On One Analytic Method of Constructing Program Controls

Abstract The article proposes an analytical method for constructing control function that ensures transferring linear inhomogeneous stationary system from an initial state to a given final state. Conditions under which the specified transfer is guaranteed are presented. Mathematics Subject Classification: 34H15, 93C15, 93B0

Health technology assessment of hyaluronans in osteoarthritis treatment

Health technology assessment has been performed for osteoarthritis treatment. Several technologies were evaluated — NSAIDs, steroid therapy and hyaluronans viscosupplementation for inter joint injection. Expertise based on literature data and modeling evaluated outcomes during 2.5 years in the fourth stage of illness including knee replacement. Only one strategy — with Synvisk® injection has been eff ective in the endpoint of modeling. Expenditures for NSAIDs, steroids and Synvisk® were calculated. Synvisk® usage is more preferable based on budget impact analysis. Th is strategy can save no less than 81 million RUR (on 1000 pts.). Saved money can cover an additional quantity of patients for Synvisk® treatment. Synvisk® technology is delay a necessity of knee replacement surgeon in patients with fourth stage of osteoarthritis following to budget economy during 6-12 months treatment already

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 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

Pharmacoeconomic evaluation of mirabegron: results of the healthcare budget impact analysis

Overactive bladder (OAB) is a chronic disease that correlates with the age of the patient, and occurs in almost one in seven women and men. Pharmacotherapy is one of the main methods for correction of this nosology. Taking into account the absence of additional therapeutic option on the Vital and Essential Drugs List for patients with contraindications for the prescription of solifenacin and BTX-A, patients with intolerance to these drugs conduct, an analysis of the economic consequences of the use of mirabegron under the State Guarantees for Providing Free Medical Care for the OAB treatment. Approved recommendations on carrying out the budget impact analysis were used. Results of the study show, that the expansion of the mirabegron use in the treatment of patients with OAB in the target population leads to the reduction in the cost of medical therapy for this group of patients: with an increase in the share of mirabegron up to 5 %, costs will decrease by 7.8 %; with an increase in the mirabegron share up to 10 % costs will decrease by 12.5 %; when using in 15 % of the target population – by 22.3 %. Trend analysis of changes in the average weighted costs shows the following: an increase in the use of mirabegron leads to a significant reduction in total costs, the total benefit can reach 6 250 002 576 rubles per 3 years of the drug presence in the VED List, which allows attributing the OAB treatment with mirabegron to economically feasible and resource-saving medical technologies

Health technology assessment of colorectal cancer chemotherapy with afl ibercept

Colorectal cancer (CRC) is an actual medical problem of the Russian Health Care system due to high morbidity and mortality rates. Despite the arrival of newer anti-cancer agents in the second-line setting for CRC treatment during the last years, no Health Technology Assessments (HTA) were preformed for modern agents. Aim: HTA of second line chemotherapy for metastatic CRC (mCRC) with a new anti-cancer agent afl ibercept in combination with chemotherapy regimen FOLFIRI during the short- and long-term perspectives for the Government Health Care System. Methods. Markov’s modelling has been performed based on published data of VELOUR study with 30-months horizon for two strategies of treatment: afl ibercept+FOLFIRI and FOLFIRI only for prognosis of effi cacy establishing. Overall survival (OS), time to progression (TTP) and QALY were used for effi cacy criteria defi nition. Cost-eff ectiveness analysis, including incremental, has been performed and results were compared with willingness to pay (WTP) parameter. Cost of chemotherapy, side eff ects correction, as well as expenditures for treatment in case of second line failure, have been calculated for both technologies. Costs were allowed by Governmental Health Care System expenditures. Results. It was concluded that afl ibercept+FOLFIRI is more eff ective vs FOLFIRI on all parameters of effi cacy (for OS — by 12%, for TTP — by 16%, for QALY — by 26%). CER`s for OS parameter were RUR 322 348 for afl ibercept+FOLFIRI and RUR 253 685 for FOLFIRI only (NS). For TTP parameter based on 30-months horizon ICER for afl ibercept+FOLFIRI was RUR 994 039, it was 1,35 times less than WTP. ICER for QALY was diff erent from such kind for OS and TTP. Total expenditures for 30-months modelling horizon for FOLFIRI were less by 42% due to add of afl ibercept cost in the calculation. Cost of treatment in case of second line failure was 78% of the total structure of expenditures for FOLFIRI and only 56% for afl ibercept+FOLFIRI. Probabilistic sensitivity analysis has been performed by multiplex changes of effi cacy parameters and costs of afl ibercept+FOLFIRI and FOLFIRI only and has confi rmed that afl ibercept+FOLFIRI is more eff ective and more expensive scheme. Conclusion. Second line strategy of mCRC chemotherapy with afl ibercept+FOLFIRI is more cost-eff ective vs FOLFIRI for OS and TTP criteria. When compared with afl ibercept+FOLFIRI, with FOLFIRI use, the treatment costs rise as a result of decreased effi cacy. Afl ibercept+FOLFIRI meets the criteria of WTP and is reasonable for reimbursement on Governmental level

