Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
, 15 (3), R127

The Added Value of Ordinal Analysis in Clinical Trials: An Example in Traumatic Brain Injury

Affiliations
Randomized Controlled Trial

The Added Value of Ordinal Analysis in Clinical Trials: An Example in Traumatic Brain Injury

Bob Roozenbeek et al. Crit Care.

Abstract

Introduction: In clinical trials, ordinal outcome measures are often dichotomized into two categories. In traumatic brain injury (TBI) the 5-point Glasgow outcome scale (GOS) is collapsed into unfavourable versus favourable outcome. Simulation studies have shown that exploiting the ordinal nature of the GOS increases chances of detecting treatment effects. The objective of this study is to quantify the benefits of ordinal analysis in the real-life situation of a large TBI trial.

Methods: We used data from the CRASH trial that investigated the efficacy of corticosteroids in TBI patients (n = 9,554). We applied two techniques for ordinal analysis: proportional odds analysis and the sliding dichotomy approach, where the GOS is dichotomized at different cut-offs according to baseline prognostic risk. These approaches were compared to dichotomous analysis. The information density in each analysis was indicated by a Wald statistic. All analyses were adjusted for baseline characteristics.

Results: Dichotomous analysis of the six-month GOS showed a non-significant treatment effect (OR = 1.09, 95% CI 0.98 to 1.21, P = 0.096). Ordinal analysis with proportional odds regression or sliding dichotomy showed highly statistically significant treatment effects (OR 1.15, 95% CI 1.06 to 1.25, P = 0.0007 and 1.19, 95% CI 1.08 to 1.30, P = 0.0002), with 2.05-fold and 2.56-fold higher information density compared to the dichotomous approach respectively.

Conclusions: Analysis of the CRASH trial data confirmed that ordinal analysis of outcome substantially increases statistical power. We expect these results to hold for other fields of critical care medicine that use ordinal outcome measures and recommend that future trials adopt ordinal analyses. This will permit detection of smaller treatment effects.

Figures

Figure 1
Figure 1
Distribution of the Glasgow Outcome Score at six months after injury. Data from the CRASH trial (n = 9,554). SD, severe disability (including vegetative state); MD, moderate disability; GR, good recovery

Similar articles

See all similar articles

Cited by 28 articles

See all "Cited by" articles

References

    1. Maas AI, Roozenbeek B, Manley GT. Clinical trials in traumatic brain injury: past experience and current developments. Neurotherapeutics. 2010;7:115–126. doi: 10.1016/j.nurt.2009.10.022. - DOI - PMC - PubMed
    1. Maas AI, Steyerberg EW, Murray GD, Bullock R, Baethmann A, Marshall LF, Teasdale GM. Why have recent trials of neuroprotective agents in head injury failed to show convincing efficacy? A pragmatic analysis and theoretical considerations. Neurosurgery. 1999;44:1286–1298. - PubMed
    1. Narayan RK, Michel ME, Ansell B, Baethmann A, Biegon A, Bracken MB, Bullock MR, Choi SC, Clifton GL, Contant CF, Coplin WM, Dietrich WD, Ghajar J, Grady SM, Grossman RG, Hall ED, Heetderks W, Hovda DA, Jallo J, Katz RL, Knoller N, Kochanek PM, Maas AI, Majde J, Marion DW, Marmarou A, Marshall LF, McIntosh TK, Miller E, Mohberg N. et al. Clinical trials in head injury. J Neurotrauma. 2002;19:503–557. doi: 10.1089/089771502753754037. - DOI - PMC - PubMed
    1. Maas AI, Steyerberg EW, Marmarou A, McHugh GS, Lingsma HF, Butcher I, Lu J, Weir J, Roozenbeek B, Murray GD. IMPACT recommendations for improving the design and analysis of clinical trials in moderate to severe traumatic brain injury. Neurotherapeutics. 2010;7:127–134. doi: 10.1016/j.nurt.2009.10.020. - DOI - PMC - PubMed
    1. McHugh GS, Butcher I, Steyerberg EW, Marmarou A, Lu J, Lingsma HF, Weir J, Maas AI, Murray GD. A simulation study evaluating approaches to the analysis of ordinal outcome data in randomized controlled trials in traumatic brain injury: results from the IMPACT Project. Clin Trials. 2010;7:44–57. doi: 10.1177/1740774509356580. - DOI - PubMed

Publication types

Substances

Feedback