The main advantage of an RCT is that the randomization procedure helps to prevent selection bias by the investigator. Although randomization of large groups of patients will often result in a similar distribution of measured and unmeasured variables in the experimental and control group, it is unlikely that the intended balance will be achieved for all patient characteristics. This is easy to understand given the large variability in genotypes. Though the balance will not be complete, the randomization process does guarantee that any differences between the two groups are due to chance and not to the investigator’s choice.
However, RCTs are often inappropriate to answer research questions relating to etiology, diagnosis, prognosis, and adverse effects and in these cases an observational study design is a better choice than an RCT. Observational studies are in general more useful for non-therapeutic studies than RCTs and even in therapeutic studies there are a number of cases in which RCTs are impossible, inappropriate, inadequate, or unnecessary. Because of the extremely large number of existing and new health care interventions, it will not be possible to test all of them in an RCT. This is not only due to the scale of the task, but also to
financial constraints, since RCTs are much more expensive than observational studies. In addition, ethical objections may prevent interventions to be tested within an RCT setting. Furthermore, there are examples of cases where RCTs are possible but inappropriate, such as the detection of adverse events that are rare or take years to develop. Finally, there are some exceptional, historical, examples (e.g. insulin in type 1 Diabetes mellitus) where the effects of health interventions were dramatic and observational studies were sufficiently adequate to demonstrate the effectiveness of the intervention.
These facts emphasize that also observational studies are essential in research and we can conclude that both observational studies and RCTs fulfill a complementary and valuable role in nephrology.

For further reading:
1. Stel VS, Jager KJ, Zoccali C, Wanner C, Dekker
FW. The randomized clinical trial: An unbeatable
standard in clinical research? Kidney Int 2007; 72:
539-542
2. Jager KJ, Stel VS, Wanner C, Zoccali C, Dekker
FW. The valuable contribution of observational studies
to nephrology. Kidney Int 2007; 72: 671-675

Marlies Noordzij, ERA-EDTA Registry epidemiologist