Pharmacovigilance System Research Articles

Antibiotic-induced neurological adverse drug reactions

Antibiotics are drugs widely used all around the world. Central nervous system adverse drug reactions (CNS ADRs) are mostly under-suspected with antibiotics. Nevertheless, these ADRs could lead to severe complications such as encephalopathy. To illustrate the clinical patterns of these off-target ADRs, we here present data from pharmacovigilance system, through different populations and points of view (worldwide, French population, vulnerable population and individual). These data could help clinicians to better know about CNS ADRs with antibiotics, to better identify risk factors and vulnerable patients and to highlight the importance to set up the right diagnostic explorations in the best timing to avoid complications. Clinicians should request a pharmacological opinion from pharmacologist (biologists and pharmacovigilance clinicians) in front of vulnerable population before or during antibiotics. Pharmacovigilance advice could help clinicians in the diagnosis and the management of an ADR. Therapeutic drug monitoring is particularly contributive to adjust doses of antibiotics administered in vulnerable patients. Pharmacovigilance advice and TDM are essential to perform personalized medicine, and contribute to the proper use of drugs.

Cutaneous adverse drug reactions

Cutaneous adverse drug reactions (ADRs) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Maculopapular exanthema and urticaria are the most common types of cutaneous ADR. Serious cutaneous ADRs, which may cause permanent sequelae or have fatal outcome, may represent 2% of all cutaneous ADR and must be quickly identified to guide their management. These serious reactions include bullous manifestations (epidermal necrolysis i.e. Stevens-Johnson syndrome and toxic epidermal necrolysis), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Some risk factors for developing cutaneous ADRs have been identified, including immunosuppression, autoimmunity or genetic variants. All drugs can cause cutaneous ADRs, the most commonly implicated being antibiotics (especially aminopenicillins and sulfonamides), anticonvulsants, allopurinol, antineoplastic drugs, non-steroidal anti-inflammatory drugs and iodinated contrast media. Pathophysiology is related to immediate or delayed "idiosyncratic" immunologic mechanisms, i.e., usually not related to dose, and pharmacologic/toxic mechanisms, commonly dose-dependent and/or time-dependent. If an immuno-allergic mechanism is suspected, allergological explorations (including epicutaneous patch testing and/or intradermal test) are often possible to clarify drug causality, however these have a variable sensitivity according to the drug and to the ADR type. No in vivo or in vitro test can consistently confirm the drug causality. To determine the origin of a rash, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis (especially infectious etiologies) is required, completed with a literature search. Reporting to pharmacovigilance system is therefore essential both to analyze drug causality at individual level, and to contribute to knowledge of the drug at population level, especially for serious cutaneous ADRs or in cases involving newly marketed drugs.

Adverse Events Following mRNA COVID-19 Vaccine in 2021 and 2022: A Retrospective Analysis in Costa Rica and Italy.

Introduction Pharmacovigilance plays a crucial role in evaluating and monitoring the safety of medicines, which is essential for preventing harm to patients and improving public health. This study aims to compare the pharmacovigilance systems of Costa Rica and Italy and assess the safety profile of coronavirus disease 2019 (COVID-19) vaccines in both countries. Methods Data were collected from the official pharmacovigilance platforms in Costa Rica and Italy. Adverse events following immunization (AEFIs) were categorized by system organ class. Reports of suspected AEFIs associated with COVID-19 vaccines were analyzed for the period from January 1, 2021, to December 31, 2022. Results Both countries achieved high vaccination rates, with 84.9% in Italy and 92.9% in Costa Rica. A higher proportion of AEFIs occurred in females in both countries, with 53% and 65% in Naples and Costa Rica, respectively. Most AEFIs were observed in individuals aged 18-64 years. The rate of serious adverse reactions was lower in both countries than the international average. However, Naples reported a higher incidence of serious events per 100,000 inhabitants. Discussion The study sheds light on the importance of vaccine safety profiling and the significance of a comprehensive understanding of vaccine safety and effectiveness, specific population data, and collaborative strategies to mitigate and improve safety. Additionally, the study highlighted the significance of considering sex and gender when evaluating vaccine safety and efficacy, as sex-specific differences may impact vaccine outcomes. Conclusion Continuous pharmacovigilance efforts, collaborative approaches, and comprehensive data analysis are critical in ensuring vaccine safety and efficacy and safeguarding global public health. Lessons learned from the COVID-19 pandemic highlight the importance of proactive measures in addressing emerging challenges in vaccine safety and rollout programs worldwide.

