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Background: This study aimed to analyze the cost effectiveness of camrelizumab in the second-line treatment of advanced or metastatic esophageal squamous cell carcinoma in China.Methods: On the basis of the ESCORT clinical trial, a partitioned survival model was constructed to simulate the patient’s lifetime quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). One-way sensitivity and probability sensitivity analyses were performed to test the stability of the model.Results: Treatment of esophageal squamous cell carcinoma with camrelizumab added 0.36 QALYs and resulted in an incremental cost of $1,439.64 compared with chemotherapy, which had an ICER of $3,999 per QALY gained. The ICER was far lower than the threshold of willingness to pay for one time the GDP per capita in China. Sensitivity analysis revealed that the ICERs were most sensitive to the cost of drugs, but the parameters did not have a major effect on the results of the model.Conclusion: Camrelizumab is likely to be a cost-effective option compared with chemotherapy for patients with advanced or metastatic esophageal squamous cell carcinoma. This informs patient selection and clinical path development.

Gelsemium elegans Benth (GEB), also known as heartbreak grass, is a highly poisonous plant belonging to the family Loganiaceae and genus Gelsemium that has broad application prospects in medicine. This article reviews its chemical components, pharmacological effects, toxicity mechanisms, and research progress in clinical applications in recent years. Indole alkaloids are the main active components of GEB and have a variety of pharmacological and biological functions. They have anti-tumor, anti-inflammatory, analgesic, and immunomodulation properties, with the therapeutic dose being close to the toxic dose. Application of small-dose indole alkaloids fails to work effectively, while high-dose usage is prone to poisoning, aggravating the patient’s conditions. Special caution is needed, especially to observe the changes in the disease condition of the patients in clinical practice. In-depth research on the chemical components and mechanisms of GEB is essential to the development of promising lead compounds and lays the foundation for extensive clinical application and safe usage of GEB in the future.

Gelsemium elegans (Gardner and Champ.) Benth. (Gelsemiaceae) (GEB) is a toxic plant indigenous to Southeast Asia especially China, and has long been used as Chinese folk medicine for the treatment of various types of pain, including neuropathic pain (NPP). Nevertheless, limited data are available on the understanding of the interactions between ingredients-targets-pathways. The present study integrated network pharmacology and experimental evidence to decipher molecular mechanisms of GEB against NPP. The candidate ingredients of GEB were collected from the published literature and online databases. Potentially active targets of GEB were predicted using the SwissTargetPrediction database. NPP-associated targets were retrieved from GeneCards, Therapeutic Target database, and DrugBank. Then the protein-protein interaction network was constructed. The DAVID database was applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis. Molecular docking was employed to validate the interaction between ingredients and targets. Subsequently, a 50 ns molecular dynamics simulation was performed to analyze the conformational stability of the protein-ligand complex. Furthermore, the potential anti-NPP mechanisms of GEB were evaluated in the rat chronic constriction injury model. A total of 47 alkaloids and 52 core targets were successfully identified for GEB in the treatment of NPP. Functional enrichment analysis showed that GEB was mainly involved in phosphorylation reactions and nitric oxide synthesis processes. It also participated in 73 pathways in the pathogenesis of NPP, including the neuroactive ligand-receptor interaction signaling pathway, calcium signaling pathway, and MAPK signaling pathway. Interestingly, 11-Hydroxyrankinidin well matched the active pockets of crucial targets, such as EGFR, JAK1, and AKT1. The 11-hydroxyrankinidin-EGFR complex was stable throughout the entire molecular dynamics simulation. Besides, the expression of EGFR and JAK1 could be regulated by koumine to achieve the anti-NPP action. These findings revealed the complex network relationship of GEB in the “multi-ingredient, multi-target, multi-pathway” mode, and explained the synergistic regulatory effect of each complex ingredient of GEB based on the holistic view of traditional Chinese medicine. The present study would provide a scientific approach and strategy for further studies of GEB in the treatment of NPP in the future.

BACKGROUND Cancer pain is a significant public health issue. Mobile health offers improved and cost-effective care to people with cancer pain. However, the efficiency of engagement strategies and modules of this technology need to be reviewed and standardized according to expert perspectives. The use of applications (apps) for cancer pain management has increased over recent years. However, evidence regarding the efficacy and safety of these apps remains lacking. This study used the modified Delphi process on the design of cancer pain management apps. OBJECTIVE The study aimed to design the most agreed-upon modules for cancer pain management mobile apps. METHODS This study recruited experts in the domain of cancer pain management and applied a modified Delphi method to design the most relevant app modules. We used the positive coefficient and authority of expert indexes, such as the degree of coordination with expert opinions and other modules to test the reliability of the consultation. Cronbach’s α coefficient, content validity index (CVI), were used for data analysis. RESULTS A total of 23 experts with a mean age of 42.3 years (SD 5.7) consented to participate in the study. All of them had worked more than 10 years in the cancer pain management field. Overall, five app modules were generated. The Cronbach’s a coefficient was 0.81 for the overall scale.The scale-level CVI was 0.78. CONCLUSIONS This study is the first in China to recruit a local panel of experts from the cancer pain management field. We used an iterative process to combine the experts’ opinions into a group consensus. The results of this study could benefit developers of health apps and inform future decision making on cancer pain management.

