On estimands and the analysis of adverse events in the presence of varying follow-up times within the benefit assessment of therapies.
adverse events
benefit assessment
clinical trials
estimands
safety data
Journal
Pharmaceutical statistics
ISSN: 1539-1612
Titre abrégé: Pharm Stat
Pays: England
ID NLM: 101201192
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
03
05
2018
revised:
19
09
2018
accepted:
23
10
2018
pubmed:
21
11
2018
medline:
18
4
2019
entrez:
21
11
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30458579
doi: 10.1002/pst.1915
pmc: PMC6587465
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
166-183Informations de copyright
© 2018 The Authors. Pharmaceutical Statistics Published by John Wiley & Sons Ltd.
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