title: Studies with group treatments required special power calculations, allocation methods, and statistical analyses.
abstract: OBJECTIVE
  In some trials, the intervention is delivered to individuals in groups, for example, groups that exercise together. The group structure of such trials has to be taken into consideration in the analysis and has an impact on the power of the trial. Our aim was to provide optimal methods for the design and analysis of such trials.
  
  
  METHODS
  We described various treatment allocation methods and presented a new allocation algorithm: optimal batchwise minimization (OBM). We carried out a simulation study to evaluate the performance of unrestricted randomization, stratification, permuted block randomization, deterministic minimization, and OBM. Furthermore, we described appropriate analysis methods and derived a formula to calculate the study size.
  
  
  RESULTS
  Stratification, deterministic minimization, and OBM had considerably less risk of imbalance than unrestricted randomization and permuted block randomization. Furthermore, OBM led to unpredictable treatment allocation. The sample size calculation and the analysis of the study must be based on a multilevel model that takes the group structure of the trial into account.
  
  
  CONCLUSIONS
  Trials evaluating interventions that are carried out in subsequent groups require adapted treatment allocation, power calculation, and analysis methods. From the perspective of obtaining overall balance, we conclude that minimization is the method of choice. When the number of prognostic factors is low, stratification is an excellent alternative. OBM leads to better balance within the batches, but it is more complicated. It is probably most worthwhile in trials with many prognostic factors. From the perspective of predictability, a treatment allocation method, such as OBM, that allocates several subjects at the same time, is superior to other methods because it leads to the lowest possible predictability.
authors.affiliation: Department of Geriatric Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. m.faes@ger.umcn.nl
authors.forename: Miriam C
authors.initials: MC
authors.lastname: Faes
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Reelick
authors.forename: Marieke
authors.initials: M
authors.lastname: Perry
authors.forename: Marcel G M
authors.initials: MG
authors.lastname: Olde Rikkert
authors.forename: George F
authors.initials: GF
authors.lastname: Borm
mesh_terms: D000465:Algorithms; D002986:Clinical Trials as Topic; D006127:Group Structure; D006801:Humans; D011379:Prognosis; D011615:Psychotherapy, Group; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic; D012107:Research Design