The relationship between blinding integrity and medication efficacy in randomised-controlled trials in patients with anxiety disorders: A systematic review and meta-analysis.

Of the 247 RCTs that met inclusion criteria, we were able to obtain assessments of blinding integrity from nine (3.64%). Overall, blinding failed in five of these trials (55.56%), but blinding was intact in 80% of placebo arms. We found a significant association between reduced blinding integrity among assessors and increased treatment effect size (betas < -1.30, p's < 0.001), but this analysis involved only four studies of which two were outlying studies. In patients, we saw a non-significant trend where reduced blinding integrity in the placebo groups was associated with increased treatment efficacy, which was not present in active medication arms. [Correction added on 19 August 2024, after first online publication: Results of the RCTs and its assessment of blinding integrity have been updated.] CONCLUSION: Consistent with work in other psychiatric disorders, blinding integrity is rarely reported in anxiolytic RCTs. Where it is reported, blinding appears to often fail. We found signals that suggest unblinding of clinician assessors (driven by two studies with complete unblinding), and of patients in placebo arms, might be associated with larger treatment effect sizes. We recommend that data regarding blinding integrity, along with the reasons patients and assessors offer for their beliefs regarding group allocation, are systematically collected in RCTs of anxiolytic treatment.