Pharmacogenomic Testing Research Articles

Utilization of supportive care medications and opportunities for pre-emptive pharmacogenomic testing in pediatric and young adults with leukemia

This study aimed to evaluate the utilization of drugs with pharmacogenomic guidelines (PGx-drugs) for personalized dosing in pediatric leukemia. A retrospective observational study of pediatric leukemia patients admitted between 2009–2019 at a single-center academic children’s hospital was conducted to determine PGx-drug exposure within 3 years of diagnosis. Along with baseline demographic and clinical characteristics of these patients, data regarding dates of diagnosis, relapse, death were collected. During the study period, inclusion criteria were met by 714 patients. The most frequently given medications were ondansetron (96.1%), morphine (92.2%), and allopurinol (85.3%) during the study period. In this cohort, 82% of patients received five or more PGx-drugs. Patients diagnosed with acute myeloid leukemia and leukemia unspecified were prescribed more PGx-drugs than other types of leukemia. There was a significant relationship between age at diagnosis and the number of PGx-drugs prescribed. Adolescents and adults both received a median of 10 PGx-drugs, children received a median of 6 PGx-drugs, and infants received a median of 7 PGx-drugs (p < 0.001). Patients with recurrent leukemia had significantly more PGx-drugs prescribed compared to those without recurrent disease, 10 drugs and 6 drugs, respectively (p < 0.001). Patients diagnosed with childhood leukemia are high utilizers of PGx-drugs. There is a vital need to understand how PGx testing may be utilized to optimize treatment and enhance quality of life. Preemptive PGx testing is a tool that aids in optimization of drug therapy and decreases the need for later treatment modifications. This can result in financial savings from decreased health-care encounters.

Precision medicine in pharmacy: assessing pharmacogenomics competence among pharmacists and pharmacy students.

Pharmacogenomics, a key component of precision medicine, aims to improve healthcare outcomes. As pharmacists play a pivotal role in this evolving field, an assessment of their preparedness to apply pharmacogenomics is imperative. In this cross-sectional study, a validated questionnaire (Content Validity Ratio > 0.741, p < 0.05) that demonstrated reliability (Cronbach's alpha for all scales > 0.7) gathered data on demographics, knowledge, attitudes, barriers, and confidence in pharmacogenomics among pharmacists and pharmacy students in Jordan. Statistical analysis assessed associations and their strength within the collected data and variables. This study included 514 pharmacists and pharmacy students. Knowledge scores were moderate and correlated with academic level and pharmacy school attended. Most participants were open to providing pharmacogenomics testing and interpretation through pharmacy services, but the majority demonstrated concerns about potential misinterpretation of test results and the resulting patients' anxiety. Students cited limited accessibility, while pharmacists identified the lack of standardised guidelines as the main roadblock. This study highlights the need for education to prepare pharmacists for their role in pharmacogenomics. Despite positive attitudes from pharmacists, addressing knowledge gaps, the low confidence in recommending pharmacogenomics tests, and concerns about implementation are essential.

Precision Medicine Approach Using Triple Combination Antifungal Therapy for Fusarium Brain Abscesses and Endocarditis in an Adult Burn Patient.

We report a management strategy for disseminated Fusarium solani fungal infection in an adult 35% total body surface area burn patient with brain abscesses and concomitant pulmonic valve endocarditis resulting in the longest survival reported in a burn patient. Early in his hospital course, the patient was diagnosed with a Fusarium burn wound infection with concomitant fungemia and was treated with a prolonged course of intravenous (IV) antifungal monotherapy. Shortly thereafter, he developed focal neurologic deficits and was found to have brain abscesses on MRI. He underwent emergent craniotomy with debridement, and triple antifungal therapy was initiated. Transesophageal echocardiography demonstrated pulmonic valve vegetations, which resolved with triple antifungal therapy. Disseminated Fusarium solani infection is quite rare with mortality approaching 100%. Given the rarity of this disease process, there are no established antifungal treatment guidelines. However, this patient survived for approximately 1 year after diagnosis with treatment including source control via craniotomy and debridement coupled with prolonged courses of combination antifungal therapy (given the near pan-resistance of his fungal infection). Pharmacogenomic testing was utilized to establish the patient's metabolism of voriconazole and dosing adjusted accordingly to improve the efficacy of the combination therapy. To our knowledge, an adult burn patient surviving this length of time after Fusarium brain abscesses with disseminated infection has not been previously described.

