19 Exploring the relationship between pre-clinical and diagnostic sensitivity in cancer screening: a natural history model-based analysis

Oregon Convention Center 

Test sensitivity in cancer screening, defined as the likelihood that a screening test will correctly identify the presence of pre-clinical disease, is a key driver of its potential benefit. However, studies on new biomarkers often reports sensitivity at the point of clinical diagnosis, which is generally higher than what is observed in pre-clinical stages. Our study investigates the relationship between diagnostic and pre-clinical sensitivities in cancer screening and explore the factors contributing to their discrepancies. We model the true sensitivity increasing over time after pre-clinical onset, within a natural history model of disease progression. This increase continues until the point of clinical diagnosis and sensitivity at this point is pre-specified. The pre-clinical sensitivity is determined by averaging the true sensitivity observed at the time of screening. Further, we introduce a multi-state model of disease progression that accounts for varying sensitivity levels at different stages of clinical diagnosis. We find the overall pre-clinical sensitivity would generally underestimate the diagnostic sensitivity, whereas the sensitivity measured at the early stages of pre-clinical disease may be optimistic. The model using clinical sensitivity to project the benefits of novel biomarkers in cancer screening maybe overly optimistic. Models using stage-specific sensitivity maybe more appropriate.

Test sensitivity

Stage-specific sensitivity

Retrospective study

Prospective study 

Section on Medical Devices and Diagnostics