A comparison of the estimated costs of erlotinib,docetaxel and pemetrexed for the second-line treatment of non-small cell lung cancer from the German healthcare perspective

Summary

The estimated costs of second-line therapy with erlotinib versus docetaxel or pemetrexed were analysed in patients with advanced non-small cell lung cancer (NSCLC) assuming the survival benefits delivered by these three drugs are comparable. Direct total costs to the German statutory health insurance system per patient per quarter were compared, including the impact of grade 3/4 side effects. Resource utilisation data came from clinical studies and/or were supplemented on the basis of guidelines/prescribing information. Basic costs per patient per quarter were: erlotinib €8,172; docetaxel €8,055; and pemetrexed €15,870. Including the cost of managing side effects, the total cost per patient per quarter with erlotinib was €8,376 compared with €9,976 for docetaxel and €16,596 for pemetrexed. The main influence on the cost analysis was the management of haematological side effects associated with docetaxel and to a lesser extent pemetrexed. Sensitivity analyses confirmed the robustness of the results. Based on its favourable side-effect profile, erlotinib offers health economic advantages over docetaxel and pemetrexed in relapsed advanced NSCLC in Germany.     

Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis

Objectives:

A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan.

Methods:

The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty.

Results:

In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses.

Conclusions:

Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients’ quality-of-life were included.     

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.     

Financial consequences of a payment-by-results scheme in Catalonia: gefitinib in advanced EGFR-mutation positive non-small-cell lung cancer

Background: In 2011 the first payment-by-results (PbR) scheme in Catalonia was signed between the Catalan Institute of Oncology (ICO), the Catalan Health Service, and AstraZeneca (AZ) for the introduction of gefitinib in the treatment of advanced EGFR-mutation positive non-small-cell lung cancer. The PbR scheme includes two evaluation points: at week 8, responses, stabilization and progression were evaluated, and at week 16 stabilization was confirmed. AZ was to reimburse the total treatment cost of patients that failed treatment, defined as progression at weeks 8 or 16.

Objective: To estimate the financial consequences of this PbR reimbursement model and determine the perception of the stakeholders involved in the agreement.

Methods: Differential drug costs between two scenarios, with and without the PbR, were calculated. A qualitative investigation of the organizational elements was performed by interviewing the parties involved in the agreement.

Results: Forty-one patients were included from June 2011 to October 2013 and assessed at two evaluation points. Clinical results were comparable to those observed in the pivotal studies of gefitinib. The difference in the cost of gefitinib using the PbR compared to the traditional purchasing scenario was 6.17% less at 8 weeks, 11.18% at 16 weeks and 4.15% less for the overall treatment. The PbR resulted in total savings of around €36,000 (€880 per patient). From an operational and organizational perspective, the availability of adequate data systems to measure outcomes and monitor accountability and the involvement of healthcare professionals were acknowledged as crucial.

Conclusions: Tangible and intangible benefits were identified with respect to the interests of the parties involved. This has led to the incorporation of innovation for patients under acceptable conditions.     

Budget impact of erlotinib for maintenance therapy in advanced non-small cell lung cancer

Abstract

Objective:

Assess the budgetary impact of adding erlotinib for maintenance therapy (MTx) in advanced non-small cell lung cancer (NSCLC) from a US health plan perspective.

Methods:

A budget impact model was developed to analyze the costs (drug, administration, adverse events) associated with adding erlotinib MTx to a hypothetical 500,000 member US health plan. Treatment durations and dosing were derived from randomized controlled trials, FDA labeling, and National Comprehensive Cancer Network guidelines. Treatment patterns and assumptions were based on market research data, the SEER registry, and published literature. Cost data were obtained from Centers for Medicare and Medicaid Services payment rates and a drug pricing database. Sensitivity analyses were conducted to assess uncertainty.

Results:

Overall health plan expenditures increased by $0.010 per member per month (PMPM). The main driver of additional cost was the erlotinib drug cost (～$66,000) with the administration ($464) and side-effect ($47) costs being relatively modest. One-way sensitivity analyses showed that the results were most sensitive to the proportion of members receiving MTx; however, the PMPM did not exceed $0.013.

