prevent them from offering it. Thus, implementation should focus on integrating pharmacogenetic testing into primary care and using strategies to support prescribers' interactions with patients.
Sujet(s)
Antidépresseurs , Test pharmacogénomique , Soins de santé primaires , Humains , Test pharmacogénomique/économie , Antidépresseurs/usage thérapeutique , Trouble dépressif majeur/traitement médicamenteux , Trouble dépressif majeur/diagnostic , Trouble dépressif majeur/génétique , Qualité des soins de santéRÉSUMÉ
BACKGROUND: Empirical use of pharmacogenetic test(PGT) is advocated for many drugs, and resource-rich setting hospitals are using the same commonly. The clinical translation of pharmacogenetic tests in terms of cost and clinical utility is yet to be examined in hospitals of low middle income countries (LMICs). AIM: The present study assessed the clinical utility of PGT by comparing the pharmacogenetically(PGT) guided- versus standard of care(SOC)- warfarin therapy, including the health economics of the two warfarin therapies. METHODS: An open-label, randomized, controlled clinical trial recruited warfarin-receiving patients in pharmacogenetically(PGT) guided- versus standard of care(SOC)- study arms. Pharmacogenetic analysis of CYP2C9*2(rs1799853), CYP2C9*3(rs1057910) and VKORC1(rs9923231) was performed for patients recruited to the PGT-guided arm. PT(Prothrombin Time)-INR(international normalized ratio) testing and dose titrations were allowed as per routine clinical practice. The primary endpoint was the percent time spent in the therapeutic INR range(TTR) during the 90-day observation period. Secondary endpoints were time to reach therapeutic INR(TRT), the proportion of adverse events, and economic comparison between two modes of therapy in a Markov model built for the commonest warfarin indication- atrial fibrillation. RESULTS: The study enrolled 168 patients, 84 in each arm. Per-protocol analysis showed a significantly high median time spent in therapeutic INR in the genotype-guided arm(42.85%; CI 21.4-66.75) as compared to the SOC arm(8.8%; CI 0-27.2)(p < 0.00001). The TRT was less in the PG-guided warfarin dosing group than the standard-of-care dosing warfarin group (17.85 vs. 33.92 days) (p = 0.002). Bleeding and thromboembolic events were similar in the two study groups. Lifetime expenditure was â¹1,26,830 in the PGT arm compared to â¹1,17,907 in the SOC arm. The QALY gain did not differ in the two groups(3.9 vs. 3.65). Compared to SOC, the incremental cost-utility ratio was â¹35,962 per QALY gain with PGT test opting. In deterministic and probabilistic sensitivity analysis, the base case results were found to be insensitive to the variation in model parameters. In the cost-effectiveness-acceptability curve analysis, a 90% probability of cost-effectiveness was reached at a willingness-to-pay(WTP) of â¹ 71,630 well below one time GDP threshold of WTP used. CONCLUSION: Clinical efficacy and the cost-effectiveness of the warfarin pharmacogenetic test suggest its routine use as a point of care investigation for patient care in LMICs.
Sujet(s)
Anticoagulants , Cytochrome P-450 CYP2C9 , Pharmacoéconomie , Rapport international normalisé , Vitamin K epoxide reductases , Warfarine , Humains , Warfarine/économie , Warfarine/administration et posologie , Warfarine/usage thérapeutique , Femelle , Mâle , Adulte d'âge moyen , Cytochrome P-450 CYP2C9/génétique , Sujet âgé , Vitamin K epoxide reductases/génétique , Anticoagulants/administration et posologie , Anticoagulants/économie , Anticoagulants/usage thérapeutique , Test pharmacogénomique/économie , Adulte , Pharmacogénétique/économie , Analyse coût-bénéficeRÉSUMÉ
BACKGROUND: Genetic-guided pharmacotherapy (PGx) is not recommended in clinical guidelines for coronary artery disease (CAD). We aimed to examine the extent and quality of evidence from economic evaluations of PGx in CAD and to identify variables influential in changing conclusions on cost-effectiveness. METHODS AND RESULTS: From systematic searches across 6 databases, 2 independent reviewers screened, included, and rated the methodological quality of economic evaluations of PGx testing to guide pharmacotherapy for patients with CAD. Of 35 economic evaluations included, most were model-based cost-utility analyses alone, or alongside cost-effectiveness analyses of PGx testing to stratify patients into antiplatelets (25/35), statins (2/35), pain killers (1/35), or angiotensin-converting enzyme inhibitors (1/35) to predict CAD risk (8/35) or to determine the coumadin doses (1/35). To stratify patients into antiplatelets (96/151 comparisons with complete findings of PGx versus non-PGx), PGx was more effective and more costly than non-PGx clopidogrel (28/43) but less costly than non-PGx prasugrel (10/15) and less costly and less effective than non-PGx ticagrelor (22/25). To predict CAD risk (51/151 comparisons), PGx using genetic risk scores was more effective and less costly than clinical risk score (13/17) but more costly than no risk score (16/19) or no treatment (9/9). The remaining comparisons were too few to observe any trend. Mortality risk was the most common variable (47/294) changing conclusions. CONCLUSIONS: Economic evaluations to date found PGx to stratify patients with CAD into antiplatelets or to predict CAD risk to be cost-effective, but findings varied based on the non-PGx comparators, underscoring the importance of considering local practice in deciding whether to adopt PGx.
