Publications

Background: Accurate determination of stroke etiology is essential for effective secondary stroke prevention, yet 25% to 40% of ischemic strokes are classified as cryptogenic. Patent foramen ovale (PFO), a common finding in cryptogenic stroke, elevates the risk of strokes. However, underuse of diagnostic practices may lead to underdiagnosis of PFO, missing opportunities for guideline-recommended PFO closures and preventable recurrent strokes. This study estimates the value of improving testing for PFO among patients with cryptogenic stroke in the US.

Methods: A cost-effectiveness analysis was conducted, employing a hybrid model including a decision tree and a Markov model to assess health outcomes and economic impacts from a US payor perspective over a life-time horizon. The model compared two PFO testing scenarios: the Current Diagnostic Scenario (54% testing) and Optimal PFO Diagnostics (100% testing). The decision tree evaluated diagnostic pathways for PFO (TTE, TEE, TCD), while the Markov model simulated patient progression through various health states (recurrent ischemic stroke, TIA, and death). Cost-effectiveness was determined using the incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $75,000 per Quality-Adjusted Life Year (QALY).

Results: In a simulated cohort of 1,000 patients, increasing the diagnostic testing rate for PFO from 54% to 100% is expected to prevent 63 recurrent strokes, resulting in 23 life years saved and 286 QALYs gained. This led to cost-savings of $1.9 million for payors, indicating a dominant economic position (ICER = -$6,770/QALY). The model estimated screening four patients would lead to identifying and closing one PFO, while screening seven would prevent one recurrent stroke. Thorough sensitivity analyses confirmed the robustness of these findings.

Conclusion: Improving PFO diagnostic testing among patients with cryptogenic stroke is projected to result in improved health outcomes for patients, while yielding cost-savings, underscoring the importance of adhering to PFO diagnostic guidelines.

Objective: This study compares the direct healthcare costs of anti-VEGF therapies, including treat-and-extend (T&E) and other durable regimens, for unilateral neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO) in Switzerland.

Methods: An adapted cost-minimisation model estimated healthcare costs over two years for aflibercept 2 mg, aflibercept 8 mg, faricimab, ranibizumab, and ranibizumab biosimilars using clinical trial injection frequencies. Break-even analyses identified the medication prices and injection frequencies required for higher-cost therapies to achieve cost parity with the least expensive options. A one-way sensitivity analysis (OWSA) assessed key drivers of cost outcomes.

Results: Aflibercept 8 mg was estimated to be associated with the lowest treatment costs for both indications (CHF 11,814 for nAMD; CHF 11,242 for DMO). Faricimab (CHF 13,737) and aflibercept 2 mg (CHF 15,243) followed in nAMD and DMO. Ranibizumab and its biosimilars incurred the highest costs: for nAMD, biosimilars ranged from CHF 16,243 to CHF 17,497 and the reference product reached CHF 18,424; for DMO, biosimilars ranged from CHF 18,187 to CHF 19,596, with the reference product at CHF 20,637. Break-even analyses for nAMD showed that prices would need to drop by −22% (faricimab, CHF 644) to −64% (ranibizumab reference, CHF 218) relative to aflibercept 8 mg. For DMO, reductions ranged from −42% (aflibercept 2 mg, CHF 493) to −81% (ranibizumab reference, CHF 114). The OWSA highlighted medication price and injection frequency as primary cost drivers.

Conclusion: This study estimated that the potentially minimized injection frequency of aflibercept 8 mg in a clinical trial regimen may result in the lowest treatment costs for nAMD and DMO, followed by faricimab and aflibercept 2 mg, respectively.

Introduction: One in three patients with type 2 diabetes (T2D) suffers from any stage of chronic kidney disease (CKD), a chronic illness associated with a high global burden that impacts not only the healthcare system but also societal costs. Addition of finerenone to the standard of care (SoC) for patients with advanced CKD and T2D has been shown to be cost-effective by reducing healthcare and societal costs. This analysis explores the cost-effectiveness of finerenone in patients with CKD (stages 1–4 with albuminuria) associated with T2D from a societal perspective, as broader societal costs are a crucial consideration in managing chronic illnesses.

Methods: The validated FINE-CKD model was populated with data from the pooled FIDELITY analysis (ie, a patient population with early-to-late stage CKD associated with T2D) to investigate the cost-effectiveness of the addition of finerenone to SoC compared with SoC alone, from a Dutch societal perspective. Sensitivity analyses were conducted to evaluate the impact of parameter uncertainty on the robustness of the model.

Results: Our analysis shows that by adding finerenone to SoC, patients with mild to severe stage CKD and T2D gain 0.14 quality-adjusted life years (QALYs) compared with SoC alone, mainly due to a reduction in renal and cardiovascular events. The societal costs of these events are considerable (ie, €8481 and €9799 per patient over a lifetime in the finerenone and SoC arm, respectively), showing the relevance of a societal perspective in chronic diseases. Overall, finerenone leads to savings of €2713 per patient over a lifetime. Therefore, the addition of finerenone to SoC emerges as the dominant treatment option when compared with SoC alone. The sensitivity analysis shows that finerenone has a 62.3% chance to be dominant and an 83.8% chance to be cost-effective, considering a willingness-to-pay threshold of €20 000/QALY.