Conclusions:

The overall budget impact to a health plan of expanding the use of erlotinib from the 2nd/3rd-line advanced NSCLC setting to include the maintenance setting was relatively small. This was primarily due to the proportion of patients who would receive erlotinib MTx, the low cost of side-effects and minimal cost of drug administration. Additional research may be warranted to estimate the relative clinical and economic impacts of erlotinib MTx versus alternative MTx treatments.     

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.     

Treatment cost of non-small cell lung cancer in three European countries: comparisons across France,Germany, and England using administrative databases

Abstract

Introduction:

Lung cancer is a highly prevalent condition with non-small cell lung cancer (NSCLC), representing ～ 80%. Given its high prevalence and poor survival rates, it is important to understand costs associated with NSCLC treatment.     

Cost-effectiveness of osimertinib in the UK for advanced EGFR-T790M non-small cell lung cancer

Aim: This study presents the cost-utility analysis that was developed to inform the NICE health technology assessment of osimertinib vs platinum-based doublet chemotherapy (PDC) in patients with EGFR-T790M mutation-positive non-small cell lung cancer (NSCLC) who have progressed on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy.

Methods and materials: A partitioned survival model with three health states (progression-free, progressed disease, and death) from a UK payer perspective and over lifetime (15 years) was developed. Direct costs included disease management, treatment-related (acquisition, administration, monitoring, adverse events), and T790M testing costs. Efficacy and safety data were taken from clinical trials AURA extension and AURA2 for osimertinib and IMPRESS for PDC. An adjusted indirect treatment comparison was applied to reduce the potential bias in the non-randomized comparison. Parametric functions were utilized to extrapolate survival beyond the observed period. Health state utility values were calculated from EQ-5D data collected in the trials and valued using UK tariffs. Resource use and costs were based on published sources.

Results: Osimertinib was associated with a gain of 1.541 quality-adjusted life-years (QALYs) at an incremental cost of £64,283 vs PDC (incremental cost-effectiveness ratio [ICER]: £41,705/QALY gained). Scenario analyses showed that none of the plausible scenarios produced an ICER above £44,000 per QALY gained, and probabilistic sensitivity analyses demonstrated a 63.4% probability that osimertinib will be cost-effective at a willingness-to-pay threshold of £50,000.

Limitations: The analysis is subject to some level of uncertainty inherent to phase 2 single-arm data and the immaturity of the currently available survival data for osimertinib.

Conclusions: Osimertinib may be considered a cost-effective treatment option compared with PDC in the second-line setting in patients with EGFR-T790M mutation-positive NSCLC from a UK payer perspective. Further data from the ongoing AURA clinical trial program will reduce the inherent uncertainty in the analysis.     

Healthcare costs associated with bevacizumab and cetuximab in second-line treatment of metastatic colorectal cancer

Abstract

Objective:

To compare the health care costs of patients with metastatic colorectal cancer (mCRC) who received second-line treatment with Avastin (bevacizumab) versus Erbitux (cetuximab), from the third-party payer’s perspective.

Methods:

Patients with mCRC were selected from the PharMetrics claims database if they received second-line therapy containing either bevacizumab (second-line bevacizumab cohort) or cetuximab (second-line cetuximab cohort). Six-month costs following second-line therapy start date and average monthly healthcare costs while on second-line therapy (in 2009 US$) were calculated and compared between the two groups.

Results:

A total of 2188 patients with mCRC who met the eligibility criteria were included in the analysis, including 1808 patients receiving bevacizumab and 380 patients receiving cetuximab in second-line treatment. Demographic and baseline characteristics were similar between the two groups. Patients’ mean age was 61 years and 56% were males. In second-line treatment, bevacizumab was commonly used with oxaliplatin (43.5%) and irinotecan-based regimens (40.4%), whereas cetuximab was commonly used with irinotecan-based regimens (68.2%). Bevacizumab patients had significantly lower total all-cause healthcare costs than cetuximab patients (adjusted difference: –$10,231, p?=?0.020), and lower medical costs (–$10,796, p?=?0.012) during the 6 months following second-line therapy initiation. Approximately half of the difference in total all-cause healthcare costs was attributable to the lower chemotherapy and targeted therapy costs (–$5635, p?=?0.032) of bevacizumab patients than those of cetuximab patients. While on second-line therapy, bevacizumab patients also had lower average monthly all-cause healthcare costs than cetuximab patients.