Sujet(s)
Maladie des artères coronaires , Analyse coût-bénéfice , Antiagrégants plaquettaires , Humains , Maladie des artères coronaires/traitement médicamenteux , Maladie des artères coronaires/économie , Maladie des artères coronaires/génétique , Antiagrégants plaquettaires/usage thérapeutique , Antiagrégants plaquettaires/économie , Test pharmacogénomique/économie , Variants pharmacogénomiques , Coûts des médicaments , Médecine de précision/économie , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/usage thérapeutique , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/économie , Appréciation des risquesRÉSUMÉ
Despite the known contributions of genes, genetic-guided pharmacotherapy has not been routinely implemented for venous thromboembolism (VTE). To examine evidence on cost-effectiveness of genetic-guided pharmacotherapy for VTE, we searched six databases, websites of four HTA agencies and citations, with independent double-reviewers in screening, data extraction, and quality rating. The ten eligible studies, all model-based, examined heterogeneous interventions and comparators. Findings varied widely; testing was cost-saving in two base-cases, cost-effective in four, not cost-effective in three, dominated in one. Of 22 model variables that changed decisions about cost-effectiveness, effectiveness/relative effectiveness of the intervention was the most frequent, albeit of poor quality. Studies consistently lacked details on the provision of interventions and comparators as well as on model development and validation. Besides improving the reporting of interventions, comparators, and methodological details, future economic evaluations should examine strategies recommended in guidelines and testing key model variables for decision uncertainty, to advise clinical implementations.
Sujet(s)
Coûts des médicaments , Fibrinolytiques/économie , Fibrinolytiques/usage thérapeutique , Test pharmacogénomique/économie , Médecine de précision/économie , Thromboembolisme veineux/traitement médicamenteux , Thromboembolisme veineux/économie , Adolescent , Adulte , Enfant , Enfant d'âge préscolaire , Prise de décision clinique , Analyse coût-bénéfice , Femelle , Fibrinolytiques/effets indésirables , Prédisposition génétique à une maladie , Hémorragie/induit chimiquement , Humains , Mâle , Adulte d'âge moyen , Variants pharmacogénomiques , Phénotype , Valeur prédictive des tests , Récidive , Appréciation des risques , Facteurs de risque , Résultat thérapeutique , Thromboembolisme veineux/génétique , Jeune adulteRÉSUMÉ
Aim: To assess providers' knowledge, attitudes, perceptions, and experiences related to pharmacogenomic (PGx) testing in pediatric patients. Materials & methods: An electronic survey was sent to multidisciplinary healthcare providers at a pediatric hospital. Results: Of 261 respondents, 71.3% were slightly or not at all familiar with PGx, despite 50.2% reporting prior PGx education or training. Most providers, apart from psychiatry, perceived PGx to be at least moderately useful to inform clinical decisions. However, only 26.4% of providers had recent PGx testing experience. Unfamiliarity with PGx and uncertainty about the clinical value of testing were common perceived challenges. Conclusion: Low PGx familiarity among pediatric providers suggests additional education and electronic resources are needed for PGx examples in which data support testing in children.
Sujet(s)
Personnel de santé/normes , Pédiatrie/normes , Test pharmacogénomique/normes , Connaissances, attitudes et pratiques en santé , Personnel de santé/économie , Humains , Pédiatrie/économie , Pharmacogénétique/économie , Pharmacogénétique/tendances , Test pharmacogénomique/économie , Médecine de précision/tendancesRÉSUMÉ
Aim: 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. Materials & methods: Data are based on a sample of 347 primary care older adults. Results: 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. Conclusion: Education and beliefs about medicines are important factors in the acceptability of pharmacogenomic testing in older adults.
