Best–worst scaling methodology to evaluate constructs of the Consolidated Framework for Implementation Research: application to the implementation of pharmacogenetic testing for antidepressant therapy

Implementation Science Communications, Journal Year: 2022, Volume and Issue: 3(1)

Published: May 14, 2022

Despite the increased demand for pharmacogenetic (PGx) testing to guide antidepressant use, little is known about how implement in clinical practice. Best-worst scaling (BWS) a stated preferences technique determining relative importance of alternative scenarios and increasingly being used as healthcare assessment tool, with potential applications implementation research. We conducted BWS experiment evaluate factors PGx use.We surveyed 17 organizations that either had implemented or were process implementing antidepressants. The survey included Consolidated Framework Implementation Research (CFIR) constructs from perspective sites.Participating sites varied on their platform methods returning recommendations providers patients, but they consistent ranking several CFIR most important implementation: patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength quality, identification champions.This study demonstrates feasibility using choice experiments systematically determinants organizations. findings can inform other interested mental health. Further, this application PGx, which may be by health disorders.

Language: Английский

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A Narrative Review on Pharmacogenomics in Psychiatry

Journal of Clinical Psychopharmacology, Journal Year: 2023, Volume and Issue: 44(1), P. 49 - 56

Published: Nov. 12, 2023

Pharmacogenetics (PGx) studies the genetic factors underlying interindividual variability in drug response. Only a few countries around world are already using PGx testing psychiatric clinical practice, whereas others still far from adopting it. The main barrier to adoption of seems be limited knowledge among psychiatrists regarding relevance specific variants personalize therapies and accessibility data. This review aims at further highlighting importance PGx-driven decision making for psychotropic medications raising psychiatrists' awareness value psychiatry.We summarize genes which substantial evidence exists about utility integrating their psychiatry. Specifically, we systematically describe functional role clinically relevant allelic variants, frequency across different ethnic groups, how they contribute classify patients relation capability metabolizing drugs.Briefly, guidelines recommend considering cytochrome class 2 C9 (CYP2C9), C19 (CYP2C19), D6 (CYP2D6) human leukocyte antigen (HLA)-A -B several drugs.Extensive have been carried out provide solid rationale inclusion Comprehensive readily accessible support health care providers tailoring prescription drugs based on patient's genotype information. approach presents tangible opportunity significantly improve individual responses medications.

Language: Английский

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Pharmacogenetic testing of CYP2D6, CYP2C19 and CYP2C9 in Denmark: Agreement between publicly funded genotyping tests and the subsequent phenotype classification

Basic & Clinical Pharmacology & Toxicology, Journal Year: 2024, Volume and Issue: 134(5), P. 756 - 763

