Dataset Information

An algorithm to detect unexpected increases in frequency of reports of adverse events in EudraVigilance.

ABSTRACT:

Purpose

The European Medicines Agency developed an algorithm to detect unexpected increases in frequency of reports, to enhance the ability to detect adverse events that manifest as increases in frequency, in particular quality defects, medication errors, and cases of abuse or misuse.

Methods

An algorithm based on a negative binomial time-series regression model run on 6 sequential observations prior to the monitored period was developed to forecast monthly counts of reports. A heuristic model to capture increases in counts when the previous 4 observations were null supplemented the regression. Count data were determined at drug-event combination. Sensitivity analyses were run to determine the effect of different methods of pooling or stratifying count data. Positive retrospective detections and positive predictive values (PPVs) were determined.

Results

The algorithm detected 8 of the 13 historical concerns, including all concerns of quality defects. The highest PPV (1.29%) resulted from increasing the lower count threshold from 3 to 5 and including literature reports in the counts. Both the regression model and the heuristic model components to the algorithm contributed to the detection of concerns. Sensitivity analysis indicates that stratification by commercial product reduces the PPV but suggests that pooling counts of related events may improve it.

Conclusion

The results are encouraging and suggest that the algorithm could be useful for the detection of concerns that manifest as changes in frequency of reporting; however, further testing, including in prospective use, is warranted.

SUBMITTER: Pinheiro LC

PROVIDER: S-EPMC5765515 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

An algorithm to detect unexpected increases in frequency of reports of adverse events in EudraVigilance.

Pinheiro Luis C LC Candore Gianmario G Zaccaria Cosimo C Slattery Jim J Arlett Peter P

Pharmacoepidemiology and drug safety 20171116 1

<h4>Purpose</h4>The European Medicines Agency developed an algorithm to detect unexpected increases in frequency of reports, to enhance the ability to detect adverse events that manifest as increases in frequency, in particular quality defects, medication errors, and cases of abuse or misuse.<h4>Methods</h4>An algorithm based on a negative binomial time-series regression model run on 6 sequential observations prior to the monitored period was developed to forecast monthly counts of reports. A he ...[more]

PMID: 29143393

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Project description:Introduction and objectiveEuropean Union legislation has mandated the submission of European Economic Area non-serious reports to the EudraVigilance database since November 2017. As spontaneous reports of suspected adverse reactions to medicines represent a key source of safety signals, the European Medicines Agency has undertaken this work to assess the effects of this requirement on the characteristics of the reports submitted to EudraVigilance and on the detection of adverse drug reactions through routine analyses of the database.MethodsChanges in the numbers of serious and non-serious reports transmitted to EudraVigilance were examined over the period during which the legislation was implemented. The numbers and nature of potential safety signals emerging from established statistical algorithms used at the European Medicines Agency applied either to only the serious reports or to all reports in EudraVigilance were compared.ResultsUp to November 2017, less than 25% of European Economic Area reports in EudraVigilance were classified as non-serious, since than this figure was slightly above 60%. This change accompanied an increase in the total number of reports received. Addition of non-serious reports to the signal detection process resulted in a small overall increase in signals of disproportionate reporting with some new signals of disproportionate reporting appearing and some existing signals of disproportionate reporting disappearing; the sensitivity of the signal detection system was slightly increased and the proportion of signals of disproportionate reporting that corresponded to known adverse drug reactions (a measure of efficiency) was unchanged.ConclusionsThe change in legislation has led to a small increase in sensitivity, without affecting the efficiency of the routine statistical measures used. The number of non-serious reports as a proportion of reports in EudraVigilance is likely to increase over time and further monitoring of the impact on signal detection is required. Further work is also required on the qualitative impact of non-serious reports on the nature of signals detected and on their evaluation.

