eprintid: 24291
rev_number: 10
eprint_status: archive
userid: 1589
dir: disk0/00/02/42/91
datestamp: 2018-04-24 09:15:06
lastmod: 2018-04-25 13:24:41
status_changed: 2018-04-24 09:15:06
type: article
metadata_visibility: show
creators_name: Ozga, Ann-Kathrin
creators_name: Kieser, Meinhard
creators_name: Rauch, Geraldine
title: A systematic comparison of recurrent event models for application to composite endpoints
subjects: 610
divisions: 911800
abstract: Background: Many clinical trials focus on the comparison of the treatment effect between two or more groups concerning a rarely occurring event. In this situation, showing a relevant effect with an acceptable power requires the observation of a large number of patients over a long period of time. For feasibility issues, it is therefore often considered to include several event types of interest, non-fatal or fatal, and to combine them within a composite endpoint. Commonly, a composite endpoint is analyzed with standard survival analysis techniques by assessing the time to the first occurring event. This approach neglects that an individual may experience more than one event which leads to a loss of information. As an alternative, composite endpoints could be analyzed by models for recurrent events. There exists a number of such models, e.g. regression models based on count data or Cox-based models such as the approaches of Andersen and Gill, Prentice, Williams and Peterson or, Wei, Lin and Weissfeld. Although some of the methods were already compared within the literature there exists no systematic investigation for the special requirements regarding composite endpoints.

Methods: Within this work a simulation-based comparison of recurrent event models applied to composite endpoints is provided for different realistic clinical trial scenarios.

Results: We demonstrate that the Andersen-Gill model and the Prentice- Williams-Petersen models show similar results under various data scenarios whereas the Wei-Lin-Weissfeld model delivers effect estimators which can considerably deviate under commonly met data scenarios.

Conclusion: Based on the conducted simulation study, this paper helps to understand the pros and cons of the investigated methods in the context of composite endpoints and provides therefore recommendations for an adequate statistical analysis strategy and a meaningful interpretation of results.
date: 2018
publisher: BioMed Central ; Springer
id_scheme: DOI
id_number: https://doi.org/10.1186/s12874-017-0462-x
ppn_swb: 1655217097
own_urn: urn:nbn:de:bsz:16-heidok-242918
language: eng
bibsort: OZGAANNKATASYSTEMATI2018
full_text_status: public
publication: BMC Medical Research Methodology
volume: 18
number: 2
place_of_pub: London ; Berlin ; Heidelberg
pagerange: 1-12
issn: 1471-2288
citation:   Ozga, Ann-Kathrin ; Kieser, Meinhard ; Rauch, Geraldine  (2018) A systematic comparison of recurrent event models for application to composite endpoints.  BMC Medical Research Methodology, 18 (2).  pp. 1-12.  ISSN 1471-2288     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/24291/1/12874_2017_Article_462.pdf