Question

Explain how randomization, in general, can obtain balance on measured and unmeasured confounding

Answer 1

Randomization is the most optimal method of controlling for confounders. It has the advantage of balancing both measured and unmeasured confounders between study groups, which reduces the uncertainty as to whether the observed associations might be confounded by prognostic factors in the study. In our previous example, a well-designed and powered RCT to study the effect of surgical approach (open v. laparoscopic appendectomy) on postoperative wound infection would more likely provide a balanced number of obese and nonobese patients between the open and laparoscopic groups. Since the method of randomization is based on probability, it is unlikely that this balance will be achieved for all patient characteristics, even with a large number of observations. However, randomization does guarantee that any differences between the 2 groups (open and laparoscopic appendectomy) are owing to chance, rather than the choice of the surgeon. Thus, although differences between patient characteristics may still exist after randomization, their confounding effects are likely minimized. The chances of achieving balanced groups with respect to prognostic factors will increase if larger numbers of patients are studied.Randomization may be insufficient to achieve balanced groups with small sample sizes (i.e., fewer than 200 patients) The larger the sample size, the more confidence one may have that balance of prognostic factors in an RCT has been achieved. The methods of optimizing the chances of achieving balanced groups in RCTs of surgical interventions are explained elsewhere.