A validated artificial intelligence-based pipeline for population-wide primary immunodeficiency screening

Identification of patients with underlying inborn errors of immunity and inherent susceptibility to infection remains challenging. The ensuing protracted diagnostic odyssey for such patients often results in greater morbidity and suboptimal outcomes, underscoring a need to develop systematic methods for improving diagnostic rates.

The principal aim of this study is to build and validate a generalizable analytical pipeline for population-wide detection of infection susceptibility and risk of primary immunodeficiency.

This prospective, longitudinal cohort study coupled weighted rules with a machine learning classifier for risk stratification. Claims data were analyzed from a diverse population (n = 427,110) iteratively over 30 months. Cohort outcomes were enumerated for new diagnoses, hospitalizations, and acute care visits. This study followed TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) standards.

Cohort members initially identified as high risk were proportionally more likely to receive a diagnosis of primary immunodeficiency compared to those at low-medium risk or those without claims of interest respectively (9% vs 1.5% vs 0.2%; P < .001, chi-square test). Subsequent machine learning stratification enabled an annualized individual snapshot of complexity for triaging referrals. This study's top-performing machine learning model for visit-level prediction used a single dense layer neural network architecture (area under the receiver-operator characteristic curve = 0.98; F1 score = 0.98).

A 2-step analytical pipeline can facilitate identification of individuals with primary immunodeficiency and accurately quantify clinical risk.