PurposeInvestigation of drug safety signals is one of the major tasks in pharmacovigilance. Among many potential signals identified, only a few reflect adverse drug reactions requiring regulatory actions, such as product information (PI) update. Limited information is available regarding the signal characteristics that might predict PI update following signal evaluation. The objective of this study was to identify signal characteristics associated with PI updates following signal evaluation by the European Medicines Agency Pharmacovigilance Risk Assessment Committee during 2012 to 2016.MethodsA comparative study was performed based on data from 172 safety signals. Characteristics of signals were extracted from the European Pharmacovigilance Issues Tracking Tool database. Multivariable logistic regression analysis was used to assess the relationship between signal characteristics and the decision to update the PI.ResultsMultivariable logistic regression analysis showed that the presence of evidence in multiple types of data sources (adjusted odds ratio [OR] 7.8 95% CI [1.5, 40.1]); mechanistic plausibility of the drug‐event association (adjusted OR 3.9 95% CI [1.9, 8.0]); seriousness of the event (adjusted OR 4.2 95% CI [1.3, 13.9]); and age of drugs ≤5 years (adjusted OR 3.9 95% CI [1.2, 12.7]) were associated with the decision to change the PI (P < 0.05).ConclusionsThis study identified 4 characteristics of drug safety signals that have shown to be associated with PI changes as outcome of signal evaluation. These characteristics may be used as criteria for selection and prioritization of potential signals that are more likely to necessitate product information updates.

There is a wide range of prioritization criteria described in the literature; however, few of them demonstrated predictive value. Many criteria with predictive value were related to strength of evidence category and to novelty. There were few attempts at integrating different criteria in decision support frameworks. Five of the frameworks were tested for validity and showed usefulness, while at least three are already in use for prioritization. Copyright © 2016 John Wiley & Sons, Ltd.

The aim of the study is to characterise safety signals based on the Dutch spontaneous reporting system (SRS) and to investigate the association between signal characteristics and Product Information (PI) update stratified by approval type: centrally authorised products (CAPs) versus nationally and decentralised authorised products (NAPs). Methods: This study evaluates the full cohort of signals disseminated from the Dutch SRS in the period from 2008 to 2017. Each retrieved signal was characterised on a number of aspects. The signal management process from signal generation to a potential PI update was analysed in four steps: (1) signal characterisation; (2) proposed actions by the Dutch national competent authority (NCA) for the signals;(3) presence of PI update (yes/no) and association with signal characteristics;(4) timing from the moment the signal was issued to PI update. For step 1-3 we stratified products in CAPs and NAPs.Results: Of all signals, 88.7% led to a proposed regulatory action by the NCA. Signals from the Dutch SRS for CAPs versus NAPs more often concerned biologicals, important medical events, class effects and shorter periods since marketing authorization.We detected PI updates for 26.2% of CAP signals and 61.3% of NAP signals. Conclusions:The Dutch SRSs remains an important source of signals. There are some notable differences in the characteristics of signals for CAPs versus NAPs. Signals for NAPs more frequently led to PI updates. Why is this important?While previous studies showed that the characteristics of drug safety signals from a variety of sources may affect regulatory actions, there is little information on how characteristics of safety signals derived specifically from national spontaneous reporting systems are associated with regulatory actions. The aim of the study is to characterise signals based on the Dutch spontaneous reporting system and to investigate the association between signal characteristics and Product Information updates for products with a centralised marketing authorization and those without.

Keywords adverse drug reaction, muscle rupture, statins AIMStatins are used in the treatment of hyperlipidaemia. They are among the most commonly prescribed drugs worldwide. Statins have been linked to musculoskeletal adverse drug reactions. However muscle rupture has not been discussed as an adverse drug reaction to statins so far. The aim of this article is to give an overview of cases of muscle rupture associated with the use of statins. METHODWe analyzed the cases of muscle rupture associated with the use of statins that were collected by the Netherlands Pharmacovigilance Centre Lareb complemented with the review of cases from the EudraVigilance database. RESULTSFifteen cases of muscle rupture associated with statin use have been identified in the database of the Netherlands Pharmacovigilance Centre. Overall, there was a plausible temporal association of events in most cases. In addition, the EudraVigilance database contained 165 reports of muscle rupture reported in patients using statins. Muscle rupture was disproportionally associated with statin use in both databases. The reporting odds ratio was 23.4 (95% CI 11.9, 46.0) and 14.6 (95% CI 12.3, 17.2), respectively. CONCLUSIONData from spontaneous reporting systems suggest that use of statins is associated with muscle rupture. Physicians and patients should be aware that this can occur. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Statins are among the most commonly prescribed drugs worldwide and are usually well tolerated.• However 10-15% of statin users develop statin-related musculoskeletal side effects, but muscle rupture has not been discussed as an adverse drug reaction to statins. WHAT THIS STUDY ADDS• Data from spontaneous reporting systems suggest that use of statins is associated with muscle rupture.• Physicians and patients should be aware that this can occur.

Introduction Previous studies have found differences in the communication of safety issues among medicines regulatory agencies. Objectives To explore (1) to what extent regulators’ opinions regarding the need to communicate safety issues related to sodium-glucose cotransporter-2 (SGLT2) inhibitors might be influenced by their concern about the safety issue, and (2) whether regulators’ concerns might be influenced by certain characteristics of the safety issue or by the demographic and professional characteristics and attitudes of the regulators. Methods An online cross-sectional survey study with a rating-based conjoint analysis among clinical and pharmacovigilance assessors from the EU regulatory network was performed between April and June 2021. Regulators were invited by email, and participants were asked about their level of concern and their opinion regarding the need to communicate about 12 scenarios defined by four characteristics: adverse drug reaction, source of information, causality, and frequency. The outcomes for the first objective were to update the summary of product characteristics (SmPC; yes/no) and to send direct healthcare professional communications (DHPC; yes/no). The determinant was regulators’ level of concern (range 0–100%). The outcome of the second objective was regulators’ level of concern, and the determinants were the characteristics of the safety issue, demographic and professional characteristics, and attitudes of the regulators (beliefs about medicines and risk perception). Results A total of 222 regulators completed the survey (64% women; mean age 46 ± 10 years). Depending on the scenario, 54–94% and 25–74% of the participants would update the SmPC or send a DHPC, respectively. The participants’ level of concern influenced their opinions regarding the need to update the SmPC and send a DHPC (odds ratio (OR) 13.0; 95% confidence interval (CI) 7.8–21.7 and OR 13.6; 95% CI 9.5–19.2, respectively, for every 10% increase in the level of concern). All characteristics of the safety issue influenced the level of concern. Younger participants, women, and those working for Eastern European agencies had a higher level of concern than older participants, men, and those working in other regions. Beliefs about medicines and general risk perception also influenced their concern. Conclusions The opinion regarding the need to communicate safety issues was influenced by the concern of regulators. Regulators’ concern was influenced by the characteristics of the safety issue, demographic characteristics, and attitudes. Diverse groups of experts regarding such factors would ensure that various views are incorporated in risk communication decisions. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-022-01270-4.