Pharmacoeconomic analysis of denosumab in patients with breast cancer and bone metastases

Skeletal-related events - a significant medical and economic problem for women with metastases during the treatment of breast cancer. Clinico-economic evaluation was performed to compare the use of denosumab and zoledronic acid in this category of patients. The recommended pharmacoeconomic methods such as modelling (time horizon - 10 years) with Markov cycles were used. Direct and indirect costs were calculated. Number of skeletal-related events and QALY gained were used as efficacy criteria. As a result, it was shown that denosumab had greater efficacy than zoledronic acid. Using 10 years’ time horizon total costs per patient were less for zoledronic acid than for denosumab. Regardless of efficacy criteria and direct or indirect costs, ICER was below the willingness-to-pay threshold (1,341,308 rubles). The results of the multivariative probabilistic sensitivity analysis confirmed the findings of the basic scenario. Thus, the use of denosumab in patients with breast cancer and bone metastases is cost-effective strategy

An update of pharmacoeconomic analysis of trastuzumab emtanzine in patients with HER2+ breast cancer and central nervous system metastases

Introduction. Regardless the pharmacoeconomic evaluation of trastuzumab emtanzine (T-DM-1) has been done before new data concerning T-DM1 effectiveness and also costs data require an update of pharmacoeconomic evaluation. Aim. To update pharmacoeconomic evaluation of T-DM1 in patients with HER2+ breast cancer (BC) and CNS metastases. Materials and methods. Cost-effectiveness analysis along with sensitivity analysis were performed. Direct medical costs and indirect costs (GDP loss) were accounted. Results. At 5 years modeling horizon total cost of trastuzumab emtanzine were higher comparing to lapatinib+capecitabine due to significantly higher overall survival (OS) observed in T-DM1 group. CER OS for T-DM1 was by 21% lower comparing to CER lapatinib+capecitabine (2 099 940 RUR/patient/year and 2 541 879 RUR/patient/year, consequently). Conclusions. The study showed T-DM1 is a cost-effective strategy in patient with HER2+ metastatic BC and CNS metastases

Pharmacoeconomic evaluation of ipragliflozin in combination with metformin in comparison with other regimens of therapy for type 2 diabetes mellitus

Ipragliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduce plasma glucose concentrations by inhibiting glucose reabsorption by the kidney through inhibiting SGLT2 sodium-glucose cotransporter and induce glycosuria. SGLT2 inhibitors are a new class of glucose lowering drugs most recently approved for treatment of type 2 diabetes mellitus (T2DM). Unlike other antidiabetic agents, SGLT2 inhibitors improve glycemic control (by HbA1c) and provide multiple additional benefits, including decreased body weight, blood pressure, and other multiple pleiotropic effects. The completed clinical trials and real world data have provided evidence that including of SGLT2 inhibitors in the treatment of T2DM has benefits of reduction of cardiovascular and renal outcomes. Goal. The aim of the study was to conduct a clinical and economic examination of ipragliflozin in comparison with other regimens of glucose-lowering therapy with other SGLT2 inhibitors. Methods. In carrying out the pharmacoeconomic analysis itself, a cost-effectiveness analysis (CEA) was applied with the calculation of the corresponding cost-effectiveness ratio (CER), incremental cost-effectiveness ratio (ICER) according to the formula, as well as an a «budget impact analysis». Multiple one-way sensitivity analysis, check the robustness of the results of the main scenario results to changes in key parameters such as the cost of drugs and complications of diabetes. The time horizon for analyzing the dynamics of economic consequences when using ipragliflozin as a glucose-lowering therapy for T2DM was 5 years. Results. The weighted average cost per patient per year when using the ipragliflozin treatment strategy is 31,182 rubles. The costs of the empagliflozin strategy are 61,291 rubles per patient. In the case of using dapagliflozin, the weighted average costs are 30,032 rubles per patient per year, the total direct medical costs for the current drug therapy option, calculated on the initial number of target practice in 72,143 patients with type 2 diabetes, amounted to 3,068,642,442 rubles. Analysis of the trend of changes in weighted average costs showed that the broader use of ipragliflozin for the treatment of T2DM in the target population leads to reducing in diabetes related direct medical costs by 6.7 %, while the total economic effect of ipragliflozin introduction over five years will be 501,539,327 rubles. Conclusions. Use of ipragliflozin + metformin in T2DM treatment is a cost-effective strategy compared to empagliflozin + metformin. The combination of ipragliflozin with metformin versus dapagliflozin + metformin is economically feasible in terms of cost-effectiveness