Maobai Liu,1,2,* Sijie Han,2,* Bin Zheng,1,2 Hongfu Cai,1,2 Jing Yang,1,2 Qian Zhuang,1,2 Na Li1,2 1Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 2The School of Pharmacy, Fujian Medical University, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Na LiDepartment of Pharmacy, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian 350001, People’s Republic of ChinaEmail fjxhlina1983@fjmu.edu.cnBackground: Pembrolizumab, a programmed cell death-1 (PD-1) inhibitor, has recently gained prominence as a second-line treatment for recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC). This study compares the acceptance and different influencing factors of pembrolizumab in the treatment of R/M HNSCC in developed (i.e., the United States) and developing (i.e., China) countries through cost-effectiveness analysis and provides valuable suggestions for clinical decision making.Methods: A Markov model was constructed using TreeAge Pro 2015 software to evaluate the economic value of four treatment strategies. Quality-adjusted life years (QALY) and incremental cost-effectiveness ratio (ICER) were used as economic indicators for incremental cost-effectiveness analysis. The stability of the model was evaluated by one-way sensitivity and probability sensitivity analyses.Results: The ICERs for the pembrolizumab group versus PD-L1 CPS treatment in China and the US were $7892/QALY and $11,900/QALY, respectively. All ICERs were less than the threshold of $29,306 in China and $50,000 in the US; thus, pembrolizumab is cost effective. Sensitivity analysis confirmed a stable economic advantage in the single-drug regimen of pembrolizumab in China and the US.Conclusion: Pembrolizumab monotherapy as a second-line treatment for R/M HNSCC presents more health benefits in comparison with the standard, PD-L1 TPS and PD-L1 CPS groups in China and the US.Keywords: pembrolizumab, head and neck cancer, cost-effectiveness

Purpose The aim of this study is to assess the bioequivalence of a new generic formulation and the branded formulation of levocetirizine dihydrochloride in healthy Chinese volunteers under fasting and fed conditions, and food-intake effect on the pharmacokinetic properties is also evaluated. Patients and methods Volunteers were randomly allocated into two groups to receive a single oral dose of generic formulation and branded formulation under fasting or fed conditions, respectively. Blood samples were collected at designated time points. Plasma concentrations of levocetirizine were determined by UFLC-MS/MS. Safety evaluations were carried out through the study. The main pharmacokinetic parameters of the two formulations of levocetirizine were calculated using non-compartmental analysis incorporated in WinNonlin® 7.0 software. Results Forty-nine volunteers were enrolled; 46 completed the studies. Under fasting and fed conditions, the 90% confidence intervals for the geometric mean of generic/branded ratios were in the range of 94.75–107.24% and 99.98–114.69% for the maximum observed concentration, and 97.13–102.50% and 98.36–103.98% for the area under the concentration–time curve. As a result of food intake before administration, the reduced rate and extent of absorption of levocetirizine were observed. Both formulations were generally well tolerated, with no serious adverse reactions reported. Conclusion The two formulations demonstrated essentially identical pharmacokinetic profiles and were all well within the FDA/CFDA bioequivalence standards. Meanwhile, food intake can delay the absorption rate and reduced the bioavailability of levocetirizine in healthy Chinese volunteers., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/-Xhw5uFbQfw

Background: Of two main alkaloids extracted from Gelsemium, koumine was shown to be a promising analgesic, while gelsemine proved to be deleterious. Many patients suspected to be poisoned by Gelsemium cannot be timely diagnosed due to the lack of UPLC-MS/MS. Additionally, the concentration of alkaloids in humans has never been reported. The aim of this study was to establish a more economical and accessible method using HPLC-UV for diagnosis and quantitative analysis of Gelsemium poisoning. Methods: Plasma spiked with an internal standard, oxcarbazepine, was prepared with solid-phase extraction. Koumine and gelsemine were separated on a C18 column using a mobile phase consisting of methanol, water, and di-n-butylamine (58:42:0.01) pumped at a flow rate of 1.00 mL/min. The detection wavelength was set at 263 nm. Plasma concentrations of two different times were determined for the patients. Results: The calibration curves for both monomers possessed good linearity from 0.05-50 mg/L (r=0.9997 and 0.9999, respectively). The extraction recoveries were greater than 88.5 %. Variation for intraday and interday assays of koumine and gelsemine were less than 8.3% and 7.7%, respectively. The concentrations of the two alkaloids were identified in 5 patients with Gelsemium poisoning by using the established method. Conclusion: The established method by using HPLC-UV is applicable for diagnosis and quantitative analysis of Gelsemium poisoning in such cases. TDM of koumine and gelsemine in patients with Gelsemium poisoning may provide additional information for the clinic to improve rescue strategy.

