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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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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. |
format | Online Article Text |
id | pubmed-6587465 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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