June 2024 Assessing screening efficacy in the presence of cancer overdiagnosis
Ying Huang, Ziding Feng
Author Affiliations +
Ann. Appl. Stat. 18(2): 1543-1564 (June 2024). DOI: 10.1214/23-AOAS1848


Cancer screening facilitates the early detection of cancer at a stage when treatment is often most effective. However, it also brings the risk of overdiagnosis, where a diagnosis made through screening would not have led to symptoms or death during the patient’s lifetime. In this paper we tackle a significant unresolved issue in the evaluation of screening efficacy: selecting primary endpoints and inferential procedures that efficiently consider potential overdiagnosis in screening trials. This is motivated by the necessity to design and analyze a phase IV Early Detection Initiative (EDI) trial for evaluating a pancreatic cancer screening strategy. We introduce two novel approaches for assessing screening efficacy, grounded on cancer stage shift. These methods address potential overdiagnosis by: (i) borrowing information about clinical diagnosis from the control arm that hasn’t undergone screening (the BR approach) and (ii) performing sensitivity analysis, contingent upon a conservative bound of the overdiagnosis magnitude (the SEN-T approach). Analytical methods and extensive simulation studies underscore the superiority of our proposed methods, demonstrating enhanced efficiency in estimating and testing screening efficacy compared to existing methods. The latter either overlook overdiagnosis or adhere to a valid, yet conservative, cumulative incidence endpoint. We illustrate the practical application of these approaches using ovarian cancer data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The results affirm that our methods bolster an efficient and robust study design for cancer screening trials.

Funding Statement

This work was supported by NIH Grants NCI R01 CA277133 and U24 CA086368. The PLCO ovarian data was requested from NCI Cancer Data Access System (CDAS).


Download Citation

Ying Huang. Ziding Feng. "Assessing screening efficacy in the presence of cancer overdiagnosis." Ann. Appl. Stat. 18 (2) 1543 - 1564, June 2024. https://doi.org/10.1214/23-AOAS1848


Received: 1 April 2023; Revised: 1 October 2023; Published: June 2024
First available in Project Euclid: 5 April 2024

Digital Object Identifier: 10.1214/23-AOAS1848

Keywords: biomarker , Cancer screening , cumulative incidence , overdiagnosis , sensitivity analysis , stage shift

Rights: Copyright © 2024 Institute of Mathematical Statistics


This article is only available to subscribers.
It is not available for individual sale.

Vol.18 • No. 2 • June 2024
Back to Top