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. Stratifying patients based on age and insulin treatment followed by a risk assessment questionnaire, a laboratory test and genetic testing was the most cost-effective strategy, saving EUR 12 and generating 0.0047 quality-adjusted life years gained per screened patient. This screening strategy could be considered for reimbursement, especially in countries with limited resources.

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

Background: The HEcoPerMed consortium developed a methodological guidance for the harmonization and improvement of economic evaluations in personalized medicine. Materials & methods: In three therapeutic areas, health economic models were developed to scrutinize the recommendations of the guidance. Results: Altogether, 20 of the 23 recommendations of the guidance were addressed by the models. Seven recommendations were applied in all studies, six in two of the studies and seven in one of the studies. Recommendations with an essential role on the final conclusions of the analyses were identified in each study. Conclusion: The guidance was found to be best used as a tool to identify and prioritize issues, verify solutions and justify decisions during the economic analysis of personalized interventions.

Cost-effectiveness of extended DPYD 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 DPYD 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. The mean additional quality-adjusted life years per person from 1000 simulations was 0.23 savings (95% CI: 0.22-0.24) at £99,000 (95% CI: £95-102,000). Varying input parameters independently by range of 20% was unlikely to change the results in the main analysis. The probabilistic sensitivity analysis showed ~97% probability of the ToxNav strategy to be dominant.

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

Background: 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. Materials & Methods: 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. Results: 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. The addition of autoantibody testing dominated the no screening strategy. The budget impact of the strategies ranges between 0.001 and 0.025% of annual public healthcare spending. Conclusion: The analysed strategies are considered good value for money with potential cost savings in the long term.

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

The cost-effectiveness and budget impact of introducing extended DPYD testing prior to fluoropyrimidine-based chemotherapy in metastatic breast cancer patients in the UK, The Netherlands and Hungary were examined. DPYD 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. In Hungary, the ToxNav strategy produced more quality-adjusted life years at a higher cost compared with no testing and standard dose. The ToxNav strategy was found to offer budget savings in the UK and in The Netherlands, while in Hungary it resulted in additional budget costs.

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. The recommendations could be used by health authorities for designing a sequence of policy steps to ensure the timely access to beneficial PM.

Prospective cohort study for assessment of integrated care with a triple aim approach: hospital at home as use case.

BACKGROUND: Applicability of comprehensive assessment of integrated care services in real world settings is an unmet need. To this end, a Triple Aim evaluation of Hospital at Home (HaH), as use case, was done. As ancillary aim, we explored use of the approach for monitoring the impact of adoption of integrated care at health system level in Catalonia (Spain). METHODS: Prospective cohort study over one year period, 2017-2018, comparing hospital avoidance (HaH-HA) with conventional hospitalization (UC) using propensity score matching. Participants were after the first episode directly admitted to HaH-HA or the corresponding control group. Triple Aim assessment using multiple criteria decision analysis (MCDA) was done. Moreover, applicability of a Triple Aim approach at health system level was explored using registry data. RESULTS: HaH-HA depicted lower: i) Emergency Room Department (ER) visits (p < .001), ii) Unplanned re-admissions (p = .012); and iii) costs (p < .001) than UC. The weighted aggregation of the standardized values of each of the eight outcomes, weighted by the opinions of the stakeholder groups considered in the MCDA: i) enjoyment of life; ii) resilience; iii) physical functioning; iv) continuity of care; v) psychological wellbeing; (vi) social relationships & participation; (vii) person-centeredness; and (viii) costs, indicated better performance of HaH-HA than UC (p < .05). Actionable factors for Triple Aim assessment of the health system with a population-health approach were identified. CONCLUSIONS: We confirmed health value generation of HaH-HA. The study identified actionable factors to enhance applicability of Triple Aim assessment at health system level for monitoring the impact of adoption of integrated care. REGISTRATION: ClinicalTrials.gov (26/04/2017; NCT03130283).

Financing and Reimbursement Models for Personalised Medicine: A Systematic Review to Identify Current Models and Future Options.

BACKGROUND: The number of healthcare interventions described as 'personalised medicine' (PM) is increasing rapidly. As healthcare systems struggle to decide whether to fund PM innovations, it is unclear what models for financing and reimbursement are appropriate to apply in this context. OBJECTIVE: To review financing and reimbursement models for PM, summarise their key characteristics, and describe whether they can influence the development and uptake of PM. METHODS: A literature review was conducted in Medline, Embase, Web of Science, and Econlit to identify studies published in English between 2009 and 2021, and reviews published before 2009. Grey literature was identified through Google Scholar, Google and subject-specific webpages. Articles that described financing and reimbursement of PM, and financing of non-PM were included. Data were extracted and synthesised narratively to report on the models, as well as facilitators, incentives, barriers and disincentives that could influence PM development and uptake. RESULTS: One hundred and fifty-three papers were included. Research and development of PM was financed through both public and private sources and reimbursed largely through traditional models such as single fees, Diagnosis-Related Groups, and bundled payments. Financial-based reimbursement, including rebates and price-volume agreements, was mainly applied to targeted therapies. Performance-based reimbursement was identified mainly for gene and targeted therapies, and some companion diagnostics. Gene therapy manufacturers offered outcome-based rebates for treatment failure for interventions including Luxturna®, Kymriah®, Yescarta®, Zynteglo®, Zolgensma® and Strimvelis®, and coverage with evidence development for Kymriah® and Yescarta®. Targeted testing with OncotypeDX® was granted value-based reimbursement through initial coverage with evidence development. The main barriers and disincentives to PM financing and reimbursement were the lack of strong links between stakeholders and the lack of demonstrable benefit and value of PM. CONCLUSIONS: Public-private financing agreements and performance-based reimbursement models could help facilitate the development and uptake of PM interventions with proven clinical benefit.

