Ljiljana Tasic

Validation of the osteoporosis quality of life questionnaire QUALEFFO-41 for the Serbian population

BackgroundVertebral fractures could lead to reduced physical, social and mental functioning, and loss of personal independence. Therefore, during the treatment of osteoporosis, it has become necessary to examine the changes in everyday functioning, well-being and health related quality of life (HRQOL). To that effect, this study aims to translate, culturally adapt, and validate the Serbian version of Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) for patients with vertebral fractures.MethodsNine female patients with osteoporosis participated in the pre-validation study. A validation, case–control study included two groups of female patients: one that consisted of 50 female patients with osteoporosis, and with at least one vertebral fracture, and another one that consisted of 50 control patients with osteoporosis but without fractures. They completed the QUALEFFO-41 and the EuroQol group questionnaire with five dimensions (EQ-5D) twice within a month. The validation study examined internal consistency, concurrent validity, test-retest reliability, sensitivity and specificity.ResultsDuring the pre-validation study, three of the items in the QUALEFFO-41 were slightly changed. Afterwards, during the validation study, the statistically significant differences (adjusted for: age, duration of menopause, current employment and marital status) in the mean values of all domains and total scores between the groups were noted. For the case group, the internal consistency of the QUALEFFO-41 domains and of total questionnaire was above 0.70. The test-retest reliability was tested by the intraclass correlation coefficients (ICC) that were in range 0.87 – 0.96 for the case, and 0.15 – 0.83 for the control group. Correlations between the total scores of the QUALEFFO-41 and the EQ-5D health state value, for both groups were negative and statistically significant (r = -0.78, p<0.001 and r = -0.73, p<0.001, respectively). The QUALEFFO-41 had a better prediction of the value of HRQOL of cases compared to the generic questionnaire EQ-5D (the AUC difference was 0.099, p = 0.013).ConclusionsThe Serbian QUALEFFO-41 version is reliable, valid, sensitive and predictive for examinations of HRQOL in patients with prevalent vertebral fractures and can be used in further studies.

Surface Treatment of Indomethacin Agglomerates with Eudragit

Indomethacin is a widely used anti‐inflammatory drug with serious side‐effects. This drug was used as a model drug for the coating of agglomerates with a permeable film (Eudragit NE). The agglomeration of the crystals increased the flowability of the bulk crystals. The coating further improved the flowability, and also the uniformity of the mass of the filled capsules. The coating film also influenced the wetting of the samples. The coating decreased the surface free energy and therefore reduced the adhesion forces between both the dry and the wet particles. The modification of the flow properties and the even capsule filling can be explained by this phenomenon. Since coating film does not dissolve in the artificial gastric juice, the dissolution test was performed only in the artificial intestinal juice. The dissolution of indomethacin from the coated sample was changed significantly. Accordingly, coating of the crystals can be performed in order to protect the mucosa of the gastrointestinal tract or to promote the preparation of solid dosage form.

Examination of the Regulatory Frameworks Applicable to Biologic Drugs (Including Stem Cells and Their Progeny) in Europe, the U.S., and Australia: Part I—A Method of Manual Documentary Analysis

Recent development of a wide range of regulatory standards applicable to production and use of tissues, cells, and other biologics (or biologicals), as advanced therapies, indicates considerable interest in the regulation of these products. The objective of this study was to analyze and compare high‐tier documents within the Australian, European, and U.S. biologic drug regulatory environments using qualitative methodology. Cohort 1 of the selected 18 high‐tier regulatory documents from the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and the Therapeutic Goods Administration (TGA) regulatory frameworks were subject to a manual documentary analysis. These documents were consistent with the legal requirements for manufacturing and use of biologic drugs in humans and fall into six different categories. Manual analysis included a terminology search. The occurrence, frequency, and interchangeable use of different terms and phrases were recorded in the manual documentary analysis. Despite obvious differences, manual documentary analysis revealed certain consistency in use of terminology across analyzed frameworks. Phrase search frequencies have shown less uniformity than the search of terms. Overall, the EMA frameworks documents referred to “medicinal products” and “marketing authorization(s),” the FDA documents discussed “drug(s)” or “biologic(s),” and the TGA documents referred to “biological(s).” Although high‐tier documents often use different terminology they share concepts and themes. Documents originating from the same source have more conjunction in their terminology although they belong to different frameworks (i.e., Good Clinical Practice requirements based on the Declaration of Helsinki, 1964). Automated (software‐based) documentary analysis should be obtained for the conceptual and relational analysis.

Economic burden of cardiovascular diseases in Serbia.

