Pharmacovigilance Program Research Articles

Adverse Drug Reactions to β-Lactam Antibiotics: A Portuguese Pharmacovigilance Database Analysis

Abstract Background The β-lactam antibiotics are one of the most relevant drug classes globally. They accounted for the largest share of systemic antibiotics consumption in Portugal across both community and hospital settings. Due to their significance, continuous monitoring of adverse drug reactions (ADR) associated with β-lactams is fundamental. Aim To analyse and characterise cases related to β-lactam antibiotics received by the Portuguese National Pharmacovigilance System. Methods Retrospective analysis of cases containing at least one medicinal product classified as suspect under the Anatomical Therapeutic Chemical (ATC) code J01C or J01D, reported to the Portuguese Pharmacovigilance System between 2014 and 2023. Characterisation of cases considered patient demographics, reported suspected medicines, MedDRA Preferred Term (PT), seriousness and type of reporter. Results A total of 3557 cases were identified (54.0% females; median age = 42.0 years; interquartile range = 52.2), with 95.9% originating from spontaneous reporting and 93.5% being reported by healthcare professionals. The most frequently reported medicines were those belonging to ATC J01CR. Around 70% of cases were classified as serious, with 38.7% being related to situations of disability or other criteria of greater seriousness. Most frequently reported PTs were related to skin disorders. Anaphylactic reaction was the most reported Designated Medical Event term. The PTs “Drug ineffective” and “Off label use” were reported in 5.2% and 2.4% of the cases, respectively. Conclusions Despite the majority of cases are serious, most of the ADR identified are related to already known hypersensitivity reactions. To improve the knowledge regarding these medicines and to generate evidence to address emerging public health issues it is of paramount importance to strength the Portuguese Pharmacovigilance System. This can be achieved through enhancing spontaneous reporting and implementing active pharmacovigilance programs. Key messages • Monitoring the efficacy and safety profile of β-lactams in a real-world context is crucial to mitigate the impact in public health and associated economic burden. • Enhancing the surveillance systems improves data collection and evidence generation, supporting tailoring treatment approaches and implementation of public health policies.

A Retrospective Observational Study of Adverse Drug Reactions (ADR) Reported to ADR Monitoring Centre from 2010 to 2020.

Adverse Drug Reactions (ADR) are one of the essential causes of hospital admissions and pose a significant clinical and economic burden on the healthcare system. The Adverse Drug Reaction Monitoring Centre (AMC) in JIPMER functioning under the Pharmacovigilance Programme of India (PvPI) plays a vital role in ensuring medication safety by routinely detecting and monitoring ADRs. Hence, this study aimed to assess the characteristics of ADR reported from 2010 to 2020 in AMC JIPMER and to detect signals, if any. To study the characteristics of Adverse Drug Reactions (ADR) reported to a regional ADR monitoring center from 2010 to 2020 and to detect signals of disproportionate reporting (SDRs) if any from the reported ADRs. A total of 6007 ADR reports with a single suspect drug were included for analysis from 2010 to 2020. The characteristics of these reports, including patient's age and gender, Number and percentage of ADRs, the causality of ADR using WHO UMC (World Health Organization-Uppsala Monitoring Scale), the seriousness of the ADR, and outcome were collected from the ADR reports. MedDRA (Medical Dictionary for Regulatory Activities) Preferred Terms (PT) were used to classify adverse drug reactions. Causality analysis using the Naranjo Algorithm and Preventability using Modified Schumock and Thornton criteria were performed for the ADRs. The number and percentage of severe ADRs were analyzed. The System Organ class of all the ADRs was enumerated. ADRs not mentioned in the US FDA (United States Food and Drug Administration) product label (unlabelled reactions) were documented. Unlabeled reactions with ≥3 ADR reports were included for signal detection by disproportionality analysis. Antineoplastic drugs, followed by antimicrobials, anticonvulsants, Anti snake venom, and NSAID were the most common drugs implicated in ADRs. Skin and subcutaneous tissue disorders were the most common System Organ Class (SOC) involved in the ADRs. Among the 6007 reports, 19.2% were serious ADRs. Most of the ADR reports were of possible causality followed by probable and certain as per WHO UMC and Naranjo causality scales. Only ten ADRs were preventable and one reaction (Tamoxifen-induced neuropathy) was eligible for signal detection. Disproportionality analysis using a 2x2 contingency table showed insignificant signal detection using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). Analysis of ADRs from an ADR Monitoring center functioning in a tertiary care hospital shows antineoplastic drugs to be the most common drugs associated with adverse drug reactions, with rash being the most common adverse effect. The majority of the ADRs were not preventable. No Signals of Disproportionate Reporting (SDR) were detected in our study.