Perceptions of undergraduate medical students of old traditional and new CBME curriculum about pharmacovigilance and adverse drug reactions reporting at a tertiary care teaching hospital: a comparative study

Background: National pharmacovigilance program is an ongoing program to monitor the adverse drug reactions and reporting at the earliest. The effectiveness and success of any pharmacovigilance system depends highly on the participation of all health care professionals. As medical students are future health-care givers, this study is aimed to measure perceptions on Pharmacovigilance and ADR reporting among medical students of two different curriculum. Methods: A validated and standardized KAP Questionnaire based cross sectional study. It consists of 22 questions divided into four sections of total of 22 items (six related to Personal details, eight related to knowledge, four related to attitude, and four related to practice) The filled questionnaires were collected and analyzed by MS excel Results: A comparative sample of 100 from old (phase 4) and 100 from New CBME (phase 3) curriculum undergraduate medical students of Government Medical College are included in our study. The average score of phase 3 and phase 4 medical students for knowledge was 85.37% and 75.87%, for attitude was 95.5% and 84% and for practices was 88.75% and 67.5% respectively. Conclusions: The overall knowledge, attitude and practices of new curriculum students found to be better than old curriculum students as CBME curriculum was introduced from the academic year 2019–2020 in all Medical Institutions of India to impart knowledge, communication and leadership skills using various teaching–learning methods among students.

Análisis de las notificaciones de úlceras cutáneas inducidas por medicamentos en España

Skin ulcers are a serious health problem with significant socioeconomic and labour repercussions and a high tendency to chronicity and recurrence; approximately, up to 50% remain active between six months to one year. AimTo study the role of drugs in the aetiology of skin ulcers. Material and methodA comprehensive study of all spontaneous reports related to skin ulcers that appear in the Spanish Pharmacovigilance System of Medicines for Human Use database. ResultsA total of 292 reports were identified containing suspected adverse drug reactions (ADRs) of ulcer lesion type. Three hundred sixty-nine medications with 427 active ingredients were identified. The ulcers appeared mainly in women with a mean age of 56.6 years. The most frequently reported suspected drugs were SGLT-2, vaccines against COVID-19, methotrexate, hydroxycarbamide, trimethoprim-sulfamethoxazole, foscarnet trisodium hexahydrate, ribavirin, docetaxel, acenocumarol and imiquimod, and the combination of lidocaine Hcl-pentosan polysulfate sodium-triamcinolone acetonide. DiscussionNumerous medications may cause ulcers as an adverse reaction. This possibility should not be ruled out when a new skin lesion appears after the administration of new drugs since 25% of the ADRs were unknown at the time of their notification, as were the cases of ulcers associated with i-SGLT2 and vaccines against COVID at the beginning of their commercialization. However, informative health alerts can be generated by continuously notifying suspected ADRs, so we strongly advise reporting any suspected ADRs to the regional pharmacovigilance system.

Strengthening the Pharmacovigilance System in Mexico: Implementation of VigiFlow and VigiLyze, as ICSR and Signal Detection Management Systems.

