Selection of Analysis Method for GOS-E in Future TBI Clinical Trials Using Retrospective Data

• Activity Number: 518 - Estimand, Causal Inference, and Other Statistical Considerations in Clinical Trials
• Type: Contributed
• Date/Time: Thursday, August 11, 2022 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Yu Wang* and Byron Gajewski
• Companies: University of Kansas Medical Center and University of Kansas Medical Center
• Keywords: Glasgow Outcome Scale-Extended; Sliding Scoring; Bayesian Design; Traumatic Brain Injury; Clinical Trials

Abstract

The Glasgow Outcome Scale-Extended (GOS-E), is often selected as the primary outcome for clinical trials of traumatic brain injury (TBI). The common practice is to use a sliding dichotomy of the GOS-E that incorporates subject’s baseline prognosis, which results in loss of statistical information due to the collapse of adjacent categories. To improve on power, a recent paper by Yeatts et al. proposed a sliding scoring of the GOS-E. However, drawback is treating ordinal as continuous endpoint based on normal approximation without continuity correction. We proposed analyzing the sliding scoring of the GOS-E as either ordinal or continuous with continuity correction. We used retrospective data from a TBI trial for prospective Bayesian design using dichotomous, continuous, or ordinal model, and evaluated the design operating characteristics and estimation efficiency (bias, variance, MSE) via simulations. We also illustrated a connection between the ordinal data and time-to-event (TTE) data censored to integers allowing use of Bayesian software that utilize TTE-based models.