Multivariate Probabilistic Sensitivity Analyses Research Articles

Cost-effectiveness of severe acute malnutrition treatment delivered by community health workers in the district of Mayahi, Niger

BackgroundA non-randomized controlled trial, conducted from June 2018 to March 2019 in two rural communes in the health district of Mayahi in Niger, showed that including community health workers (CHWs) in the treatment of severe acute malnutrition (SAM) resulted in a better recovery rate (77.2% vs. 72.1%) compared with the standard treatment provided solely at the health centers. The present study aims to assess the cost and cost-effectiveness of the CHWs led treatment of uncomplicated SAM in children 6–59 months compared to the standard national protocol.MethodsTo account for all relevant costs, the cost analysis included activity-based costing and bottom-up approaches from a societal perspective and on a within-trial time horizon. The cost-effectiveness analysis was conducted through a decision analysis network built with OpenMarkov and evaluated under two approaches: (1) with recovery rate and cost per child admitted for treatment as measures of effectiveness and cost, respectively; and (2) assessing the total number of children recovered and the total cost incurred. In addition, a multivariate probabilistic sensitivity analysis was carried out to evaluate the effect of uncertainty around the base case input data.ResultsFor the base case data, the average cost per child recovered was 116.52 USD in the standard treatment and 107.22 USD in the CHWs-led treatment. Based on the first approach, the CHWs-led treatment was more cost-effective than the standard treatment with an average cost per child admitted for treatment of 82.81 USD vs. 84.01 USD. Based on the second approach, the incremental cost-effectiveness ratio of the transition from the standard to the CHWs-led treatment amounted to 98.01 USD per additional SAM case recovered.ConclusionsIn the district of Mayahi in Niger, the CHWs-led SAM treatment was found to be cost-effective when compared to the standard protocol and provided additional advantages such as the reduction of costs for households.Trial registration: ISRCTN with ID 31143316. https://doi.org/10.1186/ISRCTN31143316

First-Line Camrelizumab Plus Rivoceranib in Advanced Hepatocellular Carcinoma: A China-Based Cost-Effectiveness Analysis.

Hepatocellular carcinoma poses a significant public health burden in China, necessitating the economic evaluation of new therapeutic strategies for policy-makers and clinicians. The international, randomized phase 3 trial CARES-310 revealed that camrelizumab plus rivoceranib provided a substantial clinical benefit in patients with advanced hepatocellular carcinoma, but the economic outcome remains unclear. This study aimed to evaluate the cost-effectiveness of camrelizumab plus rivoceranib versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CARES-310) from the perspective of the Chinese health care system. A partitioned survival model was developed to estimate the lifetime cost and clinical outcomes of camrelizumab plus rivoceranib versus sorafenib in first-line treatment of advanced hepatocellular carcinoma. Survival data from the CARES-310 trial were used to create a hypothetical cohort of 543 patients with advanced hepatocellular carcinoma for modeling disease progression. The life-year, quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER) was used to measure the model's outcome, with the willingness-to-pay threshold set at 3 times China's gross domestic product (GDP) per capita (US$36 780). Univariate, multivariable probabilistic sensitivity analyses, and subgroup analysis were performed to assess parameter uncertainty, complemented by a scenario analysis using health utilities reported in literature. The camrelizumab group yielded an additional 0.239 QALYs at an added cost of US$8340 compared with sorafenib, resulting in an ICER of US$34 897/QALY. Univariate sensitivity analysis indicated that the model results were most sensitive to the utility of progression-free survival in the camrelizumab group, sorafenib cost, and camrelizumab cost. Probabilistic sensitivity analysis revealed a 56% probability of cost-effectiveness of camrelizumab plus rivoceranib among all patients. The results of the subgroup analysis demonstrated camrelizumab plus rivoceranib was the most cost-effective in the subgroup with albumin-bilirubin grade 2. At a willingness-to-pay threshold of US$36 780/QALY, camrelizumab plus rivoceranib is likely to be a cost-effective option compared with sorafenib as first-line treatment for advanced hepatocellular carcinoma in China.

