Personalized treatment of women with early breast cancer: a risk-group specific cost-effectiveness analysis of adjuvant chemotherapy accounting for companion prognostic tests OncotypeDX and Adjuvant!Online

Background: Due to high survival rates and the relatively small benefit of adjuvant therapy, the application of personalized medicine (PM) through risk stratification is particularly beneficial in early breast cancer (BC) to avoid unnecessary harms from treatment. The new 21-gene assay (OncotypeDX, ODX) is a promising prognostic score for risk stratification that can be applied in conjunction with Adjuvant!Online (AO) to guide personalized chemotherapy decisions for early BC patients. Our goal was to evaluate risk-group specific cost effectiveness of adjuvant chemotherapy for women with early stage BC in Austria based on AO and ODX risk stratification. Methods: A previously validated discrete event simulation model was applied to a hypothetical cohort of 50-year-old women over a lifetime horizon. We simulated twelve risk groups derived from the joint application of ODX and AO and included respective additional costs. The primary outcomes of interest were life-years gained, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness (ICER). The robustness of results and decisions derived were tested in sensitivity analyses. A cross-country comparison of results was performed. Results: Chemotherapy is dominated (i.e., less effective and more costly) for patients with 1) low ODX risk independent of AO classification; and 2) low AO risk and intermediate ODX risk. For patients with an intermediate or high AO risk and an intermediate or high ODX risk, the ICER is below 15,000 EUR/QALY (potentially cost effective depending on the willingness-to-pay). Applying the AO risk classification alone would miss risk groups where chemotherapy is dominated and thus should not be considered. These results are sensitive to changes in the probabilities of distant recurrence but not to changes in the costs of chemotherapy or the ODX test. Conclusions: Based on our modeling study, chemotherapy is effective and cost effective for Austrian patients with an intermediate or high AO risk and an intermediate or high ODX risk. In other words, low ODX risk suggests chemotherapy should not be considered but low AO risk may benefit from chemotherapy if ODX risk is high. Our analysis suggests that risk-group specific cost-effectiveness analysis, which includes companion prognostic tests are essential in PM. Electronic supplementary material The online version of this article (10.1186/s12885-017-3603-z) contains supplementary material, which is available to authorized users

Real-World Use of 3rd Line Therapy for Multiple Myeloma in Austria: An Austrian Myeloma Registry (AMR) Analysis of the Therapeutic Landscape and Clinical Outcomes prior to the Use of Next Generation Myeloma Therapeutics

Objective: Clinical trials demonstrate improving survival in patients with multiple myeloma (MM) after treatment. However, it is unclear whether increased survival translates to a similar benefit in a real world setting. Methods: We analyzed the overall survival of 347 multiple myeloma patients in Austria by means of a national registry (AMR), focused on results from 3rd and later lines of therapy. This benchmark was chosen to define a baseline prior to the broad application of upcoming 2nd generation drugs (carfilzomib, pomalidomide). Results: Projected 10 years survival for patients with MM in Austria is estimated to be 56% in patients diagnosed in between the years 2011–2014, 21% in patients with a diagnosis made between 2000–2005, and 39% in those with a diagnosis made between 2006–2010). For the same intervals a significant increase in the use of both bortezomib, lenalidomide and thalidomide—so called IMiDs (from 2005 onwards) and their simultaneous use in combination therapies (from 2010 onwards) could be shown. The use of autologous transplantation (ASCT) remained more or less constant at ~ 35% of patients in the 1st line setting over the whole period, comparing well to international practice patterns, while the use of 2nd line ASCT increased from 5.5% to 18.7% of patients. Patients in 3rd or later line treatment (n = 105), showed that even in relapsed and refractory disease median survival was 27 months with a considerable proportion of long-term survivors (~20%). Conclusion & Perspective With the expected emergence of additional active anti-myeloma compounds, we aim to assess survival in patients with relapsed and refractory MM

Study design recommendations in guidance documents for high-risk medical devices. A systematic review.d

This review is one of the tasks in the Horizon 2020 project Coordinating Research and Evidence for Medical Devices (CORE-MD), which started in April 2021 and will end in March 2024 (https://www.core-md.eu). Its mission is "Translating expert knowledge into advice for EU regulatory guidance and building expertise in regulatory science in the clinical community". This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ or send a letter to Creative Commons, PO Box 1866, Mountain View, CA 94042, USA. The objectives of this systematic review are firstly to identify guidance on the design, conduct, analysis, and reporting of confirmatory pivotal clinical trials and other clinical investigations for high-risk medical devices, from regulators, international standardization organizations, medical professional associations, academic consortia, and HTA agencies; secondly, to compare their similarities and differences; and thirdly, to identify gaps for further research on trial methodology

Survival of Multiple Myeloma patients in Austria overtime and extrapolated Weibull model survival estimates.

