Emulating target trials comparing early and delayed intubation strategies.

May 08, 2023

Experts: Kerollos Nashat Wanis,Arin L Madenci,Sicheng Hao,Mira Moukheiber,Lama Moukheiber,Dana Moukheiber,Sulaiman Moukheiber,Jessica G Young,Leo Anthony Celi

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.
Do treatment strategies that intubate patients early in their critical care admission improve 30-day survival compared to strategies that delay intubation?
We estimated the effect of strategies that require early intubation of critically ill patients compared to 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.
Under unrealistically strict treatment strategies with broad eligibility criteria, the 30-day mortality risk was 7.1 percentage points higher for intubating early compared to delaying intubation [95% CI, 6.2, 7.9]. Risk differences were 0.4 [95% CI, -0.1, 0.9] and -0.9 [95% CI, -2.5, 0.7] percentage points in subsequent target trial emulations which included more realistic treatment strategies and eligibility criteria.
When realistic treatment strategies and eligibility criteria are used, strategies that delay intubation result in similar 30-day mortality risks compared to those that intubate early. Delaying intubation ultimately avoids intubation in most patients.

Copyright © 2023. Published by Elsevier Inc.

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ABOUT THE EXPERTS

Kerollos Nashat Wanis,Arin L Madenci,Sicheng Hao,Mira Moukheiber,Lama Moukheiber,Dana Moukheiber,Sulaiman Moukheiber,Jessica G Young,Leo Anthony Celi

Kerollos Nashat Wanis

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Division of General Surgery, Department of Surgery, Western University, London, ON, Canada. Electronic address: knwanis@g.harvard.edu.

Arin L Madenci

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA.

Sicheng Hao

Laboratory for Computational Physiology, Massachusetts Institute of Technology, Cambridge, MA, USA.

Mira Moukheiber

The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.

Lama Moukheiber

Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.

Dana Moukheiber

Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.

Sulaiman Moukheiber

Department of Computer Science, Worcester Polytechnic Institute, Worcester, MA, USA.

Jessica G Young

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Leo Anthony Celi

Laboratory for Computational Physiology, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.