title: Randomization in clinical trials: stratification or minimization? The HERMES free simulation software.
abstract: OBJECTIVE
  Operative clinical trials are often small and open-label. Randomization is therefore very important. Stratification and minimization are two randomization options in such trials. The first aim of this study was to compare stratification and minimization in terms of predictability and balance in order to help investigators choose the most appropriate allocation method. Our second aim was to evaluate the influence of various parameters on the performance of these techniques.
  
  
  METHODS
  The created software generated patients according to chosen trial parameters (e.g., number of important prognostic factors, number of operators or centers, etc.) and computed predictability and balance indicators for several stratification and minimization methods over a given number of simulations. Block size and proportion of random allocations could be chosen. A reference trial was chosen (50 patients, 1 prognostic factor, and 2 operators) and eight other trials derived from this reference trial were modeled. Predictability and balance indicators were calculated from 10,000 simulations per trial.
  
  
  RESULTS
  Minimization performed better with complex trials (e.g., smaller sample size, increasing number of prognostic factors, and operators); stratification imbalance increased when the number of strata increased. An inverse correlation between imbalance and predictability was observed.
  
  
  CONCLUSIONS
  A compromise between predictability and imbalance still has to be found by the investigator but our software (HERMES) gives concrete reasons for choosing between stratification and minimization; it can be downloaded free of charge.
  
  
  CONCLUSIONS
  This software will help investigators choose the appropriate randomization method in future two-arm trials.
authors: Sorbonne Paris Cité, Faculté de chirurgie dentaire, Biomaterials department (URB2i, EA4462), Clinical Research Unit, Université Paris Descartes, 1 rue Maurice Arnoux, Montrouge, 92120, France, helene.fron@parisdescartes.fr.
authors: Hélène
authors: H
authors: Fron Chabouis
authors: Francis
authors: F
authors: Chabouis
authors: Florence
authors: F
authors: Gillaizeau
authors: Pierre
authors: P
authors: Durieux
authors: Gilles
authors: G
authors: Chatellier
authors: N Dorin
authors: ND
authors: Ruse
authors: Jean-Pierre
authors: JP
authors: Attal
mesh_terms: D003198:Computer Simulation; D006801:Humans; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D012984:Software