Reisensburg 1997: Abstract Hauschke
Statistical Computing '97 - Schloß Reisensburg

Sample Size Determination for the Cross-over Design

Dieter Hauschke, Martin Burke, Edgar Diletti

Department of Biometry
Byk Gulden Pharmaceuticals

The recent note for guidance "Biostatistical methodology in clinical trials in applications for marketing authorizations for medical products" , published in 1994 by the European Committee for Proprietary Medicinal Products (CPMP), requires that for the primary efficacy characteristic the sample size determination has to be stipulated in the study protocol prior to starting the clinical trial.

A commonly used experimental setting in clinical trials is the two-period, two-sequence cross-over design. However, only a limited number of publications address to the corresponding sample size calculation.

Therefore, consideration of this topic is given in this presentation for equivalence and difference testing between two treatments.


  1. Diletti, E., Hauschke, D. and Steinijans, V.W. (1991): Sample size determination for bioequivalence assessment by means of confidence intervals. International Journal of Clinical Pharmacology and Toxicology 29, 1-8.
  2. Hauschke, D., Steinijans, V.W., Diletti, E. and Burke, M. (1992): Sample size determination for bioequivalence assessment using a multiplicative model. Journal of Pharmacokinetics and Biopharmaceutics 20, 557-561.
  3. Hauschke, D. Burke, M. and Diletti, E. (1997): Sample size determination for the cross-over design. In: Vollmar, J. and Hothorn, L.A. (eds) Biometrie in der chemisch-pharmazeutischen Industrie, Vol. 8: Cross-over clinical trials (to appear).
  4. Owen, D.B. (1965): A special case of a bivariate non-central t-distribution. Biometrika 52, 437-446.
  5. Phillips, K.F. (1990): Power of the two one-sided tests procedure in bioequivalence. Journal of Pharmacokinetics and Biopharmaceutics 18, 137-144.

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