Published: Feb. 25, 2024

The cytochrome P450 (CYP) enzyme family catalyses the metabolism of approximately 80% all medications.1, 2 Many genes encoding CYP enzymes exhibit high levels polymorphism that affect their expression and activity. most frequent clinically important variations exist within CYP2D6, CYP2C19 CYP2C9.1 extensively studied drug-metabolizing enzyme, has over 100 allelic variants is responsible for metabolizing about 25% marketed 3 CYP2C9 are collectively 20% medications. It estimated 74%–97% Caucasian individuals possess at least one genetic variation in gene, potentially affecting quarter prescribed medications.4 Testing this can help identify whom medication safety efficacy be improved through dose adjustment.1 Pharmacogenetic (PGx) testing assesses by identifying a patient's genotype assigning predicted phenotype. phenotype an inherited allele classified as loss function, decreased normal function or increased function.3 Numerous PGx tests have been developed both public private use. evidence whether these actually improve treatment outcomes controversial, but large implementation study recently showed pre-emptive may reduce incidence adverse reactions.5 normally based on genotyping panels with predefined alleles, between providers approach genotype-to-phenotype translation result conflicting recommendations.6, 7 Current guidelines from Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend classifying phenotypes into four, five three categories CYP2C9, respectively.8 Despite recommendations, recent Bousman Dunlop found substantial reported genotype, resulting recommendations four commercial tests. Based this, authors called standardization development specifying which alleles should included test.7 In response, recommendation selection relevant CYP2D6 were published 2021.9 Denmark, 800 conducted annually across laboratories. Evaluation agreement determined subsequent assignment essential credibility to ensure clinicians will utilize approach. objectives pilot (1) assess how well laboratories agreed genotypes, (2) (3) potential causes observed discrepancies genotypes This data previously described clinical trial titled Optimization Nutrition Medication Acutely Admitted Older Medical Patients (OptiNAM).10, 11 OptiNAM older (age ≥65 years) patients presenting Emergency Department Copenhagen University Hospital Hvidovre, Denmark. All provided informed written consent, analyses approved Regional Ethical Review Board (H-18023853) Danish Data Protection Agency (H-18023853). was accordance Declaration Helsinki registered ClinicalTrials.gov (NCT03741283). Additionally, current Basic & Pharmacology Toxicology experimental investigation.12 Additional details including inclusion exclusion criteria elsewhere.10 total, 126 received commercially available test (Personal Medicine Profile, GeneTelligence, Denmark [hereafter: 'PMP-test']). Blood samples (EDTA plasma buffy coat) collected day hospitalization stored −80°C local biobank. Demographic information such gender, age, height weight hospital's electronic patient record system. To achieve comprehensive dataset, 18 individual selected represent respectively, according CPIC classification.13 Patient methodically identification (ID) numbers PMP-test. Initially, we chose sample lowest ID number each metabolizer category, starting poor metabolizers (PM), followed intermediate (IM), (NM) ultrarapid (UM) metabolizers. process replicated then CYP2C9. Our ensured gene classification, 12 samples. six unselected also included, totalling Genomic DNA extracted coat using paramagnetic particle-based platform consisting Maxwell® 16 Purification Kit Instrument (Promega Corporation, Madison, WI, United States). Genotyping performed Denmark: College Absalon, Roskilde, ('Absalon'); Institute Biological Psychiatry, Mental Health Centre Sct. Hans, ('Sct. Hans'); Epilepsy Center, Filadelfia, Dianalund, ('Filadelfia'). offered predict CYP2C19, only Absalon Filadelfia Hans done Luminex Corporation (Luminex Austin, TX, laboratory kits used permitted determination *1, *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *15, *17, *29, *35, *41 duplications. Using kits, *10 *17. designed in-house 5′nuclease-based PCR. panel duplications, *4 Laboratory *2 *3. For laboratories, *1 (the common variant Caucasians) identified absence other alleles. A detailed overview frequencies Table S1, descriptions assays instruments S2. Genotype-to-phenotype inconsistent utilized PharmGKB classifications CPIC.13 internal classification resembling predicting did not use Rapid Metabolizer (RM) CYP2C19. Consequently, limited PM, IM, NM UM. Similarly, its own system UM, UM recognized presence duplicate (Table 1). NM, (Sct. Hans) (Absalon Filadelfia) (Filadelfia) RM, (Absalon) Phenotype evaluated official classifications.13 However, due differences systems 1), Hans. includes phenotypes, IM converted Hans' classification. Filadelfia's RM Finally, same classification: NM. primary outcome Classification percent Conger's Kappa statistic (к)14: 0.21 0.40 interpreted 'fair' agreement, 0.41 0.60 'moderate', 0.61 0.80 'substantial' 0.81 1.00 'almost perfect'.15 Agreement possible comparisons (i.e., 1–2, 1–3 2–3). patient, comparisons, comparison zero comparisons. estimate calculated agreements out total (three times compared). estimates 95% confidence interval (CI). cases where identical (к = kappa value had variance 0 (resulting CI width). Given relatively small sample, however, do believe sufficiently representative suggest width. If single disagreement present samples, example, width would expand 0.26. Therefore, omitted calculations R 4.1.0.16 Due manufacturer's discontinuation reagent, completed 13 laboratory. when included. shows patients' corresponding Genotype shown 3. *35/*35 *2/*2 *1/*1 *1/*3 (IM) *4/*5 (PM) *2/*35 *1/*2 *4/*35 *2/*4 *1/*41 *4/*41 *1/*17 *1/*9 *2/*5 *2/*3 *17/*17 *2/*9 *4/*4 *2/*17 × *1*1 Overall 85% 0.83, 0.64:1.00) 100% 1.0) phenotyping 90% 0.82, 0.56:1.00), 52% 0.32, 0.14:0.51) 94% 0.32) respectively. When collapsing categories), 100%. 78%. study, assignments largely consistent public-founded resulted notable translation. There several considerations selecting panels, cost, additional ethnicity group.9 service free healthcare system, decide "optimal test" considerations. CYP2D6. whereas 10 (see S1). *35 patients, Since phenotype, particular discrepancy does determination. could different phenotypes.7 implications indicates need cross-validation alignment approaches higher follows classifications, while follow strategies. difference drug metabolism, way, focused relevance, simpler more conservative than CPIC's nearly complies CPIC, include instead identifies it phenotype.17 likely explained lack international consensus relevance *17 conversion analysis developed; field since evolved without reassessment simplified clinically-oriented some disadvantages. impact prescribing medications clopidogrel.18 initial dosing proton pump inhibitors decision prescribe citalopram/escitalopram.19, 20 Altogether, our results indicate genotype–phenotype schemes relevant, recommendcontinuous updating essential. national poses challenges. First, complicate internationally accepted systems. Second, genotype-phenotype makes challenging nationwide Third, limit future PGx.21, 22 first evaluate limitation size, compromise accuracy generalizability findings. retrospective design allow assessment patient-related everyday practice. Another focus exclusively who degree homogeneity. Including range ethnicities yielded lower assay sensitivity, even greater concordance providers. prediction theoretically performing study. represents laboratories' performance reality, strength work. findings demonstrate pivotal ensuring Concept, methodology: Morten Baltzer Houlind, Luise Hansen, Henrik Berg Rasmussen, Jens Borggaard Larsen, Kim Dalhoff, Per Damkier, Anne B. Walls, Charlotte Vermehren, Trine Rune Høgh Andersen, Thomas Kallemose, Lona Christrup, Niels Westergaard; collection data: Esben Iversen, Steffen Jørgensen, interpretation: statistical analysis: Kallemose; funding: Christrup; writing—original draft preparation: Hansen; writing—review editing: Westergaard. read version manuscript. part Academic Group (ACUTE-CAG) Recovery Capacity funded Greater Science Partners (GCHSP). We thank staff involved (OptiNAM) declare they no conflict interest. request restrictions. presented publicly legislation. Request access dataset require inquiry agency approval. S1. Frequencies functional annotation Assays Filadelfia. Please note: publisher content functionality any supporting supplied authors. Any queries (other missing content) directed author article.

