Avoiding Missed Opportunities by Analyzing the Sensitivity of Our Decisions

Drug discovery is
a multiparameter optimization process in which
the goal of a project is to identify compounds that meet multiple
property criteria required to achieve a therapeutic objective. However,
once a profile of property criteria has been chosen, the impact of
these criteria on the decisions made regarding progression of compounds
or chemical series should be carefully considered. In some cases the
decision is very sensitive to a specific property criterion, and such
a criterion may artificially distort the direction of the project;
any uncertainty in the “correct” value or the importance
of this criterion may lead to valuable opportunities being missed.
In this paper, we describe a method for analyzing the sensitivity
of the prioritization of compounds to a multiparameter profile of
property criteria. We show how the results can be easily interpreted
and illustrate how this analysis can highlight new avenues for exploration.