Evaluating an integrated care pathway for frail elderly patients in Norway using multi-criteria decision analysis.

BACKGROUND: To provide value-based care for patients with multi-morbidity, innovative integrated care programmes and comprehensive evaluations of such programmes are required. In Norway, a new programme called "Holistic Continuity of Patient Care" (HCPC) addresses the issue of multi-morbidity by providing integrated care within learning networks for frail elderly patients who receive municipal home care services or a short-term stay in a nursing home. This study conducts a multi-criteria decision analysis (MCDA) to evaluate whether the HCPC programme performs better on a large set of outcomes corresponding to the 'triple aim' compared to usual care. METHODS: Prospective longitudinal survey data were collected at baseline and follow-up after 6-months. The assessment of HCPC was implemented by a novel MCDA framework. The relative weights of importance of the outcomes used in the MCDA were obtained from a discrete choice experiment among five different groups of stakeholders. The performance score was estimated using a quasi-experimental design and linear mixed methods. Performance scores were standardized and multiplied by their weights of importance to obtain the overall MCDA value by stakeholder group. RESULTS: At baseline in the HCPC and usual care groups, respectively, 120 and 89 patients responded, of whom 87 and 41 responded at follow-up. The average age at baseline was 80.0 years for HCPC and 83.6 for usual care. Matching reduced the standardized differences between the groups for patient background characteristics and outcome variables. The MCDA results indicated that HCPC was preferred to usual care irrespective of stakeholders. The better performance of HCPC was mostly driven by improvements in enjoyment of life, psychological well-being, and social relationships and participation. Results were consistent with sensitivity analyses using Monte Carlo simulation. CONCLUSION: Frail elderly with multi-morbidity represent complex health problems at large costs for society in terms of health- and social care. This study is a novel contribution to assessing and understanding HCPC programme performance respecting the multi-dimensionality of desired outcomes. Integrated care programmes like HCPC may improve well-being of patients, be cost-saving, and contribute to the pursuit of evidence based gradual reforms in the care of frail elderly.

Evaluating Complex Health and Social Care Program Using Multi-Criteria Decision Analysis: A Case Study of "Better Together in Amsterdam North".

OBJECTIVES: Multi-criteria decision analysis (MCDA) has been recommended to support policy making in healthcare. However, practical applications of MCDA are sparse. One potential use for MCDA is for the evaluation of programs for complex and vulnerable patients. These complex patients benefit from integrated care programs that span healthcare and social care and aim to improve more than just health outcomes. MCDA can evaluate programs that aim to improve broader outcomes because it allows the evaluation of multiple outcomes alongside each other. In this study, we evaluate an innovative integrated care program in the Netherlands using MCDA. METHODS: We used an innovative MCDA framework with broad outcomes of health, well-being, and cost to evaluate the Better Together in Amsterdam North (BSiN) program using preferences of patients, partners, providers, payers, and policy makers in the Netherlands. BSiN provides case management support for a period of 6 months. Seven outcomes that previous research has deemed important to complex patients were measured, including physical functioning and social relationships and participation. RESULTS: We find that the program improved the overall MCDA score marginally, and, thus, after 6 and after 12 months, BSiN was preferred to usual care by all stakeholders. BSiN was preferred to usual care, mostly owing to improvements in psychological well-being and social relationships and participation. CONCLUSIONS: The integrated healthcare and social care program BSiN in the Netherlands was preferred to usual care according to an MCDA evaluation. MCDA seems a useful method to evaluate complex programs with benefits beyond health.

Projecting the COPD population and costs in England and Scotland: 2011 to 2030.

We aimed to estimate the prevalence, healthcare costs and number of deaths among people with chronic obstructive pulmonary disease (COPD) in England and Scotland 2011-2030. We adapted the Dutch COPD Model by using English and Scottish demographic, COPD incidence, COPD prevalence, smoking prevalence and mortality data to make projections. In England, the prevalence of COPD was estimated to be 1.79% (95% uncertainty interval 1.77-1.81) in 2011, increasing to 2.19% (1.85-2.33) by 2030. In Scotland, prevalence was 2.03% (1.96-2.10) in 2011 increasing to 2.20% (1.98-2.40) in 2030. These increases were driven by more women developing COPD. Annual direct healthcare costs of COPD in England were estimated to increase from £1.50 billon (1.18-2.50) in 2011 to £2.32 (1.85-3.08) billion in 2030. In Scotland, costs increased from £159 million (128-268) in 2011 to £207 (165-274) million in 2030. The deaths in England were estimated to increase from 99,200 (92,500-128,500) in 2011, to 129,400 (126,400-133,400) by 2030. In Scotland, in 2011 there were 9,700 (9,000-12,300) deaths and 13,900 (13,400-14,500) deaths in 2030. The number of people with COPD will increase substantially over the coming years in England and Scotland, particularly in females. Services need to adapt to this increasing demand.