Non-specific effects are an important consideration in the interpretation of clinical trial results. The term “non-specific effect” refers to a phenomenon where a treatment or intervention produces a statistically significant positive effect, but the effect is not due to the specific action of the intervention, rather it is due to a combination of non-specific factors. Non-specific effects can be subtle and difficult to detect and include factors such as the placebo effect, the Hawthorne effect, the regression effect, and the nocebo effect.

The placebo effect is the most widely known non-specific effect. This occurs when a patient receives a treatment, such as a pill or injection, which they believe will make them feel better, but in reality, the treatment has no active ingredients. This belief in the treatment can lead to a real improvement in the patient’s condition.

The Hawthorne effect is another non-specific effect which occurs when subjects in a study are aware that they are being observed. This can lead to a change in the behaviour of the subjects, which can cause an artificial increase in the results of the study.

The regression effect is a non-specific effect that can occur when the subjects in a study are randomly selected from a population with a wide range of baseline values. If the subjects with the most extreme baseline values tend to improve with the treatment, this can produce an artificially large effect size.

The nocebo effect is a phenomenon in which the belief that a treatment will have a negative effect can lead to the actual experience of negative effects, even when the treatment is inert.

Non-specific effects can have a major impact on the interpretation of clinical trial results, and should be taken into account when evaluating the efficacy of a treatment or intervention. Careful consideration should be given to the design and implementation of clinical trials to ensure that non-specific effects are minimized.


Ludwig, L. S., Rubin, D. B., & Roughead, E. E. (2012). Non-specific effects of interventions in clinical trials: implications for evidence based medicine. Journal of Clinical Epidemiology, 65(7), 772–779.

Collins, P. (2015). The nocebo effect: How expectations can influence treatment outcomes. BMJ, 350, h2467.

Kirsch, I. (1985). Response expectancy as a determinant of experience and behavior. American Psychologist, 40(11), 1189–1202.

Parker, H. A., & Peng, J. (2005). The Hawthorne effect in small-group decision making. Small Group Research, 36(3), 355–378.

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