Gutenberg Open Science: A comparison of semiparametric approaches to evaluate composite endpoints in heart failure trials

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7703

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DC Field	Value	Language
dc.contributor.author	Toenges, Gerrit	-
dc.contributor.author	Mütze, Tobias	-
dc.contributor.author	Jahn-Eimermacher, Antje	-
dc.date.accessioned	2022-09-07T10:35:09Z	-
dc.date.available	2022-09-07T10:35:09Z	-
dc.date.issued	2021	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/7718	-
dc.description.abstract	In heart failure (HF) trials efficacy is usually assessed by a composite endpoint including cardiovascular death (CVD) and heart failure hospitalizations (HFHs), which has traditionally been evaluated with a time-to-first-event analysis based on a Cox model. As a considerable fraction of events is ignored that way, methods for recurrent events were suggested, among others the semiparametric proportional rates models by Lin, Wei, Yang, and Ying (LWYY model) and Mao and Lin (Mao-Lin model). In our work we apply least false parameter theory to explain the behavior of the composite treatment effect estimates resulting from the Cox model, the LWYY model, and the Mao-Lin model in clinically relevant scenarios parameterized through joint frailty models. These account for both different treatment effects on the two outcomes (CVD, HFHs) and the positive correlation between their risk rates. For the important setting of beneficial outcome-specific treatment effects we show that the correlation results in composite treatment effect estimates, which are decreasing with trial duration. The estimate from the Cox model is affected more by the attenuation than the estimates from the recurrent event models, which both demonstrate very similar behavior. Since the Mao-Lin model turns out to be less sensitive to harmful effects on mortality, we conclude that, among the three investigated approaches, the LWYY model is the most appropriate one for the composite endpoint in HF trials. Our investigations are motivated and compared with empirical results from the PARADIGM-HF trial (ClinicalTrials.gov identifier: NCT01035255), a large multicenter trial including 8399 chronic HF patients.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	A comparison of semiparametric approaches to evaluate composite endpoints in heart failure trials	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-7703	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Statistics in medicine	de
jgu.journal.volume	40	de
jgu.journal.issue	26	de
jgu.pages.start	5702	de
jgu.pages.end	5724	de
jgu.publisher.year	2021	-
jgu.publisher.name	Wiley	de
jgu.publisher.place	Chichester u.a.	de
jgu.publisher.issn	1097-0258	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.1002/sim.9149	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	JGU-Publikationen

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