Фармакоэкономическая эффективность применения препарата атезолизумаб в сравнении с другими ингибиторами PD-1 у пациентов с распространенным немелкоклеточным раком легкого после предшествующей химиотерапии

Aim: to evaluate the pharmacoeconomic efficacy of the application of the atesolizumab (PD-L1 inhibitor) preparation compared with other control point inhibitors (PD-1 inhibitors) in patients with advanced non-small cell lung cancer (NSCLC) after chemothe rapy.Materials and methods. Study design included a retrospective analysis of literature data and modeling. Based on the calculations conducted in a Microsoft Excel model, we analyzed the effect of minimizing costs on using comparable drugs with comparable efficacy; we evaluated how the provision of all patients with NSCLC will impact the health system budget taking into consideration the fact that all these patients are currently provided with PD-1 inhibitors in the second and third lines and with the atezolizumab preparation. For calculations, we used the prices stated in the state register of maximum selling prices; the weighted average maximum wholesale premium was calculated according to the Federal Antimonopoly Service (FAS). Results. In the analysis of cost minimization, atesolizumab proved itself to be highly clinically and economically effective. It allowed reducing the costs by 28.6% over 3 years compared with the use of nivolumab, and by 31.3% compared with the use of pembrolizumab in the second- and third-line NSCLC treatment regimen. Analysis of the impact on the budget showed that if all 848 patients currently receiving PD-1/PD-L1 inhibitors in the second- and third-line NSCLC treatment regimens had been initially provided with atesolizumab, this would have reduced the pressure on budget by 21.90% or 664.25 million rubles for 3 years.Conclusion. The use of the atesolizumab preparation is pharmacoeconomically reasonable and appropriate in comparison with the use of nivolumab and pembrolizumab. It will allow reducing the cost of PD-1/PD-L1 inhibitors in the second- and third-line NSCLC treatment regimens. Цель – оценить фармакоэкономическую эффективность применения препарата атезолизумаб (ингибитор PD-L1) в сравнении с другими ингибиторами контрольных точек (ингибиторы PD-1) у пациентов с распространенным немелкоклеточным раком легкого (НМРЛ) после предшествующей химиотерапии.Материалы и методы. Дизайн исследования – ретроспективный анализ литературных данных и моделирование. На основании расчетов, проведенных в модели, построенной на базе программного обеспечения Microsoft Excel, проведен анализ минимизации затрат на применение сравниваемых препаратов, обладающих сопоставимой эффективностью, оценено влияние на бюджет системы здравоохранения при обеспечении всех пациентов с НМРЛ, в настоящее время обеспечиваемых ингибиторами PD-1 во второй и третьей линии, препаратом атезолизумаб. Для расчетов использовали зарегистрированные цены согласно государственному реестру предельных отпускных цен, средневзвешенная предельная оптовая надбавка – по данным Федеральной антимонопольной службы (ФАС).Результаты. В анализе минимизации затрат препарат атезолизумаб показывает большую клинико-экономическую эффективность – его применение позволяет снизить затраты на 28,6% за 3 года в сравнении с применением ниволумаба, и на 31,3% в сравнении с применением пембролизумаба во второй и третьей линии терапии НМРЛ. Анализ влияния на бюджет показал, что если бы все 848 пациентов, в настоящее время получающие ингибиторы PD-1/PD-L1 во второй и третьей линии терапии НМРЛ, изначально были обеспечены атезолизумабом, это позволило бы снизить нагрузку на бюджет за 3 года на 21,90%, или на 664,25 млн руб.Заключение. Применение препарата атезолизумаб является фармакоэкономически обоснованным и целесообразным по сравнению с применением ниволумаба и пембролизумаба и позволит снизить расходы на ингибиторы PD-1/PD-L1 во второй и третьей линии терапии НМРЛ

Сравнительный фармакоэкономический анализ использования генноинженерных биологических препаратов при лечении больных неконтролируемой среднетяжелой и тяжелой атопической бронхиальной астмой

