Cost-effectiveness analysis of tislelizumab vs. camrelizumab for the treatment of second-line locally advanced or metastatic esophageal squamous cell carcinoma.

BACKGROUND: Esophageal carcinoma is a type of cancer that occurs in the esophagus. For patients with locally advanced or metastatic esophageal squamous cell carcinoma who have either experienced disease progression following first-line standard chemotherapy or are intolerant to it, the prognosis is typically poor. Additionally, these patients often bear a substantial economic burden during the course of their treatment. Tislelizumab is a selective PD-1 inhibitor with efficacy proven in locally advanced or metastatic esophageal squamous cell carcinoma. The study aims to evaluate the cost-effectiveness of tislelizumab versus camrelizumab as the second-line treatment in locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients in China. METHODS: From the perspective of China's healthcare system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime horizon. Anchored matching adjusted indirect comparison was used for survival analyses based on individual patient data from RATIONALE 302 trial and the published ESCORT study due to the lack of head-to-head clinical trials. Only direct medical costs were included. Costs and utility values were derived from local charges, the published literature, and related databases. Sensitivity analyses and a scenario analysis were also performed to verify the robustness of the model results. RESULTS: Compared with camrelizumab monotherapy, tislelizumab monotherapy incurred a lower lifetime cost ($8,346 vs. $8,851) and yielded higher quality-adjusted life-years (QALYs) (0.87 vs. 0.63), which resulted in an incremental cost-effectiveness ratio (ICER) of -$2,051/QALY. Tislelizumab monotherapy is a dominant option over camrelizumab monotherapy in China. The three primary parameters upon which this result was most sensitive were the unit cost of camrelizumab, the unit cost of tislelizumab, and the duration of reactive cutaneous capillary endothelial proliferation (RCCEP). According to the probabilistic sensitivity analysis (PSA), tislelizumab monotherapy was 100% cost-effective when the WTP was 1-3 times GDP per capita in China($11,207/QALY∼$33,621/QALY). Scenario analysis showed that the result was consistent. CONCLUSION: Tislelizumab monotherapy is a dominant option compared with camrelizumab monotherapy as the second-line treatment for locally advanced or metastatic ESCC in China.

Cost-effectiveness of edaravone dexborneol versus human urinary kallidinogenase for acute ischemic stroke in China.

BACKGROUND: Clinical trials have demonstrated the efficacy of edaravone dexborneol in the treatment of acute ischemic stroke. This study aims to determine the cost-effectiveness of edaravone dexborneol compared with human urinary kallidinogenase from China's healthcare system perspective. METHODS: A combination of the decision tree and Markov model was constructed to evaluate the cost-effectiveness of edaravone dexborneol versus human urinary kallidinogenase in the treatment of acute ischemic stroke over a lifetime horizon. Efficacy data were derived from pivotal clinical trials of edaravone dexborneol and human urinary kallidinogenase (TASTE trial and RESK trial, respectively) and adjusted using matching-adjusted indirect comparison. Cost and health utility inputs were extracted from published literature and open databases. One-way deterministic sensitivity and probabilistic sensitivity analyses were performed to examine the robustness of the results. RESULTS: Compared with human urinary kallidinogenase, edaravone dexborneol generated 0.153 incremental quality-adjusted life years (QALYs) with an incremental cost of ¥856, yielding an incremental cost-effectiveness ratio of ¥5,608 per QALY gained under the willingness-to-pay threshold (one-time gross domestic product per capita). Both one-way deterministic sensitivity analysis and probabilistic sensitivity analysis demonstrated the robustness of the base case results. CONCLUSIONS: Edaravone dexborneol is a cost-effective treatment choice for acute ischemic stroke patients compared with human urinary kallidinogenase in China.

Methods for Economic Evaluations of Novel Oral Anticoagulants in Patients with Atrial Fibrillation: A Systematic Review.