Background Pulmonary arterial hypertension (PAH) is a rare disease in children, with significant mortality. Because of the limited research on pediatric PAH, firstly systematic review of related drugs is conducted, and then economic evaluation of PAH drug treatment programs is conducted, which to provide a reference for the choice of more cost-effective treatment options. Methods The search includes electronic databases such as Pubmed, ScienceDirect, Embase. Through inclusion and exclusion criteria, screen high-quality randomized controlled trials. We used TreeAge Pro 2011 software to construct the markov model, that to simulate the total medical cost and quality-adjusted life years (QALYs), and to calculate the incremental cost-effectiveness ratio (ICER). Sensitivity analysis of transfer probability, utility and cost was carried out. Results Incorporate two studies that meet the criteria, one compared the therapeutic effects of bosentan and placebo on pediatric PAH, the other compared therapeutic effects of sildenafil and placebo on pediatric PAH, both articles were of good quality. Compared with the sildenafil group (3.38QALYs and $161120.14),the QALY of the bosentan treatment group (3.33QALYs and $257411.29) was reduced by 0.05, and the cost increased by $96291.15. The estimated improvement to quality of life and reduced costs result in an estimate of economic dominance for sildenafil over bosentan. This dominant result persisted probabilistic analyses. Conclusions Based on this model, a more cost-effective treatment drug for PAH in children is sildenafil. This article is protected by copyright. All rights reserved.

Background Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Gelsemium elegans Benth (GEB) is a traditional Chinese medicine commonly used for treatment for gastrointestinal cancer, including CRC. However, the underlying active ingredients and mechanism remain unknown. This study aims to explore the active components and the functional mechanisms of GEB in treating CRC by network pharmacology-based approaches. Methods Candidate compounds of GEB were collected from the Traditional Chinese Medicine@Taiwan, Traditional Chinese Medicines Integrated Database, Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine, and published literature. Potentially active targets of compounds in GEB were retrieved from SwissTargetPrediction databases. Keywords “colorectal cancer”, “rectal cancer” and “colon cancer” were used as keywords to search for related targets of CRC from the GeneCards database, then the overlapped targets of compounds and CRC were further intersected with CRC related genes from the TCGA database. The Cytoscape was applied to construct a graph of visualized compound-target and pathway networks. Protein-protein interaction networks were constructed by using STRING database. The DAVID tool was applied to carry out Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis of final targets. Molecular docking was employed to validate the interaction between compounds and targets. AutoDockTools was used to construct docking grid box for each target. Docking and molecular dynamics simulation were performed by Autodock Vina and Gromacs software, respectively. Results Fifty-three bioactive compounds were successfully identified, corresponding to 136 targets that were screened out for the treatment of CRC. Functional enrichment analysis suggested that GEB exerted its pharmacological effects against CRC via modulating multiple pathways, such as pathways in cancer, cell cycle, and colorectal cancer. Molecular docking analysis showed that the representative compounds had good affinity with the key targets. Molecular dynamics simulation indicated that the best hit molecules formed a stable protein-ligand complex. Conclusion This network pharmacology study revealed the multiple ingredients, targets, and pathways synergistically involved in the anti-CRC effect of GEB, which will enhance our understanding of the potential molecular mechanism of GEB in treatment for CRC and lay a foundation for further experimental research.

Objective Primary aldosteronism (PA) is an underdiagnosed cause of hypertension. Although the medical costs will increase if all patients with elevated blood pressure are screened, the number of missed diagnosed patients with PA and the medical resources subsequently consumed by adverse cardiovascular and cerebrovascular events can be reduced. This study aimed to conduct economic evaluation PA screening strategies in Chinese patients with hypertension, that is PA screening in patients with high-risk hypertension and all patients with hypertension, to determine the cost-effective method. Methods The decision tree and Markov model were constructed using TreeAge Pro 2020. Using the latter, a 30-year course of hypertension after different screening strategies was simulated, with a cycle of one year. The model parameters included epidemiological data, clinical efficacy, cost and effectiveness. The total cost of treatment and quality-adjusted life year (QALY) were simulated to conduct a cost-effectiveness analysis. Univariate and probabilistic sensitivity analyses of the model were also performed. Results PA screening patients with high-risk hypertension and all patients with hypertension obtained 15.75 and 15.77 QALYs and the costs were $2488.39 and $2482.15, respectively. The strategy of PA screening in all patients with hypertension is cost-saving and produces more health outcomes. The sensitivity analysis showed that the results were reliable. Conclusion From the perspective of China's health system, the strategy of screening all hypertensive patients for PA may be more cost-effective than screening only high-risk patients and providing standard antihypertensive treatment for low-risk hypertensive patients.