Conclusion: This study highlights the burden that chronic diseases impose on healthcare systems and society, emphasising the relevance of incorporating a societal perspective in cost-effectiveness analyses. The analysis estimates that adding finerenone to SoC treatment for patients with mild to advanced CKD associated with is cost-effective from a healthcare and societal perspective.

Background: Spinal muscular atrophy (SMA) is a rare genetic disease resulting in loss of motor function and, in severe cases (e.g., SMA type 1), infantile death. While treatments like nusinersen and onasemnogene abeparvovec improve prognosis for patients with SMA, costs for these medications can contribute to economic burden.

Objective: Direct costs were compared for onasemnogene abeparvovec, a one-time gene replacement therapy, versus nusinersen, a lifelong therapy, for patients with SMA type 1 and/or three or more survival motor neuron 2 (SMN2) gene copies in the Netherlands.

Methods: A cost comparison analysis model of 1-year incident patient population from the Netherlands was used to compare costs of onasemnogene abeparvovec versus nusinersen for patients eligible for onasemnogene abeparvovec immediately after diagnosis. Multiple analyses were conducted for economic outcomes (e.g., base-case, break-even, deterministic sensitivity, probabilistic sensitivity, scenario analyses).

Results: Cost differences of –€2.9 million (undiscounted) and –€1.5 million (discounted) per patient with SMA type 1 treated with onasemnogene abeparvovec versus nusinersen over a 20-year time horizon were identified (base-case). Reduced costs with onasemnogene abeparvovec versus nusinersen were evident after 8.25 years.

Conclusion: Onasemnogene abeparvovec was less costly than nusinersen after 8.25 years of treatment of patients with SMA type 1 in the Netherlands.

Introduction: Frequent intravitreal injections of anti-vascular endothelial growth factors (VEGFs) for diabetic macular oedema (DMO) pose challenges for healthcare systems, patients, and society. This study assessed the efficacy, safety, resource utilization, and costs of anti-VEGFs from a Dutch societal perspective.

Methods: A systematic literature review and indirect treatment comparison (ITC) compared the efficacy and safety of aflibercept 8 mg with aflibercept 2 mg, ranibizumab, faricimab, and bevacizumab. A Markov model estimated lifetime costs for unilateral or bilateral DMO treatment over 5 years from a Dutch societal perspective. Break-even prices determined the cost-neutral price for each anti-VEGF compared to the least expensive option.

Results: The ITC found no significant differences in efficacy or safety among anti-VEGFs, leading to a cost-minimisation analysis. Over 5 years, the mean number of injections ranged from 15.0 (aflibercept 8 mg, flexible Q16 regimen) to 24.9 (bevacizumab, pro re nata regimen). Bevacizumab had the lowest 5-year per-patient cost (€80,315). Aflibercept 8 mg followed at €83,577, with a break-even price of €560 per injection (− 23% vs. current price). Aflibercept 2 mg (fixed regimen), faricimab, and ranibizumab (treat-and-extend) required price reductions of 74%, 63%, and 71%, respectively, to match bevacizumab.

Conclusion: Despite similar efficacy and safety, differences in treatment burden were identified among the anti-VEGFs, with the more durable regimen of aflibercept 8 mg potentially reducing overall injection frequency compared to current care. Nevertheless, on the basis of current list prices, bevacizumab is the least expensive anti-VEGF for treating DMO. Aflibercept 8 mg, aflibercept 2 mg, faricimab, and ranibizumab could achieve cost-equivalence to bevacizumab if their medication prices were reduced by at least 23%, 74%, 63%, and 71%. These results could support future decision-making of healthcare providers and payers, encompassing aspects of medical costs, healthcare capacity use, and burden on patients as well as the healthcare system as a whole.

Introduction: Methodological choices need to be made during model development. These choices can influence the outcome of a National Institute for Health and Care Excellence (NICE) assessment.

Areas covered: This review aims to identify, assess, and describe possible trends within the methodological aspects of economic evaluations used in NICE assessments of treatments for metastatic breast cancer (mBC). The NICE website was searched to identify technology appraisals submitted between 1 January 2009, and 31 December 2023. In this review methodological aspects are analyzed and discussed in three clusters – input data, model settings, and model outcomes – across the following characteristics: clinical trial information, quality-of-life measures, treatments used, model structure, health states, time horizon, threshold applied, and the NICE recommendations. This review provides a reference for stakeholders who want to understand previous NICE assessments of treatments for mBC, and the settings used in those, which can optimize decisions during model development.

Expert Opinion: Uniformity in the methodological choices made during model development and the economic evaluations can increase transparency, increase comparability, and reduce complexity of the NICE assessment.

Objectives: This study summarizes the concepts that have been used to date to demonstrate societal impact of healthcare interventions and establish an analytical framework to comprehensively organize and describe the different elements of societal impact.

