Juan Jose Garcia Sanchez

Uncontrolled hypertension (ucHTN) and treatment-resistant hypertension (trHTN) are associated with a substantial increase in the risk of cardiorenal events and mortality compared with well-controlled hypertension. Treatment strategies that can optimise blood pressure management are urgently needed to improve health outcomes in ucHTN and trHTN populations; health economic models play a key role in assessing the economic value of new and existing treatments and supporting resource allocation. This systematic literature review critically assesses the construct and quality of existing health economic modelling used in the evaluation of management approaches for ucHTN and trHTN, to inform the design and development of future health economic models. This review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist. Searches were conducted on Medline, Embase, EconLit, the Cost-effectiveness Analysis and the International HTA database. Searches were run from inception to May 2024 and re-run in February 2026. Although no date limits were placed on the electronic searches, a limit of 2005 and onwards was applied during study selection. Economic model studies were included if they assessed pharmacological or renal denervation (RDN) interventions for treatment of either ucHTN or trHTN in adult populations. Study eligibility, data extraction and quality assessment using the Drummond checklist were conducted independently by two reviewers. After deduplication, a total of 2754 records were identified. Of these, 2556 did not meet the eligibility criteria after title and abstract screening; 198 full texts were reassessed for eligibility. A total of 21 modelling studies were included: 16 economic evaluations (14 cost-utility analyses, 1 cost-effectiveness analysis and 1 cost-minimization analysis), 4 burden-of-illness studies and 1 budget impact analysis. The majority of studies focused on people with ucHTN and employed a healthcare system perspective. Economic evaluations were based on treatment effects on systolic blood pressure estimated from clinical trials. Several models predicted long-term cardiorenal events and mortality on the basis of published, validated risk equations; however, these risk equations were not developed in populations with ucHTN or trHTN. Although models were generally assessed to be of good quality, models incorporated health-related quality of life and cost data from controlled hypertensive or non-hypertensive populations, rather than those with ucHTN and trHTN. A range of economic models were identified and considered structurally relevant. These models demonstrated that treatment related improvements in blood pressure were cost-effective and robust in scenario analysis. However, important model limitations include their lack of use of population-specific health-related quality-of-life data and risk equations which may result in underestimation of treatment cost effectiveness. To reduce uncertainty and support improved economic modelling that can accurately contextualize emerging therapies for ucHTN and trHTN, future economic model analyses in ucHTN and trHTN need appropriate population health and cost data for these underserved populations.

Introduction Chronic kidney disease (CKD) symptom burden and associated treatments can impact patients’ ability to work and financial well-being. Informal caregivers provide support and may also be affected. This multinational study aimed to characterise the impact of CKD on work productivity and the financial health of patients and caregivers. Methods National cohorts of patients with CKD, caregivers and matched general populations were recruited for Australia, Germany, Egypt, UK, Italy, Taiwan, and the US and surveyed via the Work Productivity and Activity Impairment (WPAI) questionnaire and the Consumer Financial Protection Bureau (CFPB) Financial Well-Being Scale. Financial toxicity was assessed using the COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (FACIT-COST). Results A total of 1303 patients and 674 caregivers were recruited. Compared with matched general populations, patients showed marked impairment in work and daily activities, particularly in presenteeism (difference: min, 7.4%; max, 43.6%) and activity impairment (difference: min, 25.9%; max, 46.4%). Work productivity and activity impairment were greatest among dialysis patients, a trend also observed among caregivers for patients on dialysis. CFPB Financial Well-Being scores indicated poorer financial health in patients versus general populations; variable outcomes were reported by caregivers. Financial toxicity, assessed by FACIT-COST, showed inter-country variation, and was most pronounced in younger, working-age patients. Conclusion The indirect burden of CKD extends beyond clinical costs to include significant financial and work productivity impacts on patients and caregivers, with greater challenges for patients on dialysis. Strategies to prevent CKD progression appear warranted to alleviate burden on financial health and work productivity for patients and caregivers. Graphical Abstract

Introduction Chronic kidney disease (CKD) can negatively impact the quality of life (QoL) of patients and caregivers. Determinants of QoL may vary between countries and healthcare systems. Given the global prevalence of CKD, this multinational study aimed to quantify the impact of CKD on QoL for patients and caregivers worldwide. Methods Patients with CKD, caregivers and matched general population participants were recruited in Australia, Germany, Egypt, Italy, Mexico, Taiwan, the UK and the US. QoL was assessed by patient and caregiver response to EQ-5D-5L, and also to the CarerQol-7D instrument for caregivers. Subgroups were stratified by dialysis-dependence status. Results A total of 1382 patients and 813 caregivers were recruited. Across the surveyed country cohorts, patients reported significantly decreased EQ-5D-5L index scores versus matched general population cohorts (0.57–0.89 vs. 0.93–0.96, respectively; all p < 0.005), with greater impairment in dialysis-dependent patients versus non-dialysis-dependent patients (0.51–0.79 vs. 0.65–0.93, respectively). Patients typically reported significantly greater impairments across all EQ-5D-5L domains versus the general population. Caregivers reported lower mean EQ-5D-5L index scores versus matched general population cohorts (0.73–0.93 vs. 0.93–0.97, respectively). Caregivers reported mean CarerQol-7D index scores between 63.0 and 79.6, with numerically lower scores for caregivers of dialysis-dependent patients. Conclusion This is the first study that characterises the QoL burden of CKD in patients and caregivers on a multinational scale. Patients and caregivers experience a considerable QoL burden, particularly when dialysis-dependent. Strategies to alleviate burden, including prevention of CKD progression, financial and social supports, are required but may vary according to local context. Graphical Abstract

