Interim Design Modifications in Time-to-Event Studies
We propose a flexible method for interim design modifications in time-to-event studies. With this method, it is possible to inspect the data at any time during the course of the study, without the need for prespecification of a learning phase, and to make certain types of design modifications depending on the interim data without compromising the Type I error risk. The method can be applied to studies designed with a conventional statistical test, fixed sample, or group sequential, even when no adaptive interim analysis and no specific method for design adaptations (such as combination tests) had been foreseen in the protocol. Currently, the method supports design changes such as an extension of the recruitment or follow-up period, as well as certain modifications of the number and the schedule of interim analyses as well as changes of inclusion criteria. In contrast to existing methods offering the same flexibility, our approach allows us to make use of the full interim information collected until the time of the adaptive data inspection. This includes time-to-event data from patients who have already experienced an event at the time of the data inspection, and preliminary information from patients still alive, even if this information is predictive for survival, such as early treatment response in a cancer clinical trial. Our method is an extension of the so-called conditional rejection probability (CRP) principle. It is based on the conditional distribution of the test statistic given the final value of the same test statistic from a subsample, namely the learning sample. It is developed in detail for the example of the logrank statistic, for which we derive this conditional distribution using martingale techniques.
If you experience problems downloading a file, check if you have the proper application to view it first. In case of further problems read the IDEAS help page. Note that these files are not on the IDEAS site. Please be patient as the files may be large.
As the access to this document is restricted, you may want to look for a different version under "Related research" (further below) or search for a different version of it.
Volume (Year): 107 (2012)
Issue (Month): 497 (March)
|Contact details of provider:|| Web page: http://www.tandfonline.com/UASA20|
|Order Information:||Web: http://www.tandfonline.com/pricing/journal/UASA20|
When requesting a correction, please mention this item's handle: RePEc:taf:jnlasa:v:107:y:2012:i:497:p:341-348. See general information about how to correct material in RePEc.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: (Chris Longhurst)
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
If references are entirely missing, you can add them using this form.
If the full references list an item that is present in RePEc, but the system did not link to it, you can help with this form.
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your profile, as there may be some citations waiting for confirmation.
Please note that corrections may take a couple of weeks to filter through the various RePEc services.