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. 2009 Oct 30;28(24):2941-51.
doi: 10.1002/sim.3684.

An adaptive design for identifying the dose with the best efficacy/tolerability profile with application to a crossover dose-finding study

Anastasia Ivanova  1 , Ken Liu, Ellen Snyder, Duane Snavely
Affiliations

An adaptive design for identifying the dose with the best efficacy/tolerability profile with application to a crossover dose-finding study

Anastasia Ivanova et al. Stat Med. .

Erratum in

  • Stat Med. 2010 Dec 20;29(29):3068

Abstract

Proof-of-concept in clinical trials has traditionally focused on the identification of a maximum tolerated dose with the assumption that the higher doses provide better efficacy. However, adverse events associated with a maximum tolerated dose may have a negative effect on efficacy. We present an efficient adaptive dose-finding strategy that concentrates patient assignments at and around the dose which has the best efficacy/tolerability profile based on a utility function. The strategy is applied within the setting of a crossover design. While the strategy may also be applied to parallel studies, a crossover design provides more power for a given sample size for comparisons between the optimal dose versus placebo and/or active control when it is reasonable to assume no carryover effects.

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Figures

Figure 1
Figure 1
Six efficacy-tolerability scenarios showing the values for utility (Utl), efficacy (Eff) and tolerability (AE). Utility is computed as Efficacy − 10×Tolerability.
See this image and copyright information in PMC

References

    1. O’Quigley J, Huges MD, Fenton T. Dose-finding designs for HIV studies. Biometrics. 2001;57:1018–1029. - PubMed
    1. Thall PF, Inoue LY, Martin TG. Adaptive decision-making in a lymphocyte infusion trial. Biometrics. 2002;58:560–568. - PubMed
    1. Ivanova A. A new dose-finding design for bivariate outcomes. Biometrics. 2003;59:1003–1009. - PubMed
    1. Dragalin V, Fedorov V. Adaptive designs for dose-finding based on efficacy—toxicity response. Journal of Statistical Planning and Inference. 2006;136:1800–1823.
    1. Thall PF, Cook JD. Dose-finding based on efficacy-toxicity trade-offs. Biometrics. 2004;60:684–693. - PubMed

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