Mortality associated with clozapine: what is the evidence?

While clozapine has risks, relative risk of fatality is overestimated. The UK pharmacovigilance programme is efficient, but comparisons with other drugs can mislead because of reporting variations. Clozapine actually lowers mortality, partly by reducing schizophrenia-related suicides, but preventable deaths still occur. Clozapine should be used earlier and more widely, but there should be better monitoring and better management of toxicity.

Adverse Drug Reaction and Pharmacovigilance in Elder Patient’s Health

A pharmacist is a medical expert who is dedicated to helping patients take medications in a safe and efficient manner. Many Indian hospitals do not consider a pharmacist’s responsibility for medication use or their role as a health care provider in clinical practice. The study's first goal is to comprehend how healthcare professionals view and interact with the clinical role of the Pharmacist. According to the study, general practitioners were only made aware of the role of the clinical Pharmacist following an intervention. The study makes the strong recommendation that other hospital-affiliated health care providers be allowed to take part in educational programs on drug-related topics and be open to collaborating with the clinical Pharmacist to improve patient care. According to the current study, pharmacovigilance program implementation in hospitals is crucial for ensuring safe medication use, preventing adverse drug reactions, and, ultimately, improving patient care quality.

Promoting Patient Engagement in Adverse Drug Reaction Reporting: A Novel Approach Utilizing Set Induction-Based Skill Questionnaires.

All stakeholders must address the global health concern of an increasing frequency of adverse drug reactions (ADRs), regardless of the practice settings. Adverse drug reactions have been found to be a significant cause of morbidity and death across all age groups, hospital admissions, and a significant financial burden on society and healthcare systems. The main objective of this study was to measure patients' awareness and knowledge of reporting adverse drug reactions using a questionnaire and then to help patients become more aware of and sensitive to reporting ADRs. The current investigation was carried out in the OPD Block of the All India Institute of Medical Sciences in Deoghar using a pre-experimental study with one group pre-test post-test design. One hundred and ninety-nine patients who were visiting different OPDs and IPDs participated in this study. The average age of the 199 study participants was 34.6 years. The majority of participants were male, illiterate and belonged to rural areas. We found a statistically significant difference [-11.90(0.000*)] in the pre-test and post-test knowledge questionnaire scores of the participants, indicating the efficacy of awareness and sensitization for patients on ADR reporting. This survey aims to inform patients about the pharmacovigilance Program in India. The questions are structured in a way that allows patients to reflect and become more selfaware while reading them. They also function as a set introduction to ADR (Adverse Drug Reaction) monitoring centers and increase patient awareness of reporting ADRs.

Safety Profile of Mass Administration of Albendazole Among School Children (6-19 Years): A Prospective Active Surveillance Study.

