Adverse Drug Reactions to Opioids: A Study in a National Pharmacovigilance Database.

Introduction: Opioids are commonly used as analgesics; however, like any medicine, they can produce adverse drug reactions (ADRs), including nausea, constipation, dependence, and respiratory depression, that result in harmful and fatal events. Therefore, it is essential to monitor the safety of these drugs in clinical practice.

Objective: This study aimed to characterize the safety profile of opioids by conducting a descriptive study based on a spontaneous reporting system (SRS) for ADRs in The Netherlands, focusing on abuse, misuse, medication errors, and differences between sexes.

Spontaneously reported adverse events following COVID-19 basic and booster immunizations in the Netherlands.

Introduction: The rapid roll-out of novel COVID-19 vaccines made near real-time post-marketing safety surveillance essential to identify rare and long-term adverse events following immunization (AEFIs). In light of the ongoing booster vaccination campaigns, it is key to monitor changes in observed safety patterns post-vaccination. The effect of sequential COVID-19 vaccinations, as well as heterologous vaccination sequences, on the observed post-vaccination safety pattern, remains largely unknown.

Optimizing Safety Surveillance for COVID-19 Vaccines at the National Pharmacovigilance Centre Lareb: One Year of COVID-19 Vaccine Experience.

Introduction: Due to the COVID-19 vaccination campaign, national pharmacovigilance (PV) centres had to deal with high volumes of Individual Case Safety Reports (ICSRs) that needed to be processed and assessed in a short time span. This necessitated the development of a dedicated system to enable near real-time vaccine safety monitoring at the Dutch PV Centre Lareb.

Objectives: To describe infrastructure, processes and Adverse Events Following Immunisation (AEFIs) reported for vaccine safety monitoring of COVID-19 vaccines during a large-scale vaccination campaign in the Netherlands.

Quantification of Adverse Drug Reactions Related to Drug Switches in The Netherlands.

We performed a retrospective cohort study in the Dutch patient population to identify active substances with a relatively high number of adverse drug reactions (ADRs) potentially related to drug switching. For this, we analyzed drug switches and reported ADRs related to switching between June 1, 2009, and December 31, 2016, for a selection of 20 active substances. We also compared pharmacovigilance analyses based on the absolute, switch-corrected, and user-corrected numbers of ADRs.

Time to onset in statistical signal detection revisited: A follow-up study in long-term onset adverse drug reactions.

Purpose: In a previous study, we developed a signal detection method using the time to onset (TTO) of adverse drug reactions (ADRs). The aim of the current study was to investigate this method in a subset of ADRs with a longer TTO and to compare its performance with disproportionality analysis.

Methods: Using The Netherlands's spontaneous reporting database, TTO distributions for drug-ADR associations with a median TTO of 7 days or more were compared with other drugs with the same ADR using the two-sample Anderson-Darling (AD) test.

Sex Differences in Reported Adverse Drug Reactions of Selective Serotonin Reuptake Inhibitors.

Introduction: Several studies have investigated sex as a risk factor for the occurrence of adverse drug reactions (ADRs) and found that women are more likely to experience ADRs than men.

Objective: The aim of this explorative study was to investigate whether differences exist in reported ADRs of selective serotonin reuptake inhibitors (SSRIs) for men and women in the database of the Netherlands Pharmacovigilance Centre Lareb.

Methods: A ratio of reports concerning women and men, corrected for the number of users, was calculated for all the ADRs reported on SSRIs.

A prediction model-based algorithm for computer-assisted database screening of adverse drug reactions in the Netherlands.

Purpose: The statistical screening of pharmacovigilance databases containing spontaneously reported adverse drug reactions (ADRs) is mainly based on disproportionality analysis. The aim of this study was to improve the efficiency of full database screening using a prediction model-based approach.

Methods: A logistic regression-based prediction model containing 5 candidate predictors was developed and internally validated using the Summary of Product Characteristics as the gold standard for the outcome.

When More Is Less: An Exploratory Study of the Precautionary Reporting Bias and Its Impact on Safety Signal Detection.

Concerns have been expressed that large numbers of nonvalue-added reports have been accumulating in adverse drug reaction (ADR) databases, for example, via patient support programs. We performed an assessment of the impact of such reports, which we refer to as "precautionary reports," on safety signal detection in the Netherlands. The case narratives of ADR reports of three case products were screened with text-mining algorithms to identify those reports that lack a causal relationship with the suspected medicinal product.

Nanomedicinal products: a survey on specific toxicity and side effects.

Due to their specific properties and pharmacokinetics, nanomedicinal products (NMPs) may present different toxicity and side effects compared to non-nanoformulated, conventional medicines. To facilitate the safety assessment of NMPs, we aimed to gain insight into toxic effects specific for NMPs by systematically analyzing the available toxicity data on approved NMPs in the European Union. In addition, by comparing five sets of products with the same active pharmaceutical ingredient (API) in a conventional formulation versus a nanoformulation, we aimed to identify any side effects specific for the nano aspect of NMPs.

The value of time-to-onset in statistical signal detection of adverse drug reactions: a comparison with disproportionality analysis in spontaneous reports from the Netherlands.

Purpose: In pharmacovigilance, the commonly used disproportionality analysis (DPA) in statistical signal detection is known to have its limitations. The aim of this study was to investigate the value of the time to onset (TTO) of ADRs in addition to DPA.

Methods: We performed a pilot study using individual case safety reports (ICSRs) for three drugs (Cervarix®, nitrofurantoin and simvastatin) from the Lareb spontaneous reporting database.

Traceability of Biologics in The Netherlands: An Analysis of Information-Recording Systems in Clinical Practice and Spontaneous ADR Reports.

Introduction And Objective: Pharmacovigilance requirements for biologics mandate that EU Member States shall ensure that any biologic that is the subject of a suspected adverse drug reaction (ADR) is identifiable by brand name and batch number. Recent studies showed that brand name identification is well established, whereas batch numbers are (still) poorly reported. We evaluated information-recording systems and practices in the Dutch hospital setting to identify determinants for brand name and batch number recording as well as success factors and bottlenecks for traceability.

Parametric time-to-onset models were developed to improve causality assessment of adverse drug reactions from antidiabetic drugs.

Objectives: The aim of this study was to investigate whether the time to onset (TTO) of common adverse drug reactions (ADRs) of antidiabetic drugs could be modeled using parametric distributions and whether these TTO distributions were dependent on patient characteristics. Furthermore, information relevant for daily clinical practice was to be obtained.

Study Design And Setting: We performed an exploratory TTO modeling study, using a cohort of diabetes mellitus patients.

Hearing impairment associated with oral terbinafine use: a case series and case/non-case analysis in the Netherlands Pharmacovigilance Centre Lareb database and VigiBase™.

Background: The Netherlands Pharmacovigilance Centre Lareb received reports of six cases of hearing impairment in association with oral terbinafine use. This study describes these cases and provides support for this association from the Lareb database for spontaneous adverse drug reaction (ADR) reporting and from Vigibase™, the ADR database of the WHO Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre.

Objectives: The objective of the current study was to identify whether the observed association between oral terbinafine use and hearing impairment, based on cases received by Lareb, constitutes a safety signal.