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Monitoring a Three-Armed Clinical Trial with Survival Endpoints: Fisher's Least Significant Difference Approach

Authors: Pai-Lien, Chen; Rosalie, Dominik;

Monitoring a Three-Armed Clinical Trial with Survival Endpoints: Fisher's Least Significant Difference Approach

Abstract

Researchers have long recognized the importance of monitoring trials to determine whether to terminate a trial early or change a trial because of a substantial treatment effect. Fisher's least significant difference (LSD) procedure has been suggested by Proschan et al. [Proschan, M. A., Follmann, D. A., Geller, N. L. (1994). Monitoring multi-armed trials. Stat. Med. 13:1441-1452] to control the overall type I error rate for trials with three or more arms and survival endpoints. In this paper we propose an alternative Fisher's LSD interim monitoring procedure that uses the same adjusted significance levels for the pairwise tests as for the global test; it continues performing a global hypothesis test at looks subsequent to a look where a global null hypothesis was rejected. We also examine revised Proschan et al. approach that uses the O'Brien-Fleming two-armed trial boundaries for pairwise tests. A simulation study shows that compared to the approach proposed by Proschan et al., the procedure we propose is more powerful and produces overall type I error rates closer to the nominal values when all groups are truly equivalent. For the scenarios examined, the overall type I error rates and power of the proposed approach are virtually equivalent to those of the revised Proschan et al. approach.

Related Organizations
Keywords

Clinical Trials as Topic, Endpoint Determination, Survival Analysis, Pregnancy, Research Design, Data Interpretation, Statistical, Humans, Computer Simulation, Female, Algorithms

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
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