Demonstrating proof of concept for value-based agreements in Europe: two real-world cases.

OBJECTIVES: Value-based agreements (VBAs) link access, reimbursement, or price to the real-world usage and impact of a medicine, thereby enabling patient access while reducing clinical or financial uncertainty for the payer. VBAs have the potential to support improved patient outcomes, given the value-oriented approach to care, and lead to overall savings, while enabling payers to share risk and reduce uncertainty. METHODS: This commentary outlines the key challenges, enablers, and a framework for successful implementation by comparing the experience of two VBAs for AstraZeneca medicines, aiming to increase confidence in their future use. RESULTS: Engagement by payers, manufacturers, physicians, and provider institutions, and robust data collection systems that are accessible, simple to use, and add little burden to physicians were key to successfully negotiating a VBA that worked for all stakeholders. In both country systems, a legal/policy framework enabled innovative contracting. CONCLUSIONS: These examples demonstrate proof of concept for VBA implementation in different settings, and may inform future VBAs.

Cost-Effectiveness Analysis of Tisagenlecleucel in the Treatment of Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia in Children and Young Adults in Spain.

PURPOSE: Tisagenlecleucel, a chimeric antigen receptor T-cell (CAR-T) therapy, is a promising alternative for the management of children and young adults with relapsed and refractory B-cell acute lymphoblastic leukemia (r/r ALL). The aim of this study was to determine whether treatment with tisagenlecleucel is a cost-effective intervention compared with salvage chemotherapy in paediatric and young adult patients with r/r ALL in Spain. MATERIALS AND METHODS: A partitioned survival model of monthly cycles with three health states was used (event-free survival, progressive/relapsed disease and death). A lifetime time horizon and the Spanish National Health System perspective were adopted. During the first 5 years, permanence in the different health states was determined according to the results in the clinical studies. In successive years, mortality tables of the Spanish general population adjusted by standardized mortality rate for survivors of childhood cancer were used. Clinical, economic, and quality of life parameters were drawn from clinical trials and the literature. Only direct health costs (pharmacological costs and the costs derived from health resource use) were included. The robustness of the results was evaluated in a sensitivity analysis. RESULTS: This cost-effectiveness analysis showed a greater benefit (10.10 and 8.97 life-years gained [LYGs] and quality-adjusted life-years [QALYs] gained, respectively) and a higher cost (€ 258,378.40) for tisagenlecleucel compared to salvage chemotherapy. The resulting incremental cost-effectiveness and cost-utility ratios were € 25,576.80 per LYG and € 28,818.52 per QALY gained, respectively. In the sensitivity analysis, all the results were below € 50,000/QALY. CONCLUSION: Tisagenlecleucel would represent a cost-effective intervention for the treatment of children and young adults with r/r ALL in Spain.

Cost-Effectiveness Of Midostaurin In The Treatment Of Acute Myeloid Leukemia With The FLT3 Mutation In Spain.

PURPOSE: The addition of midostaurin to standard chemotherapy (cytarabine and daunorubicin) has shown significant improvements in the survival of patients with acute myeloid leukemia with the FLT3 mutation (FLT3-AML). The objective of this study was to determine whether this intervention would be cost-effective in Spain. METHODS: A partitioned survival model with five health states was developed (diagnosis and induction, complete remission, no complete remission, transplantation and death). A lifetime time horizon and the Spanish National Health System perspective were adopted. During the first three years, permanence in the different health states was determined according to the results of the RATIFY study. In successive years, the death rates of the Spanish population adjusted by a factor to reflect long-term disease-related mortality were used. Utilities were obtained from the literature. Pharmacological costs (first and second line) and the costs of other health resources (hospitalizations, visits and tests) were included. The robustness of the model was evaluated by deterministic and probabilistic sensitivity analyses. RESULTS: The addition of midostaurin resulted in 1.46 life years gained (LYG) and 1.23 quality-adjusted life years (QALY) gained and implied an additional cost of € 47,955, resulting in an incremental cost-effectiveness ratio (ICER) of € 32,854/LYG and an incremental cost-utility ratio of € 38,985/QALY. In the univariate sensitivity analysis, the threshold of € 50,000/QALY was not exceeded in any case; taking into consideration potential discounts of 20-40% in the PVL of midostaurin the ICER would be below € 30,000/QALY, a commonly accepted threshold in Spain. In the probabilistic analysis, when the threshold was € 50,000/QALY, midostaurin was cost-effective in 82.3% of simulations. CONCLUSION: According to our modeling, midostaurin, in combination with standard chemotherapy, could be an efficient alternative for the treatment of FLT3-AML in Spain.

