Emulating Target Trials Comparing Early and Delayed Intubation Strategies

Chest. 2023 Oct;164(4):885-891. doi: 10.1016/j.chest.2023.04.048. Epub 2023 May 5.


Background: Whether intubation should be initiated early in the clinical course of critically ill patients remains a matter of debate. Results from prior observational studies are difficult to interpret because of avoidable flaws including immortal time bias, inappropriate eligibility criteria, and unrealistic treatment strategies.

Research question: Do treatment strategies that intubate patients early in the critical care admission improve 30-day survival compared with strategies that delay intubation?

Study design and methods: We estimated the effect of strategies that require early intubation of critically ill patients compared with those that delay intubation. With data extracted from the Medical Information Mart for Intensive Care-IV database, we emulated three target trials, varying the flexibility of the treatment strategies and the baseline eligibility criteria.

Results: Under unrealistically strict treatment strategies with broad eligibility criteria, the 30-day mortality risk was 7.1 percentage points higher for intubating early compared with delaying intubation (95% CI, 6.2-7.9). Risk differences were 0.4 (95% CI, -0.1 to 0.9) and -0.9 (95% CI, -2.5 to 0.7) percentage points in subsequent target trial emulations that included more realistic treatment strategies and eligibility criteria.

Interpretation: When realistic treatment strategies and eligibility criteria are used, strategies that delay intubation result in similar 30-day mortality risks compared with those that intubate early. Delaying intubation ultimately avoids intubation in most patients.

Keywords: causal inference; high-flow nasal cannula; intubation; machine learning; noninvasive ventilation; target trial.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Critical Care
  • Critical Illness* / therapy
  • Humans
  • Intubation, Intratracheal
  • Noninvasive Ventilation* / methods
  • Respiration, Artificial