Factors associated with hematological adverse reactions of drugs authorized via the centralized procedure.

Serious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization and even cause death. The aim of this study was to determine the regulatory factors associated with HADRs caused by drugs that were authorized up to July 2023 by the European Medicines Agency (EMA) and to evaluate the frequency of HADRs. Using a cross-sectional approach, the type and frequency of HADRs were collected from the Summaries of Product Characteristics of Drugs Authorized by the EMA and analyzed within proprietary, nonproprietary, and biosimilar/biological frameworks. Multivariate statistical analysis was used to investigate the associations of generic status, biosimilar status, conditional approval, exceptional circumstances, accelerated assessment, orphan drug status, years on the market, administration route, and inclusion on the Essential Medicines List (EML) with HADRs. In total, 54.78% of proprietary drugs were associated with HADRs at any frequency, while anemia, leucopenia, and thrombocytopenia were observed in approximately 36% of the patients. The predictors of any HADR, anemia, and thrombocytopenia of any frequency are generic status, biosimilar status, and inclusion on the EML, while the only protective factor is the administration route. Biosimilars and their originator biologicals have similar frequencies of HADRs; the only exception is somatropin. Knowledge of the regulatory factors associated with HADRs could help clinicians address monitoring issues when new drugs are introduced for the treatment of patients.

Prospective systematic risk analysis of the digital technology use within pharmaceutical care.

BACKGROUND: Digital technologies are present in every phase of a drug lifecycle, from drug design and development to its dispensing and use. However, given the rapid development and implementation of digital solutions, their monitoring, evaluation and risk assessment are limited and lacking. OBJECTIVE: This research is aiming to identify potential errors, quantify and prioritize associated risks in the context of certain technologies used in pharmaceutical care, as well as define corrective measures to improve patient safety and the quality of pharmaceutical care. METHODS: A ten-member multidisciplinary team conducted Failure Mode & Effect Analysis (FMEA) to identify critical risks, their causes and effects, along with developing corrective measures within the selected digital health components: Telepharmacy, mHealth, Artificial intelligence (AI) and Software infrastructure and systems. Critical risks were determined by calculating risk priority numbers (RPNs) from severity, occurence, and detectability scores. RESULTS: This study identified 42 risks regarding the 4 components. After calculating RPNs and the threshold RPN (RPN=30), 8 critical risks were identified. Corrective measures were proposed for these failure modes, after which the risks were re-evaluated (RPN sum was reduced from 414 to 156). The risk with the highest RPN value was Internet/identity fraud, while the rest included inadequate and incomplete data entry and management, flawed implementation, human and technology errors, and lack of transparency, personalization and infrastructure. For the critical risks, 42 different causes were recognized on a system, technological and individual level while their effects were discussed in terms of patient safety and business management in pharmacies. CONCLUSION: Digitalization of pharmaceutical practice promises greater effectiveness of pharmaceutical care, but in order to achieve this, efforts, resources and initiatives must be directed towards timely identification of problems, appropriate monitoring and building adequate infrastructure that can support safe implementation of digital tools and services despite the swift development of innovations.

Exploring experiences of pharmacists and pharmacy students using mHealth apps: A qualitative study of user experience.

PURPOSE: Pharmacists can enhance mHealth delivery by promoting the awareness and use of health apps, while pharmacy students and early career pharmacists allow broader perspective for further development. This study aimed to explore the experiences and attitudes of pharmacy students and pharmacists, on the use, advantages and possible improvement of available mHealth platforms in Serbia. METHODS: One-on-one interviews were conducted online in two phases, during March and April 2020 (n = 40) and during March 2021 (n = 20), using a published, validated interview guide which was adapted for this study. Interviews were transcribed ad verbatim, coded and thematically analysed. RESULTS: Although participants recognized room for optimization, most apps had satisfactory user experience. Participants used health apps as a source of updated information and tools in education and work, but also for self-development. During working hours, participants mostly used medication-related apps, however, it was shown that they use different health apps in order to provide the best possible care to patients. CONCLUSIONS: Greater insight into usage, expectations, benefits and challenges of mHealth in pharmacy was obtained and can lead into better informed design of health apps to encourage students and pharmacists, both as professionals and individuals, on the path of their continuous improvement.