Infections with Soil-transmitted Helminths (STHs) impact about 24% of the global population. A disproportionate number of individuals, particularly those from low socioeconomic backgrounds, live in emerging nations. In India, between the ages of one and fourteen, almost 220 million children are susceptible to intestinal worm infestations caused by parasites. The National Deworming Day (NDD) initiative was started by the Indian government in February 2015 as a part of the National Health Mission to address this problem. Though the adverse effects of albendazole in routine therapy are known, the mass administration of the medicine in children as part of a public health program has not been adequately studied. This study aimed to determine the occurrence, type, and severity of adverse drug reactions resulting from mass administration of albendazole in school children aged 6-19 years in a district of northern India. Twenty specified clusters were randomly chosen from a total of 94 clusters in the state to participate in this prospective, descriptive, observational study that was carried out in Karnal, Haryana. Both a passive approach and an active adverse drug reaction reporting system were used in the study. The six-step process known as Deb's Active Surveillance & Assisted Reporting System was employed in our study. Adverse drug reactions were recorded using the suspected Adverse Drug Reaction (ADR) reporting form of the Pharmacovigilance Programme of India (PvPI). Twenty clusters with a combined total of 94 schools and 12,751 students were observed during the study. In this study, there were more female participants (N = 8,060; 63.21%) than male participants (N = 4,691; 36.78%). A total of 29 ADRs were reported. All reported ADRs were mild in nature. It was discovered that there were 1.37 incidences for every 1000 individuals. As illustrated in Fig. (1), the most frequently reported Adverse Drug Reactions (ADRs) were vomiting (N = 10), nausea (N = 4), abdominal pain (N = 2), and headache (N = 1). The majority of ADRs were categorized as probable (N=18; 62.06%), followed by possible (N=11; 37.93%). An active surveillance system alongside voluntary passive reporting during the mass administration of medicines can help evaluate the safety profile of the medicinal products. The occurrence of ADRs following mass administration of albendazole in school children was found to be only 1.37 incidences for every 1000 recipients, being mild in nature, with vomiting being the most common.

Clozapine-associated adverse drug reactions in 38,349 psychiatric inpatients: drug surveillance data from the AMSP project between 1993 and 2016

Clozapine is a second-generation antipsychotic drug that offers superior treatment results in patients with schizophrenia but is also associated with significant risks. This study analyzes data on pharmacotherapy with clozapine and the associated adverse drug reactions (ADRs) in an inpatient setting including 38,349 patients. Data about the use of clozapine and reports of severe ADRs within the period 1993–2016 were obtained from the multicentered observational pharmacovigilance program “Arzneimittelsicherheit in der Psychiatrie” (AMSP). In total, 586 severe clozapine-associated ADRs were documented (1.53% of all patients exposed). Patients aged ≥65 years had a higher risk of ADRs than patients aged <65 years (1.96 vs. 1.48%; p = 0.021). Significantly more ADRs were attributed to clozapine alone (396; 67.6% of all 586 ADRs) than to a combination with other drugs. The most frequent ADRs were grand mal seizures (0.183% of all 38,349 patients exposed), delirium (0.180%), increased liver enzymes (0.120%), and agranulocytosis (0.107%). We detected 24 cases (0.063%) of clozapine-induced extrapyramidal symptoms, of which 8 (0.021%) were attributed to clozapine alone. Five ADRs resulted in death (0.013%): 2 due to agranulocytosis (41 cases total) (mortality = 4.88%) and 3 due to paralytic (sub)ileus (16 cases) (mortality = 18.75%). The median dose of clozapine in all patients treated was 300 mg/day, in patients who developed ADRs 250 mg/day. The main risk factor for an ADR was pre-existing damage of the affected organ system. Overall, the results of this study highlight the importance of alertness—especially of frequently overlooked symptoms—and appropriate monitoring during treatment with clozapine, even at low doses.

A Text-Inception-Based Natural Language Processing Model for Sentiment Analysis of Drug Experiences

The study of sentiment in Natural Language Processing (NLP) is among the most successful research areas because of the availability of millions of user opinions online since the turn of the century. The economic, political, and medical fields are just some of the many that have benefited from studies of sentiment research. While numerous studies have examined more mainstream topics like consumer electronics, movies, and restaurants, relatively few have examined health and medical concerns. Considerable insight into where to direct efforts to improve public health might be gained by a study of how people feel about healthcare as a whole and of individual drug experiences in particular. When it comes to medicine, automatic analysis of online user evaluations paves the way for sifting through massive amounts of user feedback to find information regarding medications' efficacy and side effects that might be used to enhance pharmacovigilance programs. Simple rules-based methods have given way to more complex machine learning approaches like deep learning, which is developing as a technology for many natural language processing jobs. The opensource datasets have been analyzed with models that use word embeddings and term frequency-inverse document frequency (TF-IDF). A feature-enhanced text-inception model for sentiment classification was presented to work in tandem with this approach. The model first employed a cutting-edge text-inception module to glean useful shallow features from the text. K-MaxPooling was subsequently employed to reduce the dimensionality of its shallow and deep includes as well as enhance the generalization of characteristics, and a deep feature extraction module was formed using the bidirectional gated recurrent unit (Bi-GRU) and the capsule neural network to comprehend the text's semantic data. By combining traditional methods with cutting-edge artificial intelligence techniques, this hybrid approach can revolutionize public health initiatives, decision-making, and pharmacovigilance in the healthcare industry. This model achieved an exceptional accuracy rate of 99%, underscoring its effectiveness in sentiment classification and demonstrating its potential to significantly contribute to advancing healthcare and medical research.

