Modeling and the Use of Surrogate Endpoints: Is This a Valid Approach?

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.