Analysis of Rare Events in Outcomes Research Using Department of Defense Data: Intravenous Immune Globulin Therapy for Bullous Pemphigoid

Abstract

Abstract Introduction: Rare events data have proven difficult to explain and predict. Standard statistical procedures can sharply underestimate the probability of rare events, such as intravenous immune globulin therapy (IVIg) for bullous pemphigoid. Methods This retrospective cross-sectional study used Department of Defense TRICARE data to determine factors associated with IVIg therapy among bullous pemphigoid patients. We used prior and weighted correction methods for logit regression to solve rare event bias. Results We identified 2,720 individuals diagnosed with bullous pemphigoid from 2019 to 2022, of which 14 were treated with IVIg. Patients who received IVIg therapy were younger (65.07 vs. 75.85, P = .0016) and more likely to be female (13 vs. 1, P = .0036). The underestimation with the standard regression model for event probabilities ranged from 11–102% using the prior correction method and from 15–107% using the weighted correction method. Conclusion Rare events are low-frequency, high-severity problems that can have significant consequences. Rare diseases and rare therapies are individually unique but collectively contribute to substantial health and social needs. Therefore, correct estimation of the events is the first step toward assessing the burden of rare diseases and the pricing of their therapies.