We used three independently developed microsimulation models to evaluate the cost-effectiveness of CTC screening for colorectal cancer and found that the number of life-years gained from 5-yearly CTC (with referral of individuals with findings of ≥6 mm for a diagnostic colonoscopy) were similar to the number gained from 10-yearly colonoscopy screening, assuming perfect adherence to all tests. However, if CTC was reimbursed at $488 per test, slightly less than the reimbursement for a colonoscopy without polypectomy, the overall costs of the CTC strategies were greater than the costs of all of the other screening strategies considered, and CTC was therefore dominated by other screening strategies in the cost-effectiveness analysis.
At first, it may seem surprising that CTC was not cost-effective when compared with the other colorectal cancer screening tests, considering that the sensitivity of CTC for large adenomas and colorectal cancer was almost comparable to that of colonoscopy and that the base-case estimate of the cost to CMS per CTC scan was slightly less than the CMS reimbursement rate for colonoscopy. However, the recommended screening interval is 5 years with CTC vs 10 years with colonoscopy (21
), and individuals with CTC findings measuring 6 mm or larger require a follow-up colonoscopy. Thus, even for people who never have an abnormality detected, the costs of CTC are incurred twice as frequently as the cost of colonoscopy, whereas those who have a positive finding on CTC accrue the cost of a diagnostic colonoscopy in addition to the cost of the screening CTC. We found that at a cost of $108–$205 per scan, CTC would be a cost-effective strategy for colorectal cancer screening, assuming that the CTC performance characteristics in the Department of Defense study and the National CTC Trial are achievable in routine clinical practice.
CTC is a rapidly evolving technology. After we presented these findings to CMS, the Munich Colorectal Cancer Prevention Trial (7
), a prospective trial that compared the performance characteristics of CTC, colonoscopy, flexible sigmoidoscopy, immunochemical FOBT, and FOBT for the detection of advanced colonic neoplasia among 307 asymptomatic adults, reported a CTC specificity of 93% using a 5-mm threshold for referral for a follow-up colonoscopy, which is higher than the CTC specificity of 80% in the Department of Defense study and of 88% in the National CTC Trial (both with 6-mm thresholds) and CTC sensitivity estimates that were as high or higher than those in the Department of Defense study and the National CTC Trial. If these more favorable test characteristics are replicated in larger studies, then the threshold cost of a CT scan would increase. However, the increase is likely to be small because, as noted above, individuals with positive findings on CTC require a second procedure, the follow-up colonoscopy. Therefore, research on techniques to improve detection rates with CTC may be less important in informing future coverage decisions than studies that assess whether or not individuals who have yet to be screened for colorectal cancer deem CTC more acceptable than other colorectal cancer screening options. Our analysis showed that if the availability of CTC enticed 25% of otherwise unscreened individuals to be screened, CTC would be cost-effective at the base-case cost estimate of $488. If only 10% of unscreened persons adopted CTC screening, CTC would become cost-effective at $204–$408 per scan. To our knowledge, no clinical study has evaluated whether the addition of CTC to the menu of colorectal cancer screening options increases adherence among those who were previously unwilling to be screened.
Because colonoscopy reimbursement rates might be higher among non-Medicare providers, we evaluated how threshold costs for CTC changed as the cost of a colonoscopy increased. In two of the models, threshold costs for CTC decreased as the cost of a colonoscopy increased. In one model, threshold costs exceeded the base-case estimate of $488 per scan when the cost of a colonoscopy was 4.5 times higher than the base-case estimate, although at this high colonoscopy cost the incremental cost-effectiveness ratio for CTC screening was in excess of $150
000 per life-year gained.
