Clinical Validation of a Primary Antibody Deficiency Screening Algorithm for Primary Care

Area of Science:

• Immunology
• Primary Care Medicine
• Health Informatics

Background:

• Diagnostic delay in primary antibody deficiencies (PADs) leads to severe health consequences and increased costs.
• Early detection of PADs is crucial for improving patient outcomes.
• A screening algorithm was previously developed to aid early PAD detection in primary care settings.

Purpose of the Study:

• To clinically validate and optimize a screening algorithm for early detection of primary antibody deficiencies (PADs).
• To apply the algorithm to a large primary care electronic health record (EHR) database in the Netherlands.

Main Methods:

• The screening algorithm was applied to 61,172 EHRs.
• High-scoring EHRs underwent exclusion screening, followed by serum immunoglobulin analysis for eligible patients.
• The algorithm was refitted using high-risk patient data to enhance efficiency.

Main Results:

• The study identified 10 new PAD patients, significantly increasing the detection rate (approx. 1:10) compared to the general population (1:1700-1:25,000).
• Refitting the algorithm improved its performance (AUC-ROC 0.80).
• A proposed two-step screening process involves initial broad screening followed by optimized selection for laboratory analysis.

Conclusions:

• The validated screening algorithm successfully reduces diagnostic delay for primary antibody deficiencies in primary care.
• The optimized algorithm and proposed two-step process enhance screening efficiency.
• Further validation in diverse populations and cost-effectiveness analyses are recommended.