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Neurotherapeutics

, Volume 7, Issue 1, pp 127–134 | Cite as

IMPACT recommendations for improving the design and analysis of clinical trials in moderate to severe traumatic brain injury

  • Andrew I. R. MaasEmail author
  • Ewout W. Steyerberg
  • Anthony Marmarou
  • Gillian S. McHugh
  • Hester F. Lingsma
  • Isabella Butcher
  • Juan Lu
  • James Weir
  • Bob Roozenbeek
  • Gordon D. Murray
Review Article

Summary

Clinical trials in traumatic brain injury (TBI) pose complex methodological challenges, largely related to the heterogeneity of the population. The International Mission on Prognosis and Clinical Trial Design in TBI study group has explored approaches for dealing with this heterogeneity with the aim to optimize clinical trials in TBI. Extensive prognostic analyses and simulation studies were conducted on individual patient data from eight trials and three observational studies. Here, we integrate the results of these studies into the International Mission on Prognosis and Clinical Trial Design in TBI recommendations for design and analysis of trials in TBI:
  • • Details of the major baseline prognostic characteristics should be provided in every report on a TBI study; in trials they should be differentiated per treatment group. We also advocate the reporting of the baseline prognostic risk as determined by validated prognostic models.

  • • Inclusion criteria should be as broad as is compatible with the current understanding of the mechanisms of action of the intervention being evaluated. This will maximize recruitment rates and enhance the generalizability of the results.

  • • The statistical analysis should incorporate prespecified covariate adjustment to mitigate the effects of the heterogeneity.

  • • The statistical analysis should use an ordinal approach, based on either sliding dichotomy or proportional odds methodology.

Broad inclusion criteria, prespecified covariate adjustment, and an ordinal analysis will promote an efficient trial, yielding gains in statistical efficiency of more than 40%. This corresponds to being able to detect a 7% treatment effect with the same number of patients needed to demonstrate a 10% difference with an unadjusted analysis based on the dichotomized Glasgow outcome scale.

Key Words

Traumatic brain injury clinical trials study design sliding dichotomy covariate adjustment prognosis 

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Copyright information

© Springer New York 2010

Authors and Affiliations

  • Andrew I. R. Maas
    • 1
    Email author
  • Ewout W. Steyerberg
    • 2
  • Anthony Marmarou
    • 3
  • Gillian S. McHugh
    • 4
  • Hester F. Lingsma
    • 2
  • Isabella Butcher
    • 4
  • Juan Lu
    • 3
  • James Weir
    • 4
  • Bob Roozenbeek
    • 1
  • Gordon D. Murray
    • 4
  1. 1.Department of NeurosurgeryUniversity Hospital AntwerpEdegemBelgium
  2. 2.Center for Medical Decision Making, Department of Public HealthErasmus MC, University Medical CenterRotterdamThe Netherlands
  3. 3.Department of NeurosurgeryVirginia Commonwealth University Medical CenterRichmond
  4. 4.Public Health Sciences, Centre for Population Health SciencesUniversity of Edinburgh Medical SchoolEdinburghUK

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