Health-economic analysis of tocilizumab in patients with rheumatoid arthritis and systemic juvenile arthritis

Rationale. Rheumatoid arthritis (RA) and systemic juvenile arthritis (sJA) are the most frequent rheumatic diseases in adults and adolescents, consequently. Biologics disease modifying antirheumatic drugs (bDMARDs) are eff ective in treatment of RA and s JA. Aim. To perform health-economic analysis of tocilizumab for subcutaneous and intravenous injections in patients with RA and sJA comparing to TNF-α inhibitors. Materials and methods. Cost-minimizing analysis was used from the perspective of healthcare system (accounting for direct medical costs) with the modelling horizon — 1 year. We included into the model cost of RA and sJA bDMARDs, cost of adverse events correction and costs of laboratory and instrumental diagnostic. Results. Cost minimizing ratio of tocilizumab (subcutaneous form) in RA patients comparing to adalimumab (Humira), сertolizumab pegol, golimumab were 111 536; 129 094; 85 244 RUR, consequently favour to tocilizumab. Tocilizumab was less costly comparing to adalimumab (Humira), certolizumab pegol, golimumab by 12.8, 14.5, 10,0 %, consequently. Cost minimizing ratio of tocilizumab in RA patients comparing to adalimumab (Dalibra), etanercept, infl iximab (Remicade) were 40 497; 54 355; 28 419 RUR in favour to comparators. Tocilizumab was more costly comparing to adalimumab (Dalibra) etanercept, infl iximab (Remicade) by 5.6; 7.7; 3.9 %, consequently. Cost minimizing ratio of tocilizumab in sJA patients comparing to kanakinumab, adalimumab (Humira) and adalimumab (Dalibra) were 6 535 234; 478 297 and 323 263 RUR. Tocilizumab was less costly comparing to kanakinumab, adalimumab (Humira) and adalimumab (Dalibra) by 93.3; 50.6 and 41.1 %, consequently. Conclusions. Tocilizumab is economically reasonable comparing to others TNF-α inhibitors in patients with RA and sJA

Pharmacoeconomic analysis of trastuzumab emtanzine comparing to lapatinib + capecitabine in pa-tients with HER2+ breast cancer and central nervous system metastases

Aim. To perform health-economic evaluation of trastuzumab emtansine (T-DM1) in patients with HER2+ breast cancer and CNS metastases. Materials and methods. Cost-effectiveness analysis along with sensitivity analysis and budget impact analysis were performed. Direct medical costs and indirect costs (GDP loss) were accounted. Results. At 3 years modeling horizon total cost of trastuzumab emtanzine were higher comparing to lapatinib+capecitabine due to significantly higher overall survival (OS) observed in trastuzumab emtanzine group. CER OS for T-DM1 and lapatinib+capecitabine were 1 686 222 RUR/patient/ year and 1 704 486 RUR/patient/year, consequently. T-DM1 ICER (OS) was lower than cost-effectiveness threshold in Russia in 2016. Conclusions. The study showed T-DM1 is a cost-effective strategy in patient with HER2+ metastatic BC and CNS metastases

