Economic burden associated with the management of cervical cancer,cervical dysplasia and genital warts in Belgium

Abstract

Objective: Human papillomavirus (HPV) infections can lead to cervical intraepithelial neoplasia (CIN) lesions, cervical cancer (CC) and genital warts (GWs). This study intended to assess the annual cost of CC, CIN and GW management in Belgium.

Method: A retrospective study using a Belgian Hospital Disease Database (for yearly hospital cost of CC and GW patients) and a clinical expert survey were performed to assess the medical management of CC, CIN and GW patients. Belgian official sources were used to estimate the annual costs of management of CC, CIN and GW patients both from a healthcare payer perspectives (HCPP) and a societal perspective.

Results: Based on the 667 patients diagnosed annually in Belgium with CC and an annual cost per patient of €9,716, the total annual cost of CC is €6.5 million (HCPP). The 10,495 estimated CIN 1, 2 and 3 patients led to an annual cost of €1.97 million (HCPP). The 7,989 estimated annual number of diagnosed GW patients led to an estimated annual cost of €2.53 million (HCPP).

Conclusion: HPV-related diseases represent an important burden on Belgian society, especially when considering that the estimates in this study are probably underestimations, as the management costs of other HPV-related diseases (vulvar, vaginal, penile, oropharyngeal (pre-) cancers, recurrent respiratory papillomatosis etc.) are not included in this analysis.     

Modelling the economic value of cross- and sustained-protection in vaccines against cervical cancer

Objective: Two human papillomavirus (HPV) vaccines are on the market. Based on expected differences in sustained- and cross-protection between the two vaccines, their long-term economic value is modelled and compared for France, Ireland and Italy.

Methods: A Markov cohort model reproducing the natural history of HPV infections, screening and vaccination, is adapted to country-specific data. Two hypothetical HPV vaccines (VA and VB) are compared. At baseline VA provides lifetime protection against HPV‐16 and 10-year protection against HPV‐18 before waning. VB is the same as VA with a 10-year protection against HPV‐6 and 11. Sustained- and cross-protection is varied over wide ranges in VA to define the levels that could make VA cost-effective or dominant compared with VB.

Results: Under baseline conditions VB dominates VA. VA becomes cost-effective when the difference in cross-protection alone reaches 13–15% (undiscounted), and 22–44% (discounted). A combination of sustained- and cross-protection is required for VA to dominate VB (discounted). The results are dependent upon country, the base-case value and the discount applied.

Conclusion: Realistic additional sustained- and cross-protection in one HPV vaccine may confer benefits that offset the economic value of protection against low-risk HPV in the other. The results are country specific.     

The economic advantages of response in the treatment of advanced breast cancer

Summary

The introduction of a new class of drugs, the taxoids, has dramatically improved the outlook for patients with advanced, metastatic breast cancer. Second-line monotherapy with the most effective taxoid, docetaxel, in patients with anthracycline-resistant metastatic breast cancer, shows an overall response rate up to 55% in this patient population. Increased response rate is associated with improved quality of life for these patients.

We carried out a cost analysis to determine the economic benefits of being in a response state compared with the other health states associated with advanced breast cancer: stable, progressive or terminal disease.

We found that the cost of care for responders is 40% of that for early progressive disease and just over a third of that for late progressive disease. The costs associated with stable disease are only a little less than those for progressive disease, and are more than double the costs for patients who have responded to chemotherapy. The costs during terminal disease are the highest, and are more than nine times those associated with caring for responders.

Our findings confirm other studies which demonstrate that the cost of chemotherapy can be offset against the reduction in costs incurred for patients who remain in healthier states for longer. The key parameter determining the economic efficiency of treatments for advanced breast cancer is response rate.     

Cost of adverse events during treatment with everolimus plus exemestane or single-agent chemotherapy in patients with advanced breast cancer in Western Europe

Objective:

Treatment options for recurrent or progressive hormone receptor-positive (HR+) advanced breast cancer include chemotherapy and everolimus plus exemestane (EVE?+?EXE). This study estimates the costs of managing adverse events (AEs) during EVE?+?EXE therapy and single-agent chemotherapy in Western Europe.

Methods:

An economic model was developed to estimate the per patient cost of managing grade 3/4 AEs for patients who were treated with EVE?+?EXE or chemotherapies. AE rates for patients receiving EVE?+?EXE were collected from the phase III BOLERO-2 trial. AE rates for single-agent chemotherapy, capecitabine, docetaxel, or doxorubicin were collected from published clinical trial data. AEs with at least 2% prevalence for any of the treatments were included in the model. A literature search was conducted to obtain costs of managing each AE, which were then averaged across Western European countries (when available). Per patient costs for managing AEs among patients receiving different therapies were reported in 2012 euros (€).

