Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Oct 1;200(7):828-836.
doi: 10.1164/rccm.201810-2050CP.

Reappraisal of Ventilator-Free Days in Critical Care Research

Nadir Yehya  1   2 , Michael O Harhay  3   4 , Martha A Q Curley  2   5   6 , David A Schoenfeld  7   8   9 , Ron W Reeder  10
Affiliations
Review

Reappraisal of Ventilator-Free Days in Critical Care Research

Nadir Yehya et al. Am J Respir Crit Care Med. .

Abstract

Ventilator-free days (VFDs) are a commonly reported composite outcome measure in acute respiratory distress syndrome trials. VFDs combine survival and duration of ventilation in a manner that summarizes the "net effect" of an intervention on these two outcomes. However, this combining of outcome measures makes VFDs difficult to understand and analyze, which contributes to imprecise interpretations. We discuss the strengths and limitations of VFDs and other "failure-free day" composites, and we provide a framework for when and how to use these outcome measures. We also provide a comprehensive discussion of the different analytic methods for analyzing and interpreting VFDs, including Student's t tests and rank-sum tests, as well as competing risk regressions treating extubation as the primary outcome and death as the competing risk. Using simulations, we illustrate how the statistical test with optimal power depends on the relative contributions of mortality and ventilator duration on the composite effect size. Finally, we recommend a simple analysis and reporting framework using the competing risk approach, which provides clear information on the effect size of an intervention, a statistical test and measure of confidence with the ability to adjust for baseline factors and allow interim monitoring for trials. We emphasize that any approach to analyzing a composite outcome, including other "failure-free day" constructs, should also be accompanied by an examination of the components.

Keywords: ARDS; VFDs; acute respiratory distress syndrome; competing risk regression; ventilator-free days.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Different clinical trajectories of subjects assigned to (A) 0 or (B) 14 ventilator-free days. A criticism of ventilator-free days is that the “net effect” being reported does not adequately discriminate between these distinct patient outcomes.
Figure 2.
Figure 2.
Cumulative incidence functions for the primary event (extubation) in five ARDSNet (Acute Respiratory Distress Syndrome Clinical Network) trials. The subdistribution hazard ratio (SHR) and 95% confidence intervals are provided. Intervention (blue) and control (red) arms are displayed, and SHR greater than 1 is interpreted as greater hazard of intact extubation. ARMA (Respiratory Management in ARDS) and FACTT (Fluid and Catheter Treatment Trial) demonstrated a benefit of the intervention related to the probability of extubation, whereas OMEGA (Omega Nutritional Supplement Trial) demonstrated harm. ALTA = Albuterol for the Treatment of Acute Lung Injury; ALVEOLI = Assessment of Low Tidal Volume and Elevated End-expiratory Volume to Obviate Lung Injury; PEEP = positive end-expiratory pressure.
See this image and copyright information in PMC

References

    1. Schoenfeld DA, Bernard GR ARDS Network. Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome. Crit Care Med. 2002;30:1772–1777. - PubMed
    1. Schoenfeld DA, Hayden D, Oldmixon C, Ringwood N, Thompson BT. Statistical design and analysis issues for the ARDS Clinical Trials Network: the coordinating center perspective. Clin Invest. 2012;2:275–289.
    1. Bernard GR, Wheeler AP, Arons MM, Morris PE, Paz HL, Russell JA, et al. The Antioxidant in ARDS Study Group. A trial of antioxidants N-acetylcysteine and procysteine in ARDS. Chest. 1997;112:164–172. - PubMed
    1. Matthay MA, Brower RG, Carson S, Douglas IS, Eisner M, Hite D, et al. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Randomized, placebo-controlled clinical trial of an aerosolized β2-agonist for treatment of acute lung injury. Am J Respir Crit Care Med. 2011;184:561–568. - PMC - PubMed
    1. Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, Moss M, et al. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012;307:795–803. - PMC - PubMed

Publication types