Approaches to Incorporation of Preferences into Health Economic Models of Genomic Medicine: A Critical Interpretive Synthesis and Conceptual Framework.

Introduction: Genomic medicine has features that make it preference sensitive and amenable to model-based health economic evaluation. Preferences of patients, caregivers, and clinicians related to the uptake and delivery of genomic medicine technologies and services that are not captured in health state utility weights can affect the intervention's cost-effectiveness and budget impact. However, there is currently no established or agreed-on approach for integrating preference information into economic evaluations.

Health Care Costs After Genome-Wide Sequencing for Children With Rare Diseases in England and Canada.

Importance: Etiologic diagnoses for rare diseases can involve a diagnostic odyssey, with repeated health care interactions and inconclusive diagnostics. Prior studies reported cost savings associated with genome-wide sequencing (GWS) compared with cytogenetic or molecular testing through rapid genetic diagnosis, but there is limited evidence on whether diagnosis from GWS is associated with reduced health care costs.

Objective: To measure changes in health care costs after diagnosis from GWS for Canadian and English children with suspected rare diseases.

Using orthopaedic health care resources efficiently: A cost analysis of day surgery for unicompartmental knee replacement.

Background: Day surgery for unicompartmental knee replacement (UKR) could potentially reduce hospital costs. We aimed to measure the impact of introducing a day surgery UKR pathway on mean length of stay (LOS) and costs for the UK NHS, compared to an accelerated inpatient pathway. Secondly, the study aimed to compare the magnitude of costs using three costing approaches: top-down costing; simple micro-costing; and real-world costing.

Stereotactic radiotherapy for neovascular age-related macular degeneration (STAR): a pivotal, randomised, double-masked, sham-controlled device trial.

Background: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness. The first-line therapy is anti-vascular endothelial growth factor (anti-VEGF) agents delivered by intravitreal injection. Ionising radiation mitigates key pathogenic processes underlying nAMD, and therefore has therapeutic potential.

Paving the path for implementation of clinical genomic sequencing globally: Are we ready?

Despite the emerging evidence in recent years, successful implementation of clinical genomic sequencing (CGS) remains limited and is challenged by a range of barriers. These include a lack of standardized practices, limited economic assessments for specific indications, limited meaningful patient engagement in health policy decision-making, and the associated costs and resource demand for implementation. Although CGS is gradually becoming more available and accessible worldwide, large variations and disparities remain, and reflections on the lessons learned for successful implementation are sparse.

Cost-effectiveness of alternative testing strategies in cancer patients followed by histology-independent therapy with entrectinib: an analysis of three European countries.

To explore variations in the cost-effectiveness of entrectinib across different testing strategies and settings. Four testing strategies where adult cancer patients received entrectinib if they tested positive for  gene fusions compared with 'no testing' and standard of care (SoC) for all patients were evaluated. Immunohistochemistry for all patients followed by RNA-based next-generation sequencing after a positive result was the optimal strategy in all included countries.

Lessons learned from the application of the HEcoPerMed guidance to three modeling case studies.

The HEcoPerMed consortium developed a methodological guidance for the harmonization and improvement of economic evaluations in personalized medicine. In three therapeutic areas, health economic models were developed to scrutinize the recommendations of the guidance. Altogether, 20 of the 23 recommendations of the guidance were addressed by the models.

Cost-effectiveness of genetic-based screening strategies for maturity-onset diabetes of the young.

Maturity-onset diabetes of the young (MODY) is often misdiagnosed as Type I or II diabetes. This study was designed to assess the cost-effectiveness of MODY screening strategies in Hungary, which included a recent genetic test compared with no routine screening for MODY. A simulation model that combined a decision tree and an individual-level Markov model was constructed to assess the costs per quality-adjusted life year of screening strategies.

Cost-effectiveness and budget impact analysis of screening strategies for maturity-onset diabetes of the young in three European countries.

Correct diagnosis of maturity-onset diabetes of the young (MODY), which is often misdiagnosed as Type 1 or 2 diabetes, is important for providing appropriate treatment. A diabetes model was adapted to Hungary, the Netherlands, and the UK to analyse the cost-effectiveness and budget impact of different screening strategies for MODY with 20 years time horizon. Compared with no screening, screening with the MODY calculator then genetic testing is considered cost-effective with respect to each country's willingness to pay threshold.

