the added value of ordinal analysis in clinical trials an example in traumatic brain injury序数的附加价值分析在临床试验中一个例子在创伤性脑损伤.pdf

Roozenbeek et al. Critical Care 2011, 15:R127 /content/15/3/R127 RESEARCH Open Access The added value of ordinal analysis in clinical trials: an example in traumatic brain injury 1,2* 2 3 3 3 4 Bob Roozenbeek , Hester F Lingsma , Pablo Perel , Phil Edwards , Ian Roberts , Gordon D Murray , Andrew IR Maas1 and Ewout W Steyerberg2 for the IMPACT (International Mission on Prognosis and Clinical Trial Design in Traumatic Brain Injury) Study Group and the CRASH (Corticosteroid Randomisation After Significant Head Injury) Trial Collaborators 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 proport