Blinding and Expectancy Confounds in Psychedelic Randomised Controlled Trials
OpenAlex – March 08, 2021
Source: OpenAlex
Summary
Psychedelics, with their known neurotransmitter receptor influence on behavior, are gaining traction in medicine for treating conditions like major depression. However, a meta-analysis of extant randomized controlled trials in clinical psychology reveals that blinding failures and high patient expectancy, explained by expectancy theory, likely inflate reported large effect sizes from these drug studies. Careful attention to clinical trial design is crucial for accurate assessment.
Abstract
There is increasing interest in the potential for psychedelic drugs such as psilocybin, LSD and ketamine to treat a number of mental health disorders. To gain evidence for the therapeutic effectiveness of psychedelics, a number of randomised controlled trials (RCTs) have been conducted using the traditional RCT framework and these trials have generally shown promising results, with large effect sizes reported. However, in this paper we argue that estimation of treatment effect sizes in psychedelic clinical trials are likely over-estimated due to de-blinding of participants and high levels of response expectancy generated by RCT trial contingencies. The degree of over-estimation is at present difficult to estimate. We conduct systematic reviews of psychedelic RCTs and show that currently reported RCTs have failed to measure and report expectancy and malicious de-blinding. In order to overcome these confounds we argue that RCTs should routinely measure de-blinding and expectancy and that careful attention should be paid to the clinical trial design used and the instructions given to participants to allow these confounds to be estimated and removed from effect size estimates. We urge caution in interpreting effect size estimates from extant psychedelic RCTs.