The mere act of being recruited into a clinical trial has clinical and biological effects. These are independent from placebo and nocebo effects. These biases are the Hawthorne effect.
Workers in a factory near Chicago, the Hawthorne Works, were observed in higher or lower amounts of light to determine which increased productivity. The conclusion was that productivity was improved only because the workers were being observed. Similarly, subjects in clinical trials often show improvement because of better attention, better observation, better care, better compliance, and better adherence. Advocates of surgical safety checklists, developed to reduce morbidity and mortality, were surprised when they learned that the mere fact that surgeons were under observation, and not any specific details of the checklist, improved performance. In clinical trials, some subjects improve between recruitment and the beginning of treatment, before any therapy has been given.
Social interaction among participants in a trial leads to more biases. Both placebo and nocebo responses can be seen. Mass psychogenic illnesses are an example of nocebo responses. They correlate with empathy scores and pain catastrophizing. These social and psychological factors may be crucial for nocebo hyperalgesia.
See Lancet Neurology, 2016, volume 15, page 736.
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