EVIDENCE-BASED MEDICINE CORNER Bias in RCTs: confounders, selection bias and allocation concealment

The double blind randomized controlled trial (RCT) is considered the gold-standard in clinical research. Evidence for the effectiveness of therapeutic interventions should rely on well conducted RCTs. The importance of RCTs for clinical practice can be illustrated by its impact on the shift of practice in hormone replacement therapy (HRT). For decades HRT was considered the standard care for all postmenopausal, symptomatic and asymptomatic women. Evidence for the effectiveness of HRT relied always on observational studies mostly cohort studies. But a single RCT that was published in 2002 (The women's health initiative trial (1) has changed clinical practice all over the world from the liberal use of HRT to the conservative use in selected symptomatic cases and for the shortest period of time. In other words, one well conducted RCT has changed the practice that relied on tens, and probably hundreds, of observational studies for decades. But what is the appeal of RCT and why does it have such a place at the very top of the hierarchy of evidence? It is because it is the least design of clinical research that can be affected by bias if it has been conducted properly. Conducting a RCT allows investigators to control many types of bias that are hardly, if ever, controllable in other study designs such as the non-randomized controlled trials, cohort and case-control studies. Thus adequate knowledge of the different types of bias