Introduction: There are positive aspects regarding the prescribing of fixed dose combinations (FDCs) versus prescribing the medicines separately. However, these have to be balanced against concerns including increased costs and their irrationality in some cases. Consequently, there is a need to review their value among lower- and middle-income countries (LMICs) which have the greatest prevalence of both infectious and noninfectious diseases and issues of affordability. Areas covered: Review of potential advantages, disadvantages, cost-effectiveness, and availability of FDCs in high priority disease areas in LMICs and possible initiatives to enhance the prescribing of valued FDCs and limit their use where there are concerns with their value. Expert commentary: FDCs are valued across LMICs. Advantages include potentially improved response rates, reduced adverse reactions, increased adherence rates, and reduced costs. Concerns include increased chances of drug:drug interactions, reduced effectiveness, potential for imprecise diagnoses and higher unjustified prices. Overall certain FDCs including those for malaria, tuberculosis, and hypertension are valued and listed in the country’s essential medicine lists, with initiatives needed to enhance their prescribing where currently low prescribing rates. Proposed initiatives include robust clinical and economic data to address the current paucity of pharmacoeconomic data. Irrational FDCs persists in some countries which are being addressed.

Introduction: Appropriately managing mental disorders is a growing priority across countries in view of the impact on morbidity and mortality. This includes patients with bipolar disorders (BD). Management of BD is a concern as this is a complex disease with often misdiagnosis, which is a major issue in lower and middle-income countries (LMICs) with typically a limited number of trained personnel and resources. This needs to be addressed. Areas covered: Medicines are the cornerstone of managing patients with Bipolar II across countries including LMICs. The choice of medicines, especially antipsychotics, is important in LMICs with high rates of diabetes and HIV. However, care is currently compromised in LMICs by issues such as the stigma, cultural beliefs, a limited number of trained professionals and high patient co-payments. Expert opinion: Encouragingly, some LMICs have introduced guidelines for patients with BD; however, this is very variable. Strategies for the future include addressing the lack of national guidelines for patients with BD, improving resources for mental disorders including personnel, improving medicine availability and patients’ rights, and monitoring prescribing against agreed guidelines. A number of strategies have been identified to improve the treatment of patients with Bipolar II in LMICs, and will be followed up.

Background To date, a multi-country review evaluating the cost-of-illness (COI) studies from the Central and Eastern European (CEE) region has not yet been published. Our main objective was to provide a general description about published COI studies from CEE. Methods A systematic search was performed between 1 January 2006 and 1 June 2017 in Medline, EMBASE, The Cochrane Library, CINAHL, and Web of Science to identify all relevant COI studies from nine CEE countries. COI studies reporting costs without any restrictions by age, co-morbidities, or treatment were included. Methodology, publication standards, and cost results were analysed. Results We identified 58 studies providing 83 country-specific COI results: Austria (n = 9), Bulgaria (n = 16), Croatia (n = 3), the Czech Republic (n = 10), Hungary (n = 24), Poland (n = 11), Romania (n = 3), Slovakia (n = 3), and Slovenia (n = 4). Endocrine, nutritional, and metabolic diseases (18%), neoplasms (12%), infections (11%), and neurological disorders (11%) were the most frequently studied clinical areas, and multiple sclerosis was the most commonly studied disease. Overall, 57 (98%) of the studies explicitly stated the source of resource use data, 45 (78%) the study perspective, 34 (64%) the costing method, and 24 (58%) reported at least one unit costs. Regardless of methodological differences, a positive relationship was observed between costs of diseases and countries’ per capita GDP. Conclusions Cost-of-illness studies varied considerably in terms of methodology, publication practice, and clinical areas. Due to these heterogeneities, transferability of the COI results is limited across Central and Eastern European countries.

