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...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2016-02, Vol.11 (2), p.e0146465-e0146465
Main Authors: Magirr, Dominic, Jaki, Thomas, Koenig, Franz, Posch, Martin
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Biometrics
Cancer
Clinical decision making
Clinical trials
Clinical Trials as Topic - methods
Decision making
Design modifications
Design standards
Follow-Up Studies
Humans
Hypotheses
Hypothesis testing
Informatics
Medical research
Medical statistics
Medicine
Medicine and Health Sciences
Normal distribution
Oncology
Pharmaceuticals
Physical Sciences
Research and Analysis Methods
Sample Size
Studies
Survival
Survival Analysis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0146465