Economic Burden of Cervical Cancer in Bulgaria.

Bulgaria is among the European Union (EU) countries with the highest burden of cervical cancers and life expectancy below the EU average. The majority of cervical cancer cases (more than 95%) are caused by the human papillomavirus (HPV). The aim of this retrospective, cost of illness study is to identify direct healthcare costs of cervical cancer in Bulgaria from the payer perspective and to calculate indirect costs and the associated years of life lost. Costs data were sourced from the National Health Insurance Fund from January 2018 to December 2020. Years of life lost were calculated based on the country and gender-specific life expectancy. Indirect costs due to productivity loss were calculated using the human capital approach. The total treatment costs for 3540 patients with cervical cancer are EUR 5,743,657 (2018), EUR 6,377,508 (2019), and EUR 6,751,182 (2020). The costs associated with drug acquisition and administration accounted for the majority (63%) of total healthcare costs followed by hospital management costs (14%). An estimated total of 20,446 years of life were lost due to cervical cancer for the period 2018-2020. The costs of productivity losses are estimated at EUR 7,578,014. Our study showed that the economic burden of cervical cancer in Bulgaria is substantial. Focus on cervical cancer prevention via vaccination against the human papillomavirus, timely screening, early diagnosis, and higher vaccine coverage rates could reduce its economic burden in Bulgaria.

Survey on Sildenafil, Tadalafil, and Vardenafil Concentrations in Food Supplements for Erectile Dysfunction.

The aim of the study was to analyze the presence of undeclared sildenafil, tadalafil, and vardenafil in food supplements (FSs) for erectile dysfunction. The presence of sildenafil, tadalafil, and vardenafil was determined using the generated ultraviolet (UV)-spectra and mass-spectrometry (MS)-spectra as well as chromatograms produced by the photodiode array (PDA)-detector and ion trap MS-detector. The results were processed by Xcalibur ver. 2.0.7. Fourteen of the 20 analyzed FSs contained undeclared ingredients. Sildenafil was present in 12 of them. Many violations and discrepancies between the label information and the real composition of the FS were identified. 70% of the samples contained undeclared ingredients of an erectile dysfunction medicinal product. The quantities varied within broad limits from 2 mg per tablet to 116.55 mg per tablet. Sildenafil was present in amounts exceeding 16.55 mg that is the maximum recommended dose, thus creating risk of overdose. Besides that, food supplements adulterated with sildenafil analogues are a health risk for consumer's health as there is no evidence of modified sildenafil toxicity. All analyzed FSs were claimed to be 100% natural, not provoking side effects. No information for any FS contained indications of age limits or risk for interaction with other FSs or medical products.

Study of clinical experience with different approaches to controlled ovarian hyperstimulation: a focus on safety and efficacy.

OBJECTIVES: Current retrospective cohort study analyses clinical database records of 4792 assisted reproduction procedures to assess the significance of target effectiveness endpoints from a safety perspective. METHODS: Stimulation protocols with urinary, recombinant or combination of both types gonadotrophin preparations are compared according to the following primary endpoints: incidence of ovarian hyperstimulation syndrome (OHSS), cycle cancellation, follicle count, induced estradiol values, clinical pregnancy achieved and cycles reached embryo transfer/freezing. We have investigated the incidence of cases evaluated as 'risky for OHSS' by secondary efficacy endpoints (exogenous gonadotrophin exposure, luteinising hormone and progesterone values, oocyte yield, eggs with normal maturation). The following statistical methods were applied: descriptive statistics, Mann-Whitney U test, Kruskal-Wallis test, Pearson chi-square test, Fisher's exact test, binary logistic regression. RESULTS: Only 16 cases (0.42%) of moderate and delayed OHSS were established. Three hundred and seven (8.6%) stimulation cycles have been cancelled, principally among urinary protocols. Although the clinical pregnancy rate does not differ significantly in compared groups, punctured follicle count, oocyte yield and progesterone level were higher for recombinant preparations, followed by combined and urinary protocols. Follicle count, mean estradiol and luteinising hormone levels are within the 'safe window' for all investigated groups, associated with minimised risk of stimulation cancellation. The mean follicle-stimulating hormone (FSH) dose was highest in urinary protocols at the same duration of stimulation compared with recombinant products. The younger age, bigger follicle count, oocytes yield, mature oocytes count, percentage of fertilised oocytes, more embryos transferred and the later day of embryo transfer are critical for both assisted reproduction techniques (ART) success rate and the safety profile of sterility treatment. CONCLUSIONS: Safety surveillance of ART exceeds the incidence of OHSS. Suboptimal effectiveness of stimulation protocols may also jeopardise the well-being of ART patients. Gonadotrophin exposure, induced values of sex hormones, and quantity and quality of extracted oocytes should be considered to minimise any unintended suffering of treated couples.

Pharmacotherapeutic recommendations for application of target oncological drug therapies for treatment of breast cancer in Bulgaria - therapeutic efficacy and cost effectiveness.

