This comment, written by Dean Ornish and published on the Edge.org blog What scientific idea is ready for retirement, argues that larger studies do not always equate to more rigorous or definitive results and that randomized control trials (RCTs) may in fact introduce their own biases. The post goes on to argue that due to the issues that RCTs raise new and more thoughtful experimental designs and systems approaches need to be developed.
"...in practice a RCT can often introduce its own set of biases and thus undermine the validity of the findings.
For example, a RCT may be designed to determine if dietary changes may prevent heart disease and cancer. Investigators identify patients who meet certain selection criteria, e.g., that they have heart disease. When they meet with prospective study participants, investigators describe the study in great detail and ask, "If you are randomly-assigned to the experimental group, would you be willing to change your lifestyle?" In order to be eligible for the study, the patient needs to answer, "Yes."
However, if that patient is subsequently randomly-assigned to the control group, it is likely that this patient may begin to make lifestyle changes on their own, since they have already been told in detail what these lifestyle changes are. If they're studying a new drug that only is available to the experimental group, then it is less of an issue. But in the case of behavioral interventions, those who are randomly-assigned to the control group are likely to make at least some of these changes because they believe that the investigators must think that these lifestyle changes are worth doing or they wouldn't be studying them."