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Abstract:
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In the era of breakthrough for development of oncology products, sequential phase I, II, and III studies may not be feasible, and thus selection of a recommended dose may occur in an abbreviated manner. In these cases, the historical approach of selecting the maximum tolerated dose (MTD) as the recommended dose, often using the 3+3 algorithm, may not be optimal, and other approaches should be considered. Through this approach, a drug may fail in later phase trials due to an unacceptable toxicity profile, even if the drug exceeds expectations for efficacy. In such case, post-market trials are needed to find optimal doses, but the designs of such trials are usually too simple to answer any questions. The goal of this discussion is twofold: first, we discuss the best practice in designing phase I and II trials to recommend good doses for phase III confirmatory trials; second, we discuss clinical trial designs for post-marketing trials finding optimal doses.
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