To estimate the sample size needed to establish efficacy, we needed to specify the effect size to be detected by our outcome measures. We do not have any human data to definitively establish the effect size expected as a result of treatment. Based on animal models, we conservatively posit that progesterone will improve neurological outcome (i.e., dichotimized GOS, DRS, GOAT at one month post-injury) by 25%. We expect to enroll 100 subjects at a 4:1 randomization (80 treated and 20 controls) into our pilot study. With respect to duration of coma, the number of patients that would allow us to achieve 80% power to detect a difference of at least 0.6 standard deviation between treatment groups at the two-sided 0.05 significance level was 50 treated and 50 controls. For this outcome, a difference of 0.6 standard deviation units translates into a difference of + 1.1 days, or 29%, based on the findings of Stambrook, et al.6 However, since we have changed our protocol to a 4:1 randomization, we no longer have the power to detect this difference. Similarly, in the subgroup of patients monitored for differences in the ICP-TIL, in the original 1:1 randomization scheme we would have been able to achieve 80% power to detect a difference of at least 1.0 standard deviation between treatment groups at the two-sided 0.05 significance level, but with the 4:1 scheme no longer have the power to detect a difference. With respect to mortality, our pilot will have insufficient power (<50%) to definitively detect an effect size equal to 25% reduction in the rate of death. Similarly there is insufficient power to detect a "good" neurological outcome at hospital discharge or at one month post-injury using a dichotomized GOS (good or moderate recovery versus severe disability), with the expectation of 50% with good outcome in the placebo group, based on the findings of Levin, et al. However, this study should allow us to perceive trends in the data as well as determine the range and prevalence of outcomes that we might anticipate for a multi-center study of this therapy. This will allow us to refine our future power calculations appropriately.