The risk of acute liver injury associated with the use of antibiotics--evaluating robustness of results in the pharmacoepidemiological research on outcomes of therapeutics by a European consortium (PROTECT) project

Renate Udo; Stéphanie Tcherny-Lessenot; Ruth Brauer; Paul Dolin; David Irvine; Yunxun Wang; Laurent Auclert; Juhaeri Juhaeri; Xavier Kurz; Lucien Abenhaim; Lamiae Grimaldi; Marie L De Bruin

doi:10.1002/pds.3841

The risk of acute liver injury associated with the use of antibiotics--evaluating robustness of results in the pharmacoepidemiological research on outcomes of therapeutics by a European consortium (PROTECT) project

Renate Udo, Stéphanie Tcherny-Lessenot, Ruth Brauer, Paul Dolin, David Irvine, Yunxun Wang, Laurent Auclert, Juhaeri Juhaeri, Xavier Kurz, Lucien Abenhaim, Lamiae Grimaldi, Marie L De Bruin

7 Citations (Scopus)

Abstract

PURPOSE: To examine the robustness of findings of case-control studies on the association between acute liver injury (ALI) and antibiotic use in the following different situations: (i) Replication of a protocol in different databases, with different data types, as well as replication in the same database, but performed by a different research team. (ii) Varying algorithms to identify cases, with and without manual case validation. (iii) Different exposure windows for time at risk.

METHODS: Five case-control studies in four different databases were performed with a common study protocol as starting point to harmonize study outcome definitions, exposure definitions and statistical analyses.

RESULTS: All five studies showed an increased risk of ALI associated with antibiotic use ranging from OR 2.6 (95% CI 1.3-5.4) to 7.7 (95% CI 2.0-29.3). Comparable trends could be observed in the five studies: (i) without manual validation the use of the narrowest definition for ALI showed higher risk estimates, (ii) narrow and broad algorithm definitions followed by manual validation of cases resulted in similar risk estimates, and (iii) the use of a larger window (30 days vs 14 days) to define time at risk led to a decrease in risk estimates.

CONCLUSIONS: Reproduction of a study using a predefined protocol in different database settings is feasible, although assumptions had to be made and amendments in the protocol were inevitable. Despite differences, the strength of association was comparable between the studies. In addition, the impact of varying outcome definitions and time windows showed similar trends within the data sources.

Original language	English
Journal	Pharmacoepidemiology and Drug Safety
Volume	25 Suppl 1
Pages (from-to)	47-55
Number of pages	9
ISSN	1053-8569
DOIs	https://doi.org/10.1002/pds.3841
Publication status	Published - 1 Mar 2016
Externally published	Yes

Keywords

Journal Article

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Udo, R., Tcherny-Lessenot, S., Brauer, R., Dolin, P., Irvine, D., Wang, Y., Auclert, L., Juhaeri, J., Kurz, X., Abenhaim, L., Grimaldi, L., & De Bruin, M. L. (2016). The risk of acute liver injury associated with the use of antibiotics--evaluating robustness of results in the pharmacoepidemiological research on outcomes of therapeutics by a European consortium (PROTECT) project. Pharmacoepidemiology and Drug Safety, 25 Suppl 1, 47-55. https://doi.org/10.1002/pds.3841

The risk of acute liver injury associated with the use of antibiotics--evaluating robustness of results in the pharmacoepidemiological research on outcomes of therapeutics by a European consortium (PROTECT) project. / Udo, Renate; Tcherny-Lessenot, Stéphanie; Brauer, Ruth et al.
In: Pharmacoepidemiology and Drug Safety, Vol. 25 Suppl 1, 01.03.2016, p. 47-55.

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

Udo, R, Tcherny-Lessenot, S, Brauer, R, Dolin, P, Irvine, D, Wang, Y, Auclert, L, Juhaeri, J, Kurz, X, Abenhaim, L, Grimaldi, L & De Bruin, ML 2016, 'The risk of acute liver injury associated with the use of antibiotics--evaluating robustness of results in the pharmacoepidemiological research on outcomes of therapeutics by a European consortium (PROTECT) project', Pharmacoepidemiology and Drug Safety, vol. 25 Suppl 1, pp. 47-55. https://doi.org/10.1002/pds.3841

Udo R, Tcherny-Lessenot S, Brauer R, Dolin P, Irvine D, Wang Y et al. The risk of acute liver injury associated with the use of antibiotics--evaluating robustness of results in the pharmacoepidemiological research on outcomes of therapeutics by a European consortium (PROTECT) project. Pharmacoepidemiology and Drug Safety. 2016 Mar 1;25 Suppl 1:47-55. doi: 10.1002/pds.3841