Budget Impact of the Oncotype DX Breast Recurrence Score® Test in Patients with Early Primary Hormone-Receptor-Positive, HER2-Negative, Node-Positive Breast Cancer in Germany

Background: Gene expression tests can inform decisions on whether to recommend or omit chemotherapy for patients with early HR+, HER2− breast cancer. The benefit of these tests is well established and fully reimbursed by sickness funds for lymph node-negative (pN0) patients in Germany. A budget impact model was built to evaluate the effect of using the Oncotype DX Breast Recurrence Score^® test also for node-positive (pN1: 1–3 positive lymph nodes) patients. Methods: The prospective randomized clinical trial, RxPONDER, defined conditions (Recurrence Score result 0–25 for postmenopausal patients with 1–3 positive lymph nodes) under which omitting chemotherapy does not significantly impact invasive disease-free survival with results currently reported for 5-year follow-up. The present budget impact model calculates average total cost per node-positive patient versus no testing from a sickness funds perspective, taking into account not only the budgetary impact of avoiding chemotherapy and associated side effects, but also the costs of treating those patients who develop distant metastasis. The stability of the results was investigated by probabilistic multivariate sensitivity analysis. Results: After deducting testing cost, applying the Oncotype DX Breast Recurrence Score test yielded an average savings per node-positive patient of EUR 4,272. Without the test costs, the greatest savings resulted from reductions in direct treatment costs and costs arising from the treatment of chemotherapy-related side effects, which together averaged EUR 6,677. The targeted use of chemotherapy after testing also resulted in slightly lower costs for treatment of distant metastasis, if it did occur. The multivariate sensitivity analysis also almost exclusively resulted in cost savings. Conclusion: Analogous to the pN0 situation, this budget impact model demonstrates that the Oncotype DX Breast Recurrence Score test can also reduce healthcare costs in Germany in treatment of node-positive (pN1: 1–3 positive lymph nodes) patients by minimizing both unnecessary chemotherapy and undertreatment. Additional benefits to patients would include reduced morbidity and improved quality of life for those patients who can safely avoid chemotherapy or undertreatment.

Cost-effectiveness of Axicabtagene Ciloleucel and Tisagenlecleucel as Second-line or Later Therapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Chimeric antigen receptor (CAR) T cell therapies are approved as a third-line or later therapy for several hematological malignant neoplasms. Recently, randomized clinical trials have investigated their efficacy as a second-line treatment in high-risk relapsed or refractory diffuse large B-cell lymphoma (DLBCL) compared with salvage chemotherapy followed by hematopoietic stem cell transplantation (HSCT). To evaluate the cost-effectiveness of axicabtagene ciloleucel and tisagenlecleucel vs standard care (SC) as second-line or later therapy for relapsed or refractory DLBCL, from both US health care sector and societal perspectives at a cost-effectiveness threshold of $150 000 per quality-adjusted life-year (QALY). This economic evaluation assessed cost-effectiveness using a partitioned survival model with 2021 US dollars and QALYs over a lifetime horizon. Model inputs were derived from 2 randomized clinical trials (ZUMA-7 and BELINDA) and published literature. In the trials, patients who did not respond to SC received CAR T cells (treatment switching or crossover), either outside the protocol (ZUMA-7) or as part of the protocol (BELINDA). A separate scenario analysis compared second-line axicabtagene ciloleucel with SC alone without treatment crossover to CAR T cell therapy. Data analysis was performed from December 18, 2021, to September 13, 2022. CAR T cell therapy (axicabtagene ciloleucel and tisagenlecleucel) compared with salvage chemotherapy followed by HSCT. Costs and QALYs were used to derive incremental cost-effectiveness ratios (ICERs) for the health care sector and societal perspectives. Cost and QALYs were discounted at 3.0% annually. Univariate and multivariate probabilistic sensitivity analysis using 10 000 Monte Carlo simulations were applied to test model uncertainty on the ICER. Second-line axicabtagene ciloleucel was associated with an ICER of $99 101 per QALY from the health care sector perspective and an ICER of $97 977 per QALY from the societal perspective, while second-line tisagenlecleucel was dominated by SC (incremental costs of $37 803 from the health care sector and $39 480 from the societal perspective with decremental QALY of -0.02). Third-line or later tisagenlecleucel was associated with an ICER of $126 593 per QALY from the health care sector perspective and an ICER of $128 012 per QALY from the societal perspective. Based on the scenario analysis of no treatment switching, second-line axicabtagene ciloleucel yielded an ICER of $216 790 per QALY from the health care sector perspective and an ICER of $218 907 per QALY from the societal perspective, compared with SC. When accounting for patients achieving prolonged progression-free survival who would not incur progression-related costs, in this scenario ICER changed to $125 962 per QALY from the health care sector perspective and $122 931 per QALY from the societal perspective. These results were most sensitive to increased list prices of CAR T cell therapy and QALY losses associated with axicabtagene ciloleucel and tisagenlecleucel. These findings suggest that second-line axicabtagene ciloleucel and third-line or later tisagenlecleucel were cost-effective in treating patients with relapsed or refractory DLBCL at the cost-effectiveness threshold of $150 000 per QALY. However, uncertainty remains regarding the best candidates who would experience value gains from receiving CAR T cell therapy.

