I don’t quite follow the obsession with the concept of “the placebo response” for randomized trials, which seems to be a propeller for trial designs such as the enriched enrollment, randomized withdrawal design (EERWD) in mood disorders and pain research. The idea of an EERWD is to enrich a study with “responders” to reduce the number of participants required to demonstrate efficacy and increase statistical power.
I’m concerned with the idea of identifying “responders” in conditions with a remitting and relapsing nature. The EERWD design may just be capturing patients in a remitting phase, which simply reflects the natural fluctuations of the condition rather than a true response to treatment. My feeling is that we can’t truly identify “responders” without employing a rigorous, repeated cross-over or N-of-1 trials type of design. I also suspect “the placebo response” is likely derived using change from baseline, which is invalid. A great article discusses this topic here: https://academic.oup.com/aje/article/190/1/2/5876955?login=false
Do others have any thoughts on the EERWD design? Many thanks.
Attaching a reference below for a background on placebo response:
https://www.sciencedirect.com/science/article/abs/pii/S0022395611000409
The above reference defines placebo response as “the change that occurs after administration of placebo and is caused by a study effect plus a placebo effect” where “the study effect is the tendency for a patient’s state to be modified solely from participation in a clinical trial and not to a treatment administered therein” and “the placebo effect is the nonspecific, psychological, or psychophysiologic therapeutic effect often attributed to the expectation that improvement will follow the administration of treatment”.