Cost-effectiveness analysis of different rescue therapies in patients with lamivudine-resistant chronic hepatitis B in China.

BACKGROUND: Several rescue therapies have been used in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB); however, the economic outcome of these therapies is unclear. The object of the current analysis was to evaluate the lifetime cost-effectiveness of rescue therapies among patients with LAM-resistant CHB. METHODS: A Markov model was developed to simulate the clinical course of patients with LAM-resistant CHB. From the perspective of Chinese health care, a lifetime cost-utility analysis was performedfor 4 rescue strategies: adefovir (ADV), entecavir (ETV) or tenofovir (TDF) monotherapy and combination therapy using LAM and ADV. A hypothetical cohort of 45-year-old patients with genotypic or clinical LAM-resistant CHB entered the model, and the beginning health state was LAM-resistant CHB without other complications. The transition probabilities, efficacy and resistance data for each rescue therapy as well as the costs and utility data were estimated from the literature. The discount rate (3%) utilized for costs and benefits. Sensitivity analyses were used to explore the impact of uncertainty on the results. RESULTS: In LAM-resistant HBeAg-positive and HBeAg-negative CHB cohorts, TDF monotherapy and combination therapy were on the efficiency frontier for both positive and negative populations. Compared with no treatment, the use of combination therapy cost an additional $6,531.7 to gain 1 additional quality-adjusted life year (QALY) for HBeAg-positive patients and $4,571.7 to gain 1 additional QALY for HBeAg-negative patients. TDF monotherapy for HBeAg-positive patients, shows greater increase in QALYs but higher incremental cost-effectiveness ratio (ICER) in comparison with combination therapy. In probabilistic sensitivity analyses, combination therapy was the preferred option for health care systems with limited health resources, such as Chinese health care system. CONCLUSION: In Chinese patients with LAM-resistant CHB, combination therapy is a more cost-effective option than the competing rescue therapies.

Subgroup economic analysis for glioblastoma in a health resource-limited setting.

BACKGROUND: The aim of this research was to evaluate the economic outcomes of radiotherapy (RT), temozolomide (TMZ) and nitrosourea (NT) strategies for glioblastoma patients with different prognostic factors. METHODOLOGY/PRINCIPAL FINDINGS: A Markov model was developed to track monthly patient transitions. Transition probabilities and utilities were derived primarily from published reports. Costs were estimated from the perspective of the Chinese healthcare system. The survival data with different prognostic factors were simulated using Weibull survival models. Costs over a 5-year period and quality-adjusted life years (QALYs) were estimated. Probabilistic sensitivity and one-way analyses were performed. The baseline analysis in the overall cohort showed that the TMZ strategy increased the cost and QALY relative to the RT strategy by $25,328.4 and 0.29, respectively; and the TMZ strategy increased the cost and QALY relative to the NT strategy by $23,906.5 and 0.25, respectively. Therefore, the incremental cost effectiveness ratio (ICER) per additional QALY of the TMZ strategy, relative to the RT strategy and the NT strategy, amounts to $87,940.6 and $94,968.3, respectively. Subgroups with more favorable prognostic factors achieved more health benefits with improved ICERs. Probabilistic sensitivity analyses confirmed that the TMZ strategy was not cost-effective. In general, the results were most sensitive to the cost of TMZ, which indicates that better outcomes could be achieved by decreasing the cost of TMZ. CONCLUSIONS/SIGNIFICANCE: In health resource-limited settings, TMZ is not a cost-effective option for glioblastoma patients. Selecting patients with more favorable prognostic factors increases the likelihood of cost-effectiveness.

Economic evaluation of first-line treatments for metastatic renal cell carcinoma: a cost-effectiveness analysis in a health resource-limited setting.

BACKGROUND: To estimate, from the perspective of the Chinese healthcare system, the economic outcomes of five different first-line strategies among patients with metastatic renal cell carcinoma (mRCC). METHODS AND FINDINGS: A decision-analytic model was developed to simulate the lifetime disease course associated with renal cell carcinoma. The health and economic outcomes of five first-line strategies (interferon-alfa, interleukin-2, interleukin-2 plus interferon-alfa, sunitinib and bevacizumab plus interferon-alfa) were estimated and assessed by indirect comparison. The clinical and utility data were taken from published studies. The cost data were estimated from local charge data and current Chinese practices. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the sunitinib patient assistant program (SPAP) was evaluated via scenario analysis. The base-case analysis showed that the sunitinib strategy yielded the maximum health benefits: 2.71 life years and 1.40 quality-adjusted life-years (QALY). The marginal cost-effectiveness (cost per additional QALY) gained via the sunitinib strategy compared with the conventional strategy was $220,384 (without SPAP, interleukin-2 plus interferon-alfa and bevacizumab plus interferon-alfa were dominated) and $16,993 (with SPAP, interferon-alfa, interleukin-2 plus interferon-alfa and bevacizumab plus interferon-alfa were dominated). In general, the results were sensitive to the hazard ratio of progression-free survival. The probabilistic sensitivity analysis demonstrated that the sunitinib strategy with SPAP was the most cost-effective approach when the willingness-to-pay threshold was over $16,000. CONCLUSIONS: Our analysis suggests that traditional cytokine therapy is the cost-effective option in the Chinese healthcare setting. In some relatively developed regions, sunitinib with SPAP may be a favorable cost-effective alternative for mRCC.

