Cost Effectiveness of Endovascular Ultrasound Renal Denervation in Patients with Resistant Hypertension.

BACKGROUND: Resistant hypertension (rHTN) is defined as blood pressure (BP) of ≥ 140/90 mmHg despite treatment with at least three antihypertensive medications, including a diuretic. Endovascular ultrasound renal denervation (uRDN) aims to control BP alongside conventional BP treatment with antihypertensive medication. This analysis assesses the cost effectiveness of the addition of the Paradise uRDN System compared with standard of care alone in patients with rHTN from the perspective of the United Kingdom (UK) health care system. METHODS: Using RADIANCE-HTN TRIO trial data, we developed a state-transition model. Baseline risk was calculated using Framingham and Prospective Cardiovascular Münster (PROCAM) risk equations to estimate the long-term cardiovascular risks in patients treated with the Paradise uRDN System, based on the observed systolic BP (SBP) reduction following uRDN. Relative risks sourced from a meta-analysis of randomised controlled trials were then used to project cardiovascular events in patients with baseline SBP ('control' patients); utility and mortality inputs and costs were derived from UK data. Costs and outcomes were discounted at 3.5% per annum. Modelled outcomes were validated against trial meta-analyses and the QRISK3 algorithm and real-world evidence of RDN effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty surrounding the model inputs and sensitivity of the model results to changes in parameter inputs. Results were reported as incremental cost-effectiveness ratios (ICERs). RESULTS: A mean reduction in office SBP of 8.5 mmHg with uRDN resulted in an average improvement in both absolute life-years (LYs) and quality-adjusted life-years (QALYs) gained compared with standard of care alone (0.73 LYs and 0.67 QALYs). The overall base-case ICER with uRDN was estimated at £5600 (€6500) per QALY gained (95% confidence interval £5463-£5739 [€6341-€6661]); modelling demonstrated > 99% probability that the ICER is below the £20,000-£30,000 (€23,214-€34,821) per QALYs gained willingness-to-pay threshold in the UK. Results were consistent across sensitivity analyses and validation checks. CONCLUSIONS: Endovascular ultrasound RDN with the Paradise system offers patients with rHTN, clinicians, and healthcare systems a cost-effective treatment option alongside antihypertensive medication.

Recent advances in addressing the market failure of new antimicrobials: Learnings from NICE's subscription-style payment model.

Background: Antimicrobial resistance (AMR) is a growing threat to global health. With pathogenic bacteria inevitably becoming more resistant to existing antimicrobials, mortality and costs due to AMR will significantly increase over the next few decades if adequate action is not taken. A major challenge in addressing AMR is the lack of financial incentives for manufacturers to invest in developing new antimicrobials. This is partly because current approaches in health technology assessment (HTA) and standard modeling methods fail to capture the full value of antimicrobials. Aim: We explore recent reimbursement and payment frameworks, particularly pull incentives, aimed to address the market failures in antimicrobials. We focus on the "subscription-style" payment model recently used in the UK and discuss the learnings for other European countries. Methods: A pragmatic literature review was conducted to identify recent initiatives and frameworks between 2012 and 2021, across seven European markets. The National Institute for Health and Care Excellence (NICE) technology appraisals for cefiderocol and for ceftazidime with avibactam were reviewed to evaluate how the new UK model has been applied in practice and identify the key challenges. Conclusion: The UK and Sweden are the first European countries to pilot the feasibility of implementing pull incentives through fully and partially delinked payment models, respectively. The NICE appraisals highlighted the complexity and large areas of uncertainty of modeling antimicrobials. If HTA and value-based pricing are part of the future in tackling the market failure in AMR, European-level efforts may be needed to overcome some of the key challenges.

Varying Willingness to Pay Based on Severity of Illness: Impact on Health Technology Assessment Outcomes of Inpatient and Outpatient Drug Therapies in The Netherlands.

OBJECTIVES: Since 2015, Zorginstituut Nederland (ZIN) has linked disease severity ranges of 0.10 to 0.40, 0.41 to 0.70, and 0.71 to 1.00 with willingness-to-pay (WTP) reference values of €20 000, €50 000, and €80 000 per quality-adjusted life year gained, respectively. We sought to review whether these changes have affected ZIN health technology assessment (HTA) outcomes for specialist and outpatient drugs. METHODS: ZIN recommendations for specialist and outpatient drugs published between January 1, 2012, and December 31, 2020, that included a pharmacoeconomic report were reviewed. Data were extracted on disease severity, proportional shortfall calculation, reported WTP reference value, outcomes related to the cost-effectiveness of the product, budget impact, and ZIN's recommendation including rationale for their advice. RESULTS: A total of 51 HTAs were included. Of the 20 HTAs published before June 2015, a total of 9 received positive recommendations, 7 were conditionally reimbursed, and 4 received negative recommendations. None reported WTP reference values. Of the 31 evaluations published after June 2015, a total of 4 products received positive recommendations, 1 was conditionally approved, and 26 received negative recommendations initially. Most products (65%) reported disease severity to be >0.70. CONCLUSIONS: Since 2015, most products have fallen within the highest category of disease severity. Although pre-2015 outcomes were varied, post-2015 products overwhelmingly received negative recommendations, and the proportion of products for which price negotiations were recommended has increased. These differences in outcomes may result from the introduction of an explicit WTP reference value, whether or not in combination with the severity-adjusted ranges, but may also reflect other national policy changes in 2015.

