Control of public expenditure on drug products in Bulgaria – Policies and outcomes

Aim: The aim of this study was to assess the economic performance of the application of the policy for negotiating discounts on drug products and agreements on the controlled access of patients in Bulgaria. Methods: The methodology involves comparison of the amounts of public spending on medicines in two periods – during the course of the analyzed drug policies (January 2007 – June 2009), and the period in which negotiations on the price of medicines and programs for the controlled access of the patients was discontinued (July 2009 – December 2012). Results: In Bulgaria, the government did not apply methods for controlling publicexpenditure on medicines bargaining price concessions from manufacturers andimplementing agreements on controlled access of patients after June 2009. This led to an annual increase in the expenditures on drug products for home treatment (on average, 17% for the period 2009-2012). Conclusion: This trend in Bulgaria will continue in the future since expenditure control only through price control by means of a reference system and the positive list of medicines is ineffective. There is a need for implementation of combined drug policies in Bulgaria in the form of negotiations on rebates with manufacturers and agreements on controlled access of patients and reference pricing

Analysis Of The Efficiency Of Historical Treatment Costs Of Patients With Invasive Fungal Infections

Изследването представя моделиране на локални данни за разходи и здравни ползи на CYP51 инхибиторите (CYP51i) за лечение на инвазивни гъбични инфекции, и реализиране на косвено сравнение, базирано на мрежов метаанализ. Резултатите от нашата оценка се потвърждават от резултатите от оценките на същите технологии, проведени в Испания и САЩ. Voriconazole е разходно ефективна терапия в сравнение с fluconazole за лечение и профилактика на инвазивни гъбични инфекции (ICER 1020 лв./QALY) и доминира itraconazole с подобрена терапевтична ефикасност и по-нисък разход за курс на лечение. Posaconazole не е разходно ефективна терапия в сравнение с voriconazole поради твърде високата си цена и неблагоприятно инкрементално съотношение на допълнителни разходи и допълнителни здравни ползи (ICER 145 000 лв./QALY).The study presents the modeling of local data on the costs and health benefits of CYP51 inhibitors (CYP51i) for the treatment of invasive fungal infections and the implementation of an indirect comparison based on network meta-analysis. The results of our assessment are confirmed by the results of the same health technology assessments conducted in Spain and the United States. Voriconazole is a cost-effective therapy compared to fluconazole for pharmacotherapy and prevention of invasive fungal infections (ICER 1020 lv / QALY) and dominates itraconazole with improved therapeutic efficacy and lower cost of treatment. Posaconazole is not cost-effective therapy compared to voriconazole because of its too high cost and an unfavorable incremental cost-benefit ratio and additional health benefits (ICER 145 000 lv./QALY)

Public expenditure and drug policies in Bulgaria in 2014

Aim: The objective of this study was to provide an analysis of the factors which have a significant impact on the growth of public expenditure on medical products in Bulgaria. Methods: This research work consists of a critical analysis of the data reported by theNational Health Insurance Fund in Bulgaria on the stability of the healthcare insurance model and the implementation of the budget for 2014. Results: The results from the current analysis indicate that the growth of public expenditure is directly proportional to the number of reimbursed medical products and that the pattern of prescriptions including the innovative medical products mainly for the treatment of oncological and rare diseases has a significant impact on it. Conclusion: The reasons for the increase of public expenditure in Bulgaria include the non-transparent decisions in pricing and reimbursement of the products, the lack of guidelines for presenting pharmacological evidence and the lack of legislatively-defined drug policies for the management and control of the patterns of medical prescriptions

Clinical And Cost Efficacy Of Immunotherapy As A First Line Of Treatment Of Nonsquamous Metastatic Non-Small-Cell Lung Cancer

The aim of the study was to modelling local data on costs and health benefits of alternative immunotherapies for first-line treatment of patients with non-squamous metastatic non-small cell lung cancer (ncqNSCLS) and to make an indirect comparison of their health cost ratios and benefits based on network meta-analysis. The inputs data for the model were measured and evaluated clinical endpoints in the randomized multicentre clinical trials IM power 130, KEYNOTE 189, and Check Mate 026. Modelling data for future health benefits and costs after the end of clinical trials using Markov model had three health states, one of which is an absorbent condition. Tree Age Pro Healthcare software was used to modelling the data. Atezolizumab in combination with chemotherapy (nab-paclitaxel, carboplatin) is a cost-effective first-line therapy for patients with nsqNSCLC compared to pembrolizumab in combination with chemotherapy (pemetrexed, carboplatin) and nivolumab immunotherapy alone. A probabilistic susceptibility analysis found that the probability of atezolizumab in combination with chemotherapy being a cost-effective therapy compared to pembrolizumab in combination with chemotherapy and compared to nivolumab monotherapy was 88% and 75%, respectively. Modelling data on health benefits and costs after the end of clinical trials creates some uncertainty about therapeutic efficacy and safety in the long-term monitoring