Pharmacovigilance (PV) activities aim to identify potential risks of medicines and vaccines after they have been authorised in the market by collecting and analysing information on suspected adverse events from different stakeholders. These can be captured and transmitted electronically in the form of Individual Case Safety Reports (ICSRs). Hence, up-to-date ICSRs management systems, like VigiFlow and signal detection and management systems as VigiLyze, have an important role in the PV system of a country. In 2019, after various attempts to establish a PV database that could fulfil the needs of the country, Mexico's National Regulatory Authority, COFEPRIS (Federal Commission for the Prevention against Sanitary Risks) decided to implement these tools. This has been a successful project that is still ongoing, it has involved national and international organisations, and has required the participation and integration of different components of the national PV system. The implementation of these tools has allowed COFEPRIS to increase its reporting trends and quality of reporting, while contributing to make more efficient interactions and processes with PV stakeholders, even during the COVID-19 pandemic. It has also allowed them to strengthen their commitment to the WHO-Programme for International Drug Monitoring, while highlighting opportunities for improvement in the national PV scenario and in the PV tools themselves. The aim of this article is to describe the implementation process, give an overview of current results regarding ICSR data and processes, and highlight the achievements, challenges, and opportunities for improvement after the three years since the beginning of the project.

Knowledge and Attitude among Community Pharmacists regarding Pharmacovigilance – A Cross Sectional Survey

The adverse drug reaction reporting system or pharmacovigilance, as a part of post-marketing surveillance, is the responsibility of every country and national government. Therefore, optimization of knowledge and attitude regarding the system were very essential. This study aimed to examine the relationship between knowledge and attitude regarding pharmacovigilance among pharmacists working in public healthcare services in the rural area. This study was a cross-sectional analytical observational research involving 48 hospital and community pharmacists carried out from July to December 2021 at Bantul Regency, Yogyakarta, Indonesia. Descriptive statistics and frequency distribution analysis were conducted to obtain an overview of knowledge and attitude regarding pharmacovigilance system, while chi-square examined the relationship between them. The results showed that 60.4% of participants had good knowledge, and 52.1% had a positive attitude regarding the system. It was also confirmed that there was a relationship between knowledge and attitude with a p-value of 0.045. Therefore, there was a relationship between knowledge and attitude regarding pharmacovigilance among pharmacists working in rural public healthcare. Based on the results of this study, it was highly recommended for healthcare practitioners, especially pharmacists, to learn and practice pharmacovigilance in their respective practice.

Benchmarking Drug Regulatory Systems for Capacity Building: An Integrative Review of Tools, Practice, and Recommendations.

Benchmarking has been increasingly used on drug regulatory systems to achieve sustainable pharmaceutical system strengthening. This study aimed to identify the scope, tools and benefits of benchmarking regulatory capacities and the most recent development in such phenomenon. Method: This study employed an integrative and critical review of the literature and documents on benchmarking drug regulatory capacities identified from 6 databases and 5 websites of related organizations and government agencies in compliance with the Preferred Reporting Items for Systematic Review (PRISMA) guidelines. Forty-three studies and 6 documents about regulatory benchmarking published between 2005 and 2022 were included in this review. Five benchmarking assessment tools or programmes recommended or adopted by international organizations or government agencies had been identified, which collectively covered 12 major regulatory functions (4 at system level and 8 at operational level) involving 9 indicator categories and 382 sub-indicators. Benchmarking drug regulatory systems was reportedly employed at national, regional and international levels for either internal assessment (mostly on regulatory system establishment, drug review process and post marketing surveillance) or external evaluation (mostly on regulatory standards, drug review process and pharmacovigilance systems) to assess current status, monitor performance, determine major challenges and inform actions for capacity building. Priority of actions in areas such as regulatory process, resources allocation, cooperation and communication, and stakeholder engagement have been suggested for strengthening drug regulatory systems. Nevertheless, the evidence about benchmarking in optimizing regulatory capacities remained underreported. This integrative review depicted a framework for decision-makers about why and how benchmarking drug regulatory systems should be undertaken. For effective benchmarking, well-informed decisions about the goals, the scope, the choice of reference points and benchmarking tools are essential to guide the implementation strategies. Further studies about the positive effects of regulatory benchmarking are warranted to engage continuous commitment to the practice.