Cost Effectiveness of Durvalumab in Unresectable Stage III NSCLC: 4-Year Survival Update and Model Validation from a UK Healthcare Perspective.

BACKGROUND: In the phase III PACIFIC study, durvalumab improved survival versus placebo in patients with unresectable stage III non-small-cell lung cancer (NSCLC) whose disease had not progressed after platinum-based concurrent chemoradiotherapy. The appraisal by the UK's National Institute for Health and Care Excellence (NICE) included a cost-effectiveness analysis based on an early data readout from PACIFIC [March 2018 data cut-off (DCO); median follow-up duration 25.2 months; range 0.2-43.1]. Uncertainties regarding long-term survival outcomes with durvalumab led to some challenges in estimating the cost effectiveness of this therapy. OBJECTIVE: Here, we validate the survival extrapolations used in the original company base-case analysis by benchmarking them against updated survival data from the 4-year follow-up analysis of PACIFIC (i.e. approximately 4 years after the last patient was randomised; March 2020 DCO; median follow-up duration 34.2 months; range 0.2-64.9). Moreover, we update the original analysis with these more mature survival data to examine the consistency of key economic outputs with the original analysis. METHODS: The original analysis used a semi-Markov (state-transition) approach and was based on patients whose tumours expressed programmed cell death-ligand 1 on ≥ 1% of cells (to reflect the European licence for durvalumab). We benchmarked the survival extrapolations used in the original company base-case analysis against survival data from the 4-year follow-up of PACIFIC and updated the cost-effectiveness analysis with these more mature survival data. Early deaths avoided by the adoption of durvalumab into the UK Cancer Drugs Fund (CDF) in March 2019 were estimated using the 4-year follow-up survival data and an assumed uptake of 125 patients/year (lower estimate) and 367 patients/year (higher estimate). RESULTS: The original company base-case analysis had a good visual fit with the observed overall survival (OS) distribution for the durvalumab arm and accurately predicted the 48-month OS rate (predicted 55%; observed 55%); by comparison, the fit was less precise for the placebo arm, for which the analysis underestimated the 48-month OS rate (predicted 32%; observed 38%). In the updated company base-case analysis, durvalumab yielded 2.51 incremental quality-adjusted life-years (QALYs) (- 0.43 vs. the original company base-case analysis), corresponding to an incremental cost-effectiveness ratio of £22,665/QALY (+£3298 vs. the original analysis), which falls within the upper bound of NICE's willingness-to-pay threshold (£30,000/QALY gained). We estimate that between 31 and 91 early patient deaths may have been avoided by the adoption of durvalumab into the CDF. CONCLUSIONS: These findings reinforce the patient benefit observed with durvalumab in unresectable stage III NSCLC, support the routine use and cost effectiveness of this therapy, and demonstrate how appropriate modelling can inform the early adoption of therapies by payers to achieve patient benefit.

Based on the results of a clinical trial, the European Medicines Agency approved durvalumab for the treatment of adults with a specific type of advanced lung cancer whose tumours cannot be removed surgically and whose disease has not progressed after chemotherapy and radiotherapy. The UK's National Institute for Health and Care Excellence (NICE) invites companies to submit cost-effectiveness analyses to help with decision making about adopting new therapies. The company included an analysis based on early trial data that suggested durvalumab was cost effective compared with other previous treatments. As patients in the study at the time of the initial submission to NICE were only followed for approximately 2 years, the long-term survival benefit that could be achieved with durvalumab was uncertain. Therefore, NICE recommended durvalumab for use within the Cancer Drugs Fund (CDF) to allow patients to access the drug while more data were being collected. Here, we demonstrate that the original cost-effectiveness model accurately predicted the rates of long-term survival for patients receiving durvalumab and that durvalumab remains a cost-effective use of healthcare resources based on recently published data from the trial (which added approximately 2 further years of follow-up). Moreover, we estimate that adopting durvalumab into the CDF may have avoided 31­91 early patient deaths from lung cancer. These findings support NICE's early decision to make durvalumab available within the CDF and the adoption of durvalumab for routine use within the UK national health service.

