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Biostatistical Design and Analyses of Long-Term Animal Studies Simulating Human Postmenopausal Osteoporosis

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Abstract

Using three well-designed experimental studies as illustration, we demonstrate that the biostatistical design and analysis of long-term animal studies simulating human osteoporosis should be analogous to the design and analysis of randomized clinical trials. This principal is in accordance with the recommendations from the International Conference on Harmonisation guidelines concerning statistical principles in clinical trials (1). An important element of biostatistical study design is sample size. The three studies that are described herein used an a-priori sample size estimation for the one-way layout that included controls and several treatment and dose groups.

In these k-sample designs, with at least one control group, both the multiple comparison procedure and trend tests within procedures for identification of the minimal-effective dose are recommended. Although p-values in pharmacology are quite common, confidence intervals should be used according to their interpretation for both statistical significance and clinical relevance. The use of one-sided confidence intervals for both the difference and the ratio to control for proving either superiority or at least noninferiority is demonstrated by real data examples. Relevant and relatively straightforward software is available for biostatistical analysis and can also be used to aid design. In summary, referring to published, well-designed experimental studies can help to assist with ensuring the quality of future investigations.

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Authors and Affiliations

  1. Unit of Bioinformatics, Hannover University, Herrenhaeuserstrasse 2, D-30419, Hannover, Germany

    Ludwig A. Hothorn PhD

  2. Roche Diagnostics GmbH, Pharma Research Penzberg, Penzberg, Germany

    Frieder Bauss PhD

  3. Institute of Pharmacology and Toxicology, Heidelberg University, Mannheim, Germany

    Frieder Bauss PhD

Authors
  1. Ludwig A. Hothorn PhD
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  2. Frieder Bauss PhD
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Correspondence to Ludwig A. Hothorn PhD.

Additional information

Presented at the Third International DIA Workshop on “Statistical Methodology in Non-Clinical R&D,” Barcelona, Spain, September 2002.

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Hothorn, L.A., Bauss, F. Biostatistical Design and Analyses of Long-Term Animal Studies Simulating Human Postmenopausal Osteoporosis. Ther Innov Regul Sci 38, 47–56 (2004). https://doi.org/10.1177/009286150403800107

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