Sujet(s)
Culture (sociologie) , Dépenses de santé , Connaissances, attitudes et pratiques en santé , Acceptation des soins par les patients , Test pharmacogénomique/économie , Facteurs socioéconomiques , Facteurs âges , Sujet âgé , Femelle , Études de suivi , Dépenses de santé/tendances , Humains , Mâle , Acceptation des soins par les patients/psychologie , Test pharmacogénomique/tendances , Enquêtes et questionnairesRÉSUMÉ
This study examined rates of genetic testing in two cohorts of publicly insured individuals who have newly prescribed medication with FDA pharmacogenomic labeling guidance. Genetic testing was rare (4.4% and 10.5% in Medicaid and Medicare cohorts, respectively) despite the fact that all participants selected were taking medications that contained pharmacogenomic labeling information. When testing was conducted it was typically done before the initial use of a target medication. Factors that emerged as predictors of the likelihood of undergoing genetic testing included White ethnicity (vs. Black), female gender, and age. Cost analyses indicated higher expenditures in groups receiving genetic testing vs. matched comparators with no genetic testing, as well as disparities between proactively and reactively tested groups (albeit in opposite directions across cohorts). Results are discussed in terms of the possible reasons for the low base rate of testing, mechanisms of increased cost, and barriers to dissemination and implementation of these tests.
Sujet(s)
Étiquetage de médicament/normes , Pharmacogénétique/statistiques et données numériques , Test pharmacogénomique/statistiques et données numériques , Adulte , Facteurs âges , Sujet âgé , , Études de cohortes , Coûts et analyse des coûts , Bases de données factuelles , Agrément de médicaments , Étiquetage de médicament/économie , Ethnies , Femelle , Humains , Mâle , Medicaid (USA) , Medicare (USA) , Adulte d'âge moyen , Mississippi , Pharmacogénétique/économie , Test pharmacogénomique/économie , Médicaments sur ordonnance , Facteurs sexuels , États-Unis , Food and Drug Administration (USA) ,RÉSUMÉ
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.
Sujet(s)
Hôpitaux pédiatriques/statistiques et données numériques , Test pharmacogénomique/statistiques et données numériques , Types de pratiques des médecins/statistiques et données numériques , Hôpitaux pédiatriques/économie , Humains , Test pharmacogénomique/économie , Types de pratiques des médecins/économie , Mécanismes de remboursement , États-UnisSujet(s)
Allopurinol/effets indésirables , Syndrome d'hypersensibilité médicamenteuse/génétique , Ethnies/génétique , Antigoutteux/effets indésirables , Antigènes HLA-B/génétique , Médecine de précision , Syndrome de Stevens-Johnson/génétique , /génétique , /génétique , Analyse coût-bénéfice , Syndrome d'hypersensibilité médicamenteuse/étiologie , Hispanique ou Latino/génétique , Humains , Américain origine mexicaine/génétique , Test pharmacogénomique/économie , Test pharmacogénomique/méthodes , Variants pharmacogénomiques , Guides de bonnes pratiques cliniques comme sujet , Porto Rico/ethnologie , Syndrome de Stevens-Johnson/étiologie , États-UnisRÉSUMÉ
Pharmacogenomics test coverage and reimbursement are major obstacles to clinical uptake. Several early adopter programs have been successfully initiated through dedicated investments by federal and institutional research funding. As a result of research endeavors, evidence has grown sufficiently to support development of pharmacogenomics guidelines. However, clinical uptake is still limited. Third-party payer support plays an important role in increasing adoption, which to date has been limited to reactive single-gene testing. Access to and interest in direct-to-consumer genetic testing are driving demand for increasing healthcare providers and third-party awareness of this burgeoning field. Pharmacogenomics implementation models developed by early adopters promise to expand patient access and options, as testing continues to increase due to growing consumer interest and falling test prices.
