Purpose: Genomic technologies make it increasingly possible to identify patients most likely to benefit from a molecularly targeted drug. This creates the opportunity to conduct targeted clinical trials with eligibility restricted to patients predicted to be responsive to the drug.
Experimental design: We evaluated the relative efficiency of a targeted clinical trial design to an untargeted design for a randomized clinical trial comparing a new treatment to a control. Efficiency was evaluated with regard to number of patients required for randomization and number required for screening.
Results: The effectiveness of this design, relative to the more traditional design with broader eligibility, depends on multiple factors, including the proportion of responsive patients, the accuracy of the assay for predicting responsiveness, and the degree to which the mechanism of action of the drug is understood. Explicit formulas were derived for computing the relative efficiency of targeted versus untargeted designs.
Conclusions: Targeted clinical trials can dramatically reduce the number of patients required for study in cases where the mechanism of action of the drug is understood and an accurate assay for responsiveness is available.