Design and Analysis of Randomized Controlled Trials in Traumatic Brain Injury

Randomized controlled trials in traumatic brain injury (TBI) are challenging due to the inherent heterogeneity of the patient population, the lack of early mechanistic end points, and relative insensitivity of outcome measures. Approaches to deal with the heterogeneity of the patient population are presented in this thesis. The use of strict enrollment criteria is not recommended, as this is inefficient. Rather, broad enrollment criteria may be preferred combined with covariate adjustment in the analysis phase. Dichotomization of the Glasgow Outcome Scale as the primary outcome measure in most trials is not recommended. Ordinal approaches to analysis of treatment effects offer greater statistical power and better sensitivity. To this purpose the use of proportional odds methodology or the sliding dichotomy may be considered. To practically apply these analysis techniques, well-validated prognostic models for TBI are currently available. Combining an ordinal approach to the analysis of treatment effects with covariate adjustment can increase statistical power by 40 – 50%. These recommendations are expected to enhance chances for detecting clinically relevant treatment effects for the benefit of future TBI patients.

• View at Worldcat

Free Full Text ( Final Version , 3mb )