Sujet(s)
Planification de la santé communautaire/économie , Accessibilité des services de santé/économie , Remboursement par l'assurance maladie/économie , Test pharmacogénomique/économie , Planification de la santé communautaire/tendances , Personnel de santé/économie , Personnel de santé/enseignement et éducation , Personnel de santé/tendances , Accessibilité des services de santé/tendances , Humains , Remboursement par l'assurance maladie/tendances , Aide médicale/économie , Aide médicale/tendances , Test pharmacogénomique/tendances , Médecine de précision/économie , Médecine de précision/tendancesRÉSUMÉ
In this Perspective, the authors discuss the state of pharmacogenomics testing addressing a number of advances, challenges and barriers, including legal ramifications, changes to the regulatory landscape, coverage of testing and the implications of direct-to-consumer genetic testing on the provision of care to patients. Patient attitudes toward pharmacogenomics testing and associated costs will play an increasingly important role in test acquisition and subsequent utilization in a clinical setting. Additional key steps needed include: further research trials demonstrating clinical utility and cost-effectiveness of pharmacogenetic testing, evidence review to better integrate genomic information into clinical practice guidelines in target therapeutic areas to help providers identify patients that may benefit from pharmacogenetic testing and engagement with payers to create a path to reimbursement for pharmacogenetic tests that currently have sufficient evidence of clinical utility. Increased adoption of testing by payers and improved reimbursement practices will be needed to overcome barriers, especially as the healthcare landscape continues to shift toward a system of value-based care.
Sujet(s)
Dépistage et analyse proposés directement au consommateur/économie , Dépistage et analyse proposés directement au consommateur/législation et jurisprudence , Test pharmacogénomique/économie , Test pharmacogénomique/législation et jurisprudence , Médecine de précision/économie , Analyse coût-bénéfice/économie , Analyse coût-bénéfice/législation et jurisprudence , Étiquetage de médicament/économie , Étiquetage de médicament/législation et jurisprudence , Humains , Faute professionnelle/économie , Faute professionnelle/législation et jurisprudenceRÉSUMÉ
INTRODUCTION: There is growing interest to adopt pharmacogenetic (PGx) testing in psychiatric medicine, despite mixed views regarding its clinical utility. Nevertheless, providers are utilizing PGx testing among patients with mental health disorders. This study sought to assess genotyped patients' perspectives and experiences with psychiatric PGx testing. METHODS: Individual semi-structured interviews were conducted among patients with depression who had undergone psychiatric PGx testing. The audio-recorded interviews were transcribed and analyzed inductively and deductively for salient themes. RESULTS: Twenty patients (100% Caucasian, 60% female, mean age 39±18 years) were interviewed. The majority of the PGx tests were provider-initiated for patients who failed multiple pharmacotherapies (50%) and/or had medication intolerances (45%). Patients' pre-testing expectations ranged from hopefulness to indifference to skepticism. Their post-testing experiences varied from optimism to disappointment, with the perceived value of the test influenced by the results and cost of the test. DISCUSSION: Genotyped patients had mixed perspectives, expectations, and experiences with psychiatric PGx testing. Their perceived value of the test was influenced by the test outcomes and its cost.
Sujet(s)
Patients , Test pharmacogénomique/économie , Psychiatrie/méthodes , Adulte , Sujet âgé , Attitude , Coûts et analyse des coûts , Femelle , Génotype , Humains , Mâle , Troubles mentaux/traitement médicamenteux , Troubles mentaux/génétique , Adulte d'âge moyen , Médecine de précision , Échec thérapeutique , Jeune adulteRÉSUMÉ
This narrative review describes implementation, current status and perspectives of a pharmacogenomic (PGx) program at the Brazilian National Cancer Institute (INCA), targeting the cancer chemotherapeutic drugs - fluoropyrimidines, irinotecan and thiopurines. This initiative, designed as a research project, was supported by a grant from the Brazilian Ministry of Health. A dedicated task force developed standard operational procedures from recruitment of patients to creating PGx reports with dosing recommendations, which were successfully applied to test 100 gastrointestinal cancer INCA outpatients and 162 acute lymphoblastic leukemia pediatric patients from INCA and seven other hospitals. The program has been subsequently expanded to include gastrointestinal cancer patients from three additional cancer treatment centers. We anticipate implementation of routine pre-emptive PGx testing at INCA but acknowledge challenges associated with this transition, such as continuous financing support, availability of trained personnel, adoption of the PGx-informed prescription by the clinical staff and, ultimately, evidence of cost-effectiveness.