BackgroundThe aim of the present study was to evaluate the cost-effectiveness of durvalumab plus platinum–etoposide versus platinum–etoposide as first-line treatments for small-cell lung cancer from the perspective of the US payer.MethodsThis study established a partition survival model for three health states, metastasis probability, and safety data based on the CASPIAN clinical trial. The health utility value was mainly derived from the published literature. Only direct medical costs were considered. Sensitivity analyses were conducted to assess the robustness of the incremental cost per quality-adjusted life year (QALY).ResultsDurvalumab plus platinum–etoposide increased QALY by 0.220 compared to that observed with platinum–etoposide only. The cost increased by $78,198.75 and the incremental cost per QALY increased by $355,448.86. One-way and probability sensitivity analyses indicated that the model parameters varied within a limited range and had no significant effect on the results.ConclusionsAlthough durvalumab plus platinum–etoposide can improve quality of life, it also substantially increases the cost of medical treatment. Under a willingness-to-pay threshold of $100,000, durvalumab does not have a cost-effective comparative advantage.

Longfeng Zhang,1 Na Li,2 Maobai Liu,2 Bin Zheng,2 Zhijuan Wu,3 Hongfu Cai2 1Department of Thoracic Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Pharmacy, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of ChinaCorrespondence: Hongfu Cai; Maobai LiuDepartment of Pharmacy, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, People’s Republic of ChinaEmail caihongfu31@126.com; liumaobai@126.comBackground: The objective of the study was to evaluate the economics of dacomitinib and gefitinib in the first-line treatments for EGFR-positive advanced or metastatic non-small cell lung cancer (NSCLC) from a US payer perspective.Methods: We developed the partition survival model to compare the lifetime cost and health outcomes of dacomitinib versus gefitinib. Transition probabilities were collected from the ARCHER 1050 trial. The model only considered the direct medical costs. Utility values were taken from published research.Results: Compared to gefitinib, dacomitinib increased 0.706 QALY and the cost increased $232,359.32. The incremental cost-effectiveness ratio (ICER) was $329,120.85 per QALY in the base case. One-way sensitivity analysis showed that the cost of drugs and the utility had more influence on the results than other parameters. Probability sensitivity analysis reflected that the parameters had little effect on the results.Conclusion: Dacomitinib could improve the health benefits and increase the overall costs. In this simulation, dacomitinib is not likely to be economical for first-line therapy of EGFR-mutated NSCLC.Keywords: dacomitinib, gefitinib, cost-effectiveness, non-small cell lung cancer

BACKGROUND Delayed excretion of methotrexate can lead to life-threatening toxicity that may result in treatment cessation, irreversible organ damage, and death. Various factors have been demonstrated to influence the pharmacokinetic process of methotrexate, including genetic and nongenetic factors. METHODS We investigated the genetic factors primarily related to the metabolic pathway of methotrexate in children with acute lymphoblastic leukemia with delayed elimination, defined as C44-48h ≥ 1.0μmol/L in this study. A total of 196 patients (delayed excretion group: 98; normal excretion group: 98) who received CCCG-ALL-2015 protocol after propensity score-matched analysis were included in the study. Twenty-eight target single-nucleotide polymorphisms (SNPs) were analyzed by multiplex polymerase chain reaction and sequencing, and 25 SNPs were finally included in the study. RESULTS The genotype distribution of SLCO1B1 rs2306283 SNP was different between the delayed and normal excretion groups. SLCO1B1 rs2306283 AA carriers had a significantly lower methotrexate C44-48h /D ratio than GG carriers in both groups. Furthermore, compared with the normal excretion group, SLCO1B1 rs2306283 AG and GG were risk factors for developing oral mucositis (odds ratio [OR]: 2.13; 95% confidence interval [CI]: 1.11-4.08; P

Objective This review aimed to assess the quality of available evidence on the economic evaluations of immune checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC) and provide evidence to improve the efficiency of healthcare resources. Materials and Methods Literature search was performed using some electronic databases (PubMed, Embase and Cochrane Central Register of Controlled Trials). Final search was performed in December 2019. Study characteristics and results were recorded and compared. The quality of the studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklists. We did not elaborate the restrictions on the target population. We included patients with squamous or non-squamous NSCLC and metastatic or advanced cancer. Results Of 98 papers considered, 21 were chosen for this review. Most of them are cost-effectiveness analysis. Comparative regimens consisted of either immune checkpoint inhibitor monotherapy, immune checkpoint inhibitor plus chemotherapy, or chemotherapy alone. Fourteen, four, and three studies were about pembrolizumab, nivolumab, and atezolizumab, respectively. The methods mostly used in these studies were modeling and sensitivity analysis. All studies used quality-adjusted life year (QALY) and life years (LY) as outcomes. Most studies were conducted in high-income countries. Based on the willingness to pay threshold, atezolizumab, and pembrolizumab were found to be cost-effective in one and 10 studies, respectively. None of the studies concluded that nivolumab was cost-effective. For quality assessment, all studies fulfilled more than 50% of the CHEERS checklist. Conclusion The included studies indicated that pembrolizumab regimens are cost-effective as first-line treatment for patients with NSCLC in developed countries. Nivolumab and atezolizumab are likely to be cost-effective as second-line treatment but not as first-line treatment.

