Navigating duplication in pharmacovigilance databases: a scoping review.

OBJECTIVES: Pharmacovigilance databases play a critical role in monitoring drug safety. The duplication of reports in pharmacovigilance databases, however, undermines their data integrity. This scoping review sought to provide a comprehensive understanding of duplication in pharmacovigilance databases worldwide. DESIGN: A scoping review. DATA SOURCES: Reviewers comprehensively searched the literature in PubMed, Web of Science, Wiley Online Library, EBSCOhost, Google Scholar and other relevant websites. ELIGIBILITY CRITERIA: Peer-reviewed publications and grey literature, without language restriction, describing duplication and/or methods relevant to duplication in pharmacovigilance databases from inception to 1 September 2023. DATA EXTRACTION AND SYNTHESIS: We used the Joanna Briggs Institute guidelines for scoping reviews and conformed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Two reviewers independently screened titles, abstracts and full texts. One reviewer extracted the data and performed descriptive analysis, which the second reviewer assessed. Disagreements were resolved by discussion and consensus or in consultation with a third reviewer. RESULTS: We screened 22 745 unique titles and 156 were eligible for full-text review. Of the 156 titles, 58 (47 peer-reviewed; 11 grey literature) fulfilled the inclusion criteria for the scoping review. Included titles addressed the extent (5 papers), prevention strategies (15 papers), causes (32 papers), detection methods (25 papers), management strategies (24 papers) and implications (14 papers) of duplication in pharmacovigilance databases. The papers overlapped, discussing more than one field. Advances in artificial intelligence, particularly natural language processing, hold promise in enhancing the efficiency and precision of deduplication of large and complex pharmacovigilance databases. CONCLUSION: Duplication in pharmacovigilance databases compromises risk assessment and decision-making, potentially threatening patient safety. Therefore, efficient duplicate prevention, detection and management are essential for more reliable pharmacovigilance data. To minimise duplication, consistent use of worldwide unique identifiers as the key case identifiers is recommended alongside recent advances in artificial intelligence.

First results from the lessons learnt from the deployment of the Med Safety App for reporting adverse drug reactions in Ghana.

Background: The use of mobile phone technology for reporting adverse drug reactions (ADRs) in pharmacovigilance is relatively new.The objective of the study was to explore challenges and facilitators for the use of the Med Safety App for reporting ADRs in Ghana. A comparative evaluation of ADR reports received through the app and the standard paper-based form was also conducted. Methods: This was a cross-sectional study with a purposive sampling technique. The study population was persons who had downloaded the Med Safety App launched in Ghana 18 months before the study. Results: Of the 350 participants, 121 provided answers to the questionnaire sent as a Google form, representing a response rate of 34.6%.Ninety-five (78.5%) of the participants were healthcare professionals, and the remaining were patients. Seventy-five (64.7%) of the participants were using the app after initial installation because they thought it had helpful features. However, only 33 (27.3%) participants used the app to report ADRs, and of these, seven (21.2%) participants indicated that they would continue to use the app because it was easier than the other means of reporting ADRs. Most of the respondents, 109 (94%), indicated that they would recommend the app to someone else. There were some differences between the reports received through the app and between the paper-based Council for International Organizations of Medical Sciences (CIOMS) 1 form and the app, which warrant further exploration. Conclusion: Most participants indicated that the app is a useful tool and easy to use, and they were satisfied with the features of the app. Given that only just under one-third of participants had used the app to report ADRs, more time and training may be required to fully evaluate the feasibility of the use of the app going forward. The findings will help improve introduction of the app in other countries.

Facilitators and Barriers to Uptake of the Med Safety Mobile App for Adverse Drug Reaction Reporting by Health Workers in Uganda: A Qualitative Study.

