Mixture Experimental Design

Abstract

There is a general consensus, based on a number of surveys and analytic efforts, that mixture study designs have historically been lacking. Although there has been considerable progress over the past decades, further improvement is necessary both in the development and application of experimental designs to yield data suitable for quantitative analytic methods and in the implementation of appropriate statistical analyses. This chapter reviews the state of the science with regard to the experimental and statistical quality of mixture studies. The importance of properly powering mixture experiments is emphasized; in particular when the focus is on the low-dose/low-effect region. Issues with powering defined mixture and complex mixture experiments are explored. Some designs that have proven useful in mixture experimentation are reviewed, including full and fractional factorial designs and statistical mixture designs such as the isobologram and the fixed ratio ray. General considerations are provided that will aid in the development of both experimental design and analysis strategies that address the question(s) being asked.