title: Designs for clinical trials to test the efficacy of therapeutics in progressive multifocal leukoencephalopathy.
abstract: The design of a comparative treatment trial to evaluate the efficacy of therapeutics for progressive multifocal leukoencephalopathy (PML) is outlined. We propose a large simple randomized trial with patient survival as its primary endpoint, completed in a short period of time and involving a cohort with as few enrollment restrictions as possible. We use stratification as the counterweight to the lack of exclusion criteria and suggest that proper stratification will attenuate differences inherent in a heterogeneous subject cohort. Estimation of power, sample size, and study duration, implementation of interim analyses, toxicity management, and validation of secondary clinical measures are also addressed.
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts 02115, USA. costas@hsph.harvard.edu
authors.forename: C T
authors.initials: CT
authors.lastname: Yiannoutsos
authors.forename: A
authors.initials: A
authors.lastname: De Luca
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
chemical_list: D000998:Antiviral Agents