Designs for clinical trials to test the efficacy of therapeutics in progressive multifocal leukoencephalopathy

The design of a comparative treatment trial to evaluate the efficacy of the rapeutics for progressive multifocal leukoencephalopathy (PML) is outlined. We propose a large simple randomized trial with patient survival as its pr imary endpoint, completed in a short period of time and involving a cohort with as few enrollment restrictions as possible. We use stratification as t he counterweight to the lack of exclusion criteria and suggest that proper stratification will attenuate differences inherent in a heterogeneous subje ct cohort. Estimation of power, sample size, and study duration, implementa tion of interim analyses, toxicity management, and validation of secondary clinical measures are also addressed.