Assessing the Cost-Utility of Universal Hepatitis B Vaccination Among Adults.

Although effective against hepatitis B virus (HBV) infection, hepatitis B (HepB) vaccination is only recommended for infants, children, and adults at higher risk. We conducted an economic evaluation of universal HepB vaccination among US adults. Using a decision analytic model with Markov disease progression, we compared current vaccination recommendations (baseline) with either 3-dose or 2-dose universal HepB vaccination (intervention strategies). In simulated modeling of 1 million adults distributed by age and risk groups, we quantified health benefits (quality-adjusted life years, QALYs) and costs for each strategy. Multivariable probabilistic sensitivity analyses identified key inputs. All costs reported in 2019 US dollars. With incremental base-case vaccination coverage up to 50% among persons at lower risk and 0% increment among persons at higher risk, each of 2 intervention strategies averted nearly one-quarter of acute HBV infections (3-dose strategy, 24.8%; 2-dose strategy, 24.6%). Societal incremental cost per QALY gained of $152722 (interquartile range, $119113-$235086) and $155429 (interquartile range, $120302-$242226) were estimated for 3-dose and 2-dose strategies, respectively. Risk of acute HBV infection showed the strongest influence. Universal adult vaccination against HBV may be an appropriate strategy for reducing HBV incidence and improving resulting health outcomes.

Safety and cost-effectiveness of ponatinib versus other tyrosine kinase inhibitors as second-line therapy in patients with chronic myeloid leukemia in the United States

To evaluate the cost-effectiveness of ponatinib compared with second-line TKIs in the treatment of adult patients with CML who failed, or were intolerant to, first-line TKIs. A Markov state transition model was conducted. Model transition, adverse-effect probabilities, utility data and medical costs were obtained from clinical trials and literature. Measurements included medications, follow-ups, adverse events, allogeneic stem cell transplantation and quality-adjusted life years (QALYs). Univariable and Bayesian multivariable probabilistic sensitivity analyses were conducted using Monte Carlo simulations. Dasatinib resulted in an ICER of $79,086/QALY compared to nilotinib. Ponatinib yielded an ICER of $176,278/QALY and $141,563/QALY compared to dasatinib and nilotinib, respectively. Dasatinib was the optimal treatment at a $100,000/QALY threshold. The probability (36%–40%) for ponatinib or dasatinib optimal treatment was associated with thresholds of $160,000–$180,000/QALY. Dasatinib and ponatinib can be considered cost-effective options and provide clinical benefits compared to other second-line TKIs for CML in the US.

Cost-effectiveness of population-based screening for diabetes and hypertension in India: an economic modelling study

India faces a high burden of diabetes and hypertension. Currently, there is a dearth of economic evidence about screening programmes, affected age groups, and frequency of screening for these diseases in Indian settings. We assessed the cost effectiveness of population-based screening for diabetes and hypertension compared with current practice in India for different scenarios, according to type of screening test, population age group, and pattern of health-care use. We used a hybrid decision model (decision tree and Markov model) to estimate the lifetime costs and consequences from a societal perspective. A meta-analysis was done to assess the effectiveness of population-based screening. Primary data were collected from two Indian states (Haryana and Tamil Nadu) to assess the cost of screening. The data from the National Health System Cost Database and the Costing of Health Services in India study were used to determine the health system cost of diagnostic tests and cost of treating diabetes or hypertension and their complications. A total of 962 patients were recruited to assess out-of-pocket expenditure and quality of life. Parameter uncertainty was evaluated using univariate and multivariable probabilistic sensitivity analyses. Finally, we estimated the incremental cost per quality-adjusted life-year (QALY) gained with alternative scenarios of scaling up primary health care through a health and wellness centre programme for the treatment of diabetes and hypertension. The incremental cost per QALY gained across various strategies for population-based screening for diabetes and hypertension ranged from US$0·02 million to $0·03 million. At the current pattern of health services use, none of the screening strategies of annual screening, screening every 3 years, and screening every 5 years was cost-effective at a threshold of 1-time per capita gross domestic product in India. In the scenario in which health and wellness centres provided primary care to 20% of patients who were newly diagnosed with uncomplicated diabetes or hypertension, screening the group aged between 30 and 65 years every 5 years or 3 years for either diabetes, hypertension, or a comorbid state (both diabetes and hypertension) became cost-effective. If the share of treatment for patients with newly diagnosed uncomplicated diabetes or hypertension at health and wellness centres increases to 70%, from the existing 4% at subcentres and primary health centres, annual population-based screening becomes a cost saving strategy. Population-based screening for diabetes and hypertension in India could potentially reduce time to diagnosis and treatment and be cost-effective if it is linked to comprehensive primary health care through health and wellness centres for provision of treatment to patients who screen positive. Department of Health Research, Government of India.

