Clinical Trial Considerations in Developing Treatments for Early Stages of Common, Chronic Kidney Diseases: A Scientific Workshop Cosponsored by the National Kidney Foundation and the US Food and Drug Administration.

In the past decade, advances in the validation of surrogate end points for chronic kidney disease (CKD) progression have heightened interest in evaluating therapies in early CKD. In December 2020, the National Kidney Foundation sponsored a scientific workshop in collaboration with the US Food and Drug Administration (FDA) to explore patient, provider, and payor perceptions of the value of treating early CKD. The workshop reviewed challenges for trials in early CKD, including trial designs, identification of high-risk populations, and cost-benefit and safety considerations. Over 90 people representing a range of stakeholders including experts in clinical trials, nephrology, cardiology and endocrinology, patient advocacy organizations, patients, payors, health economists, regulators and policy makers attended a virtual meeting. There was consensus among the attendees that there is value to preventing the development and treating the progression of early CKD in people who are at high risk for progression, and that surrogate end points should be used to establish efficacy. Attendees also concluded that cost analyses should be holistic and include aspects beyond direct savings for treatment of kidney failure; and that safety data should be collected outside/beyond the duration of a clinical trial. Successful drug development and implementation of effective therapies will require collaboration across sponsors, patients, patient advocacy organizations, medical community, regulators, and payors.

Cardiorenal disease in the United States: Future health care burden and potential impact of novel therapies.

BACKGROUND: Currently, concerted efforts to identify, prevent, and treat type 2 diabetes mellitus (T2DM), heart failure (HF), and chronic kidney disease (CKD) comorbidities are lacking at the institutional level, with emphasis placed on individual specialties. An integrated approach to tackle T2DM, HF, and CKD within the context of cardiorenal disease has the potential to improve outcomes and reduce costs at the system level. OBJECTIVE: To synthesize published evidence describing the burden of those diagnosed with T2DM, HF, and CKD in the United States as individual discrete chronic conditions, in order to evaluate the potential economic impact of novel therapies in this population. METHODS: We developed a compartmental Markov model with an annual time cycle to model an evolving prevalent US patient population with T2DM, HF, or CKD over the period 2021-2030 (either in isolation or combined). The model was used to explore the potential impact of novel therapies such as sodium-glucose cotransporter 2 inhibitors on future disease burden, by extrapolating the results of relevant clinical trials to representative patient populations. RESULTS: The model estimates that total prevalence across all disease states will have increased by 28% in 2030. Cumulatively, the direct health care cost of cardiorenal disease between 2021 and 2030 is estimated at $4.8 trillion. However, treatment with dapagliflozin has the potential to reduce disease prevalence by 8.0% and estimated cumulative service delivery costs by 3.6% by 2030. CONCLUSIONS: Considering a holistic approach when managing patients with cardiorenal disease offers an opportunity to reduce the disease burden over the next 10 years in the US population. DISCLOSURES: This work was funded by AstraZeneca, which provided support for data analysis. McEwan, Morgan, and Boyce are employees of Health Economics and Outcomes Research Ltd., Cardiff, UK, which received fees from AstraZeneca in relation to this study. Song and Huang are employees of AstraZeneca. Bergenheim is an employee of AstraZeneca and holds AstraZeneca stocks/stock options. Green has no conflicts of interest to declare.

Estimating HIV Management and Comorbidity Costs Among Aging HIV Patients in the United States: A Systematic Review.