Background: This study evaluated the cost-effectiveness of nivolumab plus chemotherapy (NC) or ipilimumab versus chemotherapy as a first-line treatment for advanced esophageal squamous cell carcinoma (ESCC) in the United States and China. Methods: A partitioned survival model was constructed from the perspective of the US third-party payers and Chinese healthcare system. Health states and transition probabilities were modeled based on the survival data from the CheckMate-648 clinical trial (NCT03143153). The time horizon for the model was 10 years. Only direct medical costs were considered. One-way and probabilistic sensitivity analyses were conducted to assess the robustness of the results. Results: In the United States, nivolumab plus ipilimumab (NI) led to an incremental cost-effectiveness ratio (ICER) of $155,159.82/quality-adjusted life year (QALY) and $104,297.07/QALY gained in the overall population and in patients with tumor cell programmed death-ligand 1 (PD-L1) expression of ⩾1% (subgroup), respectively. The ICER for the subgroup was between the willingness-to-pay (WTP) threshold values of $100,000/QALY and $150,000/QALY, and the other case was higher than $150,000/QALY. NC led to an ICER of $518,062.85/QALY and $193,169.49/QALY gained in the overall population and the subgroup, respectively. Both ICERs were significantly higher than the WTP threshold of $150,000/QALY. In China, the ICERs for patients treated with the addition of nivolumab were >$90,000/QALY in all cases, significantly exceeding the WTP threshold of $37,654/QALY. Conclusions: NI is more cost-effective than NC or chemotherapy alone for treating advanced ESCC with PD-L1 expression ⩾1% in the United States. Chemotherapy alone is the only cost-effective option in China.

Summary Background The incidence of Clostridium difficile-associated diarrhoea (CDAD) in hospitalized children and adolescents has been increasing year-on-year. Paediatric CDAD places a significant economic burden on healthcare systems. Probiotics are live organisms thought to improve the microbial balance of the host, counteract disturbances in intestinal flora, and reduce the risk of colonization by pathogenic bacteria. Aim A cost-effectiveness analysis was conducted to assess the economy of probiotics for the prevention of CDAD in children and adolescents receiving antibiotics. Methods A decision tree model combining clinical effectiveness, utility and cost data was used. Sensitivity analyses were conducted to determine the robustness of the model outcomes. Finding The ‘oral probiotics’ strategy and ‘no probiotics’ strategy offered patients 0.05876 and 0.056 quality-adjusted life years (QALYs) at a cost of $16,668.70 and $20,355.28, respectively. The oral probiotics strategy exhibited higher QALY and lower cost, and represents the cost-saving strategy. The results were robust for sensitivity analyses. Conclusion From the perspective of the medical system, oral probiotics as a preventive strategy for CDAD in hospitalized children and adolescents receiving a therapeutic course of antibiotics reduced the risk of CDAD and represents a cost-saving strategy.

Maobai Liu,1,* Longfeng Zhang,2,* Qishu Huang,3 Na Li,1 Bin Zheng,1 Hongfu Cai1 1Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3College of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongfu CaiDepartment of Pharmacy, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou 350001, Fujian Province, People’s Republic of ChinaEmail caihongfu31@126.comBackground: This study aimed to analyze the cost-effectiveness of crizotinib versus ceritinib or alectinib as first-line-targeted drug therapy for anaplastic lymphoma kinase-positive advanced non-small cell lung cancer in China.Methods: The Markov model was used to simulate the medical cost and quality-adjusted life years (QALYs) of patients using crizotinib, ceritinib, or alectinib over a 10-year period by establishing three health states: progression-free, post-progression, and death. Randomized controlled clinical data were collected from the open-label, randomized phase 3 trials ALEX and ASCEND-4. Cost and utility values were derived from local charges and literature. Sensitivity analyses included one-way and probabilistic sensitivity analyses.Results: Compared with patients who used crizotinib as first-line treatment, patients in the ceritinib and alectinib groups yielded an additional 1.32 and 3.30 QALYs with an incremental cost of $84,728.20 and $339,114.36, respectively. Thus, the incremental cost-effectiveness ratio (ICER) was $64,398.83 and $102,675.74 per QALY in the ceritinib and alectinib groups, respectively. Alectinib was estimated to be more effective (4.68 QALY) and more costly ($432,063.06) with an ICER of $128,019.42 per QALY compared with ceritinib (2.69 QALY and $177,676.90). Results were robust to deterministic and probabilistic sensitivity analyses.Conclusion: As a first-line treatment regimen, ceritinib and alectinib can extend the survival time of patients compared with crizotinib, but the medical cost also increases accordingly. According to the World Health Organization’s three-percent GDP measurement, first-line treatment with Crizotinib is the most cost-effective.Keywords: crizotinib, ceritinib, alectinib, NSCLC, cost-effectiveness

This study analyzed the cost utility on the use of ixazomib/lenalidomide/dexamethasone (IRD), lenalidomide/dexamethasone (RD), bortezomib/thalidomide/dexamethasone (VTD), or bortezomib/dexamethasone (VD) for patients with refractory or relapsed multiple myeloma (rrMM). Patients' lifelong direct medical costs and quality-adjusted life years (QALYs) are simulated by using the Markov model on the basis of the China's healthcare system. VTD, RD, and IRD are 0.12, 0.32, and 0.42 QALYs higher than VD, and $9401, $16,868, and $39,671 higher than those of VD in terms of lifelong cost. The incremental cost-effectiveness ratios are 78,342, 52,713, and 94,455, respectively. IRD can extend the life years of patients with rrMM, improve the quality of life, and increase the cost of medical treatment. The use of VD has a comparative advantage of cost utility. For patients who cannot tolerate bortezomib or were drug-fast with first-line bortezomib, RD plan is another economical and effective strategy.

