LAUSR

Abstract The placebo effect, often dismissed as statistical noise, is a real mind–body phenomenon caused by conditioning and expectation. We should distinguish between the placebo effect (the psychobiological process) and the placebo response (the outcome). This commentary argues that placebo effects are often underestimated in randomized controlled trials (RCTs) because trial outcomes are reported as averages of both responders and non-responders. Averaging can conceal meaningful effects, distort comparisons with active treatments, and generate inaccurate conclusions about treatment efficacy. To illustrate this, I use data from my research to show how averaging across participants diminishes the statistics-based placebo effect. Therefore, ignoring response heterogeneity can reduce accuracy and mask actual effects in responders. This issue extends beyond methodology. Underestimating placebo responses can lead to Type I errors in drug approvals, while in clinical practice, it can prevent practitioners from leveraging placebo mechanisms as part of holistic care. Ethical concerns also arise when the total placebo response approaches that of a drug, raising questions about exposing patients to unnecessary medication risks. Future trials should capture individual differences, such as expectancy assessments, prior-experience measures, stratified randomization, latent-class models, and biomarker research. Although these approaches pose challenges, they could incorporate heterogeneity into analysis and practice. In conclusion, embracing variability in placebo and treatment responses is more than a technical change; it is a shift toward greater validity, reliability, and personalized medicine. Moving beyond group averages and recognizing individual differences can help research produce more reliable evidence to guide treatment decisions. KEY MESSAGES Averaging placebo responders and non-responders hides the true power of placebo effects. Diluted placebo effects can falsely elevate drug efficacy in clinical trials. Identifying placebo responders could help in the development of valid, ethical, and personalized medicine. PLAIN LANGUAGE SUMMARY When people take a “sugar pill” or another treatment with no active medicine, they can still experience improvement. This phenomenon is known as the placebo effect, which occurs due to the strong link between the mind and body: our expectations and past experiences can lead to genuine changes in how we feel. In medical research, the placebo effect is often underestimated. This is because results from people who respond strongly to placebos are averaged with those who do not respond at all. As a result, placebos can appear less effective than they actually are, which can also influence our judgment of the effectiveness of actual medicines. This article shows, with a simple example, how this problem occurs. It also explains why it’s important to study placebo responses carefully and separately. Doing so could improve the testing of new treatments and lead to healthcare that is more personalized, ethical, and effective.