Incremental QALYs Research Articles

Cost-Effectiveness of Lisocabtagene Maraleucel Versus Axicabtagene Ciloleucel and Tisagenlecleucel in the Third-Line or Later Treatment Setting for Relapsed or Refractory Large B-cell Lymphoma in the United States.

The objective of this study was to evaluate the cost-effectiveness of lisocabtagene maraleucel (liso-cel) versus other available chimeric antigen receptor T-cell therapies, including axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), in patients who had received at least two prior therapies from a United States (US) commercial third-party payer perspective. To capture this heterogeneity in survival outcomes, we used mixture cure models to extrapolate progression-free survival (PFS) and overall survival (OS). Patient-level data from TRANSCEND NHL 001 for liso-cel and reconstructed patient-level data from ZUMA-1 for axi-cel, JULIET for tisa-cel, and SCHOLAR-1 for salvage chemotherapy, derived using the Guyot method, were used for OS and PFS. The model included adverse events associated with liso-cel, axi-cel, and tisa-cel. Liso-cel was less costly (incremental cost of - $74,980) and marginally more effective (0.002 incremental quality-adjusted life-years [QALY]) than axi-cel and had an incremental cost of $67,925 and 2.02 incremental QALYs over tisa-cel in the base case. Results remained consistent in sensitivity analyses, with the liso-cel OS cure fraction being the main driver of cost-effectiveness compared with both axi-cel and tisa-cel. This analysis estimated that liso-cel is cost-effective compared with tisa-cel and axi-cel from a commercial US payer perspective.

A Cost-effectiveness Analysis of Adding Cetuximab to the First-line Treatment of Metastatic Colorectal Carcinoma in Iran; Considering Genetic Screening for Precision Medicine.

This study aimed to evaluate the cost-effectiveness of cetuximab in different genetic populations of metastatic colorectal carcinoma patients, including KRAS and RAS wild types and mutants, when added to FOLFIRI treatment regimens for evidence-based disease management in Iran. A Markov decision model was designed in TreeAge software with the three states of stable, progress, and death. Clinical outcomes were extracted from published clinical studies, and costs were extracted from the Iranian local data. The primary outcome was an incremental cost-effectiveness ratio (ICER) in the simulated population. The cost-utility model from the perspective of the health system indicated that the average direct medical costs of a patient that has not been genetically screened are $56,985.27 and $20,767.74 in FOLFIRI + cetuximab and FOLFIRI regimens, respectively. However, costs per patient in the KRAS wild-type population were $21,845.52 in FOLFIRI and $78,321.22 in FOLFIRI + cetuximab. In RAS wild-type patients, FOLFIRI and FOLFIRI + cetuximab costs per patient were $23,111.62 and $84,976.39, respectively. Incremental QALYs for the above scenarios were 0.069, 0.193, and 0.285, respectively. Therefore, the ICER of add-on cetuximab in Iran compared to the treatment alternatives in the scenarios with and without KRAS screening was $520,771.55/QALY, $292,768.16/QALY, and $217,460.51/QALY. Although genetic screening in precision medicine reduces costs per outcome, according to the willingness-to-pay threshold of $4349.50 in the Iranian health system, add-on cetuximab to the FOLFIRI regimen is not a cost-effective strategy even with genetic screening and a 20% price reduction.

Cost-Effectiveness of Tepotinib Versus Capmatinib for the Treatment of Adult Patients With Metastatic Non–Small Cell Lung Cancer Harboring Mesenchymal–Epithelial Transition Exon 14 Skipping

ObjectivesFrom the US Medicare perspective, this study compared the cost-effectiveness of tepotinib and capmatinib for treating metastatic non–small cell lung cancer with tumors harboring mesenchymal–epithelial transition factor gene exon 14 skipping. MethodsA 3-state partitioned survival model assessed outcomes over a lifetime horizon. Parametric survival analysis of the phase 2 VISION trial informed clinical inputs for tepotinib. Capmatinib inputs were captured using hazard ratios derived from an unanchored matching-adjusted indirect comparison study and published literature. National cost databases, trial data, and literature furnished drug, treatment monitoring, and disease/adverse event management expenditures (2021 US dollars) and utility inputs. Outcomes were discounted at 3% annually. ResultsIn the base case, tepotinib dominated capmatinib in frontline settings (incremental discounted quality-adjusted life-years [QALYs] and costs of 0.2127 and −$47 756, respectively) while realizing an incremental cost-effectiveness ratio of $274 514/QALY in subsequent lines (incremental QALYs and costs of 0.3330 and $91 401, respectively). In a line agnostic context, tepotinib produced an incremental cost-effectiveness ratio of $105 383/QALY (incremental QALYs and costs of 0.2794 and $29 447, respectively). Sensitivity and scenarios analyses for individual lines typically supported the base case, whereas those for the line agnostic setting suggested sensitivity to drug acquisition costs and efficacy inputs. ConclusionsTepotinib could be cost-effective versus capmatinib in frontline and line agnostic contexts, considering the range of willingness-to-pay thresholds recommended by the Institute for Clinical and Economic Review ($100 000-$150 000/QALY). Tepotinib could be cost-effective in subsequent lines at higher willingness-to-pay levels. These results are to be interpreted cautiously, considering uncertainty in key model inputs.

