On the efficiency of targeted clinical trials

The development of genomics-based technologies is demonstrating that many common diseases are heterogeneous collections of molecularly distinct entities. Molecularly targeted therapeutics is often effective only for some subsets patients with a conventionally defined disease. We consider the problem of design of phase III randomized clinical trials for the evaluation of a molecularly targeted treatment when there is an assay predictive of which patients will be more responsive to the experimental treatment than to the control regimen. We compare the conventional randomized clinical trial design to a design based on randomizing only patients predicted to preferentially benefit from the new treatment. Trial designs are compared based on the required number of randomized patients and the expected number of patients screened for randomization eligibility. Relative efficiency depends upon the distribution of treatment effect across patient subsets, prevalence of the subset of patients who respond preferentially to the experimental treatment, and assay performance.