CHEST Guidelines-The-Impact-of-Sample-Size-Misestimations-on-the-In

The-Impact-of-Sample-Size-Misestimations-on-the-In

Pdf Summary

The systematic review and meta-analysis conducted by Saha et al. investigates sample size misestimations in Acute Respiratory Distress Syndrome (ARDS) randomized controlled trials (RCTs) and their potential impact on rejecting beneficial therapies. Despite five decades of research and more than 150 RCTs, there is still a lack of drug treatments that significantly improve ARDS outcomes. The review focused on RCTs that began post-1994 and ended before October 2020, examining discrepancies between predicted and observed sample sizes, control event rates (CER), and average treatment effects (ATE). Only 56% of the identified 150 ARDS RCTs reported sample size estimations, with many revealing overestimation in CER and ATE, particularly in mortality outcomes.<br /><br />In trials where mortality was a primary endpoint, the predicted ATE often fell short, with interventions needing to prevent a higher percentage of deaths than anticipated. The study found no correlation between observed CER and ATE, challenging the strategy of using mortality for prognostic enrichment. Through Bayesian analysis, the research prioritized three interventions for future trials: corticosteroids, airway pressure release ventilation, and noninvasive ventilation, based on moderate existing evidence.<br /><br />The study highlights significant inconsistencies in sample size estimation reporting and suggests the potential efficacy of abandoned interventions. It also underscores the necessity for a shift in trial designs to address these limitations, suggesting that future ARDS research focus on ARDS-specific mortality risks rather than all-cause mortality. Bayesian methods are recommended for detailed analysis, promoting efficiency and resourceful planning for future trials to provide more definitive results.

Keywords

ARDS

randomized controlled trials

sample size misestimation

meta-analysis

mortality outcomes

Bayesian analysis

corticosteroids

airway pressure release ventilation

noninvasive ventilation

trial design