Cost‐effectiveness of Anti‐CD19 chimeric antigen receptor T‐Cell therapy in pediatric relapsed/refractory B‐cell acute lymphoblastic leukemia. A societal view

Introduction: In several studies, the chimeric antigen receptor T-cell therapy tisagenlecleucel demonstrated encouraging rates of remission and lasting survival benefits in pediatric patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL). We assessed the cost-effectiveness of tisagenlecleucel (list price: 320 000 EUR) among these patients when compared to clofarabine monotherapy (Clo-M), clofarabine combination therapy (Clo-C), and blinatumomab (Blina) from both a healthcare and a societal perspective. We also assessed future medical and future non-medical consumption costs. Methods: A three-state partitioned survival model was used to simulate a cohort of pediatric patients (12 years of age) through different disease states until the end of life (lifetime horizon). Relevant outcomes were life years, quality-adjusted life years (QALYs), healthcare costs, societal costs, and the incremental cost-effectiveness ratio (ICER). Uncertainty was explored through deterministic and probabilistic sensitivity analyses as well as through several scenario analyzes. Results: Total discounted costs for tisagenlecleucel were 552 679 EUR from a societal perspective, which was much higher than the total discounted costs from a healthcare perspective (ie, 409 563 EUR). Total discounted societal costs for the comparator regimens ranged between 160 803 EUR for Clo-M and 267 259 EUR for Blina. Highest QALYs were estimated for tisagenlecleucel (11.26), followed by Blina (2.25), Clo-C (1.70) and Clo-M (0.74). Discounted societal ICERs of tisagenlecleucel ranged between 31 682 EUR/QALY for Blina and 37 531 EUR/QALY for Clo-C and were considered cost-effective with a willingness-to-pay (WTP) threshold of 80 000 EUR/QALY. None of the scenarios exceeded this threshold, and more than 98% of the iterations in the probabilistic sensitivity analysis were cost-effective. Discussion: At the current price and WTP threshold, tisagenlecleucel is cost-effective from both a healthcare and a societal perspective. Nevertheless, long-term effectiveness data are needed to validate the several assumptions that were necessary for this model

Cost-effectiveness of Anti-CD19 chimeric antigen receptor T-Cell therapy in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia. A societal view

Introduction: In several studies, the chimeric antigen receptor T-cell therapy tisagenlecleucel demonstrated encouraging rates of remission and lasting survival benefits in pediatric patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL). We assessed the cost-effectiveness of tisagenlecleucel (list price: 320 000 EUR) among these patients when compared to clofarabine monotherapy (Clo-M), clofarabine combination therapy (Clo-C), and blinatumomab (Blina) from both a healthcare and a societal perspective. We also assessed future medical and future non-medical consumption costs. Methods: A three-state partitioned survival model was used to simulate a cohort of pediatric patients (12 years of age) through different disease states until the end of life (lifetime horizon). Relevant outcomes were life years, quality-adjusted life years (QALYs), healthcare costs, societal costs, and the incremental cost-effectiveness ratio (ICER). Uncertainty was explored through deterministic and probabilistic sensitivity analyses as well as through several scenario analyzes. Results: Total discounted costs for tisagenlecleucel were 552 679 EUR from a societal perspective, which was much higher than the total discounted costs from a healthcare perspective (ie, 409 563 EUR). Total discounted societal costs for the comparator regimens ranged between 160 803 EUR for Clo-M and 267 259 EUR for Blina. Highest QALYs were estimated for tisagenlecleucel (11.26), followed by Blina (2.25), Clo-C (1.70) and Clo-M (0.74). Discounted societal ICERs of tisagenlecleucel ranged between 31 682 EUR/QALY for Blina and 37 531 EUR/QALY for Clo-C and were considered cost-effective with a willingness-to-pay (WTP) threshold of 80 000 EUR/QALY. None of the scenarios exceeded this threshold, and more than 98% of the iterations in the probabilistic sensitivity analysis were cost-effective. Discussion: At the current price and WTP threshold, tisagenlecleucel is cost-effective from both a healthcare and a societal perspective. Nevertheless, long-term effectiveness data are needed to validate the several assumptions that were necessary for this model

Cost of health care for paediatric patients with sickle cell disease: An analysis of resource use and costs in a European country

Background: While multiple studies have examined the cost of health care for one aspect of sickle cell disease care, few have focussed on the overall cost of comprehensive care for sickle cell disease. Methods: We conducted a retrospective cohort study of children with sickle cell disease treated in a comprehensive care centre from 1 January 2015 to 31 December 2016. Health care utilisation of included patients was based upon data from two main sources. The clinical practice guideline was used to determine the expected resource use of routine comprehensive care (planned elective care), and the financial claims database was used to estimate real-world resource use associated with acute and inpatient care (additional care). Results: A total of 125 children with sickle cell disease were analysed. Expenditures for these patients averaged €5049 [standard deviation (SD) €1634] per child per year. Total yearly costs per patient varied considerably, ranging from €669 to €84 010, and less than 15% of patients were responsible for 50% of the health care costs. The majority (37%) of costs was associated with inpatient hospital care, which increased by age group, 27% with diagnostics, 19% with treatment, 11% with outpatients’ visits and 6% with emergency care. Conclusion: We have described real-world resource use and expenditures for children with sickle cell disease in a European comprehensive care centre. It seems that costs of a comprehensive approach with effective management in the outpatient setting is favourable when compared to episodic health care

