Sequential Rank Tests with Repeated Measurements in Clinical Trials

Abstract

For comparing responses in two groups of subjects observed repeatedly, we propose a group sequential procedure based on linear rank statistics. The asymptotic normality of the sequentially computed linear rank statistics is obtained, and construction of the group sequential boundaries is based on this distribution theory. By virtue of this asymptotic approximation, the proposed procedure can be applied to interim analyses with either continuous or discrete repeated measurements. Even for staggered patient entry, simulation results suggest the theory is approximately correct. It can also be useful for testing the equality of two changes and rates of change, as well as the equality of two means of the responses. This procedure is illustrated with a real example.

Key Words:

• Group sequential testing
• Linear rank statistics
• Rank-order test
• Repeated measurements
• Staggered entry