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Clinical Pharmacology and Therapeutics Dec 2022Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta-analyzed clinical trials for an association between the use of PGx-guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each trial was assessed for risk of bias and a random-effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx-guided antidepressant therapy (n = 2,395) were 1.41 (95% confidence interval (CI) = 1.15-1.74, P = 0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n = 2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13-1.88) and 1.26 (95% CI = 0.84-1.88), respectively. These results suggest that PGx-guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx-guided antidepressant therapy in the literature.
Topics: Adult; Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Pharmacogenomic Testing; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 36111494
DOI: 10.1002/cpt.2748 -
BMC Psychiatry Aug 2022The main goal of this work was to identify, describe, characterize, and classify the scientific evidence regarding the use of pharmacogenomic biomarkers in...
OBJECTIVE
The main goal of this work was to identify, describe, characterize, and classify the scientific evidence regarding the use of pharmacogenomic biomarkers in antidepressant treatment.
METHODS
The work was developed in two phases: i) a search for pharmacogenomic biomarkers in summaries of antidepressant drugs with marketing authorization in Portugal; and ii) a systematic literature review based on the data obtained in the first phase, with the main objective of finding international literature that could describe and characterize previously reported biomarkers and identify other relevant biomarkers. Finally, the levels of evidence and recommendation grades were classified.
RESULTS
Among the 26 drugs with marketing authorization in Portugal, only 16 had pharmacogenomic information. The most widely studied pharmacogenomic biomarker was CYP2D6. These results were mostly supported by the systematic literature review, which yielded 103 papers, 63 of which were ultimately included in the review. The systematic literature review also revealed the existence of other relevant biomarkers. Most of the included studies show a good level of evidence, which guarantees reliability and good recommendation grades. For the database (built during phase i), the results were informative but resulted in no specific recommendations.
CONCLUSIONS
Most pharmacogenomic variants are not studied or acknowledged by genetic tests, and more scientific research is needed to confirm their usefulness. Therefore, only a small number of variants are considered when prescribing antidepressant drugs. In addition, genotyping of patients is not common in clinical practice.
Topics: Antidepressive Agents; Biomarkers; Genetic Testing; Humans; Pharmacogenetics; Reproducibility of Results
PubMed: 36042420
DOI: 10.1186/s12888-022-04225-2 -
Journal of Personalized Medicine Jun 2022Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical...
Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical practice. We performed a systematic review and meta-analysis on the impact of pharmacogenomics on LTMs response. Studies published until May 2022 were searched using PubMed, EMBASE, and Cochrane databases. Pharmacogenomics/genetics studies of patients with asthma using LTMs with or without other anti-asthmatic drugs were included. Statistical tests of the meta-analysis were performed with Review Manager (Revman, version 5.4, The Cochrane Collaboration, Copenhagen, Denmark) and R language and environment for statistical computing (version 4.1.0 for Windows, R Core Team, Vienna, Austria) software. In total, 31 studies with 8084 participants were included in the systematic review and five studies were also used to perform the meta-analysis. Two included studies were genome-wide association studies (GWAS), which showed different results. Furthermore, none of the SNPs investigated in candidate gene studies were identified in GWAS. In candidate gene studies, the most widely studied SNPs were ALOX5 (tandem repeats of the Sp1-binding domain and rs2115819), LTC4S-444A/C (rs730012), and SLCO2B1 (rs12422149), with relatively inconsistent conclusions. LTC4S-444A/C polymorphism did not show a significant effect in our meta-analysis (AA vs. AC (or AC + CC): −0.06, 95%CI: −0.16 to 0.05, p = 0.31). AA homozygotes had smaller improvements in parameters pertaining to lung functions (−0.14, 95%CI: −0.23 to −0.05, p = 0.002) in a subgroup of patients with non-selective CysLT receptor antagonists and patients without inhaled corticosteroids (ICS) (−0.11, 95%CI: −0.14 to −0.08, p < 0.00001), but not in other subgroups. Variability exists in the pharmacogenomics of LTMs treatment response. Our meta-analysis and systematic review found that LTC4S-444A/C may influence the treatment response of patients taking non-selective CysLT receptor antagonists for asthma, and patients taking LTMs not in combination with ICS for asthma. Future studies are needed to validate the pharmacogenomic influence on LTMs response.
PubMed: 35887565
DOI: 10.3390/jpm12071068 -
The Pharmacogenomics Journal Dec 2022The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This...
The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This creates a number of barriers to widespread adoption of PGx, including privacy concerns related to the storage and movement of identifiable genomic data. Informatic solutions that support secure and equitable data access for genomic data are therefore important to PGx. Here we propose a methodology that uses smart contracts implemented on a blockchain-based framework, PGxChain, to address this issue. The design requirements for PGxChain were identified through a systematic literature review, identifying technical challenges and barriers impeding the clinical implementation of pharmacogenomics. These requirements included security and privacy, accessibility, interoperability, traceability and legal compliance. A proof-of-concept implementation based on Ethereum was then developed that met the design requirements. PGxChain's performance was examined using Hyperledger Caliper for latency, throughput, and transaction success rate. The findings clearly indicate that blockchain technology offers considerable potential to advance pharmacogenetic data sharing, particularly with regard to PGx data security and privacy, large-scale accessibility of PGx data, PGx data interoperability between multiple health care providers and compliance with data-sharing laws and regulations.
