Concerning placebos and the “placebo effect,” there is a distinction that I have struggled to articulate, a distinction I have also noticed highly intelligent humans failing to make. I recently found an excellent explanation of the distinction in a paper questioning the meaning of recent “open-label placebo” trials, and thought it was worth a short piece explaining why it’s important.
Here is the distinction as the authors put it, with citations removed:
Before reviewing findings from OLP studies, it is crucial to clearly demarcate between two distinctive uses for the term placebo. First, is the usage of placebos in RCTs. Here the term is often understood to refer to a certain kind of ‘thing’ (eg, saline injections or sugar pills). Strictly speaking, this interpretation is incorrect: instead, placebos in RCTs ought to be conceived as methodological tools since their function is to duplicate the ‘noise’ associated with clinical trials including spontaneous remission, regression to the mean, Hawthorne effects and placebo effects. Properly understood, then, these types of placebos are deployed as controls that are specifically designed to evaluate the difference—if any—between a control group and a particular treatment under scrutiny. Ideally, in RCTs, controls should mimic the appearance and modality of the particular treatment or medical intervention under investigation. In contrast, placebos in clinical contexts are interventions that may be intentionally or unintentionally administered by practitioners either with the goal of placating patients and/or of eliciting placebo effects.Blease, C. R., Bernstein, M. H., & Locher, C. (2020). Open-label placebo clinical trials: is it the rationale, the interaction or the pill?. BMJ evidence-based medicine, 25(5), 159-165.
On the one hand, there is the use of placebos in randomized controlled trials, in which the point is to “duplicate the noise” that’s likely to exist in the treatment group. On the other hand, there are hypothesized “placebo effects” that may take the form of real healing, which is not at all the same.
For a specific example, just because antidepressant trials result in enormous placebo effects does not mean that depression responds to placebo in real life. The proper conclusion to the size of placebo effects in these trials is that the measurement of depression is extremely noisy, to put it in the most polite way.
While true “placebo effects” of the healing variety may exist, it’s worth engaging with these authors’ concerns over how that may be demonstrated, particularly in open-placebo design trials in which the hope is to pave the way toward ethical placebo treatment. The choice of control is particularly tricky; for example, as with antidepressant treatments, simply using “treatment as usual” or “wait list” as controls likely inflates apparent effects. True blinding requires a great deal of subtlety and effort in research design.
In summary: noise isn’t healing.
Now we can all pretend that we knew it all along and never mistook the one for the other!