Economic analysis of Lixisenatide in Diabetes Mellitus Type 2

Usage of glucagon like peptide-1 receptors’ agonists (aGLP-1) is a new step in the treatment of Diabetes Mellitus Type 2 (DM 2). General attractive effects are positive effect on bodyweight, lower risk of hypoglycemia, compliance and possibility of combination with insulin or it’s analogues etc. Clinical-economic analysis of Lixisenatide in combination with insulin glargine has been performed for evaluation of reasons for state or insurance budgeting. Methods: Model of DM 2 has been used for comparison of Direct Costs (DC) of glargine+lixisenatid and basal bolus glargine+glulisine, detemir+aspart, glargine+aspart, glargine+lispro, detemir+lispro, detemir+glulisis as well as with combnations of metformin with exenatide or liraglutide. Efficacy criteria were amount of patient-years without complications during one-year period and amount of patient-years with targeted HbA1c level. Calculation cost has included: expenditures on pharmacotherapy of DM2 and complications, costs of out-patients aid, emergency and hospital treatment. Cost-efficacy ratio and incremental cost-efficacy rate as well Budget Impact have been performed. Results: Highest DC based on 2-year horizon of modelling were calculated for detemir+aspart -277 356 RUR, DC for glargine+lixisenatide was less on 5,6%. Costs of aGLP-1 and insulins were different, and expenditures on hypoglycemia too. Thus detemir+aspart were most expensive 77 763 RUR. Also in this group treatment of hypoglycemia was very costly. CERs (cost- effectiveness ratios) were 2 456 RUR, 3 752 RUR and 3 980 RUR. for glargine+glulisine, glargine+lixisenatide and detemir+aspart accordingly. Highest level of DC has been done for detemir+glulisine 281 628 RUR and detemir+lispro 278 744 RUR. Lixisenatide has led to insulin (glargine) dose reduction in compare with other combinations that reflected in less cost (54 186 RUR for glargine vs 81 289 RUR for detemir+glulisine during 2 years). Amount of patient-years with targeted level of HbA1c was the same in different treatment options but scheme glargine+lixisenatide was less costly DC among schemes with another aGLP-1 was less in glargine+lixisenatide on 65% in compare with metformin+liraglutide (741 531 RUR with 2-years of modelling horizon). Conclusion: Scheme glargine+lixisenatide more cost-saving regimen in compare with metformin+exenatide, metformin+liraglutide, detemir+short acting insulin analogues Scheme glargine+lixisenatide has not benefits in compare with glargine+glulisin but has less hypoglycemia level. Glargine+lixisenatide is an economic appropriate scheme for state (insurance) budgeting

Фармакоэкономический анализ лекарственных средств, применяемых в лечении ревматоидного артрита при неэффективности базовых противовоспалительных средств

Objective. To perform health economic evaluation of several antirheumatic drugs in patients with rheumatoid arthritis (RA) progressed after DMARDs.Materials and methods. Three consequent line of rheumatoid arthritis therapy in patients progressed after methotrexate were modeled in Russian economic conditions. Markov modelling and CEA accounting for direct medical costs were used. The effectiveness criteria of RA treatment were: patient-years in remission and patient-years in low disease activity. We compared 12 different treatment regimens of second, third and fourth therapy line in patients progressed after methotrexate.Results. The health economic analysis of different RA treatment regimen after progression on methotrexate showed that evaluated regimens do not differs in terms of effectiveness and safety. At the mean time the model account for the patients compliance and showed that the maximum number of patient-years in remission can be reached with etanercept and tofacitinib treatment. Moreover, above mentioned combination in comparison to adalimumab and infliximab showed the positive budget impact.Conclusion. The choice of etanercept and tofacitinib in case of similar economics should be done accounting for individual patient features.Цель исследования – изучение фармакоэкономической целесообразности различных лекарственных средств в лечении ревматоидного артрита при неэффективности базовых противовоспалительных средств.Материалы и методы. В российских экономических условиях проведено моделирование последовательных трех линий терапии ревматоидного артрита у пациентов после неэффективности терапии метотрексатом. Использовали фармакоэкономический анализ с расчетом прямых затрат и анализом эффективности затрат. Критерием эффективности терапии артрита были: число пациенто-лет в ремиссии заболевания; число пациенто-лет с низкой активностью заболевания. Применяли цикл Маркова. Рассматривали двенадцать сценариев, включающие различные лекарственные средства в качестве второй, третьей и четвертой линий терапии (после неэффективности метотрексата).Результаты. Проведенный фармакоэкономический анализ различных сценариев при неэффективности терапии метотрексатом продемонстрировал, что согласно результатам клинических исследований, оцениваемые лекарственные средства мало отличаются с точки зрения эффективности и безопасности терапии. В свою очередь, результаты построения фармакоэкономической модели, также учитывающей данные о приверженности пациентов к лечению, демонстрируют возможность достижения наибольшего числа пациенто-лет в ремиссии на фоне комбинации лекарственных средств этанерцепт и тофацитиниб. Более того, данная комбинация позволяла минимизировать объем бюджета системы здравоохранения, необходимый для лечения пациентов РА в сравнении с наиболее часто применяемыми ГИБП – адалимумабом и инфликсимабом.Заключение. Выбор в пользу этанерцепта или тофацитиниба, учитывая схожие экономические показатели, целесообразно делать с учетом индивидуальных особенностей пациента

Реальная практика проведения клинико-экономических исследований лекарственных средств, входящих в федеральную программу высокозатратных нозологий

