Pro: The value of randomized controlled studies in dialysis methods.

Willis R. Whitney, a chemist, who founded the General Electric Company laboratory once said ‘Necessity is not the mother of invention. Knowledge and experiment are its parents’ [1]. Twardowski and Misra reject the primacy of experimentation. They wish us to abandon the necessity to demonstrate by rigorous randomized trials that longer duration and/or more frequent is superior to intermittent dialysis. They argue that randomized controlled studies (RCTs) are inadequate as a research methodology in evaluating a dialysis method citing limitations with each of the four RCTs—the National Cooperative Dialysis Study [2], the HEMO study [3], the Frequent Hemodialysis Network (FHN) study [4] and the FHN Nocturnal trial [5]. Twardowski and Misra suggest that ‘all progress in dialysis methods was made in research presented in case reports, case control studies and other observational studies. ‘and that’ four RCTs in hemodialysis did not provide any useful data.... observational studies allow clinical research to represent the full breadth of treated patients and offer tremendous power...’. The approach that Twardowski and Misra is questionable. We can hardly blame rigorous experimentation because a handful of studies that have been performed so far do not support a belief, however strongly held the belief is. After all any given study may have asked the wrong question, or inadvertently reached the wrong conclusion, or been null because of lack of power, or may have problems with study quality (for example, imbalances between the randomized groups or an excessive drop-out rate). Surely, this does not mean that the whole methodological approach embodied in RCTs is wrong? RCTs have value in the investigation of interventions like the choice of dialysis methods, just as they are important to other forms of human investigation. Twardowski and Misra acknowledge that RCTs represent the most rigorous method to determine whether a cause-andeffect relation exists between any treatment and an outcome. However, they understate the true advantage of RCTs over observational studies. In the study of interventions, RCTs are superior to observational studies because RCTs are based on random allocation of subjects to two or more intervention groups. The possibility of a systematic error is reduced because patient-related confounding factors are balanced across different interventions. While skilled biostatisticians and epidemiologists might try to attenuate the effect of confounding, these attempts are generally imperfect and residual confounding almost always exists. Besides, in RCTs, the intervention groups are treated identically, except for the experimental treatment. Subjects are analyzed within the group to which they were allocated, irrespective of whether they experience the intended intervention or not (intention to treat analysis) further reducing the chance of bias. Knowledge and experimentation are the founding principles of evidence-based medicine. The randomized trial represents the most rigorous method to get to the truth of whether an intervention causes an outcome. We should embrace RCTs not abandon them. RCTs are essential, because as Chertow has written [6] ‘Wishing Don’t Make it So’.