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Ontario Health Technology Assessment... 2017A large proportion of the Ontario population lives with a diagnosed mental illness. Nearly 5% of Ontarians have major depressive disorder, and another 5% have another... (Review)
Review
BACKGROUND
A large proportion of the Ontario population lives with a diagnosed mental illness. Nearly 5% of Ontarians have major depressive disorder, and another 5% have another type of depressive disorder, bipolar disorder, schizophrenia, anxiety, or some other disorder not otherwise specified. Medications are commonly used to treat mental illness, but choosing the right medication for each patient is challenging, and more than 40% of patients discontinue their medication within 90 days because of adverse effects or lack of response. The Assurex GeneSight Psychotropic test is a pharmacogenomic panel that provides clinicians with a report to guide medication selection that is unique to each patient based on their individual genetic profile. However, it is uncertain whether guided treatment using GeneSight is effective compared with unguided treatment (usual care).
METHODS
We performed a systematic review to identify English-language studies published before February 22, 2016, that compared GeneSight-guided care and usual care among people with mood disorders, anxiety, or schizophrenia. Primary outcomes of interest were prevention of suicide, remission of depression symptoms, response to depression therapy, depression score, and quality of life. Secondary outcomes of interest were impact on therapeutic decisions and patient and clinician satisfaction. Risk of bias was evaluated, and the quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group criteria.
RESULTS
Four studies met the inclusion criteria. These studies used a version of GeneSight that included the , and genes; one of the studies also included . Patients who received the GeneSight test to guide psychotropic medication selection had improved response to depression treatment, greater improvements in measures of depression, and greater patient and clinician satisfaction compared with patients who received treatment as usual. We observed no differences in rates of complete remission from depression. The findings were based on GRADE assessment of low to very low quality evidence, and the body of evidence had several limitations: the included studies used an older version of GeneSight and were limited to a population with major depression, so results may not be generalizable to other versions of the test or different populations such as patients with anxiety or schizophrenia.
CONCLUSIONS
There is uncertainty about the use of GeneSight Psychotropic pharmacogenomic genetic panel to guide medication selection. It was associated with improvements in some patient outcomes, but not others. As well, our confidence in these findings is low because of limitations in the body of evidence.
Topics: Clinical Trials as Topic; Depressive Disorder, Major; Drug Administration Schedule; Genotype; Humans; Pharmacogenomic Testing; Psychotropic Drugs; Quality of Life; Treatment Outcome
PubMed: 28515818
DOI: No ID Found -
Scientific Reports Mar 2017Methotrexate (MTX) is widely used and considered a first-line disease modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Many of the... (Meta-Analysis)
Meta-Analysis Review
Methotrexate (MTX) is widely used and considered a first-line disease modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX effectiveness in RA patients, although inconsistent results have been reported. A systematic review and meta-analysis were performed to identify genetic variants associated with MTX efficacy. A total of 30 publications that included 34 genes and 125 SNPs associated with the transporters, enzymes, and metabolites of MTX or the progression of RA were included in the systematic review (SR), and 21 studies were included in 9 meta-analyses. Associations between MTX response in RA patients in MTHFR 1298A > C (rs1801131), ATIC 347C > G (rs2372536), RFC-1 80G > A (rs1051266), SLC19A1 A > G (rs2838956) and SLC19A1 G > A (rs7499) genetic polymorphisms were found, but not observed between the MTHFR 677C > T (rs1801133), TYMS 28 bp VNTR (rs34743033), MTRR 66A > G (rs1801394), and ABCB1 3435C > T (rs1045642). However, for the polymorphisms not being associated following meta-analysis could still be associated if larger cohorts were used, and studies of other polymorphisms are necessary in large cohorts and a rigorous way, which may provide more accurate results for the effect of the gene polymorphisms on the MTX response.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Methotrexate; Pharmacogenomic Testing; Polymorphism, Single Nucleotide; Treatment Outcome
PubMed: 28266606
DOI: 10.1038/srep44015 -
Scientific Reports Feb 2017Anthracyclines play an important role in the management of patients with cancer but the development of anthracycline-induced cardiotoxicity (ACT) remains a significant... (Meta-Analysis)
Meta-Analysis
Anthracyclines play an important role in the management of patients with cancer but the development of anthracycline-induced cardiotoxicity (ACT) remains a significant concern for most clinicians. Recently, genetic approach has been used to identify patients at increased risk of ACT. This systematic review assessed the association between genomic markers and ACT. A systematic literature search was performed in Medline, PubMed, Cochrane Central Register of Controlled Studies, CINAHL Plus, AMED, EMBASE and HuGE Navigator from inception until May 2016. Twenty-eight studies examining the association of genetic variants and ACT were identified. These studies examined 84 different genes and 147 single nucleotide polymorphisms. Meta-analyses showed 3 risk variants significantly increased the risk for ACT; namely ABCC2 rs8187710 (pooled odds ratio: 2.20; 95% CI: 1.36-3.54), CYBA rs4673 (1.55; 1.05-2.30) and RAC2 rs13058338 (1.79; 1.27-2.52). The current evidence remains unclear on the potential role of pharmacogenomic screening prior to anthracycline therapy. Further research is needed to improve the diagnostic and prognostic role in predicting ACT.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Cardiotoxicity; Genetic Association Studies; Humans; Multidrug Resistance-Associated Protein 2; Pharmacogenomic Testing; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 28232737
DOI: 10.1038/s41598-017-00075-1 -
PloS One 2016Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in... (Review)
Review
BACKGROUND
Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing.