Improvement in Adverse Drug Reaction (ADR) Knowledge: A Pre- and Post-video Intervention Study Among Doctors.

Background Adverse drug reactions (ADRs) represent a significant public health concern, contributing to mortality, morbidity, and healthcare costs worldwide. Healthcare practitioners especially doctors play a vital role in identifying and reporting ADR. This study investigates the prevalence of knowledge regarding ADR among doctors and enhances it with educational intervention. It also explores the association between demographic factors and baseline ADR awareness. Methods A prospective cross-sectional interventional study was conducted among doctors in Ahmedabad, India, to evaluate their knowledge of ADR reporting and the effectiveness of an educational video intervention. Pre- and post-intervention questionnaires were administered to assess knowledge improvement. Statistical analysis, including paired t-tests and chi-square tests, was performed to evaluate the intervention's impact and explore associations between demographic factors and ADR awareness. Results Analysis of pre- and post-intervention questionnaires revealed a significant increase in correct response rates post-intervention, indicating the effectiveness of the educational video intervention. Demographic factors, particularly age, were associated with ADR awareness. Following the intervention, participants demonstrated an improved understanding of ADR definitions, WHO causality assessment, reporting mechanisms, and challenges faced by pharmacovigilance programs. All participants found the video helpful and expressed intent to share their knowledge post-intervention. Conclusion The results of the study suggest that educational video intervention can serve as an effective tool for understanding ADRconcepts and pharmacovigilance practices. Moreover, the association of demographic factors, particularly age, with ADR awareness further emphasizes the importance of educational interventions in addressing specific population needs.

Implementing pharmacogenetic testing to optimize proton-pump inhibitors use among Indian population based on CPIC-CYP2C19-PPI dosing guidelines: The need of the hour.

Proton-pump inhibitors (PPIs) are widely prescribed to decrease stomach acid and treat various acid-related Gastrointestinal tract (GIT) diseases. However, genetic variations, particularly in the CYP2C19 gene, affect PPIs metabolism and efficacy. Variants in CYP2C19 can result in different rates of PPI metabolism, influencing their effectiveness. Personalized medicine strategies, such as genotyping for CYP2C19, have the potential to enhance the effectiveness of PPI therapy and patient safety. This review aims to describe the relevance of CYP2C19 genetic profiling in the indian population, including normal function (e.g. CYP2C19*1, *11, *13, *15, *18, *28, and 38), decreased function (e.g., CYP2C19*9, *10, *16, *19, *25, and 26), loss of function (e.g., CYP2C19*2, *3, *4, *5, *6, *7, *8, *22, *24, *35, *36, and *37), and increased function (e.g., CYP2C19*17) variants. This review also examines the clinical pharmacogenomics implementation consortium (CPIC)-CYP2C19-PPI guidelines to highlight the importance of pharmacogenomics (PGx)-informed personalized PPI therapy for gastroesophageal reflux disease and peptic ulcer disease treatment. On average, each person in India possesses eight pharmacogenetic (PGx) variants that can be clinically significant, underscoring the need for preemptive testing. Implementing CYP2C19 genetic testing in India requires expanding laboratory capacity, increasing accessibility in primary care, increasing public awareness, collaboration between pharmacovigilance and PGx programs, investing in advanced sequencing technologies, data management systems, and integration with electronic health records and clinical decision support systems. Addressing challenges such as genetic diversity, socioeconomic factors, health-care access issues, and shortage of trained professionals is essential for implementation. Due to the lack of definitive country-specific policies and PGx guidelines from Indian drug regulatory agencies, guidelines from international consortia such as the Clinical Pharmacogenetics Implementation Consortium and drug labeling offer crucial foundational evidence. This evidence can be used to enhance patient outcomes and ensure the safe and effective use of PPIs in India.

Sodium Valproate-Induced Hyperammonemia: A Case Series in a Tertiary Care Hospital.

