| Abstract: |
Background: The sensitivity of a cancer screening biomarker Results: Clinical sensitivity is generally optimistic. Archived-to detect prevalent preclinical cancer drives screening benefit. sample sensitivity is optimistic near clinical diagnosis but may be Studies estimate sensitivity at different points in the biomarker pessimistic at longer look-back intervals, with bias also dependent on development process. We examine how closely these estimates test specificity. Prospective empirical sensitivity is optimistic when reflect the sensitivity to detect preclinical cancer (preclinical the sojourn time is long relative to the screening interval. Bias in sensitivity). prospective empirical sensitivity also depends on the frequency and Methods: We posit that preclinical sensitivity is inversely accuracy of confirmation testing following a positive screening test. proportional to the preclinical sojourn time. We simulate studies Conclusions: Sensitivity estimates from different phases of and estimates of sensitivity corresponding to the Early Detection biomarker development should be distinguished and labeled ac-Research Network's Phases of Biomarker Development. Sensi- cordingly to facilitate a realistic assessment of diagnostic pertivity estimates based on clinically diagnosed cases (phase II, formance and prediction of potential benefit. clinical sensitivity), archived-sample studies (phase III, archived- Impact: Our study highlights the need for clearer terminology sample sensitivity), and prospectively screened cohorts (phases to describe the sensitivity of cancer early detection biomarkers. IV and V, prospective empirical sensitivity) are defined and We introduce new labels, explain biases in sensitivity estimates, compared against the corresponding expected preclinical and advocate for improved communication to enhance under-sensitivity. standing of diagnostic test performance. © 2025 American Association for Cancer Research. |