OBJECTIVE
To explore the prevalence of CYP2C9 and VKORC1 variants in MENA, and the effect of these variants along with other non-genetic factors in predicting warfarin dose.
METHODS
In this systematic review, we included observational cross sectional and cohort studies that enrolled patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose as the primary outcome. We searched PubMed, Medline, Scopus, PharmGKB, PHGKB, Google scholar and reference lists of relevant reviews.
RESULTS
We identified 17 studies in eight different populations: Iranian, Israeli, Egyptian, Lebanese, Omani, Kuwaiti, Sudanese and Turkish. Most common genetic variant in all populations was the VKORC1 (-1639G>A), with a minor allele frequency ranging from 30% in Egyptians and up to 52% and 56% in Lebanese and Iranian, respectively. Variants in the CYP2C9 were less common, with the highest MAF for CYP2C9*2 among Iranians (27%). Variants in the VKORC1 and CYP2C9 were the most significant predictors of warfarin dose in all populations. Along with other genetic and non-genetic factors, they explained up to 63% of the dose variability in Omani and Israeli patients.
CONCLUSION
Variants of VKORC1 and CYP2C9 are the strongest predictors of warfarin dose variability among the different populations from MENA. Although many of those populations share the same ancestry and are similar in their warfarin dose predictors, a population specific dosing algorithm is needed for the prospective estimation of warfarin dose.
Topics: Africa, Northern; Cytochrome P-450 CYP2C9; Female; Genetic Variation; Humans; Male; Middle East; Pharmacogenomic Testing; Vitamin K Epoxide Reductases; Warfarin
PubMed: 27992547
DOI: 10.1371/journal.pone.0168732 -
Advances in Therapy Sep 2016The use of targeted therapies has recently increased. Pharmacogenetic tests are a useful tool to guide patient treatment and to test a response before administering... (Review)
Review
Cost-Effectiveness of Pharmacogenomic and Pharmacogenetic Test-Guided Personalized Therapies: A Systematic Review of the Approved Active Substances for Personalized Medicine in Germany.
BACKGROUND
The use of targeted therapies has recently increased. Pharmacogenetic tests are a useful tool to guide patient treatment and to test a response before administering medicines. Pharmacogenetic tests can predict potential drug resistance and may be used for determining genotype-based drug dosage. However, their cost-effectiveness as a diagnostic tool is often debatable. In Germany, 47 active ingredients are currently approved. A prior predictive test is required for 39 of these and is recommended for eight. The objective of this study was to review the cost-effectiveness (CE) of pharmacogenetic test-guided drug therapy and compare the application of drugs with and without prior genetic testing.
METHODS
A systematic literature review was conducted to identify the CE and cost-utility of genetic tests. Studies from January 2000 until November 2015 were searched in 16 databases including Medline, Embase, and Cochrane. A quality assessment of the full-text publications was performed using the validated Quality of Health Economic Studies (QHES) instrument.
RESULTS
In the majority of the included studies, the pharmacogenetic test-guided therapy represents a cost-effective/cost-saving treatment option. Only seven studies lacked a clear statement of CE or cost-savings, because of uncertainty, restriction to specific patient populations, or assumptions for comparative therapy. Moreover, the high quality of the available evidence was evaluated.