BACKGROUND: Atrial fibrillation (AF) is a severe epidemiological and public health concern among the elderly population worldwide, with substantial economic and social burdens. Economic evaluations can play an essential role in optimizing the utilization of scarce resources. In recent years, the number of economic evaluation studies related to AF has increased due to the rising number of AF patients, the continuous updating of clinical data, and the emergence of real-world evidence. However, there are still deficiencies in model settings and parameter sources in relevant studies. OBJECTIVE: This study aims to review the existing economic evaluations of novel oral anticoagulants (NOACs) in patients with AF and summarize the evidence and methods applied. METHODS: A comprehensive and systematic search was conducted on electronic databases, including PubMed, Embase, Web of Science (WOS), and The Cochrane Library, from the date of database creation to November 2022. The reporting quality of included literature was assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement. RESULTS: A total of 102 studies were included in the review, with 200 comparisons between NOACs and vitamin K antagonists (VKAs), as well as 58 comparisons between different NOACs. The healthcare sector and payer perspectives were the most common, and accordingly, the majority of the evaluations considered only direct medical costs. Most studies used Markov cohort models with the number of health states ranging from 4 to 29. Of included studies, 80 (78%) considered event recurrence and complications, and 78 (76%) considered discontinuation and second-line therapy. All of the studies applied uncertainty analysis to explore the robustness of the results. Of all 200 NOACs-VKAs comparisons, 149 (75%) showed that NOACs were more cost-effective; this proportion was 84% (139 out of 165) in high-income countries but decreased to 29% (10 out of 35) in middle- and low-income countries. Most (82%) of the 28 items in the CHEERS 2022 checklist were elucidated in the majority of included studies. A minority (only 39%) of included studies demonstrated high reporting quality. CONCLUSION: NOACs may be more cost-effective than VKAs in patients with AF, but this conclusion applies to high-income countries, whereas VKAs may be more cost-effective in middle- and low-income countries. The reporting quality of included studies was variable, and certain methodological issues were presented. This study highlights the economic evaluation methodology of NOACs in patients with AF and provides recommendations for modeling methods and future studies.

Economic evaluation of sintilimab plus chemotherapy vs. pembrolizumab plus chemotherapy for the treatment of first-line advanced or metastatic squamous NSCLC.

Background and objective: Sintilimab has superior efficacy and safety in patients with advanced or metastatic squamous non-small cell lung cancer (NSCLC), but its cost-effectiveness in China is unclear. This study is to evaluate the cost-effectiveness of sintilimab plus chemotherapy vs. pembrolizumab plus chemotherapy for locally advanced or metastatic squamous NSCLC in China. Methods: From the perspective of the Chinese health system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime time horizon. The two-stage method was used to estimate the overall survival hazard ratios to avoid the bias by crossover design in ORIENT-12 and KEYNOTE-407 studies. The anchored matching adjusted indirect comparison method (MAIC) was used for indirect comparison based on the individual patient data from ORIENT-12 and the publicly published KEYNOTE-407 study due to the lack of head-to-head clinical trials. Only direct medical costs were included, and utilities were derived from the published literature in the base case analysis. Sensitivity analysis was also performed to verify the robustness of the model results. In addition, the scenario analysis where the utilities were derived from the Quality of Life Questionnaire-Core 30 (QLQ-C30) scale in the ORIENT-12 by mapping to the EuroQol-5-dimension 5-level (EQ-5D-5L) was carried out to explore the uncertainty of the results. Results: Compared with pembrolizumab + chemotherapy, sintilimab + chemotherapy incurred a lower lifetime cost ($12,321 vs. 36,371) and yielded fewer quality-adjusted life-years (QALYs) (0.9902 vs. 1.0085), which resulted in an incremental cost-effectiveness ratio (ICER) of $1,314,208/QALY. A sintilimab strategy is a cost-effectiveness option under the WTP of 1-3 times the GDP per capita in China ($11,250/QALY~$33,749/QALY). The utility value of the post-progression, the unit cost of albumin paclitaxel, and the utility value of the progression-free state were the main drivers in the deterministic sensitivity analysis (DSA). According to the probabilistic sensitivity analysis (PSA), sintilimab + chemotherapy was 100% cost-effective when the WTP was 1-3 times China's per capita GDP. The results of the scenario analysis showed that sintilimab + chemotherapy obtained more QALYs (1.2319 vs. 1.1815) and lower costs ($12,321 vs. 36,371), which implied that sintilimab + chemotherapy may dominate the pembrolizumab + chemotherapy. Conclusion: Compared with pembrolizumab + chemotherapy, sintilimab + chemotherapy is more cost-effective for first-line treatment in Chinese patients with locally advanced or metastatic squamous NSCLC.

Health utilities in pediatric cancer patients and survivors: a systematic review and meta-analysis for clinical implementation.

