A Stochastic Economic Evaluation of Letrozole versus Tamoxifen as a First-Line Hormonal Therapy: For Advanced Breast Cancer in Postmenopausal Patients

Background: Letrozole is a third-generation aromatase inhibitor that is a feasible alternative to tamoxifen as a first-line hormonal therapy for patients with advanced breast cancer. Objective: This paper presents the results of an economic evaluation comparing letrozole and tamoxifen as first-line hormonal therapies in postmenopausal women diagnosed with advanced breast cancer. Perspective: UK National Health Service. Design: A decision model (Markov process) was built describing possible patient pathways from the point of diagnosis to death. The model was populated using patient-specific clinical trial data, data from the existing literature, and expert opinion. Stochastic analyses of the model were undertaken, whereby the majority of the input parameters were described as probability distributions to represent the uncertainty about their true value. Costs were presented in year 2000 values. Results: The baseline results showed that letrozole is a cost-effective alternative to tamoxifen with a mean incremental cost per life-year gained of Lstg 2342, whilst the incremental cost increases to just over Lstg 10 Conclusions: The results of the economic analysis indicate that letrozole is a cost-effective alternative first-line therapy compared with tamoxifen for postmenopausal women with advanced breast cancer, achieving additional life-years with a modest increase in costs.Advanced-breast-cancer, Aromatase-inhibitors, Cost-analysis, Estrogen receptor modulators, Letrozole, Menopause, Tamoxifen, Pharmacoeconomics

“Economic evaluation of gemcitabine in the treatment of pancreatic cancer in the UK”

Gemcitabine, Economic evaluation, Expected value of information,

Cost-Effectiveness Analysis of Adjuvant Therapy for Operable Breast Cancer from a Chinese Perspective: Doxorubicin plus Cyclophosphamide versus Docetaxel plus Cyclophosphamide

Background: An oncology trial compared four cycles of doxorubicin/cyclophosphamide (AC) with four cycles of docetaxel/cyclophosphamide (TC) in operable breast cancer patients (71% were diagnosed with hormone receptor positive and 48% with node-negative breast cancer). The objective of this study was to estimate the lifetime cost effectiveness of AC versus TC, from a Chinese healthcare provider perspective, based on a clinical trial. Abstract: Methods: A lifetime cost-effectiveness analysis was performed using a Markov model. Events rates and utilities in the Markov model were derived from published papers. Data on cost of breast cancer care were obtained from the Second Xiangya Hospital of Central South University, Changsha, PR China. One-way sensitivity analysis and probabilistic sensitivity analysis were undertaken. Cost estimates were valued in Chinese yuan (Y), year 2008 values. All costs and outcomes were discounted at 3% per annum. Abstract: Results: Patients receiving TC gained 14.45 QALYs, 0.41 QALYs more than patients receiving AC. The lifetime costs of patients receiving TC were Y93 511, Y10 116 more than that of AC patients. The incremental cost-effectiveness ratios were Y26 742 per life-year gained (£2719.8 per year) and Y24 305 per QALY gained (£2471.9 per QALY). The most sensitive parameter in the model was the cost of primary cancer treatments in the TC arm. At a threshold willingness to pay of Y86 514 per QALY, the probability of TC being cost effective was 90%. Abstract: Conclusions: Our model suggests that TC may be considered cost effective from a Chinese healthcare provider perspective, according to the threshold defined by the WHO.

The value of value of information: best informing research design and prioritization using current methods

Value of information (VOI) methods have been proposed as a systematic approach to inform optimal research design and prioritization. Four related questions arise that VOI methods could address. (i) Is further research for a health technology assessment (HTA) potentially worthwhile? (ii) Is the cost of a given research design less than its expected value? (iii) What is the optimal research design for an HTA? (iv) How can research funding be best prioritized across alternative HTAs? Following Occam's razor, we consider the usefulness of VOI methods in informing questions 1–4 relative to their simplicity of use. Expected value of perfect information (EVPI) with current information, while simple to calculate, is shown to provide neither a necessary nor a sufficient condition to address question 1, given that what EVPI needs to exceed varies with the cost of research design, which can vary from very large down to negligible. Hence, for any given HTA, EVPI does not discriminate, as it can be large and further research not worthwhile or small and further research worthwhile. In contrast, each of questions 1–4 are shown to be fully addressed (necessary and sufficient) where VOI methods are applied to maximize expected value of sample information (EVSI) minus expected costs across designs. In comparing complexity in use of VOI methods, applying the central limit theorem (CLT) simplifies analysis to enable easy estimation of EVSI and optimal overall research design, and has been shown to outperform bootstrapping, particularly with small samples. Consequently, VOI methods applying the CLT to inform optimal overall research design satisfy Occam's razor in both improving decision making and reducing complexity. Furthermore, they enable consideration of relevant decision contexts, including option value and opportunity cost of delay, time, imperfect implementation and optimal design across jurisdictions. More complex VOI methods such as bootstrapping of the expected value of partial EVPI may have potential value in refining overall research design. However, Occam's razor must be seriously considered in application of these VOI methods, given their increased complexity and current limitations in informing decision making, with restriction to EVPI rather than EVSI and not allowing for important decision-making contexts. Initial use of CLT methods to focus these more complex partial VOI methods towards where they may be useful in refining optimal overall trial design is suggested. Integrating CLT methods with such partial VOI methods to allow estimation of partial EVSI is suggested in future research to add value to the current VOI toolkit.Simon Eckermann, Jon Karnon and Andrew R. Willa

