Effectiveness, benefit harm and cost effectiveness of colorectal cancer screening in Austria

Background Clear evidence on the benefit-harm balance and cost effectiveness of population-based screening for colorectal cancer (CRC) is missing. We aim to systematically evaluate the long-term effectiveness, harms and cost effectiveness of different organized CRC screening strategies in Austria. Methods A decision-analytic cohort simulation model for colorectal adenoma and cancer with a lifelong time horizon was developed, calibrated to the Austrian epidemiological setting and validated against observed data. We compared four strategies: 1) No Screening, 2) FIT: annual immunochemical fecal occult blood test age 40–75 years, 3) gFOBT: annual guaiac-based fecal occult blood test age 40–75 years, and 4) COL: 10-yearly colonoscopy age 50–70 years. Predicted outcomes included: benefits expressed as life-years gained [LYG], CRC-related deaths avoided and CRC cases avoided; harms as additional complications due to colonoscopy (physical harm) and positive test results (psychological harm); and lifetime costs. Tradeoffs were expressed as incremental harm-benefit ratios (IHBR, incremental positive test results per LYG) and incremental cost-effectiveness ratios [ICER]. The perspective of the Austrian public health care system was adopted. Comprehensive sensitivity analyses were performed to assess uncertainty. Results The most effective strategies were FIT and COL. gFOBT was less effective and more costly than FIT. Moving from COL to FIT results in an incremental unintended psychological harm of 16 additional positive test results to gain one life-year. COL was cost saving compared to No Screening. Moving from COL to FIT has an ICER of 15,000 EUR per LYG. Conclusions Organized CRC-screening with annual FIT or 10-yearly colonoscopy is most effective. The choice between these two options depends on the individual preferences and benefit-harm tradeoffs of screening candidates.


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Economic data 38 Direct-medical costs were derived from the perspective of the Austrian public health care 39 system. Both medical outpatient-and inpatient-care costs were based on original data from the 40 Main Association of Austrian Social Security Institutions (10). These costs are explained in 41 more detail below taking into account the relative frequency distribution of cancer location, 42 cancer stage and medication options, which is reported in Table S4 (1).

Costs of tests 44
The costs of a colonoscopy includes the cost of colonoscopy without polypectomy as well as 45 lump compensation, outpatient visits, clinical report, the medical consultation and digital rectal 46 examination, each as a national average of charges of internists and surgeons. The costs of 47 polypectomy are measured as the mean costs for an endoscopic removal of polyps of the colon 48 and the rectum.

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The costs for the guaiac-based fecal occult blood test include lump compensation, outpatient 50 visits, the medical consultation and digital rectal examination. The costs are measured as 51 national average of charges of internists and surgeons.

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The costs for the immunochemical fecal occult blood test additionally include the reagents for 53 the examination, the laboratory examination, the transport costs and the physician's fee per 54 patient. The costs for both types of fecal occult blood test kit are listed separately.

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Staging costs 56 The staging costs were collected separately for colorectal cancer (i.e., cancer location ICD-10 57 C18 and ICD-10 C19) and rectal cancer (i.e., cancer location ICD-10 C20). These costs include 58 in both cases the outpatient visit, laboratory work with the tumor marker (carcinoembryonic 59 antigen), sonography of the upper abdomen and computed tomography (CT) of the abdomen 60 and thorax. In addition, the costs for the staging of rectal cancer include also both a magnetic 61 resonance tomography (MR) of the lesser pelvis and a rectal endosonography (10).

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The staging costs were used to produce a weighted mean of these two cancer types. For this 63 purpose, they were multiplied with the mean relative frequency of colorectal cancer and the average of the three medication types using the above mentioned proportional shares.

Follow-up costs for rectal cancer 101
In the first year, the follow-up costs for rectal cancer include a quarterly medical consultation 102 (after 3, 6, 9 and 12 months), the tumor marker laboratory four times a year (after 3, 6, 9 and 103 12 months), a rectoscopy after 6 months, a colonoscopy after 12 months and a CT of the

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CRC -colorectal cancer, UICC -Union for International Cancer Control classification. Averaged data from Statistics Austria 2010-2014 for diagnosis (ICD-10 C18-C20) including screen and non-screen 182 detected patients for 1-year-to 5-year, 6-year and following data were extrapolated applying logarithmic functions 183 to mortality probabilities.

Base-case analysis screening-related benefits and harms
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