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On estimands and the analysis of adverse events in the presence of varying follow‐up times within the benefit assessment of therapies

The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit‐risk ratio. The statistical analysis of AEs is complicated by the...

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Autores principales: Unkel, Steffen, Amiri, Marjan, Benda, Norbert, Beyersmann, Jan, Knoerzer, Dietrich, Kupas, Katrin, Langer, Frank, Leverkus, Friedhelm, Loos, Anja, Ose, Claudia, Proctor, Tanja, Schmoor, Claudia, Schwenke, Carsten, Skipka, Guido, Unnebrink, Kristina, Voss, Florian, Friede, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587465/
https://www.ncbi.nlm.nih.gov/pubmed/30458579
http://dx.doi.org/10.1002/pst.1915
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author Unkel, Steffen
Amiri, Marjan
Benda, Norbert
Beyersmann, Jan
Knoerzer, Dietrich
Kupas, Katrin
Langer, Frank
Leverkus, Friedhelm
Loos, Anja
Ose, Claudia
Proctor, Tanja
Schmoor, Claudia
Schwenke, Carsten
Skipka, Guido
Unnebrink, Kristina
Voss, Florian
Friede, Tim
author_facet Unkel, Steffen
Amiri, Marjan
Benda, Norbert
Beyersmann, Jan
Knoerzer, Dietrich
Kupas, Katrin
Langer, Frank
Leverkus, Friedhelm
Loos, Anja
Ose, Claudia
Proctor, Tanja
Schmoor, Claudia
Schwenke, Carsten
Skipka, Guido
Unnebrink, Kristina
Voss, Florian
Friede, Tim
author_sort Unkel, Steffen
collection PubMed
description The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit‐risk ratio. The statistical analysis of AEs is complicated by the fact that the follow‐up times can vary between the patients included in a clinical trial. This paper takes as its focus the analysis of AE data in the presence of varying follow‐up times within the benefit assessment of therapeutic interventions. Instead of approaching this issue directly and solely from an analysis point of view, we first discuss what should be estimated in the context of safety data, leading to the concept of estimands. Although the current discussion on estimands is mainly related to efficacy evaluation, the concept is applicable to safety endpoints as well. Within the framework of estimands, we present statistical methods for analysing AEs with the focus being on the time to the occurrence of the first AE of a specific type. We give recommendations which estimators should be used for the estimands described. Furthermore, we state practical implications of the analysis of AEs in clinical trials and give an overview of examples across different indications. We also provide a review of current practices of health technology assessment (HTA) agencies with respect to the evaluation of safety data. Finally, we describe problems with meta‐analyses of AE data and sketch possible solutions.
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spelling pubmed-65874652019-07-02 On estimands and the analysis of adverse events in the presence of varying follow‐up times within the benefit assessment of therapies Unkel, Steffen Amiri, Marjan Benda, Norbert Beyersmann, Jan Knoerzer, Dietrich Kupas, Katrin Langer, Frank Leverkus, Friedhelm Loos, Anja Ose, Claudia Proctor, Tanja Schmoor, Claudia Schwenke, Carsten Skipka, Guido Unnebrink, Kristina Voss, Florian Friede, Tim Pharm Stat Main Papers The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit‐risk ratio. The statistical analysis of AEs is complicated by the fact that the follow‐up times can vary between the patients included in a clinical trial. This paper takes as its focus the analysis of AE data in the presence of varying follow‐up times within the benefit assessment of therapeutic interventions. Instead of approaching this issue directly and solely from an analysis point of view, we first discuss what should be estimated in the context of safety data, leading to the concept of estimands. Although the current discussion on estimands is mainly related to efficacy evaluation, the concept is applicable to safety endpoints as well. Within the framework of estimands, we present statistical methods for analysing AEs with the focus being on the time to the occurrence of the first AE of a specific type. We give recommendations which estimators should be used for the estimands described. Furthermore, we state practical implications of the analysis of AEs in clinical trials and give an overview of examples across different indications. We also provide a review of current practices of health technology assessment (HTA) agencies with respect to the evaluation of safety data. Finally, we describe problems with meta‐analyses of AE data and sketch possible solutions. John Wiley and Sons Inc. 2018-11-20 2019 /pmc/articles/PMC6587465/ /pubmed/30458579 http://dx.doi.org/10.1002/pst.1915 Text en © 2018 The Authors. Pharmaceutical Statistics Published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Main Papers
Unkel, Steffen
Amiri, Marjan
Benda, Norbert
Beyersmann, Jan
Knoerzer, Dietrich
Kupas, Katrin
Langer, Frank
Leverkus, Friedhelm
Loos, Anja
Ose, Claudia
Proctor, Tanja
Schmoor, Claudia
Schwenke, Carsten
Skipka, Guido
Unnebrink, Kristina
Voss, Florian
Friede, Tim
On estimands and the analysis of adverse events in the presence of varying follow‐up times within the benefit assessment of therapies
title On estimands and the analysis of adverse events in the presence of varying follow‐up times within the benefit assessment of therapies
title_full On estimands and the analysis of adverse events in the presence of varying follow‐up times within the benefit assessment of therapies
title_fullStr On estimands and the analysis of adverse events in the presence of varying follow‐up times within the benefit assessment of therapies
title_full_unstemmed On estimands and the analysis of adverse events in the presence of varying follow‐up times within the benefit assessment of therapies
title_short On estimands and the analysis of adverse events in the presence of varying follow‐up times within the benefit assessment of therapies
title_sort on estimands and the analysis of adverse events in the presence of varying follow‐up times within the benefit assessment of therapies
topic Main Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587465/
https://www.ncbi.nlm.nih.gov/pubmed/30458579
http://dx.doi.org/10.1002/pst.1915
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