Repeated significance tests on accumulating survival data.
The aim of the study was to compare the properties of two well-known group sequential methods and to demonstrate the effect of performing interim analyses on accumulating survival data without making appropriate adjustments of the nominal significance level. The properties of a group sequential method with fixed nominal significance level (Pocock stopping boundaries) and a method with increasing nominal level with each interim analysis (O'Brien-Fleming boundaries) were compared by stochastic simulation. Simulation experiments with survival times sampled from a breast cancer trial and from exponential distributions were performed. The true overall significance level with unplanned interim analyses increased from 5% to 14% when a maximum of five tests were performed. Both group sequential methods maintained the desired overall significance level. The O'Brien-Fleming method had higher power than Pocock's method. It also reduced the risk of early stopping based on immature data and should usually be preferred.
Skovlund
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The Norwegian Cancer Society and Section of Medical Statistics, University of Oslo, Montebello. eva.skovlund@klinmed.uio.no
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D011336:Probability; D012189:Retrospective Studies; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen