Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study

Dear Editor:

Is the Meta-BLIND study a game changer for complex intervention trials?

We congratulate the authors of the Meta-BLIND* study on their recent BMJ publication. This has resulted in a significant number of online responses and social media comments questioning the current conventions about the role of blinding in randomised controlled trials (RCTs)

The results of the Meta-BLIND study are of particular relevance to those conducting complex intervention RCTs, as such trials have long struggled with the challenges of blinding. The nature of complex interventions often makes blinding of study participants and healthcare providers impossible; furthermore the primary outcome of interest may be participant reported. Tools for quality assessment of RCTs traditionally downgrade the level of evidence associated with complex interventions, as the difficulty in achieving this level of blinding makes it impossible for the results of such a trial to be assessed as having a high level of evidence. The disadvantaged status of such trials has negative impacts on the uptake, adoption and funding of complex interventions in comparison to other interventions where all forms of blinding (participants, providers and outcome assessors) have been possible. The results of the Meta-BLIND study suggest that this evidence downgrading urgently needs revisiting

Whilst outcome assessment blinding is potentially possible in complex intervention trials it is often hard to ensure - as it requires considerable additional efforts by trialists (instructing participants not to reveal their allocation to the assessor, checking fidelity of this blinding) and it adds to the cost of trials, including possible increased assessment burden for participants. The Meta-BLIND study found no evidence to support an association between outcome blinding and exaggerated treatment effects; again suggesting that complex intervention trialists, trial funders, journal editors and reviewers should revisit the methodological dogma that outcome blinding is an essential requirement for producing robust evidence of treatment effect.

The preliminary indications of the Meta-BLIND study, which challenge the status quo about the importance of blinding, provide encouragement to researchers engaged in complex intervention RCTs. The lack of significant difference in the size of the effect between blinded and non-blinded trials may offer the non-blinded design of complex intervention RCTs new recognition. There is cautious optimism among complex intervention trialists that there may be a real chance, for the first time, to amend the risk of bias criteria regarding blinding. This may also facilitate the rise in status of complex intervention RCTs - as reviewers can be confident in the quality of evidence produced by a non-blinded trial.

Recently, a group of researchers, under the umbrella of MRC & Trial Methodology Research Partnership (TMRP), has commenced investigating the value of outcome assessment blinding in complex intervention RCTs.

We support Moustgaard and colleagues’ call for further meta-epidemiological research (drawing upon different trials in different populations, interventions, comparators and outcomes) to determine if their finding - of the lack of risk of bias associated with different types of blinding - is replicable. We also argue that these Meta-BLIND findings are a potential ‘game changer’, requiring prompt debate of their implications for trial design, delivery and evidence grading.

Reference:
* Moustgaard H, Clayton GL, Jones HE, et al. Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study. BMJ 2020;368:l6802. doi: 10.1136/bmj.l6802 [published Online First: 2020/01/23]

Authors:
1-Abdullah Yonis
Clinical Research Fellow, Heart &Lung Unit, Torbay and South Devon NHS, Speciality Reg. in Pharmaceutical Medicine and PhD Studentship at College of Medicine and Health, University of Exeter, College House, University of Exeter, St Luke's Campus, Heavitree Road, Exeter, EX1 2LU, UK. Email: ay302@exeter.ac.uk
2- Rod Taylor
Professor of Population Health Research Rod Taylor, MSc, PhD is Chair of Population Health Research, Institute of Health and Wellbeing, University of Glasgow.He is part of the Complexity programme at the MRC/CSO Social and Public Health Sciences Unit and Robertson Centre for Biostatistics/Glasgow Clinical Trials Unit. Email:Rod.Taylor@glasgow.ac.uk
3-Dr Fiona Warren
Senior Lecturer in Medical Statistics
Smeall Building, University of Exeter, St Luke's Campus, Heavitree Road, Exeter, EX1 2LU, UK.
Email: f.c.warren@exeter.ac.uk
4- Jean Hay-Smith
Professor and Director of the Rehabilitation Teaching and Research Unit, Department of Medicine, University of Otago, PO Box 7343, Wellington South 6242, New Zealand. Email: jean.hay-smith@otago.ac.nz
5- William Levack
William is Dean of the University of Otago, Wellington, and a Professor in Rehabilitation, University of Otago, Wellington, PO Box 7343, Wellington 6242 New Zealand. Email: william.levack@otago.ac.nz
6- Sarah Dean
Professor in Psychology Applied to Rehabilitation and Health, College House, University of Exeter, St Luke's Campus, Heavitree Road, Exeter, EX1 2LU, UK. Email: S.Dean@exeter.ac.uk