The effect of exposure misclassification in spontaneous ADR reports on the time to detection of product-specific risks for biologicals: a simulation study

Niels S Vermeer; Hans C Ebbers; Sabine M J M Straus; Hubert G M Leufkens; Toine C G Egberts; Marie L De Bruin

doi:10.1002/pds.3929

The effect of exposure misclassification in spontaneous ADR reports on the time to detection of product-specific risks for biologicals: a simulation study

Niels S Vermeer, Hans C Ebbers, Sabine M J M Straus, Hubert G M Leufkens, Toine C G Egberts, Marie L De Bruin

6 Citations (Scopus)

Abstract

BACKGROUND AND OBJECTIVE: The availability of accurate product-specific exposure information is essential in the pharmacovigilance of biologicals, because differences in the safety profile may emerge between products containing the same active substance. In spontaneous adverse drug reaction (ADR) reports, drug exposure may, however, be misclassified, that is, attributed to the incorrect product. The aim of this study was to explore the effect of exposure misclassification on the time to detection of product-specific risks in spontaneous reporting systems.

METHODS: We used data simulations to explore the effect of exposure misclassification. We simulated an active substance-specific subset of a spontaneous reporting system and used the proportional reporting ratio for signal detection. The effect of exposure misclassification was evaluated in three test cases representing product-specific ADRs that may occur for biologicals and studied in relative terms by varying the model parameters (market share and relative risk).

RESULTS: We found that exposure misclassification results in the largest delay in identification of risks that have a weak association (relative risk < 2 or 3) with the product of interest and in situations where the product associated with the unique risk has a large (>50%) market share. The absolute public health impact of exposure misclassification, in terms of cases/time to detection, varied considerably across the test cases.

CONCLUSION: Exposure misclassification in ADR reports may result in a delayed detection of product-specific risks, particularly in the detection of weak drug-event associations. Our findings can help inform the future implementation and refinement of product-specific and batch-specific signal detection procedures.

Original language	English
Journal	Pharmacoepidemiology and Drug Safety
Volume	25
Issue number	3
Pages (from-to)	297-306
Number of pages	10
ISSN	1053-8569
DOIs	https://doi.org/10.1002/pds.3929
Publication status	Published - 1 Mar 2016
Externally published	Yes

Keywords

Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/pds.3929

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The effect of exposure misclassification in spontaneous ADR reports on the time to detection of product-specific risks for biologicals: a simulation study. / Vermeer, Niels S; Ebbers, Hans C; Straus, Sabine M J M et al.
In: Pharmacoepidemiology and Drug Safety, Vol. 25, No. 3, 01.03.2016, p. 297-306.

Research output: Contribution to journal › Journal article › Research › peer-review

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abstract = "BACKGROUND AND OBJECTIVE: The availability of accurate product-specific exposure information is essential in the pharmacovigilance of biologicals, because differences in the safety profile may emerge between products containing the same active substance. In spontaneous adverse drug reaction (ADR) reports, drug exposure may, however, be misclassified, that is, attributed to the incorrect product. The aim of this study was to explore the effect of exposure misclassification on the time to detection of product-specific risks in spontaneous reporting systems.METHODS: We used data simulations to explore the effect of exposure misclassification. We simulated an active substance-specific subset of a spontaneous reporting system and used the proportional reporting ratio for signal detection. The effect of exposure misclassification was evaluated in three test cases representing product-specific ADRs that may occur for biologicals and studied in relative terms by varying the model parameters (market share and relative risk).RESULTS: We found that exposure misclassification results in the largest delay in identification of risks that have a weak association (relative risk < 2 or 3) with the product of interest and in situations where the product associated with the unique risk has a large (>50%) market share. The absolute public health impact of exposure misclassification, in terms of cases/time to detection, varied considerably across the test cases.CONCLUSION: Exposure misclassification in ADR reports may result in a delayed detection of product-specific risks, particularly in the detection of weak drug-event associations. Our findings can help inform the future implementation and refinement of product-specific and batch-specific signal detection procedures.",

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AB - BACKGROUND AND OBJECTIVE: The availability of accurate product-specific exposure information is essential in the pharmacovigilance of biologicals, because differences in the safety profile may emerge between products containing the same active substance. In spontaneous adverse drug reaction (ADR) reports, drug exposure may, however, be misclassified, that is, attributed to the incorrect product. The aim of this study was to explore the effect of exposure misclassification on the time to detection of product-specific risks in spontaneous reporting systems.METHODS: We used data simulations to explore the effect of exposure misclassification. We simulated an active substance-specific subset of a spontaneous reporting system and used the proportional reporting ratio for signal detection. The effect of exposure misclassification was evaluated in three test cases representing product-specific ADRs that may occur for biologicals and studied in relative terms by varying the model parameters (market share and relative risk).RESULTS: We found that exposure misclassification results in the largest delay in identification of risks that have a weak association (relative risk < 2 or 3) with the product of interest and in situations where the product associated with the unique risk has a large (>50%) market share. The absolute public health impact of exposure misclassification, in terms of cases/time to detection, varied considerably across the test cases.CONCLUSION: Exposure misclassification in ADR reports may result in a delayed detection of product-specific risks, particularly in the detection of weak drug-event associations. Our findings can help inform the future implementation and refinement of product-specific and batch-specific signal detection procedures.

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The effect of exposure misclassification in spontaneous ADR reports on the time to detection of product-specific risks for biologicals: a simulation study

Abstract

Keywords

UN SDGs

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