BACKGROUND/AIM Cardiovascular disease imposes a burden to society in terms of mortality, morbidity and economic losses. The aim of this study was to estimate the economic burden of cardiovascular disease in Serbia in 2009 from the perspective of the society. METHODS For the purpose of the study cardiovascular disease was defined by the International Classification of Diseases, 10th revision, as the following diagnosis: hypertension, coronary heart disease, cardiomyopathy, heart failure and cerebrovascular disease. The prevalence, top-down method was used to quantify the annual cardiovascular costs. Productivity losses were estimated using the human capital approach and the friction cost method. A discount rate of 5% was used to convert all future lifetime earnings into the present value. RESULTS The total direct costs of cardiovascular disease in 2009 were Euro 400 million. The results showed that more than half a million working days were lost due to incapacity resulting from cardiovascular diseases, yielding the Euro 113.9 millon. The majority of total costs (Euro 514.3 million) were for: medication (29.94%), hospital days (28.97%) and hospital inpatient care--surgical and diagnostic interventions (17.84%). The results were robust to a change in 20% of volume or the unit price of all direct and indirect cost and to discount rate 2% and 10%. CONCLUSIONS; The total cardiovascular disease costs in 2009 represented approximately 1.8% of the Serbian gross domestic product. The results of the study would be valuable to health policy makers to bridge the gap between invested resources and needs, in order to improve cardiovascular disease outcomes.

From experimental design to quality by design in pharmaceutical legislation

Quality by design (QbD) is a concept first outlined by Juran, who believed that quality could be planned and that most quality crises and problems relate to the way in which quality was planned in the first place. Experimental design is a powerful technique and tool for QbD, used for exploring new processes, gaining increased knowledge of the existing processes and optimizing these processes for achieving internationally competitive performance. It is also used for the investigation of relationship between parameters of ill-defined process. In this paper, the experimental design principles in pharmaceutical development and impact of these principles on pharmaceutical legislation have been reviewed. Also, slow implementation of QbD in pharmaceutical industries has been discussed. Pharmaceutical legislation is necessary for companies to continue benefiting from knowledge gained and to continually improve throughout the process lifecycle by making adaptations to assure that root causes of manufacturing problems are quickly corrected.

Translation and factor analysis of structural models of Edinburgh Postnatal Depression Scale in Serbian pregnant and postpartum women – Web-based study

BACKGROUND The Edinburgh Postnatal Depression Scale (EPDS) is well accepted for detecting symptoms of postnatal depression. The aim of this study was to examine psychometric properties and to evaluate structural models of the Serbian translation of EPDS in pregnant and postpartum women. METHODS The original English version of the EPDS was translated into Serbian, and checked by means of back-translation. Data were collected via an anonymous online questionnaire posted on a Serbian website devoted to pregnancy topics. The study sample included 201 women (76 pregnant, 125 postpartum). The internal consistency of the scale was measured by Cronbachs α coefficient. Principal component analysis was used to determine scale dimensions while confirmatory factor analysis was used to evaluate model fit. FINDINGS Cronbach α coefficient was 0.84 and 0.83 in pregnant and postpartum women, respectively, which indicated good internal consistency of the Serbian EPDS. Three dimensions of the scale were revealed in both groups of women. Goodness of fit indices described good and excellent model in pregnant and postpartum women, respectively. High level of depression symptoms (score ≥13) was recorded in 27.6% and 24.8% (p>0.05) of pregnant and postpartum women, respectively. Moderate level of depression symptoms (score 10-12) was recorded in 21.1% and 16.8% (p>0.05) of pregnant and postpartum women, respectively. CONCLUSION The Serbian translation of the EPDS showed good consistency and good model characteristics in pregnant and postpartum women. However, cut-off values, sensitivity and specificity of the scale should be determined in the further studies with more representative samples of women.

Development of a Shorter Version of the Osteoporosis Knowledge Assessment Tool

The aim of the authors of this study was to develop a short version of the Osteoporosis Knowledge Assessment Tool to be used for the target population of young adult Serbian females as an easily implemented add-on questionnaire. The 20-item Osteoporosis Knowledge Assessment Tool was translated and culturally adapted using the Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes Measures. The validation study was conducted on a sample of 250 female students studying at the Faculty of Pharmacy at the University of Belgrade, during a two-month period (November–December 2010). The difficulty index, item-total correlations, and internal consistency were calculated first. Afterward, confirmatory factor analysis was applied to test the structure of the Osteoporosis Knowledge Assessment Tool models and develop a short version. The mean total Osteoporosis Knowledge Assessment Tool score was 8.31 (possible range 0–20). The confirmatory factor analysis fit indices indicated poor fit of the data to the originally hypothesized structure. The confirmatory factor analysis fit indices, difficulty indices, and content validity allowed trimming of the original model and development of a short version with nine items. The average chi-square value for the Osteoporosis Knowledge Assessment Tool short version was 31.79 (p = 0.240, SE = 0.176) with Bollen–Stine bootstrap p = 0.249, Tucker–Lewis Index = 0.925, Comparative Fit Index = 0.944 and Root Mean Square Error of Approximation = 0.027. The Osteoporosis Knowledge Assessment Tool thus had acceptable characteristics and may be used for osteoporosis knowledge assessment.

