Comparison of the effect of a lower versus a higher PEEP strategy on clinically relevant outcomes in invasively ventilated patients without acute respiratory distress syndrome: statistical re-analysis plan of the RELAx trial using a Bayesian framework

TL;DR

This paper outlines a Bayesian re-analysis of a clinical trial comparing low and high PEEP strategies in ventilated patients without ARDS to better understand their effectiveness.

Contribution

The study introduces a Bayesian framework to re-analyze the RELAx trial, offering probabilistic insights into clinical outcomes.

Findings

The Bayesian analysis will assess the probability of superiority of lower PEEP strategies.

Multiple priors will be used to evaluate outcomes like mortality and ventilation duration.

Results will provide credible intervals and probabilities for benefit, harm, and equivalence.

Abstract

The effect of different levels of positive end-expiratory pressure in invasively ventilated critically ill patients remains a matter of debate. The REstricted versus Liberal Positive End-Expiratory Pressure in Patients Without ARDS (RELAx) is a multicentric, randomized trial comparing a lower positive end-expiratory pressure strategy versus a higher positive end-expiratory pressure strategy in ventilated patients without acute respiratory distress syndrome, which demonstrated non-inferiority of lower positive end-expiratory pressure compared to higher positive end-expiratory pressure on ventilator-free days. The primary analysis was published in 2020, and a frequentist statistical approach was applied.

To present the protocol of the Bayesian analysis plan that will be used to re-analyse the RELAx trial to provide complementary and additional insight into this clinical trial.

This re-analysis will focus on the probability of superiority of the intervention. As an ordinal variable, the primary outcome will be ventilator-free days at day 28, and posterior estimates will be obtained by fitting a hierarchical cumulative logistic regression model. Secondary outcomes will be mortality at day 28, as a binary outcome, and ventilation duration, as a continuous outcome. We will adopt neutral, pessimistic, and optimistic priors informed by current literature, and a fourth prior derived from an expert's survey. Probability thresholds will be defined for superiority, severe harm, and a region of practical equivalence.

The RELAx trial findings raise the hypothesis that a lower positive end-expiratory pressure strategy may be at least as effective, if not superior, in specific patient-centred outcomes. This analysis is designed to augment and contextualize the original frequentist analysis of the largest randomized trial comparing positive end-expiratory pressure strategies in non-acute respiratory distress syndrome patients. Results will be presented with a continuum of credible intervals and probabilities of effects to facilitate a nuanced interpretation. We offer clinically meaningful insights that complement and extend the trial's original analysis by reporting probabilities of benefit, harm, and equivalence.

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