Sodium valproate (VPA) is an extensively used anti-convulsant, which is an effective drug for treatment of epilepsy in adults and children, as well as for conditions like migraine, bipolar disorder, mania, and trigeminal neuralgia. Sedation, vertigo, ataxia, dose-dependent tremors, headaches, and gastrointestinal side effects are the most often reported adverse effects associated with VPA. A potential life-threatening event reported with VPA is hyperammonemia (HA), which is defined as an increase in serum level of ammonia. Only 587 reported cases of HA were found in the VigiAccess database, representing a mere 0.6% of the 95,000 reported adverse events linked to VPA. Hence, this case series was conducted with emphasison monitoring of increased serum ammonia levels with or without hepatic enzymes increase for patients who are on VPA. To assess elevated serum ammonia levels following VPA administration, and to ascertain the percentage of individuals with hepatic enzymes increased who took VPA and subsequently had elevated serum ammonia levels. This study was conducted at the adverse drug reaction (ADR) monitoring centre (AMC) of the Pharmacovigilance Programme of India (PvPI) and Department of Psychiatry, Christian Medical College and Hospital (CMC&H), Ludhiana. The study comprised of 12 patients who were exclusively on VPA and exhibited symptoms related to elevated serum ammonia.An informed consent form (ICF) was provided to the patient prior to taking their personal details. Laboratory investigations were done to establish the diagnosis and liver function tests (LFTs), chiefly ALT (alanine transferase) and AST (aspartate aminotransferase) were also performed.It is a descriptive study which was for a time period of six months. Results: This study includes 12 patients who had HA confirmed by laboratory investigation. Out of these 12 patients, two patients (17%) had a corresponding increase in LFT. The average as of the patients was 53.08 years and average serum ammonia levels were 219.15. None of the patients who presented with HA progressed to hyperammonemic encephalopathy (HAE). This case series on valproate-induced HAshould be of interest to psychiatrists, physicians, internists, family medicine physicians, hospitalists, and surgeons who will have patients on VPA. Delay in recognition of HA can result in the development of potentially life-threatening complications.Rapid diagnosis and management will help in reducing the number of cases which progress to encephalopathy which is highly fatal.

Knowledge, attitude, and practice study of pharmacovigilance in a dental teaching institute in Western India

ABSTRACT Background: India started the National Programme of Pharmacovigilance in 2005, which was renamed as Pharmacovigilance Programme of India in 2010. This is the main portal for detecting and reporting the adverse effects of drugs. Aim: This study aimed to evaluate the knowledge, attitude, and practice (KAP) of pharmacovigilance (Pv) in a dental teaching institute in Western India. Materials and Methods: The KAP questionnaire regarding Pv was distributed among the dental faculties. The knowledge-based questions were corrected and the scoring was given as excellent knowledge, good knowledge, fair knowledge, and poor knowledge for the scores between 0–5, 6–10, 11–15, and 16–20, respectively. Descriptive statistical analysis was performed which is presented as frequencies (n) and percentages (%) in all three sections of the questionnaire. Results and Observations: The knowledge of 24 (44%) participants was found to be fair with scores between 6 and 10. The knowledge of 23 (42%) participants was found to be poor with scores between 0 and 5 and the knowledge of 8 (14%) participants was found to be good with scores between 11 and 15. A positive and promising attitude was exhibited by the dental faculties toward reporting adverse drug reactions (ADRs). Only two study participants had reported an ADR event. Conclusion: The deficiencies in knowledge appear to be the underlying factor for the underreporting of adverse reactions encountered by dental practitioners.

