Cost-effectiveness analysis of PD-1 inhibitors as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma in China: an economic evaluation based on network meta-analysis.

BACKGROUND: Several economic studies have assessed the cost-effectiveness of programmed cell death protein-1 (PD-1) inhibitors compared to second-line chemotherapy in treating esophageal squamous cell carcinoma (ESCC). However, there is a lack of economic comparisons among the different PD-1 inhibitors. AIM: This study aimed to assess the cost-effectiveness of PD-1 inhibitors (nivolumab, pembrolizumab, camrelizumab, and tislelizumab) in second-line treatment for advanced or metastatic ESCC within the Chinese healthcare system. METHOD: The clinical trials were systematically retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. We established a fractional polynomials model to conduct a network meta-analysis, enabling the calculation of hazard ratios and expected survival rates. Economic outcomes were estimated using a partitioned survival model. The costs and utilities were gathered from published sources. The threshold for willingness-to-pay (WTP) for a quality-adjusted life year (QALY) was set at three times China's per capita gross domestic product in 2022. Sensitivity analyses (SA) were performed to address uncertainties in the model. RESULTS: Four phase III randomized controlled trials were included, evaluating the cost-effectiveness of four PD-1 inhibitors, camrelizumab, nivolumab, tislelizumab, and pembrolizumab, compared to chemotherapy for the second-line treatment of advanced or metastatic ESCC. For camrelizumab, nivolumab, tislelizumab, and pembrolizumab, the corresponding incremental cost-effectiveness ratios were $27,375.43/QALY, $205,312.19/QALY, $9,266.73/QALY, and $220,368.10/QALY, respectively. The SA results indicated the robustness of the base analysis findings. CONCLUSION: From the Chinese healthcare system, under the WTP of $38,253.48/QALY, tislelizumab is a cost-effective treatment option for the second-line treatment of advanced or metastatic ESCC.

A Cost-effectiveness Analysis of iGlarLixi Versus IDegAsp and Appropriate Price Exploration of iGlarLixi for Type 2 Diabetes Mellitus Patients in China.

BACKGROUND AND OBJECTIVE: The efficacy and safety of iGlarLixi, a fixed-ratio combination (FRC) of basal insulin glargine plus lixisenatide, have been demonstrated in type 2 diabetes mellitus (T2DM) patients. However, no relevant economic analysis of iGlarLixi has been done in China. Thus, the primary objective of this study is to evaluate the cost effectiveness of iGlarLixi versus IDegAsp in Chinese T2DM patients, and then back-calculate the appropriate drug price of iGlarLixi to support its pricing after listing in China. METHODS: The United Kingdom Prospective Diabetes Study Outcome Model 2 (UKPDS OM2) was applied to estimate lifetime health and economic outcomes from the Chinese health-care system perspective. As no head-to-head comparison data are currently available, the baseline cohort characteristics and the initial clinical data for iGlarLixi were derived from the randomized LixiLan-L-China trial. The relative treatment effects for IDegAsp were based on an indirect treatment comparison. Due to the unavailability of iGlarLixi pricing data, the annual medication cost of iGlarLixi was assumed to be equal to that of IDegAsp at the beginning of the study. Afterwards, a break-even analysis using comparator drug price and the willingness-to-pay (WTP) threshold was performed to back-calculate the appropriate drug price of iGlarLixi. One-way sensitivity analysis, scenario analysis and probabilistic sensitivity analysis (PSA) were conducted to assess the robustness of the model. RESULTS: Based on the initial assumption of equal annual medication cost of iGlarLixi and IDegAsp, iGlarLixi was cost effective compared to IDegAsp with an incremental cost-effectiveness ratio (ICER) far below the WTP threshold in Chinese T2DM patients. From the back calculation for the price of iGlarLixi, the annual medication cost of iGlarLixi was $656.96 and $1075.96 to obtain an ICER of iGlarLixi versus IDegAsp close to 1 × GDP and 3 × GDP, respectively. When the discount rate was changed from the base value to 8% (the most sensitive parameter to the model results in one-way sensitivity analysis), the ICER was nearly equal to 1 × GDP and 3 × GDP with the annual medication cost of iGlarLixi decreasing to $590.41 and $865.03, respectively. Thus, iGlarLixi was dominant over IDegAsp with an annual medication cost of $590.41 to $865.03. The findings were robust to one-way sensitivity analysis, PSA and scenario analysis. CONCLUSION: This long-term cost-effectiveness analysis in Chinese T2DM patients indicates that iGlarLixi, assuming equal price to IDegAsp, is cost-effective versus IDegAsp with an ICER far below the WTP threshold. With 1 × GDP and 3 × GDP threshold set we back-calculate the appropriate annual medication cost of iGlarLixi to be $590.41 to $865.03, respectively.

