Addressing the challenges of obtaining functional outcomes in traumatic brain injury research

Missing data patterns, timing of follow-up, and three prognostic models

Leila R. Zelnick, Laurie J. Morrison, Sean M. Devlin, Eileen M. Bulger, Karen Brasel, Kellie Sheehan, Joseph P. Minei, Jeffrey D. Kerby, Samuel A. Tisherman, Sandro Rizoli, Riyad Karmy-Jones, Rardi Van Heest, Craig Newgard

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) is common and debilitating. Randomized trials of interventions for TBI ideally assess effectiveness by using long-term functional neurological outcomes, but such outcomes are difficult to obtain and costly. If there is little change between functional status at hospital discharge versus 6 months, then shorter-term outcomes may be adequate for use in future clinical trials. Using data from a previously published multi-center, randomized, placebo-controlled TBI clinical trial, we evaluated patterns of missing outcome data, changes in functional status between hospital discharge and 6 months, and three prognostic models to predict long-term functional outcome from covariates available at hospital discharge (functional measures, demographics, and injury characteristics). The Resuscitation Outcomes Consortium Hypertonic Saline trial enrolled 1282 TBI patients, obtaining the primary outcome of 6-month Glasgow Outcome Score Extended (GOSE) for 85% of patients, but missing the primary outcome for the remaining 15%. Patients with missing outcomes had less-severe injuries, higher neurological function at discharge (GOSE), and shorter hospital stays than patients whose GOSE was obtained. Of 1066 (83%) patients whose GOSE was obtained both at hospital discharge and at 6-months, 71% of patients had the same dichotomized functional status (severe disability/death vs. moderate/no disability) after 6 months as at discharge, 28% had an improved functional status, and 1% had worsened. Performance was excellent (C-statistic between 0.88 and 0.91) for all three prognostic models and calibration adequate for two models (p values, 0.22 and 0.85). Our results suggest that multiple imputation of the standard 6-month GOSE may be reasonable in TBI research when the primary outcome cannot be obtained through other means.

Original languageEnglish (US)
Pages (from-to)1029-1038
Number of pages10
JournalJournal of Neurotrauma
Volume31
Issue number11
DOIs
StatePublished - Jun 1 2014

Fingerprint

Research
Clinical Trials
Wounds and Injuries
Resuscitation
Calibration
Traumatic Brain Injury
Length of Stay
Placebos
Demography

Keywords

  • clinical trial design
  • functional outcomes
  • prognostic models
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

Cite this

Addressing the challenges of obtaining functional outcomes in traumatic brain injury research : Missing data patterns, timing of follow-up, and three prognostic models. / Zelnick, Leila R.; Morrison, Laurie J.; Devlin, Sean M.; Bulger, Eileen M.; Brasel, Karen; Sheehan, Kellie; Minei, Joseph P.; Kerby, Jeffrey D.; Tisherman, Samuel A.; Rizoli, Sandro; Karmy-Jones, Riyad; Van Heest, Rardi; Newgard, Craig.

In: Journal of Neurotrauma, Vol. 31, No. 11, 01.06.2014, p. 1029-1038.

Research output: Contribution to journalArticle

Zelnick, LR, Morrison, LJ, Devlin, SM, Bulger, EM, Brasel, K, Sheehan, K, Minei, JP, Kerby, JD, Tisherman, SA, Rizoli, S, Karmy-Jones, R, Van Heest, R & Newgard, C 2014, 'Addressing the challenges of obtaining functional outcomes in traumatic brain injury research: Missing data patterns, timing of follow-up, and three prognostic models', Journal of Neurotrauma, vol. 31, no. 11, pp. 1029-1038. https://doi.org/10.1089/neu.2013.3122
Zelnick, Leila R. ; Morrison, Laurie J. ; Devlin, Sean M. ; Bulger, Eileen M. ; Brasel, Karen ; Sheehan, Kellie ; Minei, Joseph P. ; Kerby, Jeffrey D. ; Tisherman, Samuel A. ; Rizoli, Sandro ; Karmy-Jones, Riyad ; Van Heest, Rardi ; Newgard, Craig. / Addressing the challenges of obtaining functional outcomes in traumatic brain injury research : Missing data patterns, timing of follow-up, and three prognostic models. In: Journal of Neurotrauma. 2014 ; Vol. 31, No. 11. pp. 1029-1038.
@article{52911bffeed64f74aa38123205ea0901,
title = "Addressing the challenges of obtaining functional outcomes in traumatic brain injury research: Missing data patterns, timing of follow-up, and three prognostic models",
abstract = "Traumatic brain injury (TBI) is common and debilitating. Randomized trials of interventions for TBI ideally assess effectiveness by using long-term functional neurological outcomes, but such outcomes are difficult to obtain and costly. If there is little change between functional status at hospital discharge versus 6 months, then shorter-term outcomes may be adequate for use in future clinical trials. Using data from a previously published multi-center, randomized, placebo-controlled TBI clinical trial, we evaluated patterns of missing outcome data, changes in functional status between hospital discharge and 6 months, and three prognostic models to predict long-term functional outcome from covariates available at hospital discharge (functional measures, demographics, and injury characteristics). The Resuscitation Outcomes Consortium Hypertonic Saline trial enrolled 1282 TBI patients, obtaining the primary outcome of 6-month Glasgow Outcome Score Extended (GOSE) for 85{\%} of patients, but missing the primary outcome for the remaining 15{\%}. Patients with missing outcomes had less-severe injuries, higher neurological function at discharge (GOSE), and shorter hospital stays than patients whose GOSE was obtained. Of 1066 (83{\%}) patients whose GOSE was obtained both at hospital discharge and at 6-months, 71{\%} of patients had the same dichotomized functional status (severe disability/death vs. moderate/no disability) after 6 months as at discharge, 28{\%} had an improved functional status, and 1{\%} had worsened. Performance was excellent (C-statistic between 0.88 and 0.91) for all three prognostic models and calibration adequate for two models (p values, 0.22 and 0.85). Our results suggest that multiple imputation of the standard 6-month GOSE may be reasonable in TBI research when the primary outcome cannot be obtained through other means.",
keywords = "clinical trial design, functional outcomes, prognostic models, traumatic brain injury",
author = "Zelnick, {Leila R.} and Morrison, {Laurie J.} and Devlin, {Sean M.} and Bulger, {Eileen M.} and Karen Brasel and Kellie Sheehan and Minei, {Joseph P.} and Kerby, {Jeffrey D.} and Tisherman, {Samuel A.} and Sandro Rizoli and Riyad Karmy-Jones and {Van Heest}, Rardi and Craig Newgard",
year = "2014",
month = "6",
day = "1",
doi = "10.1089/neu.2013.3122",
language = "English (US)",
volume = "31",
pages = "1029--1038",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "11",

