Cost-effectiveness analysis of tislelizumab plus chemotherapy as the first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma in China.

OBJECTIVE: We aimed to investigate the cost-effectiveness of tislelizumab plus chemotherapy compared to chemotherapy alone as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (OSCC). METHODS: A partitioned survival model was developed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic OSCC over a 10-year lifetime horizon from the perspective of the Chinese healthcare system. Costs and utilities were derived from the drug procurement platform and published literature. The model outcomes comprised of costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were conducted to address uncertainty and ensure the robustness of the model. RESULTS: Tislelizumab plus chemotherapy yielded an additional 0.337 QALYs and incremental costs of $7,117.007 compared with placebo plus chemotherapy, generating an ICER of $21,116.75 per QALY, which was between 1 time ($12,674.89/QALY) and 3 times GDP ($38,024.67/QALY) per capita. In one-way sensitivity analysis, the ICER is most affected by the cost of oxaliplatin, paclitaxel and tislelizumab. In the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set as 1 or 3 times GDP per capita, the probability of tislelizumab plus chemotherapy being cost-effective was 1% and 100%, respectively. CONCLUSION: Tislelizumab plus chemotherapy was probably cost-effective compared with chemotherapy alone as the first-line treatment for advanced or metastatic OSCC in China.

Predicting dust pollution from dry bulk ports in coastal cities: A hybrid approach based on data decomposition and deep learning.

Dust pollution from storage and handling of materials in dry bulk ports seriously affects air quality and public health in coastal cities. Accurate prediction of dust pollution helps identify risks early and take preventive measures. However, there remain challenges in solving non-stationary time series and selecting relevant features. Besides, existing studies rarely consider impacts of port operations on dust pollution. Therefore, a hybrid approach based on data decomposition and deep learning is proposed to predict dust pollution from dry bulk ports. Port operational data is specially integrated into input features. A secondary decomposition and recombination (SDR) strategy is presented to reduce data non-stationarity. A dual-stage attention-based sequence-to-sequence (DA-Seq2Seq) model is employed to adaptively select the most relevant features at each time step, as well as capture long-term temporal dependencies. This approach is compared with baseline models on a dataset from a dry bulk port in northern China. The results reveal the advantages of SDR strategy and integrating operational data and show that this approach has higher accuracy than baseline models. The proposed approach can mitigate adverse effects of dust pollution from dry bulk ports on urban residents and help port authorities control dust pollution.

Bacteriolytic therapy with Clostridium ghonii for experimental solid tumors.

Clostridium ghonii (C. ghonii) is a non-pathogenic Clostridium species and a strictly anaerobic, spore-forming bacterium. However, its bacterial oncolytic capabilities and applications have not yet been reported. This study aimed to determining the bacterial oncolytic capability of C. ghonii for the treatment of experimental solid tumors. C. ghonii secreted collagenase IV and phospholipase c and significantly promoted apoptosis and necrosis in cultured A549 cells. C. ghonii spores specially germinated and were distributed in the tumors, and elicited the immune responses after intratumoral injection in tumor-bearing mice. C. ghonii spores decreased tumor volumes and increased tumor necrosis and inhibition rates in tumor-bearing mice. Furthermore, the combination of radiation and C. ghonii exerted additive anti-tumor effects. Taken together, our data indicate that C. ghonii is a bacteriolytic therapeutic agent against solid tumors. Given the proven natural safety of C. ghonii, it is attractive as a potential novel bacteriolytic therapy for solid tumors.

Economic Value of Fosaprepitant-Containing Regimen in the Prevention of Chemotherapy-Induced Nausea and Vomiting in China: Cost-Effectiveness and Budget Impact Analysis.