The future is now: Implementation of standard of care, preemptive pharmacogenomic testing in patients with gastrointestinal cancers.

1546 Background: Preemptive germline pharmacogenomic (PGx) testing provides insight into the safety of high-risk chemotherapy and effective use of supportive care medications in gastrointestinal (GI) cancers. Advances in clinical practice guidelines and clinician support have accelerated the appetite for PGx testing, particularly for drugs with severe adverse reactions. The objective of this study was to assess operational outcomes associated with end-to-end electronic health record (EHR) integration of standard of care, preemptive multigene PGx testing in patients with GI cancers. Methods: Patients in two UCHealth GI oncology clinics were tested for five PGx genes related to 5-fluorouracil (5-FU, DPYD), irinotecan ( UGT1A1), and supportive care therapies ( CYP2C19, CYP2D6, CYP2C9). The PGx test order was embedded in all GI oncology treatment plans. Patient samples were genotyped, and PGx results were returned as discrete data to the EHR. Automated clinical decision support (CDS) tools provided PGx-guided recommendations at the point of prescribing. We leveraged the EPIS process framework and evaluated operational outcomes such as number of patients tested, lab turnaround time, patients with actionable phenotypes, and number of CDS alerts and clinical actions. Results: The analysis included 89 patients who received results for DPYD/UGT1A1 and 83 patients who received results for supportive care genes. Among samples tested, DPYD/UGT1A1 and supportive care gene results were returned to the EHR in an average of 4.7 ± 2 days (range 1-8) and 17.3 ± 3 days (range 9-24), respectively. The number of patients with abnormal phenotypes, defined as poor metabolizers for UGT1A1 and any non-normal phenotypes for the other genes, were UGT1A1, n=10 (11.2%); DPYD, n=4 (4.5%); CYP2C19, n=43 (51.8%); CYP2D6, n=31 (41.3%; 8 uninterpretable results); and CYP2C9, n=19 (22.9%). This equated to 14/89 (15.7%) and 68/83 (81.9%) patients having an abnormal result for DPYD/UGT1A1 and at least one supportive care gene, respectively. CDS alerts fired for 32 drug-gene interactions for 25 distinct patients. Of the alerts, 7 (21.9%) were for 5-FU or irinotecan, which showed for 7/89 patients (7.9%); 25 (78.1%) were for supportive care medications, which showed for 23/83 patients (27.7%). There were 9 clinical actions taken in response to the PGx alerts, 7 (77.8%) for 5-FU or irinotecan and 2 (22.2%) for supportive care drugs. Appropriate clinical actions were taken for 100% of patients with 5-FU or irinotecan drug-gene interactions. Conclusions: End-to-end EHR integration of PGx testing and prescribing guidance facilitated clinician adoption of preemptive, standard of care multigene PGx testing, with test results driving important medication changes. Future studies will evaluate the impact of PGx testing on clinical outcomes and cost effectiveness metrics in this population.

Pharmacogenomic insights in psychiatric care: uncovering novel actionability, allele-specific CYP2D6 copy number variation, and phenoconversion in 15,000 patients

Pharmacogenomic testing has emerged as an aid in clinical decision making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C-TG haplotype in patients with available medication data. Across 15,000 patients receiving clinical pharmacogenomic testing, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and phenotype assignment was impacted by CYP2D6 allele-specific CNVs in 2% of all patients. Of 4114 patients with medication data, 42% had CYP2D6 phenoconversion from drug interactions and 20% carried a novel CYP2C haplotype potentially altering actionability. A total of 87% had some form of potential actionability from genetic findings and/or phenoconversion. Genetic variation detected via next-generation sequencing led to phenotype reassignment in 22% of individuals overall (2% in CYP2D6 and 20% in CYP2C19). Ultimately, pharmacogenomic testing using next-generation sequencing identified potential actionability in most patients receiving psychiatric care. Early pharmacogenomic testing may provide actionable insights to aid clinicians in drug prescribing to optimize psychiatric care.

