Presentation (CTI)

OBJECTIVES: Clinical validation studies for two blood-based colorectal cancer (CRC) screening tests were recently conducted. Both study populations had different characteristics due to recruitment, enrichment, and sampling strategies. Test accuracy is associated with population characteristics such as age, complicating direct comparison. This study explores the impact of age-standardized test accuracy on comparative lifetime benefits and burdens.
METHODS: A highly-cited microsimulation model of the adenoma-carcinoma pathway was replicated, validated, and used to estimate the lifetime benefit, burden, and harms per 1000 adults screened triennially from age 45 to 75 years. Freenome’s cell-free blood DNA test (cf-bDNA-F) was evaluated using both unadjusted and age-standardized performance, with methodology similar as used for Guardant’s adjusted comparator test (cf-bDNA-G).
RESULTS: With unadjusted performance (79.2% CRC sensitivity, 12.5% AA sensitivity, 91.5% specificity), cf-bDNA-F was predicted to result in 37.4 CRC cases averted, 201.1 life-years gained (LYG), 7762 blood tests required and 1241 colonoscopies for follow-up and surveillance per 1000 adults. Age-standardization increased the test’s sensitivity for CRC (80.3%) and lowered its specificity (90.7%) closer to age-standardized cf-bDNA-G levels (80.8% and 89.5% respectively), while increasing the test’s AA sensitivity to greater than that of age-standardized cf-bDNA-G (13.9% vs. 12.9%). This resulted in the tests having similar (+/-1%) predicted cases averted (39.9 vs. 40.3) and LYG (208.8 vs. 211.0), and cf-bDNA-F requiring 2% more blood tests (7619 vs. 7452), but 6% fewer total COLs (1324 vs. 1408).
CONCLUSIONS: Differences in study populations can impact performance estimates and comparative outcomes. Age-standardized performance metrics resulted in similar predicted benefits and lower predicted colonoscopy burdens for a cf-bDNA test compared to an alternative test.