Objective: The purpose of this study was to evaluate the cost-effectiveness and budget impact of fosaprepitant (FosAPR)-containing regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) among patients receiving high emetogenic chemotherapy (HEC) from the Chinese payer's perspective. Methods: A decision tree model was established to measure the 5-day costs and health outcomes between the APR-containing regimen (aprepitant, granisetron, and dexamethasone) and FosAPR-containing regimen (fosaprepitant, granisetron, and dexamethasone). Clinical data were derived from a randomized, double-blind controlled trial on Chinese inpatients who received HEC. Quality-adjusted life-years (QALYs) were used to estimate the utility outcomes and the incremental cost-effectiveness ratio (ICER) was calculated to assess the economics of FosAPR. A static budget impact model was developed to assess the impact of FosAPR as a new addition to the National Reimbursement Drug List (NRDL) on the medical insurance fund within 3 years in Nanjing, China. Results: Compared with APR, FosAPR had a mean health-care savings of ¥121.56 but got a reduction of 0.0001815 QALY, resulting in an ICER of ¥669926.19 per QALY. Deterministic sensitivity analysis revealed that the cost of APR was the most influential factor to the ICER. The cost of FosAPR and the complete control rate of the delayed period also had a high impact on the results. According to the probabilistic analysis, the acceptability of FosAPR was more than 80% when the Chinese willingness-to-pay (WTP) was ¥215,999. FosAPR would lead to a 3-year medical insurance payment increase of ¥1.84 million compared with ¥1.49 million before FosAPR entered NRDL in Nanjing. The total budget increased with a cumulative cost of ¥694,829 and covered an additional 341 patients who benefited from FosAPR in Nanjing. Deterministic sensitivity analysis showed that the model of budget impact analysis was stable. Conclusion: FosAPR had a similar treatment effect to APR but was cost-effective in China at the current WTP threshold. The total budget of medical insurance payments of Nanjing slightly increased year by year after the inclusion of FosAPR. Its inclusion in the NRDL would be acceptable and also expand the coverage of patients who benefited from FosAPR.

The impact of policy on availability and price of low-price medicines in public healthcare institutions: A retrospective survey in Nanjing, China.

In an effort to promote rational drug pricing and relieve the pressure of drug shortages, the Chinese government implemented a low-price medicine (LPM) policy in July 2014, and abolished price regulations for most medications in June 2015. This study examines trends in the availability and pricing of LPMs since policy implementation. Data on price and availability of 752 LPMs during 2013-2017 were obtained from the Jiangsu Institute of Medicine Information. Availability was defined as the proportion of facilities in which a medicine was in inventory during each survey period. A price index was constructed based on purchasing prices in 40 public healthcare facilities, using a standard method developed by the International Labour Organization. Mean availability fluctuated slightly but held at low levels (<15%). Levels were conspicuously lower in primary hospitals than in secondary and tertiary hospitals. Our logistic regression model showed that the essential medicine designation was the main factor facilitating availability. The overall price index remained static before implementation of the policy, while there was a marked upward trend after implementation of the policy. Further efforts are needed to improve the pharmaceutical supply system, and simultaneously curb unreasonable inflation in medicine costs.

A hub-and-spoke design for ultra-cold COVID-19 vaccine distribution.

An orderly and effective vaccination campaign is essential in combating the global COVID-19 pandemic. As one of the pioneers, the U.S. Center for Disease Control proposes a phased plan to promote the vaccination process. This plan starts with vaccinating the high-priority population in Phase 1, then turns to the remainder of the public in Phase 2, and ends with a scale-back network in Phase 3. The phased plan not only provides a sense of hope to impacted communities that this global pandemic can be defeated, but can serve as a template for other countries. To enhance this plan, this paper develops a generalizable framework for designing a hub-and-spoke vaccination dispensing network to achieve the goals in the Phase 2, which aims to expand the vaccination coverage for the general public. We introduce a new coverage index to measure the priority of different potential dispensing sites based on geo-data and develop an optimization model for network design. The hub-and-spoke network enhances the accessibility of the vaccines to various communities and helps to overcome the challenges related to ultra-cold storage facility shortage. A case study of Middlesex County in New Jersey is presented to demonstrate the application of the framework and provide insights for the Phase 2. Results from the baseline scenario show that increasing the driving time limit from 10 min to 25 min can improve the total coverage index from 40.8 to 55.9. Additionally, we explore how the changes of parameters impact the network design and discuss potential solutions for some special cases. When we allow 4 outreach nodes per hub, all potential 45 outreach points can be covered in the vaccination network within a 20-minute drive, and the total coverage index reaches its maximum value of 58.3.

