Practical considerations for optimal designs in clinical dose finding studies
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Updated: Jun 15, 2026

Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies
Published on: February 6, 2019
Frank Bretz1, Holger Dette, Jose C Pinheiro
1Novartis Pharma AG, CH-4002 Basel, Switzerland. frank.bretz@novartis.com
Abstract:
A key objective in the clinical development of a medicinal drug is the determination of an adequate dose level and, more broadly, the characterization of its dose response relationship. If the dose is set too high, safety and tolerability problems are likely to result, while selecting too low a dose makes it difficult to establish adequate efficacy in the confirmatory phase, possibly leading to a failed program. Hence, dose finding studies are of critical importance in drug development and need to be planned carefully. In this paper, we focus on practical considerations for establishing efficient study designs to estimate relevant target doses. We consider optimal designs for estimating both the minimum effective dose and the dose achieving a certain percentage of the maximum treatment effect. These designs are compared with D-optimal designs for a given dose response model. Extensions to robust designs accounting for model uncertainty are also discussed. A case study is used to motivate and illustrate the methods from this paper.
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