Novel methods in molecular biology and advanced technologies have give
n pharmaceutical research laboratories the capability to test combinat
orial libraries rapidly against large numbers of potential targets. Me
thods to identify optimal assay conditions efficiently are very useful
in the development of robotic screening assays where there are numero
us variables and potential interactions between the variables. This re
view discusses the use of statistical experimental design in the devel
op ment and optimization of high-throughput screening assays. The auth
ors provide a brief introduction to the theoretical basis for experime
ntal design and discuss practical aspects of using these methods in a
research laboratory. Two case studies demonstrate the power of the met
hod in solving problems in assay development and illustrate the divers
ity of potential applications.