Topics: Humans; Blockchain; Pharmacogenetics; Computer Security; Information Dissemination; Pharmacogenomic Testing
PubMed: 35869255
DOI: 10.1038/s41397-022-00285-5 -
The Pharmacogenomics Journal Jul 2022Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the... (Meta-Analysis)
Meta-Analysis
Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the occurrence of a potentially fatal adverse reaction, clozapine-induced agranulocytosis (CIA). Identifying genetic variations contributing to CIA would help predict patient risk of developing CIA and personalize treatment. Here, we (1) review existing pharmacogenomic studies of CIA, and (2) conduct meta-analyses to identify targets for clinical implementation. A systematic literature search identified studies that included individuals receiving clozapine who developed CIA and controls who did not. Results showed that individuals carrying the HLA-DRB1*04:02 allele had nearly sixfold (95% CI 2.20-15.80, p = 0.03) higher odds of CIA with a negative predictive value of 99.3%. Previously unreplicated alleles, TNFb5, HLA-B*59:01, TNFb4, and TNFd3 showed significant associations with CIA after multiple-testing corrections. Our findings suggest that a predictive HLA-DRB1*04:02-based pharmacogenomic test may be promising for clinical implementation but requires further investigation.
Topics: Agranulocytosis; Alleles; Antipsychotic Agents; Clozapine; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 35710824
DOI: 10.1038/s41397-022-00281-9 -
The Pharmacogenomics Journal Mar 2022Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to... (Meta-Analysis)
Meta-Analysis Review
Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to healthcare delivery is required. Pharmacogenetics has potential as a component of medicines optimisation. Studies involving multi-medicine pharmacogenetics in adults with multimorbidity or polypharmacy, reporting on outcomes derived from relevant core outcome sets, were included in this systematic review. Narrative synthesis was undertaken to summarise the data; meta-analysis was inappropriate due to study heterogeneity. Fifteen studies of diverse design and variable quality were included. A small, randomised study involving pharmacist-led medicines optimisation, including pharmacogenetics, suggests this approach could have significant benefits for patients and health systems. However, due to study design heterogeneity and the quality of the included studies, it is difficult to draw generalisable conclusions. Further pragmatic, robust pharmacogenetics studies in diverse, real-world patient populations, are required to establish the benefit of multi-medicine pharmacogenetic screening on patient outcomes.
Topics: Humans; Multimorbidity; Pharmacists; Pharmacogenetics; Pharmacogenomic Testing; Polypharmacy
PubMed: 35194175
DOI: 10.1038/s41397-021-00260-6 -
Research in Social & Administrative... Aug 2022Pharmacogenetic testing enhances patient safety by improving medical treatment and reducing side effects. It has shown potential in both primary and secondary care.... (Review)
Review
BACKGROUND
Pharmacogenetic testing enhances patient safety by improving medical treatment and reducing side effects. It has shown potential in both primary and secondary care. However, implementation in healthcare, particularly in primary care, is slow.
OBJECTIVE
The objective was to review articles published on the attitudes towards, and knowledge on pharmacogenetic testing in primary care, among general practitioners, pharmacists, and patients.
METHODS
The review was performed according to the PRISMA checklist. A systemized literature search was followed by a 2-step screening process. Apart from the content of articles being within the scope of the review, inclusion criteria included: articles in English; primary research articles; qualitative, quantitative, or mixed methods. Content analysis was conducted as a qualitative meta-synthesis. The methodological rigor of included articles was assessed.
RESULTS
Fifteen studies were included. The analysis resulted in the following main themes: i) benefits of pharmacogenetic testing, ii) barriers to pharmacogenetic testing, iii) pharmacists' role in pharmacogenetic counselling, and iv) pharmacists' knowledge on pharmacogenetics. Methodological rigor was generally medium/high.
CONCLUSIONS
More studies are needed in this area, and there is a need for more education on pharmacogenetic testing for healthcare professionals. Issues like patient autonomy, economy, and access to tests also need to be addressed.
