Time-dependent efficacy analysis of first-line immunotherapies for advanced non-small cell lung cancer.

BACKGROUND: Many randomized controlled trials (RCTs) and network meta-analyses have demonstrated that the progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients can be improved through combination immunotherapy or monotherapies. However, time-dependent analysis of the treatment effect is currently lacking. Thus, we aimed to evaluate the efficacy of first-line immunotherapy, and establish a hazard ratio function to reflect the time-varying progression or mortality risk of patients with NSCLC. METHODS: Seventeen clinical trials were selected based on search strategy. Baseline characteristics, including the age, sex, smoking status, geographical region, and Eastern Cooperative Oncology Group (ECOG) performance status of patients, were balanced, resulting in ten immunotherapies from nine appropriate clinical trials to conduct treatment effect comparison. RESULTS: We found that nivolumab plus ipilimumab (nivo + ipi) improved the PFS and OS over time. The hazard ratio of nivo + ipi, relative to that of pembrolizumab, decreased from 1.11 to 0.36 for PFS, and from 0.93 to 0.49 for OS over a 10-year period. In terms of the response to immunotherapy in patients with different PD-L1 expression levels, patients with PD-L1 > = 50% experienced lower rates of progression and a reduced mortality risk over time. The hazard ratio of patients with PD-L1 > = 50% relative to all of the patients decreased from 0.73 to 0.69 for PFS, and from 0.78 to 0.67 for OS. CONCLUSIONS: Based on the fact that time-dependent progression and mortality risk existed during the treatment duration, physicians should select a suitable treatment regimen for patients based on the hazard ratio.

Cost-effectiveness of first-line immunotherapy for advanced non-small cell lung cancer with different PD-L1 expression levels: A comprehensive overview.

BACKGROUND: Immunotherapies can substantially improve treatment efficacy, despite their high cost. A comprehensive overview of the cost-effectiveness analysis (CEA) of immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer based on different tumor proportion scores (TPSs) was conducted. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, and NHS Economic Evaluation databases were searched from their inception until August 24, 2022. Data relevant to the CEA results were recorded, and quality assessments conducted based on the Quality of Health Economic Studies (QHES) process. FINDINGS: Fifty-one original studies from seven countries were included. The mean QHES score was 77.0 (range: 53-95). Twenty-seven studies were classified as high-quality, and the rest as fair quality. Pembrolizumab, nivolumab, ipilimumab, atezolizumab, camrelizumab, cemiplimab, sintilimab, tislelizumab, and durvalumab were identified using three TPS categories. While nivolumab plus ipilimumab and pembrolizumab plus chemotherapy were unlikely to be cost-effective in China, the results for the US were uncertain. Atezolizumab combinations were not cost-effective in China or the US, and tislelizumab and sintilimab were cost-effective in China. For TPSs ≥ 50%, the pembrolizumab monotherapy could be cost-effective in some developed countries. Cemiplimab was more cost-effective than chemotherapy, pembrolizumab, and atezolizumab in the US. For TPSs ≥ 1%, the cost-effectiveness of pembrolizumab was controversial due to the different willingness-to-pay thresholds. CONCLUSIONS: None of the atezolizumab combination regimens were found to be cost-effective in any perspective of evaluations. Camrelizumab, tislelizumab, and sintilimab have lower ICERs compared to atezolizumab, pembrolizumab, and nivolumab in China. Cemiplimab may be a more affordable alternative to pembrolizumab or atezolizumab. However, it remains unclear which ICIs are the best choices for each country. Future CEAs are required to select comprehensive regimens alongside randomized trials and real-world studies to help verify the economics of ICIs in specific decision-making settings.

Cost-effectiveness of first-line immunotherapy combinations with or without chemotherapy for advanced non-small cell lung cancer: a modelling approach.