Impact of the National Health Insurance Coverage Policy on the Utilisation and Accessibility of Innovative Anti-cancer Medicines in China: An Interrupted Time-Series Study.

Objective: The study aimed to evaluate the impact of the National Health Insurance Coverage (NHIC) policy on the utilisation and accessibility of innovative anti-cancer medicines in Nanjing, China. Methods: We used the adjusted World Health Organisation and Health Action International methodology to calculate the price and availability of 15 innovative anti-cancer medicines included in the National Health Insurance drug list in 20 tertiary hospitals and six secondary hospitals in Nanjing before and after NHIC policy implementation. Interrupted time-series regression was used to analyse the changes in the utilisation of the study medicines. Results: The price reduction rates of innovative anti-cancer medicines ranged between 34 and 65%. The mean availability rate was 27.44% before policy implementation and increased to 47.33% after policy implementation. The utilisation of anti-cancer medicines suddenly increased with a slope of 33.19-2,628.39 when the policy was implemented. Moreover, the usage rate of bevacizumab, bortezomib, and apatinib significantly increased (p < 0.001, p = 0.009, and p < 0.001, respectively) after policy implementation. With regard to price reduction and medical insurance reimbursement, the medicines became more affordable after policy implementation (0.06-1.90 times the per capita annual disposable income for urban patients and 0.13-4.46 times the per capita annual disposable income for rural patients). Conclusion: The NHIC policy, which was released by the central government, effectively improved the utilisation and affordability of innovative anti-cancer medicines. However, the availability of innovative anti-cancer medicines in hospitals remained low and the utilisation of innovative anti-cancer medicines was affected by some factors, including the incidence of cancer, limitation of indications within the insurance program, and the rational use of innovative anti-cancer medicines. It is necessary to improve relevant supporting policies to promote the affordability of patients. The government should speed up the process of price negotiation to include more innovative anti-cancer medicines in the medical insurance coverage, consider including both medical examinations and adjuvant chemotherapy in the medical insurance, and increase investment in health care.

Paricalcitol versus Calcitriol + Cinacalcet for the Treatment of Secondary Hyperparathyroidism in Chronic Kidney Disease in China: A Cost-Effectiveness Analysis.

Background: Chronic Kidney Disease (CKD) is a global chronic disease with increasing prevalence in recent years, particularly CKD accompanied by Secondary Hyperparathyroidism (SHPT) leads to reduced quality of life, increased mortality, a considerable economic burden for patients and society. The aim of this study was to investigate the cost-effectiveness analysis of paricalcitol vs. calcitriol + cinacalcet for CKD patients with SHPT in China in 2020. Methods: A Markov model was conducted employing data derived from published literature, clinical trials, official sources, and tertiary public hospital data in China, based on a 10-year horizon from the perspective of the healthcare system. Calcitriol + Cinacalcet was used as the reference group. CKD stage 5 (CKD-5) dialysis patients suffering from SHPT were included in the study. Effectiveness was measured in quality-adjusted life years (QALYs). The discount rate (5%) was applied to costs and effectiveness. Sensitivity analysis was performed to confirm the robustness of the findings. Results: The base case analysis demonstrated that Patients treated with paricalcitol could gain an increase in utility (0.183 QALYs) and require fewer expenditures (6925.612 yuan). One-way sensitivity analysis was performed to showed that impact factors were the price of cinacalcet, the hospitalization costs of patients with paricalcitol and calcitriol, the costs and utilities of hemodialysis and the costs of calcitriol, the costs of paricalcitol regardless of period. Probabilistic simulation analysis displayed when willingness-to-pay was ¥217113, the probability that Paricalcitol was dominant is 96.20%. Conclusion: The results showed that paricalcitol administrated to treat patients diagnosed with Secondary hyperparathyroidism in Chronic Kidney Disease, compared to calcitriol and cinacalcet, might be dominant in China.

Cost-effectiveness analysis of dacomitinib versus gefitinib for the first-line therapy of patients with EGFR mutation-positive non-small-cell lung cancer in the United States and China.