Cost-effectiveness analysis of adjuvant therapy for operable breast cancer from a Chinese perspective: Doxorubicin plus Cyclophosphamide versus Docetaxel plus Cyclophosphamide

Background: An oncology trial compared four cycles of doxorubicin/ cyclophosphamide (AC) with four cycles of docetaxel/cyclophosphamide (TC) in operable breast cancer patients (71% were diagnosed with hormone receptor positive and 48% with node-negative breast cancer). The objective of this study was to estimate the lifetime cost effectiveness of AC versus TC, from a Chinese healthcare provider perspective, based on a clinical trial. Methods: A lifetime cost-effectiveness analysis was performed using a Markov model. Events rates and utilities in the Markov model were derived from published papers. Data on cost of breast cancer care were obtained from the Second Xiangya Hospital of Central South University, Changsha, PR China. One-way sensitivity analysis and probabilistic sensitivity analysis were undertaken. Cost estimates were valued in Chinese yuan (Y), year 2008 values. All costs and outcomes were discounted at 3% per annum. Results: Patients receiving TC gained 14.45 QALYs, 0.41 QALYs more than patients receiving AC. The lifetime costs of patients receiving TC were Y93 511, Y10 116 more than that of AC patients. The incremental cost-effectiveness ratios were Y26742 per life-year gained (2719.8 [pounds sterling] per year) and Y24305 per QALY gained (2471.9 [pounds sterling] per QALY). The most sensitive parameter in the model was the cost of primary cancer treatments in the TC arm. At a threshold willingness to pay of Y86 514 per QALY, the probability of TC being cost effective was 90%. Conclusions: Our model suggests that TC may be considered cost effective from a Chinese healthcare provider perspective, according to the threshold defined by the WHO.Peng Liubao, Wan Xiaomin, Tan Chongqing, Jon Karnon, Chen Gannong, Li Jianhe, Cui Wei, Luo Xia and Cao Junhu

Cost-benefit analysis of endocrine therapy in the adjuvant setting for postmenopausal patients with hormone receptor-positive breast cancer, based on survival data and future prices for generic drugs in the context of the German health care system

BACKGROUND: Cost-effectiveness analyses have focused on aromatase inhibitors (AIs), but the results are inconsistent and disease-free survival has often been extrapolated to overall survival. The present study calculates the cost-effectiveness of 5 years of letrozole versus tamoxifen versus anastrozole in the context of the German health care system, using survival data from the Breast International Group (BIG) 1-98 study and the Arimidex, Tamoxifen, Alone or in Combination (ATAC) study and generic prices. MATERIALS AND METHODS: A hybrid model was developed that incorporates recurrence rates, overall survival, treatment costs and treatment-associated adverse events and the resulting costs. The basic assumption was that generic anastrozole would lead to a price reduction to 75% of the original price. Further analyses were carried out with 50% and 25% of the original prices for anastrozole and letrozole. RESULTS: The cost-benefit model showed a gain of 0.3124 or 0.0659 quality-adjusted life years (QALYs) for letrozole or anastrozole. Incremental costs of € 29,375.15/QALY for letrozole (100% of original price) were calculated and € 94,648.03/QALY for anastrozole (75% of original price). Marked increases in cost-effectiveness are observed with further decreases in price (anastrozole: 50% price € 54,715.17/QALY, 25% price € 14,779.57/QALY; letrozole 75% price € 20,988.59/QALY, 50% price € 12,602.03/QALY, 25% price € 4,215.46/QALY). CONCLUSION: The present model including the inverse probability of censoring weighted analysis (IPCW) for letrozole and generic prices for both AIs shows that letrozole is cost effective.Michael P. Lux, Claudia Reichelt, Jon Karnon, Thorsten D. Tänzer, Dragan Radosavac, Peter A. Fasching, Matthias W. Beckmann, Falk C. Thie

Taking the pulse of the health services research community: A cross-sectional survey of research impact, barriers and support