CONCLUSION
Pharmacogenetic testing constitutes an opportunity to improve the CE of pharmacotherapy. The CE of targeted therapies depends on various factors including costs, prevalence of biomarkers, and test sensitivity and specificity. To guarantee the CE comparability of stratified drug therapies, national and international standards for evaluation studies should be defined.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Germany; Humans; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 27406232
DOI: 10.1007/s12325-016-0376-8 -
PloS One 2016Due to extended application of pharmacogenetic and pharmacogenomic screening (PGx) tests it is important to assess whether they provide good value for money. This review... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Due to extended application of pharmacogenetic and pharmacogenomic screening (PGx) tests it is important to assess whether they provide good value for money. This review provides an update of the literature.
METHODS
A literature search was performed in PubMed and papers published between August 2010 and September 2014, investigating the cost-effectiveness of PGx screening tests, were included. Papers from 2000 until July 2010 were included via two previous systematic reviews. Studies' overall quality was assessed with the Quality of Health Economic Studies (QHES) instrument.
RESULTS
We found 38 studies, which combined with the previous 42 studies resulted in a total of 80 included studies. An average QHES score of 76 was found. Since 2010, more studies were funded by pharmaceutical companies. Most recent studies performed cost-utility analysis, univariate and probabilistic sensitivity analyses, and discussed limitations of their economic evaluations. Most studies indicated favorable cost-effectiveness. Majority of evaluations did not provide information regarding the intrinsic value of the PGx test. There were considerable differences in the costs for PGx testing. Reporting of the direction and magnitude of bias on the cost-effectiveness estimates as well as motivation for the chosen economic model and perspective were frequently missing.
CONCLUSIONS
Application of PGx tests was mostly found to be a cost-effective or cost-saving strategy. We found that only the minority of recent pharmacoeconomic evaluations assessed the intrinsic value of the PGx tests. There was an increase in the number of studies and in the reporting of quality associated characteristics. To improve future evaluations, scenario analysis including a broad range of PGx tests costs and equal costs of comparator drugs to assess the intrinsic value of the PGx tests, are recommended. In addition, robust clinical evidence regarding PGx tests' efficacy remains of utmost importance.
Topics: Costs and Cost Analysis; Drug Evaluation, Preclinical; Economics, Pharmaceutical; Humans; Pharmacogenetics; Time Factors; Treatment Outcome
PubMed: 26752539
DOI: 10.1371/journal.pone.0146262 -
Expert Review of Gastroenterology &... 2016While the pace of discovery of new agents, mechanisms and risk factors involved in drug-induced liver injury (DILI) remains brisk, advances in the treatment of acute... (Review)
Review
While the pace of discovery of new agents, mechanisms and risk factors involved in drug-induced liver injury (DILI) remains brisk, advances in the treatment of acute DILI seems slow by comparison. In general, the key to treating suspected DILI is to stop using the drug prior to developing irreversible liver failure. However, predicting when to stop is an inexact science, and commonly used ALT monitoring is an ineffective strategy outside of clinical trials. The only specific antidote for acute DILI remains N-acetylcysteine (NAC) for acetaminophen poisoning, although NAC is proving to be beneficial in some cases of non-acetaminophen DILI in adults. Corticosteroids can be effective for DILI associated with autoimmune or systemic hypersensitivity features. Ursodeoxycholic acid, silymarin and glycyrrhizin have been used to treat DILI for decades, but success remains anecdotal. Bile acid washout regimens using cholestyramine appear to be more evidenced based, in particular for leflunomide toxicity. For drug-induced acute liver failure, the use of liver support systems is still investigational in the United States and emergency liver transplant remains limited by its availability. Primary prevention appears to be the key to avoiding DILI and the need for acute treatment. Pharmacogenomics, including human leukocyte antigen genotyping and the discovery of specific DILI biomarkers offers significant promise for the future. This article describes and summarizes the numerous and diverse treatment and prevention modalities that are currently available to manage DILI.
