Learning by Difference: Placebo Effects and Specific Efficacy in Pharmacological RCTs

The logic underpinning randomized controlled trials depends on the assumption that any non-specific effects of treatment are equal and additive across trial arms. We label this the “assumption of specific efficacy”. There are a number of situations in which the assumption of specific efficacy does not hold. We describe the epistemic consequences that arise in these situations and discuss strategies for preserving the internal validity of randomized trials in such situations.