Theory 21/Life, Medicine & Mind /Clinical trials
Sham Effects Track Invasiveness
Placebo is treated as expectation. In surgery it may be the body's response to being opened.
Placebo responses to surgical intervention scale with the invasiveness of the sham procedure rather than with patient expectation, so trials with more invasive shams show larger placebo effects and understate the treatment.
01The evidence
Sham-controlled surgical trials show large and variable placebo effects, with the largest in the most invasive procedures.
02The tension
Placebo models attribute the effect to expectation. That predicts similar effects across procedures at similar expectation, which is not observed.
03The mechanism
Invasive procedures trigger wound healing, immune modulation and endogenous analgesia. The magnitude scales with tissue disruption, so the sham's biology sets the placebo effect.
That makes invasiveness the determinant, and predicts the effect should scale with the sham's tissue trauma.
04What this is not
Expectation models predict from belief. This predicts from tissue injury, which explains the gradient across procedures.
05Predictions
- P1Placebo effect should scale with sham invasiveness.
- P2Non-invasive shams should show smaller effects.
- P3Inflammatory markers should mediate.
06Refutation
Equal effects across invasiveness at similar expectation would favour expectation models.
07What it changes
It would change how surgical trials are designed.