Cost-effectiveness of a Digital Health Intervention for Acute Myocardial Infarction Recovery.

Acute myocardial infarction (AMI) is a common cause of hospital admissions, readmissions, and mortality worldwide. Digital health interventions (DHIs) that promote self-management, adherence to guideline-directed therapy, and cardiovascular risk reduction may improve health outcomes in this population. The "Corrie" DHI consists of a smartphone application, smartwatch, and wireless blood pressure monitor to support medication tracking, education, vital signs monitoring, and care coordination. We aimed to assess the cost-effectiveness of this DHI plus standard of care in reducing 30-day readmissions among AMI patients in comparison to standard of care alone. A Markov model was used to explore cost-effectiveness from the hospital perspective. The time horizon of the analysis was 1 year, with 30-day cycles, using inflation-adjusted cost data with no discount rate. Currencies were quantified in US dollars, and effectiveness was measured in quality-adjusted life-years (QALYs). The results were interpreted as an incremental cost-effectiveness ratio at a threshold of $100,000 per QALY. Univariate sensitivity and multivariate probabilistic sensitivity analyses tested model uncertainty. The DHI reduced costs and increased QALYs on average, dominating standard of care in 99.7% of simulations in the probabilistic analysis. Based on the assumption that the DHI costs $2750 per patient, use of the DHI leads to a cost-savings of $7274 per patient compared with standard of care alone. Our results demonstrate that this DHI is cost-saving through the reduction of risk for all-cause readmission following AMI. DHIs that promote improved adherence with guideline-based health care can reduce hospital readmissions and associated costs.

Out-of-Hospital Cervical Ripening With a Synthetic Hygroscopic Cervical Dilator May Reduce Hospital Costs and Cesarean Sections in the United States-A Cost-Consequence Analysis.

Objective: Out-of-hospital (outpatient) cervical ripening prior to induction of labor (IOL) is discussed for its potential to decrease the burden on hospital resources. We assessed the cost and clinical outcomes of adopting an outpatient strategy with a synthetic hygroscopic cervical dilator, which is indicated for use in preinduction cervical ripening.Methods: We developed a cost-consequence model from the hospital perspective with a time period from IOL to post-delivery discharge. A hypothetical cohort of women to undergo IOL at term with an unfavorable cervix (all risk levels) were assessed. As the standard of care (referred to as IP-only) all women were ripened as inpatients using the vaginal PGE2 insert or the single-balloon catheter. In the comparison (OP-select), 50.9% of low-risk women (41.4% of the study population) received outpatient cervical ripening using a synthetic hygroscopic cervical dilator and the remaining women were ripened as inpatients as in the standard of care. Model inputs were sourced from a structured literature review of peer-reviewed articles in PubMed. Testing of 2,000 feasible scenarios (probabilistic multivariate sensitivity analysis) ascertained the robustness of results. Outcomes are reported as the average over all women assessed, comparing OP-select to IP-only.Results: Implementing OP-select resulted in hospital savings of US$689 per delivery, with women spending 1.48 h less time in the labor and delivery unit and 0.91 h less in the postpartum recovery unit. The cesarean-section rate was decreased by 3.78 percentage points (23.28% decreased to 19.50%). In sensitivity testing, hospital costs and cesarean-section rate were reduced in 91% of all instances.Conclusion: Our model analysis projects that outpatient cervical ripening has the potential to reduce hospital costs, hospital stay, and the cesarean section rate. It may potentially allow for better infection-prevention control during the ongoing COVID-19 pandemic and to free up resources such that more women might be offered elective IOL at 39 weeks.

Cost-effectiveness analysis of multiple imaging modalities in diagnosis and follow-up of intermediate complex cystic renal lesions.

To compare health-economic aspects of multiple imaging modalities used to monitor renal cysts, the present study evaluates costs and outcomes of patients with Bosniak IIF and III renal cysts detected and followed-up by either contrast-enhanced computed tomography (ceCT), contrast-enhanced magnetic resonance imaging (ceMRI), or contrast-enhanced ultrasonography (CEUS). A simulation using Markov models was implemented and performed with 10 cycles of 1year each. Proportionate cohorts were allocated to Markov models by a decision tree processing specific incidences of malignancy and levels of diagnostic performance. Costs of imaging and surgical treatment were investigated using internal data of a European university hospital. Multivariate probabilistic sensitivity analysis was performed to confirm results considering input value uncertainties. Patient outcomes were measured in quality-adjusted life years (QALY), and costs as averages per patient including costs of imaging and surgical treatment. Compared to the 'gold standard' of ceCT, ceMRI was more effective but also more expensive, with a resulting incremental cost-effectiveness ratio (ICER) >€70000 (Euro) per QALY gained. CEUS was dominant compared to ceCT in both Bosniak IIF and III renal cysts in terms of QALYs and costs. Probabilistic sensitivity analysis confirmed these results in the majority of iterations. Both ceMRI and CEUS can be used as alternatives to ceCT in the diagnosis and follow-up of intermediately complex cystic renal lesions without compromising effectiveness, while CEUS is clearly cost-effective. The economic results apply to a large university hospital and must be adapted for smaller hospitals.