Limitations:

Second-line treatment in the current study was defined based on changes in mCRC medications, not based on disease progression due to the limited clinical information available in claims.

Conclusion:

The use of bevacizumab in second-line therapy was associated with significantly lower healthcare costs in mCRC patients, compared to the use of cetuximab.     

批评性语篇分析之基于系统功能语法透视三维分析模式

阐述了如何应用系统功能语法和三维分析模式进行批评性语篇分析,具体包括对Fairclough的三维分析模式和Halliday的系统功能语法的说明,以及在进行批评性语篇分析时如何采用Halliday的系统功能语法补充和发展Fairclough的三维分析模式。     

中医辨证配合化疗治疗晚期肺癌临床分析

目的探究中医辨证配合化疗对晚期肺癌患者的临床治疗效果。方法将我院2011年1月～2012年1月接诊的53例晚期肺癌患者作为研究对象,随机分为研究组与对照组。对照组患者单纯采用化疗治疗,研究组则在对照组的基础上配合中医辨证治疗。对两组病患的治疗效果进行总结与对比。结果研究组治疗前平均分为58.45分,治疗后为71.35分,对照组治疗前平均分为58.13分,治疗后为49.63分;研究组27例患者半年的生存率为81.48%,一年的生存率为48.15%,对照组26例患者半年生存率为46.15%,一年生存率为15.38%;治疗效果上,研究组总有效率为40.74%,对照组总有效率为15.38%。结论对于晚期肺癌患者而言,采用中医辨证配合西医化疗治疗,除了可以提高患者对化疗的耐受性之外,还能明显提高患者的生存质量,当属一种值得临床推广及应用的治疗方法。     

Cost drivers for breast,lung, and colorectal cancer care in a commercially insured population over a 6-month episode: an economic analysis from a health plan perspective

Aims: In the absence of clinical data, accurate identification of cost drivers is needed for economic comparison in an alternate payment model. From a health plan perspective using claims data in a commercial population, the objective was to identify and quantify the effects of cost drivers in economic models of breast, lung, and colorectal cancer costs over a 6-month episode following initial chemotherapy.

Research design and methods: This study analyzed claims data from 9,748 Cigna beneficiaries with diagnosis of breast, lung, and colorectal cancer following initial chemotherapy from January 1, 2014 to December 31, 2015. We used multivariable regression models to quantify the impact of key factors on cost during the initial 6-month cancer care episode.

Results: Metastasis, facility provider affiliation, episode risk group (ERG) risk score, and radiation were cost drivers for all three types of cancer (breast, lung, and colorectal). In addition, younger age (p?p?p?p?p?Conclusions: Value-based reimbursement models in oncology should appropriately account for key cost drivers. Although claims-based methodologies may be further augmented with clinical data, this study recommends adjusting for the factors identified in these models to predict costs in breast, lung, and colorectal cancers.     

Regression analysis of indicating multiple incremental cost-effectiveness ratios for non-small cell lung cancer treatment

Objectives:

The value of a health technology can be measured in terms of cost and benefit on two-dimensional co-ordinates. This study is to quantitatively analyze the correlation and to conduct a regression on the X-Y plane constituted by cost and QALYs (quality-adjusted life years) associated with the first line treatment, the maintenance treatment, and the second line treatment for non-small cell lung cancer (NSCLC).

Methods:

The cost-effectiveness data of the cost and QALYs were extracted, with respect to the three categories of the NSCLC treatment, from the CEA Registry at Tufts Medical Center, regarding the literature published from 2000–2011. As a result, 44 QALY-cost ratios were identified.

Results:

Based on those extracted data, the correlation and regression analyses were performed by mathematical model using log and square-root functions. The plotted ratios stratified by the three stages for the NSCLC treatment were visually grouped into three clusters. There were statistically significant differences among the correlation coefficients of the cluster. In regression, the log model was found to be better fitted than the square-root model; formulating QALY?=??1.12?+?0.16 log(Cost), ?1.99?+?0.28 log(Cost), and ?0.69?+?0.10 log(Cost) for the first line, the maintenance, and the second line treatment, respectively. Monetary units were standardized to 2008 US dollars.