Cost-Effectiveness Analysis Of The Prevention And Treatment Of Cytomegalovirus (CMV) Infections After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) In Adults

Целта на изследването е да се представи моделиране на локални данни за разходи и здравни ползи на алтернативните антивирусни терапии за профилактика и лечение на цитомегаловирус (CMV) - серопозитивни пациенти след алогенна трансплантация на хемопоетични стволови клетки (HSCT) и да се реализира косвено сравнение, базирано на мрежов метаанализ. Входящи данни в мо- дела са измерените и оценени клинични крайни точки в рандомизираното многоцентрово клинично изпитване МК-8228-001. Моделирането на данните за бъдещи здравни ползи и разходи след края на клиничните изпитвания е проведено чрез модел на Марков с 6 здравни и 1 абсорбиращо състояние. В модела са включени всички възможни здравни състояния, отразяващи хода на заболяването, и са предвидени всички вероятности за преход от едно здравно състояние в друго. Входящите данни в модела са първичните и вторичните крайни точки в рандомизираното клинично изпитвани МК- 8228-001 - клинично значима CMV инфекция на седмица 12-а и 24-та, превантивна терапия за CMV виремия и крайни органни заболявания, свързани с CMV. Времевият хоризонт на модела е до живот. Разходите и ползите са дисконтирани с 5% годишно. Избраната перспектива е гледната точка на третата страна платец.Заключението от проведените оценки е, че letermovir доминира valganciclovir с подобрена тера- певтична ефикасност и по-нисък разход за курс на лечение на CMV-серопозитивните пациенти след HSCT.The aim of the study was to model the local data on the costs and health benefits of alternative antiviral therapies for the prevention and treatment of CMV seropositive patients after HSCT and to perform an indirect comparison based on meta-analysis. Input data in the model are the measured and evaluated clinical endpoints in the randomized multicentre clinical trial MK-8228-001. The modeling of the data for future health benefits and costs after the end of the clinical trials was conducted using a Markov model with 6 health conditions and 1 absorbent state. The model includes all possible health conditions reflecting the course of the disease and all the probabilities of transition from one health condition to another are envisaged. Input data in the model are the primary and secondary endpoints in the randomized clinical trial MK-8228-001 - clinically significant CMV infection at weeks 12 and 24, preemptive therapy for CMV viremia and CMV-related terminal organ diseases.The time horizon of the model is lifelong. Costs and benefits are discounted at 5% per annum. The perspective chosen is the point of view of the third party payer. The conclusion of the evaluations is that letermovir dominates valganciclovir with improved therapeutic efficacy and lower cost of treatment for cytomegalovirus-seropositive patients after allogeneic hematopoietic stem cell transplantation

Health technology assessment of Ixekizumab for treatment of plaque psoriasis in Bulgaria

Целта на изследването е чрез анализ на публикувани данни от оценки на здравни технологии за лечение на плакатен псориазис (ПП), проведени в други страни, да се моделират разходите и здравните ползи на ixekizumab в сравнение с терапевтичните алтернативи, използвани в българската клинична практика. Косвеното сравнение чрез мрежов метаанализ включва ixekizumab, secukinumab, ustekinumab, adalimumab, etanercept, infliximab. Използваният икономически анализ е разход-полезност. Проучването стига до извода, че Ixekizumab е разходно ефективна терапия за лечение на пациенти с плакатен псориазис, след неуспех със стандартна терапия в България, в сравнение с ustekinumab, adalimumab и infliximab.The aim of the study is to analyze the published data from health technology assessments for the treatment of plaque psoriasis (PS) conducted in other countries to model the costs and health benefits of ixekizumab compared to the therapeutic alternatives used in Bulgarian clinical practice. Indirect comparison through network meta-analysis includes ixekizumab, secukinumab, ustekinumab, adalimumab, etanercept, infliximab. The economic analysis used is cost-utility. The study concludes that Ixekizumab is a cost-effective treatment for patients with plaque psoriasis after failure with standard therapy in Bulgaria compared to ustekinumab, adalimumab and infliximab

Enfortumab vedotin for the treatment of patients with urothelial cancer after failure of the treatment with PD-1/PD-L1 inhibitor—cost-effectiveness analysis

