Conceptual model
Figures 14and15present problem-orientated conceptual models79of the natural history of CRC and
pathways for adenoma surveillance, respectively. These conceptual models form the basis of the
implemented health-economic model described below (seeImplemented health-economic model structure and assumptions).
It is widely accepted that the majority of CRCs follow the adenoma–carcinoma sequence whereby malignant neoplasia develops from pre-existing pre-malignant adenomatous polyps within the bowel (seeFigure 14). There is indirect evidence to suggest that a smaller proportion of cancers may arise de novo, although there has historically been both controversy and uncertainty surrounding these competing theories of disease natural history.80The development CRC is associated with a reduction in health-related
quality of life (HRQoL) and survival.
On detection of the initial adenomatous polyp(s) at the baseline visit (seeFigure 15), either as a consequence of follow-up of a positive colorectal screening test or through opportunistic examination, the identified adenoma(s) would be removed, most likely via polypectomy (although surgery may be required in a small proportion of cases). Patients would subsequently be considered adenoma free, although it is possible that other lesions (adenomas and/or cancer) had been previously missed at the baseline visit. While undergoing adenoma surveillance, patients would no longer be invited to attend CRC screening. Patients may
subsequently develop further adenomatous polyps and CRC. Depending on the surveillance schedule adopted, further colonoscopic examination and intervention may interrupt this natural history process. TABLE 89 Economic analysis scope
Population Patients in whom intermediate-grade adenomas have been detected
Interventions and comparators S1. 3-yearly colonoscopy, maximum surveillance age=75 years S2. 5-yearly colonoscopy, maximum surveillance age=75 years S3. 10-yearly colonoscopy, maximum surveillance age=75 years S4. 3-yearly colonoscopy, no maximum surveillance age S5. 5-yearly colonoscopy, no maximum surveillance age S6. 10-yearly colonoscopy, no maximum surveillance age
S7. Once-only colonoscopy 3 years post baseline, maximum surveillance age=75 years S8. Once-only colonoscopy 5 years post baseline, maximum surveillance age=75 years S9. Once-only colonoscopy 10 years post baseline, maximum surveillance age=75 years S10. Once-only colonoscopy 3 years post baseline, no maximum surveillance age S11. Once-only colonoscopy 5 years post baseline, no maximum surveillance age S12. Once-only colonoscopy 10 years post baseline, no maximum surveillance age S13. No colonoscopy
Outcome Incremental cost per QALY gained Time horizon Patients’remaining lifetime Perspective NHS and PSS
Discount rate 3.5% per year Price year 2012–13
Subsequent adenomas identified at colonoscopic surveillance would be removed, thereby reducing the risk of CRC.10Given the imperfect test sensitivity of colonoscopy,81–83a proportion of adenomas present in the
bowel may be missed. The identification of preclinical (undiagnosed) CRC at colonoscopy surveillance would lead to the patient being referred for further investigations and treatment; again, a proportion of previously undetected cancers may be missed as a result of imperfect test sensitivity. Colonoscopy is associated with a number of relatively infrequent complications including lower gastrointestinal bleeding and perforation. Bleeding is most likely to be managed conservatively, necessitating an overnight stay in hospital. Perforation may be managed conservatively or in some cases may require more immediate surgical intervention.84In a
small proportion of cases, bowel perforation may be fatal. The diagnosis and subsequent treatment of CRC may lead to improvements in survival and HRQoL; the management of the disease and the outlook for patients is strongly influenced by stage at diagnosis.
Implemented health-economic model structure and assumptions
The health-economic model was implemented as a next-event patient-level simulation using SIMUL8®
software (SIMUL8 Corporation, Boston, MA, USA).Figures 16and17present the implemented simulation model structure and logic. The model comprises five mutually exclusive health states: (1) no adenomas; (2) adenomas; (3) preclinical CRC; (4) diagnosed CRC; and (5) dead. The structure of the health-economic model was defined in line with that of the multistate model (MSM) analysis (seeBaseline model of natural history progression and colonoscopy test characteristics, below), which, in turn, was defined according to the patients’true underlying histology and colonoscopy test characteristics. Differential prognoses by adenoma type and cancer stage are not captured within the model. Health states are defined according to the index lesion (i.e. the most AA or cancer present within the patient’s bowel). Disease natural history is assumed to follow the adenoma–carcinoma sequence, as illustrated inFigure 14. The model does not allow for the development of de novo cancers without patients first developing one or more prior adenomas.
The model simulates the experience of patients from the identification and removal of the index adenoma(s) at the baseline visit through to the development of further adenomas and CRC, and the impact of alternative colonoscopic surveillance options on this natural history process, as described above (seeConceptual model). Patients enter the model following the detection and removal of intermediate-grade adenomatous polyps at their baseline colonoscopy visit. Patient-level characteristics (age, life expectancy, time to disease progression, time to next surveillance colonoscopy) are then sampled and assigned to each patient. Four competing
Death due to other causes
Development of adenoma(s)
Malignant onset
Diagnosis of clinical cancer
Death due to CRC Normal epithelium
(no adenomas, no cancer)
Adenomatous polyp(s)
Preclinical CRC
Clinical CRC
Dead
Patient diagnosed with intermediate-grade adenoma No adenomas Adenomas Surveillance COL Complications Preclinical cancer Diagnosed cancer Dead
Adenomas removed on detection Scheduled surveillance COL
Scheduled surveillance COL
Scheduled surveillance COL
Non-fatal
Due to perforation
Adenoma(s) missed Cancer missed
Adenoma(s) detected and removed
Disease progression Disease progression Symptomatic presentation Cancer death FIGURE 15 Conceptual service pathways model. COL, colonoscopy.