Volume 154, Issue 1, Pages 105-116.e20 (January 2018) Cost Effectiveness of Age-Specific Screening Intervals for People With Family Histories of Colorectal Cancer  Steffie K. Naber, Karen M. Kuntz, Nora B. Henrikson, Marc S. Williams, Ned Calonge, Katrina A.B. Goddard, Doris T. Zallen, Theodore G. Ganiats, Elizabeth M. Webber, A. Cecile J.W. Janssens, Marjolein van Ballegooijen, Ann G. Zauber, Iris Lansdorp-Vogelaar  Gastroenterology  Volume 154, Issue 1, Pages 105-116.e20 (January 2018) DOI: 10.1053/j.gastro.2017.09.021 Copyright © 2018 AGA Institute Terms and Conditions

Figure 1 Sequential optimization method, for an example of individuals with 1 affected FDR (corresponds with the first row in Table 4). First, the optimal start age and interval for the youngest cohort (30 year olds) is determined. The resulting screening ages between ages 30 and 44 are assumed as prior screening for the 45 year olds, for whom the screening interval from age 45 is optimized. The screening ages until age 49 are then incorporated in the prior screening for 50 year olds, and so on. For 70 year olds, the optimal end age of screening is determined. In the figure, the derivation of an optimal screening strategy is given in these subsequent steps (indicated by the black arrows). Gastroenterology 2018 154, 105-116.e20DOI: (10.1053/j.gastro.2017.09.021) Copyright © 2018 AGA Institute Terms and Conditions

Model Appendix Figure 1 An overview of the natural history module of the general MISCAN-Colon model. In the general MISCAN-Colon model, sessile serrated polyps are modeled as part of the same pathway to cancer as adenomas. In the expanded MISCAN-Colon model, which was used in 2 of the sensitivity analyses, sessile serrated polyps are modeled as a separate pathway to cancer. The pathways have the same structure of disease stages, but sessile serrated polyps have longer dwelling times and are distributed differently than conventional adenomas. Gastroenterology 2018 154, 105-116.e20DOI: (10.1053/j.gastro.2017.09.021) Copyright © 2018 AGA Institute Terms and Conditions

Model Appendix Figure 2 Adenoma prevalence observed in selected autopsy studies vs simulated by MISCAN-Colon (% of individuals with adenomas).* Gastroenterology 2018 154, 105-116.e20DOI: (10.1053/j.gastro.2017.09.021) Copyright © 2018 AGA Institute Terms and Conditions

Model Appendix Figure 3 CRC incidence observed before the introduction of screening vs simulated by MISCAN-Colon (total (A), stage I CRC (B), stage II CRC (C), stage III CRC (D), stage IV CRC (E); cases per 100,000 person years). Gastroenterology 2018 154, 105-116.e20DOI: (10.1053/j.gastro.2017.09.021) Copyright © 2018 AGA Institute Terms and Conditions

Model Appendix Figure 4 Distal CRC incidence observed in the intervention group of the UK Flexible Sigmoidoscopy Trial vs simulated by MISCAN-Colon (per year of follow-up (A), cumulative (B); cases per 100,000 person years). Gastroenterology 2018 154, 105-116.e20DOI: (10.1053/j.gastro.2017.09.021) Copyright © 2018 AGA Institute Terms and Conditions

Model Appendix Figure 5 Integrating modules: two example patients (A and B). Gastroenterology 2018 154, 105-116.e20DOI: (10.1053/j.gastro.2017.09.021) Copyright © 2018 AGA Institute Terms and Conditions

Supplementary Figure 1 Cost-efficiency frontiers for people with 1 affected FDR, by age. The costs, health effects, and ICER of every strategy in the figure can be found in Supplementary Tables 1a-1g. If the same symbols appear in a single frontier, strategies begin or end at different ages (see the Supplementary Tables for the exact strategies). Strategies that are cost-effective under a willingness-to-pay threshold of $100,000 per QALY gained are marked with a red circle. Gastroenterology 2018 154, 105-116.e20DOI: (10.1053/j.gastro.2017.09.021) Copyright © 2018 AGA Institute Terms and Conditions