Cost-effectiveness analysis of ribociclib versus palbociclib in the first-line treatment of HR+/HER2- advanced or metastatic breast cancer in Spain.

PURPOSE: The aim of this study was to evaluate the cost-effectiveness of ribociclib compared to palbociclib, both in combination with letrozole, in the first-line treatment of postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (ABC) from the perspective of the Spanish National Health System (NHS). PATIENTS AND METHODS: Disease progression was simulated with a partitioned survival model developed from the parameterization and extrapolation of survival curves of postmenopausal women with HR+/HER2- ABC from clinical trials with ribociclib or palbociclib, both in combination with letrozole. The model was structured on the basis of three health states (progression-free, progressed disease, and death), with a 1-month cycle length and inclusion of subsequent treatments administered for disease progression, over a time horizon of 15 years. Clinical, economic, and quality of life parameters were drawn from clinical trials and the literature. The use of resources and clinical practice in the Spanish setting was validated by a panel of experts. The Spanish NHS perspective was adopted, taking into account exclusively direct health costs from 2017 expressed in Euros. Drug prices used were the reported ex-factory prices. Uncertainty of the parameters and robustness of the results were evaluated using deterministic and probabilistic sensitivity analyses (2,000 iterations). RESULTS: This cost-effectiveness analysis showed a greater benefit (0.437 and 0.285 life-years gained [LYGs] and quality-adjusted life years [QALYs] gained, respectively) and a slightly higher cost (€439.86) for ribociclib+letrozole compared to palbociclib+letrozole. The resulting incremental cost-effectiveness and cost-utility ratios were €1,007.69 per LYG and €1,543.62 per QALY gained, respectively. The results of the multiple sensitivity analyses showed limited dispersion of the outcomes, thus corroborating their robustness. CONCLUSION: From the NHS perspective, considering the most commonly established willingness-to-pay thresholds in the Spanish setting, ribociclib+letrozole would represent a cost-effective therapeutic option compared to palbociclib+letrozole in the first-line treatment of HR+/HER2- ABC in postmenopausal women.

Cost-effectiveness of Ruxolitinib vs Best Available Therapy in the Treatment of Myelofibrosis in Spain.

Introduction: Primary myelofibrosis (MF) is a rare hematologic disease belonging to the group of Philadelphia-negative chronic myeloproliferative neoplasms. Identification of the Janus Kinase (JAK) gene mutations inaugurated a new era in the targeted therapy of myeloproliferative diseases. Ruxolitinib is the first JAK1/JAK2 inhibitor specifically approved for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis. The objective of this study was to assess the cost-effectiveness of ruxolitinib vs best available therapy (BAT) in MF patients in Spain. Methods: A decision-tree and Markov model were adapted to the Spanish setting to assess the cost-effectiveness of ruxolitinib vs. BAT on a lifetime horizon (≤15 years) from the societal perspective, while healthcare system perspective was included in the one-way sensitivity analysis. The population was assumed to be similar to that of the COMFORT-II clinical trial (CT), which was also the source of treatment efficacy data. BAT composition was derived from the same CT and validated with Spanish experts. Utilities were derived from the COMFORT-I CT. Costs included treatment, management, hospitalizations, emergency and outpatient visits, as well as adverse events and end-of-life costs. Additionally, costs associated to productivity loss were taken into account. Resource use was validated with experts and costs were extracted from Spanish sources. A probabilistic sensitivity analysis was also performed to evaluate the consistency of the results under the uncertainty or variability of the input data. Results: Patients on ruxolitinib accumulated 6.1 life years gained (LYGs), resulting in 73% extra life-years compared to patients treated with BAT (3.5LYs gained). Ruxolitinib provided 4.4 quality-adjusted life years (QALYs), with a 99% improvement compared to BAT (2.2 QALYs). This analysis gave an incremental cost of €47 199 per LYG and an incremental cost of €55 616 per QALY gained from the societal perspective. Conclusions: Ruxolitinib would be cost-effective in Spain according to the end-of-life criteria defined by the NICE and commonly referred for Spain (cost-effectiveness threshold of €61 500/QALY), in line with results published for other European countries.

