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.
authors.affiliation: 1 Department of Biostatistics, University of Washington ROC Clinical Trial Center , Seattle, Washington.
authors.forename: Leila R
authors.initials: LR
authors.lastname: Zelnick
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Morrison
authors.forename: Sean M
authors.initials: SM
authors.lastname: Devlin
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Bulger
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Brasel
authors.forename: Kellie
authors.initials: K
authors.lastname: Sheehan
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Minei
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Kerby
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Tisherman
authors.forename: Sandro
authors.initials: S
authors.lastname: Rizoli
authors.forename: Riyad
authors.initials: R
authors.lastname: Karmy-Jones
authors.forename: Rardi
authors.initials: R
authors.lastname: van Heest
authors.forename: Craig D
authors.initials: CD
authors.lastname: Newgard
mesh_terms: D000328:Adult; D001930:Brain Injuries / Q000523:psychology / Q000628:therapy*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D008959:Models, Neurological; D008962:Models, Theoretical; D011379:Prognosis; D015203:Reproducibility of Results; D012107:Research Design; D016896:Treatment Outcome
keywords: clinical trial design; functional outcomes; prognostic models; traumatic brain injury