Obinutuzumab in Combination with Chemotherapy for the First-Line Treatment of Patients with Advanced Follicular Lymphoma: An Evidence Review Group Evaluation of the NICE Single Technology Appraisal

The National Institute for Health and Care Excellence (NICE), as part of the institute’s single technology appraisal (STA) process, invited the company that makes obinutuzumab (Roche Products Limited) to submit evidence of the clinical and cost effectiveness of the drug in combination with chemotherapy, with or without obinutuzumab as maintenance therapy for adult patients with untreated, advanced follicular lymphoma (FL) in the UK. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company’s submission, the ERG review, and NICE’s subsequent decisions. The clinical evidence was derived from two phase III, company-sponsored, randomised, open-label studies. Most evidence on obinutuzumab was based on the GALLIUM trial that compared obinutuzumab in combination with chemotherapy as induction followed by obinutuzumab maintenance monotherapy with rituximab in combination with chemotherapy as induction followed by rituximab maintenance monotherapy in previously untreated patients with FL (grades 1–3a). Long-term clinical evidence was based on the PRIMA trial, studying the benefit of two years of rituximab maintenance after first-line treatment in patients with FL. The cost-effectiveness evidence submitted by the company relied on a partitioned survival cost-utility model, implemented in Microsoft® Excel. The base-case incremental cost-effectiveness ratio (ICER) presented in the company submission was <£20,000 per quality-adjusted life-year (QALY) gained. Although the ERG concluded that the economic model met the NICE reference case to a reasonable extent, some errors were identified and several assumptions made by the company were challenged. A new base-case scenario produced by the ERG suggested an ICER that was higher than the company base case, but still below £30,000 per QALY gained. However, some ERG scenario analyses were close to or even above the threshold. This was the case in particular for assuming a treatment effect that did not extend beyond trial follow-up. These results led to an initial negative recommendation by the appraisal committee. Subsequently, the company submitted a revised base case focu

Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation

BACKGROUND The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P=0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P=0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, −8.2 percentage points; 95% CI for noninferiority, −14.9 to −1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P=0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, −0.2 percentage points; 95% CI for noninferiority, −4.7 to 4.3; P=0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P=0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months

Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation

BACKGROUND The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied. METHODS We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriat

Cost-Effectiveness of Venetoclax Plus Obinutuzumab Versus Chlorambucil Plus Obinutuzumab for the First-Line Treatment of Adult Patients With Chronic Lymphocytic Leukemia: An Extended Societal View

Objectives: Efficacy of venetoclax plus obinutuzumab (VenO) compared with chlorambucil plus obinutuzumab (ClbO) for treatment-naïve adult patients with chronic lymphocytic leukemia (CLL) with coexisting medical conditions was investigated in CLL14 (NCT02242942). Our aim was to evaluate the cost-effectiveness of VenO versus ClbO for these patients from a Dutch societal perspective. Methods: A 3-state partitioned survival model was constructed to evaluate the cost-effectiveness of VenO. The outcome of the analysis was the incremental cost-effectiveness ratio (ICER) with effectiveness measured in quality-adjusted life-years (QALYs) gained. Uncertainty was explored through deterministic and probabilistic sensitivity analyses, scenario analyses, and value of information analysis (VOI). Results: The base case resulted in a discounted ICER −49 928 EUR/QALY gained (with incremental negative costs and positive effects). None of the ICERs resulted from deterministic sensitivity and scenario analyses exceeded the chosen willingness-to-pay threshold of 20 000 EUR/QALY, and > 99% of the iterations in the probabilistic sensitivity analysis were cost-effective. VOI analyses showed a maximum expected value of eliminating all model parameter uncertainty of 183 591 EUR. Conclusions: Our study demonstrated VenO being dominant over ClbO in treatment-naïve adult patients with CLL assuming a Dutch societal perspective. We concluded that our results are robust as tested through sensitivity and scenario analyses. Additionally, the VOI analyses confirmed that our current evidence base is strong enough to generate reliable results for our study. Nevertheless, further research based on real-world data or longer follow-up period could further contribute to the robustness of the current study's conclusions

Ngoc Do_Venetoclax plus Obinutuzumab vs Chlorambucil plus Obinutuzumab_Cost-Effectiveness Analysis Model.xlsm

The excel model details all the assumptions, data inputs, data sources, and data analysis codes used to output the results represented in our article titled: "Cost-effectiveness of Venetoclax plus Obinutuzumab versus Chlorambucil plus Obinutuzumab for the first-line treatment of adult patients with chronic lymphocytic leukemia - an extended social view." Please see the Data appendix file to view detailed description of the model