IntroductionThe significant burden of chronic kidney disease (CKD) is not recognized as a global public health priority, although policies aimed at delaying progression to later stages are required. Therefore, there is need for a holistic disease model to inform decision making those accounts for the multidimensional impact of CKD, and the interrelated factors that modulate progression.MethodsIMPACT CKD is a microsimulation model that simulates CKD progression and incorporates the effect of clinical events and comorbidities. CKD status is assigned using estimated glomerular filtration rate (eGFR) and albuminuria levels, and CKD progression is predicted by an annual eGFR decline rate. The model projects clinical, health care resource use, economic, patient, societal, and environmental burdens from 2022 to 2032. During development, face, technical, and external validity were evaluated, with calibration conducted to population data. Further, cross-validation was conducted against 2 published models. The United Kingdom (UK) was selected as the case study for validation.ResultsA 7.7% increase in the CKD population by 2032 was predicted, with increasing numbers of patients with CKD stage 3 to 5 (21.7%), dialysis (75.3%), and transplantation (58.7%). The increase of patients on renal replacement therapy (RRT) results in an increase of 75% across freshwater use, fossil fuel depletion, and CO2 emissions over the next decade, and an estimated cost of £1.95 billion in 2032. Projections reflect validated findings from other models.ConclusionThe IMPACT CKD model is a robust simulation that delivers validated forecasts of the holistic CKD burden, which can support evaluation of diverse health policies and treatment strategies.
Abstract Background and Aims Chronic kidney disease (CKD) is a growing health problem in Europe exacerbated by aging and the rise of comorbidities such as diabetes mellitus (DM) and hypertension (HTN). Patients with CKD are often multi-morbid and commonly present with cardiovascular (CV) complications. While CV events including myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF) occur more often in patients with advanced CKD, patients with early-stage CKD are also at increased risk. Patients with CKD also experience an increased risk of CV-related mortality, with many patients dying from CV events prior to kidney failure and renal replacement therapy. CV events also present a significant burden to clinicians and healthcare systems due to the high costs and resource use required to manage and treat them. Despite this multidimensional burden, CKD is currently underdiagnosed in Europe, and CKD screening and treatment are rarely included in public health strategies to improve mortality and health outcomes. This study aims to explore the impact of targeted CKD screening followed by guideline-directed therapy in high-risk populations on CV event occurrence and associated treatment costs across Europe. Method The IMPACT CKD microsimulation model simulates CKD progression, CV events, and comorbidities. CKD status is assigned based on estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio levels (UACR), and CKD progression is predicted by an annual eGFR decline rate. The model was used to compare two scenarios in four country populations (Germany, Netherlands, Spain, United Kingdom [UK]): 1) targeted screening for people with DM and/or HTN followed by optimal compliance to guideline-directed therapy and 2) current practice (no screening, underdiagnosis, low treatment rates). Annual targeted screening assumed both eGFR and UACR testing. Treatment initiation for people diagnosed with CKD was based on Kidney Disease Improving Global Outcomes guidelines with a 90% compliance assumed to approximate maximum clinical benefit. Therapies were assumed to have a multiplicative treatment effect on eGFR decline and CV events. Current practice assumed observed diagnosis rates without screening and observed treatment rates in each country. For both scenarios, the model projected incidence of CV events and associated management costs in year 10 (2032) and cumulatively over the 10 simulated years (2023-2032). Results Results compare the targeted screening followed by guideline-directed treatment scenario to continuation of current practices for Germany, Netherlands, Spain, and UK (Table 1). The timely diagnosis of patients with CKD and effective treatment was associated with a reduction of 46.7-53.3%, 38.9-41.6%, and 42.1-50.5% in the number of MI, stroke, and HHF events, respectively in 2032 across the four countries. These decreases in the number of CV events were accompanied by proportional reductions in costs to treat the events. Additionally, this policy approach resulted in declines in the cumulative 10-year CV event development and associated healthcare costs, with MI having the largest reductions (40.6-47.2%), followed by HHF (37.4-43.0%), and stroke (29.8-36.1%) across the four countries. Conclusion This study illustrated that early identification of high-risk patients with CKD coupled with guideline-directed treatment would yield substantial clinical and economic benefits from reducing CV events across all four European countries. Fewer MI, stroke, and HHF events were projected in patients with CKD in both 2032 and cumulatively from 2023 to 2032 due to delayed disease progression following effective interventions. Driven by the reduced clinical burden, lower healthcare costs for CV event management were also predicted. These findings support the need for the adoption of policies for early diagnosis and treatment of CKD to slow disease progression and mitigate the growing CV disease burden among patients with CKD and for health systems. Future studies should explore the costs associated with targeted CKD screening and the guideline-directed pharmacological therapies for CKD.