Results:

The EVE?+?EXE combination had the lowest average per patient cost of managing AEs (€730) compared to all chemotherapies during the first year of treatment (doxorubicin: €1230; capecitabine: €1721; docetaxel: €2390). The most costly adverse event among all patients treated with EVE?+?EXE was anemia (on average €152 per patient). The most costly adverse event among all patients treated with capecitabine, docetaxel, or doxorubicin was lymphocytopenia (€861 per patient), neutropenia (€821 per patient), and leukopenia (€382 per patient), respectively.

Conclusions:

The current model estimates that AE management during the treatment of HR+ advanced breast cancer will cost one-half to one-third less for EVE?+?EXE patients than for chemotherapy patients. The consideration of AE costs could have important implications in the context of healthcare spending for advanced breast cancer treatment.     

Cost-effectiveness analysis of neoadjuvant pertuzumab and trastuzumab therapy for locally advanced,inflammatory, or early HER2-positive breast cancer in Canada

Abstract

Objective:

The NeoSphere trial demonstrated that the addition of pertuzumab to trastuzumab and docetaxel for the neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early breast cancer (eBC) resulted in a significant improvement in pathological complete response (pCR). Furthermore, the TRYPHAENA trial supported the benefit of neoadjuvant dual anti-HER2 therapy. Survival data from these trials is not yet available; however, other studies have demonstrated a correlation between pCR and improved event-free survival (EFS) and overall survival (OS) in this patient population. This study represents the first Canadian cost-effectiveness analysis of pertuzumab in the neoadjuvant treatment of HER2-positive eBC.

Methods:

A cost-utility analysis (CUA) was conducted using a three health state Markov model (‘event-free’, ‘relapsed’, and ‘dead’). Two separate analyses were conducted; the first considering total pCR (ypT0/is ypN0) data from NeoSphere, and the second from TRYPHAENA. Published EFS and OS data partitioned for patients achieving/not achieving pCR were used in combination with the percentage achieving pCR in the pertuzumab trials to estimate survival. This CUA included published utility values and direct medical costs including drugs, treatment administration, management of adverse events, supportive care, and subsequent therapy. To address uncertainty, a probabilistic sensitivity analysis (PSA) and alternative scenarios were explored.

Results:

Both analyses suggested that the addition of pertuzumab resulted in increased life-years and quality-adjusted life-years (QALYs). The incremental cost per QALY ranged from $25,388 (CAD; NeoSphere analysis) to $46,196 (TRYPHAENA analysis). Sensitivity analyses further support the use of pertuzumab, with cost-effectiveness ratios ranging from $9230–$64,421. At a threshold of $100,000, the addition of pertuzumab was cost-effective in nearly all scenarios (93% NeoSphere; 79% TRYPHAENA).

Conclusion:

Given the improvement in clinical efficacy and a favorable cost per QALY, the addition of pertuzumab in the neoadjuvant setting represents an attractive treatment option for HER2-positive eBC patients.     

Cost-effectiveness implications of increased survival with anastrozole in the treatment of advanced breast cancer

Summary

Anastrozole (Arimidex*) has a survival benefit compared with megestrol acetate in postmenopausal women with advanced breast cancer who have failed on tamoxifen. It was felt appropriate that such a clinical finding should be subjected to economic evaluation.

A cost-effectiveness analysis was undertaken from the viewpoint of a third-party payer, of the data from a combined analysis of two clinical studies. The outcome measures were duration of drug treatment and life years gained. The incremental cost effectiveness ratio (ICER) of anastrozole was £1,608 per life year gained based on UK NHS drug prices in April 1998. Sensitivity analysis showed that the ICER could vary between £5 and £1,643, depending on relative drug costs in a number of countries, between £1,056 and £1,761, depending on the method used to calculate duration of treatment and survival, and could increase to £3,730, based on treatment provided during the extra period of survival.

Anastrozole is a highly cost-effective alternative to megestrol acetate for postmenopausal women with advanced breast cancer.     

The economic burden of end-of-life care in metastatic breast cancer

Objective: To assess end-of-life (EOL) total healthcare costs and resource utilization during the last 6 months of claims follow-up among patients with metastatic breast cancer (MBC) who received systemic anti-neoplastic therapy.

Methods: Newly diagnosed females with MBC initiating treatment January 1, 2003–June 30, 2011 were identified in a large commercial claims database. Two cohorts were defined based on a proxy measure for EOL 1 month prior to the end of last recorded follow-up within the study period: patients who were assumed dead at end of claims follow-up (EOL cohort) and patients who were alive (no-end-of-life [NEOL] cohort). Proxy measures for EOL were obtained from published literature and clinical expert opinion. Cost and resource utilization were evaluated for the 6 months prior to end of claims follow-up. Baseline variables, resource utilization, and costs were compared between cohorts with univariate statistical tests. Adjusted relative risks were calculated for resource utilization measures. A covariate-adjusted generalized linear model evaluated 6-month total healthcare costs.