Osteoporosis has become an important public health problem in China, especially among elderly postmenopausal women. Massive amounts of medical and health resources have been devoted to patients with osteoporosis and osteoporosis-related fractures. This study estimated the cost-effectiveness of alendronate, zoledronate, raloxifene, teriparatide, and calcium/vitamin D as treatments for osteoporosis in elderly postmenopausal women in China from the medical system perspective.A Markov model was constructed by using TreeAge Pro 2015 software. This model simulated the disease process over 40 years in response to the five investigated therapeutic strategies. Each cycle lasted for 1 year. The model parameters included Chinese epidemiological data, clinical effectiveness, cost, and utility. Total treatment costs and quality-adjusted life-years (QALYs) were estimated, and incremental cost-effectiveness analysis was performed. Univariate and probabilistic sensitivity analyses were conducted to verify the model.The calcium/vitamin D strategy, zoledronate, alendronate, teriparatide, and raloxifene offered patients 10.24, 10.83, 10.70, 10.88, and 10.54 QALYs at the cost of $3,799.72, $8,425.61, $9,849.89, $34,843.72, and $13,353.33 for over 40 years, respectively. The alendronate and raloxifene strategies were eliminated because they were less effective and more expensive than the other strategies. The base-case analysis revealed that the incremental cost-effectiveness ratios (ICERs) of the zoledronate strategy relative to those of the calcium/vitamin D strategy were $7,864.59/QALY. This result indicated that the zoledronate strategy was more cost-effective than other strategies and was within the willingness-to-pay threshold of China ($28,624/QALY). The ICERs of the teriparatide versus zoledronate strategies were $4,70,797.08/QALY, which exceeded the threshold.From the perspective of the Chinese medical system, zoledronate is more cost-effective than the calcium/vitamin D strategy, alendronate, raloxifene, and teriparatide for the treatment of osteoporosis in elderly postmenopausal women. Not factoring the parameters of adherence and persistence in, and consequent variability in treatment effectiveness relative risks, seems like a major limitation, but it can be speculated that it would not change the conclusion that zoledronate is the most economical strategy.

• To test the feasibility/effects of an online anticoagulation clinic for patients in rural areas

BACKGROUND The incidence and degree of cancer pain often progresses in discharged patients because of discontinued standard treatments and reductions in medication compliance. Motivated by the need for better pain management in discharged patients, our research team developed a mobile phone application (Pain Guard) for providing continuous treatment for discharged patients suffering from pain. OBJECTIVE We aimed to design, construct, and test the Pain Guard in patients managing cancer pain, and evaluate the total remission rate of pain and improvement in quality of life (QoL), in order to realize convergence management of patients within and outside the hospital. The system’s usability, feasibility, compliance, and satisfaction were also assessed. METHODS This randomized controlled double-arm study involved 58 patients with cancer pain symptoms. Participants were randomly assigned into the group receiving care through the Pain Guard and the control group receiving only traditional pharmaceutical care. In a pretest, participants were rated using a baseline cancer pain assessment and QoL evaluation. During treatment, the consumption levels of analgesic drugs were recorded every week. After a 4-week study period, another round of cancer pain assessment and QoL evaluation was conducted. Our primary outcome was remission rate of pain, and secondary outcomes were compliance with medication, improvements in QoL, frequency of breakthrough cancer pain (BTcP), incidence of adverse reactions, and satisfaction of patients. RESULTS All participants (58 patients) successfully completed the study. There were no significant differences in baseline pain score or baseline QoL scores between groups (P>0.1). At the end of the study, the rate of pain remission in the trial group was significantly higher than that in the control group (P CONCLUSIONS Pain Guard can effectively resolve the management dislocation of patients with cancer pain at home, control pain steadily, reduce the incidence of adverse reactions, improve patient compliance, and significantly improve patients’ quality of life. Additionally, Pain Guard operability is good and easily accepted by patients. CLINICALTRIAL identifier: ChiCTR1800016066