Abstract Background and Aims Despite the rising and substantial burden of chronic kidney disease (CKD), there is a lack of recognition of CKD as a health priority in Europe. This contributes to underdiagnosis of CKD despite the potential for early detection and effective intervention to delay progression to late-stages (associated with costly and resource-intensive renal replacement therapy [RRT; i.e., dialysis and transplantation]). Further, diagnosed patients are undertreated when compared to current and upcoming CKD guidelines, leading to increased risk for progression to RRT and cardiovascular (CV) or other events. Early detection and intervention in high-risk populations, such as those with diabetes mellitus (DM) and hypertension (HTN) have shown cost-effectiveness; however, the broader implications of these strategies on CKD progression and clinical outcomes in a European context remains underexplored. Our study aims to illustrate the clinical benefit of targeted screening followed by an optimal compliance to guideline-directed treatment use to provide insight into potential CKD policies across Europe. Method Four country populations (Germany, Netherlands, Spain, United Kingdom [UK]) were simulated for 10-years (baseline: 2022; simulated years: 2023-2032) using the validated IMPACT CKD model to compare two scenarios: targeted screening for people with DM and/or HTN followed by 90% compliance to guideline-directed therapy versus current practice (i.e., underdiagnosis without screening and low treatment rates). Annual targeted screening was modelled using estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing. Initiation of therapies for people with diagnosed CKD was based on Kidney Disease Improving Global Outcomes guidelines. A 90% compliance to guideline-directed therapies was assumed to approximate maximum clinical benefit. Current practice was modelled based on the observed diagnosed rate without screening and the observed treatment rate in each country. The incremental population initiated on recommended therapies were modelled to experience a multiplicative treatment effect on GFR decline, CV events, and acute kidney injury (AKI) events. The model projected CKD and RRT prevalence, incidence of CV and AKI events with results shown for year 10 (2032), as well as cumulative all-cause mortality over the simulated 10-years. Results Results compare the high-risk population screening followed by guideline-directed treatment scenario to continuation of current practices for the four countries (Fig. 1). The identification of undiagnosed CKD, as well as lower rates of progression due to guideline-directed treatment was associated with a small rise in the number of total CKD patients, with increases in stage 1-2 by 3.5% to 5.0%, and stage 3-5 by 0.2% to 1.2%. There was a reduction in the number of undiagnosed CKD stage 1-2 patients by 49.2% to 71.6%, and stage 3-5 by 60.2% to 69.8%. The largest reductions were predicted for CV events (44.6% to 49.1%) followed by dialysis (22.6% to 41.9%). The strategy resulted in a decrease in cumulative 10-year all-cause mortality between 4.5% to 9.1% in CKD patients. Conclusion The study predicted significant clinical benefits from targeted CKD screening followed by guideline-directed interventions across all four European countries. Notably, this approach was forecasted to reduce undiagnosed CKD cases, dialysis, CV events, and mortality. These findings underscore the potential of acting earlier on CKD to mitigate the future CKD burden.
