Designs for Dose Finding Studies on Safety and Efficacy

Conference paper
Part of the Contributions to Statistics book series (CONTRIB.STAT.)


In early phase clinical trials usually only the safety and tolerability of a new drug are investigated at first. We suggest a model with which safety, measured on a categorical scale, and efficacy, a binary response, can be evaluated simultaneously. Subsequently we derive locally optimal designs for this model. Additionally, we apply this model in a sequential approach and compare its features with approaches considering only one endpoint.


Optimal Design Maximum Tolerate Dose Design Point Information Matrix Dose Escalation Study 


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The author is very grateful to Rainer Schwabe (University of Magdeburg) and Thomas Schmelter (Bayer Schering Pharma AG) for their support.


  1. Dragalin, V. and Fedorov, V. (2006). Adaptive designs for dose-finding based on efficacy-toxicity response. Journal of Statistical Planning and Inference 136, 1800–1823.MATHCrossRefMathSciNetGoogle Scholar
  2. Ford, I., Torsney, B., and Wu, C. F. J. (1992). The use of a canonical form in the construction of locally optimal designs for non-linear problems. Journal of the Royal Statistical Society, Series B 54, 569–583.MATHMathSciNetGoogle Scholar
  3. Gerke, O. and Siedentop, H. (2007). Optimal phase I dose escalation trial designs in oncology - A simulation study. Statistics in Medicine 27, 5329–5344.CrossRefGoogle Scholar
  4. Ivanova, A. (2006). Dose-finding in oncology – nonparametric methods. In Ting, N., Editor, Dose Finding in Drug Development, 49–58. New York: Springer-Verlag.CrossRefGoogle Scholar
  5. Kotz, S., Balakrishnan, N., and Johnson, N. (2000). Continuous Multivariate Distributions, Vol. 1. New York: Wiley.MATHGoogle Scholar
  6. National Cancer Institute (2006). Common Terminology Criteria for Adverse Events.Google Scholar
  7. Roth, K. (2009a). Adaptive designs for dose escalation studies. In Ermakov, S., Melas, V., and Pepelyshev, A., editors, Proceedings of the 6th Saint Petersburg Workshop on Simulation, 133–142.Google Scholar
  8. Roth, K. (2009b). Optimal Design for Dose Finding Studies on Safety and Efficacy. PhD thesis, Otto-von-Guericke-Universität Magdeburg, Germany.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Bayer Schering Pharma AGBerlinGermany
  2. 2.Otto-von-Guericke-UniversitätMagdeburgGermany

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