More Equity in Implementation of Pharmacogenomic Testing in Oncology

More Equity in Implementation of Pharmacogenomic Testing in Oncology

Effect of pharmacogenomic testing on the clinical treatment of patients with depressive disorder: A randomized clinical trial

BackgroundPharmacotherapy is one of the primary treatment modalities for depression. However, there is considerable variability in the individual response to antidepressant medications. Personalized medicine guided by pharmacogenomic testing may hold promise in addressing this issue. MethodsIn this study, 665 depressive patients were randomly enrolled into two groups: the pharmacogenomic testing group (n = 333) and the control group (n = 332). In the testing group, participants underwent pharmacogenomic testing, and clinicians customized the treatment plan with the result, while the control group relied solely on clinicians' experience. The primary outcomes were the proportion of remission and response, assessed with Hamilton Depression Rating Scale (HDRS). The secondary outcomes included changes in HDRS scores over time and frequency of adverse drug reactions by the participants. ResultsAt week 8, the pharmacogenomic testing group showed significantly higher remission rates (24.0 % v.s. 15.1 %; RR = 1.117; P = 0.007) and response rates (39.3 % v.s. 25.7 %; RR = 1.225; P < 0.001) compared to the control group. By week 12, the pharmacogenomic testing group continued to demonstrate significant advantages in remission (31.0 % v.s. 20.0 %; RR = 1.159; P = 0.003) and response (48.7 % v.s. 37.3 %; RR = 1.224; P = 0.006). Additionally, adverse drug reactions were less frequent in the pharmacogenomic testing group. LimitationsThis study is not blind to clinicians and it's a single-center study.Conclusions: Pharmacogenomic testing-guided drug therapy can provide greater assistance in the treatment of depression.

Cost-Effectiveness Analysis of Pharmacogenomics-Guided Versus Standard Dosing of Warfarin in Patients with Mechanical Prosthetic Heart Valve.

Warfarin is the only approved anticoagulant for antithrombotic treatment in patients with mechanical prosthetic heart valves (MPHV). However, dosing warfarin is challenging due to its narrow therapeutic window and highly variable clinical outcomes. Both low and high doses of warfarin can lead to thrombotic and bleeding events, respectively, with these complications being more severe in individuals with sensitive genetic polymorphisms. Incorporating genetic testing could enhance the accuracy of warfarin dosing and minimize its adverse events. This study aims to evaluate the utilities and cost-effectiveness of pharmacogenomics-guided versus standard dosing of warfarin in patients with MPHV in Iran. In this economic evaluation study, a cost-effectiveness analysis was conducted to compare pharmacogenomics-guided versus standard warfarin dosing. Data related to quality of life (QoL) were collected through a cross-sectional study involving 105 randomly selected MPHV patients using the EuroQol-5D (EQ-5D) Questionnaire. Costs were calculated with input from clinical experts and a review of relevant guidelines. Additional clinical data were extracted from published literature. The pharmacoeconomic threshold set for medical interventions within Iran's healthcare system was $1,500. A decision tree model was designed from the perspective of Iran's healthcare system with a one-year study horizon. Sensitivity analyses were also performed to assess the uncertainty of input parameters. The utility scores derived from the questionnaire for standard and pharmacogenomics-guided warfarin treatments were 0.68 and 0.76, respectively. Genotype-guided dosing of warfarin was more costly compared to the standard dosing ($246 vs $69), and the calculated incremental cost-effectiveness ratio (ICER) was $2474 per quality-adjusted life year (QALY) gained. One-way sensitivity analyses showed that our model is sensitive to the percentage of time in the therapeutic range (PTTR), the cost of genetic tests, and the utility of both pharmacogenomics-guided and standard dosing arms. However, the probabilistic sensitivity analysis demonstrates the robustness of our model. Warfarin dosing with pharmacogenomics testing is currently not cost-effective. However, if the cost of genotyping tests decreases to $118, the ICER would become cost-effective.