Pharmacoeconomic analysis of botulinum toxin in complex therapy for cerebral palsy

We have performed the fi rst-ever pharmacoeconomic analysis in a Russian context of botulin toxin drugs as part of combined therapy for juvenile cerebral palsy (JCP) compared to standard clinical practice. Along with health economic modelling, an analysis of “routine clinical practice” was conducted by means of a survey of experts (practicing neurologists). Th ree medical approaches were evaluated: treatment with the use of drug-induced local myorelaxation via Botox® combined with standard clinical practice; treatment with the use of drug-induced local myorelaxation via Dysport® combined with standard clinical practice, and treatment in accordance with standard clinical practice, including rehabilitative and orthopedic care. Markov cycles, probabilistic sensitivity analysis, and budget impact analysis were used for modelling. Th e results show that the use of Botox® combined with standard clinical practice for treatment of focal spasticity in patients with JCP is an economically advantageous medical approach. Th is strategy was characterized by high clinical eff ectiveness with the lowest expenses of the medical approaches compared for treatment of spastic syndrome in JCP patients. As for the budget impact analysis, use of Botox® combined with standard clinical practice would allow saving up to an additional RUB 239 387 964 per 1000 patients with JCP over three years. Th e results of mathematical modelling correspond with information from “typical” clinical practice

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

Pharmacoeconomic analysis of the use of botulinum toxin in the treatment of poststroke spasticity

We conducted a comparative pharmacoeconomic analysis of the use of botulin toxin drugs in complex therapy of poststroke spasticity syndrome under Russian conditions. Together with a health economic modelling, we conducted a “standard practice” analysis through polling of experts (neurologist physicians) with subsequent use of the Delphi method. We evaluated three medical technologies for treatment of poststroke spasticity in combination with standard clinical practice: treatment using drug-induced local miorelaxation by Botox®, Dysport® and Xeomin®. In the modelling, we used a Markov cycle, a probabilistic sensitivity analysis and budget impact analysis. It was determined that, in conducting one course of therapy, the strategy using Botox® was least expensive and most effective, both in the case of examining one course of therapy and according to the results of three-year observation. According to the results of the cost-effectiveness analysis for therapy of the various strategies, the strategy using Botox® was predominant. That result was observed both when examining efficacy and when examining effectiveness according to the results of the three-year modelling of using the treatment strategies. From the standpoint of the budget impact analysis, Botox® is also the most preferable strategy: using this drug saves up to 141 million rubles of budgetary funds and makes it possible to treat an additional 227 patients with this strategy. The results obtained in the mathematical modelling correlate to the “standard” data of clinical practice and the pharmacoepidemiological analysis conducted concurrently

Pharmacoeconomic analysis of the use of ibrutinib in therapy of the first line of a chronic lymphocytic leukaemia for patients with 17p deletion

We have performed the first-ever comparative pharmacoeconomic analysis in a Russian context of ibrutinib in the first line of therapy of chronic lymphocytic leukemia at patients with a 17p deletion. Research was conducted from a position of the state health system by means of mathematical modeling. It was considered direct and indirect costs. Markov modeling and the sensitivity analysis were used. It was as a result shown that application of Imbruvica® in therapy of chronic lymphocytic leukemia at patients with a 17p deletion is an economically advantageous medical technology from the point of view of a ratio of cost and efficiency in comparing with strategy of an ofatumumab. It was as a result shown that application of Imbruvica® in therapy of chronic lymphocytic leukemia at patients with a 17p deletion is economically expedient medical technology from the point of view of a ratio of cost and efficiency when comparing with strategy of an ofatumumab. Also, this strategy was characterized by high clinical effectiveness and a comparable profile of safety among other medical technologies. As for the budget impact analysis, comparing with strategy of an ofatumumab widespread use of ibrutinib would allow saving up to an additional 80.5 millions rub per 1 000 patients with chronic lymphocytic leukemia, thus the saved means allow to treat with this strategy in addition 16 patients