Cost-effectiveness of extended testing before fluoropyrimidine chemotherapy in metastatic breast cancer in the UK.

The aim of this study was to evaluate the cost-effectiveness of ToxNav, a multivariant genetic test, to screen for followed by personalized chemotherapy dosing for metastatic breast cancer in the UK compared with no testing followed by standard dose, standard of care. In the main analysis, ToxNav was dominant over standard of care, producing 0.19 additional quality-adjusted life years and savings of £78,000 per patient over a lifetime.

Long-term cost-effectiveness of a melanoma prevention program using genomic risk information compared with standard prevention advice in Australia.

Purpose: Evidence indicates that a melanoma prevention program using personalized genomic risk provision and genetic counseling can affect prevention behaviors, including reducing sunburns in adults with no melanoma history. This analysis evaluated its longer-term cost-effectiveness from an Australian health system perspective.

Methods: The primary outcome was incremental cost effectiveness ratio (ICER) of genomic risk provision (intervention) compared with standard prevention advice.

Financial incentives to promote personalized medicine in Europe: an overview and guidance for implementation.

The implementation of adequate financing and reimbursement of personalized medicine (PM) in Europe is still turbulent. The views and experience of stakeholders about barriers in financing and reimbursing PM and potential solutions were elicited and supplemented with literature findings to draft a set of recommendations. Key recommendations to overcome the barriers for adequately financing and reimbursing PM in different healthcare systems in Europe included the provision of legal foundations and establishment of large pan-European databases, use of financial-based agreements and regulation of transparency of prices and reimbursement, and creating a business-friendly environment and attractive market for innovation.

Budget impact and transferability of cost-effectiveness of testing in metastatic breast cancer in three health systems.

The cost-effectiveness and budget impact of introducing extended testing prior to fluoropyrimidine-based chemotherapy in metastatic breast cancer patients in the UK, The Netherlands and Hungary were examined. testing with ToxNav was cost-effective in all three countries. In the UK and The Netherlands, the ToxNav strategy led to more quality-adjusted life years and fewer costs to the health systems compared with no genetic testing and standard dosing of capecitabine/5-fluorouracil.

Impact of video-assisted thoracoscopic lobectomy versus open lobectomy for lung cancer on recovery assessed using self-reported physical function: VIOLET RCT.

Background: Lung cancer is the leading cause of cancer death. Surgery remains the main method of managing early-stage disease. Minimal-access video-assisted thoracoscopic surgery results in less tissue trauma than open surgery; however, it is not known if it improves patient outcomes.

Integrating genome-wide polygenic risk scores and non-genetic risk to predict colorectal cancer diagnosis using UK Biobank data: population based cohort study.

Objective: To evaluate the benefit of combining polygenic risk scores with the QCancer-10 (colorectal cancer) prediction model for non-genetic risk to identify people at highest risk of colorectal cancer.

Design: Population based cohort study.

Setting: Data from the UK Biobank study, collected between March 2006 and July 2010.

Cost-Effectiveness Analysis of Treating Patients With NTRK-Positive Cancer With the Histology-Independent Therapy Entrectinib.

Objectives: This study tackles several challenges of evaluating histology-independent treatments using entrectinib as an example. Histology-independent treatments are provided based on genetic marker(s) of tumors, regardless of the tumor type. We evaluated the lifetime cost-effectiveness of testing all patients for NTRK fusions and treating the positive cases with entrectinib compared with no testing and standard of care (SoC) for all patients.

Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients.

Aim: To independently assess the impact of mandatory testing using an extended DPYD variant panel (ToxNav®) and consequent dose adjustment of Capecitabine/5-FU on recorded quantitative toxicity, symptoms of depression, and hospital costs.

Methods: We used propensity score matching (PSM) to match 466 patients tested with ToxNav® with 1556 patients from a historical cohort, and performed regression analysis to estimate the impact of ToxNav®on toxicity, depression, and hospital costs.

Results: ToxNav® appeared to reduce the likelihood of experiencing moderate (OR: 0.