The placebo response in clinical trials—the current state of play

SummaryWhile randomized, placebo-controlled double-blinded trials have become the pharmacological standard over the last 60 years, the gain in knowledge of the mechanisms behind the placebo response in recent years has raised substantial concerns about the appropriateness of some of its underlying assumptions. The following questions will be addressed: Is the assumed model of drug and placebo being additive (still) valid? Does the likelihood of receiving active treatment affect the placebo response? What is the size of the placebo response in “active comparator studies”? Minimizing the placebo response/maximizing the drug-placebo difference? How to maximize the placebo response in daily medicine? What is the placebo response with personalized medicines in the future? This and other questions require answers that can only be generated with more experimental studies on the placebo response and with thorough meta- and re-analyses of placebo responses in clinical trials.