Role of Economic Evaluations on Pricing of Medicines Reimbursed by the Italian National Health Service.

The main objective of this study was to explore the extent to which the incremental cost-effectiveness ratio (ICER), alongside other factors, predicts the final outcome of medicine price negotiation in Italy. The second objective was to depict the mean ICER of medicines obtained after negotiation. Data were extracted from company dossiers submitted to the Italian Medicines Agency (AIFA) from October 2016 to January 2021 and AIFA's internal database. Beta-based regression analyses were used to test the effect of ICER and other variables on the outcome of price negotiation (ΔP), defined as the percentage difference between the list price requested by manufacturers and the final price paid by the Italian National Health Service (INHS). In our dataset of 48 pricing and reimbursement procedures, the ICER before negotiation was one of the variables with a major impact on the outcome of negotiation when ≥ 40,000€/QALY. As resulting from multiple regression analyses, the effect of the ICER on ΔP seemed driven by medicines for non-onco-immunological and non-rare diseases. Overall, the negotiation process granted mean incremental costs of €64,688 and mean incremental QALYs of 1.96, yielding an average ICER of €33,004/QALY. This study provides support on the influence of cost-effectiveness analysis on price negotiation in the Italian context, providing an estimate of the mean ICER of reimbursed medicines, calculated using net confidential prices charged by the INHS. The role and use of economic evaluations in medicines pricing should be further improved to get the best value for money.

Economic evaluation of cladribine tablets in high disease activity (HDA) relapsing multiple sclerosis (RMS) patients in Lebanon

BackgroundCladribine tablets are a newly launched short course oral treatment approved for high disease activity (HDA) relapsing multiple sclerosis (RMS). The current analysis assessed the cost-utility and budgetary impact of introducing cladribine tablets in HDA-RMS patients compared with other HDA-RMS therapies in Lebanon. MethodsThe global cost-utility and budget impact models were adapted from Lebanese National Social Security Fund (NSSF) perspective. The data for the models’ adaptation were retrieved from the literature and validated by Lebanese experts. The comparators considered in the cost-utility model were alemtuzumab, fingolimod, and natalizumab while budget impact analysis additionally considered dimethyl fumarate. A sensitivity analysis was also performed to assess the uncertainty in the analysis. ResultsThe cost-utility results showed that cladribine tablets are an economically dominant therapeutic strategy (i.e., less costly and better quality-adjusted life year [QALY]) compared to all comparators. The cost saving was driven by drug acquisition, administration, and monitoring costs; while incremental QALY gain was driven by differences in delayed Expanded Disability Status Scale progression. Sensitivity analysis showed that cladribine tablets have a high probability (99.3–100%) of being dominant at a threshold of 22,000 United States Dollars (approximately three times of gross domestic product) per QALY gained against different comparators. The budget impact analysis showed that the introduction of cladribine tablets would result in 5.0% to 21.5% savings in the overall budget over a period of five years. ConclusionsCladribine tablets are a cost-effective and a budget-saving treatment option for the treatment of HDA-RMS patients in Lebanon from the NSSF perspective.

Cost-Effectiveness of Ticagrelor for Acute Coronary Disease to Prevent Cardiovascular Events in Three Hospitals in Indonesia

