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Bias, precision and timeliness of historical (background) rate comparison methods for vaccine safety monitoring: an empirical multi-database analysis

Abstract:
Using real-world data and past vaccination data, we conducted a large-scale experiment to quantify bias, precision and timeliness of different study designs to estimate historical background (expected) compared to post-vaccination (observed) rates of safety events for several vaccines. We used negative (not causally related) and positive control outcomes. The latter were synthetically generated true safety signals with incident rate ratios ranging from 1.5 to 4. Observed vs. expected analysis using within-database historical background rates is a sensitive but unspecific method for the identification of potential vaccine safety signals. Despite good discrimination, most analyses showed a tendency to overestimate risks, with 20%-100% type 1 error, but low (0% to 20%) type 2 error in the large databases included in our study. Efforts to improve the comparability of background and post-vaccine rates, including age-sex adjustment and anchoring background rates around a visit, reduced type 1 error and improved precision but residual systematic error persisted. Additionally, empirical calibration dramatically reduced type 1 to nominal but came at the cost of increasing type 2 error.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.3389/fphar.2021.773875

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Botnar Research Centre
Role:
Author
ORCID:
0000-0002-6872-5804
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Role:
Author
ORCID:
0000-0002-0847-6682


Publisher:
Public Library of Science
Journal:
Frontiers in Pharmacology More from this journal
Volume:
12
Article number:
773875
Publication date:
2021-11-24
Acceptance date:
2021-11-02
DOI:
EISSN:
1663-9812
Pmid:
34899334


Language:
English
Keywords:
Pubs id:
1224885
Local pid:
pubs:1224885
Deposit date:
2022-05-20
ARK identifier:

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