Meta-Analyses and Adaptive Group Sequential Designs in the Clinical Development Process

Abstract

ABSTRACT The clinical development process can be viewed as a succession of trials, possibly overlapping in calendar time. The design of each trial may be influenced by results from previous studies and other currently proceeding trials, as well as by external information. Results from all of these trials must be considered together in order to assess the efficacy and safety of the proposed new treatment. Meta-analysis techniques provide a formal way of combining the information. We examine how such methods can be used in combining results from: (1) a collection of separate studies, (2) a sequence of studies in an organized development program, and (3) stages within a single study using a (possibly adaptive) group sequential design. We present two examples. The first example concerns the combining of results from a Phase IIb trial using several dose levels or treatment arms with those of the Phase III trial comparing the treatment selected in Phase IIb against a control. This enables a “seamless transition” from Phase IIb to Phase III. The second example examines the use of combination tests to analyze data from an adaptive group sequential trial.