Objective: A basic issue in randomized controlled trials (RCTs) is
whether we can safely assume comparability between groups at baseline with
respect to all potentially important prognostic factors. In other words, did
randomization work sufficiently well? In small trials balanced allocation
procedures are employed, whereas in large-scale trials simple randomization
will do. The question is: When should balancing be considered?
Methods: We performed a simulation study in which we varied the
number of categories in the prognostic factors and the number of patients.
Results: Simulation showed that, in all instances, a balancing
procedure almost always led to perfect or almost perfect balance, while the
imbalance with simple randomization was larger. To study the effect of
balanced and random allocation on subgroup analyses in our OME trial, we
compared the quotient of the width of the confidence intervals (CI). The
widest CI in random allocation over the 13 hospitals was on average 13% wider
than in balanced allocation.
Conclusion: Investigators should always consider balanced
allocation, especially in categories with a low number of patients and when
subgroup analysis over many categories is requested.