Topics: Attitude of Health Personnel; General Practitioners; Humans; Pharmacists; Pharmacogenomic Testing; Primary Health Care
PubMed: 34996718
DOI: 10.1016/j.sapharm.2021.12.002 -
Pharmacogenomics Jan 2022Pharmacogenomic testing can indicate which drugs may have limited therapeutic action or lead to adverse effects, hence guiding rational and safe prescribing. However,... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic testing can indicate which drugs may have limited therapeutic action or lead to adverse effects, hence guiding rational and safe prescribing. However, in the UK and other countries, there are still significant barriers to implementation of testing in primary care. This systematic review presents the barriers and enablers to the implementation of pharmacogenomics in primary care setting. MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched through to July 2020 for studies that reported primary qualitative data of primary care professionals and patient views. Following screening, data extraction and quality assessment, data synthesis was undertaken using meta-aggregation based on the theoretical domain's framework (TDF). Confidence in the synthesized findings relating to credibility and dependability was established using CONQual. Eligible papers were categorized into six TDF domains - knowledge; social and professional roles; behavioral regulation; beliefs and consequences; environmental context and resources; and social influences. From 1669 citations, eighteen eligible studies were identified across seven countries, with a sample size of 504 participants including both primary care professionals and patients. From the data, 15 synthesized statements, all with moderate CONQual rating emerged. These categories range from knowledge, awareness among Primary Care Physicians and patients, professional relationships, negative impact of PGx, belief that PGx can reduce adverse drug reactions, clinical evidence, cost-effectiveness, informatics, reporting issues and social issues. Through use of TDF, fifteen synthesized statements provide policymakers with valuable recommendations for the implementation of pharmacogenomics in primary care. In preparation, policymakers need to consider the introduction of effective educational strategies for both PCPs and patients to raise knowledge, awareness, and engagement. The actual introduction of PGx will require reorganization with decision support tools to aid use of PGx in primary care, with a clear delegation of roles and responsibilities between general professionals and pharmacists supplemented by a local pool of experts. Furthermore, policy makers need to address the cost effectiveness of pharmacogenomics and having appropriate infrastructure supporting testing and interpretation including informatic solutions for utilizing pharmacogenomic results.
Topics: Health Services Accessibility; Humans; Pharmacogenomic Testing; Primary Health Care
PubMed: 34911350
DOI: 10.2217/pgs-2021-0131 -
Future Healthcare Journal Nov 2021Personalised medicine (PM) is becoming increasingly integrated into standard clinical practice for treating numerous diseases, including cancer. Implementing PM into... (Review)
Review
Personalised medicine (PM) is becoming increasingly integrated into standard clinical practice for treating numerous diseases, including cancer. Implementing PM into healthcare systems will only be successful with the acceptance and input of both patients' and public opinion. This review, therefore, aimed to identify both patients' and public understanding, and perceived benefits and concerns of PM in cancer treatment. A literature search was conducted using MEDLINE, EMBASE, PsycINFO and CINAHL databases. The eligibility criteria specified that papers must explore the public or patients' understanding of PM or pharmacogenomic (PGx) testing in relation to cancer treatment. Patients have a greater understanding of, and trust in, PM compared with members of the public, but often misunderstand how genomic testing in PM works. Key areas that can be targeted to inform future health literacy interventions include genetic literacy for the public and understanding of how PM testing and treatment works for patients.
PubMed: 34888471
DOI: 10.7861/fhj.2021-0063 -
BMC Health Services Research Oct 2021Genetic testing has potential roles in identifying whether an individual would have risk of adverse drug reactions (ADRs) from a particular medicine. Robust...
Pharmacogenetic testing for adverse drug reaction prevention: systematic review of economic evaluations and the appraisal of quality matters for clinical practice and implementation.
BACKGROUND
Genetic testing has potential roles in identifying whether an individual would have risk of adverse drug reactions (ADRs) from a particular medicine. Robust cost-effectiveness results on genetic testing would be useful for clinical practice and policy decision-making on allocating resources effectively. This study aimed to update a systematic review on economic evaluations of pharmacogenetic testing to prevent ADRs and critically appraise the quality of reporting and sources of evidence for model input parameters.
METHODS
We searched studies through Medline via PubMed, Scopus and CRD's NHS Economic Evaluation up to October 2019. Studies investigating polymorphism-based pharmacogenetic testing, which guided drug therapies to prevent ADRs, using economic evaluation methods were included. Two reviewers independently performed data extraction and assessed the quality of reporting using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines and the quality of data sources using the hierarchy of evidence developed by Cooper et al. RESULTS: Fifty-nine economic evaluations of pharmacogenetic testing to avoid drug-induced ADRs were found between 2002 and 2018. Cost-utility and cost-effectiveness analyses were the most common methods of economic evaluation of pharmacogenetic testing. Most studies complied with the CHEERS checklist, except for single study-based economic evaluations which did not report uncertainty analysis (78%). There was a lack of high-quality evidence not only for estimating the clinical effectiveness of pharmacogenetic testing, but also baseline clinical data. About 14% of the studies obtained clinical effectiveness data of testing from a meta-analysis of case-control studies with direct comparison, which was not listed in the hierarchy of evidence used.
CONCLUSIONS
Our review suggested that future single study-based economic evaluations of pharmacogenetic testing should report uncertainty analysis, as this could significantly affect the robustness of economic evaluation results. A specific ranking system for the quality of evidence is needed for the economic evaluation of pharmacogenetic testing of ADRs. Differences in parameters, methods and outcomes across studies, as well as population-level and system-level differences, may lead to the difficulty of comparing cost-effectiveness results across countries.
Topics: Cost-Benefit Analysis; Drug-Related Side Effects and Adverse Reactions; Genetic Testing; Humans; Pharmacogenomic Testing; PubMed
PubMed: 34600523
DOI: 10.1186/s12913-021-07025-8