Cost-effectiveness estimates for developed countries (mainly USA and countries in Europe) have reported a wide range of incremental costs per life year for the colorectal cancer interventions examined in this, over and above that of treatment alone. Baseline costs per life year (in USD at 2000 price levels) relative to a no screening strategy for both the one-off and repetitive screening vary considerably. Seven studies reported costs per life year of $20,000 or more [49, 58–60, 69–71], eight reported in the range $10,000 - $19,999 [47, 48, 56–59, 62, 70], three between $5,000 - $9,999 [55, 57, 58] and three between $0-$4999 [56, 64, 88]. Some models even indicated incremental cost-savings (alongside effectiveness gains), both for one-off  and repeated screening interventions [56, 72].
Such wide ranges in the cost-utility ratio and the subsequent lack of dominance of any one screening mode (reflected by different rankings between the screening methods) are a consequence of the heterogeneous nature of the model specifications (on the effectiveness side), variations in the duration of operation of screening programmes and wide variations in the estimates of the interventions unit costs. These ranged considerably, with sigmoidoscopy costing between six  to 27 times  that of FOBT, colonoscopy costing between 10  to 100 times that of FOBT [57, 66]. Our estimates showed sigmoidoscopy and colonoscopy costs to be between 18 and 48 times that of the basic FOBT test. Additional research is clearly needed on estimating screening programme costs as these considerably affect the cost per DALY outcomes, especially in developing countries.
Our epidemiological model was simpler than most of published models and lacked refinements such as taking into account the distribution of multiple polyps and biphasic polyp dwelling times . In addition, our model did not include provision for more frequent screening of persons identified as having a polyp or with a familial history of CRC.
While our model was based on regional specific age and gender distributions, information on age-specific polyp incidence distribution was based only on available USA data. If a developing country's relative distribution of polyp incidence is skewed to a younger age than the USA, then this would mean that the screening programme would have a lower efficacy (unless screening ages were adjusted) and so our cost-effectiveness ratios are likely to be upwardly biased. On the other hand, our somewhat optimistic compliancy assumption that all persons screened positive on FOBT or Sigmoidoscopy would receive a subsequent colonoscopy served to downwardly bias the presented cost per DAYS, as some cases are likely to be lost to follow-up in practice.
Our estimated cost-effectiveness ratios for the incremental addition of various screening programmes to treatment (for comparability with the literature, discounted at 3% but not age-weighted; see Additional file 2) in AmrA of $800-$2,200 per DALY (for screening from age 50 to 80) and $2,400-$3,500 (for one-off interventions) fell towards the lower end of the wide spectrum of results presented in the opening paragraph of this discussion. This could be attributed to a variety of causes, such as the use of economic costs as opposed to charges or prices for procedures and the longer duration (relative to much of the literature) of the time-horizon used to evaluate our interventions. Inclusion of morbidity gains in our denominator reduced still further our ratios, although this was somewhat counterbalanced by our use of healthy life years in the denominator (as opposed to life years as reported in most of the literature).
In general the following policy recommendations could be inferred from our results. In subregions characterised by high income, low mortality and high existing treatment coverage (eg: AmrA subregion), both the incremental (ie: the additional cost per DALY of adding a screening programme to the existing treatment provision) and general (ie: compared to the null) cost-effectiveness results point to the very cost-effective nature of the screening intervention, although no particular specific intervention is indicated as being dominant.
In subregions characterised by low income, low mortality with existing treatment coverage around 50% (eg: EurC subregion), expanding treatment with or without combining it with screening programmes appears to be cost-effective or very cost-effective. Abandoning treatment in favour of funding screening programmes that would operate in a no treatment scenario would not be a cost-effective measure.
In subregions which have low income, low mortality and low treatment levels (eg; AfrE subregion), the best strategy is to provide resources to treat persons with colorectal cancer as opposed to providing a screening programme.
Use of the DRE alone was very cost-effective in the AmrA subregion and cost-effective in EurC. However it has low efficacy and provides a low level of absolute DALY gains. Despite its low technological approach, DRE is not cost-effective in the low incidence AfrE subregion. However, the low cost simple DRE (both with and without follow-up diagnostic colonoscopy), suffers from a lack of direct evidence that the exam reduces mortality from colorectal cancer, our modelled efficacy being based on a single no-significant result (OR = 0.96, 95% CI 0.56-1.70) from a case control study from northern California . Sensitivity is low, as fewer than 10% of colorectal cancer causing polyps are within reach of the examining finger. There is therefore no solid basis for recommending this method as a stand alone screening intervention for colorectal cancer. Moreover, a comprehensive assessment of this intervention should include its effect on reducing mortality from prostate cancer.
Like the digital rectal examination, the introduction of a fruit and vegetable campaign gains fewer DALYS then any of the screening interventions. Such a campaign was however found to be very cost effective in AmrA even without the inclusion of additional benefits resulting from decreases in other diseases. The fruit and vegetable campaign was marginally cost-effective in EurC, but was not cost-effective at all in AfrE. However, the external validity of applying the effectiveness results from one health promotion campaign in Australia  to other regions of the world can be questioned.
The 20% price subsidy will actually be less effective than health promotion in increasing fruit and vegetable consumption, and hence in reducing colorectal cancer. Estimating the economic cost of such an intervention is beyond the scope of this paper. Moreover, an evaluation of such an intervention requires the effectiveness benefits of reductions in heart disease, stroke and other cancers to be included. The cost per DALY, however, might be underestimated since the income freed up by the food subsidy might result in increased consumption of red meat, which could well be a risk factor for colorectal cancer [26, 27].
Our use of a single measure of relative risk reduction for each age and gender specific intervention simplifies the reality, where the risk reduction and subsequent cost-effectiveness ratio can differ depending on the socio-economic context of the screening subgroups . One could also argue that present models on colorectal cancer screening are inadequate for aiding public health decision-making because the efficacy evidence is too preliminary for any screening modality other than FOBT . Lack of such randomized controlled trial evidence precluded an evaluation of immunological FOBT testing, which is likely to yield lower costs per QALY than guaiac-based tests , due to the higher sensitivity of immunological FOBT to detect colorectal neoplasms [90–92] outweighing increased unit costs. Our analysis also did not consider the options of targeting screening to high-risk populations which despite reducing the overall DALY gains may well increase the cost-effectiveness of the interventions .
The CEAs presented represent first order point estimates of various interventions. When allowance is made for variations of the estimates by sensitivity analysis then it appears there is no clear discernable difference in terms of cost-effectiveness between the major screening options. Perhaps another key factor in deciding what option or mix of options to adopt, would be those interventions which have the highest expected attainable coverage rates. Adoption of screening policies between the ages of 50 and 80 will only eradicate a small portion (between 14%-24%) of the existing colorectal cancer burden, since the application of the compliancy rate to the intervention efficacy, even in the case of colonoscopy every 10 years will only result in a 24.1% reduction in incidence. One-off screening policies will reduce an even lower percentage of the total disease burden.
The cost-effectiveness ratios are insensitive to changes in compliancy, particularly in scenarios that include access to treatment and where programme operational overheads are low. Basically, the increases or decreases in programme efficacy resulting from changes in compliancy are somewhat counterbalanced (except for the programme cost overheads) by decreases or increases in costs.
The cost-effectiveness ratios are also biased upwards (or downwards) to the extent that transport costs and costs of work lost due to treatment exceed (or are exceeded by) the transport costs and costs of work lost due to screening [93, 94].
Decisions to adopt interventions are usually made by health services and governments at the country level. Although the model used in this analysis is based on regions, the parameters defining the model can be adjusted to country level.