Prevalence of Adverse Drug Reactions in Diabetic patients receiving Antidiabetic Medications at Tertiary Care Hospital

Background: Diabetes mellitus is a chronic metabolic condition defined by elevated blood glucose levels caused by abnormalities in insulin secretion, insulin action, or both. Anti-diabetic drug pharmacovigilance can be extremely useful in identifying and resolving the adverse drug reactions (ADRs) and safeguarding patients from needless injury. Objective: The objective of the study was to determine the prevalence of various adverse events caused by the use of anti-diabetic medications in patients treated at tertiary care hospital. Method: It was a randomized controlled study where the participants were randomized into two groups i.e., interventional or study group and control group. All suspected ADRs were collected, analysed and confirmed by the physician-in-charge and were assessed for causality using WHO-UMC Causality Categories, Naranjo’s causality assessment scale, preventability using Modified-Schumock and Thornton scale, severity using Modified Hartwig and Siegel scale by the Causality Assessment Committee (CAC). Results: The study included a total of 300 subjects among which 218 were male (72.67%) and 82 were female (27.33%). A total of 300 patients, 104 ADRs were identified, in which 46.15% were observed in the control group and 53.85% in the interventional group. Females were more prevalent to the ADRs. The majority of ADRs were seen in age group of &gt;70 in which 15.38% were observed in the control group and 18.27% in the interventional group. The Highest observed ADR of 20 (19.23%) was Hypoglycemia in which 9(8.65) were observed in the control group and 11(10.57) in the interventional group followed by weight gain i.e, 10 (9.61%) in which 5(4.80%) were observed in the control group and 5(4.80%) in the interventional group. Conclusion: ADR relating to antidiabetic therapy utilizing oral antidiabetics and insulin was found to be prevalent. The doctors and clinical pharmacists are therefore needed to identify and report the appropriate signals generated to the nearest ADR monitoring centre or Pharmacovigilance Programme of India for the benefit of the patients.

Why Pharmacovigilance of Non-steroidal Anti-inflammatory Drugs is Important in India?

Non-steroidal Anti-Inflammatory Drugs (NSAIDs) are among the drugs that are most regularly administered to manage inflammation and pain. Over-the-Counter (OTC) NSAIDs are widely accessible, particularly in developing countries like India. This casual approach to using NSAIDs may operate as a magnet for NSAID-related adverse drug reactions (ADRs) among patients. As patients in India are less informed about the appropriate use of NSAIDs and consumption patttern, adverse drug reactions, and the importance of reporting ADRs, the current study's objective is to promote patient safety by using pharmacovigilance as a tool to educate patients. A targeted literature methodology was utilized to gather the data pertaining to NSAIDs, their ADRs and their pharmacovigilance. Different scientific databases, such as Science Direct, PubMed, Wiley Online Library, Springer, and Google Scholar, along with authentic textbooks, were explored as reference literature. In general, NSAIDs consumption pattern depends upon the different age groups. Around 1.6 billion tablets of NSAIDs are consumed in India for ailments, such as headaches, arthritis, menstrual cramps, osteoarthritis, back pain, rheumatoid arthritis, gout, osteoporosis, tendinitis, cancer pain and chronic pain. Common ADRs of NSAIDs include nausea, vomiting, headache, gastritis, abdominal pain, and diarrhoea. Also, they can cause renal damage and cardiovascular problems if not consumed in a dose-dependent manner. However, Diclofenac and Ibuprofen have both been linked to depression and dementia. There have been reports of aplastic anaemia, agranulocytosis linked to phenylbutazone, Stevens-Johnson, and Lyell's syndrome linked to isoxicam and piroxicam, as well as the vulnerability of new-borns to Reye's syndrome after aspirin use. Lack of awareness, time constraints and unpredictability, poor training in ADRs identification, etc., are some of the reasons for the under-reporting of ADR of NSAIDs in India. In order to rationally prescribe NSAIDs, it is essential to be aware of probable ADR's and establish prescription guidelines. Prescribers' behaviour can be changed toward excellent prescribing practices by conducting routine prescription assessments dealing with NSAIDs and providing feedback. In the near future, it will be critical to strengthen ADR data management and expand the reach of pharmacovigilance programs, ADR monitoring centers, and healthcare professionals' especially pharmacists' training in rural locations.