Background: Acute coronary syndromes (ACS) are life-threatening CVD associated with Indonesia's significant health and economic burdens. The study objective was to evaluate the cost-effectiveness of ticagrelor in reducing CV endpoint in the Indonesia setting.
 Methods: Markov model was used as a decision analysis to compare ticagrelor with clopidogrel. We constructed decision tree model included four health conditions (no additional events, non-fatal myocardial infarction, non-fatal stroke, and any cause death), The probability of each state and quality-adjusted life years were derived from the PLATO trial and Indonesia life table. The outcome's resource consumption and associated costs were collected from three hospitals (public, national referral, and private hospitals) in Indonesia. The study used 5 years and lifetime horizon and discounting rate of 3%.
 Results: The incremental QALYs and life-year gained (LYG) of ticagrelor in five years was 0.0410 and 0.0462, respectively; in a lifetime was 0.0828, and 0.0947, respectively. The ICER per QALY of ticagrelor versus clopidogrel in private, national referral, and public hospitals was USD 2390.276, USD 3813.638, USD 1278.361, respectively for five years; and USD 2471.392, USD 5453.987, USD 2343.269, respectively for a lifetime. The probability of ticagrelor to be cost-effective was about 66.6% on a five-year and 99.7% on a lifetime with WTP USD 3634.
 Conclusion: Compared to the clopidogrel, QALYs and life-year gained of use ticagrelor higher. The incremental cost-effectiveness ratio in five years and lifetime model showed under one-time GDP, it means the use of ticagrelor was vastly cost-effective and acceptable to apply in the Indonesian clinical setting.

Economic evaluations of adjunctive osimertinib treatment in surgically resected epidermal growth factor receptor-positive (EGFR+) non-small cell lung cancer (NSCLC): Analysis for stage 2 disease.

e20506 Background: Following surgical resection, patients with NSCLC require monitoring due to the risk of recurrence. Studies have demonstrated the clinical benefit of osimertinib, a tyrosine kinase inhibitor, as adjunctive therapy in surgically resected EGFR+ NSCLC, including in stage 2 disease. We performed a cost effectiveness/utility analysis of adjunctive osimertinib therapy in stage 2 disease following surgical resection. Methods: A two state partitioned survival model differentiating disease free survival (DFS) from disease recurrence and death was specified (US payer perspective). Parametric functions were fit to digitized overall survival (OS) and DFS curves. A 5 year time horizon was specified, with a 3% discount rate applied to costs and utilities beyond year 1. Costs of treatment (wholesale acquisition cost), adverse events (grade 3/4 except all grades for immunotherapy related AEs), and monitoring were sourced from, respectively, Redbook, literature, and Physician Fee Schedules (US $2021). DFS life years (DFSLY) and quality adjusted life years (DFSQALY), incremental cost effectiveness/utility ratios (ICER/ICUR) in terms of DFSLY and DFSQALY gained (g) were estimated in base case analyses (BSA) and probabilistic sensitivity analyses (PSA). Results: Exponential regression was used to extrapolate osimertinib and placebo Kaplan-Meier curves. As detailed below, in BCA (PSA) the incremental cost of osimertinib over placebo was $778,315 ($778,202). The incremental DFSLY was 1.740 (1.738), which yielded ICER of $447,349/DFSLYg ($447,768/DFSLYg). The incremental DFS QALY was 1.234 (1.232), yielding ICUR of $630,910/DFSQALYg ($631,498/DFSQALYg). Conclusions: As to disease recurrence in stage 2 surgically resected EGFR+ NSCLC, our model associated adjunctive osimertinib therapy with incremental clinical gains of 1.740 (1.738) DFSLY and 1.234 (1.232) DFSQALY compared to placebo, however at marked incremental cost. As adjunctive osimertinib treatment is indicated in EGFR+ NSCLC disease stages 1B and 3A, the present stage 2 cost effectiveness/utility results should be compared to those for stages 1B and 3A.[Table: see text]

Economic evaluations of adjunctive osimertinib treatment in surgically resected epidermal growth factor receptor positive (EGFR+) non-small cell lung cancer (NSCLC): Analysis for stage 3A disease.