INTRODUCTION: Adverse drug reactions (ADRs) are an important public health challenge worldwide; however, pharmacovigilance systems are plagued by under-reporting. Mobile technologies, including mobile applications such as Med Safety, could strengthen ADR reporting. We explored the acceptability, and factors that could influence uptake of, Med Safety for ADR reporting by health workers in Uganda. METHODS: The study took place between July and September 2020 in 12 HIV clinics in Uganda and employed a qualitative exploratory research design. We conducted 22 in-depth interviews and 3 mixed-gender focus group discussions (49 participants) with a diverse range of health workers. We analysed the data using a thematic approach. RESULTS: There was goodwill among the health workers to adopt Med Safety for ADR reporting and the majority would recommend the app to other health workers. Training with practice increased acceptability of the app. Uptake of the app was favoured by the younger, technology proficient, health worker demographic; the app's offline and two-way risk communication functionalities; availability of free internet hotspots at some health facilities; goodwill and willingness of health workers to report ADRs; and the cumbersome nature of conventional ADR reporting tools. Potential barriers to the uptake of Med Safety were the perceived lengthy processes of initial app registration and completion of multiple screens during ADR reporting; challenges with health workers' smartphones (incompatibility with application, no space for more applications, low battery charge); high cost of internet data; poor internet connectivity; difficulty in recognising ADRs, language barrier and poor feedback to ADR reporters. CONCLUSION: There was goodwill among the health workers to adopt Med Safety for ADR reporting and the majority would recommend the app to other health workers. Training with practice increased acceptability of the app and should be integral in all future app roll-out campaigns. The identified facilitators and barriers could be used to appropriately guide future research and implementation to promote the uptake of Med Safety for pharmacovigilance in low- and middle-income countries.

Effectiveness of the Med Safety mobile application in improving adverse drug reaction reporting by healthcare professionals in Uganda: a protocol for a pragmatic cluster-randomised controlled trial.

INTRODUCTION: Combination antiretroviral therapy (cART) has massively reduced HIV mortality. However, long-term cART increases the risk of adverse drug reactions (ADRs), which can lead to higher morbidity, mortality and healthcare costs for people living with HIV (PLHIV).Pharmacovigilance-monitoring the effects of medicines-is essential for understanding real-world drug safety. In Uganda, pharmacovigilance systems have only recently been developed, and rates of ADR reporting for cART are very low. Thus, the safety profile of medicines currently used to treat HIV and tuberculosis in our population is poorly understood.The Med Safety mobile application has been developed through the European Union's Innovative Medicines Initiative WEB-Recognising Adverse Drug Reactions project to promote digital pharmacovigilance. This mobile application has been approved for ADR-reporting by Uganda's National Drug Authority. However, the barriers and facilitators to Med Safety uptake, and its effectiveness in improving pharmacovigilance, are as yet unknown. METHODS AND ANALYSIS: A pragmatic cluster-randomised controlled trial will be implemented over 30 months at 191 intervention and 191 comparison cART sites to evaluate Med Safety. Using a randomisation sequence generated by the sealed envelope software, we shall randomly assign the 382 prescreened cART sites to the intervention and comparison arms. Each cART site is a cluster that consists of healthcare professionals and PLHIV receiving dolutegravir-based cART and/or isoniazid preventive therapy. Healthcare professionals enrolled in the intervention arm will be trained in the use of mobile-based, paper-based and web-based reporting, while those in the comparison arm will be trained in paper-based and web-based reporting only. ETHICS AND DISSEMINATION: Ethical approval was given by the School of Biomedical Sciences Research and Ethics Committee at Makerere University (SBS-REC-720), and administrative clearance was obtained from Uganda National Council for Science and Technology (HS1366ES). Study results will be shared with healthcare professionals, policymakers, the public and academia. TRIAL REGISTRATION NUMBER: PACTR202009822379650.

Implementation of a peer support intervention to promote the detection, reporting and management of adverse drug reactions in people living with HIV in Uganda: a protocol for a quasi-experimental study.

INTRODUCTION: Patients have contributed <1% of spontaneous adverse drug reaction (ADR) reports in Uganda's pharmacovigilance database. Peer support combined with mobile technologies could empower people living with HIV (PLHIV) to report ADRs and improve ADR management through linkage to care. We seek to test the feasibility and effect of a peer support intervention on ADR reporting by PLHIV receiving combination antiretroviral therapy (cART) in Uganda; identify barriers and facilitators to the intervention; and characterise ADR reporting and management. METHODS AND ANALYSIS: This is a quasi-experimental study to be implemented over 4 months at 12 intervention and 12 comparison cART sites from four geographical regions of Uganda. Per region, two blocks each with a tertiary, secondary and primary care cART site will be selected by simple random sampling. Blocks per region will be randomly assigned to intervention and comparison arms.Study units will include cART sites and PLHIV receiving cART. PLHIV at intervention sites will be assigned to peer supporters to empower them to report ADRs directly to the National Pharmacovigilance Centre (NPC). Peer supporters will be expert clients from among PLHIV and/or recognised community health workers.Direct patient reporting of ADRs to NPC will leverage the Med Safety App and toll-free unstructured supplementary service data interface to augment traditional pharmacovigilance methods.The primary outcomes are attrition rate measured by number of study participants who remain in the study until the end of follow-up at 4 months; and number of ADR reports submitted to NPC by PLHIV as measured by questionnaire and data abstraction from the national pharmacovigilance database at baseline and 4 months. ETHICS AND DISSEMINATION: The study received ethical approval from: School of Health Sciences Research and Ethics Committee at Makerere University (MAKSHSREC-2020-64) and Uganda National Council for Science and Technology (HS1206ES). Results will be shared with PLHIV, policy-makers, the public and academia. TRIAL REGISTRATION NUMBER: ISRCTN75989485.

