Improving the application of quantitative methods in validation work

The acceptance of quantitative methods in in vitro studies has seen a stead y increase over the last 5 years. ECVAM's Biostatistics Task Force report i n the mid-1990s (Holzhutter, H.-G., Archer, G., Dami, N., Lovall, D.P., Sal telli, A., Sjostrom, M., 1996. Recommendations for the application of biost atistical methods during the development and validation of alternative toxi cological methods. ECVAM Biostatistics Task Force Report 1. ATLA 24, 511-53 0) laid out clear guidelines for biologists in this field. Nevertheless, th e application of more formal approaches to experimental design and statisti cs is still far from complete in many studies. Furthermore, the regulatory paradigm often does not encourage the use of standard statistical technique s; for example, lowest detectable concentration levels in assays are define d in international guidelines as a simple multiple of standard deviation, r ather than tests which are accepted in the statistical field as more reliab le and more powerful. ECVAM is currently defining a new approach to facilit ate the improved acceptance of these methods into the development and valid ation process. This will cover a review of appropriate quantitative approac hes that can be applied in the validation of alternative methods, as well a s an educational element for the community as a whole. This paper will disc uss some issues of concern, and outline the milestones planned to help faci litate the acceptance of quantitative methods. (C) 2001 Published by Elsevi er Science Ltd.