BACKGROUND: Many studies have explored the cost-effectiveness of immunotherapy versus chemotherapy alone. However, there is paucity of evidence on direct pharmacoeconomic studies related to immunotherapy combinations. Thus, we aimed at assessing the economic outcomes of first-line immunotherapy combinations in the treatment of advanced non-small cell lung cancer (NSCLC) from the Chinese health care perspective. METHODS: The mutual hazard ratios (HRs) of ten immunotherapy combinations and one chemotherapy regimen for the overall survival (OS) and progression-free survival (PFS) were obtained from a network meta-analysis. Based on proportional hazard (PH) assumption, adjusted OS and PFS curves were established to make the effects comparable. With the parameters of cost and utility, and of scale and shape from the fit of adjusted OS and PFS curves obtained from previous studies, a partitioned survival model was designed to estimate the cost-effectiveness of immunotherapy combinations versus chemotherapy alone. Parameter uncertainty in model inputs was assessed using one-way deterministic and probabilistic sensitivity analyses. RESULTS: The incremental cost of camrelizumab plus chemotherapy versus chemotherapy alone was $13,180.65, the lowest among all the other immunotherapy combinations. Furthermore, sintilimab plus chemotherapy (sint-chemo) provided the highest quality-adjusted life-year (QALY) benefit versus chemotherapy alone (incremental QALYs = 0.45). Sint-chemo yielded the best incremental cost-effectiveness ratio (ICER) versus chemotherapy alone (ICER = $34,912.09/QALY), at the current price. The cost-effectiveness probabilities were 32.01% and 93.91% for pembrolizumab plus chemotherapy, and atezolizumab plus bevacizumab plus chemotherapy, respectively (if the original price of the pembrolizumab, atezolizumab, and bevacizumab were decreased by 90%). CONCLUSIONS: Based on the fact that there is fierce competition in the PD-1/PD-L1 market, pharmaceutical enterprises should strive for greater efficacy, and optimal pricing strategy for therapies.

Cost-Effectiveness Analysis of Pembrolizumab Plus Pemetrexed and Platinum Versus Chemotherapy Alone as First-Line Treatment in Metastatic Non-Squamous Non-Small Cell Lung Cancer: A Reconstruction of Partitioned Survival Model Based on Time Dependent Pricing Mechanism of Patient Assistance Program.

OBJECTIVES: A new patient assistance program (PAP) for pembrolizumab was started in China in 2021. The researchers aimed to evaluate the economic outcomes of pembrolizumab plus pemetrexed and platinum versus chemotherapy alone in the first-line treatment of patients with metastatic non-squamous non-small cell lung cancer, based on the pricing mechanism of PAP. MATERIAL AND METHODS: Survival analysis and partitioned survival model were performed to evaluate the incremental cost-effectiveness ratio (ICER) in the pembrolizumab group compared with the chemotherapy group. Survival probabilities were extracted from the data of the KEYNOTE-189 trial. Cost and utility data were gathered from published literature. The pricing mechanism of PAP was set in each cycle in the partitioned survival model, according to the progression-free survival (PFS) data of the KEYNOTE-189 trial, which included PFS-1 and PFS-2. Deterministic sensitivity analysis and probabilistic sensitivity analysis were conducted. RESULTS: The ICER of the pembrolizumab group versus chemotherapy group was $65,272/quality-adjusted life year (QALY), which still exceeded the willingness-to-pay threshold of three times per capita gross domestic product (GDP) of China ($33,581.22), although PAP was calculated. Sensitivity analysis implied that the price of chemotherapeutic drugs combined with pembrolizumab was one of the main influencing factors of ICER. CONCLUSIONS: Due to various prices set by PAP and the payment for combined chemotherapy, the economic advantage of pembrolizumab plus chemotherapy in the first-line treatment of non-small cell lung cancer (NSCLC) is still not achieved in China.

The effects of DRGs-based payment compared with cost-based payment on inpatient healthcare utilization: A systematic review and meta-analysis.