e20505 Background: Patients with surgically resected EGFR+ NSCLC remain at risk of recurrence after surgery. Osimertinib, a tyrosine kinase inhibitor, had been assessed clinically as adjunctive therapy in surgically resected EGFR+ NSCLC including stage 3A. We conducted a cost effectiveness/utility analysis of adjunctive osimertinib therapy in stage 3A surgically resected EGFR+ NSCLC. Methods: We specified a two state partitioned survival model of disease free survival (DFS) versus disease recurrence and death in a), with a 5 year time horizon (US payer perspective). DFS and overall survival curves were extrapolated per parametric functions. A 3% discount rate was utilized to costs and utilities beyond year 1. Costs of therapies (wholesale acquisition cost), adverse events (AE; grade 3/4; all grades for immunotherapy related AEs), and monitoring costs were based on Redbook, publications, and Physician Fee Schedules, respectively (US $2021). Costs, DFS life years (DFSLY) and DFS quality adjusted life years (DFSQALY) were used to determine the incremental cost effectiveness/utility ratios (ICER/ICUR) of the additional cost needed to gain (g) a DFSLY and DFSQALY in base case (BSA) and probabilistic sensitivity analyses (PSA). Results: Exponential regression was used to extrapolate the Kaplan-Meier curves of osimertinib and placebo,. As shown in the table, the BCA (PSA) estimated the incremental cost at $669,369 ($670,274). The incremental DFSLY was 1.895 (1.899), yielding ICER of $353,125/DFSLYg ($352,963/DFSLYg). The incremental DFS QALY was 1.35, yielding an ICUR of $497,905/DFSQALYg ($497,676/DFSQALYg). Conclusions: In stage 3A surgically resected EGFR+ NSCLC, adjunctive osimertinib therapy showed incremental benefits of 1.895 (1.899) DSFLYg and 1.344 (1.349) QALYg compared to placebo, however at marked incremental cost. As adjunctive osimertinib treatment is indicated in EGFR+ NSCLC disease stages1B and 2, the present stage 3A cost effectiveness/utility results should be compared to those for stages 1B and 2.[Table: see text]

Cost-effectiveness analysis of sintilimab + chemotherapy versus camrelizumab + chemotherapy for the treatment of first-line locally advanced or metastatic nonsquamous NSCLC in China

Background and objective Sintilimab is a selective PD-1 inhibitor with efficacy in advanced or metastatic nonsquamous non-small-cell lung cancer (NSCLC) patients. This study evaluated the cost-effectiveness of sintilimab + chemotherapy versus camrelizumab + chemotherapy as the first-line treatment for locally advanced or metastatic nonsquamous NSCLC in Chinese patients. In addition, this study aimed to reveal the impact of the reference treatment choice on the incremental cost-effectiveness ratio (ICER) results. Methods A partitioned survival model (PSM) with three health states was constructed in a 3-week cycle with a lifetime horizon from the Chinese healthcare system perspective. Anchored matching adjusted indirect comparison was used for survival analyses based on individual patient data from Orient-11. Sintilimab + chemotherapy was chosen as the reference treatments in scenarios 1 and 2, while the camrelizumab + chemotherapy was chosen as the reference treatments in scenario 3. The utility values of different health states were derived from the patient-level European Organization for Research and Treatment Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) scores by mapping to the EQ-5D-5L, and QALYs were calculated as the health outcomes. One-way deterministic sensitivity analysis (DSA) and probability sensitivity analysis (PSA) were performed to explore model uncertainty. Results Compared to camrelizumab + chemotherapy, sintilimab + chemotherapy was associated with higher effectiveness (incremental QALYs ranged from 0.13–0.62) and lower total costs (incremental costs ranged from $1,099–$5,201), resulting in an ICER ranging from $6,440–$8,454/QALY. Conclusions Sintilimab + chemotherapy is a cost-effective option compared with camrelizumab + chemotherapy as the first-line treatment for locally advanced or metastatic nonsquamous NSCLC in China.

Monthly migraine days, tablet utilization, and quality of life associated with Rimegepant \u2013 post hoc results from an open label safety study (BHV3000\u2013201)

BackgroundThe objective of this study was to describe patterns in monthly migraine days (MMD) and tablet utilization, and to estimate health-related quality of life (HRQoL) measures in patients treated as needed (PRN) with rimegepant 75 mg over 52-weeks.MethodsEligible subjects were adults with ≥1 year history of migraine and ≥ 6 MMD at baseline, who used rimegepant 75 mg up to once daily PRN (at their discretion) for up to 52-weeks in an open-label safety study (BHV3000–201; NCT03266588). Mean MMD were calculated at each 4-week period, along with mean monthly tablets taken. Migraine-specific quality of life (MSQv2) data were mapped to EQ-5D utilities and used to characterize HRQoL over time. A published network meta-analysis was used to characterize pain hours as well as time periods spent migraine free.ResultsOne thousand forty four subjects were included in this post-hoc analysis. Overall mean MMD were 10.9 at baseline and decreased to 8.9 by week 52. Tablet use remained stable over the follow-up period. A total of 0.08 incremental QALYs were associated with rimegepant use.ConclusionFor subjects with 6 or more MMD, acute treatment of migraine attacks with rimegepant 75 mg on a PRN basis over one-year of follow-up was found to be associated with reduced MMD frequency without an increase in monthly tablet utilization, and improved HRQoL. There was no evidence of medication-related increases in MMDs when rimegepant 75 mg was used as needed for the acute treatment of migraine over 52-weeks.Trial registrationClinicalTrials.gov identifier NCT03266588.

