An overview of methodological flaws of real-world studies investigating drug safety in the post-marketing setting.

INTRODUCTION: The evaluation of the post-marketing safety profile of drugs is a continuous monitoring process for approved and marketed medicines and it is crucial for detecting new adverse drug reactions. As such, real-world studies are essential to complement pre-marketing evidence with information concerning drug risk-benefit profile and use in wider patient populations and they have a great potential to support post-marketing drug safety evaluations. AREAS COVERED: A detailed description of the main limitations of real-world data sources (i.e. claims databases, electronic healthcare records, drug/disease registers and spontaneous reporting system databases) and of the main methodological challenges of real-world studies in generating real-world evidence is provided. EXPERT OPINION: Real-world evidence biases can be ascribed to both the methodological approach and the specific limitations of the different real-world data sources used to carry out the study. As such, it is crucial to characterize the quality of real-world data, by establishing guidelines and best practices for the assessment of data fitness for purpose. On the other hand, it is important that real-world studies are conducted using a rigorous methodology, aimed at minimizing the risk of bias.

Evaluation of health care professionals' knowledge, attitudes, practices and barriers to pharmacovigilance and adverse drug reaction reporting: A cross-sectional multicentral study.

BACKGROUND: Healthcare professionals' involvement and reporting of adverse drug reactions are essential for the success of a pharmacovigilance program. The aim of this study was to assess healthcare professionals (medical doctors, pharmacists, nurses, dentists, midwives, and paramedics) current knowledge, attitude, practices, and barriers regarding pharmacovigilance and adverse drug reactions reporting in multicentral healthcare settings. METHODS: A cross-sectional face-to-face survey was conducted among currently working healthcare professionals in various hospitals in ten districts of Adana province, Türkiye from March to October 2022. A self-administered, pretested questionnaire (Cronbach's alpha = 0.894 for knowledge, attitudes and practices variables) was used for data collection. The questionnaire's final draft included five sections (sociodemographic/general information, knowledge, attitude, practices, and barriers) with 58 questions. The collected data was analyzed in SPSS (version 25) using descriptive statistics, the chi-square test, and logistic regression. RESULTS: Of the total 435 distributed questionnaires, 412 completed the entire questionnaire, yielding a 94% response rate. The majority of healthcare professionals (60.4%; n = 249) had never received pharmacovigilance training. Among healthcare professionals 51.9% (n = 214), 71.1% (n = 293) and 92.5% (n = 381) had poor knowledge, positive attitudes and poor practices, respectively. Only 32.5% of healthcare professionals kept the record of an adverse drug reaction and only 13.1% reported adverse drug reactions. The profession (medical doctors, pharmacists, nurses, dentists, midwives, and paramedics) of healthcare professionals and a lack of training were predictors of poor adverse drug reaction reporting (p < 0.05). A statistically significant difference in healthcare professionals and knowledge, attitude and practices scores was also observed (p < 0.05). The main barriers which were supposed to discourage adverse drug reactions reporting by the healthcare professionals were higher workload (63.8%) followed by thinking that a single adverse drug reaction report makes no impact (63.6%) and lack of a professional atmosphere (51.9%). CONCLUSION: In the current study, most healthcare professionals had poor knowledge and practice, but they had a positive attitude toward pharmacovigilance and adverse drug reactions reporting. Barriers to under-reporting of adverse drug reactions were also highlighted. Periodic training programs, educational interventions, systematic follow-up of healthcare professionals by local healthcare authorities, interprofessional links between all healthcare professionals, and the implementation of mandatory reporting policies are critical for improving healthcare professionals knowledge, practices, patient safety and pharmacovigilance activities.

Self-medication practices with conventional and herbal drugs among ear, nose, and throat patients.