Language: Английский

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Proportion of Antipsychotics with CYP2D6 Pharmacogenetic (PGx) Associations Prescribed in an Early Intervention in Psychosis (EIP) Cohort: A Cross-Sectional Study

Journal of Psychopharmacology, Journal Year: 2024, Volume and Issue: 38(4), P. 382 - 394

Published: March 17, 2024

Background: Prescribing drugs for psychosis (antipsychotics) is challenging due to high rates of poor treatment outcomes, which are in part explained by an individual’s genetics. Pharmacogenomic (PGx) testing can help clinicians tailor the choice or dose genetics, particularly with known variable response CYP2D6 gene variants (‘CYP2D6-PGx antipsychotics’). Aims: This study aims investigate differences between demographic groups prescribed ‘CYP2D6-PGx antipsychotics’ and estimate proportion patients eligible PGx based on current pharmacogenomics guidance. Methods: A cross-sectional took place extracting data from 243 patients’ medical records explore drug prescribing, including transitions. Demographic such as age, sex, ethnicity, clinical sub-team were collected summarised. Descriptive statistics explored antipsychotic’ prescribing nature We used logistic regression analysis associations variables prescription versus ‘non-CYP2D6-PGx antipsychotic’. Results: Two-thirds (164) had been a (aripiprazole, risperidone, haloperidol zuclopenthixol). Over fifth (23%) would have met suggested criteria testing, following two trials. There no statistically significant ethnicity likelihood being Conclusions: demonstrated ‘CYP2D6-PGx-antipsychotics’ EIP cohort, providing rationale further exploration how be implemented services personalise psychosis.

Language: Английский

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Pharmacogenomic Testing to Guide Treatment of Major Depressive Disorder: A Systematic Review

Current Treatment Options in Psychiatry, Journal Year: 2024, Volume and Issue: 11(2), P. 123 - 140

Published: May 31, 2024

Abstract Purpose of review Major depressive disorder is a prevalent psychiatric illness associated with significant morbidity, mortality, and economic burden worldwide. Despite the widespread use antidepressants, remission rates among those treated antidepressants remain low. Opportunities to personalize medication choices doses optimize clinical outcomes using pharmacogenomic testing have been evaluated. Recent findings Several prospective trials recent meta-analysis evaluated impact PGx-guided prescribing compared treatment as usual found no difference in for patients MDD. Summary We performed systematic all evaluating effect pharmacogenomic-guided on being major disorder. A literature search was PubMed, Scopus, Web Science, PsychINFO databases articles English published from January 2010 December 2022. Studies that did not report any patient-level were excluded. total 2489 studies screened eligibility. Full-text screening 315 yielded 293 exclusions; thus, 22 included. Sixteen randomized-controlled durations varying 90 days 52 weeks. The this suggest routine may yield changes when usual. These results or be generalizable persons taking given guideline recommendations specific antidepressants. Future are warranted utility such these subpopulations.

Language: Английский

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