Cost-Utility Analysis of Screening for Diabetic Retinopathy in China.

Background. Diabetic retinopathy (DR) has been primarily indicated to cause vision impairment and blindness, while no studies have focused on the cost-utility of telemedicine-based and community screening programs for DR in China, especially in rural and urban areas, respectively.Methods. We developed a Markov model to calculate the cost-utility of screening programs for DR in DM patients in rural and urban settings from the societal perspective. The incremental cost-utility ratio (ICUR) was calculated for the assessment.Results. In the rural setting, the community screening program obtained 1 QALY with a cost of $4179 (95% CI 3859 to 5343), and the telemedicine screening program had an ICUR of $2323 (95% CI 1023 to 3903) compared with no screening, both of which satisfied the criterion of a significantly cost-effective health intervention. Likewise, community screening programs in urban areas generated an ICUR of $3812 (95% CI 2906 to 4167) per QALY gained, with telemedicine screening at an ICUR of $2437 (95% CI 1242 to 3520) compared with no screening, and both were also cost-effective. By further comparison, compared to community screening programs, telemedicine screening yielded an ICUR of 1212 (95% CI 896 to 1590) per incremental QALY gained in rural setting and 1141 (95% CI 859 to 1403) in urban setting, which both meet the criterion for a significantly cost-effective health intervention.Conclusions. Both telemedicine and community screening for DR in rural and urban settings were cost-effective in China, and telemedicine screening programs were more cost-effective.

Can we increase efficiency of CT lung cancer screening by combining with CVD and COPD screening? Results of an early economic evaluation

ObjectivesEstimating the maximum acceptable cost (MAC) per screened individual for low-dose computed tomography (LDCT) lung cancer (LC) screening, and determining the effect of additionally screening for chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), or both on the MAC.MethodsA model-based early health technology assessment (HTA) was conducted to estimate whether a new intervention could be cost-effective by calculating the MAC at a willingness-to-pay (WTP) of €20k/quality-adjusted life-year (QALY) and €80k/QALY, for a population of current and former smokers, aged 50–75 years in The Netherlands. The MAC was estimated based on incremental QALYs gained from a stage shift assuming screened individuals are detected in earlier disease stages. Data were obtained from literature and publicly available statistics and validated with experts.ResultsThe MAC per individual for implementing LC screening at a WTP of €20k/QALY was €113. If COPD, CVD, or both were included in screening, the MAC increased to €230, €895, or €971 respectively. Scenario analyses assessed whether screening-specific disease high-risk populations would improve cost-effectiveness, showing that high-risk CVD populations were more likely to improve economic viability compared to COPD.ConclusionsThe economic viability of combined screening is substantially larger than for LC screening alone, primarily due to benefits from CVD screening, and is dependent on the target screening population, which is key to optimise the screening program. The total cost of breast and cervical cancer screening is lower (€420) than the MAC of Big-3, indicating that Big-3 screening may be acceptable from a health economic perspective.Key Points• Once-off combined low-dose CT screening for lung cancer, COPD, and CVD in individuals aged 50–75 years is potentially cost-effective if screening would cost less than €971 per screened individual.• Multi-disease screening requires detailed insight into the co-occurrence of these diseases to identify the optimal target screening population.• With the same target screening population and WTP, lung cancer-only screening should cost less than €113 per screened individual to be cost-effective.

A Cost-Effectiveness Analysis of Exalt Model D Single-Use Duodenoscope Versus Current Duodenoscope Reprocessing Methods

Background and AimsThe spread of duodenoscope-related infections has led to the recognition that reprocessing of duodenoscopes using high-level disinfection (HLD), if done perfectly, narrowly meets the advised thresholds of endoscope decontamination. In 2019, the US Food and Drug Administration (FDA) recommended a transition to duodenoscopes designed to pose less risk, including the use of disposable duodenoscopes. The Exalt Model D (Boston Scientific Corp, Marlborough, MA) single-use duodenoscope (EXALT) has been shown to be substantially equivalent to reusable duodenoscopes for clinical use. The aim of this study was to estimate the cost-effectiveness of EXALT in the United States healthcare system. MethodsA cost-effectiveness model was developed comparing HLD, culture-and-quarantine (CQ), Ethylene oxide sterilization (ETO), and EXALT in a simulated cohort undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) for choledocholithiasis. Published information was leveraged describing clinical estimates, infectious outbreaks, and hospital costs. ResultsIn a base analysis, HLD was the least costly ($962), and EXALT was the costliest ($3000), but yielded the most QALYs (0.0172 incremental QALYs). The incremental cost-effectiveness ratio was $38,461 for ETO gas sterilization and $62,185 for EXALT. However, with the availability of device-specific reimbursement for EXALT in the US in the form of transitional pass-through payment (TPT) and new technology add-on payment (NTAP), EXALT provided the highest cost-savings to the hospital versus alternative strategies by maintaining QALY gains while decreasing estimated net costs. Probabilistic sensitivity analyses showed EXALT to be preferred compared to HLD over a range of willingness-to-pay. ConclusionEXALT is a viable and cost-effective strategy that should be strongly considered for ERCP.

