Kurylev A A

Balykina Y.E., Kolbin A.S., Kurylev A.A., Pavlysh A.V., Proskurin M.A. 5095

Abstract: A pharmacoeconomic evaluation of sunitinib as the firstline metastatic renal-cell carcinoma targeted agent in the Russian healthcare settings was performed in comparison with sorafenib and bevacizumab + interferon. A pharmacoeconomic Markov model was created and used to assess the costs and effectiveness (including mean overall survival in months) of each therapeutic regimen. The evaluation presented also includes a probabilistic multivariate sensitivity analysis. The results show that sunitinibbased treatment is dominant over sorafenib and bevacizumab + interferon, which makes it the most costeffectiveness treatment option.

Balykina Y.E., Kolbin A.S., Kurylev A.A., Proskurin M.A. 4731

Objective of this study was to determine cost-effectiveness of vemurafenib in treatment of inoperable or metastatic melanoma in patients with BRAF V600 mutation from Russian healthcare system perspective and a long-term use. Cost-effectiveness analysis (CEA) has been used and cost-effectiveness ratio (CER) has been calculated. Incremental analysis has been conducted with calculation of incremental cost-effectiveness ratio (ICER) when exceeding the costs and effectiveness of one of the studied regimens as compared to the other one. Cost analysis included calculation of the following direct costs (DC): the cost of the main disease treatment (cutaneous melanoma, CM) – costs of the drug; the cost of laboratory and instrumental methods of investigation as well as hospitalizations and out-patient treatment; the cost required to determine exon 15 BRAF mutation in melanoma; the cost of the drug therapy aimed at management of adverse events (AEs) caused by the drug when treating the main disease. Two medical technologies have been assessed (anti-tumor regimens depending on the chosen method): vemurafenib at a dose of 960 mg twice a day; dacarbazine at a dose of 1000 mg/m2 i/v every 3 weeks. Mathematical modelling underlies this study. As a result it has been demonstrated that the use of vemurafenib strategy in treatment of metastatic melanoma in patients with BRAF V600 mutation had better progression-free survival (PFS) rate throughout the entire modelling horizon. The use of vemurafenib in treatment of metastatic and inoperable melanoma in patients with BRAF V600 mutation is economically advisable taking into account the data on effectiveness (PFS). The use of vemurafenib in patients with BRAF V600 mutation is an absolutely innovative medical technology which currently does not have any alternative. Vemurafenib may be indicated for inclusion in reimbursement lists for treatment of patients with this mutation.

Balykina Y.E., Globin M.V., Kolbin A.S., Kurylev A.A., Litvinova A.A., Proskurin M.A. 1612

Balykina Y.E., Kolbin A.S., Kurylev A.A., .., Proskurin M.A. 1245

Glycemic control is a clinical goal in the treatment of diabetes mellitus. Currently available bolus insulin analogues do not follow the physiological pattern of insulin secretion after meals because they are slowly absorbed from the injection site. Insulin aspart+nicotinamide is an ultra-fast acting human insulin analog that can be administered before or after meals and the nicotinamide (vitamin B3) molecule provides optimal glycemic control. Aim. To evaluate clinical and economic efficacy of the drug insulin aspart+nicotinamide in comparison with insulin aspart in patients with diabetes mellitus. Materials and Methods. Clinical and economic analysis was performed in accordance with the standards and recommendations valid in the Russian Federation, the method of cost-effectiveness analysis for the first model population of patients with type 1 diabetes and the method of cost-minimization analysis for the second model population of patients with type 2 diabetes, modeling horizon was 26 weeks. Since the study is conducted from the per- spective of the health care system only direct medical costs were considered, that is, the cost of insulin therapy and the cost of complications treatment (hypoglycemia). During the budget impact analysis, the source of data on the target population was the registry of patients with diabetes mellitus of the Russian Federation. Probabilistic sensitivity analysis was performed to assess the impact of changes in the input parameters of the models. Results. Insulin aspart+nicotinamide has a clinical advantage in the effective- ness of HbA1c reduction in type 1 diabetes population. In patients with type 2 diabetes, the effectiveness of insulin aspart+nicotinamide and insulin aspart is comparable by a similar criterion. Direct medical costs of insulin aspart+nicotinamide are 10.64% lower in comparison with insulin aspart use in type 1 and type 2 diabetes patients’ population. The CER value in type 1 diabetes patient population for insulin aspart is 70% higher compared to insulin aspart+nicotinamide (7,410,353.83 and 4,348,513.94 RUR respectively). Budget impact analysis results are the following: that complete replacement of insulin aspart with insulin aspart+nicotinamide over 3 years is accompanied by a 5.3% re- duction of regional drug benefit budget costs. Conclusion. The clinical and economic analysis confirms the economic feasibility of insulin aspart + nicotinamide use