SMART Pharmacists Serving the New Needs of the Post-COVID Patients, Leaving No-One Behind.

This study aims to demonstrate the improvements in clinical symptoms in patients with post-COVID syndrome after a community pharmacy-based intervention in Serbia. The Pharmaceutical Chamber of Serbia ("Chamber") invited pharmacists to deliver post-COVID patient care counselling, supported by the SMART Pharmacist Program, offering education and guidance. Present symptoms, duration and patient self-reported severity of symptoms on a scale of 1-5 on the first visit were recorded. After the counselling and proposed self-medication treatment, the time of the follow-up visit and the severity of the recorded symptoms were also recorded. The prospective data collection lasted from December 2021 to September 2022. In total, 871 patients with post-COVID symptoms were included in the study, served by 53 pharmacists. The most frequently reported post-COVID symptoms coincided with the literature, mostly related to the respiratory system (51.2%), immunity status (32.2%), fatigue and exhaustion (30.7%), skin, hair and nails (27.4%) and cognitive functions (27.9%). A total of 26.5% of patients were referred to their family physician (general practitioner), and 69.5% returned to the pharmacist for a follow-up visit. On the first visit, the median severity of patients' symptoms was three, while on the second visit it dropped to one. The pharmacists' intervention led to a significant improvement in the post-COVID patients' condition.

A cross-sectional study comparing emotional intelligence and perceived stress amongst community pharmacists delivering and not delivering a new service.

BACKGROUND: Community pharmacists contribute substantially to public health and person-centred care. Emotional intelligence (EI) may help health professionals better engage with patients, handle stress in challenging situations and, presumably, better introduce and implement new services. AIM: The study's aims were to compare the EI and perceived stress (PS) levels of community pharmacists who provided a new service to patients with diabetes with their controls who provided standard pharmaceutical services and to test the correlations between the two constructs. METHOD: This study used a survey methodology. Well-validated instruments were distributed electronically to all participating pharmacists. To compare the continuous EI and PS data between the two study groups, the paired-samples t test was used. Pearson and Spearman's correlations were used to test the associations between EI and PS and their respective subdomains. RESULTS: A total of 86 pharmacists participated in the study (n = 43 in each group). The study groups did not differ by any characteristic except gender. Their mean EI and PS levels were 120.95 ± 11.53 and 17.45 ± 4.55, respectively, with no difference between the groups. In both study groups, inverse correlations were found between PS and EI levels, with statistical significance in the control group and in the overall study population (r = - 0.611 and r = - 0.370, respectively). CONCLUSION: Our results suggest that the introduction of the EI agenda into certification programmes for new community pharmacy services should be considered. The results also suggest that higher EI may have protective effects against PS. Additional research would clarify the need to invest more in such programmes.

Emotional intelligence and pharmaceutical care: A systematic review.

