The Role of Adverse Event Follow-Up in Advancing the Knowledge of Medicines and Vaccines Safety: A Scoping Review.

INTRODUCTION AND

objectiveAdverse events (AEs) associated with medication and vaccine use are of significant concern in pharmacovigilance (PV), necessitating robust detection, documentation, and reporting mechanisms. The primary objective of this scoping review is to understand and evaluate the concept, implementation, frequency, and value of "follow-up" in the context of AE assessment. Secondary objectives include providing an overview of various definitions of "follow-up," describing the requirements and studies evaluating follow-up methods, and assessing how often follow-up is undertaken in assessing an AE, by whom, and its value.

methodsThis scoping review followed the 2018 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews. The protocol was registered on the Open Science Framework (OSF). The review included peer-reviewed literature and regulatory guidelines, the search strategy involved querying MEDLINE (via PubMed) and Embase for publications indexed from January 2013 to December 2023. The Rayyan

resultsThe search yielded 4,428 articles, with 23 studies meeting the inclusion criteria. Methods for follow-up varied among the studies, with digital tools such as emails, online surveys, and SMS utilized in 22% of the studies, achieving response rates ranging from 29 to 31%. Telephone follow-up was employed in 17% of studies, showing higher response rates between 62 and 89%. In settings with limited digital access, home visits were conducted in 9% of studies; only one study reported a response rate which was 74%. The nature of the follow-up approach was diverse: 35% of studies conducted open-ended follow-up, where no pre-determined AEs were specified, whilst 22% of studies focused on specific AEs or outcomes; the remaining 43% had other reasons such as deduplication, assessing informativeness, characterizing unlisted adverse drug reactions (ADRs) or were related to studies evaluating follow-up methods. The initiation of follow-up activities, including methodological research, was driven by academia in 30% of studies, PV centers in 44%, and marketing authorization holders (MAHs) in 26%. Consent practices varied across the studies: 39% of studies did not pre-consent individuals prior to requesting follow-up, while 31% secured consent to contact prior to follow-up, and the other 30% related to studies evaluating follow-up methods.

conclusionDespite the use of follow-up across all PV organizations, and existing regulatory guidance, there is a dearth of scientific research on the topic. While rates of follow-up were quoted between 19 and 100% there is inconsistency in the use of the term, and huge variability in the way follow-up was studied and the scenarios in which it was studied, constraining the ability to generalize. Further research is needed to determine the optimal types of reports and AEs that benefit most from follow-up, the correlation between the number of questions asked and response rates, and the impact of follow-up information on the evaluability of AE reports.