PGI9 Cost-Effectiveness Comparison of Vedolizumab, Infliximab and Conventional Therapy for the Treatment of Biologic-Naïve, Moderately to Severely ACTIVE Ulcerative Colitis Patients in China

To evaluate the relative cost-effectiveness of vedolizumab (VDZ), infliximab (IFX) and conventional therapy (CVT) for treating moderately to severely active Ulcerative Colitis (UC) patients who are naïve to biologic treatments. A Markov decision model was developed to compare VDZ, IFX and CVT, currently approved in China for moderately to severely active UC patients who are biologic-naive. The evaluation was performed using a healthcare system perspective covering the life-time horizon (30 years) for a patient. Efficacy data were derived from a network meta-analysis of published clinical trial data. Utility scores, surgery risks and mortality information were obtained from a targeted literature review. Costs (China renminbi [RMB]) and outcomes (measured in quality-adjusted life-years [QALY]) were calculated and discounted at the annualized rate of 3.5%. The incremental cost effectiveness ratio (ICER) was estimated to support cost-effectiveness determination. A one-way sensitivity analyses and a multivariate probabilistic sensitivity analyses were conducted. A patient treated with VDZ, IFX and CVT accrued 11.8, 11.5 and 10.4 QALYs respectively in the 30-year simulation. Total direct medical costs for an average patient were RMB 1.573 Million for VDZ, RMB 1.560 Million for IFX and RMB 1.714 Million for CVT in the same period. The ICER for VDZ vs IFX was RMB 46,389/QALY while VDZ dominated CVT with lower cost and better outcome. In the comparison vs CVT, VDZ higher acquisition cost was offset by its lowest non-pharmacological medical costs among the three interventions. Sensitivity analysis confirmed results were stable to random parameter value fluctuations. The cost-effective analysis showed that VDZ was dominant over CVT treatment. VDZ was also cost-effective versus IFX, based on China’s 2019 per capita GDP of RMB 70,892. VDZ may provide the best value for money in treating biologic-naïve patients with moderately to severely active Ulcerative Colitis in China.

Impact of Tafamidis on Life Expectancy and Quality of Life of Transthyretin Amyloid Cardiomyopathy Patients

Background Historically, the prognosis of newly diagnosed patients with transthyretin amyloid cardiomyopathy (ATTR-CM) was poor with a median survival of only 2-6 years. The ATTR-ACT trial showed that tafamidis reduced all-cause mortality by 30.2% resulting in a hazard ratio (HR) of 0.70 [95% CI 0.51 to 0.96] compared to placebo by slowing disease progression. The aim of this study was to estimate the impact of tafamidis on mean survival and quality adjusted life years (QALY) using a disease simulation model. Methods A multi-state cohort Markov model was developed to simulate the disease course of ATTR-CM patients. In the model, patients were followed throughout a lifetime, and survival was stratified by prognostic NYHA I/II and NYHA III patient subgroups using individual patient-level data from both the ATTR-ACT and the long-term extension study to ATTR-ACT. Based on the patients’ distribution in the ATTRACT trial, the total patient cohort entering the model was comprised of 68% in NYHA class I/II and 32% in NYHA class III. Technical best practices were followed to extrapolate survival. Given that the proportional hazard assumption was violated, curves were fitted by treatment arm and by subgroup. The base case parametric distributions selected were Gompertz for NYHA class I/II and Weibull for NYHA class III, based on statistical tests of fit and clinical plausibility of the extrapolations. Utility values for the health states were derived from ATTR-ACT EQ-5D-3L using US tariffs. The outcomes were mean and incremental mean survival and QALYs. Univariate deterministic and multivariate probabilistic sensitivity analyses were conducted. Analyses were conducted for each NYHA class and weighted results presented. Results The overall predicted mean survival for the total population in the simulated patient cohort was 7.01 for tafamidis and 2.82 years for placebo, resulting in an incremental mean survival of 4.19 years [95% CI 1.32 to 5.55]. The corresponding QALYs were 5.64 and 2.09 respectively, resulting in 3.54 incremental QALYs [95% CI 1.20 to 4.72] in favor of tafamidis. The results were sensitive to parametric distributions selected for both placebo and tafamidis. Conclusions Based on the results of the disease simulation model, tafamidis is expected to increase the life expectancy and QALYs of ATTR-CM patients by 4.19 years and 3.54 QALYs, respectively. Longer term follow-up data from the ATTR-ACT extension study will further inform these findings when available.