BACKGROUND: Emotional intelligence (EI) can help perceive, understand, and manage emotions and positively impact performance in any profession, including pharmacists, and consequently may have positive influence on patient-related outcomes. Although there is strong body of evidence suggesting that developing EI in health professionals (HPs) can increase their capacity to successfully communicate and build relationships with patients, thus increasing patient satisfaction, little is known about it in pharmaceutical care (PhC). OBJECTIVES: This review aimed to synthesize available data on the probable impact of EI on PhC. METHODS: PubMed, Web of Science, and Embase databases were searched for papers in English dated between January 2000 and June 2021. Quantitative, qualitative, or mixed method studies on EI and PhC that involved practicing pharmacists were included. RESULTS: The inclusion criteria were met by 4 papers only. One reported positive impact of EI in reducing the negative correlation between autistic-like traits and empathy among hospital pharmacists. One study demonstrated that EI levels can be significantly enhanced through pharmacy leadership programs. Another study established a positive correlation between EI and entrepreneurial orientation in practicing community pharmacists. Higher EI scores were predictors of increased work innovation, proactivity, and risk-taking levels. One study reported comparative EI data between different HPs and found pharmacists' superiority in the EI subdomains of self-awareness, self-motivation, and social skills. CONCLUSION: Additional research is required to provide evidence on how EI and EI development programs can add value to the provision of PhC. Processes and resources ought to be developed and secured to support the implementation and follow-up of such programs to bring long-term benefits to practicing pharmacists and consequently positively impacting patient-reported health outcomes.

Pharmacists' clinical knowledge and practice in the safe use of contraceptives: real knowledge vs. self-perception and the implications.

BACKGROUND: Pharmacists are often the first healthcare professionals that patients contact with their illnesses and requests for medical information, which is enhanced following the recent COVID-19 pandemic. Community pharmacists are expected and required to possess a broad spectrum of knowledge and skills. Self-assessment of these competencies is needed for their self-improvement. PURPOSE OF THE STUDY: To assess pharmacists' clinical knowledge and practice in the safe use of contraceptives, and to compare the scores obtained by external observation with pharmacists' self-assessment of their knowledge as well as investigate the significance of preceptorship experiences. Contraceptives was chosen as the subject area in view of high rates of abortions as a means of contraception in Bosnia and Herzegovina. METHODS: A questionnaire approach was used. The questionnaire included the following: the first domain contained two case scenarios (safe use of contraceptives), which evaluated clinical knowledge, a second domain in which pharmacists self-assessed their knowledge to resolve cases from the first domain and a third domain that measured the demographics of pharmacists (including experience in preceptorship). Dispensing practice was evaluated in the second domain. The questionnaires were distributed to a convenient sample of 100 pharmacists at the Annual Meeting of Bosnia and Herzegovina Pharmacists. The results were presented as counts (%). The groups (preceptors and non-preceptors) were compared using Mann-Whitney U test, paired assessments were analyzed by Wilcoxon signed-rank test and Spearman's correlation was used to assess the correlation between variables. RESULTS: Of the 100 pharmacists invited to participate, 84 completed the questionnaire (84 % response rate). There was no agreement between pharmacists' real knowledge (average score - case 1: 2.71, case 2: 3.3) and their self-assessment (average score - case 1: 3.77, case 2: 3.91). There was no statistically significant difference in the actual knowledge of pharmacists (experienced/non-experienced in precepting), while the difference in the self-assessment was significant between these two groups. CONCLUSION: Pharmacists appear to overrate themselves, which leads to self-enhancement bias, in which the experience in precepting has some influence. Pharmacists' capability in performing an objective self-assessment of their clinical knowledge needs to be carefully studied in the future to fully benefit patients.

Using Prospective Risk Analysis Tools to Improve Safety in Pharmacy Settings: A Systematic Review and Critical Appraisal.

OBJECTIVES: This study aimed to review and critically appraise the published literature on 2 selected prospective risk analysis tools, Failure Mode and Effects Analysis and Socio-Technical Probabilistic Risk Assessment, as applied to the dispensing of medicines in both inpatient and outpatient pharmacy settings. METHODS: A comprehensive search of electronic databases (PubMed and Scopus) was conducted (January 1990-March 2016), supplemented by hand search of reference lists. Eligible articles were assessed for data sources used for the risk analysis, uniformity of the risk quantification framework, and whether the analysis teams assembled were multidisciplinary. RESULTS: Of 1011 records identified, 11 articles met our inclusion criteria. These studies were mainly focused on dispensing of high-alert medications, and most were conducted in inpatient settings. The main risks identified were transcription, preparation, and selection errors, whereas the most common corrective actions included electronic transmission of prescriptions to the pharmacy, use of barcode, and medication safety training. Significant risk reduction was demonstrated by implementing corrective measures in both inpatient and outpatient pharmacy settings. The main Failure Mode and Effects Analysis limitations were its subjectivity and the lack of common risk quantification criteria. CONCLUSIONS: The prospective risk analysis methods included in this review revealed relevant safety issues and hold significant potential for risk reduction. They were deemed suitable for application in both inpatient and outpatient pharmacy settings and should form an integral part of any patient safety improvement strategy.