Sujet(s)
Antinéoplasiques/usage thérapeutique , Agences gouvernementales/tendances , Tumeurs/traitement médicamenteux , Tumeurs/épidémiologie , Test pharmacogénomique/tendances , Antinéoplasiques/économie , Brésil/épidémiologie , Analyse coût-bénéfice/économie , Analyse coût-bénéfice/tendances , Agences gouvernementales/économie , Humains , Tumeurs/économie , Test pharmacogénomique/économieRÉSUMÉ
Aim: Evaluate the cost-effectiveness of combinatorial pharmacogenomic (PGx) testing, versus treatment as usual (TAU), to guide treatment for patients with depression, from the Canadian public healthcare system perspective. Materials & methods: Clinical and economic data associated with depression were extracted from published literature. Clinical (quality-adjusted life years; QALYs) and economic (incremental cost-effectiveness ratio) outcomes were modeled using combinatorial PGx and TAU treatment strategies across a 5-year time horizon. Results: With the combinatorial PGx strategy to guide treatment, patients were projected to gain 0.14-0.19 QALYs versus TAU. Accounting for test price, combinatorial PGx saved CAD $1,687-$3,056 versus TAU. Incremental cost-effectiveness ratios ranged from -$11,861 to -$16,124/QALY gained. Conclusion: Combinatorial PGx testing was more efficacious and less costly compared with the TAU for depression.
Sujet(s)
Analyse coût-bénéfice/méthodes , Dépression/économie , Dépression/épidémiologie , Programmes nationaux de santé/économie , Test pharmacogénomique/économie , Test pharmacogénomique/méthodes , Canada/épidémiologie , Dépression/diagnostic , HumainsRÉSUMÉ
BACKGROUND AND OBJECTIVES: Clopidogrel is widely used after the percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and requires activation by cytochrome P450 (CYP), primarily CYP2C19. Patients with CYP2C19 loss-of-function alleles are at increased risk of major adverse cardiovascular events, while more expensive novel antiplatelet agents (ticagrelor and prasugrel) are unaffected by the CYP2C19 mutations. This systematic review aims to answer the question about whether overall evidence supports the genotype-guided selection of antiplatelet therapy as a cost-effective strategy in post-PCI ACS. METHODS: A systematic literature search of PubMed, EMBASE, EconLit, and PharmGKB was done to identify all the economic evaluations related to genotype-guided therapy compared to the universal use of antiplatelets in ACS patients. Quality of Health Economic Studies tool was used for quality assessment. RESULTS: The search identified 13 articles, where genotype-guided treatment was compared to universal clopidogrel, ticagrelor, and/or prasugrel. Six studies showed that genotype-guided therapy was cost-effective compared to universal clopidogrel, while 5 studies showed that it was dominant. One study specified that genotype-guided with ticagrelor is cost-effective only in both CYP2C19 intermediate and poor metabolizers. Genotype-guided therapy was dominant when compared to universal prasugrel, ticagrelor, or both in 5, 1, and 3 studies, respectively. Only 2 studies reported that universal ticagrelor was cost-effective compared to genotype-guided treatment. All the included articles had good quality. CONCLUSION: Based on current economic evaluations in the literature, implementing CYP2C19 genotype-guided therapy is a cost-effective approach in guiding the selection of medication in patients with ACS undergoing PCI.
Sujet(s)
Syndrome coronarien aigu/traitement médicamenteux , Syndrome coronarien aigu/économie , Cytochrome P-450 CYP2C19/génétique , Coûts des médicaments , Test pharmacogénomique/économie , Variants pharmacogénomiques , Antiagrégants plaquettaires/économie , Antiagrégants plaquettaires/usage thérapeutique , Médecine de précision/économie , Syndrome coronarien aigu/sang , Syndrome coronarien aigu/diagnostic , Prise de décision clinique , Clopidogrel/économie , Clopidogrel/usage thérapeutique , Cytochrome P-450 CYP2C19/métabolisme , Humains , Sélection de patients , Antiagrégants plaquettaires/effets indésirables , Antiagrégants plaquettaires/pharmacocinétique , Chlorhydrate de prasugrel/économie , Chlorhydrate de prasugrel/usage thérapeutique , Valeur prédictive des tests , Ticagrélor/économie , Ticagrélor/usage thérapeutique , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: Monoclonal antibodies against epidermal growth factor receptor (EGFR) have proved beneficial