Results: Of the 3,878 females included, 18.5% (n?=?718) met the criteria for EOL. Mean observational time (MBC onset to end of claims follow-up) was shorter for the EOL cohort (EOL, 32 months vs NEOL, 35 months; p?p?2 times higher in the EOL cohort (p?Conclusions: Potential EOL presented a greater economic burden in the 6 months prior to death. EOL month-to-month costs increased precipitously in the last 2 months of life and were driven by acute inpatient care.     

Cost effectiveness of a 92-gene assay for the diagnosis of metastatic cancer

Objectives:

To estimate the clinical and economic trade-offs involved in using a molecular assay (92-gene assay, CancerTYPE ID) to aid in identifying the primary site of difficult-to-diagnose metastatic cancers and to explore whether the 92-gene assay can be used to standardize the diagnostic process and costs for clinicians, patients, and payers.

Methods:

Four decision-analytic models were developed to project the lifetime clinical and economic impact of incorporating the 92-gene assay compared with standard care alone. For each model, total and incremental costs, life-years, quality-adjusted life-years (QALYs), incremental cost–effectiveness ratios (ICERs), and the proportion of patients treated correctly versus incorrectly were projected from the payer perspective. Model inputs were based on published literature, analyses of SEER (Surveillance Epidemiology and End Results) data, publicly available data, and interviews with clinical experts.

Results:

In all four models, the 92-gene assay increased the proportion of patients treated correctly, decreased the proportion of patients treated with empiric therapy, and increased quality-adjusted survival. In the primary model, the ICER was $50,273/QALY; thus, the 92-gene assay is therefore cost effective when considering a societal willingness-to-pay threshold of $100,000/QALY. These findings were robust across sensitivity analyses.

Conclusions:

Use of the 92-gene assay for diagnosing metastatic tumors of uncertain origin is associated with reduced misdiagnoses, increased survival, and improved quality of life. Incorporating the assay into current practice is a cost-effective approach to standardizing diagnostic methods while improving patient care. Limitations of this analysis are the lack of data availability and resulting modeling simplifications, although sensitivity analyses showed these to not be key drivers of results.     

Repositioning the Chinese economy on the global economic stage

A tectonic shift in the global economic prowess became obvious around the turn of the last century. Three decades of macroeconomic reforms, sustained growth and global integration have turned China into a future economic power of global magnitude, with unmatched breadth of resources and a robust manufacturing sector. Significance of the Chinese economy has radically increased and it has traversed from the periphery of the global economy to the core. For all appearances, this progress is likely to continue in the foreseeable future. China has grown to be the fourth largest economy in the world in a short time span and the third largest trader. Events like dawning of an economic superpower occur once in several generations. China is endeavoring to make a new niche for itself in the global economy as well as formulate a new role.

国际金融危机:直向性传染到交叉性传染的动态效应分析

本文用VAR系统检验金融危机的传染.通过对5国摩根史丹利MSCI指教的Granger因果关系检验和脉冲响应函数检验分析金融危机的传染效应,得出结论:金融危机前的平稳期美国与其他4国间保持单向因果关系;金融危机爆发后美国与这些国家建立双向因果关系,危机传染存在反馈机制;金融危机在国家间的交叉传染导致危机程度不断加深;脉冲响应函微检验验证了危机传染的动态效应即美国全融市场对其他国家的冲击强度加大,持续时间增加.     

Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage III or IV classical Hodgkin lymphoma

Objective: The ECHELON-1 trial demonstrated efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A?+?AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy for stage III/IV classical Hodgkin lymphoma. This analysis evaluated the cost-effectiveness of A?+?AVD from a US healthcare payer perspective.

Methods: The incremental cost-effectiveness ratio (ICER), defined as the incremental costs per quality-adjusted life year (QALY) gained, was estimated using a non-homogenous semi-Markov cohort model with health states defined on progression following frontline treatment, and for those with progression, receipt of autologous stem-cell transplant (ASCT), and progression after ASCT. Patients undergoing ASCT were classified as refractory or relapsed based on timing of progression. Probabilities of progression/death with frontline therapy were based on parametric survival distributions fit to data on modified progression-free survival (mPFS) from ECHELON-1. Duration of frontline treatment and incidence of adverse events were from ECHELON-1. Utility values for patients in the frontline mPFS state were based on EQ-5D data from ECHELON-1. Other inputs were from published sources. A lifetime time horizon was used. Costs and QALYs were discounted at 3%. Analyses were conducted alternately using data on mPFS for the overall and North American populations of ECHELON-1.

Results: The ICER for A?+?AVD vs ABVD was $172,074/QALY gained in the analysis using data on mPFS for the overall population and $69,442/QALY gained in the analysis using data on mPFS for the North American population of ECHELON-1. The ICER is sensitive to estimated costs of ASCT and frontline failure.