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abstract = "PURPOSE: To examine the robustness of findings of case-control studies on the association between acute liver injury (ALI) and antibiotic use in the following different situations: (i) Replication of a protocol in different databases, with different data types, as well as replication in the same database, but performed by a different research team. (ii) Varying algorithms to identify cases, with and without manual case validation. (iii) Different exposure windows for time at risk.METHODS: Five case-control studies in four different databases were performed with a common study protocol as starting point to harmonize study outcome definitions, exposure definitions and statistical analyses.RESULTS: All five studies showed an increased risk of ALI associated with antibiotic use ranging from OR 2.6 (95% CI 1.3-5.4) to 7.7 (95% CI 2.0-29.3). Comparable trends could be observed in the five studies: (i) without manual validation the use of the narrowest definition for ALI showed higher risk estimates, (ii) narrow and broad algorithm definitions followed by manual validation of cases resulted in similar risk estimates, and (iii) the use of a larger window (30 days vs 14 days) to define time at risk led to a decrease in risk estimates.CONCLUSIONS: Reproduction of a study using a predefined protocol in different database settings is feasible, although assumptions had to be made and amendments in the protocol were inevitable. Despite differences, the strength of association was comparable between the studies. In addition, the impact of varying outcome definitions and time windows showed similar trends within the data sources.",

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T1 - The risk of acute liver injury associated with the use of antibiotics--evaluating robustness of results in the pharmacoepidemiological research on outcomes of therapeutics by a European consortium (PROTECT) project

AU - Udo, Renate

AU - Tcherny-Lessenot, Stéphanie

AU - Brauer, Ruth

AU - Dolin, Paul

AU - Irvine, David

AU - Wang, Yunxun

AU - Auclert, Laurent

AU - Juhaeri, Juhaeri

AU - Kurz, Xavier

AU - Abenhaim, Lucien

AU - Grimaldi, Lamiae

AU - De Bruin, Marie L

PY - 2016/3/1

Y1 - 2016/3/1

N2 - PURPOSE: To examine the robustness of findings of case-control studies on the association between acute liver injury (ALI) and antibiotic use in the following different situations: (i) Replication of a protocol in different databases, with different data types, as well as replication in the same database, but performed by a different research team. (ii) Varying algorithms to identify cases, with and without manual case validation. (iii) Different exposure windows for time at risk.METHODS: Five case-control studies in four different databases were performed with a common study protocol as starting point to harmonize study outcome definitions, exposure definitions and statistical analyses.RESULTS: All five studies showed an increased risk of ALI associated with antibiotic use ranging from OR 2.6 (95% CI 1.3-5.4) to 7.7 (95% CI 2.0-29.3). Comparable trends could be observed in the five studies: (i) without manual validation the use of the narrowest definition for ALI showed higher risk estimates, (ii) narrow and broad algorithm definitions followed by manual validation of cases resulted in similar risk estimates, and (iii) the use of a larger window (30 days vs 14 days) to define time at risk led to a decrease in risk estimates.CONCLUSIONS: Reproduction of a study using a predefined protocol in different database settings is feasible, although assumptions had to be made and amendments in the protocol were inevitable. Despite differences, the strength of association was comparable between the studies. In addition, the impact of varying outcome definitions and time windows showed similar trends within the data sources.

AB - PURPOSE: To examine the robustness of findings of case-control studies on the association between acute liver injury (ALI) and antibiotic use in the following different situations: (i) Replication of a protocol in different databases, with different data types, as well as replication in the same database, but performed by a different research team. (ii) Varying algorithms to identify cases, with and without manual case validation. (iii) Different exposure windows for time at risk.METHODS: Five case-control studies in four different databases were performed with a common study protocol as starting point to harmonize study outcome definitions, exposure definitions and statistical analyses.RESULTS: All five studies showed an increased risk of ALI associated with antibiotic use ranging from OR 2.6 (95% CI 1.3-5.4) to 7.7 (95% CI 2.0-29.3). Comparable trends could be observed in the five studies: (i) without manual validation the use of the narrowest definition for ALI showed higher risk estimates, (ii) narrow and broad algorithm definitions followed by manual validation of cases resulted in similar risk estimates, and (iii) the use of a larger window (30 days vs 14 days) to define time at risk led to a decrease in risk estimates.CONCLUSIONS: Reproduction of a study using a predefined protocol in different database settings is feasible, although assumptions had to be made and amendments in the protocol were inevitable. Despite differences, the strength of association was comparable between the studies. In addition, the impact of varying outcome definitions and time windows showed similar trends within the data sources.

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