Osimertinib in the treatment of resected EGFR-mutated non-small cell lung cancer: a cost-effectiveness analysis in the United States.

Background: In the double-blind phase III ADAURA randomized clinical trial, adjuvant osimertinib showed a substantial overall survival benefit in patients with stage IB to IIIA, EGFR-mutated, completely resected non-small cell lung cancer (NSCLC). We conduct a cost-effectiveness analysis comparing the use of adjuvant osimertinib to placebo in patients with stage IB to IIIA, EGFR-mutated, resected NSCLC. Methods: Based on the results obtained from the ADAURA trial, a Markov model with three-state was employed to simulate patients who were administered either osimertinib or placebo until disease recurrence or completion of the study period (3 years). Quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER) were calculated with a willingness-to-pay (WTP) threshold of $150,000 per QALY. Both univariate and probabilistic sensitivity analyses were carried out to explore the robustness of the model. Results: Osimertinib produced additional 1.59 QALYs with additional costs of $492,710 compared to placebo, giving rise to ICERs of $309,962.66/QALY. The results of the univariate sensitivity analysis indicated that the utility of disease-free survival (DFS), cost of osimertinib, and discount rate had the greatest impact on the outcomes. Probabilistic sensitivity analysis showed that osimertinib exhibited a 0% chance of being considered cost-effective for patients using a WTP threshold $150,000/QALY. Conclusion: In our model, osimertinib was unlikely to be cost-effective compared to placebo for stage IB to IIIA, EGFR-mutated, completely resected NSCLC patients from the perspective of a U.S. payer at a WTP threshold of $150,000 per QALY.

Cost-effectiveness of first-line versus second-line use of brigatinib followed by lorlatinib in patients with ALK-positive non-small cell lung cancer.

Background: The ALTA-1 L trial and EXP-3B arm of NCT01970865 trial found that both brigatinib and lorlatinib showed durable and robust responses in treating ALK-positive non-small cell lung cancer (NSCLC) patients. However, brigatinib and lorlatinib treatments are costly and need indefinite administration until the disease progression. Thus, it remains uncertain whether using brigatinib followed by lorlatinib before chemotherapy is cost-effective compared to reserving these two drugs until progression after chemotherapy. Methods: We used a Markov model to assess clinical outcomes and healthcare costs of treating ALK-positive NSCLC individuals with brigatinib followed by lorlatinib before chemotherapy versus a strategy of reserving these drugs until progression after chemotherapy. Transition probabilities were estimated using parametric survival modeling based on multiple clinical trials. The drug acquisition costs, adverse events costs, administration costs were extracted from published studies before and publicly available data. We calculated lifetime direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from the perspective of a United States payer. Results: Our base-case analysis indicated that the incremental cost-effectiveness ratios of using first-line brigatinib followed by lorlatinib compared with second-line brigatinib followed by lorlatinib is $-400,722.09/QALY which meant that second-line brigatinib followed by lorlatinib had less costs and better outcomes. Univariate sensitivity analysis indicated the results were most sensitive to the cost of brigatinib. Probability sensitivity analysis revealed that using brigatinib followed by lorlatinib before chemotherapy had a 0% probability of cost-effectiveness versus delaying these two drugs until progression after chemotherapy at a willingness-to-pay threshold of $150,000 per QALY. Sensitivity analyses conducted revealed the robustness of this result, as incremental cost-effectiveness ratios never exceeded the willingness-to-pay threshold. Conclusion: Using brigatinib as first-line treatment followed by lorlatinib for ALK-positive NSCLC may not be cost-effective given current pricing from the perspective of a United States payer. Delaying brigatinib followed by lorlatinib until subsequent lines of treatment may be a reasonable strategy that could limit healthcare costs without affecting clinical outcomes. More mature data are needed to better estimate cost-effectiveness in this setting.

Cost-effectiveness of tisotumab vedotin as a second- or third-line therapy for cervical cancer.

