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Optimal multi-stage designs for a phase II trial that permits one dose escalation

✍ Scribed by John J. Hanfelt


Publisher
John Wiley and Sons
Year
1999
Tongue
English
Weight
133 KB
Volume
18
Category
Article
ISSN
0277-6715

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✦ Synopsis


Simon's optimal two-stage design is widely used to conduct single-dose phase II clinical trials. We extend this basic methodology to the situation where the researcher desires to test an experimental drug for activity at a low dose level, but is willing to increase the dose part-way through the trial if the early results suggest that the low dose is ine ective. Interest is conÿned to at most one dose escalation, and no consideration is given to escalating the dose within a patient. Optimal multi-stage designs are presented that are more e cient than the naive approach of merely conducting two consecutive Simon optimal trials, one at the low dose and the second (if deemed necessary) at the high dose. As in Simon's original design, toxicity is not considered here as a primary endpoint. Hence, the designs presented in this paper are appropriate only when the toxicity of the drug is well understood at both dose levels.