Abstract Background and Aims Chronic kidney disease (CKD) is a major source of morbidity and mortality, with an increasing incidence and prevalence worldwide. Patients with CKD experience diminished quality of life associated with increased risk of cardiovascular (CV) events, acute kidney injury (AKI), and reduced renal function. Late-stage CKD (stage 5) is also associated with significant economic burden related to renal replacement therapy (RRT). Public health and policy planning should consider the broader burden of CKD, including its societal and environmental burden, in addition to its clinical impacts and direct costs. Hence, IMPACT CKD aims to quantify the clinical, economic, humanistic, societal, and environmental burden of CKD in the United Kingdom (UK). Method A patient-level simulation model was developed to simulate the UK population using parameter data from published literature, national statistics, and health surveys. Individuals were assigned key characteristics associated with CKD, such as estimated glomerular filtration rate (eGFR), albuminuria, co-morbidities (e.g., diabetes, hypertension, heart failure), and prior CV events (e.g., myocardial infarction and stroke). Individuals were categorized as not having CKD (i.e., non-CKD) or CKD stage 1, 2, 3a, 3b, 4 or 5, based on their eGFR and albuminuria levels. Among those with CKD, patients were either classified as diagnosed or undiagnosed. Progression through the CKD stages was predicted by the simulated patient's annual eGFR rate of decline. Risk of CV and AKI events, as well as co-morbidity development were also considered in the model. Clinical progression and outcomes for the CKD population were simulated over 10 years. CKD prevalence was projected by stage and diagnosis status, as well as associated CKD and RRT costs, productivity losses from patients and caregivers, and environmental impacts as determined by CO2 emissions. Extensive validation and calibration was conducted. Results From 2022 to 2032, the prevalence of CKD is expected to increase by 4% from 8.27 million to 8.61 million people in the UK. Growth in the CKD population is driven by eGFR decline and increases in albuminuria, related to kidney function decline and AKI as the model population ages. In 2032, the prevalence of CKD by stage is projected to be 30.36%, 21.07%, 29.78%, 11.86%, 4.15%, and 2.78% in stage 1, 2, 3a, 3b, 4, and 5 patients, respectively. The diagnosed CKD population is projected to be 32.43% of the total CKD population and is primarily composed of CKD stage 3a/b, 4, and 5 patients in 2032. Patients with CKD receiving RRT are projected to increase by 44% from 73,365 in 2022 to 105,860 in 2032. The increase in late-stage CKD population is associated with an increase in RRT costs from £1.09 billion in 2022 to £1.85 billion in 2032. Over the 10-year time horizon, CKD is projected to result in 81.60 million missed workdays in diagnosed patients with CKD, and 11.89 million missed workdays by caregivers of patients with CKD. Environmental impacts equivalent to 1.35 million tonnes of CO2 emissions for patients receiving in-centre hemodialysis are predicted; however, the total environmental impact would likely be larger if the total CKD care pathway was included. Conclusion The IMPACT CKD model forecasts the prevalence and burden of CKD to remain high in the UK over the next ten years. In addition to the significant clinical burden and direct costs, CKD was also associated with extensive productivity loss and detrimental environmental impact. The model provides a validated framework for testing the sensitivity of the projections to data uncertainty, thereby identifying areas for further research.
Introduction The growing burden of chronic kidney disease (CKD) in Brazil is increasingly evident, marked by its significant contributions to mortality rates and healthcare costs. Managing CKD, especially through renal replacement therapy (RRT), demands substantial resources. To enhance healthcare decision-making, a thorough examination of the relationship between the rising prevalence of CKD and its clinical and economic impacts is crucial. Methods We developed a patient-level simulation model to project the natural history of CKD, defined as the IMPACT CKD. This model integrated factors such as acute kidney injury, cardiovascular events, and comorbidities, and aimed to assess CKD’s clinical, humanistic, and economic impact on the healthcare system. It forecasted the burden of CKD over the next decade (2023 to 2032). This projection is pivotal to derive the burden of CKD for health technology assessment (HTA) evaluations. Validation was conducted against Brazil’s demographic data and cross-validated with the Inside CKD model. Results The IMPACT CKD forecast a rapid increase of CKD population in Brazil, outpacing the growth of the general population. Specifically, there is an expected 6.9 percent increase in stages 3 to 5 CKD, leading to a higher demand for dialysis (projected 370,000 cases in 2032) and transplants (projected 115,000 cases in 2032). A significant increase in cardiovascular CKD-related events (+100.6%) and mortality (+67.8%) is expected. In 2032, it is projected 15 million CKD patients will be in stages 1 to 2, and 12.7 million in stages 3 to 5. CKD-related healthcare costs will represent 25.7 percent of Brazil’s healthcare budget, and dialysis will reach USD2.7 billion in annual costs. Conclusions IMPACT CKD predicts an increasing CKD prevalence and an alarming rise in stages 3 to 5 and RRT, including thousands of premature deaths, and a substantial economic burden on the Brazilian healthcare system. This data could be informative for healthcare decision-makers when choosing strategy to reduce the impact of CKD in Brazil.