НЕОБХОДИМОСТЬ ВОВЛЕЧЕНИЯ ПОТРЕБИТЕЛЕЙ В СИСТЕМУ ФАРМАКОНАДЗОРА СТРАН ЕАЭС

One of the indicators of the effectiveness of the pharmacovigilance system is the number and quality of spontaneous reports of cases of adverse reactions (AR). It is important to receive spontaneous reports from both medical and pharmaceutical workers and from drug users in order to assess the true nature of the adverse reaction. This article discusses the problems of a limited number of spontaneous reports from patients and low awareness of the population on the safety and effectiveness of drugs in the countries of the Eurasian Economic Union (EAEU). The aim of this article was to analyze the attitude of drug users to the submission of spontaneous reports of adverse reactions to medications. To achieve this aim, a sociological study was conducted based on a survey of drug users. The study involved 800 drug users. This study found that in the EAEU countries, patients face adverse reactions or lack of effectiveness of therapy, but unlike the Russian Federation, consumers of the Republics of Belarus, Armenia and the Kyrgyz Republic don’t report this information to state regulatory authorities, pharmacy organizations, or manufacturers of medicines. Less than 20% of respondents know about filling out a notice of an adverse reaction or lack of therapeutic effect of a drug on the Roszdravnadzor website. In our opinion, the involvement of drug users in the spontaneous reporting system has many advantages and can help solve the current problem of underestimating data on adverse reactions.

Safety surveillance for PrEP in pregnant and breastfeeding women.

The risk of HIV acquisition is higher during pregnancy and postpartum than other times. Newly acquired maternal HIV infection associated with high primary viraemia, substantially increases the risk of vertical HIV transmission. Pre-exposure prophylaxis (PrEP) reduces the risk of HIV acquisition. Currently available products include oral tenofovir/emtricitabine (TDF/FTC) and tenofovir alafenamide (TAF)/FTC), long-acting cabotegravir (CAB-LA) and the dapivirine ring (DVR). All except oral TDF/FTC have limited safety data available for use in pregnant and breastfeeding women. The safety of new PrEP agents for pregnant women and the fetus, infant and child, either exposed in utero or during breastfeeding is an ongoing concern for health care workers and pregnant and breastfeeding women, particularly as the safety risk appetite for antiretroviral (ARV) agents used as PrEP is lower in pregnant and breastfeeding women who are HIV-uninfected, compared to women living with HIV taking ARVs as treatment. With the widespread rollout of TDF/FTC among pregnant women in South Africa and other low-middle income countries (LMIC) and the potential introduction of new PrEP agents for pregnant women, there is a need for safety surveillance systems to identify potential signals of risk to either the mother or fetus, measure the burden of such a risk, and where appropriate, provide specific reassurance to PrEP users. Safety data needs to be collected across the continuum of the product life cycle from pre-licensure into the post-marketing period, building a safety profile through both passive and active surveillance systems, recognising the strengths and limitations of each, and the potential for bias and confounding. Pharmacovigilance systems that aim to assess the risk of adverse birth outcomes in pregnant women exposed to PrEP and other agents need to consider the special requirements of pregnancy epidemiology to ensure that the data derived from surveillance are sufficiently robust to inform treatment policies. Here we review the known safety profiles of currently available PrEP candidates in women of child-bearing potential, pregnancy and breastfeeding and discuss pragmatic approaches for such surveillance in HIV-endemic LMICs.

Development and validation of a nomogram for predicting cefoperazone/sulbactam-induced hypoprothrombinaemia in Hospitalized adult patients.

