ADAPTing to a New Era of Comparative Effectiveness Research in Traumatic Brain Injury—Generating Evidence From Observational Data

Geoffrey T Manley,Andrew I R Maas,Hester F Lingsma

doi:10.1001/jamanetworkopen.2022.0899

Geoffrey T Manley, Andrew I R Maas + Show 1 more

Open Access

https://doi.org/10.1001/jamanetworkopen.2022.0899

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Abstract

Original Investigation Intracranial Pressure Before and After Hypertonic Saline or Mannitol in Children With TBI Patrick M. Kochanek, MD; P. David Adelson, MD; Bedda L. Rosario, PhD; James Hutchison, MD; Nikki Miller Ferguson, MD; Peter Ferrazzano, MD; Nicole O’Brien, MD; John Beca, MD; Ajit Sarnaik, MD; Kerri LaRovere, MD; Tellen D. Bennett, MD, MS; Akash Deep, MD; Deepak Gupta, MCH, PhD; F. Anthony Willyerd, MD; Shiyao Gao, PhD; Stephen R. Wisniewski, PhD; Michael J. Bell, MD; ADAPT Investigators; Shruti Agarwal; Sarah Mahoney; Laura Loftis; Kevin Morris; Lauren Piper; Anthony Slater; Karen Walson; Todd Kilbaugh; AM Iqbal O'Meara; Nathan Dean; Jessica Carpenter; Ranjit Chima; Brad Kurowski; Enno Wildshut; Naomi Ketharanathan; Mark Peters; Robert Tasker; Joan Balcells; Courtney Robertson; Sian Cooper; Sarah Murphy; Michael Whalen; John Kuluz; Warwick Butt; Neal Thomas; Sandra Buttram; Simon Erickson; J. Mahil Samuel; Rachel Agbeko; Richard Edwards; Iain Macintosh; Michele Kong; Joanne Natale; Heather Siefkes; Christopher Giza; Hari Thangarajah; David Shellington; Anthony Figaji; Elizabeth Newell; Edward Truemper; Sidharth Mahapatra; Robert Clark; Alicia Au; Sue Beers; Christopher Newth; Nadeem Shafi; Alino Nico West; Darryl Miles; Michelle Schober; Truc Le; Jerry Zimmerman; Mark Wainwright; Monica Vavilala; Stuart Friess; Jose Pineda

Highlights

An additional challenge in studies on intensive care unit therapies in traumatic brain injury (TBI) is time-varying confounding; osmolar therapies are repeatedly given based on, for example, intracranial pressure (ICP), which means that ICP on time 1 (T1) is a confounder for osmolar therapy at time 1, subsequent ICP measurement on time 2 is on the causal pathway for the effect of osmolar therapy on time 1 but a confounder for osmolar therapy on time 2, and so on
The authors decided to focus on the measurement before and after bolus administration in the analysis to avoid time-varying confounding. They could have used causal approaches, such as marginal structural models,[3] but these methods are complicated and not yet used in TBI research. Another alternative that has been used in TBI research could have been to exploit the substantial practice variation that was observed by performing instrumental variable analysis.[4]
Interpreting the results of CER requires understanding of the treatment allocation mechanisms and understanding of the methods—in other words, close collaboration between clinicians and epidemiologists or statisticians, as carried out by the ADAPT team. This large, multicenter study provides real-world evidence, in conjunction with the current pediatric TBI guidelines, that supports the use of hypertonic saline (HTS) as a first-line agent in the management of pediatric TBI

Summary

Introduction

A New Era of Comparative Effectiveness Research in Traumatic Brain Injury best-case scenario, it would be virtually impossible to predefine and collect all possible confounders. An additional challenge in studies on intensive care unit therapies in TBI is time-varying confounding; osmolar therapies are repeatedly given based on, for example, ICP, which means that ICP on time 1 (T1) is a confounder for osmolar therapy at time 1, subsequent ICP measurement on time 2 is on the causal pathway for the effect of osmolar therapy on time 1 but a confounder for osmolar therapy on time 2, and so on. The authors decided to focus on the measurement before and after bolus administration in the analysis to avoid time-varying confounding.

Results

Conclusion