Placebo response levels in many drug trials are high, especially with therapeutic areas that rely on patient-reported outcome measures. I (LT) recently read a very thoughtful paper by sexologist Andrea Bradford called “Listening to placebo in clinical trials for female sexual dysfunction” that opened my eyes to many important elements.(1) Since PRO measures are increasing in popularity during our current “lifestyle medications” era of pharmaceutical manufacture, it seems important to unpack the placebo phenomenon.
Typically, one thinks of a placebo as a “sugar pill,” an inert substance that modifies behavior, but not through any specific pharmacological impact. But this is overly simple. For one thing, new studies show that placebos do have physiologically measurable results. For another, “nonspecific” effects due to placebo and “specific” effects due to drug may be additive, interactive, or competitive – we don’t really know.
More importantly, the trials conditions under which drugs and placebos are administered (e.g., pre-trial publicity about the “great new drug” that hypes expectations, interactions with staff that focus the trial subject’s attention on one aspect or another, self-monitoring due to checklist or diary instructions, inclusion/eligibility criteria to get into trials) act as placebo elements themselves – encouraging, educating, and including people most likely to show positive results while excluding others. This biases the results of the trials. The point is that no one ever studies these factors and they remain invisible, yet everyone realizes how influential they can be. It’s absurd when you think about it.
Bradford explores at length the important interactions of perceptible physical changes and expectancies in the placebo effect. If a trial subject expects the active drug to produce some sort of subjective effect and the placebo not to, this expectancy will affect her response and totally influence the alleged objective “blinding” in the trial. An “active placebo” is a new idea – giving the placebo some side effects that won’t affect the behavior under study, but will give the trial subject a sense that something is going on. Also, debriefing study stubjects to find out which condition they thought they were in is important to see if the blinding was effective.
To me, the placebo effect is the 800 pound elephant in the room when it comes to drug trials on PRO areas such as sexual dysfunction. We must get the FDA to pay more attention!
(1) Bradford, A. (2013) Listening to placebo in clinical trials for female sexual dysfunction. Journal of Sexual Medicine, 10: 451-459.