Objective: to assess the compliance of the actual practice of conducting clinical and economic research with the requirements applicable in the Russian Federation (RF) when including drugs in the Federal Program of High-Cost Nosologies (HCN).Material and methods. In the CyberLeninka and eLibrary databases, a search was made for clinical and economic studies of medicines included in the HCN list published in the RF in the period from 2011 to June 2021.Results. Information was obtained on 23 published clinical and economic studies of the effectiveness of drugs, which is less than 30% of all drugs included in the HCN program during the specified period. More than half of the studies of chronic disabling diseases had a modeling horizon of 1 year. The sensitivity analysis of the results in over 1/3 of cases considered only the deviation of the price of the strategies under consideration, and in a quarter of cases it was not carried out at all. Only 4 studies evaluated the increase in quality-adjusted life year, although, for chronic disabling diseases, quality of life is one of the key performance indicators.Conclusion. In the RF, less than 30% of the results of pharmacoeconomical studies of drugs included in the HCN Program are published, which does not allow to make adequate evaluation of pharmacoeconomical approaches to its formation. To analyze the effectiveness of the tools used in assessing the economic efficiency of expensive medical technologies, a further retrospective research of the studies conducted in the RF is required.Цель: оценка соответствия реальной практики проведения клинико-экономических исследований действующим в Российской Федерации (РФ) требованиям, предъявляемым при включении лекарственных средств (ЛС) в федеральную программу высокозатратных нозологий (ВЗН).Материал и методы. В базах данных КиберЛенинка и eLibrary проведен поиск клинико-экономических исследований ЛС, включенных в перечень ВЗН, которые были опубликованы в РФ в период с 2011 г. по июнь 2021 г.Результаты. Получены сведения о 23 клинико-экономических исследованиях эффективности ЛС, что составляет менее 30% от всех ЛС, включенных в указанный период в программу ВЗН. Более половины исследований хронических инвалидизирующих заболеваний имели горизонт моделирования 1 год. Анализ чувствительности результатов более чем в 1/3 случаев учитывал только отклонение цены рассматриваемых стратегий, а в 1/4 случаев такой анализ вообще не проводился. Только в 4 исследованиях оценивали прирост лет качественной жизни, несмотря на то что для хронических инвалидизирующих заболеваний качество жизни – один из ключевых показателей эффективности.Заключение. В РФ публикуется менее 30% результатов фармакоэкономических исследований ЛС, включенных в программу ВЗН, что не позволяет в полной мере оценить фармакоэкономические подходы к ее формированию. Для анализа эффективности инструментов, используемых при оценке экономической эффективности дорогостоящих медицинских технологий, требуется дальнейшее ретроспективное изучение проведенных в РФ исследований.

Прогнозирование резистентности: от математического моделирования к фармакоэкономике

