A group sequential design provides detailed specifications for a group sequential trial. In addition to the usual specifications, it provides the total number of stages (the number of interim stages plus a final stage) and a stopping criterion to either reject or accept the null hypothesis at each interim stage. It also provides critical values and the sample size at each stage for the trial.
At each interim stage, all the data collected up to that point are analyzed, and statistics such as a maximum likelihood test statistic and its associated standard error are computed. The test statistic is then compared with critical values generated from the sequential design, and the trial is stopped or continued. If a trial continues to the final stage, the null hypothesis is either rejected or accepted.
The SAS/STAT group sequential design and analysis procedures include the following:
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 logrank test for two survival distributions.


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.


The purpose of the SEQTEST procedure is to perform 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.
You then use the SEQTEST procedure to compare the test statistic with the corresponding boundary values obtained with the SEQDESIGN procedure.
If the information levels do not match the information levels specified in the design, the SEQTEST procedure modifies the boundary values to adjust for new information levels.
At the end of a trial, the parameter estimate is computed. The median unbiased estimate, confidence limits, and pvalue depend on the specified sample space ordering. A sample space ordering specifies the ordering for test statistics resulting in the stopping of a trial. That is, for all the statistics in the rejection region and in acceptance region, the SEQTEST procedure provides three different sample space orderings: the stagewise ordering uses counterclockwise ordering around the continuous region, the LR ordering uses the distance between the observed Z statistic, z, and its hypothetical value, and the MLE ordering uses the observed maximum likelihood estimate.
Note that for some clinical trials, the information levels are derived from statistics based on individuals specified in the design plan and might not reach the target information levels. Thus, instead of specifying the number of individuals in the protocol, the information levels can be specified. You can then adjust the sample sizes to achieve the information levels for the trial.

