Contextual effects: how to, and how not to, quantify them.

The importance of contextual effects and their roles in clinical care controversial. A Cochrane review published in 2010 concluded that placebo interventions lack important clinical effects overall, but that placebo interventions can influence patient-reported outcomes such as pain and nausea. However, systematic reviews published after 2010 estimated greater contextual effects than the Cochrane review, which stems from the inappropriate methods employed to quantify contextual effects. The effects of medical interventions (i.e., the total treatment effect) can be divided into three components: specific, contextual, and non-specific. We propose that the most effective method for quantifying the magnitude of contextual effects is to calculate the difference in outcome measures between a group treated with placebo and a non-treated control group. Here, we show that other methods, such as solely using the placebo control arm or calculation of a 'proportional contextual effect,' are limited and should not be applied. The aim of this study is to provide clear guidance on best practices for estimating contextual effects in clinical research.