To assess the cost-effectiveness of tezepelumab as add-on maintenance therapy compared with standard of care (SoC) for the treatment of patients with severe asthma in Canada.A cost utility analysis was conducted using a Markov cohort model with five health states ("controlled asthma", "uncontrolled asthma", "previously controlled asthma with exacerbation", "previously uncontrolled asthma with exacerbation", and "death"). Tezepelumab plus SoC was compared to SoC (high-dose inhaled corticosteroids plus long-acting beta agonist) using efficacy estimates derived from the NAVIGATOR (NCT03347279) and SOURCE (NCT03406078) trials. The model included the costs of therapy, administration, resource use for disease management, and adverse events. Utility estimates were calculated using a mixed-effects regression analysis of the NAVIGATOR and SOURCE trials. A Canadian public payer perspective was used with a 50-year time horizon, a 1.5% annual discount rate, and the base case analysis was conducted probabilistically. A key scenario analysis assessed the cost-effectiveness of tezepelumab compared with currently reimbursed biologics informed by an indirect treatment comparison.The base case analysis suggested that tezepelumab plus SoC was associated with a quality-adjusted life-year (QALY) gain of 1.077 compared with SoC alone at an incremental cost of $207,101 (2022 Canadian dollars), resulting in an incremental cost-utility ratio of $192,357/QALY. The key scenario analysis demonstrated that tezepelumab was dominant against all currently reimbursed biologics, with higher incremental QALYs (ranging from 0.062 to 0.407) and lower incremental costs (ranging from -$6,878 to -$1,974). Additionally, when compared against currently reimbursed biologics in Canada, tezepelumab had the highest probability of being cost-effective across all willingness-to-pay (WTP) thresholds.Tezepelumab provided additional life years and QALYs at additional cost compared with SoC in Canada. In addition, tezepelumab dominated (i.e. more effective, less costly) the other currently reimbursed biologics.
Aims Fracture liaison services (FLS) use a multidisciplinary approach to treat patients who have experienced an osteoporotic fracture to reduce the risk of subsequent fractures. To date, there has been minimal FLS implementation in Latin America where fractures continue to be undertreated. This study aims to estimate the number of fractures averted, bed days avoided, and costs saved resulting from universal FLS implementation in Brazil, Mexico, Colombia, and Argentina.Materials and methods A calculator was developed to estimate the annual benefits of FLS programs in Brazil, Mexico, Colombia, and Argentina from a public hospital perspective. It was assumed all patients with a hip, vertebral, or wrist fracture were referred to an FLS program. Country-specific data were obtained from a previous systematic review and interviews with osteoporosis experts. Hospitalization and post-hospitalization costs were expressed in 2019 USD without discounting. Costs of FLS implementation were not considered.Results In 2019, the number of FLS patients prevented from having a subsequent hip, vertebral, or wrist fracture was estimated as 15,607 in Brazil, 8,168 in Mexico, 5,190 in Argentina, and 2,435 in Colombia with total bed days saved of 142,378 in Brazil, 75,877 in Mexico, 52,301 in Argentina, and 21,725 in Colombia. The annual cost savings in 2019 were highest in Argentina (28.1 million USD), followed by Mexico (19.6 million USD), Brazil (7.64 million USD) and Colombia (3.04 million USD). Over five years (2019–2023) the cumulative cost savings were 145 million USD in Argentina, 106 million USD in Mexico, 40.5 million USD in Brazil, and 16.1 million USD in Colombia.Conclusion Universal FLS implementation in Brazil, Mexico, Colombia, and Argentina was predicted to prevent 31,400 fractures, avoid 292,281 bed days, and save 58.4 million USD in 2019, though caution is warranted in the interpretation of these results due to high uncertainty. Increased implementation of FLS programs in Latin American countries may help to realize these benefits.
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