Open-label
An open-label trial is one in which participants know which intervention they are receiving, because it is not hidden by blinding or a matched placebo; outcome assessors may still be kept unaware.
What it means in practice
The Cochrane Handbook calls these non-blinded, or open, trials [4]. Blinding can be difficult or impossible in some settings, for example when a surgical intervention is compared with a non-surgical one [4]. The CONSORT reporting guideline notes that blinding, unlike allocation concealment, may not always be appropriate or possible [1].
In surgical trials, for example, blinding participants and surgeons is often difficult or impossible, but data collectors and outcome adjudicators can often still be blinded [1]. Open trials may also use other safeguards, such as strict criteria that stop treatments outside the protocol from being given [4].
Why it matters when reading nootropics research
CONSORT notes that blinding is particularly important when outcome measures involve some subjectivity, such as assessment of pain [1]. How much bias open designs introduce on average is less clear, and evidence is mixed.
A systematic review of 21 trials (4391 patients) that assessed the same binary outcome with both blinded and non-blinded assessors found that the non-blinded assessors exaggerated odds ratios by 36% on average; outcomes in most of these trials were subjective [2]. A larger study of 142 meta-analyses (1153 trials), which compared blinded with non-blinded trials, found no evidence of an average difference in estimated effects [3]. Its authors say this could mean that blinding matters less than often believed, or could reflect limits of their method, such as residual confounding or imprecision, and that blinding should remain a methodological safeguard [3]. The two studies differ in design: one compared assessors within the same trials, the other compared separate trials [2][3].
When a supplement study is open-label, that is worth noting before weighing its result against blinded, placebo-controlled findings.
References
- Moher D, Hopewell S, Schulz KF, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010.
- Hróbjartsson A, Thomsen AS, Emanuelsson F, et al. Observer bias in randomised clinical trials with binary outcomes: systematic review of trials with both blinded and non-blinded outcome assessors. BMJ. 2012.
- Moustgaard H, Clayton GL, Jones HE, et al. Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study. BMJ. 2020.
- Cochrane. Cochrane Handbook for Systematic Reviews of Interventions, Chapter 8: Assessing risk of bias in a randomized trial. last updated October 2019 (Handbook version 6.5).