for the treatment of metastatic colorectal cancer (mCRC), particularly when combined with predictive biomarkers of response. International guidelines recommend anti-EGFR therapy only for RAS (NRAS,KRAS) wild-type tumors because tumors with RAS mutations are unlikely to benefit. OBJECTIVES: We aimed to review the cost-effectiveness of RAS testing in mCRC patients before anti-EGFR therapy and to assess how well economic evaluations adhere to guidelines. METHODS: A systematic review of full economic evaluations comparing RAS testing with no testing was performed for articles published in English between 2000 and 2018. Study quality was assessed using the Quality of Health Economic Studies scale, and the British Medical Journal and the Philips checklists. RESULTS: Six economic evaluations (2 cost-effectiveness analyses, 2 cost-utility analyses, and 2 combined cost-effectiveness and cost-utility analyses) were included. All studies were of good quality and adopted the perspective of the healthcare system/payer; accordingly, only direct medical costs were considered. Four studies presented testing strategies with a favorable incremental cost-effectiveness ratio under the National Institute for Clinical Excellence (£20 000-£30 000/QALY) and the US ($50 000-$100 000/QALY) thresholds. CONCLUSIONS: Testing mCRC patients for RAS status and administering EGFR inhibitors only to patients with RAS wild-type tumors is a more cost-effective strategy than treating all patients without testing. The treatment of mCRC is becoming more personalized, which is essential to avoid inappropriate therapy and unnecessarily high healthcare costs. Future economic assessments should take into account other parameters that reflect the real world (eg, NRAS mutation analysis, toxicity of biological agents, genetic test sensitivity and specificity).
Sujet(s)
Tumeurs colorectales/économie , Tumeurs colorectales/génétique , Analyse de mutations d'ADN/économie , Gènes ras , Coûts des soins de santé , Mutation , Test pharmacogénomique/économie , Variants pharmacogénomiques , Médecine de précision/économie , Antinéoplasiques immunologiques/économie , Antinéoplasiques immunologiques/usage thérapeutique , Prise de décision clinique , Tumeurs colorectales/traitement médicamenteux , Tumeurs colorectales/anatomopathologie , Analyse coût-bénéfice , Coûts des médicaments , Récepteurs ErbB/antagonistes et inhibiteurs , Prédisposition génétique à une maladie , Humains , Métastase tumorale , Sélection de patients , Phénotype , Valeur prédictive des tests , Années de vie ajustées sur la qualitéRÉSUMÉ
OBJECTIVE: To evaluate the cost-effectiveness of multigene testing (CYP2C19, SLCO1B1, CYP2C9, VKORC1) compared with single-gene testing (CYP2C19) and standard of care (no genotyping) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) from Medicare's perspective. METHODS: A hybrid decision tree/Markov model was developed to simulate patients post-PCI for ACS requiring antiplatelet therapy (CYP2C19 to guide antiplatelet selection), statin therapy (SLCO1B1 to guide statin selection), and anticoagulant therapy in those that develop atrial fibrillation (CYP2C9/VKORC1 to guide warfarin dose) over 12 months, 24 months, and lifetime. The primary outcome was cost (2016 US dollar) per quality-adjusted life years (QALYs) gained. Costs and QALYs were discounted at 3% per year. Probabilistic sensitivity analysis (PSA) varied input parameters (event probabilities, prescription costs, event costs, health-state utilities) to estimate changes in the cost per QALY gained. RESULTS: Base-case-discounted results indicated that the cost per QALY gained was $59 876, $33 512, and $3780 at 12 months, 24 months, and lifetime, respectively, for multigene testing compared with standard of care. Single-gene testing was dominated by multigene testing at all time horizons. PSA-discounted results indicated that, at the $50 000/QALY gained willingness-to-pay threshold, multigene testing had the highest probability of cost-effectiveness in the majority of simulations at 24 months (61%) and over the lifetime (81%). CONCLUSIONS: On the basis of projected simulations, multigene testing for Medicare patients post-PCI for ACS has a higher probability of being cost-effective over 24 months and the lifetime compared with single-gene testing and standard of care and could help optimize medication prescribing to improve patient outcomes.