Cefoperazone/sulbactam-induced hypoprothrombinaemia is associated with longer hospital stays and increased risk of death. The aim of this study was to develop and validate a nomogram for predicting the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia in hospitalized adult patients. This retrospective cohort study involved hospitalized adult patients at Xi'an Central Hospital from January 2020 to December 2022 based on the Chinese pharmacovigilance system developed and established by the Adverse Drug Reaction Monitoring Center in China. Independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were obtained using multivariate logistic regression and were used to develop and establish the nomogram. According to the same standard, the clinical data of hospitalized patients using cefoperazone/sulbactam at the Third Affiliated Hospital of Xi'an Medical University from January 1, 2023 to June 30, 2023 were collected as the external validation group. The 893 hospitalized patients included 95 who were diagnosed with cefoperazone/sulbactam-induced hypoprothrombinaemia. Our study enrolled 610 patients: 427 in the training group and 183 in the internal validation group. The independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were surgery (odds ratio [OR] = 5.279, 95% confidence interval [CI] = 2.597-10.729), baseline platelet count ≤50×109/L (OR = 2.492, 95% CI = 1.110-5.593), baseline hepatic dysfunction (OR = 12.362, 95% CI = 3.277-46.635), cumulative defined daily doses (OR = 1.162, 95% CI = 1.162-1.221) and nutritional risk (OR = 16.973, 95% CI = 7.339-39.254). The areas under the curve (AUC) of the receiver operating characteristic for the training and internal validation groups were 0.909 (95% CI = 0.875-0.943) and 0.888 (95% CI = 0.832-0.944), respectively. The Hosmer-Lemeshow tests yielded p = 0.475 and p = 0.742 for the training and internal validation groups, respectively, confirming the goodness of fit of the nomogram model. In the external validation group (n = 221), the nomogram was equally robust in cefoperazone/sulbactam-induced hypoprothrombinaemia (AUC = 0.837, 95%CI = 0.736-0.938). The nomogram model constructed in this study had good predictive performance and extrapolation, which can help clinicians to identify patients at high risk of cefoperazone/sulbactam-induced hypoprothrombinaemia early. This will be useful in preventing the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia and allowing timely intervention measures to be performed.

Strategies and interventions to strengthen pharmacovigilance systems in low-income and middle-income countries: a scoping review

ObjectivesThe slow progress of pharmacovigilance (PV) in low-income and middle-income countries (LMIC) raises questions about core challenges on the growth of PV, and the appropriateness of strategies used so far...

Safeguarding human rights to health: a systematic review of supply chain impediments to safe medicines in developing nations

Purpose A key feature of human rights in health is access to safe, effective and affordable medicines. Pharmacovigilance is advocated for monitoring intended/unintended effects of medicines to assure their safety. The purpose of this paper is to synthesize knowledge about supply chain impediments to safe medicines in developing nations and contribute to future development of research in this field. Design/methodology/approach This paper conducts a structured literature review based on Preferred Reporting Items for the Systematic Reviews and Meta-Analyses guidelines. It aims at profiling supply chain impediments to safe medicines in developing nations by reviewing 46 recent pharmacovigilance-specific papers published between 2005 and 2020. Findings Analysis of reviewed articles identified criticality of supply chain impediments that affect constituents across pharmaceutical in developing nations, which still struggle to maintain robust national pharmacovigilance systems due to lack of awareness, policy and practices. Research limitations/implications Research results can be applied by pharmaceutical industry decision-makers and drug safety professionals in developing nations. Because the review is qualitative in nature, its implication ought to be tested after actual implementation. Practical implications This review can help identify underinvestigated impediments and methods to aid in developing new pharmacovigilance knowledge areas in developing nation context. Social implications The review uncovers gaps in global health equity dialogue in developing nations. It also recognizes that macrolevel supply chain impediments exist due to unfair disease burden and health inequities in developing nations. Originality/value The paper examines supply chain impediments to safe medicines in developing nations with insights for future pharmacovigilance research. Identifying and classifying supply chain impediments through this review is the first step toward creating effective interventions for these impediments to safe medicines.

Reports of Symptoms Associated with Supraventricular Arrhythmias as a Serious Adverse Drug Reaction in the Spanish Pharmacovigilance Database.

