Limitations of randomized, controlled, double-blinded studies in determining safety and effectiveness of treatments

Abstract

Randomized, controlled, double-blinded studies, in which treated subjects are randomly selected from the same pool as controlled (untreated) ones and neither the caregiver nor the patient knows which is which, are widely accepted as the gold standard of experimental medicine. There are well-documented advantages of such studies. There are, however, significant limitations of them as well of which it is important to be aware. Notably, physicians who rely on experience and on what they were taught in medical school and post-graduate training are not necessarily wrong when this information runs contrary to the results of such studies. Some limitations of them are widely known and taught, such as inadequate sample size, failure of proper randomization, et cetera; others are less well-known. We shall focus on the latter.

Keywords: COVID-19; clinical research; design of experiments; medical statistics; therapeutics.