Sujet(s)
Syndrome coronarien aigu/économie , Syndrome coronarien aigu/thérapie , Anticoagulants/économie , Anticoagulants/usage thérapeutique , Coûts des médicaments , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/économie , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/usage thérapeutique , Intervention coronarienne percutanée/économie , Test pharmacogénomique/économie , Variants pharmacogénomiques , Antiagrégants plaquettaires/économie , Antiagrégants plaquettaires/usage thérapeutique , Syndrome coronarien aigu/diagnostic , Syndrome coronarien aigu/mortalité , Sujet âgé , Anticoagulants/effets indésirables , Analyse coût-bénéfice , Cytochrome P-450 CYP2C19/génétique , Cytochrome P-450 CYP2C9/génétique , Arbres de décision , Femelle , Humains , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/effets indésirables , Polypeptide C de transport d'anions organiques/génétique , Mâle , Chaines de Markov , Medicare (USA)/économie , Intervention coronarienne percutanée/effets indésirables , Intervention coronarienne percutanée/mortalité , Antiagrégants plaquettaires/effets indésirables , Médecine de précision/économie , Valeur prédictive des tests , Années de vie ajustées sur la qualité , Reproductibilité des résultats , Facteurs de risque , Facteurs temps , Résultat thérapeutique , États-Unis , Vitamin K epoxide reductases/génétiqueRÉSUMÉ
OBJECTIVE: We compared economic outcomes when elderly patients with neuropsychiatric disorders received psychotropic medications guided by a combinatorial pharmacogenomic (PGx) test. METHODS: This is a subanalysis of a 1-year prospective assessment of medication cost for patients with neuropsychiatric disorders receiving combinatorial PGx testing. Pharmacy claims were used to compare per member per year (PMPY) medication cost for patients ≥65 and <65 years old when medications were congruent or incongruent with the PGx test. Polypharmacy was also assessed. RESULTS: Congruent prescribing was associated with savings of US$3497 PMPY (P < .001) for patients ≥65 years and US$2467 PMPY (P < .001) for patients <65, compared to incongruent prescribing. Congruent prescribing in patients ≥65 treated by primary care providers was associated with US$4113 PMPY (P = .026) in savings, while congruent prescribing by psychiatrists was associated with US$120 PMPY (P = .719). Congruent prescribing was also associated with one fewer neuropsychiatric medication for patients ≥65 (P = .070). CONCLUSION: Congruence with PGx testing was associated with medication cost savings in elderly patients.
Sujet(s)
Ordonnances médicamenteuses/statistiques et données numériques , Dépistage génétique/économie , Troubles mentaux/traitement médicamenteux , Pharmacogénétique/économie , Test pharmacogénomique/économie , Psychoanaleptiques/économie , Sujet âgé , Antidépresseurs/économie , Antidépresseurs/usage thérapeutique , Neuroleptiques/économie , Neuroleptiques/usage thérapeutique , Coûts des médicaments/statistiques et données numériques , Frais pharmaceutiques/statistiques et données numériques , Femelle , Dépistage génétique/méthodes , Gérontopsychiatrie , Humains , Mâle , Troubles mentaux/psychologie , Adulte d'âge moyen , Pharmacogénétique/méthodes , Médicaments sur ordonnance/économie , Études prospectives , Psychoanaleptiques/usage thérapeutiqueRÉSUMÉ
BACKGROUND: A limited evidence base and lack of clear clinical guidelines challenge healthcare systems' adoption of precision medicine. The effect of these conditions on demand is not understood. OBJECTIVE: This research estimated the public's preferences and demand for precision medicine outcomes. METHODS: A discrete-choice experiment survey was conducted with an online sample of the US public who had recent healthcare experience. Statistical analysis was undertaken using an error components mixed logit model. The responsiveness of demand in the context of a changing evidence base was estimated through the price elasticity of demand. External validation was examined using real-world demand for the 21-gene recurrence score assay for breast cancer. RESULTS: In total, 1124 (of 1849) individuals completed the web-based survey. The most important outcomes were survival gains with statistical uncertainty, cost of testing, and medical expert agreement on changing care based on test results. The value ($US, year 2017 values) for a test where most (vs. few) experts agreed to changing treatment based on test results was $US1100 (95% confidence interval [CI] 916-1286). Respondents were willing to pay $US265 (95% CI 46-486) for a test that could result in greater certainty around life-expectancy gains. The predicted demand of the assay was 9% in 2005 and 66% in 2014, compared with real-world uptake of 7% and 71% (root-mean-square prediction error 0.11). Demand was sensitive to price (1% increase in price resulted in > 1% change in demand) when first introduced and insensitive to price (1% increase in price resulted in < 0.1% change in demand) as the evidence base became established. CONCLUSIONS: Evidence of external validity was found. Demand was weak and responsive to price in the near term because of uncertainty and an immature evidence base. Clear communication of precision medicine outcomes and uncertainty is crucial in allowing healthcare to align with individual preferences.