Objective – to conduct a pharmacoeconomic analysis of using omalizumab, mepolizumab and reslizumab in the treatment of patients with uncontrolled moderate and severe atopic asthma in the healthcare setting of the Russian Federation.Materials and Methods. A pharmacoeconomic model based on clinical data was created. The cost-effectiveness ratios for omalizumab, mepolizumab and reslizumab were calculated and compared. Budget impact analysis for the partial replacement of omalizumab with mepolizumab and/or reslizumab has been performed.Results. The use of omalizumab costs 13.3% less than that of reslizumab and 1.6% more than that of mepolizumab. The cost-effectiveness ratio for omalizumab is significantly lower vs the competitors. To prevent asthma exacerbations by omalizumab requires 463 805 rubles, which is 24.80% less than for reslizumab and by 382,640 or 20.89% less than for mepolizumab. The results are robust and resistant to 10% fluctuations in prices for the compared products. According to the budget impact analysis, by introducing reslizumab instead of omalizumab for a 3-year therapy in 210 patients with asthma and blood eosinophilia ≥400 cells/µl, will increase the burden on the budget by 13.25% or by 83.2 million rubles. In a group of 594 patients with eosinophilia ≥150 cells/µl, using mepolizumab instead of omalizumab will increase the budget burden by 1.58% or by 24.0 million rubles. In the total group of 759 patients receiving genetically-engineered products, switching to mepolizumab and reslizumab will increase the budget spending by 3.3% or 67.2 million rubles for 3 years.Conclusion. The analysis shows that using omalizumab in patients with severe asthma that is uncontrolled by medium and high doses of inhaled corticosteroids, has the lowest burden on the budget of the healthcare system and is more effective compared to mepolizumab and reslizumab.Цель – провести сравнительный фармакоэкономический анализ лекарственных препаратов омализумаб, меполизумаб и реслизумаб при лечении больных неконтролируемой среднетяжелой и тяжелой атопической бронхиальной астмой в условиях российского здравоохранения.Материалы и методы. На основе опубликованных результатов клинических исследований построена фармакоэкономическая модель. Проведен сравнительный анализ «затраты-эффективность» для препаратов омализумаб, меполизумаб и реслизумаб, а также анализ влияния на бюджет при частичной замене препарата омализумаб на меполизумаб и/или реслизумаб.Результаты. Применение препарата омализумаб требует на 13,3% меньше затрат, чем применение реслизумаба, и на 1,6% больше, чем меполизумаба. Соотношение затрат и эффективности при применении препарата омализумаб существенно ниже, чем при применении препаратов сравнения. Для предотвращения обострений бронхиальной астмы при применении омализумаба потребуется потратить на 463 805 руб., или на 24,80% меньше, чем при использовании реслизумаба, и на 382 640 руб., или на 20,89% ниже, чем меполизумаба. Полученные результаты устойчивы к колебаниям цен на сравниваемые препараты на 10%. Согласно анализу влияния на бюджет, за 3 года в группе 210 пациентов с эозинофилией ≥400 клеток/мкл применение реслизумаба вместо омализумаба увеличит нагрузку на бюджет на 13,25%, или на 83,2 млн руб. В группе 594 пациентов с эозинофилией ≥150 клеток/мкл применение меполизумаба вместо омализумаба приведет к увеличению нагрузки на бюджет на 1,58%, или на 24,0 млн руб. В общей группе 759 пациентов с бронхиальной астмой, получающих генно-инженерные биологические препараты (ГИБП), переключение всех пациентов, имеющих показания, на меполизумаб и реслизумаб, приводит к увеличению нагрузки на бюджет на 3,3%, или на 67,2 млн руб. за 3 года.Заключение. Проведенный анализ показывает, что применение омализумаба у пациентов с тяжелой бронхиальной астмой, не контролируемой на средних и высоких дозах ингаляционных кортикостероидов, оказывает наименьшую нагрузку на бюджет системы здравоохранения и является наиболее фармакоэкономически эффективным в сравнении с применением меполизумаба и реслизумаба

РЕАКТОРНЫЕ И ПОСЛЕРЕАКТОРНЫЕ ИСПЫТАНИЯ И ИССЛЕДОВАНИЯ НА БЫСТРЫХ КРИТИЧЕСКИХ СБОРКАХ ВЫСОКОПЛОТНОГО НИЗКООБОГАЩЕННОГО УРАН-ЦИРКОНИЕВОГО КАРБОНИТРИДНОГО ТОПЛИВА

