title: Comparison of statistical and operational properties of subject randomization procedures for large multicenter clinical trial treating medical emergencies.
abstract: Large multicenter acute stroke trials demand a randomization procedure with a high level of treatment allocation randomness, an effective control on overall and within-site imbalances, and a minimized time delay of study treatment caused by the randomization procedure. Driven by the randomization algorithm design of A Study of the Efficacy and Safety of Activase (Alteplase) in Patients with Mild Stroke (PRISMS) (NCT02072226), this paper compares operational and statistical properties of different randomization algorithms in local, central, and step-forward randomization settings. Results show that the step-forward randomization with block urn design provides better performances over others. If the concern on the potential time delay is not serious and a central randomization system is available, the minimization method with an imbalance control threshold and a biased coin probability could be a better choice.
authors: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA. Electronic address: zhaow@musc.edu.
authors: Wenle
authors: W
authors: Zhao
authors: Genentech Inc., San Francisco, CA, USA.
authors: Yunming
authors: Y
authors: Mu
authors: Genentech Inc., San Francisco, CA, USA.
authors: Darren
authors: D
authors: Tayama
authors: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
authors: Sharon D
authors: SD
authors: Yeatts
mesh_terms: D000465:Algorithms; D001241:Aspirin / Q000627:therapeutic use*; D003198:Computer Simulation; D004311:Double-Blind Method; D004630:Emergencies; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D015337:Multicenter Studies as Topic; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D020521:Stroke / Q000188:drug therapy*; D061665:Time-to-Treatment; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D010959:Tissue Plasminogen Activator; D001241:Aspirin
keywords: Acute stroke trial; Allocation randomness; Baseline balance; Step-forward randomization; Treatment time delay
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