Conclusion:

A good methodological potential was confirmed so as to assess the Incremental Cost Effectiveness Ratio (ICER) variations, considering stratification by multiple factors such as disease and treatment categories. This study has certain limitations, such as the small number of included articles and the stratification, not reflecting a factor of new genetic findings.     

Cost effectiveness and cost utility of risedronate for osteoporosis treatment and fracture prevention in women: a Swiss perspective

Abstract

Objectives: To assess the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) of risedronate compared to no intervention in postmenopausal osteoporotic women in a Swiss perspective.

Methods: A previously validated Markov model was populated with epidemiological and cost data specific to Switzerland and published utility values, and run on a population of 1,000 women of 70 years with established osteoporosis and previous vertebral fracture, treated over 5 years with risedronate 35 mg weekly or no intervention (base case), and five cohorts (according to age at therapy start) with eight risk factor distributions and three lengths of residual effects.

Results: In the base case population, the ICER of averting a hip fracture and the ICUR per quality-adjusted life year gained were both dominant. In the presence of a previous vertebral fracture, the ICUR was below €45,000 (£30,000) in all the scenarios. For all osteoporotic women ≥ 70 years of age with at least one risk factor, the ICUR was below €45,000 or the intervention may even be cost saving. Age at the start of therapy and the fracture risk profile had a significant impact on results.

Conclusion: Assuming a 2-year residual effect, that ICUR of risedronate in women with postmenopausal osteoporosis is below accepted thresholds from the age of 65 and even cost saving above the age of 70 with at least one risk factor.     

Brain metastases in patients with ALK+ non-small cell lung cancer: clinical symptoms,treatment patterns and economic burden

Abstract

Objective:

Brain metastases (BM) are highly prevalent among anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) patients; yet little is known about their real-world treatment patterns and clinical and economic burdens. This study aimed to describe these patients’ treatment patterns, symptoms, and costs.

Research design and methods:

Retrospective study pooling data from three large administrative databases in the US (08/2011–06/2013). ALK+ NSCLC patients with BM and continuous enrollment for ≥ 60 days before and ≥30 days after the first observed BM diagnosis were identified by pharmacy records for crizotinib among patients with lung cancer and BM diagnostic codes.

Main outcome measures:

Treatment patterns, symptoms, healthcare resource utilization, and costs, before and after BM diagnosis.

Results:

Of the 213 crizotinib patients with BM diagnoses meeting the selection criteria, 23.0% had BM prior to NSCLC diagnosis; 47.4% had BM prior to crizotinib initiation; 19.2% during crizotinib treatment; and 10.3% post-crizotinib treatment. For those diagnosed with BM after NSCLC diagnosis, the median time between the NSCLC and BM diagnoses was 88 days. Following the first observed BM diagnosis, 88.7% used chemotherapy, 63.4% had radiotherapy, and 31.9% had stereotactic radiosurgery. The prevalence of BM-related symptoms substantially increased post-BM-diagnosis: fatigue (from 15% to 39%), headaches (from 5% to 24%), and depression (from 5% to 15%). Monthly costs per patient averaged $5983 before the BM diagnosis and $22,645 after diagnosis. Patients’ resource utilization increased significantly post-BM-diagnosis, with a 3-fold increase in OP visits and a 6-fold increase in IP stays. Post-BM-diagnosis costs were driven by pharmacy (42.0%), inpatient (29.6%), and outpatient costs (26.0%).

Limitations:

The study sample was limited to crizotinib-treated patients.

Conclusions:

Post-BM-diagnosis, patients experience high symptom burden. Post-BM-diagnosis, treatment is highly variable and costly: average monthly costs per patient almost quadrupled post-BM-diagnosis.     

Direct treatment cost of atrial fibrillation in the elderly American population: a Medicare perspective

Abstract

Objective: Although atrial fibrillation (AF) is the most commonly sustained arrhythmia in adults, few studies have examined the direct treatment cost of AF.

