Statistical Guidelines for Handling Missing Data in Traumatic Brain Injury Clinical Research

Jessica L. Nielson, Shelly R. Cooper, Seth A. Seabury, Davide Luciani, Anthony Fabio, Nancy R. Temkin, Adam R. Ferguson

Research output: Contribution to journalArticle

7 Scopus citations


Missing data is a persistent and unavoidable problem in even the most carefully designed traumatic brain injury (TBI) clinical research. Missing data patterns may result from participant dropout, non-compliance, technical issues, or even death. This review describes the types of missing data that are common in TBI research, and assesses the strengths and weaknesses of the statistical approaches used to draw conclusions and make clinical decisions from these data. We review recent innovations in missing values analysis (MVA), a relatively new branch of statistics, as applied to clinical TBI data. Our discussion focuses on studies from the International Traumatic Brain Injury Research (InTBIR) initiative project: Transforming Research and Clinical Knowledge in TBI (TRACK-TBI), Collaborative Research on Acute TBI in Intensive Care Medicine in Europe (CREACTIVE), and Approaches and Decisions in Acute Pediatric TBI Trial (ADAPT). In addition, using data from the TRACK-TBI pilot study (n = 586) and the completed clinical trial assessing valproate (VPA) for the treatment of post-traumatic epilepsy (n = 379) we present real-world examples of typical missing data patterns and the application of statistical techniques to mitigate the impact of missing data in order to draw sound conclusions from ongoing clinical studies.

Original languageEnglish (US)
Pages (from-to)2530-2537
Number of pages8
JournalJournal of neurotrauma
Issue number18
StatePublished - Sep 15 2021

Bibliographical note

Funding Information:
This work was supported by: Department of Defense (DoD) grants W81XWH-13-1-0441 (G.T.M.), W81XWH-14-2-0176 (N.R.T.), National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) grants NS069409 (G.T.M.), NS069409-02S1 (G.T.M.), NS106899 (A.R.F.), NS088475 (A.R.F.), MH116156 (J.L.N.), and CTSA UL1 TR002494.

Publisher Copyright:
© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.


  • TBI
  • assessment tools
  • missing data
  • statistical guidelines

PubMed: MeSH publication types

  • Journal Article
  • Review


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