Introduction: Bladder cancer (BC) is one of the most common malignancies in industrialized countries. The incidence of BC increases with age and is almost 3 times more common in men than in women. The therapy in adult patients with locally advanced or metastatic BC who have previously received chemotherapy containing platinum and a PD-1/PD-L1 inhibitor requires the inclusion of enfortumab vedotin (EV) or docetaxel- or paclitaxel-based chemotherapy.Aim: The aim of the study is to model local data on long-term costs and health benefits from the application of alternative health technologies for the treatment of patients with BC to decide which therapy has an advantage in terms of the ratio of therapeutic efficacy and cost-effectiveness.Materials and Methods: Inputs in the prognostic model used were measured and evaluated as clinical endpoints in the EV-301 multicentre randomized clinical trial. The modelled data on future health benefits and costs after the end of the clinical trial are based on Markov’s model with three health conditions, one of which is absorbent.Conclusion: Despite therapeutic superiority of enfortumab vedotin over chemotherapy (docetaxel, paclitaxel), it is not a cost-effective approach to treat patients with urothelial carcinoma after failure with PD-1/PD-L1 inhibitors. The only reason for this is its high price. The value of the cost-benefit ratio of enfortumab vedotin is around BGN 659,000/QALY and significantly exceeds the cost-effectiveness threshold (ICER ≤ BGN 50,000/QALY), which is equal to three times the gross domestic product per capita of the population in Bulgaria for the previous year

Comparative bioavailability of a newly developed Irbesartan 300 mg containing preparation

Introduction: Irbesartan (CAS registry: 138402-11-6) is a potent, orally active, selective antagonist of the angiotensin II receptors (type AT1) indicated for the treatment of arterial hypertension and chronic heart failure. Aim: The objective of the present study was to demonstrate the bioequivalence of an oral test preparation (Irbesartan 300 mg film-coated tablets Tchaikapharma High Quality Medicines Inc., Bulgaria) and a reference (Aprovel 300 mg film-coated tablets, Sanofi Clir SNC, France), by comparing the rate and extent of absorption of both products upon a single oral administration of the tablets under fasting conditions in healthy volunteers. Methodology: The study was carried out as a single-center, open-label, randomised, twoperiod, single dose, crossover oral bioequivalence study in 40 healthy male and female subjects under fasting conditions. During each study period blood samples for analysis of irbesartan were taken prior to dosing and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours after dosing. The separated plasma was analyzed in the bioanalytical division of Anapharm Europe with a validated method using reversed phase high performance liquid chromatography coupled to a tandem mass spectrometry detector (RP-LC/MS/MS). Results: The point estimates with 90% confidence intervals of the geometric mean ratios of test and reference (T/R) in the study were found to be 102.39% (95.55% - 109.71%) for Cmax and 98.56 % (92.72 % - 104.76 %) for AUC0-72. Thus, the corresponding ratios of Cmax and AUC0-72 met the predetermined criteria for bioequivalence (90% confidence intervals of the geometric mean ratios of test and reference within the 80.00% - 125.00%). Both products were generally very well tolerated. Conclusions: Irbesartan 300 mg film-coated tablets, Tchaikapharma High Quality Medicines Inc., Bulgaria) and Aprovel 300 mg film-coated tablets (Sanofi Clir SNC, France), are bioequivalent with regard to the rate and extent of absorption

Post COVID-19 Conditions and the Cardiovascular System

One out of four patients affected by COVID-19 will experience persistent (>3-4 weeks) signs and symptoms (Post COVID-19 conditions or Post-Acute Sequelae of SARS-CoV-2 – PASC) and this fact will have a major significance for the healthcare and economic systems in the upcoming years. The cardiovascular system is one of the key targets for the Post COVID-19 syndrome, given the pathogenesis of the virus and prevalence of ACE-2 receptors. According to our initial personal experience via the campaign “Life after COVID” of the Bulgarian Cardiac Institute, a substantial proportion of patients having suffered from COVID-19 develop long-term cardiovascular consequences. They could range from rhythm disorder and blood pressure variation, through impairment of myocardial mechanics and heart failure, and to acute vascular manifestations of Post COVID-19 conditions, such as acute coronary syndrome, acute pulmonary embolism, and acute limb ischemia. These cardiovascular complications require special and dedicated medical attention, and we could share our personal experience on the matter

Control of public expenditure on drug products in Bulgaria – Policies and outcomes

Aim: The aim of this study was to assess the economic performance of the application of the policy for negotiating discounts on drug products and agreements on the controlled access of patients in Bulgaria.Methods: The methodology involves comparison of the amounts of public spending on medicines in two periods – during the course of the analyzed drug policies (January 2007 – June 2009), and the period in which negotiations on the price of medicines and programs for the controlled access of the patients was discontinued (July 2009 – December 2012).Results: In Bulgaria, the government did not apply methods for controlling publicexpenditure on medicines bargaining price concessions from manufacturers andimplementing agreements on controlled access of patients after June 2009. This led to an annual increase in the expenditures on drug products for home treatment (on average, 17% for the period 2009-2012).Conclusion: This trend in Bulgaria will continue in the future since expenditure control only through price control by means of a reference system and the positive list of medicines is ineffective. There is a need for implementation of combined drug policies in Bulgaria in the form of negotiations on rebates with manufacturers and agreements on controlled access of patients and reference pricing