OBJECTIVE: To evaluate the cost-effectiveness of tisotumab vedotin to treat recurrent or metastatic cervical cancer in second- or third-line from the U.S. payer perspective. METHODS: A Markov model with three-state was employed to simulate recurrent or metastatic cervical cancer patients who were administered either tisotumab vedotin or investigator's choice of chemotherapy based on the phase II, open-labeled innovaTV 301 randomized clinical trial. The data on cost and health preferences were collected from the literature. RESULTS: Tisotumab vedotin generated an additional 0.25 quality-adjusted life-years (QALYs) compared to chemotherapy, but at an additional cost of $206,779. This results in incremental cost-effectiveness ratios of 839,107.88 per QALY. The results of the univariate sensitivity analysis indicated that cost of tisotumab vedotin, utility of progressive disease and progression-free survival had the greatest impacts on the outcomes. Probability sensitivity analysis showed that tisotumab vedotin had a 0% chance of being considered cost-effective. CONCLUSION: Tisotumab vedotin was unlikely cost-effective compared to chemotherapy for recurrent or metastatic cervical cancer patients at a willingness-to-pay threshold of $150,000/QALY from the perspective of a U.S. payer. Lowering the prices of tisotumab vedotin could potentially enhance its cost-effectiveness.

Research on factors influencing the academic entrepreneurial ability of teachers in the digital age: Evidence from China.

In the contemporary digital economy, economic development increasingly relies on the innovation and dissemination of knowledge. Academic entrepreneurship, as a direct channel for knowledge dissemination into the marketplace, is significantly influenced by digital technology. Consequently, how to improve academic entrepreneurial ability has become a hot research topic. This study is grounded in the theory of reciprocal determinism within the context of the digital economy. We use the "2019 China Digital Economy Development Index White Paper" and collect data from 1843 survey questionnaires in China to conduct empirical research with a ridge regression model. It primarily focuses on the following individual factors and social environmental factors on academic entrepreneurial ability of teachers (AEAT): digital economy (DE), organizational support (OS), policy environment (PE), and personal learning growth (PLG). First, the findings show that the DE, OS, PE, and PLG have a significant positive impact on improving AEAT. Second, the results also indicate that social environmental factors relative to personal factors will have a greater impact. Finally, this study not only presents the first attempt to establish a connection between DE and AEAT but also holds significant managerial implications for enhancing AEAT within the context of the DE. Despite the increasing body of literature on academic entrepreneurship, the research domain pertaining specifically to AEAT remains fragmented and lacks comprehensive theoretical development. There is a pressing need for more systematic and thorough investigations to unveil the black box of factors influencing AEAT in the context of the DE.

First-line versus second-line use of pralsetinib in treatment of rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer: a cost-effectiveness analysis.

Background: The ARROW study demonstrated favorable clinical efficacy and safety of pralsetinib (PRL) in treating rearranged during transfection (RET) fusion positive non-small cell lung cancer (NSCLC) in clinical trials. However, due to the high cost of PRL, evaluating its cost-effective characteristics is crucial. Currently, there has been no cost-effectiveness analysis specifically for PRL. Therefore, the aim of this study was to assess the cost-effectiveness characteristics of using PRL as a first-line therapy versus reserving it until the second-line versus solely relying on chemotherapy from the perspective of payers in the United States. Methods: A Markov model was developed to evaluate the 3 above mentioned PRL-based treatment strategies. Clinical data from the ARROW trial were incorporated into the model, and costs and utilities values were obtained through previously published literature and public databases, with both being discounted at 3% per year. To ensure the robustness of the model, both probabilistic and univariate sensitivity analyses were performed. The primary endpoints included quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results: Compared to chemotherapy, the use of PRL in the first-line therapy resulted in an additional 0.07 QALYs at a cost of $133,561, with an ICER of $1,353,849.65 per QALY. Similarly, when used in the second-line setting, PRL led to an additional 0.09 QALYs at a cost of $92,797, with an ICER of $559,232.70 per QALY. The ICER value in the first-line or in the second-line therapy strategy was higher than the US willingness-to-pay (WTP) threshold of $150,000 per QALY. Univariable sensitivity analyses revealed that the cost of PRL and the utility of progressed disease had the most significant impact on the ICER. To be considered cost-effective at a WTP threshold of $150,000 per QALY, the cost of PRL would need to be reduced by 71.34% in first-line treatment or 84.49% in second-line treatment. Conclusions: Based on current pricing, neither PRL as first-line nor second-line therapy was found to be cost-effective for patients with RET fusion-positive advanced NSCLC compared to chemotherapy. Reserving PRL until second-line therapy may be a compromise approach to maintaining control over healthcare expenses yet still achieving favorable clinical outcomes.

