Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials.
Mid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of time-to-event endpoints is not easily handled by the standard the...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4749572?pdf=render |
| _version_ | 1811289479720206336 |
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| author | Dominic Magirr Thomas Jaki Franz Koenig Martin Posch |
| author_facet | Dominic Magirr Thomas Jaki Franz Koenig Martin Posch |
| author_sort | Dominic Magirr |
| collection | DOAJ |
| description | Mid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of time-to-event endpoints is not easily handled by the standard theory. We analyze current methods that allow design modifications to be based on the full interim data, i.e., not only the observed event times but also secondary endpoint and safety data from patients who are yet to have an event. We show that the final test statistic may ignore a substantial subset of the observed event times. An alternative test incorporating all event times is found, where a conservative assumption must be made in order to guarantee type I error control. We examine the power of this approach using the example of a clinical trial comparing two cancer therapies. |
| first_indexed | 2024-04-13T03:55:36Z |
| format | Article |
| id | doaj.art-77e06436795a4bb6809faec62c017e7d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T03:55:36Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-77e06436795a4bb6809faec62c017e7d2022-12-22T03:03:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014646510.1371/journal.pone.0146465Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials.Dominic MagirrThomas JakiFranz KoenigMartin PoschMid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of time-to-event endpoints is not easily handled by the standard theory. We analyze current methods that allow design modifications to be based on the full interim data, i.e., not only the observed event times but also secondary endpoint and safety data from patients who are yet to have an event. We show that the final test statistic may ignore a substantial subset of the observed event times. An alternative test incorporating all event times is found, where a conservative assumption must be made in order to guarantee type I error control. We examine the power of this approach using the example of a clinical trial comparing two cancer therapies.http://europepmc.org/articles/PMC4749572?pdf=render |
| spellingShingle | Dominic Magirr Thomas Jaki Franz Koenig Martin Posch Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials. PLoS ONE |
| title | Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials. |
| title_full | Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials. |
| title_fullStr | Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials. |
| title_full_unstemmed | Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials. |
| title_short | Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials. |
| title_sort | sample size reassessment and hypothesis testing in adaptive survival trials |
| url | http://europepmc.org/articles/PMC4749572?pdf=render |
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