Introduction Developing effective treatments in chronic, progressive diseases like chronic kidney disease (CKD) is challenging because patients may only experience relevant outcomes such as kidney failure after long periods of disease progression. Surrogate endpoints provide a valuable alternative to definitive final patient-relevant outcomes, which may accelerate clinical development processes. However, optimal utilization of surrogate endpoints for reimbursement decisions requires alignment across multiple stakeholders, including health technology assessment (HTA) bodies and reimbursement agencies, who are generally more cautious than regulatory bodies in their acceptance of surrogate endpoint evidence. The aim of this paper is to propose a strategic roadmap to facilitate cross-stakeholder collaboration and support the consideration of surrogate endpoints in regulatory and reimbursement decisions. Methods An international group of experts in surrogate endpoints, reimbursement decisions, and kidney disease formed The REnal Surrogacy accEpTance in Chronic Kidney Disease (RESET CKD) Collaboration. This scientific steering committee held several meetings to develop a roadmap of activities with the aim of enabling the appropriate consideration of surrogate endpoints through structured multi-stakeholder engagement involving regulators, clinicians, HTA bodies, payers, industry, and patients. Results The strategic roadmap focuses on four areas: identifying the need for evidence; engaging stakeholders; collaborating in regulatory and reimbursement processes; and disseminating evidence. The RESET CKD collaboration is currently implementing the roadmap in the field of CKD through collating relevant evidence for a CKD-relevant surrogate endpoint in a scientific playbook, conducting economic evaluations, developing a position paper, and engaging patient groups. Conclusions Disparities between regulatory and reimbursement processes and decisions underscore the need for a structured approach to enhancing transparency, consistency, and timeliness in the use of surrogate endpoint evidence in healthcare decision-making. The roadmap developed through the RESET CKD Collaboration addresses this need and is already demonstrating practical value in its implementation. Although initially focused on CKD, the framework is designed to be transferable to other therapeutic areas. Key challenges remain, including the integration of surrogate endpoints into adaptive pricing models and performance-based agreements.

Aim: This study aimed to project the epidemiology of chronic kidney disease (CKD) and its economic impact in Taiwan from 2022 to 2027 using a microsimulation model.Methods: A virtual representative population of Taiwan was generated using demographic data. The cohort then underwent annual progression using a validated patient‐level microsimulation technique, projecting CKD onset and progression based on various factors, including age, sex, eGFR, and urine albumin level. The model also incorporated associated comorbidities like type 2 diabetes mellitus and hypertension and complications such as heart failure, myocardial infarction, and stroke. Healthcare costs associated with diagnosed CKD and kidney replacement therapy (KRT) were also projected.Results: In 2022, an estimated 10.6% of the total population (2.5 million individuals) in Taiwan were affected by documented or undiagnosed CKD. Without changes in care standards, this prevalence is projected to rise to 12.4% (3.0 million individuals) by 2027, a relative increase of 17.1%. The prevalence of KRT is expected to grow by 7.0% from 2022 to 2027. Complications related to CKD, including heart failure, myocardial infarction, and stroke, are also projected to increase. The annual healthcare costs for diagnosed CKD and KRT are anticipated to rise by 19.7% from TWD $51.96 billion in 2022 to TWD $62.18 billion in 2027.Conclusion: The projections underscore the escalating burden of CKD in Taiwan, emphasising the need for proactive strategies focusing on early diagnosis, effective management, and public awareness to mitigate the disease's socioeconomic impact.

Introduction While the economic and clinical burden of chronic diseases are well documented, their environmental impact remains poorly understood. We developed a framework to estimate the environmental impact of a disease care pathway using chronic kidney disease (CKD) as an example. Methods A life cycle assessment framework was developed for the CKD care pathway and validated by experts. Life cycle stages were characterised for resource utilisation based on a literature review and ecoinvent database inputs, in ten countries. The ReCiPe impact assessment method was used to calculate impacts across multiple environmental dimensions. Results At CKD stage 5, kidney replacement therapies (KRT) have highest impact; emissions ranged between 3.5 and 43.9 kg carbon dioxide equivalents (CO₂e) per session depending on dialysis modality, and 336–2022 kg CO₂e for kidney transplant surgery, depending on donor type. Hospitalisations have a substantial environmental impact: a 1-day intensive care stay had highest impact (66.4–143.6 kg CO₂e), followed by a 1-day hospital stay (28.8–63.9 kg CO₂e) and an 8-h emergency room visit (14.4–27.5 kg CO₂e). Patient transport to and from healthcare sites was a key driver of environmental impact for all life cycle stages, representing up to 99.5% of total CO₂e emissions. Conclusion Full care pathways should be analysed alongside specific healthcare processes. Application of this framework enables quantification of the environmental benefits of preventative medicine and effective management of chronic diseases. For CKD, early diagnosis, and proactive management to reduce the need for KRT and hospitalisations could improve patient outcomes and reduce environmental burden.