Methods: A Medicare database of a 5% random national sample of all beneficiaries was used to identify patients diagnosed with AF in 2003 and to follow them for 1 year after diagnosis. These patients were matched on a 1:1 basis by age, gender and race. The incremental cost of treating AF was calculated with multivariate regression models adjusting for covariates.

Results: In total, 55,260 subjects developed new AF, of which 69% were ≥75 years old, 54% were female and 91% were White. The adjusted mean incremental treatment cost of AF was $14,199 (95% confidence interval $13,201–15,001; p<0.01). Some of this cost was attributable to the incidence of stroke and heart failure at the 1-year post-AF diagnosis. A significantly higher proportion of AF patients experienced stroke (23.1 vs. 13.3%; p<0.01) and heart failure (36.7 vs. 10.4%; p<0.01) compared with Medicare beneficiaries without AF.

Conclusions: Mean incremental direct treatment costs for Medicare beneficiaries with AF were higher than previously reported. Interventions that can reduce the incidence of AF and its complications may also reduce the national economic impact of AF.     

Electronic word-of-mouth communities from the perspective of social network analysis

This paper is focused on the identification of influencers that can have an important impact over the decision-making of other users. For this purpose, a popular electronic word-of-mouth community like Ciao.com has been modelled as a social network. Using social network analysis techniques, the existence of influencers is justified by the power law distribution of user participation, and then they are identified using their topological features within the social network. The obtained results reveal that influencers are not determined by the number of performed reviews, but by the variety or scope of their performed reviews and their central position in the consumer network. The main contribution of this research is the identification of influencers based on the participation features of community users. As a difference to other studies, results are not based on surveys or opinions, but on the trace users leave when they post opinions, comments or scores.     

A cost-effectiveness analysis of MMX mesalazine compared with mesalazine in the treatment of mild-to-moderate ulcerative colitis from a UK perspective

Abstract

Objectives: To perform a cost-utility analysis of a new formulation of mesalazine (Mezavant XL, MMX mesalazine) versus an existing oral mesalazine (Asacol; mesalazine) from the UK National Health Service perspective.

Methods: A 5-year Markov cohort model was developed. Costs were obtained from the literature and utilities from an independent study. Uncertainty was evaluated using one-way and probabilistic sensitivity analyses (PSA). The potential effect of dosing frequency on adherence and possible long-term effects of remission maintenance on colorectal cancer (CRC) rates were also investigated.

Results: The model suggested that 5-year therapy with MMX mesalazine was likely to generate gains when compared with mesalazine, including a gain of 0.011 QALYs per patient, 19 more remission days, and 12% fewer hospitalizations and surgical episodes. These gains came at an increase in total NHS direct cost of £8, resulting in an incremental cost-effectiveness ratio (ICER) of £749. The PSA suggested that MMX mesalazine had a 62% chance of resulting in cost savings, and a 74% chance of being cost effective (£20,000 threshold). Extended analysis including adherence and CRC effects suggested further incremental benefit of MMX mesalazine over mesalazine could be expected. Limitations include uncertainty in extrapolation to a 5-year time horizon and impact of adherence and drug acquisition costs on outcomes.

Conclusion: The pharmacoeconomic analysis suggested that MMX mesalazine is likely to produce small, but worthwhile, increases in total NHS direct cost while increasing time in remission and associated quality of life, when compared with mesalazine. Advantages in adherence to treatment with MMX mesalazine relative to mesalazine suggested that further health gains and cost savings can be obtained. Overall, these results suggest that MMX mesalazine is a cost-effective treatment for UC.     

Analysis of open innovation communities from the perspective of social network analysis

Open innovation is an emergent paradigm by which organisations make use of their internal and external resources to perform their innovation processes. The growth of information and communication technologies has facilitated the spread of online open innovation communities, where users can share ideas as well as comment on and evaluate ideas posted by other community members. In this work, the behaviour of community members is analysed from the perspective of social network analysis. The final aim is twofold: first, to measure to what extent the different forms of participation are correlated to each other; and, second, how the collective intelligence evaluation schemes can be useful to identify those users posting ideas which are potentially applicable for the organisation. Obtained results can help community managers and organisations to improve the efficiency of the evaluation process when hundreds or thousands of ideas are shared through the online community.