Integration of a clinical pharmacist practitioner-led pharmacogenomics service in a Veterans Affairs hematology/oncology clinic.

This article describes the implementation and evaluation of pharmacogenomic testing within the hematology/oncology ambulatory care clinic at the William S. Middleton Memorial Veterans Hospital in Madison, WI. The Pharmacogenomic Testing for Veterans (PHASER) program provides preemptive pharmacogenomic testing for veterans nationally. Program implementation at the Madison Veterans Affairs site began in the hematology/oncology clinic with the goal of integrating the offer for pharmacogenomic testing, testing completion, and review of the results by the hematology/oncology clinical pharmacist practitioner (CPP) into current workflows to create a sustainable process for PHASER. The hematology/oncology CPP designed workflows outlining how testing would be offered to patients, how results would be reported and to whom, and how documentation would occur in the electronic medical record. Veterans are offered preemptive PHASER testing, before needing therapy requiring pharmacogenomic results. Exceptions to pharmacogenomic testing were patients with a history of liver or allogeneic hematopoietic stem cell transplantation. This article provides a summary of the role of the hematology/oncology CPP in the implementation of a pharmacogenomics service and the impact on medication management in a hematology/oncology clinic.

Decoding pharmacogenomic test interpretation and application to patient care

AbstractPharmacogenomics is a growing area of medicine, and pharmacists across clinical practice settings have the opportunity to individualize medication selection and dosing using genetic data. However, many practicing pharmacists may feel ill‐equipped to interpret pharmacogenomic test results because of insufficient education and training. Evidence‐based, updated, and freely available resources such as the Clinical Pharmacogenetics Implementation Consortium guidelines can help pharmacists interpret and apply pharmacogenomic test results to patient care. Although gaps for the application of pharmacogenomic information exist, this commentary aims to demystify the interpretation of pharmacogenomic test results and empower pharmacists to apply genetic data alongside other clinical variables to optimize medication‐related outcomes for their patients. An “ABCD” framework is proposed to guide pharmacists through the steps: (1) Actionability—Are the gene(s) clinically relevant for the patient? (2) Be Mindful of Limitations—What are the caveats with pharmacogenomic test results and reports? (3) Clinical Practice Guidelines—How do you use pharmacogenomic test results to guide clinical decision‐making? and (4) Document and Discuss—How do you educate the patient about their pharmacogenomic test results and document the results for future use? Key concepts are illustrated using a psychiatric patient case example.

Gastric cancer actionable genomic alterations across diverse populations worldwide and pharmacogenomics strategies based on precision oncology.

Introduction: Gastric cancer is one of the most prevalent types of cancer worldwide. The World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and the Global Cancer Statistics (GLOBOCAN) reported an age standardized global incidence rate of 9.2 per 100,000 individuals for gastric cancer in 2022, with a mortality rate of 6.1. Despite considerable progress in precision oncology through the efforts of international consortia, understanding the genomic features and their influence on the effectiveness of anti-cancer treatments across diverse ethnic groups remains essential. Methods: Our study aimed to address this need by conducting integrated in silico analyses to identify actionable genomic alterations in gastric cancer driver genes, assess their impact using deleteriousness scores, and determine allele frequencies across nine global populations: European Finnish, European non-Finnish, Latino, East Asian, South Asian, African, Middle Eastern, Ashkenazi Jewish, and Amish. Furthermore, our goal was to prioritize targeted therapeutic strategies based on pharmacogenomics clinical guidelines, in silico drug prescriptions, and clinical trial data. Results: Our comprehensive analysis examined 275,634 variants within 60 gastric cancer driver genes from 730,947 exome sequences and 76,215 whole-genome sequences from unrelated individuals, identifying 13,542 annotated and predicted oncogenic variants. We prioritized the most prevalent and deleterious oncogenic variants for subsequent pharmacogenomics testing. Additionally, we discovered actionable genomic alterations in the ARID1A, ATM, BCOR, ERBB2, ERBB3, CDKN2A, KIT, PIK3CA, PTEN, NTRK3, TP53, and CDKN2A genes that could enhance the efficacy of anti-cancer therapies, as suggested by in silico drug prescription analyses, reviews of current pharmacogenomics clinical guidelines, and evaluations of phase III and IV clinical trials targeting gastric cancer driver proteins. Discussion: These findings underline the urgency of consolidating efforts to devise effective prevention measures, invest in genomic profiling for underrepresented populations, and ensure the inclusion of ethnic minorities in future clinical trials and cancer research in developed countries.