Cost-Effectiveness of Durvalumab After Chemoradiotherapy in Unresectable Stage III NSCLC: A US Healthcare Perspective.

BACKGROUND: Durvalumab was approved by the FDA in February 2018 for patients with unresectable stage III NSCLC that has not progressed after platinum-based concurrent chemoradiotherapy (cCRT), and this regimen is the current standard of care. The objective of this study was to examine the cost-effectiveness of durvalumab following cCRT versus cCRT alone in patients with locally advanced, unresectable stage III NSCLC. METHODS: A 3-state semi-Markov model was used. Modeling was performed in a US healthcare setting from Medicare and commercial payer perspectives over a 30-year time horizon. Clinical efficacy (progression-free and post progression survival) and utility inputs were based on PACIFIC study data (ClinicalTrials.gov identifier: NCT02125461; data cutoff March 22, 2018). Overall survival extrapolation was validated using overall survival data from a later data cutoff (January 31, 2019). The main outcome was the incremental cost-effectiveness ratio (ICER) of durvalumab following cCRT versus cCRT alone, calculated as the difference in total costs between treatment strategies per quality-adjusted life-year (QALY) gained. RESULTS: In the base-case analysis, durvalumab following cCRT was cost-effective versus cCRT alone from Medicare and commercial insurance perspectives, with ICERs of $55,285 and $61,111, respectively, per QALY gained. Durvalumab was thus considered cost-effective at the $100,000 willingness-to-pay (WTP) threshold. Sensitivity analyses revealed the model was particularly affected by variables associated with subsequent treatment, although no tested variable increased the ICER above the WTP threshold. Scenario analyses showed the model was most sensitive to assumptions regarding time horizon, treatment effect duration, choice of fitted progression-free survival curve, subsequent immunotherapy treatment duration, and use of a partitioned survival model structure. CONCLUSIONS: In a US healthcare setting, durvalumab was cost-effective compared with cCRT alone, further supporting the adoption of durvalumab following cCRT as the new standard of care in patients with unresectable stage III NSCLC.

Cost Effectiveness of Secukinumab for the Treatment of Active Ankylosing Spondylitis in the UK.

OBJECTIVE: To determine the cost effectiveness of secukinumab, a fully human interleukin-17A inhibitor, for adults in the UK with active ankylosing spondylitis (AS) who have not responded adequately to previous treatment with conventional care (CC; biologic-naïve population) or previous biologic therapy (biologic-experienced population). PERSPECTIVE AND SETTING: UK National Health Service (NHS). METHODS: The model was structured as a 3-month decision tree leading into a Markov model. Comparators were licensed tumour necrosis factor inhibitors (including available biosimilars) and CC in the biologic-naïve and biologic-experienced populations, respectively. Clinical parameters captured treatment response, short-term disease activity and patient functioning, as well as long-term structural disease progression. Utilities were derived from secukinumab trial data. List prices were used for all drugs. The cost year was 2017 and costs and outcomes were discounted at 3.5%. RESULTS: In the biologic-naïve population, secukinumab dominated adalimumab and certolizumab pegol. Incremental cost-effectiveness ratios (ICERs) versus other comparators were either below £10,000 per quality-adjusted life-year (QALY) gained or south-west ICERs that implied cost effectiveness of secukinumab. In biologic-experienced patients, the ICER for secukinumab versus CC was £4927 per QALY gained. Treatment response rates, short-term treatment effects, long-term radiographic progression and biologic acquisition costs were key model drivers. Scenario analysis found results to be robust to changes in model structural assumptions. Probabilistic analysis identified greater uncertainty in results in the biologic-naïve population. CONCLUSIONS: Even at list price, secukinumab appears to represent a cost-effective use of NHS resources for biologic-naïve and biologic-experienced patients with active AS. Further research on long-term radiographic progression outcomes would be valuable for future cost-effectiveness analyses in AS.

Cost-effectiveness analysis of bortezomib in combination with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (VR-CAP) in patients with previously untreated mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin's lymphoma. Bortezomib is the first product to be approved for the treatment of patients with previously untreated MCL, for whom haematopoietic stem cell transplantation is unsuitable, and is used in combination with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (VR-CAP). The National Institute of Health and Care Excellence recently recommended the use of VR-CAP in the UK following a technology appraisal. We present the cost effectiveness analysis performed as part of that assessment: VR-CAP versus the current standard of care regimen of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in a UK setting. METHODS: A lifetime economic model was developed with health states based upon line of treatment and progression status. Baseline patient characteristics, dosing, safety and efficacy were based on the LYM-3002 trial. As overall survival data were immature, survival was modelled by progression status, and post-progression survival was assumed equal across arms. Utilities were derived from LYM-3002 and literature, and standard UK cost sources were used. RESULTS: Treatment with VR-CAP compared to R-CHOP gave an incremental quality-adjusted life year (QALY) gain of 0.81 at an additional cost of £16,212, resulting in a base case incremental cost-effectiveness ratio of £20,043. Deterministic and probabilistic sensitivity analyses showed that treatment with VR-CAP was cost effective at conventional willingness-to-pay thresholds (£20,000-£30,000 per QALY). CONCLUSIONS: VR-CAP is a cost-effective option for previously untreated patients with MCL in the UK.