There are several limitations to this analysis. First, we did not consider excess risks and costs that are associated with radiation exposure or with the detection of extracolonic findings on CTC. The magnitude of these risks and costs are unclear, but their inclusion would likely yield lower threshold costs for CTC. With regard to extracolonic findings on CTC, there has been considerable discussion about whether they represent an asset or liability (50
). Longitudinal studies are needed to determine the long-term clinical outcomes and the potential benefits and harms associated with the spectrum of extracolonic diseases and conditions that become evident with CTC. At present, such data are not available. In the Department of Defense study (3
), 56 (4.5%) of the 1233 subjects had extracolonic findings that were deemed highly important, and a higher proportion of subjects had findings that were deemed moderately important (total number with findings of moderate importance was not reported). In the National CTC Trial (5
), 16% of subjects had a finding that was deemed to require follow-up or urgent care. Estimates of the costs associated with extracolonic findings vary considerably, ranging from $28 (53
) to $248 (54
) per person screened. Although there is uncertainty regarding the magnitude of the costs of extracolonic findings, their inclusion in analyses such as this one would likely result in lower threshold costs for CTC, even if treatment of the extracolonic findings led to a small gain in life expectancy.
Second, we did not quality adjust our estimates of the numbers of life-years. Although data on the quality of life among individuals with cancer have been reported (55
), there is a lack of data on the quality-of-life implications of undergoing screening, follow-up, and surveillance procedures and, in particular, of waiting for test results.
Third, because there are no nationally representative longitudinal data to our knowledge concerning colorectal cancer screening patterns among individuals younger than 64 years, we assumed that all 65-year-olds were previously unscreened. Many individuals who are entering the Medicare program will have had prior colorectal cancer screening, whereas others will have had none; only those with no prior screening and those with no adenomas or cancer detected at a prior screening are eligible for average-risk screening. The first group may be at higher-than-average risk of harboring colorectal neoplasia, whereas the latter group would likely be at lower risk. The risk of colorectal cancer for a previously unscreened population may therefore not be very different from the true risk. If the risk of colorectal cancer for the Medicare-eligible population differs from that for a previously unscreened cohort, our estimates of the life-years gained from screening may be overstated or understated depending on the true risk. However, because the threshold costs of CTC are assessed by comparing the relative costs and life-years gained between screening strategies, the threshold CTC costs may not be greatly affected by the baseline colorectal cancer risk. Indeed, in the sensitivity analysis on a population (ie, 50-year-olds), the threshold CTC costs did not change substantially ($108–$205 for previously unscreened 65-year-olds vs $72–$179 for 50-year-olds).
Fourth, in the sensitivity analysis of screening adherence, we assumed that individuals either were fully adherent with a screening strategy or were never screened. This assumption is an oversimplification of what occurs in practice but is closer to reality than assuming that all individuals show up randomly to their scheduled screens. Furthermore, because of a lack of data on test-specific adherence patterns with repeated screening, we could not account for the fact that adherence may differ between stool-based and endoscopic tests. It is unclear which screening methods would have greater adherence, those that are less invasive but that require more frequent testing (eg, stool-based tests) or those that are more invasive but require less frequent testing (eg, endoscopic and radiological tests).
Fifth, we assumed conditional independence of repeat screenings (ie, no systematic false-negative or false-positive results on repeat screens). This is a reasonable assumption for the FOBTs because bleeding of a lesion is thought to be a random event and for CTC because it can detect lesions that may be difficult to find with endoscopy, such as those located on folds (56
). It may be a less reasonable assumption for endoscopy, in which case our estimates of the effectiveness of endoscopic strategies could be overstated. However, because colonoscopy is used for follow-up of positive results on all other screening tests and for surveillance, the effectiveness of all strategies would be similarly overstated. Accordingly, the overall effect of the assumption of conditional independence on the threshold cost of CTC is unclear.
Sixth, patient time costs were based on assumptions because estimates were not available for most screening modalities. To our knowledge, patient time costs have only been assessed for one screening modality, that is, colonoscopy. Jonas et al. (57
) reported a median time of 37 hours from initiation of colonic preparation to return to routine activities among 110 patients undergoing screening colonoscopy. This estimate is considerably higher than our estimate of 8 hours because it also includes the patients’ sleep time. Our estimates of the time spent with complications (16 hours) may also be underestimated. Although the costs of colonoscopy screening would be most affected by our assumptions about patient time, the costs of all strategies ultimately would be affected because colonoscopy is used for follow-up of positive findings on other tests and for surveillance. Accordingly, we do not expect that increasing our estimates of the amount of patient time involved with screening and complications would have a large impact on the threshold costs of CTC from the modified societal perspective.