PURPOSE: Health utility (HU) is a useful metric for evaluating cost and utility of cancer therapies or prioritizing healthcare resources. We conducted a meta-analysis to compare HUs in association with clinical parameters and identify missing cancer-related themes from the extant HU measures for pediatric cancer patients and survivors. METHODS: Studies published in the PubMed, Embase, Web of Science, and Cochrane Library were identified. Meta-analyses were performed to estimate weighted means of HUs assessed by self- and proxy-responses. Mixed-effects meta-regressions were applied to compare HUs between cancer patients/survivors and general populations. Missing themes in the extant measures were identified based on established patient-reported outcomes frameworks. RESULTS: Of 123 selected studies included pediatric cancer populations, 44% used the Health Utilities Index version 2 (HUI2), and 48% used version 3 (HUI3). Compared to general populations, cancer patients undergoing therapies for acute lymphoblastic leukemia (ALL) had 0.129 (95% CI - 0.183 to - 0.075) and brain tumor had 0.257 (95% CI - 0.354 to - 0.160) lower HUs per proxy-reported HUI3, whereas survivors of ALL had 0.028 (95% CI - 0.062 to 0.007) and brain tumor had 0.188 (95% CI - 0.237 to - 0.140) lower HUs per proxy-reported HUI3. Compared to general populations, cancer patients treated with multimodality therapy and survivors off therapy 2-5 years had significantly poorer HUs (p's < 0.05). Missing cancer-specific contents from the HU measures were identified. CONCLUSION: Pediatric cancer patients and survivors had poorer HUs than general populations. It is important to select appropriate HUs for economic evaluations, and offer interventions to minimize HU deficits for particular cancer populations.

Culture-Related Health Disparities in Quality of Life: Assessment of Instrument Dimensions Among Chinese.

Background: Health-related quality of life (HRQoL) is one of the major focuses of primary care. However, HRQoL instruments used in China are mainly developed from Western countries. Such instruments may not cover all important health concepts valued by the Chinese as health is a culture-specific concept. Objectives: The objectives of this study are to identify culture-specific health dimensions and culture-related health disparities in primary care that are considered important by Chinese living in China. Methods: A purposive sample of 164 adult Chinese (67 healthy persons and 97 patients) were interviewed face to face. In-depth open-ended questions were asked to elicit culture-specific dimensions of quality of life in primary care settings in China. Results: Twelve health dimensions were identified. Five most frequently mentioned dimensions were: mood (N = 52, 31.71%), physical activities (N = 48, 29.27%), work (N = 40, 24.39%), diet (N = 32, 19.51%), and vitality (N = 28, 17.07%). Significantly more healthy persons reported mood (49.25 vs. 19.59%, P < 0.001), mindset (16.42 vs. 0.00%, P < 0.001), and self-care (11.94 vs. 2.06%, P = 0.016) characterizing good HRQoL, while more patients emphasized on work (4.48 vs. 38.14%, P < 0.001). Diet and vitality appeared to be culture-specific dimensions related to health among Chinese. Conclusions: To better adapt or develop HRQoL instruments for Chinese, dimensions or items regarding diet might be included and disparities in the meaning of vitality between Chinese and Western cultures should be considered.

Cost-Effectiveness Analysis of Abemaciclib Plus Fulvestrant in the Second-Line Treatment of Women With HR+/HER2- Advanced or Metastatic Breast Cancer: A US Payer Perspective.

Introduction: This study evaluated the cost-effectiveness of abemaciclib plus fulvestrant (ABE + FUL) vs. palbociclib plus fulvestrant (PAL + FUL), ribociclib plus fulvestrant (RIB + FUL) and fulvestrant monotherapy (FUL) as second-line treatment for hormone receptor-positive and human epidermal growth factor receptor 2- negative advanced or metastatic breast cancer in the US. Methods: The 3 health states partitioned survival (PS) model was used over the lifetime. Effectiveness and safety data were derived from the MONARCH 2 trial, MONALEESA-3 trial, and PALOMA-3 trial. Parametric survival models were used for four treatments to explore the long-term effect. Costs were derived from the pricing files of Medicare and Medicaid Services, and utility values were derived from published studies. Sensitivity analyses including one-way sensitivity analysis, probabilistic sensitivity analysis and scenario analysis were performed to observe model stability. Results: In the PS model, compared with PAL + FUL, ABE + FUL yielded 0.44 additional QALYs at an additional cost of $100,696 for an incremental cost-utility ratio (ICUR) of $229,039/QALY. Compared with RIB + FUL, ABE + FUL yielded 0.03 additional QALYs at an additional cost of $518 for an ICUR of $19,314/QALY. Compared with FUL, ABE + FUL yielded 0.68 additional QALYs at an additional cost of $260,584 for ICUR of $381,450/QALY. From the PS model, the ICUR was $270,576 /QALY (ABE + FUL vs. PAL + FUL), dominated (ABE + FUL vs. RIB + FUL) and $404,493/QALY (ABE + FUL vs. FUL) in scenario analysis. In the probabilistic sensitivity analysis, the probabilities that ABE + FUL was cost-effective vs. PAL + FUL, RIB + FUL and FUL at thresholds of $50,000, $100,000, and $200,000 per QALY gained were 0% and the probabilities that ABE + FUL was cost-effective vs. PAL + FUL and RIB + FUL at thresholds of $50,000, $100,000, and $200,000 per QALY gained were 0.2, 0.6, and 7.3%. Conclusions: The findings from the present analysis suggest that ABE + FUL might be cost-effective compared with RIB + FUL and not cost-effective compared with PAL + FUL and FUL for second-line treatment of patients with HR+/HER2- advanced or metastatic breast cancer in the US.