BACKGROUND The incidence of cancer pain increases in discharged patients because of discontinued standard treatments and reductions in medication adherence. Motivated by the need for better pain management in discharged patients, we developed a mobile phone app (Pain Guard) to provide continuous treatment information and feedback to discharged cancer patients suffering from pain. OBJECTIVE The aim was to design, construct, and test the Pain Guard app in patients managing cancer pain, evaluate the total remission rate of pain and the improvement in quality of life (QoL) to improve pain management for cancer pain patients, and assess patient acceptance of the app. METHODS This randomized controlled double-arm study involved 58 patients with cancer pain symptoms. Participants were randomly assigned to a group receiving care through the Pain Guard app (n=31) or to a control group (n=27) who received only traditional pharmaceutical care. In a pretest, participants were rated using a baseline cancer pain assessment and QoL evaluation. During treatment, the consumption levels of analgesic drugs were recorded every week. After a 4-week study period, another round of cancer pain assessment and QoL evaluation was conducted. The system’s usability, feasibility, app compliance, and satisfaction were also assessed. Our primary outcome was remission rate of pain, and secondary outcomes were medication adherence, improvements in QoL, frequency of breakthrough cancer pain (BTcP), incidence of adverse reactions, and satisfaction of patients. RESULTS All participants (N=58) successfully completed the study. There were no significant differences in baseline pain scores or baseline QoL scores between groups. At the end of the study, the rate of pain remission in the trial group was significantly higher than that in the control group (P CONCLUSIONS Pain Guard was effective for the management of pain in discharged patients with cancer pain, and its operability was effective and easily accepted by patients. CLINICALTRIAL Chinese Clinical Trials Registry ChiCTR1800016066; http://www.chictr.org.cn/showproj.aspx?proj=27153

Background This study aims to establish a new indicator based on the anatomical therapeutic chemical/defined daily dose (ATC/DDD) system. Methods Utilization data of antibiotics of inpatients in a university hospital were used to calculate the indicators of use rate (UR), use density (UD), and ratio of use density to use rate (UD/UR). According to the professional characteristics, the recommended values of UD/UR in different departments were established respectively. Crosswise comparison and appropriateness evaluation between different treatment groups with the same profession were performed. For individual inpatients with abnormally increased drug utilization index (DUI) and ratios of antimicrobial course to length of stay (C/S), detailed analysis was performed to examine whether any irrational drug utilization occurred. Results The indicator UD/UR combines both dose and duration of treatment, which were the two main factors affecting the appropriateness of clinical application of antibiotics. Thus, it can more sensitively reveal the drug utilization of inpatients receiving antibiotics. UD/UR is also more suitable for evaluating the clinical appropriateness of antibiotic application than the macroscopic indicator, total UD, and could be applied at the macroscopic and microscopic levels. Conclusions The ratio UD/UR has great practical value and can serve as a reference for evaluating the appropriateness of clinical application of antibiotics.

Tyrosine kinase inhibitors (TKIs) have obvious effects on chronic myeloid leukemia (CML), but they are expensive in China. Moreover, the overall cost of treatment of CML is high and the medical economic burden of patients with CML on the government is heavy. This study tested the cost effectiveness of imatinib, nilotinib, and dasatinib as first-line treatment in Chinese patients who were first diagnosed with chronic myeloid leukemia in the chronic phase (CML-CP). A state-transition Markov model combining clinical effectiveness, utility, and cost data was used. Sensitivity analyses were conducted to determine the robustness of the model outcomes. The imatinib-first, dasatinib-first, and nilotinib-first strategy offered patients 9.76, 9.87, and 9.72 quality-adjusted life years (QALYs) at a cost of US$303,502.42, US$381,681.03, and US$305,509.92 over 20 years, respectively. The nilotinib-first strategy exhibited the lowest utility and highest price and was thus eliminated. An incremental cost-effectiveness analysis of the imatinib-first strategy and the dasatinib-first strategy showed that the dasatinib-first strategy yielded an incremental cost–utility ratio (ICER) of 710,714.64 $/QALY compared with the imatinib-first strategy, which exceeded the threshold; hence, the dasatinib-first strategy was not cost effective and was eliminated. The results were robust for multiple sensitivity analyses. From the perspective of the Chinese medical system, imatinib is likely to be more cost effective than dasatinib and nilotinib for patients who were first diagnosed with CML-CP.

Aim: Doxorubicin (DOX) is an effective chemotherapeutic drug. However, its clinical application may be hampered by dose-dependent cardiotoxicity. Alcohol metabolite and doxorubicinol (DOXol) were the most prominent components in DOX-induced cardiotoxicity. It is necessary to elucidate the level of DOXol in heart in vivo and whether DOXol could cause toxicity at such a concentration. Methods: The pharmacokinetics and heart distribution of DOX and its second metabolite DOXol were determined in rats. Based on this concentration level in vivo, H9C2 cell was used to examine the cardiotoxicity of DOX and DOXol. Real-time cell viability was determined using the xCelligence system and the membrane-permeable of DOX, and DOXol was also assessed by determining the intracellular and extracellular concentrations. Results: Our data showed that DOX level was higher than DOXol level in heart tissue. DOX had a high level in intracellular H9C2 cell and was the primary cytotoxic agent. DOXol had a significantly low level in heart tissue and less cytotoxicity than that of DOX in H9C2. DOXol in heart could not diffuse from plasma but only form in the heart. DOXol could not enter cell as easy as DOX. The less cardiotoxicity of DOXol might be caused by the less intracellular concentration.

