Surveillance of Antidepressant Safety (SADS): Active Signal Detection of Serious Medical Events Following SSRI and SNRI Initiation Using Big Healthcare Data
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Introduction: The current process for generating evidence in pharmacovigilance has several limitations, which often lead to delays in the evaluation of drug-associated risks. Objectives: In this study, we proposed and tested a near real-time epidemiological surveillance system using sequential, cumulative analyses focusing on the detection and preliminary risk quantification of potential safety signals following initiation of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Methods: We emulated an active surveillance system in an historical setting by conducting repeated annual cohort studies using nationwide Danish healthcare data (1996–2016). Outcomes were selected from the European Medicines Agency's Designated Medical Event list, summaries of product characteristics, and the literature. We followed patients for a maximum of 6 months from treatment initiation to the event of interest or censoring. We performed Cox regression analyses adjusted for standard sets of covariates. Potential safety signals were visualized using heat maps and cumulative hazard ratio (HR) plots over time. Results: In the total study population, 969,667 new users were included and followed for 461,506 person-years. We detected potential safety signals with incidence rates as low as 0.9 per 10,000 person-years. Having eight different exposure drugs and 51 medical events, we identified 31 unique combinations of potential safety signals with a positive association to the event of interest in the exposed group. We proposed that these signals were designated for further evaluation once they appeared in a prospective setting. In total, 21 (67.7%) of these were not present in the current summaries of product characteristics. Conclusion: The study demonstrated the feasibility of performing epidemiological surveillance using sequential, cumulative analyses. Larger populations are needed to evaluate rare events and infrequently used antidepressants.
| Original language | English |
|---|---|
| Journal | Drug Safety |
| Volume | 44 |
| Pages (from-to) | 1215–1230 |
| ISSN | 0114-5916 |
| DOIs | |
| Publication status | Published - 2021 |
Bibliographical note
Funding Information:
At the time of the study, Marie Louise De Bruin was an employee of the Copenhagen Centre for Regulatory Science (CORS). CORS is a cross-faculty university-anchored institution involving various public (Danish Medicines Agency, Copenhagen University) and private (Novo Nordisk A/S, Lundbeck A/S, Ferring pharmaceuticals A/S, LEO pharma A/S) stakeholders as well as patient organisations (Rare Diseases Denmark). The center is purely devoted to the scientific aspects of the regulatory field and has a patient-oriented focus, and the research is not a company-specific product or directly company related. Currently, Marie Louise De Bruin is employed by Utrecht University to conduct research under the umbrella of the Utrecht Centre for Pharmaceutical Policy and Regulation. This centre receives no direct funding or donations from private parties, including the pharma industry. Research funding from public–private partnerships, e.g. IMI, The Escher Project ( http://escher.lygature.org/ ), is accepted under the condition that no company-specific study is conducted. The centre has received unrestricted research funding from public sources, e.g., World Health Organization, Netherlands Organisation for Health Research and Development, the Dutch National Health Care Institute, EC Horizon 2020, the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health. During the past 10 years, Morten Andersen has participated in research projects funded by AstraZeneca, H. Lundbeck & Mertz, Janssen, Novartis, Merck Sharp & Dohme, and Pfizer, with grants paid to the institutions where he was employed; he has also personally received fees from Atrium, the Danish Pharmaceutical Industry Association, for teaching pharmacoepidemiology courses. Mia Aakjær and Murat Kulahci have no conflicts of interest that are directly relevant to the content of this article.
Funding Information:
Mia Aakjær's Ph.D. project was partly funded, and Morten Andersen's professorship was funded by a grant from the Novo Nordisk Foundation (NNF15SA0018404) to the University of Copenhagen.
Publisher Copyright:
© 2021, The Author(s).
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