Cost-utility analysis of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine in metastatic pancreatic cancer in Spain: results of the PANCOSTABRAX study.

The PANCOSTABRAX study evaluated the cost-effectiveness of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine (GEM) versus GEM alone in the treatment of patients with metastatic pancreatic cancer in Spain. Efficacy data were obtained from the MPACT study and were modeled to a lifetime horizon using a Markov model. The analysis was performed from the payer's perspective. Use of resources and key assumptions of the analysis were validated by a panel of oncologists. The addition of nab-paclitaxel to GEM showed higher effectiveness results (0.156 additional quality adjusted life years) at a higher cost (€6,477), resulting in a cost per quality-adjusted life years gained of €41,519. The combination of nab-paclitaxel and GEM has been shown to be an effective and well-tolerated option for the treatment of metastatic pancreatic cancer and, in addition to becoming the new standard of care, could also be considered a cost-effective option.

Análisis comparativo de coste-eficacia entre darunavir/ritonavir y otros inhibidores de la proteasa en el tratamiento de la infección por el virus de la inmunodeficiencia humana de tipo 1 en pacientes naïve en España / Comparative cost-effectiveness analysis between darunavir/ritonavir and other protease inhibitors in treatment-naive human immunodeficiency syndrome type 1-infected patients in Spain

INTRODUCCIÓN: Las guías GESIDA proponen pautas preferentes de inicio de tratamiento antirretroviral en pacientes infectados por el VIH. El objetivo de este análisis es comparar los costes y la eficacia de darunavir/r QD frente a otros inhibidores de la proteasa (IP) potenciados recomendados por GESIDA en pacientes naďve. MÉTODOS: Mediante un modelo de coste-eficacia se compararon los IP/r recomendados como pautas preferentes o alternativas en pacientes naďve, junto con un tratamiento de base con 2 ITIAN. La eficacia se midió mediante la respuesta virológica (carga viral < 50 copias/ml) a las 48 semanas ajustada por los niveles basales de carga viral y recuentos de CD4. Para generar la «frontera de eficiencia» y ratios de coste-eficacia se utilizaron los costes espańoles y las tasas de eficacia a las 48 semanas. RESULTADOS: El modelo estimó que el inicio del tratamiento en naďve con darunavir/r QD se mostró como la opción preferente basada en un IP/r más coste-eficaz. El coste medio del TARGA por paciente respondedor era menor para darunavir/r (13.420 €) que para atazanavir/r (14.000 €) o lopinavir/r (13.815 €). Se estimó que darunavir/r sería el IP preferente más eficiente, mientras que atazanavir/r QD y lopinavir/r BID resultarían opciones «dominadas», situándose fuera de la frontera de la eficiencia. Partiendo de un presupuesto fijo de 10 millones de €, se estimó que la pauta de inicio con darunavir/r QD conseguiría un mayor número de pacientes respondedores (745) que con atazanavir/r QD (714) o lopinavir/r BID (724). Al mismo tiempo, darunavir/r QD reduciría el número de pacientes que fracasarían al tratamiento (150) en comparación con atazanavir/r QD (172) o lopinavir/r (286). CONCLUSIONES: Según este modelo, darunavir/r QD es el IP/r preferente más coste-efectivo para el tratamiento de la infección por el VIH-1 basado en IP/r en pacientes naďve en Espańa