Recommendations for the Use of Social Media in Pharmacovigilance: Lessons from IMI WEB-RADR.

Over a period of 3 years, the European Union's Innovative Medicines Initiative WEB-RADR project has explored the value of social media (i.e., information exchanged through the internet, typically via online social networks) for identifying adverse events as well as for safety signal detection. Many patients and clinicians have taken to social media to discuss their positive and negative experiences of medications, creating a source of publicly available information that has the potential to provide insights into medicinal product safety concerns. The WEB-RADR project has developed a collaborative English language workspace for visualising and analysing social media data for a number of medicinal products. Further, novel text and data mining methods for social media analysis have been developed and evaluated. From this original research, several recommendations are presented with supporting rationale and consideration of the limitations. Recommendations for further research that extend beyond the scope of the current project are also presented.

Establishing a Framework for the Use of Social Media in Pharmacovigilance in Europe.

The Innovative Medicines Initiative (IMI) WEB-RADR (Web-Recognising Adverse Drug Reactions) project looked at opportunities and challenges in using social media in pharmacovigilance as a rapidly evolving source of large, real-time data, which could provide new information on the actual use of medicines and potential safety issues. Two of the objectives were to develop principles for continuous monitoring of the safety of medicines without overburdening established pharmacovigilance systems and to propose a regulatory framework on the use of social media in pharmacovigilance. As a starting point, a review of existing legal requirements and regulatory guidance on social media use in pharmacovigilance was performed based on a survey conducted in 2014-2015. Furthermore, input from two large stakeholder workshops and evidence gathered from the research performed by WEB-RADR on the analysis of social media data were taken into consideration. Whilst analytical results of WEB-RADR indicated limited value of social media in detecting or confirming signals for a majority of the drugs studied, it is important to establish a regulatory framework for the use of social media in pharmacovigilance. Thus, the screening and reporting of suspected adverse reactions remains an important pillar in monitoring the safety and efficacy of medicines and the identification of new safety issues. Principles as to how social media can be used in pharmacovigilance are absolutely needed to provide clarity to patients, healthcare professionals, medicines regulators and the pharmaceutical industry.

Recommendations on the Use of Mobile Applications for the Collection and Communication of Pharmaceutical Product Safety Information: Lessons from IMI WEB-RADR.

Over a period of 3 years, the European Union's Innovative Medicines Initiative WEB-RADR (Recognising Adverse Drug Reactions; https://web-radr.eu/ ) project explored the value of two digital tools for pharmacovigilance (PV): mobile applications (apps) for reporting the adverse effects of drugs and social media data for its contribution to safety signalling. The ultimate intent of WEB-RADR was to provide policy, technical and ethical recommendations on how to develop and implement such digital tools to enhance patient safety. Recommendations relating to the use of mobile apps for PV are summarised in this paper. There is a presumption amongst at least some patients and healthcare professionals that information ought to be accessed and reported from any setting, including mobile apps. WEB-RADR has focused on the use of such technology for reporting suspected adverse drug reactions and for broadcasting safety information to its users, i.e. two-way risk communication. Three apps were developed and publicly launched within Europe as part of the WEB-RADR project and subsequently assessed by a range of stakeholders to determine their value as effective tools for improving patient safety; a fourth generic app was later piloted in two African countries. The recommendations from the development and evaluation of the European apps are presented here with supporting considerations, rationales and caveats as well as suggested areas for further research.

