BACKGROUND: Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI). We investigated the efficacy and safety of progesterone for TBI. METHODS: We conducted a study, in which 1195 patients, 16 to 70 years of age, with severe TBI (Glasgow Coma Scale score, $8 [on a scale of 3 to 15, with lower scores indicating a reduced level of consciousness] and at least one reactive pupil) were randomly assigned to receive progesterone or placebo within hours after injury. The primary efficacy end point was the Glasgow Outcome Scale score at 6 months after the injury. RESULTS: Proportional-odds analysis with covariate adjustment showed no treatment effect of progesterone as compared with placebo (odds ratio, 0.96; confidence interval, 0.77 to 1.18). The proportion of patients with a favorable outcome on the Glasgow Outcome Scale (good recovery or moderate disability) was 50.4% with progesterone, as compared with 50.5% with placebo. Mortality was similar in the two groups. No relevant safety differences were noted between progesterone and placebo. CONCLUSIONS: Primary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI. a. What is the study design? b. What is the main exposure and the main outcome in this study? c. What is the measure of association reported here? Why do you think they were unable to calculate person-time and use the rate ratio