Article Text
PDF
Abstract
Introduction Evidence exists that unblinded randomised clinical trials (RCTs) overestimate intervention effects compared with blinded RCTs. It has been suggested that this is less pronounced for objective (ie, not subject to interpretation) outcome measures, including mortality. This may not apply in the intensive care unit (ICU), as most deaths are preceded by decisions to withhold or withdraw treatments. Lack of blinding of physicians in RCTs of ICU interventions may potentially influence the decision towards a higher threshold for discontinuing treatment in patients who receive the investigational treatment and/or a lower threshold for discontinuing treatment in patients who receive the comparator (control). This may have important implications for patients, caregivers, researchers and society. Accordingly, we aim to assess whether lack of blinding affects mortality effect estimates in RCTs of ICU interventions.
Methods and analysis We will conduct a systematic review with meta-analyses and assess the effect of blinding versus no blinding on mortality effect estimates in RCTs of interventions used in adult ICU patients.
We will systematically search the Cochrane Library for systematic reviews reporting mortality effect estimates of any intervention used in adult ICU patients which includes at least one RCT with ‘low risk of bias’ in the bias domains ‘blinding of participants and personnel’ and/or ‘blinding of outcome assessment’ and one RCT with ‘unclear’ or ‘high risk of bias’ in the same bias domain(s). For each intervention, we will compare summary mortality effect estimates in blinded versus unblinded trials.
Ethics and dissemination This research does not require ethical approval as we will use summary data from trials already approved by relevant ethical institutions. We will report the results in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and submit the final paper to an international peer-reviewed journal.
Trial registration number PROSPERO, registration number: CRD42017056212.
- Blinding
- Mortality
- Intensive care unit interventions
- Effect estimates
- Quality of evidence
- Risk of bias
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Statistics from Altmetric.com
Footnotes
Contributors MHM is the guarantor. CTA, AG, AP, JHL and MHM contributed to the study protocol including development of study eligibility criteria, search strategy, data extraction criteria and statistical analysis plan. CTA and MHM drafted the manuscript which was critically revised by all other authors. All authors approved the final draft of the manuscript and the publication of the protocol.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The Department of Intensive Care at364 Rigshospitalet receives support for other research projects from Fresenius Kabi, CSL Behring and Ferring Pharmaceuticals.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All relevant data from the included RCTs and systematic reviews will be reported in the manuscript.