BACKGROUND: This study aimed to investigate the cost-effectiveness of dacomitinib and gefitinib for the first-line treatment of advanced non-small-cell lung cancer (NSCLC) in epidermal growth factor receptor (EGFR) mutation-positive patients from the perspective of healthcare systems in the United States and China. METHODS: A Markov model, which included 3 health states over 10 years, was established in this study. The state transition probabilities and clinical data were extracted from the ARCHER 1050 trial (dacomitinib versus gefitinib in patients with EGFR mutation-positive advanced NSCLC). Health utilities were derived from published literature. Based on the healthcare system payer's perspective in the United States and China, the cost data were estimated from local pricing or the relevant literature. The health outcomes are expressed by quality-adjusted life years (QALYs). All costs and incremental cost-effectiveness ratios (ICERs) are presented in US dollars. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to test the robustness of the results. RESULTS: In the United States, compared with gefitinib, dacomitinib yielded an additional 0.55 QALYs, while the ICERs were $600.69 per QALY. The cost of dacomitinib was the most influential parameter. The willingness payment curve showed that dacomitinib was cost-effective at the $100,000/QALY willingness-to-pay (WTP) threshold. Meanwhile, when the WTP threshold was higher than $200,000/QALY, the probability of dacomitinib being the best treatment plan was more than 80%. In China, compared with gefitinib, dacomitinib was associated with a mean healthcare savings of $160,173.27 and 0.41 additional QALYs per patient, which was a dominant intervention over a 10-year time horizon. The cost of progressive disease was shown to have the strongest impact on the results. Dacomitinib had more than a 90% probability of being chosen as the preferred therapy when the Chinese WTP threshold was $27,000/QALY. CONCLUSIONS: As the first-line treatment for EGFR mutation-positive NSCLC, dacomitinib is likely to be more cost-effective than gefitinib from the healthcare system's perspective in the United States and China.

Availability, cost and affordability of selected antibiotics and antiviral medicines against infectious diseases from 2013 to 2019 in Nanjing, China.

OBJECTIVES: As economic globalisation develops in-depth, infectious diseases that occur in a country or region no longer remains a regional issue. Antibiotics and antiviral medicines are essential medicines for the therapy of infectious diseases. This study aims to evaluate their availability, cost and affordability of AaAMs against infectious diseases in 41 public hospitals from 2013 to 2019 in Nanjing, China. METHODS: Data on the availability and price of 17 antibiotics and 6 antiviral medicines in 41 public hospitals were obtained from the Jiangsu Institute of Medicine Information. We adopted the WHO/Health Action International method to measure the availability, cost and affordability of these medicines. RESULTS: The availability of selected medicines against infectious diseases was relatively low; the median availability of originator brands was near-zero and that of lowest-priced generics during the survey period less than 50%. The total availability of medicines was poor in primary hospitals as compared to secondary and tertiary hospitals. The median daily-defined dose cost of originator brands was expensive (range from 66.11 RMB to 107.83 RMB), whereas that of lowest price generics was fairly acceptable at < 8 RMB. The affordability of most surveyed medicines was reasonable, which showed significant improvement over time, but the daily cost of a few medicines for originator brands exceeded the average daily wage. CONCLUSIONS: In general, the affordability of medicines surveyed was acceptable, while the availability was too low. There should be a great concern for improving the reserve system of anti-infective medicines in healthcare institutions. Policy should focus on improving the availability of generic drugs in hospitals and encouraging preferentially prescribed.

The Effects of County Public Hospital Reform on the Consumption and Costs of Antibiotics: Evidence from a Quasinatural Experiment in Jiangsu, China.