}

TY - JOUR

T1 - Addressing the challenges of obtaining functional outcomes in traumatic brain injury research

T2 - Missing data patterns, timing of follow-up, and three prognostic models

AU - Zelnick, Leila R.

AU - Morrison, Laurie J.

AU - Devlin, Sean M.

AU - Bulger, Eileen M.

AU - Brasel, Karen

AU - Sheehan, Kellie

AU - Minei, Joseph P.

AU - Kerby, Jeffrey D.

AU - Tisherman, Samuel A.

AU - Rizoli, Sandro

AU - Karmy-Jones, Riyad

AU - Van Heest, Rardi

AU - Newgard, Craig

PY - 2014/6/1

Y1 - 2014/6/1

N2 - Traumatic brain injury (TBI) is common and debilitating. Randomized trials of interventions for TBI ideally assess effectiveness by using long-term functional neurological outcomes, but such outcomes are difficult to obtain and costly. If there is little change between functional status at hospital discharge versus 6 months, then shorter-term outcomes may be adequate for use in future clinical trials. Using data from a previously published multi-center, randomized, placebo-controlled TBI clinical trial, we evaluated patterns of missing outcome data, changes in functional status between hospital discharge and 6 months, and three prognostic models to predict long-term functional outcome from covariates available at hospital discharge (functional measures, demographics, and injury characteristics). The Resuscitation Outcomes Consortium Hypertonic Saline trial enrolled 1282 TBI patients, obtaining the primary outcome of 6-month Glasgow Outcome Score Extended (GOSE) for 85% of patients, but missing the primary outcome for the remaining 15%. Patients with missing outcomes had less-severe injuries, higher neurological function at discharge (GOSE), and shorter hospital stays than patients whose GOSE was obtained. Of 1066 (83%) patients whose GOSE was obtained both at hospital discharge and at 6-months, 71% of patients had the same dichotomized functional status (severe disability/death vs. moderate/no disability) after 6 months as at discharge, 28% had an improved functional status, and 1% had worsened. Performance was excellent (C-statistic between 0.88 and 0.91) for all three prognostic models and calibration adequate for two models (p values, 0.22 and 0.85). Our results suggest that multiple imputation of the standard 6-month GOSE may be reasonable in TBI research when the primary outcome cannot be obtained through other means.

AB - Traumatic brain injury (TBI) is common and debilitating. Randomized trials of interventions for TBI ideally assess effectiveness by using long-term functional neurological outcomes, but such outcomes are difficult to obtain and costly. If there is little change between functional status at hospital discharge versus 6 months, then shorter-term outcomes may be adequate for use in future clinical trials. Using data from a previously published multi-center, randomized, placebo-controlled TBI clinical trial, we evaluated patterns of missing outcome data, changes in functional status between hospital discharge and 6 months, and three prognostic models to predict long-term functional outcome from covariates available at hospital discharge (functional measures, demographics, and injury characteristics). The Resuscitation Outcomes Consortium Hypertonic Saline trial enrolled 1282 TBI patients, obtaining the primary outcome of 6-month Glasgow Outcome Score Extended (GOSE) for 85% of patients, but missing the primary outcome for the remaining 15%. Patients with missing outcomes had less-severe injuries, higher neurological function at discharge (GOSE), and shorter hospital stays than patients whose GOSE was obtained. Of 1066 (83%) patients whose GOSE was obtained both at hospital discharge and at 6-months, 71% of patients had the same dichotomized functional status (severe disability/death vs. moderate/no disability) after 6 months as at discharge, 28% had an improved functional status, and 1% had worsened. Performance was excellent (C-statistic between 0.88 and 0.91) for all three prognostic models and calibration adequate for two models (p values, 0.22 and 0.85). Our results suggest that multiple imputation of the standard 6-month GOSE may be reasonable in TBI research when the primary outcome cannot be obtained through other means.

KW - clinical trial design

KW - functional outcomes

KW - prognostic models

KW - traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=84901998123&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901998123&partnerID=8YFLogxK

U2 - 10.1089/neu.2013.3122

DO - 10.1089/neu.2013.3122

M3 - Article

VL - 31

SP - 1029

EP - 1038

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 11

ER -