This study aimed to determine the type of drugs reported as suspected of causing severe supraventricular arrhythmias from the Spanish Human Pharmacovigilance System database. A total of 1053 reports were analysed, of which 526 (50%) were on men and 516 (49%) were on women. The most affected age group was the over-65s, with 593 reports (56%). Of the 1613 drugs, those belonging to the cardiovascular system (ATC Group C) were the most numerous (414 reports, 26%), with digoxin being the most frequent drug (49 reports, 12%). Other common groups were antiinfectives for systemic use (ATC Group J; 306 reports, 19%), antineoplastic and immunomodulating agents (ATC Group L; 198 reports, 12%), and nervous system drugs (ATC Group N; 185 reports, 11%). The most common supraventricular arrhythmia was atrial fibrillation (561 reports, 51%). Regarding outcomes, 730 (66%) patients recovered, 76 (7%) did not recover, 25 (3%) recovered but with sequelae, and 23 (2%) resulted in death. This study revealed that certain drugs have reported to be associated more frequently to supraventricular arrhythmias as serious adverse reactions, especially in the older population. Proper clinical management and effective strategies to ensure medication appropriateness should always be considered to improve patient safety when prescribing drugs.

Analysis of Reports Sent to the Portuguese Pharmacovigilance System and Published Literature Regarding the Safety of Metformin in the Elderly.

The first line medication for the treatment of type 2 diabetes is metformin. This study aims to investigate the safety profile of metformin and metformin combination medications in older adults using pharmacovigilance data. A literature search was used to identify published clinical studies reporting safety of metformin in older patients (age ≥ 65 years old), which were then thoroughly evaluated. Additionally, a deep analysis was performed, taking into account suspected adverse drug reaction (ADR) reports submitted to the Portuguese Pharmacovigilance System involving patients with 65 years old or older, with metformin or metformin combination as the suspected drug. The results suggest that metformin is safer when used in combination with other antidiabetics than when used in monotherapy. Metformin prolonged-release tablets have a lower incidence of adverse effects compared to treatment with immediate-release metformin tablets. The analysis of the reports showed that "gastrointestinal disorders" was one of the most common classes reported, and metformin alone was the drug most commonly associated with serious gastrointestinal reactions that resulted in hospitalization. In addition, it was the drug most commonly associated with the lactic acidosis ADR. Even though most ADRs in the reports were serious, the majority progressed to cure. According to the analysis performed, the results suggest that the patient's renal function should be considered in order to prevent ADRs associated with metformin, such as lactic acidosis. Therefore, monitoring the safety profile of metformin remains essential to prevent serious ADRs.

Will Cape Verde attain COVID‐19 herd immunity? Progress, Challenges, and Recommendations

AbstractThe COVID‐19 pandemic has exposed the vulnerabilities of Cape Verde's healthcare system, prompting a swift and effective response. This article examines Cape Verde's comprehensive approach to the pandemic, focusing on epidemiology, the healthcare system, and the vaccination campaign. Recognizing the critical role of COVID‐19 vaccination in global efforts, Cape Verde has implemented strategic measures to achieve herd immunity. Although the country has achieved relatively high vaccination coverage in Africa, it still falls short of the necessary threshold. Challenges, including vaccine hesitancy, viral mutations, and supply chain insecurities, must be addressed. Sustained efforts, involving community participation and improved vaccine availability, are crucial. Furthermore, a robust pharmacovigilance system is essential for ensuring vaccination safety and enhancing health outcomes.

Active surveillance and clinical analysis of anaphylaxis based on the China Hospital Pharmacovigilance System.