Costs of trastuzumab in combination with chemotherapy for HER2-positive advanced gastric or gastroesophageal junction cancer: an economic evaluation in the Chinese context.

BACKGROUND: Adding trastuzumab to a conventional regimen of chemotherapy can improve survival in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (GEJ) cancer, but the economic impact of this practice is unknown. OBJECTIVE: The purpose of this cost-effectiveness analysis was to estimate the effects of adding trastuzumab to standard chemotherapy in patients with HER2-positive advanced gastric or GEJ cancer on health and economic outcomes in China. METHODS: A Markov model was developed to simulate the clinical course of typical patients with HER2-positive advanced gastric or GEJ cancer. Five-year quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were estimated. Model inputs were derived from the published literature and government sources. Direct costs were estimated from the perspective of Chinese society. One-way and probabilistic sensitivity analyses were conducted. RESULTS: On baseline analysis, the addition of trastuzumab increased cost and QALY by $56,004.30 (year-2010 US $) and 0.18, respectively, relative to conventional chemotherapy, resulting in an ICER of $251,667.10/QALY gained. Probabilistic sensitivity analyses supported that the addition of trastuzumab was not cost-effective. Budgetary impact analysis estimated that the annual increase in fiscal expenditures would be ~$1 billion. On univariate sensitivity analysis, the median overall survival time for conventional chemotherapy was the most influential factor with respect to the robustness of the model. CONCLUSIONS: The findings from the present analysis suggest that the addition of trastuzumab to conventional chemotherapy might not be cost-effective in patients with HER2-positive advanced gastric or GEJ cancer.

Cost-effectiveness of adding rh-endostatin to first-line chemotherapy in patients with advanced non-small-cell lung cancer in China.

BACKGROUND: Adding rh-endostatin to standard platinum-based chemotherapy may significantly improve progression-free and overall survival in patients with advanced non-small cell lung cancer (NSCLC), but the cost-effectiveness of this practice is unclear. OBJECTIVE: The purpose of this cost-effectiveness analysis was to estimate the effects of adding rh-endostatin to standard chemotherapy in patients with advanced NSCLC on health and economic outcomes in China. METHODS: A semi-Markov model was constructed to track 3-week patient transitions between 3 health states: progression-free survival, progressed survival, and death. Probabilities were derived mainly from the results of a pivotal Phase III trial assessing the addition of rh-endostatin to standard first-line chemotherapy with vinorelbine-cisplatin in patients with advanced NSCLC. Costs were estimated from the perspective of the Chinese health care system, and the analysis was run over a 10-year time horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER) of adding rh-endostatin at a willingness-to-pay (WTP) threshold of 3 × the per-capita gross domestic product (GDP) per quality-adjusted life-year (QALY) gained. One-way and probabilistic sensitivity analyses were performed. RESULTS: According to the model, treatment with rh-endostatin plus standard chemotherapy would increase overall survival by 0.63 years and 0.35 QALYs per patient compared with standard chemotherapy, at an additional cost of $8402.60. The ICER for adding rh-endostatin to chemotherapy was $24,454.25/QALY gained (at a 3% discounted rate). On 1-way sensitivity analysis, the utility value of progression-free survival was the most influential factor on the results, followed by the cost of rh-endostatin. On probabilistic sensitivity analysis, the probabilities of cost-effectiveness varied by region due to discrepant per-capita GDPs in China. Modeling to extrapolate clinical survival beyond trial completion was the main limitation. CONCLUSION: The findings from the present analysis suggest that the addition of rh-endostatin to standard first-line chemotherapy is unlikely to be cost-effective. However, at a high WTP, rh-endostatin might be a cost-effective treatment option.

Silencing CX3CR1 production modulates the interaction between dendritic and endothelial cells.

