Ladabaum Uri, van Duuren Luuk A, Half Elizabeth E, Levi Zohar, Silverman Barbara, Lansdorp-Vogelaar Iris
School of Medicine, Stanford University, 430 Broadway Street Pavilion C, 3Rd Floor C-326, Redwood, CA, USA.
Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands.
Dig Dis Sci. 2025 May;70(5):1711-1722. doi: 10.1007/s10620-024-08725-x. Epub 2025 Jan 8.
Development of novel colorectal cancer (CRC) screening tests is a dynamic field. Decision analytic modeling based on inputs derived from rigorous prospective studies informs CRC screening guidelines. Exploratory modeling may have a place in early phases of test development.
We explored whether (1) surrogate endpoints for long-term, programmatic effectiveness, and cost-effectiveness could be potentially informative in early stages of test development and (2) whether rapid exploratory modeling with a web-based tool would be feasible.
First, based on comparisons with published estimates for reductions in CRC mortality with various screening tests in four established decision analytic models of CRC screening, the surrogate endpoint of the number needed to colonoscope to detect one CRC or advanced precancerous lesion (APL) in round 1 of screening appears to hold promise as a measure of clinical effectiveness. Similarly, based on comparisons with published estimates for cost/quality-adjusted life-year gained with screening in the four models, the surrogate endpoint of cost to detect one CRC or APL in round 1 of screening appears to hold promise as a measure of cost-effectiveness. Second, exploration of the impact of lowering the screening initiation age in Israel from age 50 to 45 with the web-based EU-TOPIA tool, compared with the results of a recently published comprehensive modeling study, suggests that exploratory modeling of programmatic screening may be feasible with relatively low time demand vs. that required for typical full-length modeling publications.
Further validation in other models and with a broader set of test performance characteristics is prudent before surrogate endpoints or rapid modeling are incorporated into the novel test development process.
新型结直肠癌（CRC）筛查测试的开发是一个动态领域。基于严格前瞻性研究得出的输入数据进行的决策分析模型为CRC筛查指南提供了依据。探索性建模在测试开发的早期阶段可能会发挥作用。
我们探讨了（1）长期、项目有效性和成本效益的替代终点在测试开发早期阶段是否可能具有参考价值，以及（2）使用基于网络的工具进行快速探索性建模是否可行。
首先，通过与四个已建立的CRC筛查决策分析模型中各种筛查测试降低CRC死亡率的已发表估计值进行比较，在第一轮筛查中结肠镜检查发现一例CRC或高级癌前病变（APL）所需的人数这一替代终点，似乎有望作为临床有效性的衡量指标。同样，通过与四个模型中筛查获得的成本/质量调整生命年的已发表估计值进行比较，在第一轮筛查中检测一例CRC或APL的成本这一替代终点，似乎有望作为成本效益的衡量指标。其次，使用基于网络的欧盟-TOPIA工具探索将以色列的筛查起始年龄从50岁降低到45岁的影响，与最近发表的一项全面建模研究的结果相比，表明与典型的完整建模出版物所需时间相比，项目筛查的探索性建模可能在相对较低的时间需求下可行。
在将替代终点或快速建模纳入新型测试开发过程之前，谨慎地在其他模型中并结合更广泛的测试性能特征进行进一步验证是明智的。