Anciferov M.B., .., Galstyan G.R., Demidov N.A., Zilov A.V., Kolbin A.S., Koteshkova O.M., Kurganovich A.V., Kurylev A.A., Mayorov A.Y., Markova T.N., Pashkova E.Y. 1006

RELEVANCE. Traditional criteria for assessing glycemic control (HbA1c, fasting plasma glucose, and postprandial glycemia) have limited information value for assessing the risk of adverse outcomes in diabetes mellitus (DM). It was found that increased glycemic variability (GV) has a clear relationship with the risk of developing severe hypoglycemia. GV is an independent predictor of diabetes vascular complications, general and cardiovascular mortality in type 2 diabetes. Currently, the mechanisms of severe GV negative effect on the occurrence and progression of diabetes complications have been studied. According to the international consensus on the use of continuous glucose monitoring (CGM) in 2017 and 2019, the calculation of the coefficient of variation (КВ) based CGM data is used to assess GV with the optimal recommended duration of monitoring at least 14 days (Tab.1). However, the CGM procedure has its limitations: it is expensive, usually carried out within 5-7 days maximum. PURPOSE. To develop a unified method for GV assessing acceptable for widespread use in routine practice by comparing the CV calculated using CGM and self-measured blood glucose (SMBG) with the calculation of the minimum period and minimum number of measurements without loss of correlation. MATERIALS AND METHODS. The retrospective analysis based on routine research of CGM and SMBG data (583 measurements) in 35 patients with T1D. The patients performed self-control during ~ 17 days (95 CI: 14.88-18.43). The simulation was carried out by the Monte Carlo method, for each patient m = 1500 times were taken from the CGM data during each day. The following parameters were determined by the method of simulation modeling: the time of the first measurement, the number of measurements per day, the duration of the self-control period to maximize the sensitivity and specificity of the algorithm. RESULTS. An algorithm was developed and validated for assessing CV according to SMBG data, which provides for: at least 7 measurements per day. The duration of the self-control period at least 14 days. The maximum error in assessing the variability is observed when the CV value calculated from SMBG data falls within the range of 35% - 40%, which requires CGM. If CV value below 35% and above 40% it can be concluded with an accuracy of at least 95% that the true CV is low or high. CONCLUSIONS. The resulting algorithm for assessing the CV according to SMBG data provides a sensitivity and specificity of at least 96% and 84%, respectively.

Balykina Y.E., Kolbin A.S., Kurylev A.A., Pavlysh A.V., Proskurin M.A. 5095

Abstract: A pharmacoeconomic evaluation of sunitinib as the firstline metastatic renal-cell carcinoma targeted agent in the Russian healthcare settings was performed in comparison with sorafenib and bevacizumab + interferon. A pharmacoeconomic Markov model was created and used to assess the costs and effectiveness (including mean overall survival in months) of each therapeutic regimen. The evaluation presented also includes a probabilistic multivariate sensitivity analysis. The results show that sunitinibbased treatment is dominant over sorafenib and bevacizumab + interferon, which makes it the most costeffectiveness treatment option.

Balykina Y.E., Kolbin A.S., Kurylev A.A., Proskurin M.A. 4731

Objective of this study was to determine cost-effectiveness of vemurafenib in treatment of inoperable or metastatic melanoma in patients with BRAF V600 mutation from Russian healthcare system perspective and a long-term use. Cost-effectiveness analysis (CEA) has been used and cost-effectiveness ratio (CER) has been calculated. Incremental analysis has been conducted with calculation of incremental cost-effectiveness ratio (ICER) when exceeding the costs and effectiveness of one of the studied regimens as compared to the other one. Cost analysis included calculation of the following direct costs (DC): the cost of the main disease treatment (cutaneous melanoma, CM) – costs of the drug; the cost of laboratory and instrumental methods of investigation as well as hospitalizations and out-patient treatment; the cost required to determine exon 15 BRAF mutation in melanoma; the cost of the drug therapy aimed at management of adverse events (AEs) caused by the drug when treating the main disease. Two medical technologies have been assessed (anti-tumor regimens depending on the chosen method): vemurafenib at a dose of 960 mg twice a day; dacarbazine at a dose of 1000 mg/m2 i/v every 3 weeks. Mathematical modelling underlies this study. As a result it has been demonstrated that the use of vemurafenib strategy in treatment of metastatic melanoma in patients with BRAF V600 mutation had better progression-free survival (PFS) rate throughout the entire modelling horizon. The use of vemurafenib in treatment of metastatic and inoperable melanoma in patients with BRAF V600 mutation is economically advisable taking into account the data on effectiveness (PFS). The use of vemurafenib in patients with BRAF V600 mutation is an absolutely innovative medical technology which currently does not have any alternative. Vemurafenib may be indicated for inclusion in reimbursement lists for treatment of patients with this mutation.