CX3CR1, an important chemokine receptor in dendritic cells (DCs), is linked to the progression of atherosclerotic plaques. However, the mechanism(s) determining the role of CX3CR1 in atherosclerosis have not been clearly elucidated. In this study, we developed DCs from monocytes of Sprague-Dawley (SD) rats in the presence of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant human interleukin-4 (IL-4). The presence of recombinant human TNF-α and LPS forced the cells to mature. When compared to immature DCs, flow cytometry (FACS) analysis revealed that mature DCs display a sustained increase in the levels of CD11c, CD86, and CD80 expression. The expression of Fractalkine (FKN) in endothelial cells (ECs) contributes to the maturation of DCs and expression of CX3CR1. We revealed that mRNA expression levels of CX3CR1 in mature DCs are significantly higher than those of immature DCs (P<0.001). Transfection of DCs with siRNA specific for the CX3CR1 gene resulted in potent suppression of gene expression and inhibition of interactions between DCs and ECs. Based on these data, we hypothesized that CX3CR1 contributes to the DC-EC interaction. CX3CR1 may serve as a new target molecule for increasing therapeutic interactions in atherosclerosis.

Cost-effectiveness of nucleoside analog therapy for hepatitis B in China: a Markov analysis.

OBJECTIVES: The aim of this study was to investigate the economic consequences of nucleoside analog therapy for hepatitis B treatment in China. METHODS: A cost-utility analysis of treatments for HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) was conducted using a Markov model, in which patients' yearly transitions between different health states were tracked. Patients were tracked as they moved between the following health states: CHB, HBeAg seroconversion (HBeAg-positive CHB patients can have this special health state), virologic resistance, virologic response, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and death. The transition parameters were derived either from systematic reviews of the literature or from previous economic studies. Cost and utility data came from studies based on a Chinese CHB cohort. One-way sensitivity analyses as well as second-order Monte Carlo and probabilistic sensitivity analyses were performed. RESULTS: The entecavir strategy yielded the most quality-adjusted life years (QALYs) for both HBeAg-positive and HBeAg-negative patients when compared with the "no treatment," the lamivudine, the adefovir, and the telbivudine strategies. The risks of complications and mortality also decreased. In the economic analysis, the "no treatment" strategy was the least effective, whereas the entecavir strategy was both the least expensive and the most cost-effective option, followed by telbivudine and lamivudine. The probabilistic sensitivity analysis showed that the entecavir strategy would result in improved cost-effectiveness in >90% of cases at a threshold of $20,000 per QALY. In a one-way sensitivity analysis, the most influential parameters impacting the model's robustness were the utilities of the CHB and virologic response health states. CONCLUSIONS: In China, when treating both HBeAg-positive and HBeAg-negative CHB populations, entecavir is the most cost-effective option when compared with lamivudine, adefovir, and telbivudine.

Old biliverdin reductase: links to insulin resistance and may be a novel therapeutic target.

Insulin resistance has been assigned a pivotal role in the pathological progression associated with type 2 diabetes and other chronic metabolic diseases. However, the molecular mechanism involved in this progression is still incompletely understood, and there are still no effective approaches to scavenge it. Many biological molecules, such as ROS, IRS-1, PI3K, have been identified involving in the causes of insulin resistance. Restoring these molecules could ameliorate the phenomenon of insulin resistance. BVR was known for a long time solely as an enzyme reducing biliverdin to bilirubin in the heme metabolic pathway. Presently, accumulative research data showed that BVR was a strong antioxidant enzyme, which could scavenge the excess ROS, and the characteristics of kinase activity and binding with p85 could modulate the biological function of IRS-1 and PI3K. We hypothesize that BVR has a significant role in the progression of insulin resistance, and it will be a promising therapeutic target for treating insulin resistance.

Phase I safety and pharmacokinetic study of magnesium isoglycyrrhizinate after single and multiple intravenous doses in chinese healthy volunteers.

The safety and pharmacokinetics of magnesium isoglycyrrhizinate were assessed in healthy Chinese volunteers. In the single-dose format of this pharmacokinetic study, 100-, 200-, and 300-mg doses of magnesium isoglycyrrhizinate were given by intravenous infusion. The results indicated that the plasma levels were directly proportional to the administered dose, with the mean C(max) and AUC(0-72) ranging from approximately 28.79 to 99.28 mg x L(-1) and 448.68 to 1688.42 mg x h x L(-1) over the dose range. In the multiple-dose format of this pharmacokinetic study, 100 mg magnesium isoglycyrrhizinate was administrated once daily for 9 days. Moderate drug accumulation was noted, which was attributable to the drug's long terminal half-life of 19 to 31 hours. The distribution and elimination rate of magnesium isoglycyrrhizinate had no changes. It had a favorable pharmacokinetics and safety profile that enables the drug to be explored in future clinical studies that target patients with hepatic impairment.