Can Cost-effectiveness Analysis Inform Genotype-Guided Aspirin Use for Primary Colorectal Cancer Prevention?

Abstract

Background: Inherited genetic variants can modify the cancer-chemopreventive effect of aspirin. We evaluated the clinical and economic value of genotype-guided aspirin use for colorectal cancer chemoprevention in average-risk individuals.

Methods: A decision analytical model compared genotype-guided aspirin use versus no genetic testing, no aspirin. The model simulated 100,000 adults ≥50 years of age with average colorectal cancer and cardiovascular disease risk. Low-dose aspirin daily starting at age 50 years was recommended only for those with a genetic test result indicating a greater reduction in colorectal cancer risk with aspirin use. The primary outcomes were quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratio (ICER).

Results: The mean cost of using genotype-guided aspirin was $187,109 with 19.922 mean QALYs compared with $186,464 with 19.912 QALYs for no genetic testing, no aspirin. Genotype-guided aspirin yielded an ICER of $66,243 per QALY gained, and was cost-effective in 58% of simulations at the $100,000 willingness-to-pay threshold. Genotype-guided aspirin was associated with 1,461 fewer polyps developed, 510 fewer colorectal cancer cases, and 181 fewer colorectal cancer-related deaths. This strategy prevented 1,078 myocardial infarctions with 1,430 gastrointestinal bleeding events, and 323 intracranial hemorrhage cases compared with no genetic testing, no aspirin.

Conclusions: Genotype-guided aspirin use for colorectal cancer chemoprevention may offer a cost-effective approach for the future management of average-risk individuals.

Impact: A genotype-guided aspirin strategy may prevent colorectal cancer, colorectal cancer-related deaths, and myocardial infarctions, while minimizing bleeding adverse events. This model establishes a framework for genetically-guided aspirin use for targeted chemoprevention of colorectal cancer with application toward commercial testing in this population.

Conflict of interest statement

Conflicts of Interest: The authors report no conflicts of interest with the submitted work.

©2021 American Association for Cancer Research.

Figures

Figure 1.

Diagram of the decision analytic model and health state transitions. A, The health states considered in the model include no adenoma/no polyps, adenoma, preclinical CRC, CRC, and death. Over a healthy individual lifetime, they can transition from the states as indicated by the arrows with transitions allowed once per year. CRC health state included both early and advanced stage CRC. Any state could lead to death, which was considered a state from which an individual did not leave. B, The point at which a test is chosen marks the beginning of this model. After each decision, each branch has a probability associated with the event. After each path, the health state transitions begin. Abbreviations/acronyms: CRC: Colorectal Cancer

Figure 2.

Clinical outcomes associated with genotype-guided aspirin use. The number of clinical outcomes per 100,000 average risk individuals with genotype-guided aspirin use compared to no testing, no aspirin. Positive values indicate more events, while negative values indicate fewer events in the genotype-guided strategy. Abbreviations/acronyms: CRC: Colorectal Cancer, MI: Myocardial infarction

Figure 3.. Sensitivity Analyses.

A, The results of the probabilistic sensitivity analysis are depicted visually in an ICE scatterplot. The x-axis is the incremental QALYs and the y-axis is the incremental costs associated with genotype-guided aspirin use compared to no genetic testing, no aspirin. The average values of 100,000 patients going through the model, with the process repeated 1,000 times were represented as dots on the cost-effectiveness plane. The WTP thresholds are shown using the dotted vertical line. B, The cost-effectiveness acceptability curve from the probabilistic sensitivity analysis. The y-axis indicates the probability that the option is cost-effective at the given willingness-to-pay value on the x-axis. Solid line represents the no aspirin, no genetic testing strategy; the dashed line represents the genotype-guided aspirin strategy. Abbreviations/acronyms: ICE: incremental cost effectiveness, QALY: quality-adjusted life years, WTP: willingness-to-pay