Balykina Y.E., Globin M.V., Kolbin A.S., Kurylev A.A., Litvinova A.A., Proskurin M.A. 1612

Balykina Y.E., Kolbin A.S., Kurylev A.A., .., Proskurin M.A. 1245

Glycemic control is a clinical goal in the treatment of diabetes mellitus. Currently available bolus insulin analogues do not follow the physiological pattern of insulin secretion after meals because they are slowly absorbed from the injection site. Insulin aspart+nicotinamide is an ultra-fast acting human insulin analog that can be administered before or after meals and the nicotinamide (vitamin B3) molecule provides optimal glycemic control. Aim. To evaluate clinical and economic efficacy of the drug insulin aspart+nicotinamide in comparison with insulin aspart in patients with diabetes mellitus. Materials and Methods. Clinical and economic analysis was performed in accordance with the standards and recommendations valid in the Russian Federation, the method of cost-effectiveness analysis for the first model population of patients with type 1 diabetes and the method of cost-minimization analysis for the second model population of patients with type 2 diabetes, modeling horizon was 26 weeks. Since the study is conducted from the per- spective of the health care system only direct medical costs were considered, that is, the cost of insulin therapy and the cost of complications treatment (hypoglycemia). During the budget impact analysis, the source of data on the target population was the registry of patients with diabetes mellitus of the Russian Federation. Probabilistic sensitivity analysis was performed to assess the impact of changes in the input parameters of the models. Results. Insulin aspart+nicotinamide has a clinical advantage in the effective- ness of HbA1c reduction in type 1 diabetes population. In patients with type 2 diabetes, the effectiveness of insulin aspart+nicotinamide and insulin aspart is comparable by a similar criterion. Direct medical costs of insulin aspart+nicotinamide are 10.64% lower in comparison with insulin aspart use in type 1 and type 2 diabetes patients’ population. The CER value in type 1 diabetes patient population for insulin aspart is 70% higher compared to insulin aspart+nicotinamide (7,410,353.83 and 4,348,513.94 RUR respectively). Budget impact analysis results are the following: that complete replacement of insulin aspart with insulin aspart+nicotinamide over 3 years is accompanied by a 5.3% re- duction of regional drug benefit budget costs. Conclusion. The clinical and economic analysis confirms the economic feasibility of insulin aspart + nicotinamide use

Anciferov M.B., .., Galstyan G.R., Demidov N.A., Zilov A.V., Kolbin A.S., Koteshkova O.M., Kurganovich A.V., Kurylev A.A., Mayorov A.Y., Markova T.N., Pashkova E.Y. 1006

RELEVANCE. Traditional criteria for assessing glycemic control (HbA1c, fasting plasma glucose, and postprandial glycemia) have limited information value for assessing the risk of adverse outcomes in diabetes mellitus (DM). It was found that increased glycemic variability (GV) has a clear relationship with the risk of developing severe hypoglycemia. GV is an independent predictor of diabetes vascular complications, general and cardiovascular mortality in type 2 diabetes. Currently, the mechanisms of severe GV negative effect on the occurrence and progression of diabetes complications have been studied. According to the international consensus on the use of continuous glucose monitoring (CGM) in 2017 and 2019, the calculation of the coefficient of variation (КВ) based CGM data is used to assess GV with the optimal recommended duration of monitoring at least 14 days (Tab.1). However, the CGM procedure has its limitations: it is expensive, usually carried out within 5-7 days maximum. PURPOSE. To develop a unified method for GV assessing acceptable for widespread use in routine practice by comparing the CV calculated using CGM and self-measured blood glucose (SMBG) with the calculation of the minimum period and minimum number of measurements without loss of correlation. MATERIALS AND METHODS. The retrospective analysis based on routine research of CGM and SMBG data (583 measurements) in 35 patients with T1D. The patients performed self-control during ~ 17 days (95 CI: 14.88-18.43). The simulation was carried out by the Monte Carlo method, for each patient m = 1500 times were taken from the CGM data during each day. The following parameters were determined by the method of simulation modeling: the time of the first measurement, the number of measurements per day, the duration of the self-control period to maximize the sensitivity and specificity of the algorithm. RESULTS. An algorithm was developed and validated for assessing CV according to SMBG data, which provides for: at least 7 measurements per day. The duration of the self-control period at least 14 days. The maximum error in assessing the variability is observed when the CV value calculated from SMBG data falls within the range of 35% - 40%, which requires CGM. If CV value below 35% and above 40% it can be concluded with an accuracy of at least 95% that the true CV is low or high. CONCLUSIONS. The resulting algorithm for assessing the CV according to SMBG data provides a sensitivity and specificity of at least 96% and 84%, respectively.