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A loss-function based approach for dose selection in two-stage dose-response trials.

T Friede·M Kieser
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Abstract

BACKGROUND: Adaptive two-stage designs are a flexible tool in drug development and have the potential for an improvement of power over one-stage designs. In an adaptive two-stage dose-response trial, the dose-response relationship is examined in a preplanned interim analysis. If efficacy has not yet been proved, a subset of the most favourable doses may be selected for the second stage. This design offers the opportunity to combine dose selection and proof of efficacy within a single trial. METHODS: We consider a change-point regression model describing the dose-response relationship. In this framework, selection of the most favourable dose can be achieved by estimating the change point in the regression model. We introduce a change-point estimator that can be optimised by a loss-function based approach, taking into account both efficacy and safety aspects. We investigate the power characteristics of our approach. RESULTS: The proposed procedure performs well with regard to statistical power. The proposal demonstrates the feasibility of simultaneous modelling of efficacy and safety aspects by a loss-function based approach. CONCLUSION: Adaptive two-stage designs, in conjunction with an elaborated dose-selection rule, can support the decision about the suitable dose to use, leading to a considerable gain in power (or saving in sample size) and possibly speeding up the time-to-market in drug development.

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Clinical Trials as TopicDose-Response Relationship, DrugDrug EvaluationEpidemiologic Research DesignHumansModels, StatisticalPharmacoepidemiologyRisk AssessmentJournal ArticleResearch Support, Non-U.S. Gov't

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BibTeXRIS

T Friede, M Kieser. 2001. A loss-function based approach for dose selection in two-stage dose-response trials.. https://doi.org/10.1080/13595220152601783

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