Predictors and Motivation of Preceptors' Interest in Precepting of Pharmacy Interns-Do We Have a Useful Questionnaire?

PURPOSE: To determine the potential value of an adapted questionnaire to discover the predictors of preceptors' higher interest in precepting pharmacy interns and to evaluate preceptors' motivational factors and incentives for teaching as well as their professional satisfaction. METHOD: A link to the survey study of adapted questionnaire (JSAMPPP) was e-mailed to all pharmacists registered with the Pharmaceutical Chamber of the Republic of Srpska. Pharmacists' demographic and work experience characteristics, their attitudes related to motivation for precepting, value of incentives for precepting, job satisfaction, and influence of interns on pharmacists' professional practice were obtained. RESULTS: Half of the preceptors who reported feeling satisfied with their professional life also showed interest in teaching. In addition, teaching pharmacy students positively contributed to the overall job satisfaction of the preceptors. Pharmacy preceptors were found to be most motivated by intrinsic factors. The most valued incentives reported were those related to continuing education. CONCLUSIONS: The adapted questionnaire has potential value and it revealed the following predictors of preceptors' higher interest in precepting: enjoyment of teaching, satisfaction with professional life, satisfaction as a pharmacy preceptor, and interns' influence on preceptors. These identified predictors can be emphasized to improve pharmacy students' internship experiences, thereby reinforcing the pharmacy profession.

Supporting Innovative Person-Centred Care in Financially Constrained Environments: The WE CARE Exploratory Health Laboratory Evaluation Strategy.

The COST CARES project aims to support healthcare cost containment and improve healthcare quality across Europe by developing the research and development necessary for person-centred care (PCC) and health promotion. This paper presents an overview evaluation strategy for testing 'Exploratory Health Laboratories' to deliver these aims. Our strategy is theory driven and evidence based, and developed through a multi-disciplinary and European-wide team. Specifically, we define the key approach and essential criteria necessary to evaluate initial testing, and on-going large-scale implementation with a core set of accompanying methods (metrics, models, and measurements). This paper also outlines the enabling mechanisms that support the development of the "Health Labs" towards innovative models of ethically grounded and evidenced-based PCC.

Applicability of EU(7)-PIM criteria in cross-national studies in European countries.

BACKGROUND: The European Union (EU)(7)-PIM (potentially inappropriate medication) list presents the most comprehensive and up-to-date tool for evaluation of PIM prescribing in Europe; however, several country-specific studies have documented lower specificity of this list on pharmaceutical markets of some countries. The aim of our study was to describe approval rates and marketing of PIMs stated by EU(7)-PIM criteria in six EU countries [in comparison with the American Geriatric Society (AGS) Beers 2015 criteria]. METHODS: Research teams of six EU countries (Czech Republic, Spain, Portugal, Serbia, Hungary and Turkey) participated in this study conducted by WG1b EU COST Action IS1402 group in the period October 2015-November 2018. Data on approval rates of PIMs and their availability on pharmaceutical markets have been obtained from databases of national drug-regulatory institutes and up-to-date drug compendia. The EU(7)-PIM list and AGS Beers 2015 Criteria (Section 1) were applied. RESULTS: PIMs from EU(7)-PIM list were approved for clinical use more often than those from the AGS Beers 2015 criteria (Section 1). Approval rates for EU(7)-PIMs ranged from 42.8% in Serbia to 71.4% in Spain (for AGS criteria only from 36.4% to 65.1%, respectively). Higher percentages of approved PIMs were documented in Spain (71.4%), Portugal (67.1%) and Turkey (67.5%), lower in Hungary (55.5%), Czech Republic (50.2%) and Serbia (42.8%). The majority of approved PIMs were also currently marketed in all countries except in Turkey (19.8-21.7% not marketed PIMs) and less than 20% of PIMs were available as over-the-counter medications (except in Turkey, 46.4-48.1%). CONCLUSIONS: The EU(7)-PIM list was created for utilization in European studies; however, applicability of this list is still limited in some countries, particularly in Eastern and Central Europe. The EU project EUROAGEISM H2020 (2017-2021) that focuses on PIM prescribing and regulatory measures in Central and Eastern European countries must consider these limits.