Diagnosis related groups (DRGs)-based payment is increasingly used worldwide to control hospital costs instead of pre-existing cost-based payment, but the results of evaluations vary. A systematic analysis of the effects of DRGs-based payment is needed. This study aims to conduct a systematic review and meta-analysis to compare the effects of DRGs-based payment and cost-based payment on inpatient health utilization in terms of length of stay (LOS), total inpatient spending per admission and readmission rates. We included studies undertaken with designs approved by the Cochrane Effective Practice and Organisation of Care that reported associations between DRGs-based payment and one or more inpatient healthcare utilization outcomes. After a systematic search of eight electronic databases through October 2018, 18 studies were identified and included in the review. We extracted data and conducted quality assessment, systematic synthesis and meta-analyses on the included studies. Random-effects models were used to handle substantial heterogeneity between studies. Meta-analysis showed that DRGs-based payment was associated with lower LOS (pooled effect: -8.07 % [95 %CI -13.05 to -3.10], p = 0.001), and higher readmission rates (pooled effect: 1.36 % [95 %CI 0.45-2.27], p = 0.003). This meta-analysis revealed that DRGs-based payment may have cost-saving implications by lowering LOS, whereas hardly reduce the readmission rates. Policy-makers considering adopting DRGs-based payment should pay more attention to the hospital readmission rates compared with cost-based payment.

Cesarean delivery rates, costs and readmission of childbirth in the new cooperative medical scheme after implementation of an episode-based bundled payment (EBP) policy.

BACKGROUND: In the past decade, the rate of cesarean delivery increased dramatically in rural China under the fee-for-service (FFS) system. In September 2011, the New Cooperative Medical Scheme (NCMS) agency in Yong'an county in Fujian province of China adopted a policy of reforming payment for childbirth by transforming the FFS payment into episode-based bundled payment (EBP), which made the cesarean deliveries less profitable. Thus, this study was conducted to determine the effect of EBP policy on reducing cesarean use and controlling delivery costs for rural patients in the NCMS. METHODS: Data from the inpatient information database of the NCMS agency from January 2010 to March 2013 was collected, in which Yong'an county was employed as a reform county and 2 other counties as controls. We investigated the effects of EBP on cesarean delivery rate, costs of childbirth and readmission for rural patients in the NCMS using a natural experiment design and difference in differences (DID) analysis method. RESULTS: The EBP reform was associated with 33.97% (p<0.01) decrease in the probability of cesarean delivery. The EBP reform, on average, reduced the total spending per admission, government reimbursement expenses per admission, and out-of-pocket (OOP) payments per admission by ¥ 649.61, ¥ 575.01, and ¥ 74.59, respectively. The OOP payments had a net decrease of 14.24% (p<0.01); whereas the OOP payments as a share of total spending had a net increase of 8.72% (p<0.01). There was no evidence of increase in readmission rates. CONCLUSIONS: These results indicate that the EBP policy has achieved at least a short-term success in lowering the increase of cesarean delivery rate and costs of childbirth. Considering both the cesarean rate and the OOP payments as a share of total spending after the reform were still high, China still has a long way to go to achieve the ideal level of cesarean rate and improve the benefits of deliveries for rural population.

Effect of a typical systemic hospital reform on inpatient expenditure for rural population: the Sanming model in China.

BACKGROUND: Considering catastrophic health expenses in rural households with hospitalised members were unproportionally high, in 2013, China developed a model of systemic reform in Sanming by adjusting payment method, pharmaceutical system, and medical services price. The reform was expected to control the excessive growth of hospital expenditures by reducing inefficiency and waste in health system or shortening the length of stay. This study analyzed the systemic reform's impact on the financial burden and length of stay for the rural population in Sanming. METHODS: A total of 1,113,615 inpatient records for the rural population were extracted from the rural new cooperative medical scheme (NCMS) database in Sanming from 2007 to 2012 (before the reform) and from 2013 to 2016 (after the reform). We calculated the average growth rate of total inpatient expenditures and costs of different medical service categories (medications, diagnostic testing, physician services and therapeutic services) in these two periods. Generalized linear models (GLM) were employed to examine the effect of reform on out-of-pocket (OOP) expenditures and length of stay, controlling for some covariates. Furthermore, we controlled the fixed effects of the year and hospitals, and included cluster standard errors by hospital to assess the robustness of the findings in the GLM analysis. RESULTS: The typical systemic reform decreased the average growth rate of total inpatient expenditures by 1.34%, compared with the period before the reform. The OOP expenditures as a share of total expenditures showed a downward trend after the reform (42.34% in 2013). Holding all else constant, individuals after the reform spent ¥308.42 less on OOP expenditures (p < 0.001) than they did before the reform. Moreover, length of stay had a decrease of 0.67 days after the reform (p < 0.001). CONCLUSIONS: These results suggested that the typical systemic hospital reform of the Sanming model had some positive effects on cost control and reducing financial burden for the rural population. Considering the OOP expenditures as a share of total expenditures was still high, China still has a long way to go to improve the benefits rural people have enjoyed from the NCMS.