Complicated intra-abdominal infection (IAI) requires increased health care expenditures and additional resources to compensate for an ineffective starting therapy.Aim. To select the economically optimal algorithm for using antimicrobial agents (AMA) that would minimize the evolving drug-resistance of microbial flora exemplified by E. coli.Methods. Based on the published data and our own clinical experience with antimicrobial drugs,  we calculated the cost of treatment of complicated IAI when either effective or ineffective  starting antibiotic therapy was applied. The developing drug-resistance of E. coli was simulated  by a mathematical model that incorporated real data on the antimicrobial drugs usage. The  model was also able to propose the optimal mode of AMA consumption, which is expected to minimize the microbial drugresistance.Results. According to the model, the current volume of AMA consumption (which includes more than 60% of fluoroquinolones, 3d generation cephalosporins and inhibitor-protected penicillin  derivatives) will increase the proportion of the Extended-spectrum betalactamase (ESBL)-positive strains of E. coli by 7% over the next 5 years. In contrast, the proposed alternative (optimized)  mode of AMA consumption (almost complete withdrawal of inhibitor-protected penicillins and  fluoroquinolones, against an increase in carbapenems by 30% and an increase in 3d generation  cephalosporins by 20%), will decrease the proportion of ESBL (+) E. coli strains by 7%. The cost  of care of complicated IAI under the current AMA regimen will grow due to the increase in the  proportion of ESBL (+) strains of E. coli. In contrast, the alternative (optimal) AMA therapy leading to the decrease in E. coli drug-resistance is expected to reduce the cost of care of complicated IAI to the level where the real and alternative (optimized) AMA consumption expenditures are comparable.Conclusion. The proposed mathematical model allows one to predict the changes in microbial  drug-resistance and choose the optimal algorithm of AMA consumption able to restrain the growth of drug-resistance.Осложненная интраабдоминальная инфекция (ИАИ) ассоциирована с повышенным потреблением ресурсов системы здравоохранения и дополнительными расходами, связанными с  неэффективностью стартового режима антибактериальной  терапии.Цель – выбор оптимальной с точки зрения влияния на уровень  резистентности микробной флоры и экономической  целесообразности структуры потребления антимикробных  препаратов (АМП) в многопрофильном стационаре на примере  оказания специализированной стационарной медицинской помощи пациентам с осложненной ИАИ.Методы. На основании литературных данных, а также реальной практики применения АМП рассчитана стоимость  лечения одного случая осложненной ИАИ при эффективном и  неэффективном стартовом режиме антибактериальной терапии. С помощью математического моделирования спрогнозирована  динамика резистентности E. coli на фоне реальной практики  применения АМП. Спрогнозирован оптимальный режим  потребления АМП, при котором рост резистентности окажется минимальным.Результаты. Реальный уровень потребления АМП, при котором более 60% потребления приходится на фторхинолоны,  цефалоспорины 3-го поколения и ингибитор-защищенные  пенициллины, приведет к росту доли БЛРС-резистентных  штаммов E. Coli на 7% в течение 5-летнего периода. В то же  время при альтернативном (оптимальном) потреблении АМП  (практически полный вывод из клинической практики ингибитор- защищенных пенициллинов и фторхинолонов, на фоне  увеличения потребления карбапенемов на 30% и прироста  потребления цефалоспоринов 3-го поколения на 20%) приведет к снижению доли бета-лактамазы расширенного  спектра действия (БЛРС) (+) штаммов E. Coli на 7%. Стоимость  случая осложненной ИАИ при назначении АМП в соответствии с  текущей практикой потребления будет расти ввиду роста доли  БЛРС (+) штаммов E. Coli. В то же время проведение  антибактериальной терапии в условиях альтернативной  (оптимальной) структуры потребления приводит к значимому  снижению доли БЛРС (+) штаммов E. Coli и практически  сравнивает суммарную стоимость одного случая терапии, осложненной ИАИ, при реальной и альтернативной (оптимальной) структуре потребления.Заключение. Применение математического моделирования  позволяет рассчитать динамику резистентности возбудителей  инфекций различной локализации и выбрать оптимальную структуру потребления АМП, для снижения роста резистентности

Модели анализа включений лекарственных средств в ограничительные перечни (на примере ЖНВЛП) 2016 г.

Background: In 2014 we firstly analyzed the formalized system (points and expert opinions) of drug inclusion and exclusion into the reimbursement lists in Russian Federation. The liner mathematical model of decision making was developed and adopted.Aim. Update the existing model using the results of reimbursement procedures acting from 2106.Material and methods. The linear models developed and adopted in 2014 were used. In 2015 we included data on 141 drug dossiers. We analyzed the decision of the expert body, chief Ministry of Health expert and the final committee decision.Results. 43 new drugs were included into the reimbursement lists acting from 2016. The model of expert body decision had an error 7,09% (12,4% in 2014). The model of chief Ministry of Health expert decision had an error – 7% (10% in 2014). The above mentioned experts became more experienced in the formalized procedure of decision making. The model of final decision had an error about 42% (35% in 2014). Conclusion. Linear models are working tools for modelling reimbursement system decisions. At the mean time the existing system of decision making needs more formalization.Актуальность. В 2014 г. в Российской Федерации был проведен первый опыт включения (исключения) лекарственных средств в ограничительные списки на формализованном принципе (балльная система, независимые заключения). На основании опубликованных данных за 2014 г. авторами были разработаны и апробированы математические линейные модели.Цель. Построение модели по данным анализа перечней на 2016 г.Материалы и методы. Использованы ранее разработанные и принятые линейные модели. В анализ было включено 141 досье на лекарственные препараты. Анализировали заключение экспертной организации, главного специалиста и окончательное решение.Результаты. В 2016 г. в ограничительный перечень жизненно необходимых и важнейших лекарственных препаратов (ЖНВЛП) было включено 43 лекарственных препарата. В результате показано, что модель заключения для экспертной организации давала ошибку 7,09% (в 2014 г. – 12,4%). Для главных внештатных специалистов – 7% (2014 г. – 10%). Отмечается «обучение» формализованному подходу указанных выше лиц, учитывая явную положительную динамику. Модель для окончательного решения междисциплинарной комиссии давала ошибку около 42% (ранее 35%).Заключение. Линейные модели являются действующим инструментом прогнозирования включения лекарственных препаратов в ограничительные перечни. В то же время действующая система по-прежнему требует формализации