S1392 Cost-Effectiveness of Incomplete Gastrointestinal Metaplasia Surveillance in Gastric Cancer Screening

Introduction: Gastric cancer in the United States has a grim prognosis with an overall 5-year survival rate of 32%. Unfortunately, in the U.S., there are no established guidelines for screening or surveillance of gastric cancer. Widespread endoscopic screening and surveillance of the general population in East Asian countries has demonstrated significant reductions in gastric cancer mortality, owing to the high gastric cancer prevalence in these regions. Given the low prevalence of gastric cancer in the western world (a 10-year risk of 1.6%, according to the AGA), screening the general population isn’t cost-effective. However, endoscopic surveillance of individuals with atrophic gastritis, intestinal metaplasia and dysplasia (high-risk) has been shown to detect early gastric cancer in western populations. We investigated the possibility of the cost-effectiveness of routine endoscopic surveillance of individuals with incomplete gastric intestinal metaplasia (iGIM), given the higher risk of gastric cancer in this group. Methods: A Markov state-transition model was designed to analyze the cost-effectiveness of biennial esophagogastroduodenoscopy versus no surveillance (current standard) in individuals with iGIM over 20 years using a healthcare payer perspective. - A Markov cohort simulation was then carried out on a hypothetical population of 1000 patients for both arms. Utility weights, transition rates and probabilities were derived from published literature. - Costs of esophagogastroduodenoscopy, surgery and cancer care were calculated using Medicare reimbursement. - A willingness-to-pay threshold of $100,000/QALY was used to determine cost-effectiveness. Results: Base Case analysis of the data revealed that the cost of care of non-cardia gastric cancer in the biennial endoscopic surveillance arm was $ 76,357 lesser than that of the no-surveillance arm. - The total cost of non-cardia gastric cancer care in the no surveillance arm was $263,430, while the total cost of care in the biennial surveillance arm was $187,073. - The surveillance arm demonstrated incremental cost savings of $6815 and an incremental QALY value of 0.076. The endoscopic strategy was found to be dominant. Conclusion: When using a willingness-to-pay threshold of $100,000/QALY to detect overall cost-effectiveness our study demonstrates that biennial endoscopic surveillance in those with iGIM is very cost-effective. Confirmatory research should be done before specific recommendations can be given but the results are encouraging.Figure 1.: Cost-effectiveness Acceptability Curve. The curve depicts the probability of cost-effectiveness of surveillance endoscopy at different willingness to pay thresholds. X-Axis (A): Willingness to pay in dollars. Y-Axis (B): % Iteration cost-effective.

A Systematic Review of Health Technology Assessments of Chimeric Antigen Receptor T-Cell Therapies in Young Compared With Older Patients

ObjectivesThe objective of this review was to identify sources of variability in cost-effectiveness analyses of chimeric antigen receptor T-cell (CAR-T) therapies, tisagenlecleucel and axicabtagene ciloleucel, evaluated by health technology assessment (HTA) agencies, focusing on young compared with older patients. MethodsHTA evaluations in pediatric acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma (DLBCL) were included from Australia, Canada, England, Norway, and the United States. Key clinical evidence, economic approach, and outcomes (costs, quality-adjusted life-years [QALYs] and incremental cost-effectiveness ratios) were summarized. ResultsFourteen HTA evaluations were identified (5 ALL, 9 DLBCL [4 tisagenlecleucel, 5 axicabtagene]). Analyses were naive comparisons of prospective single-arm studies for the CAR-Ts with retrospective cohort studies for the comparators. Key clinical evidence and economic model approaches were generally consistent by CAR-T and indication, although outcomes varied. Notably, incremental QALYs varied substantially in ALL (3.67-10.6 QALYs gained), whereas variation in DLBCL was less (1.21-1.97 [tisagenlecleucel], 1.97-3.40 [axicabtagene]). Discounting of costs and outcomes varied, with the highest QALYs generated for tisagenlecleucel in ALL (10.95) associated with the lowest discount rate (1.5%) and vice versa (4.97 QALYs; 5% discount rate). The approach to extrapolation of overall survival data varied, even where the same empirical data were used. ConclusionModeled, long-term treatment benefit in young patients may be associated with greater uncertainty compared with adults because of potential life-long benefits with cell and gene therapies. This reflects the methodological challenges identified by HTA agencies associated with single-arm, short-term studies.