Cost-effectiveness analysis of nivolumab plus cabozantinib versus sunitinib as first-line therapy in advanced renal cell carcinoma.

Aim: To evaluate the cost-effectiveness of first-line treatment for advanced renal cell carcinoma with nivolumab plus cabozantinib versus sunitinib from a US payer perspective. Methods: Economic outcomes were estimated with Markov and partitioned survival models. Efficacy, safety and other data were taken from the CheckMate 9ER trial. Costs and utilities were gathered from published sources. Sensitivity analyses addressed model uncertainties. Results: The incremental cost-effectiveness ratio of nivolumab plus cabozantinib versus sunitinib was US$555,663 and $531,748 per quality-adjusted life year in the Markov and partitioned survival models, respectively, exceeding the willingness-to-pay threshold (US$150,000 per quality-adjusted life-year). Sensitivity analyses showed robust outcomes. Conclusion: From a US payer perspective, first-line nivolumab plus cabozantinib for advanced renal cell carcinoma is not cost effective.

Renal cell carcinoma (RCC) is a common cancer in the USA. Up to 30% of patients with RCC are in an advanced stage of disease at diagnosis. RCC is difficult to cure, with an 11% chance of survival after 5 years for patients with advanced RCC. A recent clinical study showed that nivolumab plus cabozantinib (NC) had a greater benefit in patients with advanced RCC than sunitinib. The US FDA approved NC for advanced RCC, but NC is relatively expensive. This study explored the cost­effectiveness of NC for advanced RCC versus sunitinib for a US payer using two cost­effectiveness models developed based on the results of the aforementioned clinical study. The results showed that to gain an additional year in perfect health, NC costs an average of US$555,663 or $531,748 more versus sunitinib, which is more than a US payer is willing to pay for an additional year in perfect health ($150,000). Therefore, NC for advanced RCC is not cost-effective versus sunitinib for a US payer at current prices.

Enhanced colloidal stability and protein resistance of layered double hydroxide nanoparticles with phosphonic acid-terminated PEG coating for drug delivery.

Conjugating nanoparticles with polyethylene glycol (PEG) is a useful strategy to improve the colloidal and biological stability of nanoparticles. However, studies on PEGylation of two-dimensional layered double hydroxide (LDH) nanoparticles are very limited. The present work reported two functionalization approaches to synthesize PEG-conjugated LDH nanoparticles by introducing phosphonic acid terminated PEG before and after LDH aging. The successful PEGylation was confirmed and suggested to be via electrostatic interaction and a ligand exchange process. Different functionalization approaches resulted in different binding types of PEG on/in LDH nanoparticles. The PEG coating maintained the dispersity of LDH nanoparticles in water and saline with the feeding mass ratio of 1:1. Further colloidal stability tests of PEGylated LDHs revealed that the PEGylated LDH dispersity was affected by the feeding mass ratio of PEG/LDH, the molar weight of PEG and anions intercalated in the LDHs. In a test to determine the extent of non-specific protein adsorption, the PEGylation was effective at resisting non-specific bovine serum albumin adsorption on LDH nanoparticles with both functionalization methods investigated. Moreover, PEGylated LDH nanoparticles had no effect on cell viability up to 500 µg/mL, and demonstrated enhanced cellular uptake in a SK-MEL-28 cell culture. The results in this work indicate that conjugating phosphonic acid-terminated PEG on LDH nanoparticles is a promising strategy to improve the colloidal and biological stability of LDHs for biomedical applications.