First-line tremelimumab plus durvalumab and chemotherapy versus chemotherapy alone for metastatic non-small cell lung cancer: a cost-effectiveness analysis in the United States.

Importance: In the open-label phase III POSEIDON randomized clinical trial (RCT), a limited course of tremelimumab plus durvalumab and chemotherapy (T + D + CT) indicated in the first-line treatment of metastatic non-small cell lung cancer (mNSCLC), progression-free survival, and overall survival (OS) were substantially improved without significant additional tolerance burden compared to chemotherapy (CT). However, given the high cost of T + D + CT, its value needs to be evaluated in terms of both potency and cost. Objective: To evaluate the cost-effectiveness of T + D + CT versus CT in individuals with previously untreated mNSCLC from a U.S. payer perspective. Design, setting, and participants: A three-state Markov model was adopted to weigh the lifetime costs and effectiveness of T + D + CT versus CT for the treatment of first-line mNSCLC, according to the results of the POSEIDON phase III RCT involving 675 individuals with mNSCLC. Individuals were simulated to undergo either T + D + CT for up to four 21-day cycles, followed by durvalumab once every 4 weeks until disease progression or unacceptable toxic effects and one additional tremelimumab dose, or CT for up to six 21-day cycles (with or without pemetrexed maintenance; all groups) in the analysis. Main outcomes and measures: Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were evaluated with a willingness-to-pay (WTP) threshold of $ 100,000 to $ 150,000 per QALY. The uncertainty of the model was investigated using univariate and probabilistic sensitivity analysis. Results: T + D + CT produced additional 0.36 QALYs with additional costs of $ 217,694, compared to CT, giving rise to ICERs of $ 608,667.86/QALY. The univariate sensitivity analysis demonstrated that the outcomes were most sensitive to the cost of durvalumab. Other variables with a large or moderate influence were the utility of progression-free survival state, utility of progressive disease state, and cost of tremelimumab. Probability sensitivity analysis revealed that T + D + CT had a 0% probability of cost-effectiveness in individuals with mNSCLC at a willingness-to-pay threshold of $ 100,000 to $ 150,000 per QALY. Conclusion and relevance: In this model, T + D + CT was estimated to be less cost-effective than CT for patients with mNSCLC at a WTP threshold of $ 100,000 to $ 150,000 per QALY in the United States. When new combination therapies with remarkable effect become pivotal in the first-line treatment, the price reduction of durvalumab and tremelimumab may be necessary to achieve cost-effectiveness in future possible context.

Toripalimab plus chemotherapy vs. chemotherapy in patients with advanced non-small-cell lung cancer: A cost-effectiveness analysis.