Cost-utility analysis of an integrated care program for children with asthma in a medium-income country.

To evaluate the cost-utility of an integrated care program (ASMAIRE Infantil Program [PAI]) for children with asthma compared with standard of care. A decision-analytic model was used to compare an integrated care program compared to the standard of care in children with asthma in Bogota, Colombia. Baseline characteristics of the patients were established according to the distribution of patients in the PAI database. Other inputs were obtained from published meta-analysis, local registries, medical bills, general mortality data, and expert opinion. Costs were presented in 2017 Colombian pesos. Outcomes included quality-adjusted life-years (QALYs). Costs and outcomes were discounted by 5% per year. Incremental cost-utility ratios were presented for PAI compared with standard of care. Univariate and multivariate probabilistic sensitivity analyses were conducted to assess model robustness to parameter uncertainty. The model predicted that patients that are part of the PAI would accrue more QALYs than patients on standard of care. The incremental results suggest that the PAI is a cost-effective treatment (incremental cost-utility ratio of Colombian pesos $33 753 817/QALY) compared with standard of care. Sensitivity analyses suggest that results are most sensitive to cost of care (with and without PAI) and costs of severe exacerbation. However, the PAI is cost-effective irrespective of variation in any of the input parameters. Our model predicted that an integrated intervention for the management of asthma in pediatric patients improves QALYs, reduces number of disease related exacerbations compared to standard therapy and is cost-effective for the long-term control of the disease in Colombia.

Cost-effectiveness analysis of pembrolizumab monotherapy versus chemotherapy for previously untreated advanced non-small cell lung cancer

Objective: To assess the cost-effectiveness of pembrolizumab monotherapy compared with standard chemotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) in previously untreated adults who have a high programmed death ligand 1 (PD-L1) tumor proportion score of 50% or greater in Singapore.Materials and methods: A partitioned-survival analysis model was developed from a healthcare system’s perspective that extrapolated clinical and economic outcomes of first-line pembrolizumab (maximum treatment duration of 2 years) versus platinum doublet chemotherapy over a 10-year time horizon for patients with advanced NSCLC. The model consisted of three health states: alive with no progression, alive with progression, and dead. Key clinical inputs were based on Kaplan-Meier survival curves from the interim (median follow-up = 11.2 months) and updated analysis (median follow-up = 25.2 months) of the KEYNOTE-024 randomized controlled trial. Local cost data were applied. Utilities were derived from published international estimates. Both one-way and multivariate probabilistic sensitivity analyses (PSA) were conducted to identify key drivers of the results.Results: Using the results from the updated analysis of KEYNOTE-024, patients treated with pembrolizumab experienced more quality adjusted life-years (QALYs), but incurred higher costs compared to chemotherapy over a 10-year time horizon (pembrolizumab: 1.9983 QALYs, SGD215,761; chemotherapy: 1.1317 QALYs, SGD70,444). The base-case incremental cost-effectiveness ratio (ICER) was SGD167,692 per QALY gained. One-way sensitivity analysis showed the ICER was most sensitive to the cost of pembrolizumab, followed by the time horizon. Multivariate PSA indicated that pembrolizumab had 0% probability of being cost-effective at a hypothetical willingness-to-pay threshold of SGD100,000 per QALY gained.Conclusion: While pembrolizumab is superior to standard chemotherapy in improving overall survival and progression-free survival, results suggest that it is unlikely to be cost-effective at its current price in Singapore. Factors including clinical effectiveness, safety, and budget impact should also be considered when making national funding decisions.

Cost-effectiveness Analysis of Feeding Guidelines for Infants Following Intestinal Surgery.

The aim of the study was to determine the cost-effectiveness of postoperative feeding guidelines to reduce complications in infants with intestinal surgery compared to standard feeding practices. Using outcomes from a cohort study, Markov models from health care and societal perspectives simulated costs per hospitalization among infants fed via guidelines versus standard practice. Short-term outcomes included intestinal failure-associated liver disease, necrotizing enterocolitis after feeding, sepsis, and mortality. Effectiveness was measured as length of stay. The incremental cost-effectiveness ratios (ICER) compared cost over length of stay. Univariate and multivariate probabilistic sensitivity analyses with 10,000 Monte Carlo Simulations were performed. A second decision tree model captured the cost per quality-adjusted life years (QALYs) using utilities associated with long-term outcomes (liver cirrhosis and transplantation). In the hospital perspective, standard feeding had a cost of $31,258,902 and 8296 hospital days, and the feeding guidelines had a cost of $29,295,553 and 8096 hospital days. The ICER was $-9832 per hospital stay with guideline use. More than 90% of the ICERs were in the dominant quadrant. Results were similar for the societal perspective. Long-term costs and utilities in the guideline group were $2830 and 0.91, respectively, versus $4030 and 0.90, resulting in an ICER of $-91,756/QALY. In our models, feeding guideline use resulted in cost savings and reduction in hospital stay in the short-term and cost savings and an increase in QALYs in the long-term. Using a systematic approach to feed surgical infants appears to reduce costly complications, but further data from a larger cohort are needed.