INTRODUCTION: GESIDA (AIDS Study Group) has proposed preferred regimens of antiretroviral treatment as initial therapy in HIV infected patients. The objective of this analysis is to compare the costs and effectiveness of darunavir/r QD and other ritonavir-boosted (/r) protease inhibitors (PIs) currently recommended in GESIDA guidelines for treatment-naďve patients. METHODS: A cost-efficacy model compared the boosted PIs recommended as preferred or alternative treatment choices, each used with a nucleoside reverse transcriptase inhibitor backbone. Efficacy was measured by 48-week virological response (viral load < 50 copies/mL) adjusted by baseline viral load and CD4 cell count. To generate efficiency frontiers and cost-efficacy ratios, one-year antiretroviral therapy costs in Spain, and 48-week efficacy values were used. Results The model estimated that starting treatment with darunavir/r QD was the most cost-effective choice compared with the other preferred PI/r based therapies. The average cost per patient with a virological response was lower for darunavir/r QD (13,420€) than for atazanavir/r QD (14,000€), or lopinavir/r BID (13,815€). Among the preferred PI/r-based therapies, darunavir/r QD also was estimated to be the most efficient option for treatment-naďve patients. Atazanavir/r QD and lopinavir/r BID were found to be «dominated» by darunavir/r) and, consequently, were outside the efficiency frontier of PI/r-based first-line treatment. Given a fixed budget of 10 million euros for PI/r-based first-line therapy, the model estimated that darunavir/r QD would yield more responders (745) than atazanavir/r QD (714), or lopinavir/r BID (724). At the same time, darunavir/r QD would reduce the number of individuals failing treatment (150) compared with atazanavir/r QD (172) and lopinavir/r BID (286). CONCLUSIONS: In this model, darunavir/r QD was found to be the most cost-effective choice, among the preferred PI/r-based therapies recommended in the Spanish guidelines for treatment-naïve patients

[Comparative cost-effectiveness analysis between darunavir/ritonavir and other protease inhibitors in treatment-naive human immunodeficiency syndrome type 1-infected patients in Spain]. / Análisis comparativo de coste-eficacia entre darunavir/ritonavir y otros inhibidores de la proteasa en el tratamiento de la infección por el virus de la inmunodeficiencia humana de tipo 1 en pacientes naïve en España.

INTRODUCTION: GESIDA (AIDS Study Group) has proposed preferred regimens of antiretroviral treatment as initial therapy in HIV infected patients. The objective of this analysis is to compare the costs and effectiveness of darunavir/r QD and other ritonavir-boosted (/r) protease inhibitors (PIs) currently recommended in GESIDA guidelines for treatment-naïve patients. METHODS: A cost-efficacy model compared the boosted PIs recommended as preferred or alternative treatment choices, each used with a nucleoside reverse transcriptase inhibitor backbone. Efficacy was measured by 48-week virological response (viral load < 50 copies/mL) adjusted by baseline viral load and CD4 cell count. To generate efficiency frontiers and cost-efficacy ratios, one-year antiretroviral therapy costs in Spain, and 48-week efficacy values were used. RESULTS: The model estimated that starting treatment with darunavir/r QD was the most cost-effective choice compared with the other preferred PI/r based therapies. The average cost per patient with a virological response was lower for darunavir/r QD (13,420€) than for atazanavir/r QD (14,000€), or lopinavir/r BID (13,815€). Among the preferred PI/r-based therapies, darunavir/r QD also was estimated to be the most efficient option for treatment-naïve patients. Atazanavir/r QD and lopinavir/r BID were found to be «dominated¼ by darunavir/r) and, consequently, were outside the efficiency frontier of PI/r-based first-line treatment. Given a fixed budget of 10 million euros for PI/r-based first-line therapy, the model estimated that darunavir/r QD would yield more responders (745) than atazanavir/r QD (714), or lopinavir/r BID (724). At the same time, darunavir/r QD would reduce the number of individuals failing treatment (150) compared with atazanavir/r QD (172) and lopinavir/r BID (286). CONCLUSIONS: In this model, darunavir/r QD was found to be the most cost-effective choice, among the preferred PI/r-based therapies recommended in the Spanish guidelines for treatment-naïve patients.