Use of a Patient-Friendly Terms List in the Adverse Drug Reaction Report Form: A Database Study.

INTRODUCTION: When reporting adverse drug reactions to pharmacovigilance centres, patients and consumers can describe adverse drug reactions experienced in free-text format. Recently, a patient-friendly adverse drug reaction terms list was introduced in the adverse drug reaction report form in the UK to facilitate this reporting. OBJECTIVE: The objective of this study was to evaluate the actual use of the patient-friendly terms list in the adverse drug reaction report form and its association with the type of adverse drug reactions reported. METHODS: We conducted a database study in which we reviewed the list's use for all reported adverse drug reactions by patients and consumers to the pharmacovigilance centre in the UK via the online report form between August and September 2017. Descriptive statistics were used. In addition, for adverse drug reactions reported more than 20 times, Chi-squared tests were used to test for differences in the number of reports in which the patient-friendly terms list was used and those in which the adverse drug reaction was entered as free text. RESULTS: In total, 888 reports were received. In 185 reports (21%), the patient-friendly terms list was used to enter an adverse drug reaction. In total, the reports contained 3227 adverse drug reactions. Nausea, headache, diarrhoea, dizziness, insomnia, anxiety, depression, fatigue, tiredness, vomiting, appetite lost, joint pain, chest pain, constipation and pain were reported more than 20 times. Five of these adverse drug reactions (i.e. nausea, diarrhoea, dizziness, insomnia and constipation) were reported significantly more often in reports where the adverse drug reactions were selected from the patient-friendly terms list. CONCLUSIONS: Most people chose to describe adverse drug reactions in their own words rather than selecting adverse drug reactions from a patient-friendly terms list. Although the patient-friendly terms list may be a useful feature for some patients or for some adverse drug reactions, it should not replace the option for patients to describe adverse drug reactions in their own words.

Exploring the Potential Routine Use of Electronic Healthcare Record Data to Strengthen Early Signal Assessment in UK Medicines Regulation: Proof-of-Concept Study.

INTRODUCTION: Electronic healthcare record (EHR) databases are used within pharmacoepidemiology studies to confirm or refute safety signals arising from spontaneous adverse event reports. However, there has been limited routine use of such data earlier in the signal management process, to help rapidly contextualise signals and strengthen preliminary assessment or to inform decisions regarding action including the need for further studies. This study explores the value of EHR used in this way within a regulatory environment via an automated analysis platform. METHODS: Safety signals raised at the UK Medicines and Healthcare products Regulatory Agency (MHRA) between July 2014 and June 2015 were individually reviewed by a multi-disciplinary team. They assessed the feasibility of identifying the exposure and event of interest using primary care data from the Clinical Practice Research Datalink (CPRD) within the Commonwealth Vigilance Workbench (CVW) Longitudinal Module platform, which was designed to facilitate routine descriptive analysis of signals using EHR. Three signals, where exposure and event could be well identified, were retrospectively analysed using the platform. RESULTS: Of 69 unique new signals, 20 were for drugs prescribed predominately in secondary care or available without prescription, which would not be identified in primary care. A further 17 were brand, formulation, or dose-specific issues, were related to mortality, were relevant only to a subgroup of patients, or were drug interactions, and hence could not be reviewed using the platform given its limitations. Analyses of exposure and incidence of the adverse event could be produced using CPRD within the CMV Longitudinal Module for 32 (46%) signals. The case studies demonstrated that the data provided supporting evidence for confirming initial assessment of the signal and deciding upon the need for further action. CONCLUSIONS: CPRD can routinely provide useful early insights into clinical context when assessing a large proportion of safety signals within a regulatory environment provided that a flexible approach is adopted within the analysis platform.

Good Signal Detection Practices: Evidence from IMI PROTECT.

Over a period of 5 years, the Innovative Medicines Initiative PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium) project has addressed key research questions relevant to the science of safety signal detection. The results of studies conducted into quantitative signal detection in spontaneous reporting, clinical trial and electronic health records databases are summarised and 39 recommendations have been formulated, many based on comparative analyses across a range of databases (e.g. regulatory, pharmaceutical company). The recommendations point to pragmatic steps that those working in the pharmacovigilance community can take to improve signal detection practices, whether in a national or international agency or in a pharmaceutical company setting. PROTECT has also pointed to areas of potentially fruitful future research and some areas where further effort is likely to yield less.