Validation of Quality of Life Instruments for Cancer Patients - Colorectal Cancer (QLICP-CR) in patients with colorectal cancer in Northeast China.

BACKGROUND: Measuring quality of life is important for cancer patients, but there are regional differences in age-standardized colorectal cancer incidence and mortality rates which may affect measurement. This study aimed to evaluate the reliability, validity and responsiveness of Quality of Life Instruments for Cancer Patients - Colorectal Cancer (QLICP-CR) in colorectal cancer patients in Northeast China, and assess its usefulness for evaluation of quality of life in these patients. METHODS: From November 2016 to January 2017, 152 patients with colorectal cancer from Liaoning Cancer Hospital & Institute were surveyed three times using QLICP-CR and the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) to measure their quality of life (on admission, 2-3 days later and at discharge). Reliability was evaluated by internal consistency and test-retest reliability. Validity was examined by item-domain correlation, criterion-related validity and factor construct validity analysis. Responsiveness was assessed using paired Student's t tests and calculating standardized response mean. RESULTS: Cronbach's α coefficient for QLICP-CR ranged from 0.62 to 0.93. Pearson correlation and intra-class correlation coefficients for QLICP-GM, the five domains and the total scale of QLICP-CR ranged from 0.74 to 0.91 and 0.74 to 0.90. The item-domain correlation analysis showed good convergent validity and discriminant validity. Correlation analysis of domain scores between FACT-C and QLICP-CR showed good criterion-related validity. Exploratory factor analysis revealed that nine and three principal components were extracted from items in the two modules of QLICP-CR, and the contribution rate of cumulative variance was 70.21 and 72.26%. There were significant differences in quality of life between the first and the third measurements, with standardized response mean values ranging from 0.30 to 0.81. CONCLUSIONS: The QLICP-CR was a reliable, valid and sensitive instrument to measure quality of life in colorectal cancer patients in Northeast China.

Study on the cost attributable to central venous catheter-related bloodstream infection and its influencing factors in a tertiary hospital in China.

BACKGROUND: Central venous catheters (CVC) have been widely used for patients with severe conditions. However, they increase the risk of catheter-related bloodstream infection (CRBSI), which is associated with high economic burden. Until now, no study has focused on the cost attributable to CRBSI in China, and data on its economic burden are unavailable. The aim of this study was to assess the cost attributable to CRBSI and its influencing factors. METHODS: A retrospective matched case-control study and multivariate analysis were conducted in a tertiary hospital, with 94 patients (age ≥ 18 years old) from January 2011 to November 2015. Patients with CRBSI were matched to those without CRBSI by age, principal diagnosis, and history of surgery. The difference in cost between the case group and control group during the hospitalization was calculated as the cost attributable to CRBSI, which included the total cost and five specific cost categories: drug, diagnostic imaging, laboratory testing, health care technical services, and medical material. The relation between the total cost attributable to CRBSI and its influencing factors such as demographic characteristics, diagnosis and treatment, and pathogenic microorganism, was analysed with a general linear model (GLM). RESULTS: The total cost attributable to CRBSI was $3528.6, and the costs of specific categories including drugs, diagnostic imaging, laboratory testing, health care technical services, and medical material, were $2556.4, $112.1, $321.7, $268.7, $276.5, respectively. GLM analysis indicated that the total cost was associated with the intensive care unit (ICU), pathogenic microorganism, age, and catheter number, according to the sequence of standardized estimate (ß). ICU contributed the most to the model R-square. CONCLUSION: Central venous catheter-related bloodstream infection represents a great economic burden for patients. More attentions should be paid to further prevent and control this infection in China.