OBJECTIVE: This study evaluates the self-practices with conventional and herbal drug use among ear, nose, and throat outpatients. METHODS: A cross-sectional survey-based study was carried out among all ear, nose, and throat outpatients on their first visit to the otorhinolaryngology department at a tertiary care hospital. The survey comprised a total of 14 questions with 4 different sections, including demographic characteristics, self-medication of conventional medicines, herbal medication usage, and perception regarding herbal medicines. RESULTS: Overall, 255 questionnaires were distributed among patients, of which 183 completed the questionnaire (response rate=71.7%). Respondents reported self-medication (44.8%) with conventional drugs before visiting a hospital. The most commonly used medicine was analgesics (31.7%) and antibiotics (21.9%). Nearly half of the patients (49.2%) used at least one herbal drug. The most commonly used herbal medications were Tilia cordata (78.8%), Zingiber officinale (62.2%), and Camellia sinensis (45.5%). According to the International Union for Conservation of Nature Red List, most of the medicinal herbs were considered as data deficient/least concern. About 36.6% of the participants perceived that herbal drugs are effective for ear, nose, and throat problems. Moreover, 22.9% of the patients did not know about herbal-drug interaction with other medications. CONCLUSIONS: This study observed a considerable prevalence of self-based practices with conventional and herbal medications. Strict national regulations on conventional and herbal medication access and long-term actions should be implemented to discourage inappropriate drug use.

Self-medication practices with conventional and herbal drugs among ear, nose, and throat patients

SUMMARY OBJECTIVE: This study evaluates the self-practices with conventional and herbal drug use among ear, nose, and throat outpatients. METHODS: A cross-sectional survey-based study was carried out among all ear, nose, and throat outpatients on their first visit to the otorhinolaryngology department at a tertiary care hospital. The survey comprised a total of 14 questions with 4 different sections, including demographic characteristics, self-medication of conventional medicines, herbal medication usage, and perception regarding herbal medicines. RESULTS: Overall, 255 questionnaires were distributed among patients, of which 183 completed the questionnaire (response rate=71.7%). Respondents reported self-medication (44.8%) with conventional drugs before visiting a hospital. The most commonly used medicine was analgesics (31.7%) and antibiotics (21.9%). Nearly half of the patients (49.2%) used at least one herbal drug. The most commonly used herbal medications were Tilia cordata (78.8%), Zingiber officinale (62.2%), and Camellia sinensis (45.5%). According to the International Union for Conservation of Nature Red List, most of the medicinal herbs were considered as data deficient/least concern. About 36.6% of the participants perceived that herbal drugs are effective for ear, nose, and throat problems. Moreover, 22.9% of the patients did not know about herbal-drug interaction with other medications. CONCLUSIONS: This study observed a considerable prevalence of self-based practices with conventional and herbal medications. Strict national regulations on conventional and herbal medication access and long-term actions should be implemented to discourage inappropriate drug use.

Evaluation of Consumers Perspective on the Consumption of Antibiotics, Antibiotic Resistance, and Recommendations to Improve the Rational use of Antibiotics: An Exploratory Qualitative Study From Post-Conflicted Region of Pakistan.

Background: Antibiotics misuse is a global challenge, and the situation is likely to deteriorate in conflict zones with insufficient health services. The misuse of antibiotics is not only associated with antimicrobial resistance but may also lead to serious consequences. This study was aimed to investigate the knowledge, attitude, and practices on antibiotic consumption, antibiotic resistance (ABR), and related suggestions among residents of conflicted zones in Pakistan. Methods: Semi-structured interviews were conducted at community pharmacies between June 2020 and January 2021. The primary findings were ascertained through thematic content analysis. Themes, sub-themes, and categories were drawn from the final analysis. Data analysis was carried out in six steps from getting to know the data to final report development. Results: A total of 20 consumers were interviewed with a mean interview duration of 25.4 min. The average age of participants was 35.1 years, and most of them were males. ABR was unfamiliar to the participants. Most of the participants understood the term "antibiotics," but they did not know how to use them properly. The participants were unable to distinguish between bacterial and viral illnesses. Thirteen participants believed that antibiotics have a faster effect than any other drug. Most of the participants perceived that every antibiotic could cause diarrhea, and pharmacy staff sometimes prefer other medicines such as multivitamins. Consumer practices regarding antibiotic usage and ABR were found to be poor. Most participants recommended that health officials must ensure qualified staff at pharmacies with strict regulations. Five participants said that a leaflet with antibiotic instructions in Urdu (national language) is usually beneficial, especially when making solutions from powder. Conclusions: This study underscored poor knowledge, attitude, and practices among residents of conflicted zones towards antibiotics and ABR. Low literacy rate, unavailability of healthcare facilities, absence of pharmacists at community pharmacies, and uncontrolled sales of antibiotics are some factors attributed to serious hazards, ABR, and irrational use of drugs.