Utilizing Pharmacogenomic Data for a Safer Use of Statins among the Emirati Population.

Statins are the most prescribed lipid-lowering drugs worldwide. The associated adverse events, especially muscle symptoms, have been frequently reported despite their perceived safety. Three pharmacogenes, the solute carrier organic anion transporter family member 1B1 (SLCO1B1), ATP-binding cassette subfamily G member 2 (ABCG2), and cytochrome P450 2C9 (CYP2C9) are suggested as safety biomarkers for statins. The Clinical Pharmacogenomic Implementation Consortium (CPIC) issued clinical guidelines for statin use based on these three genes. The present study aimed to examine variants in these pharmacogenes to predict the safety of statin use among the Emirati population. Analyzing 242 whole exome sequencing data at the three genes enabled the determination of the frequencies of the single nucleotide polymorphisms (SNPs), annotating the haplotypes and the predicted functions of their proteins. In our cohort, 29.8% and 5.4% had SLCO1B1 decreased and poor function, respectively. The high frequency warns of the possibility of significant side effects of some statins and the importance of pharmacogenomic testing. We found a low frequency (6%) of the ABCG2:rs2231142 variant, which indicates the low probability of Emirati patients being recommended against higher rosuvastatin doses compared with other populations with higher frequencies of this variant. In contrast, we found high frequencies of the functionally impaired CYP2C9 alleles, which makes fluvastatin a less favorable choice. Among the sparse studies available, the present one demonstrates all SLCO1B1 and CYP2C9 function-impairing alleles among Emiratis. We highlighted how population-specific pharmacogenomic data can predict safer choices of statins, especially in understudied populations.

Precision Medicine-Are We There Yet? A Narrative Review of Precision Medicine's Applicability in Primary Care.

Precision medicine (PM), also termed stratified, individualised, targeted, or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many "-omics" arising from increased capacity to understand the human genome and "big data" and data analytics, including artificial intelligence (AI). PM has the potential to transform an individual's health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review, we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM, including evidence of its real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale.

Discovery of Methylenetetrahydrofolate Reductase (MTHFR) Deficiency in Individuals With Common Psychiatric Comorbidities: A Retrospective Case Review.

A retrospective analysis was conducted of a data set collected in an outpatient behavioral health clinic to assess medication metabolism and methylenetetrahydrofolate reductase (MTHFR) and to see if there was a correlation with certain diagnoses and/or gender. The outpatient routine completed genetic testing on their patients and the test results were later collected through a third-party company, which completed the pharmacogenomic test analyzing genetic variations in DNA, medication metabolism, and an MTHFR deficiency. This study reviewed 186 patients seen in an outpatient setting who were tested for an MTHFR deficiency and compared their psychiatric diagnoses and the number of failed medication attempts. Of those 186 patients, 77 had normal MTHFR enzyme function, 85 were found to have a moderate MTHFR deficiency, and 24 had a severe MTHFR deficiency. Those with a severe MTHFR deficiency had a higher number of medication trials as compared to those without the deficiency and there were overall more patients with a moderate MTHFR deficiency in this data set. Currently, MTHFR deficiency is not commonly tested due to lack of insurance coverage and provider knowledge, and due to the cost of the test itself. Thus, the diagnosis can often be missed.