Economic model of albumin infusion in septic shock: The EMAISS study.

The cost-effectiveness of albumin-based fluid support in patients with septic shock is currently unknown. In a simulation study, we compared standard medical practice and systematic 20% albumin infusion. The study population consisted of patients with septic shock admitted to one of the 28 ICUs belonging to the Cub-Réa regional database between 1 January 2014 and 31 December 2016. Cost estimates were based on French diagnosis-related groups and fixed daily prices. Estimation of mortality reduction relied on ALBIOS trial data documenting a Risk Ratio of 0.87 in a non-preplanned subgroup of patients with septic shock. Life expectancy was estimated with follow up data of 184 patients with septic shock admitted in the year 2000 in the same ICUs. Several sensitivity analyses were performed including a one-way Deterministic Sensitivity Analysis (DSA) and a Probabilistic multivariate Sensitivity Analysis (PSA). About 6406 patients were included. In the base-case scenario, the mean live years gained with albumin was 0.49. The mean extra cost of using albumin was €480 per year. The cost per year gained was €974. Sensitivity analyses confirmed the robustness of the results. The probability of albumin being cost-effective was 95% and 97% for a threshold fixed at €20000 and €30000 per life-year saved, respectively. Based on the risk reduction observed in the septic shock subgroup analysis of the ALBIOS dataset, the application of the ALBIOS trial results to Cub-Réa data may suggest that albumin infusion is likely cost-effective in septic shock.

P201 Cost-effectiveness analysis of 3D versus 2D transesophageal echocardiography for the evaluation of patients with primary mitral regurgitation with indication of surgical treatment

Abstract Funding Acknowledgements Department of Cardiovascular Imaging / Brazilian Society of Cardiology OBJECTIVES To perform the cost-effectiveness analysis of three-dimensional transesophageal echocardiography (3DTEE) in comparison to two-dimensional transesophageal echocardiography (2DTEE) for the anatomic-functional evaluation and surgical planning of severe primary mitral regurgitation. METHODS: a complete economic study was based on a systematic review of 3DTEE and 2DTEE accuracy and private health system costs of two different surgical interventions: mitral valve plasty and mitral valve replacement. The prevalence of common postoperative complications was also predicted for elective procedures: atrial fibrillation (8.6%); acute myocardial infarction (1.4%); thrombosis (3.5%); bleeding (1.5%); endocarditis (6.3%). The decision tree method was adopted as a data analysis model. The Bayes" theorem was used based on sensitivity and specificity measurements. The costs, considering literature and professional tables, were: 3DTEE = US$ 349; 2DTEE = US$ 204; diagnostic evaluation = US$ 597; surgical procedure = US$ 3,643; surgical treatment = US$ 374. RESULTS: The deterministic analysis of the diagnostic test shows that 3DTEE (non-dominated) is superior to 2DTEE (absolutely dominated). The 3DTEE presents a cost reduction of US$ 1,147 and incremental effectiveness (true identification) of 22% when compared to 2DTEE. The multivariate probabilistic sensitivity analysis showed that after 100,000 iterations, the diagnosis based on the 3DTEE becomes the first choice regardless of the willingness to pay threshold. CONCLUSIONS: 3DTEE was cost-effective compared to 2DTEE. Thus, 3DTEE is a potential device to promote health compared to 2DTEE for surgical planning of severe primary mitral regurgitation Abstract P201 Figure. Sensitivity Analysis

PCN214 COST-EFFECTIVENESS ANALYSIS OF NIVOLUMAB IN COMBINATION WITH IPILIMUMAB VERSUS SUNITINIB FOR THE FIRST-LINE TREATMENT OF INTERMEDIATE- TO POOR-RISK ADVANCED RENAL CELL CARCINOMA IN FRANCE