Economic Burden of Myocardial Infarction Combined With Dyslipidemia.

Background: Dyslipidemia is a common comorbidity and an important risk factor for myocardial infarction (MI). This study aimed to examine the economic burden of MI combined with dyslipidemia in China. Methods: Patients who were hospitalized due to MI combined with dyslipidemia in 2016 were enrolled. Costs were measured based on electronic medical records and questionnaires. The annual costs were analyzed by conducting descriptive statistics, univariable, and multivariable analyses. Results: Data of 900 patients were analyzed, and 144 patients were dead during the follow-up. The majority of patients were aged 51-70 years (n = 563, 62.55%) and males (n = 706, 78.44%). For all-cause costs, the median annual direct medical costs, direct non-medical costs, indirect costs, and total costs were RMB 13,168 (5,212-29,369), RMB 600 (0-1,750), RMB 676 (0-1,787), RMB 15,361 (6,440-33,943), respectively; while for cardiovascular-related costs, the corresponding costs were RMB 12,233 (3,795-23,746), RMB 515 (0-1,680), RMB 587 (0-1,655), and RMB 14,223 (4,914-28,975), respectively. Lifestyle and complications significantly affected both all-cause costs and cardiovascular-related costs. Conclusions: Increasing attention should be paid to encourage healthy lifestyle, and evidence-based medicine should focus on optimal precautions and treatments for complications, to reduce the economic burden among MI patients with a comorbid dyslipidemia.

A comparison of self-reported and proxy-reported health utilities in children: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis to compare differences in health utilities (HUs) assessed by self and proxy respondents in children, as well as to evaluate the effects of health conditions, valuation methods, and proxy types on the differences. METHODS: Eligible studies published in PubMed, Embase, Web of Science, and Cochrane Library up to December 2019 were identified according to PRISMA guidelines. Meta-analyses were performed to calculate the weighted mean differences (WMDs) in HUs between proxy- versus self-reports. Mixed-effects meta-regressions were applied to explore differences in WMDs among each health condition, valuation method and proxy type. RESULTS: A total of 30 studies were finally included, comprising 211 pairs of HUs assessed by 15,294 children and 16,103 proxies. This study identified 34 health conditions, 10 valuation methods, and 3 proxy types. In general, proxy-reported HUs were significantly different from those assessed by children themselves, while the direction and magnitude of these differences were inconsistent regarding health conditions, valuation methods, and proxy types. Meta-regression demonstrated that WMDs were significantly different in patients with ear diseases relative to the general population; in those measured by EQ-5D, Health utility index 2 (HUI2), and Pediatric asthma health outcome measure relative to Visual analogue scale method; while were not significantly different in individuals adopting clinician-proxy and caregiver-proxy relative to parent-proxy. CONCLUSION: Divergence existed in HUs between self and proxy-reports. Our findings highlight the importance of selecting appropriate self and/or proxy-reported HUs in health-related quality of life measurement and economic evaluations.

Cost-Effectiveness Analysis of Oral Direct-Acting Antivirals for Chinese Patients with Chronic Hepatitis C.