Pharmacogenomics in Psychiatry: An Asian Perspective

IntroductionPharmacogenomic testing in psychiatry is an emerging area with the potential clinical application of guiding medication choice and dosing. However, this has not been adopted widely due to a combination of barriers that include a varying evidence base, clinician and patient familiarity and acceptance, uncertainty about cost-effectiveness, and regulatory requirements.ObjectivesThis review aims to examine recent updates in this field and provide a contextualised summary and recommendations for Asian populations. The recommendations serve to guide healthcare professionals in the utility of pharmacogenomic testing in psychiatric practice.MethodsA review of recent literature about current evidence and guidelines surrounding pharmacogenomics in psychiatric practice was carried out with particular attention paid to literature evaluating Asian populations. Literature was reviewed for the different classes of psychotropics with supplementary information about Asian populations included where available. Existing evidence about combinatorial pharmacogenomic panels was also reviewed.ResultsIn line with the available body of evidence, we recommend that pharmacogenomic testing should be employed as an augmenting tool to guide medication selection and dosing in certain clinical situations, and not as part of standard or routine clinical practice. Pharmacogenomic testing should also be mainly limited to the known drug-gene pairs such as the anti-depressants and CYP2C19 or CYP2D6. Clinicians should also be aware that many of the gene-drug associations have not been evaluated for clinical outcomes. Combinatorial pharmacogenomic panels are not presently recommended as there is limited and inconclusive available evidence on clinical outcomes.ConclusionsPharmacogenomic testing in psychiatry is not recommended as standard or routine clinical practice. Exceptions may include concerns about drug concentrations (due to metaboliser status) or potential severe adverse drug reactions/ Pharmacogenomic testing should be mainly limited to the known drug-gene pairs such as the anti-depressants and CYP2C19 or CYP2D6.Disclosure of InterestNone Declared

494 Expert group decision making for pharmacogenomic testing in Ontario

OBJECTIVES/GOALS: There is a need to better understand how governments develop strategies to adopt, evaluate, and implement novel health technologies in a public healthcare system. The goal of this project is to understand this strategy development process for the translation of pharmacogenomic (PGx) testing in Ontario, Canada. METHODS/STUDY POPULATION: This observational case study of the Ontario Health PGx Working Group focused on developing recommendations for a PGx testing implementation strategy in the province. The group included 9 individuals affiliated with Ontario Health and 13 healthcare experts from multiple clinical fields. Ontario Health is the government agency that oversees provincial healthcare planning and service delivery. Guided by the Translational Thinking Framework and qualitative research methods, we observed the working group’s activities for eight months. We collected meeting recordings, slideshow decks, emails, and group characteristics. We used descriptive statistics and a nine-step inductive approach to analyze the data to create process maps, a case report, and key decision summaries. RESULTS/ANTICIPATED RESULTS: There were 19 meetings conducted remotely with videoconferencing technology. Throughout the working group’s activities, we identified 15 key decisions related to either administrative processes or PGx scientific content. We further stratified these two categories into four main themes relating to decisions about 1) membership involvement, 2) logistical management, 3) discussion and recommendation scope, and 4) information dissemination. These four decision themes represent tools by which Ontario Health guided the expert group activities and achieved their goal of generating a strategic roadmap for PGx testing implementation in Ontario. DISCUSSION/SIGNIFICANCE: The Ontario government makes decisions about how expert groups function by monitoring and controlling the group’s activities to ensure efficiency, standardization, and practicality. Describing expert group decision-making increases transparency and highlights the critical role they play in the translational pathway of health technologies.

Pharmacists' Role in Pharmacogenomics: Transforming Promise to Reality Through Perseverance and Knowledge.

Enormous strides have been made in sequencing technology, multi-gene panels, evidence-based guidelines, and actionable results. We have been moving from reactive pharmacogenomic testing based on single gene analysis to broad pre-emptive testing, where the pharmacogenetic information is available in electronic health records and prescription systems enabling dosing decisions before a prescription is written.

Pharmacogenomics: Medical Advancement Caught in an Ethical and Policy Quagmire.

The emerging role of pharmacogenomic testing is a critical part of personalized medicine practices which examines how deoxyribonucleic acid (DNA) affects an individual response to medications. In most cases, DNA can determine whether the individual may experience adverse reactions as well as the likelihood of the medication's effectiveness and overall safety. While currently applied to only a limited number of conditions and medications such as HIV, certain cancers, depression and heart disease, the field of pharmacogenomic testing is rapidly expanding and being embraced by the healthcare industry as a whole.