Nivolumab in combination with ipilimumab (NIVO+IPI) is the first immuno-oncology combination to demonstrate significant, long-term overall survival (OS) benefit in previously untreated patients with intermediate- to poor-risk advanced renal cell carcinoma (1L RCC) compared with standard of care (sunitinib). The objective of this study was to assess the cost-effectiveness of NIVO+IPI compared with sunitinib in 1L RCC from the French all payers perspective. A three-state partitioned survival model (progression-free disease, progressed disease and death) was developed with a one-week cycle length and lifetime time horizon. The model used patient characteristics, progression-free survival, OS, safety data and utilities (EQ-5D-3L) from the CheckMate-214 trial (NCT02231749). French costs for drug acquisition, drug administration, monitoring, terminal care, travel and adverse events were sourced from published prices. Treatment-specific utilities were calculated using the French value set. Costs and outcomes were discounted by 4.0% annually. Univariate deterministic and multivariate probabilistic sensitivity analyses (DSA, PSA) assessed robustness of the results. Outcomes of interest were total costs, quality-adjusted life-years (QALYs), life years (LYs), the incremental cost-utility ratio (ICUR), and the incremental cost-effectiveness ratio (ICER). NIVO+IPI was associated with higher total QALYs and LYs (3.53 and 4.95) versus sunitinib (2.71 and 3.87) and increased total cost (€160,751 versus €86,596), all respectively. This resulted in an ICUR of €89,793/QALY gained and an ICER of €68,626/LY gained versus sunitinib. Based on the DSA, key model drivers were drug acquisition costs, QALY discount rate, and variation of OS function parameters (95% confidence interval). The PSA confirmed robustness of the model results, with NIVO+IPI having a 62% probability of being cost-effective at a willingness-to-pay (WTP) threshold of €100,000/QALY. Driven by an increased and sustained OS benefit, NIVO+IPI would be a cost-effective treatment when compared with sunitinib for 1L RCC patients in France at a WTP threshold of €100,000/QALY.

PMD8 COST-EFFECTIVENESS OF THERMOABLATION VERSUS SURGERY FOR TREATMENT OF LIVER METASTASIS

To perform the cost-effectiveness analysis of thermoablation versus surgery for liver metastasis treatment (lesions smaller than 3.5 cm). In the present economic evaluation, overall survival and progression-free survival probabilities for surgery and thermoablation were based on a systematic review. The model considered as horizon the Brazilian’s population average lifetime (75 years old), while the initial study population age was set at 50 years. In the health state transition model, following health states were considered: stable disease, progression and death. The costs included: thermoablation = US$ 3,328.89; surgery = US$ 7,043.22; post-procedure follow-up = US$ 190.84; thermoablation adverse events = US$ 40.26; surgery adverse events = US$ 202.11; pre-progression monitoring after thermoablation = US$ 1,120.86; pre-progression monitoring after surgery = US$ 2,666.87; palliative care after thermoablation = US$ 8,036.85; palliative care after surgery = US$ 4,0598.58. Thermoablation was superior to surgery (dominated) and presented a cost reduction of US$ 10,804.32 and incremental effectiveness of 1% when compared to surgery. The multivariate probabilistic sensitivity analysis showed that after 100,000 iterations, thermoablation had the lowest ICER regardless of the willingness to pay threshold. In the studied scenario, thermoablation was considered dominant over surgery and should be considered for the treatment of liver metastasis in Brazil.

Five-layer border dressings as part of a quality improvement bundle to prevent pressure injuries in US skilled nursing facilities and Australian nursing homes: A cost-effectiveness analysis.

The BORDER III trial found that five‐layer silicone border dressings effectively prevented pressure injuries in long‐term care, but the value of this approach is unknown. Our objective was to analyse the cost‐effectiveness of preventing facility‐acquired pressure injuries with a quality improvement bundle, including prophylactic five‐layer dressings in US and Australian long‐term care. Markov models analysed the cost utility for pressure injuries acquired during long‐term care from US and Australian perspectives. Models calibrated outcomes for standard care compared with a dressing‐inclusive bundle over 18 monthly cycles or until death based on BORDER III outcomes. Patients who developed a pressure injury simulated advancement through stages 1 to 4. Univariate and multivariate probabilistic sensitivity analyses tested modelling uncertainty. Costs in 2017 USD and quality‐adjusted life years (QALYs) were used to calculate an incremental cost‐effectiveness ratio (ICER). Dressing use yielded greater QALYs at slightly higher costs from perspectives. The US ICER was $36 652/QALY, while the Australian ICER was $15 898/QALY, both of which fell below a willingness‐to‐pay threshold of $100 000/QALY. Probabilistic sensitivity analysis favoured dressings as cost‐effective for most simulations. A quality improvement bundle, including prophylactic five‐layer dressings, is a cost‐effective approach for pressure injury prevention in all US and Australia long‐term care residents.