Article type
Year
Abstract
Background:
Allocation concealment (the concealment of the randomization sequence from personnel enrolling participants) and blinding (the concealment of the arm to which participants have been randomized from one or more individuals involved in a trial) have long been considered important to prevent bias in randomized trials.
Objective:
Assess the impact of allocation concealment and blinding on the results of COVID-19 trials.
Methods:
We searched the World Health Organization (WHO) COVID-19 database (up to February 2022). We included randomized trials that compared drug therapeutics with placebo or standard care in patients with COVID-19. We performed random-effects meta-regressions comparing the results of trials with and without allocation concealment and blinding of healthcare providers and patients.
Results:
We identified 488 trials. We found that, compared with trials with allocation concealment, trials without allocation concealment may estimate treatments to be more beneficial for mortality, mechanical ventilation, hospital admission, duration of hospitalization, and duration of mechanical ventilation, but results were imprecise. We did not find compelling evidence that, compared with trials with blinding, trials without blinding produce consistently different results for mortality, mechanical ventilation, and duration of hospitalization. We found that trials without blinding may estimate treatments to be more beneficial for hospitalizations and duration of mechanical ventilation.
Conclusions:
We did not find compelling evidence that COVID-19 trials with and without blinding produce consistently different results, but trials without allocation concealment estimate treatments to be more beneficial compared to trials with allocation concealment. Our findings have implications for the design of future COVID-19 trials and trials to inform future health emergencies and for systematic reviewers, guideline developers, and clinicians who are interpreting and applying evidence from these trials.
Patient, public, and/or healthcare consumer involvement: We involved patient partners in selecting the outcomes of interest.
Allocation concealment (the concealment of the randomization sequence from personnel enrolling participants) and blinding (the concealment of the arm to which participants have been randomized from one or more individuals involved in a trial) have long been considered important to prevent bias in randomized trials.
Objective:
Assess the impact of allocation concealment and blinding on the results of COVID-19 trials.
Methods:
We searched the World Health Organization (WHO) COVID-19 database (up to February 2022). We included randomized trials that compared drug therapeutics with placebo or standard care in patients with COVID-19. We performed random-effects meta-regressions comparing the results of trials with and without allocation concealment and blinding of healthcare providers and patients.
Results:
We identified 488 trials. We found that, compared with trials with allocation concealment, trials without allocation concealment may estimate treatments to be more beneficial for mortality, mechanical ventilation, hospital admission, duration of hospitalization, and duration of mechanical ventilation, but results were imprecise. We did not find compelling evidence that, compared with trials with blinding, trials without blinding produce consistently different results for mortality, mechanical ventilation, and duration of hospitalization. We found that trials without blinding may estimate treatments to be more beneficial for hospitalizations and duration of mechanical ventilation.
Conclusions:
We did not find compelling evidence that COVID-19 trials with and without blinding produce consistently different results, but trials without allocation concealment estimate treatments to be more beneficial compared to trials with allocation concealment. Our findings have implications for the design of future COVID-19 trials and trials to inform future health emergencies and for systematic reviewers, guideline developers, and clinicians who are interpreting and applying evidence from these trials.
Patient, public, and/or healthcare consumer involvement: We involved patient partners in selecting the outcomes of interest.