Project description:IntroductionImmune checkpoint inhibitors (ICIs) are widely used in the treatment of many cancers as they improve clinical outcomes. However, ICIs have also been associated with the development of immune-related adverse drug reactions (ADRs). Among immune-related ADRs, cardiac immune-related ADRs are rare, but also associated with high mortality rates.ObjectiveThe objective of this study was to evaluate the occurrence of cardiac ADRs reported with ICIs in the European spontaneous reporting system.MethodsWe retrieved individual case safety reports on ICI-induced cardiac ADRs from the website of suspected ADR ( www.adrreports.eu ) of the European pharmacovigilance database (Eudravigilance). Data were retrieved from the date of marketing authorization of each ICI (ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and cemiplimab) to 14 March, 2020. The reporting odds ratio and its 95% confidence interval were computed to assess the reporting frequency of cardiac ADRs for each ICI compared to all other ICIs.ResultsA total of 2478 individual case safety reports with at least one ICI as the suspected drug were retrieved from Eudravigilance, of which 249 (10%) reported more than one ICI. The three most reported ICIs were nivolumab (43.2%), pembrolizumab (32.5%), and the association of nivolumab/ipilimumab (9.4%). A total of 3388 cardiac ADRs were identified. Cardiac ADRs were serious (99.4%) and had a fatal outcome (30.1%). The most reported cardiac events were myocarditis, cardiac failure, atrial fibrillation, pericardial effusion, and myocardial infarction. Nivolumab was reported with a small increased reporting frequency of individual case safety reports with cardiac ADRs compared to all other ICIs (reporting odds ratio 1.09, 95% confidence interval 1.01-1.18).ConclusionsImmune checkpoint inhibitor-induced cardiac ADRs were serious and had unfavorable outcomes. In our study, nivolumab was the only ICI with a small increased reporting frequency of individual case safety reports with cardiac ADRs compared to all other ICIs. In this regard, further head-to-head studies are needed.

Project description:BackgroundOral adverse events (AEs) following COVID-19 vaccination have been sporadically reported during the previous months, warranting further investigation for their prevalence and suspected relationship with vaccine-elicited immune response.MethodsA retrospective analysis using the Vaccine Adverse Event Reporting System (VAERS) data was conducted to evaluate AEs within the oral cavity (mucosa, tongue, lips, palate, dentition, salivary glands) and AEs involving taste and other sensations. Oral AEs reported after receiving COVID-19 vaccination (test group) and seasonal influenza vaccination (control group) were extracted and cross-tabulated to assess their relative prevalence.ResultsAmong the 128 solicited (suspected) oral AEs, oral paresthesia (0.872%) was most reported after receiving COVID-19 vaccines, followed by the swelling of lips (0.844%), ageusia (0.722%), oral hypoesthesia (0.648%), swollen tongue (0.628%), and dysgeusia (0.617%). The reported prevalence of oral AEs was higher in the COVID-19 vaccine group than in the seasonal influenza group. The distribution pattern of the most reported oral AEs was similar for both COVID-19 and seasonal influenza vaccines. Female sex, older age (>39 years old), primer doses, and mRNA-based COVID-19 vaccines exhibited a higher reported prevalence of oral AEs.ConclusionWithin the limitations of this study, COVID-19 vaccines were found to be associated with rare oral AEs that are predominantly similar to those emerging following seasonal influenza vaccines. The most commonly reported oral AEs were oral paraesthesia (mouth-tingling), lip swelling, and ageusia, representing various pathophysiologic pathways that remain unclear. Taste-related AEs should be acknowledged in the context of the COVID-19 pandemic and the public should be adequately informed about a potential taste dysfunction after receiving the COVID-19 vaccination. Dentists and dental teams need to be aware of the prevalence, severity, and prognosis of oral AEs to inform their patients and increase public confidence in vaccines.

Dataset Information

An algorithm to detect unexpected increases in frequency of reports of adverse events in EudraVigilance.

Purpose

Methods

Results

Conclusion

Publications

An algorithm to detect unexpected increases in frequency of reports of adverse events in EudraVigilance.

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