BACKGROUND: Overuse of antibiotics is a major driver for rapid spread of antimicrobial resistance worldwide, particularly common in China. The close linkage between hospital revenue and sales of drugs has become the key incentive for overprescription of antibiotics. Since 2009, the Chinese government implemented a series of measures to cut off the link, including removing the markup of drugs, increasing financial subsidies, and adjusting charges for medical service. OBJECTIVE: To evaluate the impacts of county public hospital reform on the consumption and costs of procured antibiotics in Jiangsu province. METHODS: A quasiexperiment design was conducted in Jiangsu province where 99 county public hospitals implemented the reform successively in different periods. Of these, 37 county public hospitals implemented the reform since January 2013, which were regarded as the intervention group, and the remaining 62 hospitals were included in the control group. A difference-in-differences (DID) analysis with generalized linear regressions was used on the procurement records of antibiotics from January 2012 to December 2013. Modified Park test was used for family distribution and Box-Cox test for log link. Placebo tests were employed to test the common-trend hypothesis of two groups. RESULTS: For the intervention group, the average volume of procured restricted antibiotics and injectable antibiotics increased by 24.12% and 2.75% while the costs increased by 19.01% and 9.09%, respectively. The average costs per DDD of restricted and injectable antibiotics were much higher than unrestricted and oral antibiotics. The DID results showed that the reform had a positive impact on the average volume (p = 0.005) and costs (p = 0.001) of nonrestricted antibiotics. In addition, the implementation of the reform was associated with a reduction in volume (p = 0.031) and costs (p = 0.043) of procured oral antibiotics. The reform also contributed to an increase in average costs per DDD of total antibiotics (p = 0.049). CONCLUSIONS: The reform is effective in reducing the consumption and costs of unrestricted and oral antibiotics, but it has failed to reduce the consumption and costs of expensive restricted and injectable antibiotics, leading to increased burden of diseases. It is critical that the health policy initiatives can deincentivize overuse of antibiotics at both hospital and individual physician's levels. The reform should enforce government financial support, improve hospital governance, optimize performance evaluation, and establish specialized management approach for antibiotic use.

Microwave ablation plus chemotherapy versus chemotherapy in advanced non-small cell lung cancer: a multicenter, randomized, controlled, phase III clinical trial.

OBJECTIVES: This prospective trial was performed to verify whether microwave ablation (MWA) in combination with chemotherapy could provide superior survival benefit compared with chemotherapy alone. MATERIALS AND METHODS: From March 1, 2015, to June 20, 2017, treatment-naïve patients with pathologically verified advanced or recurrent non-small cell lung cancer (NSCLC) were randomly assigned to MWA plus chemotherapy group or chemotherapy group. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), time to local progression (TTLP), and objective response rate (ORR). The complications and adverse events were also reported. RESULTS: A total of 293 patients were randomly assigned into the two groups. One hundred forty-eight patients with 117 stage IV tumors were included in the MWA plus chemotherapy group. One hundred forty-five patients with 113 stage IV tumors were included in the chemotherapy group. The median follow-up period was 13.1 months and 12.4 months, respectively. Median PFS was 10.3 months (95% CI 8.0-13.0) in the MWA plus chemotherapy group and 4.9 months (95% CI 4.2-5.7) in the chemotherapy group (HR = 0.44, 95% CI 0.28-0.53; p < 0.0001). Median OS was not reached in the MWA plus chemotherapy group and 12.6 months (95% CI 10.6-14.6) in the chemotherapy group (HR = 0.38, 95% CI 0.27-0.53; p < 0.0001) using Kaplan-Meier analyses with log-rank test. The median TTLP was 24.5 months, and the ORR was 32% in both groups. The adverse event rate was not significantly different in the two groups. CONCLUSIONS: In patients with advanced NSCLC, longer PFS and OS can be achieved with the treatment of combined MWA and chemotherapy than chemotherapy alone. KEY POINTS: • Patients treated with MWA plus chemotherapy had superior PFS and OS over those treated with chemotherapy alone. • The ORR of patients treated with MWA plus chemotherapy was similar to that of those treated with chemotherapy alone. • Complications associated with MWA were common but tolerable and manageable.

Availability, prices and affordability of essential medicines for children: a cross-sectional survey in Jiangsu Province, China.