Background: The potency and safety of toripalimab combination with chemotherapy (TC) as the first-line therapy for advanced non-small cell lung cancer (NSCLC) have been demonstrated in the CHOICE-01 study. Our research explored whether TC was cost-effective compared to chemotherapy alone from the Chinese payer perspective. Materials and methods: Clinical parameters were obtained from a randomized, multicenter, registrational, placebo-controlled, double-blind, phase III trial. Standard fee databases and previously published literature were used to determine costs and utilities. A Markov model with three mutually exclusive health statuses (progression-free survival (PFS), disease progression, and death) was used to predict the disease course. The costs and utilities were discounted at 5% per annum. The main endpoints of the model included cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses were performed to investigate the uncertainty. Subgroup analyses were performed to verify the cost-effectiveness of TC in patients with squamous and non-squamous cancer. Results: TC combination therapy yielded an incremental 0.54 QALYs with an incremental cost of $11,777, compared to chemotherapy, giving rise to ICERs of $21,811.76/QALY. Probabilistic sensitivity analysis revealed that TC was not favorable at 1 time GDP per capita. With a prespecified willingness-to-pay threshold (WTP) of three times the GDP per capita, combined treatment had a 100% probability of being cost-effective and had substantial cost-effectiveness in advanced NSCLC. Probabilistic sensitivity analyses showed that TC was more likely to be accepted with a WTP threshold higher than $22,195 in NSCLC. Univariate sensitivity analysis showed that the utility of PFS state, crossover proportions of the chemotherapy arm, cost per cycle of pemetrexed treatment, and discount rate were the dominant influencing factors. Subgroup analyses found that in patients with squamous NSCLC, the ICER was $14,966.09/QALY. In the non-squamous NSCLC, ICER raised to $23,836.27/QALY. ICERs were sensitive to the variance of the PFS state utility. TC was more likely to be accepted when WTP increases exceeded $14,908 in the squamous NSCLC subgroup and $23,409 in the non-squamous NSCLC subgroup. Conclusion: From the perspective of the Chinese healthcare system, TC may be cost-effective in individuals with previously untreated advanced NSCLC at the prespecified WTP threshold compared to chemotherapy, and more significant in individuals with squamous NSCLC, which will provide evidence for clinicians to make the best decisions in general clinical practice.

Following Other People's Footsteps: A Contextual-Attraction Effect Induced by Biological Motion.

Our visual system is bombarded with numerous social interactions that form intangible social bonds among people, as exemplified by synchronized walking in crowds. Here, we investigated whether these perceived social bonds implicitly intrude on visual perception and induce a contextual effect. Using multiple point-light walkers and a classical contextual paradigm, we tested 72 college-age adults across six experiments and found that the perceived direction of the central walker was attracted toward the direction of the surrounding walkers. The observed contextual-attraction effect occurred even when the surrounding walkers differed from the central walker in gender and walking speed but disappeared when they were asynchronously presented or replaced by inanimate motion. Strikingly, this contextual-attraction effect partially persisted in the context of local motion rather than static figures. These findings, in contrast to the typical contextual-repulsion effect, lend support for the distinctiveness of perceived social bonds on contextual modulation and suggest a specialized contextual mechanism tuned to social factors.

Soil quality assessment of different Hevea brasiliensis plantations in tropical China.

Land degradation is a global problem caused by improper agricultural practices. In tropical China, the rubber (Hevea brasiliensis) plantations are predominantly practiced on forest-cleared lands, considering their sustainable land management potential compared to annual cropping. However, all rubber plantations may not have similar land management capacity. Soil quality index (SQI) can reveal the overall soil status with a single score, which is an efficient tool to evaluate the soil quality of each category of rubber plantations. We investigated 23 soil physical and chemical parameters of three categories of rubber plantations and a primary rainforest, and derived SQI based on these parameters. Soil samples were collected from a rubber monoculture (RM), a rubber-Camellia sinensis agroforestry (RT), a rubber-Dracaena cochinchinensis agroforestry (RD), and a primary rainforest (RF). The results showed that the SQI value of the RM decreased by 15.50% compared to the RF, with a significant degree of soil nutrient loss (18.90%). This indicates that monocultural rubber cultivation is causing land degradation to some extent. However, the SQI was significantly enhanced by rubber-based agroforestry practices (25.30% by RT and 33.10% by RD) compared to the RM, suggesting that polyculture practices are suitable to recover the soil quality in degraded agricultural lands. Moreover, the chemical parameters contributed more to the SQI than did the physical parameters, indicating that nutrient management is important in soil quality recovery. Overall, our results suggest that agroforestry should be preferred over monoculture in the rubber plantations for sustainable land management in tropical China.

The ecological risk assessment and suggestions on heavy metals in river sediments of Jinan.

