Experiences with the use of varenicline in daily practice in the Netherlands:A prospective, observational cohort study

BACKGROUND: Although a concise overview of adverse drug reactions (ADRs) to varenicline is available, little is known about the use of varenicline in daily practice and time-related information about ADRs. OBJECTIVE: The aim of this study was to gain insight in the safety and use of varenicline in daily practice. METHODS: A prospective, observational, non-interventional cohort study was performed. The study population was defined as first-time users recruited through participating pharmacies between 1 December 2008 and 31 March 2012. Patients could sign up for the study on a dedicated website. Web-based questionnaires were sent after 1, 2 and 6 weeks, 3 months and 4 months after patients started to use varenicline. Questions were asked about drug use and ADRs. Information about the ADR, its seriousness and the action taken when experiencing an ADR was gathered. RESULTS: A total of 1,418 patients signed up for the study. The response rates for the various questionnaires varied from 31.3 to 62.5 %. At least one ADR was reported by 58.8 % of the patients. The most frequently reported ADRs were nausea (30.8 %), abdominal pain (11.2 %) and abnormal dreaming (10.4 %). Most patients did not stop taking varenicline when they experienced these ADRs. The median latency times for ADRs reported more than 50 times were 3-7 days, with an exception for depressed mood, which had a latency time of 10 days. CONCLUSION: This prospective cohort study has given insight into latency time and action taken with varenicline when ADRs occur during treatment with varenicline in daily practice. It confirms the ADR pattern detected prior to marketing of the drug

Results of the Experience with the Use of Varenicline in Daily Practice Using Intensive Monitoring

Background: Although a concise overview of Adverse Drug Reactions (ADRs) of varenicline is known, little is known about the time related information about ADRs of varenicline such as for example latencies. Objectives: To gain insight in the experience and safety of varenicline in daily practice as reported by patients through web-based questionnaires using an intensive monitoring system. Methods: Design A prospective, observational, non-interventional cohort study. Setting: First-time users of varenicline were defined as patients who have not filled in a prescription of varenicline in the previous 12 months using the first prescription signal in that particular pharmacy. Participants: All first-time users of varenicline in participating pharmacies between 1 December 2008 and 31 March 2012 were invited for the study. Patients could sign up for the study on a dedicated website. Electronic questionnaires were sent after 1, 2 and 6 weeks, 3 months and 4 months after they started to use varenicline. In these questionnaires questions about drug use and ADRs were asked for. Main outcome measurements: Information about the ADR, seriousness, and action taken when experiencing an ADR. Statistical analysis: Descriptive analysis was done using Microsoft Access. Results: About 1,418 patients signed up for the study. Response rates for the various questionnaires vary from 31.3% to 62.5%. 58.8% of the patients reported at least one ADR. The most frequently reported ADRs were nausea (30.8%), abdominal pain (11.2%) and abnormal dreaming (10.3%) which are listed in the Summary of Product Characteristics (SmPC) of varenicline. Median latency times were 3-7 days, with exception for depressed mood (10 days). The number of ADRs did not abate over time. No signals were detected. During treatment 43.9% of the patients stopped using varenicline. The main reasons for stopping were the occurrence of ADRs (42.2%) and other (40%) unspecified reasons. Conclusions: This study indicates that varenicline is a relatively safe drug. The reported ADRs correspond with the ADRs mentioned in the SmPC of varenicline with a median latency of 3-7 days. The number of ADRs do not abate over time

First experiences with a tool to measure the level of clinical information present in adverse drug reaction reports