BACKGROUND: As life expectancy of patients infected with human immunodeficiency virus (HIV) approaches that of the general population, the composition of HIV management costs is likely to change. OBJECTIVES: To (a) review treatment and disease management costs in HIV, including costs of adverse events (AEs) related to antiretroviral therapy (ART) and long-term toxicities, and (b) explore the evolving cost drivers. METHODS: A targeted literature review between January 2012 and November 2017 was conducted using PubMed and major conferences. Articles reporting U.S. costs of HIV management, acquired immunodeficiency syndrome (AIDS)-defining events, end of life care, and ART-associated comorbidities such as cardiovascular disease (CVD), chronic kidney disease (CKD), and osteoporosis were included. All costs were inflated to 2017 U.S. dollars. A Markov model-based analysis was conducted to estimate the effect of increased life expectancy on costs associated with HIV treatment and management. RESULTS: 22 studies describing HIV costs in the United States were identified, comprising 16 cost-effectiveness analysis studies, 5 retrospective analyses of health care utilization, and 1 cost analysis in a resource-limited setting. Management costs per patient per month, including routine care costs (on/off ART), non-HIV medication, opportunistic infection prophylaxis, inpatient utilization, outpatient utilization, and emergency department utilization were reported as CD4+ cell-based health state costs ranging from $1,192 for patients with CD4 > 500 cells/mm3 to $2,873 for patients with CD4 < 50 cells/mm3. Event costs for AEs ranged from $0 for headache, pain, vomiting, and lipodystrophy to $31,545 for myocardial infarction. The mean monthly per-patient costs for CVD management, CKD management, and osteoporosis were $5,898, $6,108, and $4,365, respectively. Improvements in life expectancy, approaching that of the general population in 2018, are projected to increase ART-related and AE costs by 35.4% and comorbidity costs by 175.8% compared with estimated costs with HIV life expectancy observed in 1996. CONCLUSIONS: This study identified and summarized holistic cost estimates appropriate for use within U.S. HIV cost-effectiveness analyses and demonstrates an increasing contribution of comorbidity outcomes, primarily associated with aging in addition to long-term treatment with ART, not typically evaluated in contemporary HIV cost-effectiveness analyses. DISCLOSURES: This analysis was sponsored by ViiV Healthcare, which had no role in the analyses and interpretation of study results. Ward, Sugrue, Hayward, and McEwan are employees of HEOR Ltd, which received funding from ViiV Healthcare to conduct this study. Anderson is an employee of GlaxoSmithKline and holds shares in the company. Punekar and Oglesby are employees of ViiV Healthcare and hold shares in GlaxoSmithKline. Lopes was employed by ViiV Healthcare at the time of the study and holds shares in GlaxoSmithKline.

Cost-effectiveness of dapagliflozin (Forxiga®) added to metformin compared with sulfonylurea added to metformin in type 2 diabetes in the Nordic countries.

AIMS: The aim of this study was to assess the long-term cost-effectiveness of dapagliflozin (Forxiga(®)) added to metformin, compared with sulfonylurea (SU) added to metformin, in Nordic Type 2 diabetes mellitus (T2DM) patients inadequately controlled on metformin. METHODS: Data from a 52-week clinical trial comparing dapagliflozin and SU in combination with metformin was used in a Cardiff simulation model to estimate long term diabetes-related complications in a cohort of T2DM patients. Costs and QALYs were calculated from a healthcare provider perspective and estimated over a patient's lifetime. RESULTS: Compared with metformin+SU, the cost per QALY gained with dapagliflozin+metformin was €7944 in Denmark, €5424 in Finland, €4769 in Norway, and €6093 in Sweden. Metformin+dapagliflozin was associated with QALY gains ranging from 0.236 in Norway to 0.278 in Sweden and incremental cost ranging from €1125 in Norway to €1962 in Denmark. Results were robust across both one-way and probabilistic sensitivity analyses. Results were driven by weight changes associated with each treatment. CONCLUSIONS: Results indicate that metformin+dapagliflozin is associated with gains in QALY compared with metformin+SU in Nordic T2DM patients inadequately controlled on metformin. Dapagliflozin treatment is a cost-effective treatment alternative for Type 2 diabetes in all four Nordic countries.

Cost-effectiveness of saxagliptin (Onglyza®) in type 2 diabetes in Sweden.

AIM: The objective of this study was to investigate the cost-effectiveness of saxagliptin (Onglyza(®)), a DPP-4 inhibitor, plus metformin compared with a sulphonylurea (SU) (Glipizide) plus metformin in Swedish patients not well controlled on metformin alone. METHODS: Data from a 52-week clinical trial comparing saxagliptin and glipizide in combination with metformin was used in a simulation model to estimate long term complications in a cohort of type 2 diabetes patients. The model estimates the incidence of microvascular and macrovascular complications, diabetes-specific mortality, all-cause mortality, and ultimately, costs and quality-adjusted life years (QALYs) associated with the investigated treatment strategies. Costs and QALYs were estimated for a lifetime time horizon. RESULTS: Compared with SU+metformin, the cost per QALY gained with saxagliptin+metformin is approximately SEK 91,000. Patients on saxagliptin+metformin gain 0.10 QALYs on average, at an incremental cost of around SEK 9500. The cost-effectiveness results were robust to various sensitivity analyses. CONCLUSIONS: This study demonstrates that, over a patient's lifetime, the addition of saxagliptin to metformin is associated with improvements in quality-adjusted life years compared with SU in patients with type 2 diabetes. Saxagliptin treatment is a cost-effective treatment alternative for type 2 diabetes in patients not well-controlled on metformin alone.