UZrCN fuel is a high-density, high-temperature fuel that has potential for application in different type reactors. In the past, reactor tests using UZrCN HEU (96% U-235) fuel have been performed to low burnup. However, reactor-testing data are still needed at high burnup to confirm the optimal performance of this-type fuel. The SM-3 research reactor, which is a high-flux reactor located at the State Scientific Center – Research Institute of Atomic Reactors, Dimitrovgrad, Russia, will be used to test a UZrCN LEU (19.73% U-235) fuel to ~40% of burnup. The fuel will then be examined to determine its performance during irradiation.On the “Giacint” and “Kristal” critical facilities located at the Joint Institute for Power and Nuclear Research – SOSNY of the National Academy of Sciences of Belarus, Minsk, Belarus, criticality experiments on multiplying systems modeling physical features of cores with UZrCN LEU (19.75% U-235) fuel have been prepared for use in works on fast reactors with gaseous and liquid-metal coolants. Critical assemblies represent uniform hexagonal lattices of fuel assemblies, each of which consists of 7 fuel rods and has no clad. The active fuel length is 500 mm. Clad material is stainless steel or Nb. Three types of fuel assemblies with different matrix material (air, aluminum and lead) are investigated. These are side radial, top and bottom reflectors – beryllium (internal layer) and stainless steel (external layer).This article desribes the design of the experiment that will be performed in the SM-3 reactor and discusses the results of different calculations that have been performed to show that the experiment design will meet all objectives. The description of construction and composition of critical assemblies with UZrCN fuel and the calculation results are also presented. Топливо UZrCN представляет собой высокоплотное высокотемпературное топливо, которое может применяться в реакторах различных типов. В прошлом реакторные испытания ВОУ (96% U-235) UzrCN-топлива были выполнены только с низким выгоранием. Вместе с тем данные реакторных испытаний необходимы при высоком выгорании для подтверждения оптимальных характеристик этого типа топлива. Высокопоточный исследовательский реактор СМ-3, расположенный в Государственном научном центре – Научно-исследовательский институт атомных реакторов (г. Димитровград, Россия), будет использоваться для испытания НОУ (19,73% U-235) UzrCN-топлива до ~40 % выгорания. Затем топливо будет исследоваться для определения его характеристик после облучения.На критических стендах «Гиацинт» и «Кристал» в Объединенном институте энергетических и ядерных исследований – Сосны Национальной академии наук Беларуси (г. Минск, Беларусь) осуществляется подготовка к экспериментам по критичности на размножающих системах, моделирующих физические особенности активных зон с НОУ (19,75% U-235) UzrCN-топливом для использования в работах по новому поколению быстрых реакторов с газообразными и жидкометаллическими теплоносителями. Критические сборки представляют собой однородные гексагональные решетки топливных сборок, каждая из которых состоит из семи топливных стержней и не имеет оболочки. Длина активной части топливного стержня составляет 500 мм. Материал оболочки – нержавеющая сталь или ниобий. Будут исследованы три типа топливных сборок с различным материалом матрицы в них (воздух, алюминий и свинец). Боковой радиальный, верхние и нижние отражатели – бериллий (внутренний слой) и нержавеющая сталь (внешний слой).В настоящей статье описываются проектные данные эксперимента, который будет осуществлен на реакторе СМ-3, и обсуждаются результаты расчетов, призванные показать, что эксперимент будет отвечать всем поставленным целям. Также представлены описания конструкции и состава критических сборок с топливом UZrCN и результаты их расчетов.

Prototype ATLAS IBL Modules using the FE-I4A Front-End Readout Chip

The ATLAS Collaboration will upgrade its semiconductor pixel tracking detector with a new Insertable B-layer (IBL) between the existing pixel detector and the vacuum pipe of the Large Hadron Collider. The extreme operating conditions at this location have necessitated the development of new radiation hard pixel sensor technologies and a new front-end readout chip, called the FE-I4. Planar pixel sensors and 3D pixel sensors have been investigated to equip this new pixel layer, and prototype modules using the FE-I4A have been fabricated and characterized using 120 GeV pions at the CERN SPS and 4 GeV positrons at DESY, before and after module irradiation. Beam test results are presented, including charge collection efficiency, tracking efficiency and charge sharing.Comment: 45 pages, 30 figures, submitted to JINS

Pharmacoeconomic efficacy of atesolizumab compared with other PD-1 inhibitors in patients with advanced non-small cell lung cancer after chemotherapy