Ensuring Medication Safety in India: The Crucial Role of the Pharmacovigilance Programme of India (PvPI) in Adverse Drug Event Monitoring

With the establishment of 12 regional centers, India implemented a comprehensive system for monitoring drug reactions in 1986. In 1997, India became a member of the Uppsala Monitoring Centre in Sweden, which oversees the World Health Organization's Programme for International Drug Surveillance. Beginning at the outset, six regional centers were created in Chandigarh, New Delhi, Mumbai, Kolkata, Lucknow, and Pondicherry. ADR is being watched throughout the nation. Advocating for safe drug use may become a top focus for the Indian Pharmacopoeia Commission, which also functions as the National Coordination Centre for India's Pharmacovigilance Program. We currently have 179 adverse drug reactions under observation. At the moment, the National Coordination Centre receives adverse event reports from centers in India.Reporting Form; Phocomelia; Vigiflow; UMC; Death; Thalidomide

Overview on Pharmacovigilance: Ensuring Medication Safety

Pharmacovigilance plays a pivotal role in ensuring drug safety by monitoring and evaluating the effects of medications before and after their market launch. In India, a rapidly expanding pharmaceutical industry coupled with a diverse patient population and growing drug consumption necessitates robust pharmacovigilance measures. This abstract highlights the need for pharmacovigilance in India, emphasizing factors such as the expansion of the pharmaceutical sector, diverse patient demographics, increased drug consumption, limited awareness and reporting, regulatory compliance, globalization of clinical trials, and emerging safety concerns. The Pharmacovigilance Programme of India (PvPI) serves as a cornerstone for patient safety, focusing on data collection, signal detection, capacity building, and regulatory collaboration. Reporting adverse drug reactions (ADRs) to PvPI is crucial, and various reporting methods, including online reporting, Vigiflow software, ADR reporting forms, direct communication, telephone reporting, and email, are discussed. Additionally, advice on what to report, who can report, where to report, and the handling of submitted information is provided to encourage effective ADR reporting. Overall, pharmacovigilance in India is essential for ensuring the safe and effective use of pharmaceutical products, protecting public health, and minimizing risks associated with medications.

Inter-rater agreement between WHO- Uppsala Monitoring Centre system and Naranjo algorithm for causality assessment of adverse drug reactions

Determining the causality of Adverse Drug Reactions (ADRs) is essential for management and prevention of future occurrences. The WHO-Uppsala Monitoring Centre (UMC) system is recommended under the Pharmacovigilance Program of India whereas Naranjo's algorithm is commonly utilized by clinicians, but their agreement remains a subject of investigation. This study aims to compare the inter-rater agreement between these two scales for causality assessment of ADRs. In this cross-sectional study, two groups of pharmacovigilance experts were given a set of total 399 anonymized individual case safety reports, collected over six months. The raters were blinded to each other's assessments and applied the WHO-UMC system and Naranjo algorithm to each case independently. Inter-rater agreement was then evaluated utilizing Cohen's kappa. The suspected ADRs were also comprehensively analysed on parameters like age, sex, route of administration, speciality, organ system affected, most common drug categories and individual drugs, outcome of ADRs. Analysis of 399 suspected ADRs revealed that mean age of patients was 36.8 ± 18.0 years, females were more frequently affected, highest proportion of reports were from psychiatry inpatients, seen with antipsychotic drugs, involved the central nervous system, with oral administration, and 91% resolved. On causality assessment by the WHO-UMC system, 53.3% were “Certain” whereas Naranjo's algorithm categorized 96.74% of ADRs as “Probable”. Cohen's kappa showed a “Minimal” agreement (0.22) between WHO-UMC and Naranjo system of causality assessment. The considerable lack of agreement between the two commonly employed systems of causality assessment of ADRs warrants further investigation into specific factors influencing the disagreement to improve the accuracy of causality assessments.

Safety monitoring of precautionary third dose of COVID-19 vaccines in a district in Northern India.

The World Health Organization (WHO) declared Coronavirus disease-19 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) a pandemic on March 11, 2020. On 16th January 2021, India began its vaccination programme using two COVID-19 vaccines (Covishield and Covaxin). Precautionary dose (booster shots) was administered to health and front-line workers in the beginning and then to all eligible populations. This was a descriptive observational study conducted in the COVID-19 vaccination centres of Karnal district and the ADR monitoring centre, KCGMC, Karnal. During the visits to vaccination centres, all beneficiaries of the precautionary third dose of COVID-19 vaccines as well as healthcare workers were sensitized to report in case of any adverse event following vaccination as part of the policy of the vaccination programme run by the government and Pharmacovigilance Programme of India. The data were collected in suspected adverse drug reaction (ADR) reporting form version 1.4, and causality assessment was done as per the WHO-UMC scale. The data were analysed as simple proportions and percentages. The booster dose was administered to 72,853 individuals, while the 1st dose and 2nd dose were given to 13,30,042 and 10,73,050, respectively. Only three ADRs were reported with the booster dose in 34 vaccination centres in the Karnal district. These three ADRs were classified as unlikely on causality assessment and hence not included in the analysis. The booster dose administered for the prevention of COVID-19 has been found to be reasonably safe. The population who received COVID-19 booster doses was significantly less than the populations who received the first and second doses, which suggests a low acceptance rate.

