SAS/STAT Software


The purpose of the SEQDESIGN procedure is to design interim analyses for group sequential clinical trials. A group sequential trial provides for interim analyses before the formal completion of the trial while maintaining the specified overall Type I and Type II error probability levels.

The SEQDESIGN procedure assumes that the standardized test statistics for the null hypothesis at the stages have the joint canonical distribution with the information levels at the stages for the parameter. This implies that these test statistics are normally distributed. If the test statistic is not normally distributed, then it is assumed that the test statistic is computed from a large sample such that the statistic has an approximately normal distribution.

You can use the SEQDESIGN procedure to compute required sample sizes for commonly used hypothesis tests.

The applicable tests include tests for binomial proportions and the log-rank test for two survival distributions.

Output from the SEQDESIGN Procedure

In addition to computing the boundary values for a group sequential design, the SEQDESIGN procedure computes the following quantities:
  • maximum sample size (as a percentage of the corresponding fixed-sample size) if the trial does not stop at an interim stage
  • average sample sizes (as a percentage of the corresponding fixed-sample size) under various hypothetical references, including the null and alternative references
  • stopping probabilities at each stage under various hypothetical references to indicate how likely it is that the trial will stop at that stage
  • sample sizes required at each stage for the specified hypothesis test with nonsurvival data at each stage for the specified hypothesis test with survival data
  • numbers of events required at each stage for the specified hypothesis test with survival data

You can create more than one design with multiple DESIGN statements in the SEQDESIGN procedure and then choose the design with the most desirable features.

Group Sequential Methods

For a group sequential design, there are two possible boundaries for a one-sided test and four possible boundaries for a two-sided test. Each boundary consists of one boundary value (critical value) for each stage. The SEQDESIGN procedure provides the following methods for computing the boundary values:
  • fixed boundary shape methods, which derive boundaries with specified boundary shapes
  • Whitehead methods, which adjust boundaries derived for continuous monitoring so that they apply to discrete monitoring
  • error spending methods

For further details see the SEQDESIGN Procedure