Finally, although we performed sensitivity analyses on key parameters, we did not specify distributions around the uncertain parameters and sample from those distributions in a probabilistic sensitivity analysis. Instead, to address uncertainties among model parameters that relate to the natural history of colorectal cancer, we used multiple models that were developed independently before we performed the analyses presented here and as such, they provide a sensitivity analysis on the structural assumptions of the models. The models differ in their estimates of dwell time, that is, the total amount of time a clinically detected colorectal cancer spends in the adenoma and preclinical cancer phases. The dwell time in the MISCAN model is, on average, shorter than the dwell times in the SimCRC and CRC-SPIN models. On the basis of this difference, the MISCAN model estimates fewer life-years saved as a result of removing adenomas through screening compared with the SimCRC and CRC-SPIN models, and it estimates a greater benefit for shorter screening intervals for tests with relatively high sensitivities for detecting adenomas, such as colonoscopy and CTC than do the other models. Nevertheless, all three models came to similar conclusions about the cost-effectiveness and threshold costs of CTC screening, demonstrating the robustness of these results to uncertainties about the duration of the adenoma–carcinoma sequence.
Several other studies on the cost-effectiveness of CTC screening in the United States have been published (52
), and their findings are summarized in . Because these studies used different unit cost estimates, we compared the findings by calculating the threshold cost of CTC as a percentage of the study-specific estimate of the cost of a colonoscopy. We refer to this as the threshold cost percentage. In all of these studies, the threshold cost percentages for CTC were higher than the 22%–41% found in this study. However, direct comparison of threshold costs percentages across studies is difficult for three reasons. First, the studies differ with respect to the strategies against which CTC screening was compared. We compared CTC screening with all other currently reimbursed and widely used test strategies, whereas most of the other studies compared CTC with colonoscopy or with colonoscopy, sigmoidoscopy, and Hemoccult II. In only one of the three models used in this analysis (CRC-SPIN), were the costs and health effects of the colonoscopy strategy relevant in assessing the threshold cost of a CTC scan. The recommended approach for conducting a cost-effectiveness analysis is to consider all relevant comparators (46
). Second, the studies used different estimates of CTC test characteristics, different assumptions about which findings at CTC would trigger referral for a follow-up colonoscopy, and different screening intervals. Finally, the previous studies used different approaches for identifying the threshold cost of a CTC scan. In one study (61
), threshold costs were identified so that the incremental cost per life-year gained for CTC compared with no screening was equal to the incremental cost per life-year gained for colonoscopy compared with no screening. In other studies, threshold costs were identified such that the incremental cost-effectiveness ratio of CTC screening compared with the next less effective strategy was less than a specified amount (60
) or equal to the incremental cost-effectiveness ratio for colonoscopy screening (62
), whereas in another study (59
), threshold costs were assessed to yield a prohibitively high incremental cost-effectiveness ratio of colonoscopy compared with CTC. In yet another study (58
), the threshold cost of CTC was calculated such that the total cost of the CTC strategy per life-year gained vs no screening equaled the total cost of the colonoscopy strategy per life-year gained vs no screening.
Overview of studies that estimated the cost-effectiveness of computed tomographic colonography (CTC) screening in the US population*
In conclusion, with the ongoing discussions about modifying the health-care system in the United States, much emphasis is being placed on comparative effectiveness research. Some worry that comparative effectiveness research will lead to the rationing of care (65
). This analysis highlights that comparative effectiveness research, and cost-effectiveness analyses in particular, can also be used to inform reimbursement levels. Our results suggest that CTC screening every 5 years provides a benefit in terms of life-years gained compared with no screening and provides only slightly fewer life-years gained than colonoscopy screening every 10 years. If CTC screening is reimbursed at roughly the same rate as colonoscopy, the cost, relative to the benefit derived and to the availability and costs of other colorectal cancer screening tests, is too high for it to be a cost-effective screening strategy. At the current test characteristics, CTC could be a cost-effective option for colorectal cancer screening among Medicare enrollees if the test cost was substantially less than that of colonoscopy or if its availability would entice a large proportion of otherwise unscreened persons to be screened.