Knowledge, Attitude, and Practices (KAPs) of Community Pharmacists Regarding COVID-19: A Cross-Sectional Survey in 2 Provinces of Pakistan.

OBJECTIVE: The 2019 coronavirus disease (COVID-19) is a global pandemic with no therapy, and pharmacists being a part of the health care system have a vital role in the management of COVID-19. The purpose of this study is to assess the knowledge, attitude, and practices of community pharmacists (CPs) regarding COVID-19. METHOD: An online survey was conducted among 393 CPs in 2 provinces of Pakistan during the lockdown period. A validated questionnaire (Cronbach's alpha, 0.745) was used for data collection. All statistical analyses were analyzed by using SPSS, version 21 (IBM Corp, Armonk, NY). RESULTS: Among 393 participants, 71.5% (n = 281) had good knowledge, 44% (n = 175) had a positive attitude, and 57.3% (n = 225) had good practices regarding COVID-19. Social media (45.29%, n = 178) were reported as the main source to seek information of COVID-19. Good knowledge, age ≥ 26 years, and a PhD degree level were the substantial determinants (P = < 0.05) of a good attitude. Similarly, a CP with experience of > 5 years, a PhD degree, good knowledge, and a good attitude has higher odds of having good practices as compared with reference categories (P = < 0.05). CONCLUSION: In short, a majority of the CPs had good knowledge but had a poor attitude and practice toward the management of COVID-19. Standard-structured educational and counseling programs for CPs regarding COVID-19 are needed for effective management.

Prescription analysis and cost of antidepressant drugs in major depressive disorder outpatients at the tertiary care hospital of Pakistan: a prospective approach.

OBJECTIVES: To assess prescribing care indicators, utilization pattern, cost per prescription, cost ratios, and percent cost variation of antidepressants (ADs). METHOD: A prospective cross-sectional study was carried out at the tertiary care hospital of Peshawar, Pakistan among major depressive disorder (MDD) outpatients from July 2019 to February 2020. The ideal standards for World Health Organization (WHO) prescribing care indicators were used. The ePharma Guide was used to calculate the cost in Pakistani rupees (Rs) and United States dollar (USD) 2021 (exchange rate: 1 USD = 154.43 Rs). RESULTS: A total of 296 MDD patients received 846 drugs (average 2.86; range:1-8), of which 366 were ADs (average number ADs/prescription; 1.23). About 23% (n = 68) of patients received more than one AD. Only 21 (5.7%) generic ADs were prescribed, and 346 (94.5%) ADs were prescribed from the hospital formulary list. Selective serotonin reuptake inhibitors (SSRIs) were the most prescribed ADs (67.5%). The average cost of ADs per prescription per month was 700.95 Rs (4.54 USD). Escitalopram (5.69 Rs; 0.04 USD) showed highest cost ratio and maximum percentage cost variation (468.97%). CONCLUSION: This study observed low generic prescribing, a higher prescribing trend of SSRI, wide differences in cost ratio and percentage cost variation among ADs.

Knowledge, attitude, practice and barriers towards pharmacovigilance and adverse drug reactions reporting among healthcare professionals in Turkey: a systematic review.