Methods: We conducted a systematic review following Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase, gray literature from ISPOR and Value Balancing Alliance websites, and the reference lists of the identified systematic reviews. Eligible studies assessed the societal impact and described a specific approach. For each included study, we extracted relevant characteristics, such as disease area, methodology, and societal impact metrics.

Results: From a pool of 12 525 studies, 159 were included. Studies broadly examined the societal impact of an intervention at the patients, caregivers, healthcare organizations, and the societal level. Within those categories, we identified a total of 42 different concepts of societal value. We presented a frequency count of those concepts in a hierarchical framework and analyzed the studies qualitatively. We also assessed the literature against the ISPOR value flower.

Conclusion: Our findings reveal recurrent themes and highlight the demand for methodological harmonization. While addressing the limitations of the studied literature from a decision-making perspective, we propose a consensus-driven path forward. Through our research, we emphasize the importance of refining the existing methods, the need for developing a standardized reporting format for future studies, and the importance of developing concise definitions for subjective concepts for societal impact of healthcare interventions.

Background: Stroke is the second leading cause of death worldwide and the third leading cause of death and disability combined. Among ischemic strokes, 25 % to 40 % are classified as cryptogenic, with patent foramen ovale (PFO) identified as a potential underlying cause. PFO is found in 25 % of the general population. Despite the significant occurrence of PFO-associated strokes, the associated costs remain largely unexplored.

Aim: This study aimed to evaluate the annual economic burden of PFO-associated stroke in the US.

Methods: A cost-of-illness study was performed, encompassing the direct and indirect costs of PFO-associated stroke on both society and the healthcare system. The model adopted a top-down approach and a one-year, US societal perspective. A payer perspective and bottom-up costing approach were included as scenario analyses. Data was obtained by a targeted literature review.

Results: The societal model, assuming 32.5 % cryptogenic strokes, incurs an annual cost of over $1.3 billion in the US, with over $1.0 billion coming from new strokes and over $300 million from recurrent strokes. The majority of the costs are indirect—50 % from productivity losses due to premature death and 27 % from other productivity losses. Direct costs constitute 23 % of the total. From the payer perspective, the annual costs for PFO- associated strokes in the US were estimated at $302 million, with hospitalization costs comprising 44 %, followed by prescriptions and outpatient care at 19 % and 16 %, respectively.

Conclusion: The economic burden of PFO-associated strokes in the US is substantial, exceeding $1.3 billion per year. Different types of medical management or surgical treatments for PFO-associated stroke could lead to gains in both costs and health outcomes.

Background: Chikungunya virus (CHIKV), transmitted through Aedes mosquitoes, has witnessed a global surge in distribution and outbreaks, posing a significant public health threat. This study conducted two systematic literature reviews (SLRs) to examine the socio-economic burden associated with chikungunya.

Methods: Two SLRs were conducted employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020) standards. The SLRs covered electronic databases, grey literature, and bibliographic searches. Inclusion criteria were guided by the PICOS (Population, Intervention, Comparator, Outcomes, Study type) framework.

Findings: A total of 34 studies on cost and resource use and 37 studies on health-related quality of life (HRQoL) were included. Direct costs, driven by hospitalization, consultations, diagnostics, and drugs, were frequently reported, with significant variability across studies. Indirect costs, mainly attributed to absenteeism, constituted a substantial portion of the total economic burden. HRQoL studies consistently revealed high pain levels and diminished physical functioning among chikungunya patients, particularly in chronic cases, where these impacts persisted for months to years.

Conclusions: This study highlights the significant economic and public health impact of chikungunya, driven by high treatment costs, productivity losses, and chronic disability. Despite the severity of the disease, limited awareness regarding the severity and economic burden, particularly in resource-limited regions, persists. Our findings underscore the need for targeted public health strategies, standardized management approaches, and increased research to better understand the socio-economic burden of the disease and inform effective interventions.

Background: Given their crucial role in vaccine assessment, National Immunization Technical Advisory Groups (NITAGs) should be considered in the Regulation on Health Technology Assessment (EU HTAR) to maximize the benefits of the EU HTAR for vaccines. This review and perspective piece identifies the gaps arising from NITAGs potential lack of involvement and proposes strategies for involving them.

Methods: A targeted literature and guideline review was conducted to evaluate NITAGs’ current and future role in relation to the EU HTAR. The impact of the EU HTAR on diverse national HTA frameworks was explored in a three-country case study. Recommendations were developed to leverage strengths and address weaknesses to ensure consistent and cohesive vaccine assessments.

Results: The case study revealed potential overlaps between NITAGs and the EU HTAR, particularly regarding horizon scanning and joint scientific consultations. The involvement of NITAGs in national assessments varies, influencing how well joint clinical assessment reports will ultimately align with and be applicable to individual Member States.

Conclusions: Stronger consideration of vaccines within the EU HTAR and NITAG involvement can streamline assessments, reduce duplication, and improve alignment between European and national processes. Strategic actions, including capacity building and collaborations between NITAGs, are key in facilitating this process.