PURPOSE: The purpose of this study was to determine the direct costs of targeted cancer therapies for the treatment of breast cancer, calculating the effectiveness of the additional costs (ICER) and the cost of life years gained (LYG), using data from randomized clinical trials cited in the summary of product characteristics (SPC) of medicinal products approved for use under the centralized procedure. METHODS: Data from the SPC and clinical trials was analyzed. ICER and LYG of the medicinal therapies were compared using data from Phase III clinical trials cited in the Summary of product characteristics. The perspective of the payer was adopted. RESULTS: The SPCs of five drugs were analyzed. Targeted therapies were compared to placebo or to best supportive care (BSC) in some of them, while in others monoclonal antibodies (mAbs) and tyrosine kinase inhibitors were compared to existing drug therapies. Cost-effectiveness of each therapy was calculated. The value of ICER was between 56 470 Bulgarian Levs/LYG and 879 480 Bulgarian Levs/LYG. CONCLUSION: The current pharmacotherapeutic recommendations for targeted therapies for the treatment of breast cancer are based on evidence of therapeutic efficacy and cost effectiveness. Their application in therapeutic practice in Bulgaria is necessary to ensure patient access to effective therapies within the limited public funds.

Practical tool to assess reliability of web-based medicines information.

AIM: Information disseminated by medicines information systems is not always easy to apply. Nowadays internet provides access to enormous volume and range of health information that was previously inaccessible both for medical specialists and consumers. The aim of this study is to assess internet as a source of drug and health related information and to create test methodology to evaluate the top 10 visited health-related web-sites in Bulgaria. METHODS: Using existing scientific methodologies for evaluation of web sources, a new algorithm of three-step approach consisting of score-card validation of the drug-related information in the 10 most visited Bulgarian web-sites was created. RESULTS: In many cases the drug information in the internet sites contained errors and discrepancies. Some of the published materials were not validated; they were out-of-date and could cause confusion for consumers. CONCLUSION: The quality of the online health information is a cause for considerable information noise and threat to patients' safety and rational drug use. There is a need of monitoring the drugs information available online in order to prevent patient misinformation and confusion that could lead to medication errors and abuse.

Physicians' knowledge and attitude towards adverse event reporting system and result to intervention--randomized nested trial among Bulgarian physicians.

AIM: To identify the factors that influence physicians' under-reporting in Bulgaria and their attitude towards adverse event reporting system and to estimate the role of self-education by providing educational materials. METHODS: A randomized nested trial among physicians-general practitioners and specialists in Bulgaria was conducted by a validated questionnaire in order to evaluate their knowledge and attitude towards adverse event reporting system. One month after the intervention the participants were re-visited and were asked to answer the same questions again in order to estimate the change in their knowledge and attitude towards pharmacovigilance system and to obtain their evaluation for the materials provided. RESULTS: The response rate was 91. Fifty seven (46.3%) physicians were not familiar with the pharmacovigilance system. The most common reason for non-reporting adverse drug reactions (ADRs) was uncertainty concerning the relationship between the suspected drug and ADRs, the ADRs were already known and the fact that the physician was not aware where they should report. Although 103 (83.7%) respondents in the entry survey and by 102 (82.9%) of those participating in the exit survey consider ADRs reporting as their obligation (p more than 0.05), only 50 (40.7%) and 31 (25.2%), respectively answered that they had ever reported ADRs; 109 (88.6%) of the surveyed physicians assessed the provided educational materials as useful for them. CONCLUSION: The physicians in Bulgaria have poor knowledge for the pharmacovigilance system; however self-education leads to a better knowledge and positive attitude towards ADRs reporting system. National drug regulatory authority should play a more active role in improving physicians' adherence to the ADRs reporting systems and the developed educational pack can be used in nationwide campaign.

Study of obligations defined in agreements between parties involved in clinical trials of medicinal products in Bulgaria.

AIM: To analyse and assess the legislative and contractual obligations of the parties involved in the conduct of clinical trials, with identification of the needs for comprehensive contractual regulation of their rights and responsibilities. METHODS: This survey has been carried out by means of review, analysis of comprehensiveness, comparative legislative analysis and assessment of compliance with the legislation of sample of investigator and site agreements governing the process of conducting clinical trials. RESULTS: The survey comprises analyses of contractual relations between the sponsor of the study and the investigator, and between the sponsor of the study and the trial site, respectively, relevant to clinical trials which are actually conducted in Bulgaria at the time of and following the survey. Comparative method based on pre-defined structured indices was employed to outline the major variances in the volume of responsibilities and obligations of the said parties to the clinical trial, as regulated by the investigator and site agreements. The analysis of comprehensiveness showed evident omissions in the regulation of relations and interactions between the parties to the agreements. CONCLUSION: The detailed contractual regulation providing for the statutory obligations and responsibilities of the parties involved in the conduct of clinical trials is a good guarantee for proper understanding of the obligations of each party and for compliance with their relevant responsibilities in view of protecting the rights of the participants in the clinical trials - patients or healthy volunteers.