BACKGROUND: Globally, pharmacovigilance (PV) is crucial for the patient's safety and proper use of drugs. Spontaneous reporting of adverse drug reaction (ADR) is a professional obligation of every healthcare professionals (HCPs). The purpose of this systematic review was to analyze the existing literature about the knowledge, attitude, and practices (KAP) level of HCPs regarding PV and ADRs reporting in Turkey. METHODS: A systematic and comprehensive articles search strategy was carried out in different seven electronic databases (PubMed, PubMed Central, Goggle Scholar, Ovid-SP, MEDLINE, Wiley Online Library, DergiPark) from 2010 to 2020. We searched to identify existing literature about cross-sectional observational studies investigating the KAP of HCPs regarding PV and ADRs reporting in different geographical regions of Turkey. Quality assessment and risk of bias were assessed among included studies. RESULTS: Fifteen studies were chosen for full-text analysis. Finally, according to inclusion criteria, seven research articles were selected for systematic review. Overall, the KAP of HCPs varies across the studies. The lack of a standardized validated measuring tool to evaluate the KAP and differences in questionnaire items were the main limitations in included studies. Around, 69.1% (range: 54.6-100%) of HCPs were not aware of the national pharmacovigilance center in Turkey. About, 37.5% (range: 7.1-75.7%) of HCPs believed that reporting of ADRs is not important and 87.5% (range: 69.3-100%) stated that they never reported ADR previously during their practice. The most frequently highlighted barriers to PV were lack of time, uncertainty and did not know where to report. CONCLUSION: This systematic review revealed a major KAP gap in Turkey towards PV activities. Low ADR reporting practice of HCPs was a major identified issue. The creation of a mandatory unified PV education intervention for future HCPs to rationally report ADR of drugs are crucial for a better healthcare system.

Evaluation of Adverse Drug Reactions in Paediatric Patients: A Retrospective Study in Turkish Hospital.

Drug safety in paediatric patients is a serious public health concern around the world. The paediatric patients are more prone to adverse drug reactions (ADRs) than adults. Moreover, there is a scarcity of information about ADRs in paediatric patients. This study was conducted to determine the frequency, causality, severity, preventability of paediatric patients' ADRs reported in a tertiary care hospital in Adana, Turkey. A retrospective study was conducted on all spontaneously reported ADRs between January 01, 2020, to July 30, 2021, in paediatric patients. The ADRs reports were evaluated in terms of gender, age, ADR characteristics, suspected drugs and reporting source. All included ADRs reports were characterized according to the Naranjo Algorithm/World Health Organization (WHO) causality scales, Hartwig/Siegel and Common Terminology Criteria for Adverse Events (CTCAE) severity scales, the modified Schoumock and Thornton preventability scale and hospital pharmacovigilance center criteria for seriousness. Therapeutic groups were also coded using the WHO-Anatomical Therapeutic and Chemical (ATC) classification. During the study period, 8,912 paediatric patients who were admitted had 16 ADRs with 1.7 ADRs/1,000 admissions. The majority of ADRs were found in infants (31.2%) and children (56.2%) as compared to adolescents (12.5%). ADRs were observed more in females (81.2%) than males. Skin (62.5%) was the most affected organ due to the ADRs, and maculopapular rash and erythema multiforme were the most commonly reported symptoms. Most ADRs were probable/likely (93.7%), severe (50%), preventable or probably preventable (43.7%) and serious (37.5%). Antibiotics (93.7%) were found to be the most common cause of ADRs in paediatric patients. The majority of ADRs were associated with vancomycin (68.7%). Most of the ADRs were reported by a medical doctor in this study. This small sample size study highlights significant problems of ADRs in paediatric patients, mainly caused by antibiotics and with a majority of ADRs manifest as skin reactions. Furthermore, a high proportion of the identified ADRs were found to be preventable. More focused efforts are needed at the national level to avoid preventable ADRs in hospitals. Monitoring and management of ADRs and future studies would be beneficial for better patient care and safety.