Medication use in older patients and age-blind approach: narrative literature review (insufficient evidence on the efficacy and safety of drugs in older age, frequent use of PIMs and polypharmacy, and underuse of highly beneficial nonpharmacological strategies).

INTRODUCTION: The importance of rational drug therapy is increasing with the aging of the population. Since one of the main reasons for inappropriate drug prescribing is also the "age-blind" approach, which results in ageist practices, this narrative literature review focuses on the description of the main barriers related to insufficient individualization of drug regimens associated with such age-blind approaches. METHODOLOGY: A narrative literature review using the PubMed, WoS, Embase, and Scopus databases was conducted by the EU COST Action IS1402. Experts in different scientific fields from six countries (the Czech Republic, Spain, Portugal, Hungary, Serbia, and Turkey) worked in four specific areas: (1) underrepresentation of older adults in clinical trials and clinical and ethical consequences; (2) insufficient consideration of age-related changes and geriatric frailty in the evaluation of the therapeutic value of drugs; (3) frequent prescribing of potentially inappropriate medications (PIMs); and (4) frequent underuse of highly beneficial nonpharmacological strategies (e.g., exercise). RESULTS: Older patients are underrepresented in clinical trials. Therefore, rigorous observational geriatric research is needed in order to obtain evidence on the real efficacy and safety of frequently used drugs, and e.g. developed geriatric scales and frailty indexes for claims databases should help to stimulate such research. The use of PIMs, unfortunately, is still highly prevalent in Europe: 22.6% in community-dwelling older patients and 49.0% in institutionalized older adults. Specific tests to detect the majority of age-related pharmacological changes are usually not available in everyday clinical practice, which limits the estimation of drug risks and possibilities to individualize drug therapy in geriatric patients before drug prescription. Moreover, the role of some nonpharmacological  strategies is highly underestimated in older adults in contrast to frequent use of polypharmacy. Among nonpharmacological strategies, particularly physical exercise was highly effective in reducing functional decline, frailty, and the risk of falls in the majority of clinical studies. CONCLUSION: Several regulatory and clinical barriers contribute to insufficient knowledge on the therapeutic value of drugs in older patients, age-blind approach, and inappropriate prescribing. New clinical and observational research is needed, including data on comprehensive geriatric assessment and frailty, to document the real efficacy and safety of frequently used medications.

The association of clopidogrel and 2-oxo-clopidogrel plasma levels and the 40 months clinical outcome after primary PCI.

