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Aspirin as an Adjunct to Screening for Prevention of Sporadic Colorectal Cancer: A Cost-Effectiveness Analysis

Uri Ladabaum, MD, MS; Cathy Lee Chopra, MD, MS; Grace Huang, MD, MS; James M. Scheiman, MD; Michael E. Chernew, PhD; and A. Mark Fendrick, MD
[+] Article and Author Information

From University of California, San Francisco, San Francisco, California; and University of Michigan, Ann Arbor, Michigan.


Acknowledgment: The authors thank Dr. David Glidden of the University of California, San Francisco, General Clinical Research Center for assistance with the Monte Carlo simulation.

Grant Support: By grants from the National Institutes of Health to the University of Michigan and the University of California, San Francisco, General Clinical Research Centers (M01-RR00042 and M01-RR00079), including a Clinical Associate Physician Award to Dr. Ladabaum.

Requests for Single Reprints: Uri Ladabaum, MD, MS, Division of Gastroenterology, S-357, Box 0538, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0538.

Current Author Addresses: Dr. Ladabaum: Division of Gastroenterology, S-357 Box 0538, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0538.

Dr. Lee Chopra: Division of Geriatric Medicine, 1500 East Medical Center Drive, CCGCB 1127/0920, University of Michigan, Ann Arbor, MI 48109.

Dr. Huang: Mental Health Research Institute, 205 Zina Pitcher Place, University of Michigan, Ann Arbor, MI 48109-0720.

Dr. Scheiman: Division of Gastroenterology, 3912 Taubman Center, University of Michigan, Ann Arbor, MI 48109-0362.

Dr. Chernew: Department of Health Management and Policy, SPH-2 HMP, 109 Observatory, University of Michigan, Ann Arbor, MI 48109-2029.

Dr. Fendrick: Division of General Medicine, 1500 East Medical Center Drive, University of Michigan, Ann Arbor, MI 48109.

Author Contributions: Conception and design: U. Ladabaum, C. Lee Chopra, G. Huang, J.M. Scheiman, M.E. Chernew, A.M. Fendrick.

Analysis and interpretation of the data: U. Ladabaum, C. Lee Chopra, G. Huang, J.M. Scheiman, M.E. Chernew, A.M. Fendrick.

Drafting of the article: U. Ladabaum, J.M. Scheiman, A.M. Fendrick.

Critical revision of the article for important intellectual content: U. Ladabaum, J.M. Scheiman, A.M. Fendrick.

Final approval of the article: U. Ladabaum, J.M. Scheiman, M.E. Chernew, A.M. Fendrick.

Provision of study materials or patients: U. Ladabaum.

Statistical expertise: U. Ladabaum.

Administrative, technical, or logistic support: U. Ladabaum, J.M. Scheiman, M.E. Chernew, A.M. Fendrick.

Collection and assembly of data: U. Ladabaum, C. Lee Chopra.


Ann Intern Med. 2001;135(9):769-781. doi:10.7326/0003-4819-135-9-200111060-00007
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Colorectal cancer is the second leading cause of cancer-related death in the United States, with 129 400 new cases and 56 600 deaths estimated to have occurred in 1999 (1). Most cases of colorectal cancer arise from adenomatous polyps (2). Screening has been shown to decrease colorectal cancer incidence and mortality rates (34), and various decision analyses support its cost-effectiveness (510). Despite demonstrated clinical and economic benefits, however, use of screening tests is low (1113). In a large population-based study, 19.8% of respondents reported having fecal occult blood testing during the preceding year and 30.4% reported having sigmoidoscopy–proctoscopy during the preceding 5 years; 9.5% had had both tests (13).

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Figures

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Figure 1.
Colorectal cancer incidence by age.

The natural history model closely reproduces data from the Surveillance, Epidemiology, and End Results (SEER) program. In the model, aspirin chemoprevention, colorectal cancer screening, and screening and aspirin combined led to progressively lower cancer rates. ASA = aspirin; COLO = colonoscopy every 10 years; FS/FOBT = flexible sigmoidoscopy every 5 years and annual fecal occult blood testing.

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Figure 2.
Cancer cases by stage.

In our model, total cases of cancer diagnosed from 50 to 80 years of age decreased progressively with aspirin, screening, and aspirin and screening. Aspirin decreased case number without altering stage, while screening decreased case number and led to diagnosis at earlier stages. ASA = aspirin; COLO = colonoscopy every 10 years; FS/FOBT = flexible sigmoidoscopy every 5 years and annual fecal occult blood testing.

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Figure 3.
Discounted costs per person.

Total cost per person increased minimally for aspirin use alone. Screening significantly reduced the costs for cancer care but increased the total cost per person approximately 2.5-fold. The cost of aspirin-related complications accounts for most aspirin-related costs. ASA = aspirin; COLO = colonoscopy every 10 years; FS/FOBT = flexible sigmoidoscopy every 5 years and annual fecal occult blood testing.

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Figure 4.
Sensitivity analysis of reduction in colorectal cancer risk by aspirin use and screening adherence in the population.

The incremental cost-effectiveness ratio for adding aspirin therapy to screening changed sharply from very high values to lower values at all levels of screening adherence. As adherence increased, aspirin's chemopreventive benefit was required to be progressively greater to make the addition of aspirin therapy cost-effective. COLO = colonoscopy every 10 years; FS/FOBT = flexible sigmoidoscopy every 5 years and annual fecal occult blood testing.

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Figure 5.
Sensitivity analysis of reduction in colorectal cancer risk and related complication rates when aspirin therapy is added to colonoscopy.

Screening adherence rates were 25% (top) and 75% (bottom). As screening adherence or aspirin-related complications increased, aspirin's chemopreventive benefit was required to be progressively greater to make the addition of aspirin cost-effective.

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Appendix Figure.
Markov states in the natural history model.

The ovals with solid borders represent the principal Markov states of normal, polyp, localized colorectal cancer (CRC-L), regional colorectal cancer (CRC-R), distant colorectal cancer (CRC-D), and dead. The Markov states for patients who survived treatment for cancer (status after CRC-L and status after CRC-R) are also shown. The ovals without solid borders represent intermediate states associated with the symptomatic presentation of cancer. As shown, patients could remain in the same Markov state or transition to dead at the end of every cycle. Normal patients may develop a polyp or CRC-L. Polyps may progress to CRC-L. Cancer cases progressed from localized to regional to distant unless symptoms led to diagnosis and treatment. If this occurred, patients entered postcancer surveillance in status after CRC-L and status after CRC-R.

For simplicity, the addition of aspirin therapy and the screening strategies are not depicted. Aspirin decreased the transition probabilities from normal to polyp or CRC-L, and from polyp to CRC-L. In addition, aspirin-related complications, including death, may arise in any Markov state. When the screening strategies were modeled, states analogous to the principal states depicted were created with modifiers to track an individual's history (status after normal results on fecal occult blood testing, sigmoidoscopy, or colonoscopy or status after polypectomy). These modifiers determined screening and surveillance intervals and tests.

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Summary for Patients

Is Aspirin a Cost-Effective Addition to Colorectal Cancer Screening?

The summary below is from the full report titled “Aspirin as an Adjunct to Screening for Prevention of Sporadic Colorectal Cancer. A Cost-Effectiveness Analysis.” It is in the 6 November 2001 issue of Annals of Internal Medicine (volume 135, pages 769-781). The authors are U Ladabaum, CL Chopra, G Huang, JM Scheiman, ME Chernew, and AM Fendrick.

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