Cost-effectiveness of renal denervation therapy for the treatment of resistant hypertension in The Netherlands.

OBJECTIVES: Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the perspective of the healthcare payer in The Netherlands. METHODS: A previously constructed Markov state-transition model was adapted and updated with costs and utilities relevant to the Dutch setting. The cost-effectiveness of RDN was compared with standard of care (SoC) for patients with resistant hypertension. The efficacy of RDN treatment was modeled as a reduction in the risk of cardiovascular events associated with a lower systolic blood pressure (SBP). RESULTS: Treatment with RDN compared to SoC gave an incremental quality-adjusted life year (QALY) gain of 0.89 at an additional cost of €1315 over a patient's lifetime, resulting in a base case incremental cost-effectiveness ratio (ICER) of €1474. Deterministic and probabilistic sensitivity analyses (PSA) showed that treatment with RDN therapy was cost-effective at conventional willingness-to-pay thresholds (€10,000-80,000/QALY). CONCLUSION: RDN is a cost-effective intervention for patients with resistant hypertension in The Netherlands.

Quality of life improvement in patients treated with degarelix versus leuprorelin for advanced prostate cancer.

PURPOSE: We used responses to questionnaires included in the CS21 degarelix trial and published mapping algorithms to address the paucity of evidence for health related quality of life in patients with advanced hormone dependent prostate cancer treated with degarelix. MATERIALS AND METHODS: We measured health related quality of life in 610 patients enrolled in the CS21 trial using SF-12® and EORTC QLQ-C30. Based on responses to these questionnaires we estimated patient utility using 4 published mapping algorithms. Utility was tested for relationships with aspects of the symptom and side effect burden that may be affected by degarelix treatment, that is prostate specific antigen progression and adverse events. RESULTS: Average utility in patients without prostate specific antigen progression or an adverse event was 0.742, similar to previously published utilities for nonprogressed prostate cancer states. Prostate specific antigen progression was associated with a utility decrement of between 0.062 and 0.134 depending on the mapping algorithm used. Of adverse events considered in our analysis musculoskeletal events were associated with the greatest effects on patient utility with a decrement of between 0.029 and 0.086. The 4 mapping algorithms generated similar utility estimates, although values derived from SF-12 were consistently lower than those derived from EORTC QLQ-C30. CONCLUSIONS: Prostate specific antigen progression status and the incidence of treatment and disease related adverse events result in significant decrements to patient health related quality of life. By slowing prostate specific antigen progression degarelix may improve patient utility and the health related quality of life burden.

Is adding HCV screening to the antenatal national screening program in Amsterdam, the Netherlands, cost-effective?

INTRODUCTION: Hepatitis C virus (HCV) infection can lead to severe liver disease. Pregnant women are already routinely screened for several infectious diseases, but not yet for HCV infection. Here we examine whether adding HCV screening to routine screening is cost-effective. METHODS: To estimate the cost-effectiveness of implementing HCV screening of all pregnant women and HCV screening of first-generation non-Western pregnant women as compared to no screening, we developed a Markov model. For the parameters of the model, we used prevalence data from pregnant women retrospectively tested for HCV in Amsterdam, the Netherlands, and from literature sources. In addition, we estimated the effect of possible treatment improvement in the future. RESULTS: The incremental costs per woman screened was €41 and 0.0008 life-years were gained. The incremental cost-effectiveness ratio (ICER) was €52,473 which is above the cost-effectiveness threshold of €50,000. For screening first-generation non-Western migrants, the ICER was €47,113. Best-case analysis for both scenarios showed ICERs of respectively €19,505 and €17,533. We estimated that if costs per treatment were to decline to €3,750 (a reduction in price of €31,000), screening all pregnant women would be cost-effective. CONCLUSIONS: Currently, adding HCV screening to the already existing screening program for pregnant women is not cost-effective for women in general. However, adding HCV screening for first-generation non-Western women shows a modest cost-effective outcome. Yet, best case analysis shows potentials for an ICER below €20,000 per life-year gained. Treatment options will improve further in the coming years, enhancing cost-effectiveness even more.