Combining different phases in the development of medical treatments within a single trial

✍ Scribed by Peter Bauer; Meinhard Kieser

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 154 KB
• Volume: 18
• Category: Article
• ISSN: 0277-6715
• DOI: 10.1002/(sici)1097-0258(19990730)18:14<1833::aid-sim221>3.0.co;2-3

✦ Synopsis

In the development of medical treatments, identi"cation of promising therapies and inference on selected treatments are usually performed in subsequent separate trials. An adaptive two-stage design is proposed for the situation of multiple treatments to be compared with a control, allowing integration of both steps within a single con"rmatory trial controlling the multiple level . After the interim analysis, the trial may be terminated early or is continued with a second stage, where the set of treatments may be reduced due to lack of e$cacy or to safety problems. The procedure is highly #exible with respect to the distributional assumptions, stopping rules and selection criteria and allows a completely free recalculation of the sample size for the second stage. Simulations show that the method may be substantially more powerful than classical one-stage multiple treatment designs with the same total sample size. As in conventional strategies with a series of separate experiments, a reasonable selection strategy has to be applied in order to prevent proceeding with non-optimal treatments.