Trial participants who conscientiously take their placebos die less than those who have worse adherence to placebos – and the association resists being explained away by confounding.
According to the new analysis, patients who took at least 75% of their placebo beta-blockers in an earlier trial had a mortality rate almost 40% lower than those who took their placebos less often.
“There is no clear explanation for why better adherence to an inert pill should be associated with a 39% decrease in one’s mortality risk,” the study authors wrote in the journal Contemporary Clinical Trials.
They said the “perplexing association” was unlikely to be causal and so an underlying explanation probably existed.
But despite having what they described as a “unique opportunity” to study the relationship, and controlling for several possible confounders, they were unable to find any explanation.
Recognising that it “seemed intuitive” that high adherence levels would be associated with healthier lifestyle factors, they found it was independent of such factors.
“It is becoming increasingly clear that this association is not due to simple coufounding: as in several other studies, adjustment for numerous risk factors for mortality...has no appreciable effect on the presence of the association.”
Contemporary Clinical Trials 2012; doi: 10.1016/j.cct.2011.12.003