[Revisit to observation and experiment: real world study cannot replace randomized controlled trial].

ABSTRACT

In epidemiology, intervention is normally used to define what experiment is intervention studies are equaled to experimental studies. Experimental studies are also considered scientifically more rigorous than observational ones. Intervention is generally referred to human activities that can interfere or change natural conditions. The intervention by definition may not necessarily be beneficial to the study subjects (although exposing harmful interventions to humans are unethical) and activities by the researcher, by the subject himself, or by any third party and either now or in the past can all form "effective" interventions. For example, interventions that can damage the optic nerve by any of the three parties can all help the researcher establish the relation between the optic nerve and vision. In the same sense, an activity that a study subject initiated in the past, such as smoking, would also constitute a valid intervention. As a result, a cohort study on smoking and lung cancer would also be an experiment. From the above arguments, we can see that intervention alone does not suffice to distinguish between experiment and observation. As we equal experiment to higher scientific rigorousness than observation, only can study designing features of intervention studies be used to define experiment. In intervention trials, randomization is the defining feature that makes randomized controlled trials differ from, and scientifically more rigorous than, controlled observational studies and has been commonly used to define experiment. If we have to divide clinical research into experiment and observation, randomized controlled trials would be experimental and non-randomized studies of intervention are trials but not experiment. Big data, real-world studies are not experiment and cannot replace randomized trials in confirmation of efficacy if comparison groups are not formed by randomization. Real world studies cannot replace randomized controlled trials. This is the most important message this paper wishes to convey.