Background A significant number of ischemic events occur even when adhering to dual antiplatelet therapy including aspirin and clopidogrel. Objectives The aim of our study was to determine predictors of long-term patient clinical outcome, among variables such as prodrug clopidogrel and intermediary metabolite 2-oxoclopidogrel concentrations, as well as patients' clinical characteristics. Setting Department for the Treatment of Acute Coronary Syndrome in tertiary teaching hospital, Serbia. Methods This study enrolled 88 consecutive patients with first STEMI, treated with primary PCI, within 6 h of the chest pain onset and followed them 40 months. On the third day of hospitalization, blood samples were collected from each patient to measure clopidogrel and its metabolite 2-oxo-clopidogrel concentration by UHPLC-DAD-MS method. Main outcome measure Mortality from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke or hospitalization for urgent myocardial revascularization or heart failure. Results The composite clinical outcome of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for urgent myocardial revascularization or heart failure, was registered in 31 patients (35.2%) during the 40-month follow-up. Lower clopidogrel (p < 0.05) and dose-adjusted clopidogrel concentrations (p < 0.05) were associated with the higher incidence of composite outcome events. Their low plasma concentrations may be predicted by fentanyl administration (p < 0.001) and creatinine clearance (p < 0.01). The decrease in dose-adjusted clopidogrel unit for each ng/ml/mg increases the risk 21.7 times (p < 0.05). Conclusion Clopidogrel dose-adjusted plasma concentration in STEMI patients, as well as multivessel coronary artery disease, showed significance in predicting an unfavorable composite clinical outcome after 40-month follow-up.

Undiagnosed Hyperglycaemia and Hypertension as Indicators of the Various Risk Factors of Future Cardiovascular Disease Among Population of Serbian Students.

BACKGROUND: A number of risk behaviours, such as smoking, overweight, excessive alcohol intake, insufficient physical activity, excessive and frequent intake of salt, reduced fruit and vegetable intake, increased fat intake, which constitute living habits of an individual can influence the occurrence of hypertension and hyperglycaemia. The changing of these lifestyles can reduce the risk of developing prehypertension and prediabetes. METHODS: The survey was conducted at student's campuses. The respondents were subjected to the height, weight, blood glucose and blood pressure. Respondents filled in previously created questionnaire that was approved by the Ethics Committee for Biomedical Research Faculty of Pharmacy, University of Belgrade. RESULTS: The percentage of respondents with a glucose value above the reference value was 14.6% (n=19), 2.4% (n=3) had values greater than 7 mmol/L without being diagnosed with diabetes, and accordingly, 2.4% (n=3) had elevated HbA1c values (above 42 mmol/mol or 6.0%). The percentage of respondents with elevated systolic and diastolic blood pressure was 14.9% and 7.4% respectively. Regarding calculated risk scores, they showed parallel increase with increas-ing of BMI (HPS), systolic and diastolic pressure (OHS), and glucose concentration (OPS). CONCLUSIONS: When analysing all the factors that could cause the later development of diabetes, which is associated with hypertension as well, it is observed that the student population is very much exposed to those factors. The results of this study cannot be representative for the general population of students, but they can provide recommendations for further research.

Prospective systemic risk analysis of the dispensing process in German community pharmacies.

BACKGROUND: Medicine dispensing represents an error-prone activity, carrying a considerable risk for patients. OBJECTIVE: To prospectively identify and prioritize potential failure modes in the medicine dispensing process as well as to develop corrective actions for patient safety improvement in German community pharmacies. METHOD: Failure mode and effects analysis was performed in 2 community pharmacies in North Rhine-Westphalia, Germany, in October 2016. A 9-member team was assembled, comprising of a leader and process experts who prospectively assessed the medicine dispensing process by brainstorming, quantified the attributed risks, proposed corrective actions, and reassessed the risks. RESULTS: The analysis identified 39 failure modes, out of which the highest criticality scores were assigned to inadequate assessment of therapy appropriateness (Risk Priority Number 45), reluctance to deviate from rebate contracts (36), and dispensing the wrong medicine (30). The corrective actions proposed demonstrated a considerable potential for risk reduction in most failure modes, the most effective of which were introducing obligatory continuous education for pharmacists, organizing communication training, and implementing electronic prescribing. CONCLUSION: This analysis not only detected various potential safety issues concerning the dispensing in Germany but also strongly indicated that application of failure mode and effects analysis could be highly effective in prospective risk reduction in community pharmacies.

Towards medicines regulatory authorities' quality performance improvement: value for public health.