Topics: Acetylcysteine; Adrenal Cortex Hormones; Antidotes; Antioxidants; Chelating Agents; Chemical and Drug Induced Liver Injury; Cholagogues and Choleretics; Genetic Predisposition to Disease; Humans; Liver Transplantation; Liver, Artificial; Patient Selection; Pharmacogenomic Testing; Phenotype; Precision Medicine; Risk Factors; Therapeutic Irrigation; Treatment Outcome
PubMed: 26633044
DOI: 10.1586/17474124.2016.1127756 -
Epidemiologia E Prevenzione 2015To identify those studies in which economic analysis of predictive genetic and pharmacogenetic testing programs have been carried out. Since the Italian National... (Review)
Review
OBJECTIVES
To identify those studies in which economic analysis of predictive genetic and pharmacogenetic testing programs have been carried out. Since the Italian National Prevention Plan 2014-2018 foresees the implementation of genetic testing for inherited breast cancer, special attention was given to the cost-effectiveness of BRCA1/2 testing programs.
METHODS
A systematic review of primary economic evaluations (EEs) of predictive genetic and pharmacogenetic testing programs and an overview of previously published systematic reviews of economic evaluations (ERs) was performed.
RESULTS
Overall 128 EEs and 11 ERs were identified. The methodological quality of both EEs and ERs was good on average. Both predictive genetic and pharmacogenetic testing programs were mainly concerned with oncological diseases. Seventeen percent of genetic testing programs are cost-saving, while a further 44% of cost/QALY ratios fall under the commonly used threshold of €37,000 per QALY. For BRCA1/2 testing, only cascade genetic screening programs, targeted to close relatives of carriers, show clear evidence of cost-effectiveness.
CONCLUSION
Despite some limitations, EEs and ERs are powerful tools that provide indications to policy-makers on which genetic testing programs might be introduced into health care systems and public health practice.
Topics: Breast Neoplasms; Cost-Benefit Analysis; Delivery of Health Care; Early Detection of Cancer; Female; Genes, BRCA1; Genes, BRCA2; Genetic Diseases, Inborn; Genetic Predisposition to Disease; Genetic Testing; Global Health; Health Care Costs; Humans; Insurance, Health, Reimbursement; Life Expectancy; Ovarian Neoplasms; Pharmacogenomic Testing; Quality-Adjusted Life Years
PubMed: 26499415
DOI: No ID Found -
BMC Pulmonary Medicine Dec 2014Non-small cell lung cancer (NSCLC) imposes a substantial burden on patients, health care systems and society due to increasing incidence and poor survival rates. In... (Review)
Review
BACKGROUND
Non-small cell lung cancer (NSCLC) imposes a substantial burden on patients, health care systems and society due to increasing incidence and poor survival rates. In recent years, advances in the treatment of metastatic NSCLC have resulted from the introduction of targeted therapies. However, the application of these new agents increases treatment costs considerably. The objective of this article is to review the economic evidence of targeted therapies in metastatic NSCLC.
METHODS
A systematic literature review was conducted to identify cost-effectiveness (CE) as well as cost-utility studies. Medline, Embase, SciSearch, Cochrane, and 9 other databases were searched from 2000 through April 2013 (including update) for full-text publications. The quality of the studies was assessed via the validated Quality of Health Economic Studies (QHES) instrument.
RESULTS
Nineteen studies (including update) involving the MoAb bevacizumab and the Tyrosine-kinase inhibitors erlotinib and gefitinib met all inclusion criteria. The majority of studies analyzed the CE of first-line maintenance and second-line treatment with erlotinib. Five studies dealt with bevacizumab in first-line regimes. Gefitinib and pharmacogenomic profiling were each covered by only two studies. Furthermore, the available evidence was of only fair quality.
CONCLUSION
First-line maintenance treatment with erlotinib compared to Best Supportive Care (BSC) can be considered cost-effective. In comparison to docetaxel, erlotinib is likely to be cost-effective in subsequent treatment regimens as well. The insights for bevacizumab are miscellaneous. There are findings that gefitinib is cost-effective in first- and second-line treatment, however, based on only two studies. The role of pharmacogenomic testing needs to be evaluated. Therefore, future research should improve the available evidence and consider pharmacogenomic profiling as specified by the European Medicines Agency. Upcoming agents like crizotinib and afatinib need to be analyzed as well.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; Erlotinib Hydrochloride; Gefitinib; Humans; Lung Neoplasms; Molecular Targeted Therapy; Protein Kinase Inhibitors; Quinazolines
PubMed: 25471553
DOI: 10.1186/1471-2466-14-192