Exploring Undergraduate Pharmacy Students Perspectives Towards Antibiotics Use, Antibiotic Resistance, and Antibiotic Stewardship Programs Along With the Pharmacy Teachers' Perspectives: A Mixed-Methods Study From Pakistan.

Background: Antibiotic resistance (ABR) is one of the major issues around the globe. Timely education and awareness of pharmacy students regarding the appropriate use of antibiotics, ABR, and antimicrobial stewardships are required. Methods: The present study was first conducted in 12 (public and private sector) universities among undergraduate pharmacy students (UGPS) (n = 414) irrespective of their study year through a validated questionnaire, and the insights of pharmacy teachers were taken through in-depth semi-structured interviews in the second phase. For the quantitative data, different statistical methods were used, and data were presented in tabulated form, whereas inductive thematic interpretation was used to categorize themes and derive conclusions from qualitative evidence. Results: The majority of the students were males (n = 223, 54%) with the mean age group 19-23 years, and 20 faculty members were interviewed with a mean duration of 15 min. Students have good knowledge about antibiotics use and the majority purchased antibiotics through prescription (n = 277, 66.9%) during the last month and strongly agreed to stop unnecessary household storage (n = 183 44.2%). Most of the students have heard the terminologies related to antimicrobial resistance through social media while unaware (n = 104, 25.1%) of a Pakistan national action plan against AMR (antimicrobial resistance). Overall, respondents have a somewhat good understanding of the ABR. Regular use of antibiotics without consultation of a physician can lead to ABR and some wrong answers were observed (162, 39.1%; p > 0.05). The majority of the students (n = 198, 47.8%) and teachers believe that the current pharmacy syllabus must be swiftly updated with the new subjects related to ABR and AMS (antimicrobial stewardship) in Pakistan. The UGPS have emphasized (n = 220, 53.1%; Median = 1, IQR = 2) establishing a link between academia and hospitals. The ABR issue has been highlighted by pharmacy faculty members, who have urged students to take practical efforts toward ABR and AMS knowledge. Conclusion: The UGPS knowledge related to ABR and AMS must be updated. Students at the undergraduate level must get training in order to encourage the sensible use of antibiotics. Courses on ABR and AMS should be included in present pharmacy curricula.

Traditional and complementary medicine use and beliefs during COVID-19 outbreak: A cross-sectional survey among the general population in Turkey.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) caused a universal psychosocial impact, with many individuals exposed to threats preferring to try self-care interventions and non-conventional approaches such as traditional and complementary medicine (T&CM) for preventive purposes. This study was conducted to determine the use of and beliefs about T&CM among a subset of the general Turkish population during the COVID-19 outbreak. METHOD: A cross-sectional online survey was carried out among the general population (aged ≥ 18 years) of Adana, Turkey during the strict lockdown period (April 11 to April 30, 2020). The survey instrument included details about sociodemographic characteristics, general information, T&CM use and beliefs. It was distributed among eligible participants via social media channels (Instagram, WhatsApp and Facebook accounts). RESULTS: Out of a total 389 participants, 39.3% (n = 153) used T&CM and 60.7% were non-T&CM users during COVID-19. Of those using T&CM, 61 (39.8%) reported the usage of more than one form of T&CM, mostly herbal medicine (30.8%), followed by nutritional supplements/vitamins (23.8%). 33.9% (n = 52) of participants using T&CM did not report T&CM use to theirmedical physicians. A statistically significant difference was observed between T&CM users and non-T&CM users in gender, age, marital status, level of education, income, and prior use of T&CM (p < 0.05). Social media (n = 204; 52.4%) was the primary source of information for T&CM use. Overall, 33.7%, 54.8% and 39% of participants in this stduy believed that T&CM therapies are effective, have fever side-effects/safe and should be use for COVID-19, respectively. CONCLUSION: During the outbreak of COVID-19, a significant proportion of the population reported the use of T&CM, with different beliefs about T&CM being observed. Better-structured T&CM-specific educational programs, enhanced physician-patient communication and access to reliable information are needed to ensure appropriate T&CM use during pandemics in Turkey.