Pharmacy network and access to medicines in selected eastern European countries: comparative analysis.

Aim To analyze the pharmacy network (structure and resources) in Bulgaria, Croatia, Serbia, and Slovenia and its relation to public expenditures for medicines. Methods We performed a cross-sectional study using the officially published data for the period 2003-2008 in four selected countries. Data sources were relevant national institutions. Results In 2008, Serbia had 27.5, Bulgaria 66.8, Croatia 59.5, and Slovenia 71.2 pharmacists per 100 000 inhabitants. There was a significant difference in the number of pharmacists per 100 000 inhabitants between all countries except between Bulgaria and Slovenia. The number of inhabitants per one pharmacy was significantly different between all observed countries. The expenditures for medicines per capita in 2008 were between €30.34 in Bulgaria to €137.03 in Slovenia, with a significant difference between all countries except between Bulgaria and Serbia. The number of pharmacists per 100 000 inhabitants and expenditures for medicines per capita were positively correlated in all observed countries, except in Bulgaria. Conclusion There were significant difference in the structure and availability of the pharmacy service in all selected countries. Expenditures for medicines were positively correlated with the number of pharmacists in all countries, except in Bulgaria. Our findings could be valuable to national regulatory bodies for the creation of national drug policies.

Nonsteroidal Anti-Inflammatory Drug Usage and Gastrointestinal Outcomes in the Republic of Serbia

This study assessed the utilization of prescription and over-the-counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs) as well as the rate of self-medication with diclofenac, ibuprofen, and naproxen in the Braneechevo District of the Republic of Serbia. Estimation of gastrointestinal (GI) disease (morbidity) trends and GI toxicity–associated hospitalization were studied and direct costs due to NSAID-induced GI toxicity are presented. This descriptive, retrospective study addressed drug use and outcomes between 2004 and 2006 documented in the Health Insurance Fund database of the Pozarevac Public Pharmacy in the Pozarevac Public Health Centar of the Braneechevo District, which includes 200,503 inhabitants. Data type/selection were defined daily doses (DDD) per 1000 inhabitants per day for utilization of drugs, number of patients with ICD-9 diagnosis codes for GI disorders; GI hospitalization count (average annualy length of stay [in days] and number of GI hospitalizations); direct cost of hospital care. The OTC diclofenac use showed an increasing tendency: 6.2279; 6.5983; 8.2911 DDD units, as well as the utilization of OTC ibuprofen: 2.4389, 2.4899, 2.5776 DDD units, respectively (2004–2006), whereas OTC naproxen had relatively low utilization. In the same period, GI morbidity decreased: 9636, 7982, 7806, respectively, and the number of GI morbidity-associated hospitalizations increased 10.18% in 2005 and 15.06%, in versus 2004. The costs of GI morbidity-associated hospitalizations increased: 12.20% (2005) and 94.51% (2006), compared to 2004 costs with a positive correlation between utility of diclofenac and ibuprofen (self medication) and increased GI hospitalizations in Braneechevo.

An approach to TQM evaluation in pharma business

Purpose – The purpose of this paper is to explore the good practice (GxP) and standardised management system integration within total quality management (TQM) paradigm in pharmaceutical sector in Serbia. Also, the impact of all interested parties on quality management has been assessed. Design/methodology/approach – The cross-sectional study was performed, including different stakeholders within the pharmaceutical sector in Serbia: manufacturers, distributors, big pharma representative offices, as well as national regulatory authority. A survey instrument was developed, consisted of 16 questions, which were organised into four groups: questions in relation to implementation of ISO 9001, implementation of good distribution practice/good manufacturing practice, integration of management systems, and impact on TQM and business excellence. Total number of participants was 121. Findings – Standardised management systems (ISO 9001, ISO 14001, OHSAS 18001) support companies to improve business environment and management sustainability, but this survey indicated that it was ranked at the lower level then GxP, for pharmaceutical sector in Serbia. Although pharmaceutical companies has faced many challenges in recent years, the survey revealed high level of confidence in quality management systems, as well as the necessity of various management systems integration. Originality/value – The perception of TQM by the experts in pharmaceutical companies and regulatory authority is wider than the common TQM definition. From pharmaceutical point of view, TQM is a holistic approach to long-term success of organisation, oriented to all interested parties, with focus on a public health. Risk-based approach in new revision of both ISO and GxP will facilitate integration process towards TQM and business excellence.