Aim: to evaluate the pharmacoeconomic efficacy of the application of the atesolizumab (PD-L1 inhibitor) preparation compared with other control point inhibitors (PD-1 inhibitors) in patients with advanced non-small cell lung cancer (NSCLC) after chemothe rapy.Materials and methods. Study design included a retrospective analysis of literature data and modeling. Based on the calculations conducted in a Microsoft Excel model, we analyzed the effect of minimizing costs on using comparable drugs with comparable efficacy; we evaluated how the provision of all patients with NSCLC will impact the health system budget taking into consideration the fact that all these patients are currently provided with PD-1 inhibitors in the second and third lines and with the atezolizumab preparation. For calculations, we used the prices stated in the state register of maximum selling prices; the weighted average maximum wholesale premium was calculated according to the Federal Antimonopoly Service (FAS). Results. In the analysis of cost minimization, atesolizumab proved itself to be highly clinically and economically effective. It allowed reducing the costs by 28.6% over 3 years compared with the use of nivolumab, and by 31.3% compared with the use of pembrolizumab in the second- and third-line NSCLC treatment regimen. Analysis of the impact on the budget showed that if all 848 patients currently receiving PD-1/PD-L1 inhibitors in the second- and third-line NSCLC treatment regimens had been initially provided with atesolizumab, this would have reduced the pressure on budget by 21.90% or 664.25 million rubles for 3 years.Conclusion. The use of the atesolizumab preparation is pharmacoeconomically reasonable and appropriate in comparison with the use of nivolumab and pembrolizumab. It will allow reducing the cost of PD-1/PD-L1 inhibitors in the second- and third-line NSCLC treatment regimens

Pharmacoeconomic analysis of using biological agents for uncontrolled moderate-to-severe atopic asthma in the Russian Federation

Objective – to conduct a pharmacoeconomic analysis of using omalizumab, mepolizumab and reslizumab in the treatment of patients with uncontrolled moderate and severe atopic asthma in the healthcare setting of the Russian Federation.Materials and Methods. A pharmacoeconomic model based on clinical data was created. The cost-effectiveness ratios for omalizumab, mepolizumab and reslizumab were calculated and compared. Budget impact analysis for the partial replacement of omalizumab with mepolizumab and/or reslizumab has been performed.Results. The use of omalizumab costs 13.3% less than that of reslizumab and 1.6% more than that of mepolizumab. The cost-effectiveness ratio for omalizumab is significantly lower vs the competitors. To prevent asthma exacerbations by omalizumab requires 463 805 rubles, which is 24.80% less than for reslizumab and by 382,640 or 20.89% less than for mepolizumab. The results are robust and resistant to 10% fluctuations in prices for the compared products. According to the budget impact analysis, by introducing reslizumab instead of omalizumab for a 3-year therapy in 210 patients with asthma and blood eosinophilia ≥400 cells/µl, will increase the burden on the budget by 13.25% or by 83.2 million rubles. In a group of 594 patients with eosinophilia ≥150 cells/µl, using mepolizumab instead of omalizumab will increase the budget burden by 1.58% or by 24.0 million rubles. In the total group of 759 patients receiving genetically-engineered products, switching to mepolizumab and reslizumab will increase the budget spending by 3.3% or 67.2 million rubles for 3 years.Conclusion. The analysis shows that using omalizumab in patients with severe asthma that is uncontrolled by medium and high doses of inhaled corticosteroids, has the lowest burden on the budget of the healthcare system and is more effective compared to mepolizumab and reslizumab

Production and Integration of the ATLAS Insertable B-Layer

During the shutdown of the CERN Large Hadron Collider in 2013-2014, an additional pixel layer was installed between the existing Pixel detector of the ATLAS experiment and a new, smaller radius beam pipe. The motivation for this new pixel layer, the Insertable B-Layer (IBL), was to maintain or improve the robustness and performance of the ATLAS tracking system, given the higher instantaneous and integrated luminosities realised following the shutdown. Because of the extreme radiation and collision rate environment, several new radiation-tolerant sensor and electronic technologies were utilised for this layer. This paper reports on the IBL construction and integration prior to its operation in the ATLAS detector

Production and integration of the ATLAS Insertable B-Layer

During the shutdown of the CERN Large Hadron Collider in 2013-2014, an additional pixel layer was installed between the existing Pixel detector of the ATLAS experiment and a new, smaller radius beam pipe. The motivation for this new pixel layer, the Insertable B-Layer (IBL), was to maintain or improve the robustness and performance of the ATLAS tracking system, given the higher instantaneous and integrated luminosities realised following the shutdown. Because of the extreme radiation and collision rate environment, several new radiation-tolerant sensor and electronic technologies were utilised for this layer. This paper reports on the IBL construction and integration prior to its operation in the ATLAS detector.Comment: 90 pages in total. Author list: ATLAS IBL Collaboration, starting page 2. 69 figures, 20 tables. Published in Journal of Instrumentation. All figures available at: https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PLOTS/PIX-2018-00