Objective: This study aimed to develop active surveillance programs (ASPs) for anaphylaxis using the China Hospital Pharmacovigilance System (CHPS) and analyze the characteristics, allergens, and management strategies for anaphylaxis within a tertiary hospital setting in China. Methods: We retrospectively analyzed the anaphylaxis cases reported to the National Adverse Drug Reaction Monitoring System in our hospital from 2014 to 2021. Characteristic medical orders, progress notes, and diagnoses in these cases were recorded to identify initial anaphylaxis trigger entries. Based on these initial entries, the questionnaire was developed, and the Delphi method was used to establish consensus entries for anaphylaxis triggers. The CHPS was used to program these trigger entries and construct ASPs, which were then tested on the 238,194 discharged patients to evaluate their performance and analyze the related clinical data. Results: Ten anaphylaxis triggers and three ASPs were ultimately identified. The ASPs captured 309 cases, out of which 94 cases were confirmed as anaphylaxis following manual screening. After removing duplicates, we noted 76 patients who experienced anaphylaxis 79 times. The positive rate of triggers and the positive predictive value of the programs were 0.13% and 30.42%, respectively. The incidence of anaphylaxis in our study was 0.03%, and the number of anaphylaxis cases detected by the ASPs was 5.64 times higher than those detected by the spontaneous reporting system. Anaphylaxis was more common among female patients. Antibacterial drugs, antineoplastic drugs, and contrast media were the most prevalent allergens in clinical practice. Anaphylaxis to antineoplastic drugs had the highest incidence (0.6%) when compared with patients admitted during the same period. Our study revealed a significant underuse of epinephrine and overuse of second-line therapy (glucocorticoids and antihistamines) in the management of anaphylaxis. Furthermore, we found the use and dosage of epinephrine to be inappropriate. Conclusion: The CHPS can effectively utilize both structured and unstructured data to construct anaphylaxis ASPs, and this could counteract the under-reporting by the spontaneous reporting system, the primary adverse reaction monitoring method in China. The treatment and management of anaphylaxis are currently inadequate and require improvement to reduce mortality risk.

Unknown adverse drug reactions from spontaneous reports in a hospital setting: characterization, follow-up, and contribution to the pharmacovigilance system.

Introduction: Post-marketing identification and report of unknown adverse drug reactions (ADRs) are crucial for patient safety. However, complete information on unknown ADRs seldom is available at the time of spontaneous ADR reports and this can hamper their contribution to the pharmacovigilance system. Methods: In order to characterize the seriousness and outcome of unknown ADRs at the time of report and at follow-up, and analyze their contribution to generate pharmacovigilance regulatory actions, a retrospective observational study of those identified in the spontaneous ADR reports of patients assisted at a hospital (January, 2016-December, 2021) was carried out. Information on demographic, clinical and complementary tests was retrieved from patients' hospital medical records. To evaluate the contribution to pharmacovigilance system we reviewed the European Union SmPCs, the list of the pharmacovigilance signals discussed by the Pharmacovigilance Risk Assessment Committee, and its recommendations reports on safety signals. Results: A total of 15.2% of the spontaneous reported cases during the study contained at least one unknown drug-ADR pair. After exclusions, 295 unknown drug-ADR pairs were included, within them the most frequently affected organs or systems were: skin and subcutaneous tissue (34, 11.5%), hepatobiliary disorders (28, 9.5%), cardiac disorders (28, 9.5%) and central nervous system disorders (27, 9.2%). The most frequent ADRs were pemphigus (7, 2.4%), and cytolytic hepatitis, sudden death, cutaneous vasculitis and fetal growth restriction with 6 (2%) each. Vaccines such as covid-19 and pneumococcus (68, 21.3%), antineoplastics such as paclitaxel, trastuzumab and vincristine (39, 12.2%) and immunosuppressants such as methotrexate and tocilizumab (35, 11%) were the most frequent drug subgroups involved. Sudden death due to hydroxychloroquine alone or in combination (4, 1.4%) and hypertransaminasemia by vincristine (n = 3, 1%) were the most frequent unknown drug-ADR pairs. A total of 269 (91.2%) of them were serious. Complementary tests were performed in 82.7% of unknown-ADR pairs and helped to reinforce their association in 18.3% of them. A total of 18 (6.1%) unknown drug-ADR pairs were evaluated by the EMA, in 8 (2.7%) the information was added to the drug's SmPC and in 1 case the risk prevention material was updated. Conclusion: Identification and follow-up of unknown ADRs can be of great relevance for patient safety and for the enrichment of the pharmacovigilance system.

