Confirmatory adaptive group sequential designs for clinical trials with multiple time-to-event outcomes in Markov models
Fuente:
arXiv
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Preprint |
| Published: |
2023
|
| Subjects: | |
| Online Access: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1866914356734722048 |
|---|---|
| author | Danzer, Moritz Fabian Faldum, Andreas Simon, Thorsten Hero, Barbara Schmidt, Rene |
| author_facet | Danzer, Moritz Fabian Faldum, Andreas Simon, Thorsten Hero, Barbara Schmidt, Rene |
| contents | The analysis of multiple time-to-event outcomes in a randomised controlled clinical trial can be accomplished with exisiting methods. However, depending on the characteristics of the disease under investigation and the circumstances in which the study is planned, it may be of interest to conduct interim analyses and adapt the study design if necessary. Due to the expected dependency of the endpoints, the full available information on the involved endpoints may not be used for this purpose. We suggest a solution to this problem by embedding the endpoints in a multi-state model. If this model is Markovian, it is possible to take the disease history of the patients into account and allow for data-dependent design adaptiations. To this end, we introduce a flexible test procedure for a variety of applications, but are particularly concerned with the simultaneous consideration of progression-free survival (PFS) and overall survival (OS). This setting is of key interest in oncological trials. We conduct simulation studies to determine the properties for small sample sizes and demonstrate an application based on data from the NB2004-HR study. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2306_16056 |
| institution | arXiv |
| publishDate | 2023 |
| record_format | arxiv |
| spellingShingle | Confirmatory adaptive group sequential designs for clinical trials with multiple time-to-event outcomes in Markov models Danzer, Moritz Fabian Faldum, Andreas Simon, Thorsten Hero, Barbara Schmidt, Rene Methodology 62N03 G.3.16 The analysis of multiple time-to-event outcomes in a randomised controlled clinical trial can be accomplished with exisiting methods. However, depending on the characteristics of the disease under investigation and the circumstances in which the study is planned, it may be of interest to conduct interim analyses and adapt the study design if necessary. Due to the expected dependency of the endpoints, the full available information on the involved endpoints may not be used for this purpose. We suggest a solution to this problem by embedding the endpoints in a multi-state model. If this model is Markovian, it is possible to take the disease history of the patients into account and allow for data-dependent design adaptiations. To this end, we introduce a flexible test procedure for a variety of applications, but are particularly concerned with the simultaneous consideration of progression-free survival (PFS) and overall survival (OS). This setting is of key interest in oncological trials. We conduct simulation studies to determine the properties for small sample sizes and demonstrate an application based on data from the NB2004-HR study. |
| title | Confirmatory adaptive group sequential designs for clinical trials with multiple time-to-event outcomes in Markov models |
| topic | Methodology 62N03 G.3.16 |
| url | https://arxiv.org/abs/2306.16056 |