Corrigendum: Evaluation of Adverse Drug Reactions in Paediatric Patients: A Retrospective Study in Turkish Hospital.

[This corrects the article DOI: 10.3389/fphar.2021.786182.].

Anti COVID-19 Drugs: Need for More Clinical Evidence and Global Action.

The World Health Organization (WHO) called the outbreak of coronavirus infectious disease-2019 (COVID-19) a "Public Health Emergency of International Concern" (PHEIC). According to the WHO, Centers for Disease Control and Prevention (CDC), and the US Food and Drug Administration (FDA), currently there are no medicines or vaccines that have been claimed to be useful in the prevention or treatment of COVID-19. Several existing antiviral drugs, previously developed or used as treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), human immunodeficiency virus (HIV), and malaria, are being investigated as COVID-19 treatments and some of them are being used in clinical trials. According to the CDC and Chinese treatment guidelines for COVID-19, chloroquine, hydroxychloroquine, lopinavir/ritonavir, and one of the investigational agents (remdesivir) are recommended in critically ill older patients. The use of other potential drugs reported in different studies may be considered if treatment with first-line drugs is ineffective. There are currently no complete data available from large randomized clinical trials (RCTs) to provide clinical guidance on the use, dosing, or duration to validate the effective role, safety profile, and adverse effects of all of the trial drugs for prophylaxis or treatment of COVID-19. Until now, it is still unclear which drug can successfully fight against the disease. Therefore, for the better safety of patients with COVID-19, further clinical trials and large randomized controlled studies are needed to validate the effective role, safety profile, and adverse effects of all the potential drugs. Such a measure requires action at the global level.

Evaluation of lipid profiles in patients treated with capecitabine

Background/aim: Capecitabine is a prodrug of 5-fluorouracil and has shown significant antitumor activity. The main adverse effects are hand-foot syndrome, diarrhea, and dermatitis. In recent years, hypertriglyceridemia has been reported in patients treated with capecitabine. Dyslipidemia is a rare but important side effect of capecitabine. The aim of this study is to examine the changes in lipid levels during capecitabine treatment and to raise awareness of pharmacovigilance. Materials and methods: In this retrospective study, it was aimed to analyze lipid metabolism after capecitabine treatment and is intended to contribute to the formation of a pharmacoepidemiological database. For this purpose, triglyceride, cholesterol, HDL, LDL, ALT, AST, ALP, MCV, and Hb blood levels of 57 patients treated with capecitabine at the Department of Medical Oncology, Faculty of Medicine, Çukurova University, were examined before and after five cycles of treatment. Results: Blood triglyceride and cholesterol levels were significantly increased after capecitabine treatment. The increase in triglyceride levels was higher than the increase in cholesterol levels. Conclusion: In the light of these findings, monitoring of the lipid profile should be considered in cancer patients treated with capecitabine.

An evaluation of knowledge of pharmacovigilance among nurses and midwives in Turkey.

This study aimed to evaluate the awareness of nurse/midwives regarding pharmacovigilance as well as their knowledge and experience in identifying and reporting adverse reactions of drugs. Nurse/midwives (n = 329), working in four state hospitals, were provided a questionnaire with a view of identifying their knowledge and skills pertaining to pharmacovigilance. Around 45% of the participants claimed to have knowledge of pharmacovigilance but only 23.3% of them could define it correctly. Although 24.3% of the participants acknowledged that adverse reactions should be reported to a centre, only 1.2% of them named this centre (Turkey Pharmacovigilance Centre-TUFAM). The present study indicates that nurse/midwives have insufficient knowledge of pharmacovigilance practices. Hence, it is essential to include pharmacovigilance training in their undergraduate and graduate education programs, and to promote reporting of adverse reactions.