Assessment of Knowledge, Attitude and Practice of Pharmacovigilance among Healthcare Professionals: A Cross-sectional Study at a Tertiary Hospital in Eastern Nepal

Introduction: Adverse drug reactions (ADRs) pose a major concern worldwide causing substantial morbidity and mortality. Healthcare professionals involved in identification, documentation and reporting of ADRs are the pillars of a pharmacovigilance program. Lack of knowledge influence the ADR reporting by healthcare professionals. Objective: To assess knowledge, attitude and practice of pharmacovigilance among healthcare professionals working at Koshi Hospital, Biratnagar, Nepal. Methodology: A descriptive cross-sectional study was conducted among healthcare professionals working at Koshi Hospital, Biratnagar, Nepal from August-December 2021 using a semi-structured proforma. Ethical clearance was obtained from Nepal Health Research Council, Kathmandu (396/2021P). The data were entered into Microsoft Excel 2010 and the descriptive statistics like mean, standard deviation, frequency and percentage were calculated. Statistical Package for the Social Sciences (version 11.5) was used for all statistical analysis. The findings were presented as tables and graphs. Results: Out of 88 healthcare professionals, 57 (64.77%) were females and 35 (39.77%) were staff nurse. Fifty-six (63.64%) participants knew that Department of Drug Administration is the authorized National center for pharmacovigilance program in Nepal. Thirty-six (40.91%) participants had good knowledge and 52 (59.09%) had poor knowledge of pharmacovigilance. Seventy-nine (89.77%) participants had positive attitude and 41 (46.59%) participants had poor practice. Seventy (79.55%) participants had not seen ADR reporting form. Conclusion: The healthcare professionals had insufficient knowledge, positive attitude and poor practice of pharmacovigilance. Efforts are required to enhance knowledge and good practice among healthcare professionals toward pharmacovigilance and ADR reporting which would ultimately strengthen the pharmacovigilance program.

Artificial intelligence in pharmacovigilance - Opportunities and challenges.

Pharmacovigilance (PV) is a data-driven process to identify medicine safety issues at the earliest by processing suspected adverse event (AE) reports and extraction of health data. The PV case processing cycle starts with data collection, data entry, initial checking completeness and validity, coding, medical assessment for causality, expectedness, severity, and seriousness, subsequently submitting report, quality checking followed by data storage and maintenance. This requires a workforce and technical expertise and therefore, is expensive and time-consuming. There has been exponential growth in the number of suspected AE reports in the PV database due to smart collection and reporting of individual case safety reports, widening the base by increased awareness and participation by health-care professionals and patients. Processing of the enormous volume and variety of data, making its sensible use and separating "needles from haystack," is a challenge for key stakeholders such as pharmaceutical firms, regulatory authorities, medical and PV experts, and National Pharmacovigilance Program managers. Artificial intelligence (AI) in health care has been very impressive in specialties that rely heavily on the interpretation of medical images. Similarly, there has been a growing interest to adopt AI tools to complement and automate the PV process. The advanced technology can certainly complement the routine, repetitive, manual task of case processing, and boost efficiency; however, its implementation across the PV lifecycle and practical impact raises several questions and challenges. Full automation of PV system is a double-edged sword and needs to consider two aspects - people and processes. The focus should be a collaborative approach of technical expertise (people) combined with intelligent technology (processes) to augment human talent that meets the objective of the PV system and benefit all stakeholders. AI technology should enhance human intelligence rather than substitute human experts. What is important is to emphasize and ensure that AI brings more benefits to PV rather than challenges. This review describes the benefits and the outstanding scientific, technological, and policy issues, and the maturity of AI tools for full automation in the context to the Indian health-care system.