Statistical Analysis
proptosis
PROPTOSIS
The sample size was determined assuming that the mean difference in proptosis change between the groups is at least 2.0 mm (clinically relevant difference) with a standard deviation of proptosis change values of 2.5 for both groups (larger than observed in Phase 2 and Phase 3 active TED trials). A total of 57 patients (38 in the teprotumumab, and 19 in the placebo group) was planned to detect at least a 2-mm mean difference between the treatment groups in the change from baseline of proptosis values at Week 24, in order to have 81% power at the 2-sided .05 level of significance. Efficacy endpoints were sequentially tested in a prespecified order and were significant only if statistical significance was achieved for the primary efficacy endpoint, and each preceding endpoint at the .05 significance level.The primary analysis dataset was the intention-to-treat (ITT) analysis set (all randomized patients). Supplementary analyses were also conducted in the modified intention-to-treat (mITT) analysis set who received ≥ 1 dose of study drug and had ≥ 1 post-baseline measurement of the primary efficacy endpoint and per protocol analysis set, which included randomized patients who received ≥ 1 dose of drug during the masked period, had ≥ 1 post-baseline measurement, completed the masked period, without major protocol violations that would challenge data validity. The safety analysis set included patients who had received ≥ 1 dose of study drug. Missing data was not imputed unless methods for handling missing data are specified. For categorical endpoints, patients who were missing Week 24 evaluation were considered nonresponders.