The purpose of this article is to explore the possibility of implementing total quality management (TQM) principles in national medicines regulatory authorities in Europe to achieve all public health objectives. Bearing in mind that medicines regulation is a governmental function that serves societal objectives to protect and promote public health, measuring the effective achievement of quality objectives related to public health is of utmost importance. A generic TQM model for meeting public health objectives was developed and was tested on 10 European national medicines regulatory authorities with different regulatory performances. Participating national medicines regulatory authorities recognised all TQM factors of the proposed model in implemented systems with different degrees of understanding. An analysis of responses was performed within the framework of two established criteria-the regulatory authority's category and size. The value of the paper is twofold. First, the new generic TQM model proposes to integrate four public health objectives with six TQM factors. Second, national medicines regulatory authorities were analysed as public organisations and health authorities to develop a proper tool for assessing their regulatory performance. The paper emphasises the importance of designing an adequate approach to performance measurement of quality management systems in medicines regulatory authorities that will support their public service missions.

[Contribution of pharmacists to the development of healthcare culture in Vranje by the end of the 19th century and in the first half of the 20th century].

INTRODUCTION: Healthcare enlightenment and healthcare culture in Vranje and its region were under Turkish influence until the liberation in 1878, when the organisation of education, schooling and healthcare were initiated in the Vranje region OBJECTIVE: The aims of this study were to shed light on the beginning of the development of pharmaceutical personnel, and their contribution to healthcare culture development in Vranje and its region, with a focus on healthcare legislation and its impact on pharmaceutical service availability, and the analysis of pharmaceutical personnel development within the healthcare services. METHODS: We used the methods of documentation analysis and the desk analysis of the secondary information. RESULTS: At the beginning of the 19th century healthcare services in Vranje were still inexistent. After the liberation from the Turks, Naum's medical office with pharmacy was opened in Vranje. Although it did not comply with regulations, it presented the only formal source of supply of medications and sanitary material, and as such it gave its contribution to healthcare service at that time in Vranje. Mr ph. Stevan Varjacic, 1st class pharmacy assistant, worked at a temporary hospital from 1880 until January 1881, suppling with medications soldiers and residents of Vranje. The development of pharmaceutical schooling began in 1883, when a pharmacy was opened by the pharmacist Velimir Karic according to the Law on Healthcare Organisation and People's Healthcare Maintenance. By the end of the 1930s there were ten civilian healthcare institutions in Vranje, even three of which were pharmacies. By the end of 1948, they were nationalized, and were renamed the City National Pharmacy of Vranje. CONCLUSION: By the end of the 10th century, passing of the legislation on the regulations of pharmaceutical industry within healthcare services had an impact on Vranje that resulted in opening pharmacies with educated pharmaceutical personnel. Pharmacy owners changed, and the quality and continuity of medical supplies was always secured.

[Analysis of regulatory-ethical framework of clinical trials].

INTRODUCTION: Every clinical trial has to meet all ethical criteria in addition to the scientific ones. The basic ethical principles in the clinical trials are the following: nonmaleficence, beneficence, respect for autonomy and the principle of justice. OBJECTIVE: The aim of the study was to analyse clinical cases with the outcomes leading to the changes in regulatory-ethical framework related to the clinical trials, as well as the outcomes of key clinical trials that influenced the introduction of the ethical principles into clinical trials. METHODS: This was a descriptive research (methods of analysis and documentation; desk analysis of the secondary data). RESULTS: By analysing the cases from the secondary sources as well as clinical and ethical outcomes, it may be noticed that the codes, declarations and regulations have been often preceded by certain events that caused their adoption. Moral concern and public awareness of the ethical issues have initiated not only the development of numerous guidelines, codes, and declarations, but also their incorporation into the legislative acts. CONCLUSION: It is desirable that ethical instruments become legally binding documents, because only in this way will be possible to control all phases of the clinical trials and prevent abuse of the respondents.