Integrating pharmacogenomic testing into personalized medicine practices in the USA: Implications for medication quality control and therapeutic efficacy

This concept paper explores the integration of pharmacogenomic testing into personalized medicine practices in the USA and its implications for medication quality control and therapeutic efficacy. By leveraging genetic information to optimize medication selection and dosing, this paper aims to improve patient outcomes and minimize adverse drug reactions, thereby enhancing medication safety and efficacy in clinical practice. Integrating pharmacogenomic testing into personalized medicine practices has the potential to revolutionize healthcare by improving medication quality control and therapeutic efficacy. This concept paper explores the implications of pharmacogenomic testing for personalized medicine practices in the USA. The paper begins by discussing the current landscape of personalized medicine and the role of pharmacogenomic testing in optimizing medication selection and dosing. It then examines the benefits of integrating pharmacogenomic testing into clinical practice, including improved medication safety, efficacy, and cost-effectiveness. Key considerations for implementing pharmacogenomic testing in personalized medicine practices are discussed, including regulatory considerations, reimbursement challenges, and ethical considerations. The paper also highlights the importance of healthcare provider education and patient engagement in the successful implementation of pharmacogenomic testing. Through a comprehensive analysis, this concept paper aims to provide insights into the implications of integrating pharmacogenomic testing into personalized medicine practices in the USA. By leveraging pharmacogenomic testing, healthcare providers can personalize medication selection and dosing, leading to improved medication quality control and therapeutic efficacy for patients.

A Canadian Simulation Model for Major Depressive Disorder: Study Protocol.

Major depressive disorder (MDD) is a common, often recurrent condition and a significant driver of healthcare costs. People with MDD often receive pharmacological therapy as the first-line treatment, but the majority of people require more than one medication trial to find one that relieves symptoms without causing intolerable side effects. There is an acute need for more effective interventions to improve patients' remission and quality of life and reduce the condition's economic burden on the healthcare system. Pharmacogenomic (PGx) testing could deliver these objectives, using genomic information to guide prescribing decisions. With an already complex and multifaceted care pathway for MDD, future evaluations of new treatment options require a flexible analytic infrastructure encompassing the entire care pathway. Individual-level simulation models are ideally suited for this purpose. We sought to develop an economic simulation model to assess the effectiveness and cost effectiveness of PGx testing for individuals with major depression. Additionally, the model serves as an analytic infrastructure, simulating the entire patient pathway for those with MDD. Key stakeholders, including patient partners, clinical experts, researchers, and modelers, designed and developed a discrete-time microsimulation model of the clinical pathways of adults with MDD in British Columbia (BC), including all publicly-funded treatment options and multiple treatment steps. The Simulation Model of Major Depression (SiMMDep) was coded with a modular approach to enhance flexibility. The model was populated using multiple original data analyses conducted with BC administrative data, a systematic review, and an expert panel. The model accommodates newly diagnosed and prevalent adult patients with MDD in BC, with and without PGx-guided treatment. SiMMDep comprises over 1500 parameters in eight modules: entry cohort, demographics, disease progression, treatment, adverse events, hospitalization, costs and quality-adjusted life-years (payoff), and mortality. The model predicts health outcomes and estimates costs from a health system perspective. In addition, the model can incorporate interactive decision nodes to address different implementation strategies for PGx testing (or other interventions) along the clinical pathway. We conducted various forms of model validation (face, internal, and cross-validity) to ensure the correct functioning and expected results of SiMMDep. SiMMDep is Canada's first medication-specific, discrete-time microsimulation model for the treatment of MDD. With patientpartner collaboration guiding its development, it incorporates realistic care journeys. SiMMDep synthesizes existing information and incorporates provincially-specific data to predict the benefits and costs associated with PGx testing. These predictions estimate the effectiveness, cost-effectiveness, resource utilization, and health gains of PGx testing compared with the current standard of care. However, the flexible analytic infrastructure can be adapted to support other policy questions and facilitate the rapid synthesis of new data for a broader search for efficiency improvements in the clinical field of depression.