BackgroundThe incidence of cancer pain increases in discharged patients because of discontinued standard treatments and reductions in medication adherence. Motivated by the need for better pain management in discharged patients, we developed a mobile phone app (Pain Guard) to provide continuous treatment information and feedback to discharged cancer patients suffering from pain. ObjectiveThe aim was to design, construct, and test the Pain Guard app in patients managing cancer pain, evaluate the total remission rate of pain and the improvement in quality of life (QoL) to improve pain management for cancer pain patients, and assess patient acceptance of the app. MethodsThis randomized controlled double-arm study involved 58 patients with cancer pain symptoms. Participants were randomly assigned to a group receiving care through the Pain Guard app (n=31) or to a control group (n=27) who received only traditional pharmaceutical care. In a pretest, participants were rated using a baseline cancer pain assessment and QoL evaluation. During treatment, the consumption levels of analgesic drugs were recorded every week. After a 4-week study period, another round of cancer pain assessment and QoL evaluation was conducted. The system’s usability, feasibility, app compliance, and satisfaction were also assessed. Our primary outcome was remission rate of pain, and secondary outcomes were medication adherence, improvements in QoL, frequency of breakthrough cancer pain (BTcP), incidence of adverse reactions, and satisfaction of patients. ResultsAll participants (N=58) successfully completed the study. There were no significant differences in baseline pain scores or baseline QoL scores between groups. At the end of the study, the rate of pain remission in the trial group was significantly higher than that in the control group (P

Clopidogrel or aspirin are indicated for patients with recent ischemic stroke (IS) or established peripheral artery disease (PAD). We compared the cost effectiveness of clopidogrel with that of aspirin in Chinese patients with recent IS or established PAD. A discrete-event simulation was developed to evaluate the economic implications of secondary prevention with clopidogrel versus aspirin. All available evidence was derived from clinical studies. Costs from a Chinese healthcare perspective in 2013 US dollars and quality-adjusted life-years (QALYs) were projected over patients’ lifetimes. Uncertainties were addressed using sensitivity analyses. Compared with aspirin, clopidogrel yielded a marginally increased life expectancy by 0.46 and 0.21 QALYs at an incremental cost-effectiveness ratio of $US5246 and $US9890 per QALY in patients with recent IS and established PAD, respectively. One-way sensitivity analyses showed that the evaluation of patients with PAD and recent IS was robust except for the parameter of patient age. Given a willingness-to-pay of $US19,877 per QALY gained, clopidogrel had a probability of 90 and 68 % of being cost effective in the recent IS or established PAD subgroups compared with aspirin, respectively. The analysis suggests that clopidogrel for secondary prevention is cost effective for patients with either PAD or recent IS in a Chinese setting in comparison with aspirin.

Background:The aim of the study was to test the cost-effectiveness of dasatinib compared to high-dose imatinib and nilotinib in Chinese patients who were diagnosed with imatinib-resistant chronic myeloid leukemia in the chronic phase (CML-CP).Methods:A Markov model combined with clinical eff

732 Background: To test the cost-effectiveness of cetuximab and bevacizumab treatment as first-line treatment for patients with left-side metastatic colorectal cancer (mCRC). Methods: A Markov model was developed to Chinese clinical practice. The model incorporated clinical and utility data from published literatures, resource utilization and unit prices based on local charge. The lifetime horizontal was used and sensitivity analyses were carried out to test the robustness of the model results. The impact of patient assistance program (PAP) was also evaluated in scenario analyses. Results: Baseline analysis showed that the addition of cetuximab gained additional 0.364 QALYs with more $39,450 relative to bevacizumab therapy, resulting in an ICER of $108,287 /QALY. When PAP was available, the incremental cost decreased to $2,464, which yielded an ICER of $6,764 /QALY, which indicated that the strategy might be very cost-effective at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China ($22,200/QALY). Sensitivity analyses found that the costs of cetuximab and bevacizumab were the most influential parameters. Conclusions: When PAP was available in Chinese context, cetuximab treatment is likely to be cost-effective versus bevacizumab therapy for patients with left-side mCRC.

777 Background: To test the cost-effectiveness of bevacizumab treatment compared with cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for patients with right-side metastatic colorectal cancer (mCRC). Methods: A Markov model was developed to Chinese clinical practice. The model incorporated clinical and utility data from published literatures, resource utilization and unit prices based on local charge. The lifetime horizontal was used and sensitivity analyses were carried out to test the robustness of the model results. The impact of patient assistance program (PAP) was also evaluated in scenario analyses. Results: Baseline analysis showed that the addition of cetuximab gained additional 0.232 QALYs with more $60,371 relative to bevacizumab therapy, resulting in an ICER of $259,775 /QALY. When PAP was available, the incremental cost decreased to $24,161, which yielded an ICER of $60,371 /QALY, which indicated that the strategy was not cost-effective at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China ($22,200/QALY). Sensitivity analyses found that the costs of bevacizumab was the most influential parameter. Conclusions: Bevacizumab treatment for right-side mCRC is not a cost-effective option in comparison with standard chemotherapy in Chinese context.