BACKGROUND AND OBJECTIVE: All oral direct-acting antivirals (DAAs) have shown excellent efficacy and safety in Chinese patients with chronic hepatitis C (CHC). However, the cost of DAAs used to be expensive; therefore, large numbers of patients had no access to DAAs in China. Recently, prices have been greatly reduced. The objective of this study was to evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF), sofosbuvir/velpatasvir (SOF/VEL), elbasvir/grazoprevir (EBR/GZR) and glecaprevir/pibrentasvir (GLE/PIB) in Chinese CHC patients stratified by hepatitis C virus (HCV) genotype (GT), cirrhosis status, and treatment history. METHODS: On the basis of a Chinese healthcare perspective, a Markov model was constructed to estimate the lifetime costs and health outcomes of patients treated with different DAA regimens. Chinese-specific clinical, cost, and utility inputs were obtained or calculated from published sources and expert opinions. Costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were reported as primary outcomes. Base-case analysis and sensitivity analysis were conducted. RESULTS: At a willing-to-pay (WTP) threshold of US$30,081/QALY (calculated by three times the GDP per capita in China), SOF/VEL was cost-effective in patients with HCV GT 1, 3, and 6 infections, and the probabilities that SOF/VEL was cost-effective were 9.7-75.7%, 39.1-63.9%, and 35.6-88.0%, respectively. For GT2 patients, noncirrhotic patients, treatment-naïve patients, and treatment-experienced patients, LDV/SOF was the most cost-effective regimen, and the probabilities of cost-effectiveness for each of these groups was 92.1-99.8%, 89.9-99.0%, 61.6-91.2%, and 99.3-100.0%, respectively below the WTP threshold. The GLE/PIB regimen (12-week duration) was the most cost-effective in cirrhotic patients, whereas the probability of its cost-effectiveness varied with that of EBR/GZR (4.1-93.8% versus 6.2-93.3%) below the WTP threshold. CONCLUSIONS: Overall, SOF/VEL and LDV/SOF regimens are more likely to be cost-effective among various subgroups of Chinese patients with CHC.

Cost-Effectiveness of Elbasvir/Grazoprevir Versus Daclatasvir Plus Asunaprevir in Patients with Chronic Hepatitis C Virus Genotype 1b Infection in China.

BACKGROUND AND OBJECTIVE: New direct-acting antivirals (DAAs) have high efficacy and tolerability in the treatment of hepatitis C virus (HCV) infection. The objective of this study was to assess the cost-effectiveness of elbasvir/grazoprevir (EBR/GZR) versus daclatasvir plus asunaprevir (DCV + ASV) in Chinese patients with chronic HCV genotype (GT) 1b infection stratified by cirrhosis status and treatment history. METHODS: A cohort state-transition model was constructed to simulate the course of chronic HCV infection in patients stratified by cirrhosis status and treatment history. The model projected lifetime outcomes and costs in terms of HCV treatment, laboratory tests, clinical procedures, and hospitalizations. Mean age of the study cohort at baseline was 45 years, based on published sources. Sustained virologic response (SVR) rates were derived from clinical trials. Healthcare resource utilization and health utilities were extracted or estimated from published studies in Chinese populations. The stability of the base-case analysis was validated by deterministic and probabilistic sensitivity analyses. RESULTS: In each subpopulation of Chinese patients, treatment with EBR/GZR dominated treatment with DCV + ASV, with lower costs and higher quality-adjusted life-years (QALYs). Sensitivity analysis demonstrated that EBR/GZR was the cost-effective option compared to DCV + ASV in 77.4-97.4% or 94.1-100% of model simulations in Chinese treatment-naïve or treatment-experienced patients, respectively, as the cost-effectiveness threshold changed from zero to US$24,150/QALY (three times GDP per capita in China). CONCLUSIONS: Treatment with EBR/GZR was the cost-effective option for patients with chronic HCV GT1b infection in China, regardless of cirrhosis status or treatment history.

Measuring the environmental efficiency of countries: a directional distance function metafrontier approach.

This paper measures environmental efficiency (EE) in 63 countries over the period 1981-2005 and analyzes whether the adoption of the Kyoto Protocol is accompanied by an increase in environmental efficiency during the same period. Differences in EE across countries under distinct country-specific production frontiers are measured using a directional distance function model, which incorporates a desirable output (GDP) and an undesirable output (CO2 emissions). It is further assumed that a stochastic meta-technology-frontier exists and represents potential outputs available to all countries given inputs. The metafrontier for four country groups, high income countries, upper-middle income countries, low-middle income countries, and low income countries, are estimated using balanced panel data for the sample countries over the study period. The overall results indicate that the four country groups operated under distinct stochastic production frontiers and therefore used different production technologies. It is found that high income countries achieved the highest progress in their average environmental efficiency relative to the metafrontier, while lower-middle income countries and low income countries recorded negative growth in their average EE relative to the metafrontier.