Were patients in the treatment and control groups similar with respect to known prognostic factors?
The purpose of randomization is to create groups for which the prognosis, with respect to the target outcome, is similar. Sometimes, through bad luck, randomization will fail to achieve this goal. The smaller the sample size, the more likely it is that the trial will suffer from prognostic imbalance. Consider a trial for the evaluation of a new osteoinductive agent for fracture-healing, in which patients with both closed and high-grade open fractures are enrolled. Patients with open fractures have a much worse prognosis than do those with closed fractures. The trial is small, with only eight patients. One would not be surprised if, by chance, all four closed fractures happened to be randomized to the new treatment and all four high-grade open fractures, to the control group. Such a result would seriously bias the study in favor of the new treatment. Were the trial to enroll 800 patients, the chances would be much smaller that randomization would place all 400 closed fractures in the tr