The concentrations of eight heavy metals (Cr, Hg, As, Pb, Cd, Cu, Zn, Ni) in six river sediment samples were collected for evaluation of the degree of the heavy metals pollution distribution and ecological risk of three main rivers' sediments in Jinan. Multivariate statistical techniques were used to determine the most common pollution sources. The results illustrated that all of the metals in Damatou and Xinfengzhuang sections of the Xiaoqing River were much higher than the background value, and the level of potential ecological risk index was very high. The remaining four sections had a low or moderate degree of ecological risk. Principal component analysis (PCA) showed that all metals, with the exception of As, formed the first component explaining 86.85% of the total variance and industry sources could be considered as the first component, while As alone could be the second component, representing agricultural source. The elements Cr and Zn were grouped together while the remaining six metals formed a separate category. Among all heavy metals, Hg and Cd were the most significant contributors to the pollution. Therefore, the prevention of pollution should pay more attention to controlling the sources, especially Hg and Cd.

Pollution characteristics and potential ecological risk assessment of metals in the sediments of Xiaoqing River, Jinan.

The spatial-temporal changing characteristics and potential ecological risk combined with local policies and industrial status were analyzed. The metal contamination was studied by sediment quality guidelines (SQGs), potential ecological risk index (PERI), and geoaccumulation index (I geo) of metals (Hg, Cr, Cd, As, Pb, and Cu) in the sediments of Xiaoqing River in Jinan from 1996 to 2014. Results showed that the concentrations of metals were in fluctuation and had a decreasing trend in the past 19 years, which was influenced by industry and policy. The concentrations of metals from upstream to downstream presented a change from low to high and then a gradual decrease which were mainly related to anthropogenic activities. The assessment suggested that Hg presented the highest levels of I geo and was the largest contributor to RI, while Cd was the second contributor. This finding indicated that Hg and Cd had a strong effect on potential ecological risk. Damatou had the largest pollution level and potential ecological risk, whereas Mulizhuang was the least polluted area. SQGs indicated that Cd was below the TEC while it was the second contributor to potential ecological risk. Indeed, the pollution control of Xiaoqing River had a certain effect, but it needs long-term effective management measures and a strengthened source control. The suggestions of targeted management have been proposed in the paper.

[Application of immature platelet fraction absolute immature platelet fraction and thrombelastograph on assessment of bleeding risk in patients with immune thrombocytopenia].

OBJECTIVE: To explore the clinical value of immature platelet fraction (IPF), absolute immature platelet fraction (A- IPF) and thrombelastograph (TEG) on assessment of bleeding risk of immune thrombocytopenia (ITP). METHODS: two hundred and seventy- one patients with ITP were assessed based on ITP-BAT bleeding grading system. IPF, A-IPF were determined in 271 patients ,TEG in 125 patients. The correlations between bleeding grades and IPF, A-IPF, variables of TEG in subgroups were analyzed by statistical method. The predictive value of IPF, A-IPF, and variables of TEG on bleeding risk of ITP patients was evaluated. RESULTS: There were no significant differences in bleeding degree in all patients with different gender and disease stage (P>0.05). Mild bleeding rate in children was higher than that in adult (P<0.05). PLT inversely correlated with bleeding grade for the entire cohort (P<0.001). In all subjects, PLT< 30 × 109/L and pediatric cohorts with PLT< 30 × 109/L, PLT were negatively correlated with IPF (P<0.05), positive correlated with A-IPF (P<0.001) and the maximum amplitude (MA (P<0.05). Bleeding grades were significantly correlated with IPF, A-IPF, MA in all subjects and patients with PLT< 30 × 109/L (P<0.001). IPF, A-IPF and MA did not correlate with bleeding grades in children with PLT< 30 × 109/L (P>0.05). ROC curve analysis revealed IPF, A-IPF and MA had better predictive value (AUC 0.745, 0.744, 0.813, P<0.001). Multivariate analysis showed that IPF and MA were independence factors for predicting bleeding risk in ITP patients and comprehensive predictive value was higher (AUC 0.846, P<0.001) than single variable. CONCLUSION: IPF, A-IPF and MA could accurately evaluate bleeding risk in ITP patients. It may be considered as reference index of the treatment and observation index of curative effect.