Biological medicines are considered as a cornerstone in the therapy of rheumatoid arthritis (RA). They change the course of the disease and improve the quality of life of patients. To this date there has been no study comparing the quality of life of and cost of RA therapy in Bulgaria. This fact is what provoked our interest toward this research. The aim of this study is to analyse the cost and quality of life of patients with RA threated with biological medicines in Bulgaria. This is an observational, real life study of 124 patients treated with biological medicines during 2012–2016 at the University hospital “St. Ivan Riskli” in Sofia, specialized in rheumatology disease therapy. Patients were recruited after their consecutive transfer from non-biological to biological medicines. The yearly pharmacotherapy cost was calculated with tocilizumab (n = 30), cetrolizmab (n = 16), golimumab (n = 22), etanercept (n = 20), adalimumab (n = 20), rituximab (n = 16). Three measurements of the quality of life (QoL) were performed with EQ5D—at the beginning of the therapy, after 6 months and after 1 year of therapy. Both section of EQ5D were used—VAS and EQ5D questionnaire. Cost—effectiveness was calculated for unit of improvement in EQ5D score for a one year period and decision model was built with TreeAgePro software. The observed cost of therapy varied between 12 thousand Euros for tocilizumab to 6 thousand Euros for rituximab. All biological medicines let to substantial increase in the quality of life of the patients. Patients on tocilizumab increased their QoL from 0.43 to 0.63 after 1 year; on cetrolizumab from 0.32 to 0.56; on golimumab from 0.41 to 0.67; on etanercept from 0.45 to 0.62; on adalimumab from 0.43 to 0.57; on rhituximab from 0.46 to 0.66. The cost-effectiveness estimates of different biological therapies also varied between 66 to 30 thousand Euros for unit of improvement in the EQ5D during one the course of the year. Therapy with biological medicines improves statistically significant the quality of life of patients, measured through VAS and EQ5D scales. Despite the improvement in the quality of life all biological medicines appears not to be note cost-effective due to their high incremental cost-effectiveness ration (ICER). Rituximab's incremental ratio has (ICER) falls closer to the three times gross domestic product per capita threshold and should be considered as preferred alternatives for RA therapy. In general we can conclude that the treatment of rheumatoid arthritis with biologicals improves quality of life significantly. Only rituximab was cost-effective.

The purpose of the present analysis is to calculate and compare the costs and results of the implication of the inactivated vaccine against hepatitis A virus (HAV) in the Bulgarian healthcare setting in the period of 2002–2012. A combined pharmacoeconomic and epidemiological study was performed on the basis of the prevalence of hepatitis A infection in this 10-year period. The investments in the vaccination were considered as costs and the avoided costs in the case of vaccination of all one-year old children in the population – as benefits. The results show that the vaccination of one-year-old children would be cost effective to the healthcare system in the years with an epidemiologic outbreak, as in these years the total cost of treatment of patients with hepatitis A infection exceeds the cost for vaccination of the whole one-year-old cohort. The critical threshold is 4600 infected patients per year that equalize the benefits to costs. The inclusion of HAV vaccine in the National Immunization Calendar would be cost effective for the healthcare system when the vaccination is performed in certain risk groups and could help to decrease the circulation of the virus in the general population.

The aim of this study was to calculate the economic and social burden of chronic obstructive pulmonary disease (COPD) in Bulgaria generated from the loss of productivity due to absence from work (absenteeism), due to premature retirement, due to reduced productivity (presenteeism), and the disability adjusted life years (DALY). An observational study among 426 Bulgarian COPD patients was conducted for the period 2014–2015. Human capital approach was used to calculate the productivity losses and the DALY methodology of the World Health Organization was applied. The patients with moderate (50%) and severe (48%) disease were absent from work more frequently than those with mild COPD (2%) and generated productivity losses of 521.45€ per patient per year. The average indirect costs per patient for the remaining working ages due to premature retirement account for 25,000€ (6250 per patient on average), while those due to presenteeism, for about 3750.64€ per year. Accordingly, the DALYs in the group of patients with mild severity were lowest due to the low disutility index and number of patients in this sample group. On average, a patient with mild COPD spends 0.62 years of his life in disability due to the disease, while those with moderate and severe disease spend 6.00 and 9.00 years, respectively. This amounted to the following indirect costs experienced by patients: 3596.52€; 34,204.01€; 51,332.20€, respectively. We demonstrated a significant indirect financial and societal burden of COPD in Bulgaria, which is in correlation with the severity of the disease.