Objective: This study reports on the characteristics of individuals conducting health service research (HSR) in Australia and New Zealand, the perceived accessibility of resources for HSR, the self-reported impact of HSR projects and perceived barriers to conducting HSR. Methods: A sampling frame was compiled from funding announcements, trial registers and HSR organisation membership. Listed researchers were invited to complete online surveys. Close-ended survey items were analysed using basic descriptive statistics. Goodness of fit tests determined potential associations between researcher affiliation and access to resources for HSR. Open-ended survey items were analysed using thematic analysis. Results: In all, 424 researchers participated in the study (22% response rate). Respondents held roles as health service researchers (76%), educators (34%) and health professionals (19%). Most were employed by a university (64%), and 57% held a permanent contract. Although 63% reported network support for HSR, smaller proportions reported executive (48%) or financial (26%) support. The least accessible resources were economists (52%), consumers (49%) and practice change experts (34%) researchers affiliated with health services were less likely to report access to statisticians (P Conclusions: The data highlight opportunities to sustain the HSR community through dedicated funding, improved access to methodological expertise and greater engagement with end-users. What is known about the topic?: HSR faces several challenges, such as inequitable funding allocation and difficulties in quantifying the effects of HSR on changing health policy or practice. What does this paper add?: Despite a vibrant and experienced HSR community, this study highlights some key barriers to realising a greater effect on the health and well-being of Australian and New Zealand communities through HSR. These barriers include limited financial resources, methodological expertise, organisational support and opportunities to engage with potential collaborators. What are the implications for practitioners?: Funding is required to develop HSR infrastructure, support collaboration between health services and universities and combine knowledge of the system with research experience and expertise. Formal training programs for health service staff and researchers, from short courses to PhD programs, will support broader interest and involvement in HSR.</p

Cost-effectiveness of letrozole versus tamoxifen as initial adjuvant therapy in hormone receptor-positive postmenopausal women with early-stage breast cancer

Background: In Breast International Group (BIG) 1-98, a randomized, double-blind trial comparing 5 years of initial adjuvant therapy with letrozole versus tamoxifen in postmenopausal women with hormone receptor–positive early breast cancer, letrozole significantly improved disease-free survival by 19% and reduced risk of breast cancer recurrence by 28% and distant recurrence by 27%. Patients and Methods: A Markov model was used to estimate the incremental cost per quality-adjusted life year (QALY) gained with 5 years of initial adjuvant therapy with letrozole versus tamoxifen from a US health care system perspective. Probabilities and costs of breast cancer recurrence and treatment-related adverse events and health-state utilities were based on published results of BIG 1-98 and other published studies. Costs and QALYs were estimated over the lifetime of a cohort of postmenopausal women with hormone receptor–positive early breast cancer, aged 60 years at initiation of therapy. In our base case, we assumed that benefits of letrozole on risk of breast cancer recurrence are maintained for 5 years after therapy discontinuation (“carry-over effect”) and examined the effects of this assumption on results in sensitivity analyses. Results: Under base-case assumptions, letrozole yields an additional 0.409 QALYs versus tamoxifen at an additional cost of $9705, yielding a cost per QALY gained for letrozole versus tamoxifen of$23,743 (95% confidence interval, $14,087-$51,129). Assuming no carry-over effects, letrozole yields 0.264 QALYs at a cost of $10,341, for a cost per QALY gained of$39,098 (95% confidence interval, $23,968-$83,501). Conclusion: In postmenopausal women with hormone receptor–positive early breast cancer, initial adjuvant treatment with letrozole is cost-effective from the US health care system perspective.Thomas E. Delea, Jon Karnon, Oleg Sofrygin, Simu K. Thomas, Natalie L. Papo, Victoria Barghou

Cost-effectiveness of letrozole in the extended adjuvant treatment of women with early breast cancer

Adjuvant tamoxifen therapy for 5 years reduces recurrence in hormone receptor positive, post-menopausal women with early breast cancer, but offers no advantage when prolonged to another 5 years, during which the risk of recurrence remains high. Treating patients, who remain disease-free after 5 years of tamoxifen, with letrozole significantly reduces recurrence, regardless of nodal status. This study evaluated the life-time cost-utility of extended adjuvant letrozole therapy in 62-year-old patients from a third-party payer perspective. A Markov model incorporated locoregional, contralateral, and metastatic recurrences. The comparator was placebo. Event rates were based on published trials. Utility values were taken from a clinical trial and published literature. Costs were obtained from published literature, provincial payment schedules, cancer agencies, and drug plans formularies. Resource use reflected Canadian treatment patterns. Robustness of the model was tested using deterministic and probabilistic sensitivity analyses. Extended adjuvant letrozole therapy of a cohort consisting of 50% node-negative and 50% node-positive patients prolonged their lives on average by 0.466 years or 0.267 quality-adjusted life years (QALYs) at an additional cost of Can$8,031 per patient, yielding an incremental cost-utility ratio (ICUR) of$34,058 per QALY. Letrozole was more cost-effective in node-positive than in node-negative patients (Can$26,553 vs Can$46,049 per QALY). Results were robust to variations in age, healthcare costs, and utilities. The degree of confidence that the cost per QALY would be below Can$50,000 reached 100$50,000/QALY.Ouagari, Khalid; Karnon, Jon; Delea, Thomas; Talbot, Willena and Brandman, Jan