Background: To make a proper causality assessment of an adverse drug reaction (ADR) report, a certain level of clinical information is necessary. A tool was developed to measure the level of clinical information present in ADR reports. The aim of this study was to test the validity and reliability of the clinical documentation tool (ClinDoc) in an international setting. Methods: The tool was developed by a panel of pharmacovigilance experts. It includes four domains: ADR, chronology of the ADR, suspected drug and patient characteristics. The final score categorizes reports into: excellent, well, moderately or poorly documented. In two rounds, eight pharmacovigilance assessors of different countries made a total of 224 assessments using the tool, with the expert panels judgement as a standard. Sensitivity and specificity were calculated. Results: The tool with four outcome-categories demonstrated low sensitivity. A lack of distinctiveness was demonstrated between the categories moderate and well. Results for the second round were reanalysed using three categories. This demonstrated a better validity. Conclusion: This is the first tool to give insight in the level of relevant clinical information present in ADR reports. It can be used internationally to compare reports coming from different reporting methods and different types of reporters in pharmacovigilance

Expectations for feedback in adverse drug reporting by healthcare professionals in the Netherlands

Background: In 2010, the Netherlands Pharmacovigilance Centre Lareb received more than 4000 reports from healthcare professionals (HCPs). All HCPs received individual personal feedback containing information about the reported drug-adverse drug reaction (ADR) association. It is unclear what type of information HCPs expect in this feedback letter. Objective: The aim of the study was to examine the expectations of the personal feedback of HCPs who reported an ADR to the Netherlands Pharmacovigilance Centre Lareb. Methods: A questionnaire survey was conducted among a random sample of 1200 pharmacists, general practitioners (GPs) and medical specialists who reported an ADR to the Netherlands Pharmacovigilance Centre Lareb between 1 January 2009 and 27 January 2010. Responders and non-responders were compared on the basis of profession, number of reports submitted to the pharmacovigilance since 2007 and their last report being serious or not. Questions were asked about the importance of personal feedback and the type of information reporters would like to see in their personal feedback. Both linear and logistic regression analysis were performed, with correction for possible confounding factors. Results: The response rate to the questionnaire was 34.6% (n = 399). The type of information the respondents generally would like to see in their personal feedback is information about the time course of the ADR and information about the pharmacological mechanism. However, GPs were, in general, less interested in receiving feedback than pharmacists and medical specialists. Most of the respondents were (very) unsatisfied if they received only a confirmation letter instead of personal feedback. Personalized feedback was considered to be (very) important for reporting an ADR in the future. Most of the respondents (80.3%) stated that the personal feedback increased their knowledge. Only 0.6% of respondents had not read the personalized feedback. No differences were found between responders and non-responders, with the exception that responders had reported statistically more often to the Netherlands Pharmacovigilance Centre Lareb in the past 3 years. Conclusions: Most of the respondents would like personal feedback instead of a standard confirmation letter. In general, pharmacists and medical specialists would like more information than GPs. The information in this study is useful in generating more customized personal feedback in the future, and could be useful for other pharmacovigilance centres that are interested in writing personalized feedback to make available to reporters

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. METHODS: A COVID-19 tailored vaccine web-based reporting form collected information on the vaccine administered, AEFIs and other (medical) information. A fully automated process for ICSRs enabled the handling of the majority of common and known reported AEFIs. All other ICSRs were triaged daily and processed separately. There were daily signal detection meetings and weekly reports for batch analysis. RESULTS: In 2021, Lareb received 184,411 ICSRs, a reporting rate of 0.67% for vaccines given in the Netherlands. 887,954 AEFIs were reported, mostly well-known, nonserious AEFIs; 2.4% were serious and 0.3% were fatal. 33.1% of all ICSRs were processed fully automatically. Based on the daily triage, 4.2% were flagged as ‘high priority’; 62.7% as ‘low-priority’. Twenty-seven signals and news stories about the COVID-19 vaccines were disseminated. CONCLUSIONS: Due to automatic processing of well-known AEFIs, daily triage and signal detection meetings, 99.9% of the ICSRs were processed within the compliance timeframe to Eudravigilance, and signal detection was performed during a large-scale vaccination campaign. These experiences may serve as a blueprint for future mass vaccination programs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40264-022-01253-5