Cargando…
A marginal estimate for the overall treatment effect on a survival outcome within the joint modeling framework
Joint models for longitudinal and survival data are increasingly used and enjoy a wide range of application areas. In this article, we focus on the application of joint models on clinical trial data with special interest in the treatment effect on the survival outcome. Within a joint model, the esti...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674249/ https://www.ncbi.nlm.nih.gov/pubmed/32838484 http://dx.doi.org/10.1002/sim.8713 |
_version_ | 1783611468743180288 |
---|---|
author | van Oudenhoven, Floor M. Swinkels, Sophie H. N. Ibrahim, Joseph G. Rizopoulos, Dimitris |
author_facet | van Oudenhoven, Floor M. Swinkels, Sophie H. N. Ibrahim, Joseph G. Rizopoulos, Dimitris |
author_sort | van Oudenhoven, Floor M. |
collection | PubMed |
description | Joint models for longitudinal and survival data are increasingly used and enjoy a wide range of application areas. In this article, we focus on the application of joint models on clinical trial data with special interest in the treatment effect on the survival outcome. Within a joint model, the estimated treatment effect on the survival outcome is an aggregate comprising the indirect treatment effect through the longitudinal outcome and the direct treatment effect on the survival outcome. This overall treatment effect is, however, conditional on random effects, and therefore has a subject‐specific interpretation. The conditional interpretation arises from the shared random effects between the longitudinal and survival process in combination with the nonlinear link function of the survival model. The overall treatment effect is, therefore, not valid for population‐based inference, which is the goal for most clinical trials. We propose a method to obtain a marginal estimate of the overall treatment effect on the survival outcome in a joint model. Additionally, we extend our proposal to allow for different parameterizations for the association between the longitudinal and survival outcome. The proposed method is demonstrated on data of a clinical study on the effect of synbiotic on the gut microbiota of cesarean delivered infants, where we estimate the marginal overall treatment effect on the risk of eczema or atopic dermatitis using longitudinal information on fecal bifidobacteria. |
format | Online Article Text |
id | pubmed-7674249 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76742492020-12-28 A marginal estimate for the overall treatment effect on a survival outcome within the joint modeling framework van Oudenhoven, Floor M. Swinkels, Sophie H. N. Ibrahim, Joseph G. Rizopoulos, Dimitris Stat Med Research Articles Joint models for longitudinal and survival data are increasingly used and enjoy a wide range of application areas. In this article, we focus on the application of joint models on clinical trial data with special interest in the treatment effect on the survival outcome. Within a joint model, the estimated treatment effect on the survival outcome is an aggregate comprising the indirect treatment effect through the longitudinal outcome and the direct treatment effect on the survival outcome. This overall treatment effect is, however, conditional on random effects, and therefore has a subject‐specific interpretation. The conditional interpretation arises from the shared random effects between the longitudinal and survival process in combination with the nonlinear link function of the survival model. The overall treatment effect is, therefore, not valid for population‐based inference, which is the goal for most clinical trials. We propose a method to obtain a marginal estimate of the overall treatment effect on the survival outcome in a joint model. Additionally, we extend our proposal to allow for different parameterizations for the association between the longitudinal and survival outcome. The proposed method is demonstrated on data of a clinical study on the effect of synbiotic on the gut microbiota of cesarean delivered infants, where we estimate the marginal overall treatment effect on the risk of eczema or atopic dermatitis using longitudinal information on fecal bifidobacteria. John Wiley and Sons Inc. 2020-08-24 2020-12-10 /pmc/articles/PMC7674249/ /pubmed/32838484 http://dx.doi.org/10.1002/sim.8713 Text en © 2020 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles van Oudenhoven, Floor M. Swinkels, Sophie H. N. Ibrahim, Joseph G. Rizopoulos, Dimitris A marginal estimate for the overall treatment effect on a survival outcome within the joint modeling framework |
title | A marginal estimate for the overall treatment effect on a survival outcome within the joint modeling framework |
title_full | A marginal estimate for the overall treatment effect on a survival outcome within the joint modeling framework |
title_fullStr | A marginal estimate for the overall treatment effect on a survival outcome within the joint modeling framework |
title_full_unstemmed | A marginal estimate for the overall treatment effect on a survival outcome within the joint modeling framework |
title_short | A marginal estimate for the overall treatment effect on a survival outcome within the joint modeling framework |
title_sort | marginal estimate for the overall treatment effect on a survival outcome within the joint modeling framework |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674249/ https://www.ncbi.nlm.nih.gov/pubmed/32838484 http://dx.doi.org/10.1002/sim.8713 |
work_keys_str_mv | AT vanoudenhovenfloorm amarginalestimatefortheoveralltreatmenteffectonasurvivaloutcomewithinthejointmodelingframework AT swinkelssophiehn amarginalestimatefortheoveralltreatmenteffectonasurvivaloutcomewithinthejointmodelingframework AT ibrahimjosephg amarginalestimatefortheoveralltreatmenteffectonasurvivaloutcomewithinthejointmodelingframework AT rizopoulosdimitris amarginalestimatefortheoveralltreatmenteffectonasurvivaloutcomewithinthejointmodelingframework AT vanoudenhovenfloorm marginalestimatefortheoveralltreatmenteffectonasurvivaloutcomewithinthejointmodelingframework AT swinkelssophiehn marginalestimatefortheoveralltreatmenteffectonasurvivaloutcomewithinthejointmodelingframework AT ibrahimjosephg marginalestimatefortheoveralltreatmenteffectonasurvivaloutcomewithinthejointmodelingframework AT rizopoulosdimitris marginalestimatefortheoveralltreatmenteffectonasurvivaloutcomewithinthejointmodelingframework |