CE1 A Modeled Health Outcomes Evaluation of Darolutamide Plus Androgen Deprivation Therapy for High-Risk NON-Metastatic Castration-Resistant Prostate Cancer in China

Novel antiandrogens have demonstrated clinical benefit for patients with non-metastatic castration resistant prostate cancer (nmCRPC). We modeled the incremental life-years and QALYs of darolutamide+ADT compared to apalutamide+ADT and enzalutamide+ADT, for high-risk nmCRPC, in a Chinese setting. A partitioned survival model with three health states (nmCRPC, metastatic CRPC and death) was devised. Data from the ARAMIS, PROSPER and SPARTAN trials were used, in the absence of head-to-head studies. Hazard ratios (HRs) characterizing overall survival (OS) were derived from formal indirect treatment comparisons of the OS HRs between the three trials; the point estimates of the OS HRs characterizing the indirect comparison of darolutamide+ADT vs apalutamide+ADT and enzalutamide+ADT were 0.88 and 0.95, respectively. Parametric survival functions were selected for extrapolation based on the goodness of fit. The baseline characteristics, treatment patterns and utilities for this modeled Chinese cohort were validated with 12 urologists from 11 hospitals. A discount rate of 5% was applied. Univariate and probabilistic sensitivity analyses were performed. With a 20-year modeling horizon, darolutamide+ADT yielded more life years (5.98LYs) and QALYs (4.61QALYs) than both apalutamide+ADT (5.64LYs, 4.43QALYs) and enzalutamide+ADT (5.82LYs, 4.55QALYs). The incremental QALY gains with darolutamide+ADT vs. apalutamide+ADT (+0.18QALYs) and vs. enzalutamide+ADT (+0.06QALYs) were mainly driven by the improved life years during post-progression survival (+0.92LYs vs. apalutamide+ADT and +0.65LYs vs. enzalutamide+ADT). Results were sensitive to the HRs and utility inputs; however, the probabilities of darolutamide+ADT having incremental QALYs reached 70.4% and 56.8% when compared to apalutamide+ADT and enzalutamide+ADT, respectively. This modeled evaluation indicates that darolutamide+ADT is likely to be associated with incremental health outcomes over apalutamide+ADT and enzalutamide+ADT, for a high-risk nmCRPC Chinese cohort, over a 20-year time-frame.

PIN27 Cost-utility Analysis Focused on Nosocomial Pneumonia Antimicrobial Therapy - Is Ceftolozane/Tazobactam an Option to Fight Antimicrobial Resistance Sustaining Public Health System Affordability in Brazil?

Gram-negative bacterial (GNB) infections have become increasingly difficult to treat due to raising antimicrobial resistance rates in certain geographic regions such as Latin America. Ceftolozane-tazobactam (C/T) is a beta-lactam-beta-lactamase inhibitor agent that can be considered a clinical option for nosocomial pneumonia in critically ill patients caused by suspected meropenem and piperacillin-tazobactam resistant isolates in public Brazilian hospitals. We applied a model previously described by Naik et al. for patients that could be at risk of nosocomial pneumonia (NP) caused by Enterobacterales or Pseudomonas aeruginosa and should receive empiric antimicrobial therapy. The pathogens’ distribution was adapted from a 2018-2019 Brazil subsample in a global pathogen surveillance database. Clinical outcomes were extracted from a phase 3 trial of NP patients comparing C/T against meropenem. Piperacillin-tazobactam and meropenem were selected as comparators, being the most used antimicrobials in NP. Costs considered in this model were obtained through publications and publicly available databases such as SIGTAP and SIH that represent the Brazilian public healthcare system perspective on costs and care. A 5% discount rate was applied to costs and outcomes. When compared to meropenem the use of C/T can reduce mortality from 32.7% to 29.0%. The use of C/T resulted in 0.28 additional LYs and 0.22 incremental QALYs with R$8,592.87 incremental costs resulting in an ICER of R$39,723.33/QALY. Considering piperacillin-tazobactam as comparator, C/T could reduce mortality from 36.3% to 29.0%, generating 1.12 incremental LYs and 0.93 additional QALYs with R$3,987.06 additional costs. Resulting in an ICER of R$4,286.93/QALY. Antimicrobials accounts for 29.1% of total costs when considering treatment, hospital resource use, adverse events and patient monitoring. Against both comparators the C/T arm patients presented shorter ventilator and ICU length of stay. C/T could be a cost-effective option for NP in the Brazilian public healthcare system according to the World Health Organization's threshold.

