Comparing screening frameworks for populations with multiple overlapping high-risk factors: A case of tuberculosis screening in China

Background: Public health initiatives increasingly target multiple overlapping high-risk groups to maximize impact. However, a common challenge in modelling these initiatives is to capture these overlapping risk factors, leading to potential misallocation of resources and biased effectiveness estimates. Using China's tuberculosis (TB) control program as an example, this study explores different possible frameworks to account for population heterogeneity and risk overlap. Methods: We examined four risk allocation frameworks: (i) Direct Summation (DS), a simple additive benchmark; (ii) Probabilistic Union Deduplication (PUD), using inclusion-exclusion principles; (iii) Risk population combination (RPC), modeling interaction effects; and (iv) Agent-Based Framework (ABF), a granular microsimulation. To show how these frameworks could be used in epidemiological modelling, we embedded each within a deterministic transmission model of TB epidemiology in China, to simulate the impact of China's National Tuberculosis Strategic Plan (NTSP). We explored each framework when implemented in both static and dynamic versions. We compared them using methodological principles and indicators of intervention cost (screening volume) and benefits (cases/deaths averted). Results: Under the static version, the detection yield of active cases followed a consistent hierarchy: DS > PUD > RPC {approx} ABF. The DS method systematically overestimated yields by double-counting overlapping populations, while PUD corrected for overlap but ignored interaction. The RPC and ABF methods provided the most granular estimates by incorporating Risk population combinations. Additionally, comparing static versus dynamic versions revealed that for the same multi-risk screening framework, mortality reductions remained stable and incidence reductions varied significantly. Conclusion: This study presents potential screening frameworks for overlapping risk populations. The RPC method offers optimal balance of real-world plausibility and computational efficiency. We propose the dynamic RPC method as the preferred tool for routine analysis where multimorbidity and intersectional risks exist, providing a robust evidence base for optimizing resource allocation in heterogeneous populations.