OBJECTIVE: China has undertaken several initiatives to improve the accessibility of safe and effective medicines for children. The aim was to determine the availability, price and affordability of essential medicines for children. DESIGN: Cross-sectional survey. SETTING: Six cities of Jiangsu Province, China. PARTICIPANTS: 30 public hospitals and 30 retail pharmacies. PRIMARY AND SECONDARY OUTCOME MEASURES: The WHO/Health Action International standardised methodology was used to collect the availability and price data for 40 essential medicines for children. Availability was measured as the percentage of drug outlets per sector where the individual medicine was found on the day of data collection, and prices were measured as median price ratios (MPRs). Affordability was measured as the number of days' wages required for the lowest paid unskilled government worker to purchase standard treatments for common conditions. RESULTS: The mean availabilities of originator brands (OBs) and lowest priced generics (LPGs) were 7.5% and 34.2% in the public sector and 8.9% and 29.4% in the private sector. The median MPRs of LPGs in both sectors ranged from 1.41 to 2.12 and 1.10 to 2.24, respectively. However, the patient prices of OBs far exceeded the critical level in both sectors, with median MPRs ranging from 2.47 to 8.22. More than half of these LPGs were priced at 1.5 times their international reference prices in the public sector. Most LPGs were affordable for treatment of common conditions in both public and private sectors, as they each cost less than the daily wage for the lowest paid unskilled government worker. CONCLUSIONS: Access to essential medicines for children is hampered by low availability. Further measures to enhance access to paediatric essential medicines should be taken, such as developing a national essential medicine list for children and mobilising the enthusiasm of pharmaceutical firms to develop and manufacture paediatric medicines.

Targeted percutaneous microwave ablation at the pulmonary lesion combined with mediastinal radiotherapy with or without concurrent chemotherapy in locally advanced non-small cell lung cancer evaluation in a randomized comparison study.

Concurrent chemoradiotherapy is the standard treatment for patients with locally advanced lung cancer. The most common dose-limiting adverse effect of thoracic radiotherapy (RT) is radiation pneumonia (RP). A randomized comparison study was designed to investigate targeted percutaneous microwave ablation at pulmonary lesion combined with mediastinal RT with or without chemotherapy (ablation group) in comparison with RT (target volume includes pulmonary tumor and mediastinal node) with or without chemotherapy (RT group) for the treatment of locally advanced non-small cell lung cancers (NSCLCs). From 2009 to 2012, patients with stage IIIA or IIIB NSCLCs who refused to undergo surgery or were not suitable for surgery were enrolled. Patients were randomly assigned to the RT group (n = 47) or ablation group (n = 51). Primary outcomes were the incidence of RP and curative effectiveness (complete response, partial response, and stable disease); secondary outcome was the 2-year overall survival (OS). Fifteen patients (31.9%) in the RT and two (3.9%) in the ablation group experienced RP (P < 0.001). The ratio of effective cases was 85.1 versus 80.4% for mediastinal lymph node (P = 0.843) and 83.0 versus 100% for pulmonary tumors (P = 0.503), respectively, for the RT and ablation groups. Kaplan-Meier analysis demonstrated 2-year OS rate of NSCLC patients in ablation group was higher than RT group, but no statistical difference (log-rank test, P = 0.297). Percutaneous microwave ablation followed by RT for inoperable stage III NSCLCs may result in a lower rate of RP and better local control than radical RT treatments.

Chemical ablation therapy of recurrent mediastinal nodal metastasis in post-radiotherapy cancer patients.

The aim of our study was to evaluate the treatment of post-radiotherapy recurrent mediastinal nodal metastasis. Post-radiotherapy esophageal cancer patients with mediastinal lymph node recurrence were enrolled in this study. Patients were randomized into the radiation (±chemotherapy) or the chemoablation group. Patients randomized to the chemoradiotherapy group received additional radiotherapy, second-line chemotherapy, or both. Patients randomized to the chemoablation group received CT-guided percutaneous chemical ablation. Clinical remission was assessed at 1 month by contrast CT. Reirradiation dose ranged from 2,200 to 3,600 cGy depending on dose-limiting constraints in consideration of prior radiotherapy dose. The RECIST criteria were used in the evaluation of response to therapy. The median length of follow-up is 6 months. Thirty-one patients were enrolled in the study. In the chemoradiation group, all patients underwent CT imaging at 1-month follow-up. Among these patients, seven had progressive disease, five had stable disease (SD), and four had partial response (PR). The 6-month survival rate was 12.5%. In the chemoablation group at 1-month follow-up, 12 patients had SD and three patients had PR, and the 6-month survival rate was 46.6%. Our results suggest that chemoablation therapy as salvage treatment after post-radiotherapy relapse is efficacious and safe.