EM1 When Are Breakthrough Therapies Cost-Effective?

The US Food and Drug Administration (FDA)-designated breakthrough therapies offer substantial potential to improve health outcomes, but it is unclear whether their health gains represent favorable value for money. Using the Tufts Medical Center Cost-Effectiveness (CE) Analysis Registry we: (1) summarized the cost-effectiveness of breakthrough therapies (BT), as measured by the cost-per-quality-adjusted-life-year (QALY) metric; (2) compared the cost-effectiveness of BT and non-breakthrough therapies (NBT) in the US; and (3) identified factors associated with BT cost-effectiveness, using logistic regression models with a range of value benchmarks ($50K-$150K/QALY). Between 2013 and 2018, FDA approved 264 drugs, designating 84 (32%) as breakthrough therapies. We identified published US CE studies for 26% of BT drugs (48 studies, 227 CE ratios) and 23% of NBT drugs (60 studies, 96 CE ratios). Publications focused on hepatitis C (HepC) or other infectious diseases (38% of BT studies, 23% of NBT studies) and neoplasms (48% of BT studies, 11% of NBT studies). Median BT incremental costs and QALYs exceeded corresponding values for NBT ($29,231 vs. $20,263 and 0.7 vs. 0.2 QALYs, respectively), and CE ratios trended toward greater favorability for BT compared to NBT drugs (median values $38,000/QALY vs. $50,000/QALY, respectively). For BTs, HepC drugs had the most favorable CE ratios, as removing HepC studies increased the median CE ratio to more than $140,000 (with median $65,000 incremental cost and 0.61 QALYs gained). Further, BTs for new molecular entities (NME) had median CE ratios about 40% lower than non-NME BTs, reflecting their smaller incremental costs and greater QALY gains. Breakthrough drugs may confer greater health benefits than NBTs in terms of QALYs gained. However, nuances, such as target condition, NME, and choice of comparator greatly influence whether greater relative health gains represent favorable value for money.

Cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or standard of care in patients with type 2 diabetes and established cardiovascular disease

IntroductionEmpagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, is approved in the USA to reduce risk of cardiovascular (CV) death in adults with type 2 diabetes mellitus (T2DM) and established CV disease,...

Cost-utility analysis: Mechanical thrombectomy plus thrombolysis in ischemic stroke due to large vessel occlusion in the public sector in Chile

Several studies demonstrate the therapeutic superiority of thrombolysis plus mechanical thrombectomy versus thrombolysis alone to treat stroke. To analyze the cost-utility of thrombolysis plus mechanical thrombectomy versus thrombolysis in patients with ischemic stroke due to large vessel occlusion. Cost-utility analysis. The model used is blended: Decision Tree (first 90 days) and Markov in the long term, of seven health states based on a disease-specific scale, from the Chilean public insurance and societal perspective. Quality-Adjusted Life-Years and costs are evaluated. Deterministic (DSA) and probabilistic (PSA) analyses were carried out. From the public insurance perspective, in the base case, mechanical thrombectomy is associated with lower costs in a lifetime horizon, and with higher benefits (2.63 incremental QALYs, and 1.19 discounted incremental life years), at a Net Monetary Benefit (NMB) of CLP 37,289,874, and an Incremental Cost-Utility Ratio (ICUR) of CLP 3,807,413/QALY. For the scenario that incorporates access to rehabilitation, 2.54 incremental QALYs and 1.13 discounted life years were estimated, resulting in an NMB of CLP 35,670,319 and ICUR of CLP 3,960,624/QALY. In the scenario that incorporates access to long-term care from a societal perspective, the ICUR falls to CLP 951,911/QALY, and the NMB raises to CLP 43,318,072, improving the previous scenarios. In the DSA, health states, starting age, and relative risk of dying were the variables with the greatest influence. The PSA for the base case corroborated the estimates. Thrombolysis plus mechanical thrombectomy adds quality of life at costs acceptable for decision-makers versus thrombolysis alone. The results are consistent with international studies.