Interim analyses are a common feature of clinical trial design, especially for large trials in high mortality conditions such as cancer or cardiovascular disease in which the primary endpoint is often the survival time from randomization to death. A plan for a series of interim analyses in which the criteria for stopping are specified in advance is known as a sequential design, and can be constructed to prevent patients from being randomized to an evidently inferior treatment and avoid continuation of a trial that is obviously futile.
In this paper, methods for predicting the final sample size and total duration of a sequential survival study are described, and the play-off between speed of recruitment and length of follow-up is examined. The use of interim analyses to review the event rate, recruitment period, and model assumptions is discussed and software for the implementation of the methods is described. The approach is illustrated in the context of a trial seeking to establish noninferiority.
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