Conclusion: The ICER for A?+?AVD vs ABVD based on ECHELON-1 is within the range of threshold values for cost-effectiveness in the US. A?+?AVD is, therefore, likely to be a cost-effective frontline therapy for patients with stage III/IV classical Hodgkin lymphoma from a US healthcare payer perspective.

Trial registration: ClinicalTrials.gov identifier: NCT01712490.     

Cost-effectiveness analysis of utidelone plus capecitabine for metastatic breast cancer in China

Abstract

Objective: To estimate the cost-effectiveness of utidelone plus capecitabine therapy compared to capecitabine alone in patients with metastatic breast cancer (MBC) resistant to anthracyclines and taxanes treatment in the Chinese context and provide a reference for the marketing of utidelone in China.

Methods: A Markov model was developed based on the NCT02253459 clinical trial to simulate the clinical course of patients with metastatic breast cancer who had received taxanes and anthracycline therapy. The quality-adjusted life years (QALYs) and Incremental Cost Effectiveness Ratio (ICER) were then analyzed to evaluate the benefits. Two-parametric Weibull distribution was conducted to fit PFS and OS curves by using R. Sensitivity analyses were performed to evaluate the stability of the model designed.

Results: The addition of utidelone increased the cost and QALYs by $13,370.25 and 0.1961, respectively, resulting in an increased ICER of $68,180.78 per QALY. The most sensitive influential parameter on ICER was the price of utidelone. At the threshold of willingness-to-pay (WTP) of $24,380 (3 per capita GDP of China), the cost of utidelone per 30?mg of less than $18.5, $33.7, and greater than $48.8 resulted in a 100%, 50%, and 0% possibility of cost-effectiveness, respectively. The addition of utidelone was not cost-effective when it was $115.4 per 30?mg—the price of its analog paclitaxel. In consideration of varied economics levels across China, cost-effectiveness could be achieved with the price of utidelone ranging from $5.2 to $35.9.

Limitations: The survival curves extended beyond the follow-up time horizon, of which data were generated not from the real analyses but from our established two-parameter Weibull survival model.

Conclusion: It is recommended that the price of utidelone would be less than $18.5 per 30?mg in order to obtain cost-effectiveness for metastatic breast cancer patients resistant to anthracyclines and taxanes treatment in China.     

论科学问题的意义标准

哲学家和科学家都将“科学问题”视为科学理论发展的源泉和动力,然而科学问题作为科学哲学一个重要研究领域的氛围却远未形成。从科学哲学的层面,对科学问题作了一些尝试性探索并提出了一些新的见解：①科学问题存在于特殊定义下的世界3中,从而厘清了针对不同问题的划界问题;②通过命题的预设概念定义科学问题的预设,得出科学问题是遵循三值逻辑的;③通过定义科学问题信息域两个维度的概念——秩和矩,从而解决了不同但又相关的科学问题之间的难度比较问题,进而为科学问题逻辑系统的建构提供了方法上的可行性。     

Evaluation of the costs and resource use associated with adjuvant chemotherapy for breast cancer in France

Abstract

Objectives:

There is a paucity of recent data on breast cancer costs, particularly on the burden of chemotherapy. The present study was designed to estimate resource use and costs associated with the current standard of care for adjuvant chemotherapy for breast cancer.

Methods:

Costs and resource use were assessed by retrospective analysis of medical records at a single comprehensive cancer care center, Hôpital Tenon, Paris, France. Data were extracted from files of female patients having undergone surgical resection of breast cancer between January–July 2010. Patients were included if they received chemotherapy at the hospital and had medical records available. Patients were followed from the start of adjuvant chemotherapy (including pre-chemotherapy) to the end of treatment. Costs were collected for each resource use item from a societal perspective using standard, published sources and expressed in 2011 Euros (€). Limitations of the analysis included the single-center study design and the use of pre-defined questionnaires on resource use (which may conservatively estimate costs).

Results:

A total of 62 patients were included in the study with a mean age of ～54 years. Most patients had stage II (50.8%) or stage III (40.7%) disease. Anthracycline plus taxane-based chemotherapy regimens were most commonly prescribed (77% of patients). Mean cost of adjuvant chemotherapy was estimated to be ～€15,740 per patient from a societal perspective. The acquisition costs of chemotherapy agents were responsible for 26% of the total, with lost productivity (27%), chemotherapy administration (19%), and adverse events (16%) also contributing substantially.

Conclusions:

Evaluation of costs in patients with non-metastatic breast cancer in France has shown that the costs of adjuvant chemotherapy are substantial. The main components of total cost were the cost of chemotherapy agents, lost productivity, chemotherapy administration, and management and prevention of adverse events.