Knowledge, attitude and practice of physicians and nurses at the cape coast teaching hospital in the Central Region of Ghana on spontaneous adverse drug reaction reporting

Ghana’s rate of reporting adverse drug reaction (ADRs) over the past years has consistently been below the WHO standard despite utilizing the spontaneous or voluntary reporting system. While underreporting undermines the pharmacovigilance system and poses a huge threat to public health safety, there is limited information on the perspectives of healthcare workers directly involved in drug administration. The present study investigated the knowledge, attitude and practice of physicians and nurses at the Cape Coast Teaching Hospital (CCTH) towards spontaneous reporting of ADRs (SR-ADRs). A descriptive cross-sectional survey was employed in the study. Pre-tested (Cronbach’s alpha value of 0.72) and validated questionnaires comprising 37 open-ended and close-ended questions were administered to 44 doctors and 116 nurses at the CCTH who had been practicing for at least six months prior to study. Out of the 160 administered questionnaires, 86 was administered face-to-face and the remaining via e-mails. Descriptive analysis was performed and the results were presented in simple frequencies and percentages. Binary logistic regression model was used to test association of the independent variables with SR-ADRs. With a response rate of 86.4% for physicians and 59.5% for nurses, 38 (35.5%) physicians and 69 (64.5%) nurses completed the questionnaires and returned same. Majority (82.3%, 88) of the respondents knew that it is their responsibility to report ADRs although their knowledge levels was found to be inadequate (that is ≤80%) in majority (66.7%) of the text items that assessed knowledge levels. On the attitude of respondents, it was found that 57% (61) of them agreed that under-reporting was due to complacency whereas 80.4% (86) of them agreed that it was due the lack of adequate training. On the issues of practice, the prevalence of encountering, assisting in the management, and reporting of ADRs were 26.1% (28), 17.8% (19) and 7.5% (8) respectively. Also, nurses were 1.22 times more likely to encounter a patient with ADRs and twice more likely to fill and forward ADR form than doctors during management. Respondents with more than six months but less than one year of practice experience were more likely (AOR = 1.38, 95% CI: 2.72–7.3) to encounter a patient with ADRs as compared to those with just six months of practice experience. Furthermore, male respondents were more likely (AOR = 2.42, 95% CI: 1–5.85) to encounter patients with ADRs but less likely (AOR = 0.49, 95% CI: 0.91–2.6) to fill and forward ADR form compared to their female counterparts. In conclusion, doctors and nurses at the CCTH had inadequate knowledge about ADRs and its existing pharmacovigilance systems, thus accounting for the low spontaneous ADRs reporting in the facility.

Will the future of pharmacovigilance be more automated?

ABSTRACT Introduction Artificial intelligence (AI) based tools offer new opportunities for pharmacovigilance (PV) activities. Nevertheless, their contribution to PV needs to be tailored to preserve and strengthen medical and pharmacological expertise in drug safety. Areas covered This work aims to describe PV tasks in which the contribution of AI and intelligent automation (IA) tools is required, in the context of a continuous increase of spontaneous reporting cases and regulatory tasks. A narrative review with expert selection of pertinent references was performed through Medline. Two areas were covered, management of spontaneous reporting cases and signal detection. Perspective The use of AI and IA tools will assist a large spectrum of PV activities, both in public and private PV systems, in particular for tasks of low added value (e.g. initial quality check, verification of essential regulatory information, search for duplicates). Testing, validating, and integrating these tools in the PV routine are the actual challenges for modern PV systems, to guarantee high-quality standards in terms of case management and signal detection.