<p>The upper part (Fig 2A) illustrates the survival of Myeloma patients in Austria respective to the date of their first diagnosis in between 2000–2005 (blue line), 2006–2010 (red line), and 2011–2014 (green line). The x-axis represents time in years, and the y-axis represents the proportion of patients surviving. The dotted lines give the respective Weibull extrapolation of the patients’ 10 years survival. The lower part (Fig 2B) illustrates the survival of Myeloma patients in Austria respective to the date of their first diagnosis in between 2000–2005 (blue line), 2006–2010 (red line), and 2011–2014 (green line). The x-axis represents time in years, and the y-axis represents the proportion of patients surviving. The dotted lines give the respective Weibull extrapolation of the patients’ 10 years survival.</p

Patients and treatment lines.

<p>illustrates the distribution of treatment lines and patients (pts.) documented in the Austrian Myeloma Registry (AMR). Patients who had received at least 3 lines of therapy were included in the analysis (yellow boxes).</p

Patient disposition in patients receiving or not receiving 3^rd line therapy for Multiple myeloma in Austria.

<p>Patient disposition in patients receiving or not receiving 3^rd line therapy for Multiple myeloma in Austria.</p

Survival of Multiple Myeloma patients in Austria from start of 3^rd line.

<p><b>Therapy.</b> illustrates the survival of Myeloma patients in Austria from start of 3^rd line therapy in 105 patients documented in AMR median survival was found to be 27 months (0–170 months/ongoing).</p

Effectiveness and Cost-Effectiveness of Sequential Treatment of Patients with Chronic Myeloid Leukemia in the United States: A Decision Analysis

Currently several tyrosine kinase inhibitors (TKIs) are approved for treatment of chronic myeloid leukemia (CML). Our goal was to identify the optimal sequential treatment strategy in terms of effectiveness and cost-effectiveness for CML patients within the US health care context. We evaluated 18 treatment strategies regarding survival, quality-adjusted survival, and costs. For model parameters, the literature data, expert surveys, registry data, and economic databases were used. Evaluated strategies included imatinib, dasatinib, nilotinib, bosutinib, ponatinib, stem-cell transplantation (SCT), and chemotherapy. We developed a Markov state-transition model, which was analyzed as a cohort simulation over a lifelong time horizon with a third-party payer perspective and discount rate of 3%. Remaining life expectancies ranged from 5.4 years (3.9 quality-adjusted life years (QALYs)) for chemotherapy treatment without TKI to 14.4 years (11.1 QALYs) for nilotinib→dasatinib→chemotherapy/SCT. In the economic evaluation, imatinib→chemotherapy/SCT resulted in an incremental cost-utility ratio (ICUR) of $171,700/QALY compared to chemotherapy without TKI. Imatinib→nilotinib→chemotherapy/SCT yielded an ICUR of$253,500/QALY compared to imatinib→chemotherapy/SCT. Nilotinib→dasatinib→chemotherapy/SCT yielded an ICUR of $445,100/QALY compared to imatinib→nilotinib→chemotherapy/SCT. All remaining strategies were excluded due to dominance of the clinically superior strategies. Based on our analysis and current treatment guidelines, imatinib→nilotinib→chemotherapy/SCT and nilotinib→dasatinib→chemotherapy/SCT can be considered cost-effective for patients with CML, depending on willingness-to-pay

Long-Term Effectiveness and Cost Effectiveness of Multiple Myeloma Treatment Strategies for Elderly Transplant-Ineligible Patients in Serbia

Evidence on long-term effectiveness and cost effectiveness of treatment sequences for multiple myeloma (MM) is sparse. We used published data and country-specific data to assess the cost effectiveness of four-line treatment sequences for elderly transplant-ineligible patients with MM in Serbia