Results
Sensitivity analysis results
In one-way sensitivity analyses comparing each screening strategy to NH, FIT consistently remained below the WTP threshold, demonstrating robustness to variations in parameter estimates. The model was most sensitive to the cost of FIT, cost of colonoscopy, and the specificity of FIT when comparing NH with FIT (Fig. 3).
Probabilistic sensitivity analysis indicated that with a WTP threshold of $11,692 per DALY averted, FIT was the cost-effective strategy in 66.9% of 10,000 iterations (Fig. 4).
We explored how varying levels of screening adherence impacted CRC outcomes and model results. At a 100% adherence rate to initial screening tests and all follow-up diagnostic testing (when applicable), FIT remained the preferred strategy, reducing CRC incidence and mortality by 49% and 61% respectively, with a lifetime cost per person of $119.26 and an ICER of $2,134.75 (Supplementary Table 3).
We further compared the performance of FIT and Colo under different follow-up adherence assumptions (Supplementary Fig. 2). As expected, the Colo strategy consistently produced greater reductions in CRC incidence and mortality at equivalent levels of initial screening adherence. However, similar outcomes were predicted with FIT under more favorable screening adherence levels. For example, a 20% reduction in CRC incidence could be attained with approximately 25% adherence to Colo, 40% adherence to FIT and 100% colonoscopy follow-up, or 55% adherence to FIT and 60% colonoscopy follow-up.
When varying screening start age, FIT was optimal if screening started at age 40 and 45, but Colo became the preferred strategy when screening started at age 50 (Supplementary Table 4). These results prompted us to evaluate a scenario of starting CRC screening with FIT at age 45 and switching to Colo at age 50, but this strategy was not on the efficiency frontier compared to the base case screening strategies (Supplementary Fig. 3). When high-risk adenoma surveillance ended at age 75 (instead of 85 in the base-case), FIT remained the preferred strategy (Supplementary Table 5).
Changes in CRC incidence also influenced the optimal strategy. When CRC incidence was halved, FIT remained optimal while when incidence was doubled, Colo emerged as the optimal strategy (Supplementary Table 6). We also assessed an alternative CRC stage distribution derived from US SEER 8 data which had a more favorable stage distribution than the single-institution retrospective data used in our base case scenario. Under this assumption, FIT remained the optimal screening strategy (Supplementary Table 7).
Discussion
In this study, we constructed a Markov decision-analytic model to analyze the cost-effectiveness of four established CRC screening strategies in the DR compared to the current status quo of no CRC screening. To our knowledge, this is the first published economic analysis to evaluate the cost-effectiveness of CRC screening in the DR or any Caribbean country. Biennial FIT was the optimal strategy, reducing CRC incidence and mortality by 30% and 37%, respectively, compared to no screening, assuming 60.6% adherence to FIT and 100% adherence to follow-up colonoscopy if FIT is positive. This strategy was estimated to require 371 lifetime colonoscopies per 1,000 persons screened at a lifetime cost of $101.39 per person. The resulting ICER was $2,134.75 per DALY gained, well below our WTP threshold set at the DR’s 2024 GDP per capita of $11,692, and far less than half of this value – and thus considered “very cost-effective” per WHO standards.26
Probabilistic sensitivity analysis showed that biennial FIT was the cost-effective strategy in 66.9% of 10,000 iterations of the base-case scenario. However, there were specific scenarios in which colonoscopy became the preferred strategy, namely if CRC screening was initiated at age 50 instead of age 45, and if CRC incidence in the DR doubled. In these scenarios, the ICER for colonoscopy was $9,390.74 and $6,107.10 respectively, which is below our WTP threshold set at the DR’s 2024 GDP per capita, but remains above the WHO’s “very cost-effective” threshold of half the GDP per capita. In a 2023 publication, Pichon-Riviere et al. empirically derive country-specific thresholds for health interventions for 174 countries using local health expenditures per capita and life expectancy at birth and show that in upper-middle income countries like the DR, the derived cost-effectiveness threshold per quality adjusted life year (QALY) gained was less than 1x GDP per capita for 100% of the countries included, and less than half the GDP per capita for 76% of countries included.26 Based on this analysis, any CRC screening intervention intended to be implemented in the public healthcare sector in the DR should cost less than half the GDP per capita threshold to be considered cost-effective. Only biennial FIT meets this criterion in our analysis. Results from our initial scenario analyses raised the possibility of implementing biennial FIT-based CRC screening for average-risk individuals between the ages of 45–50 and switching to colonoscopy-based CRC screening after age 50, especially if CRC incidence continues to steadily increase in the DR. However, compared to the base case screening strategies, this switching strategy was not on the efficiency frontier in a sensitivity analysis (Supplementary Fig. 3).
Our results strongly support the cost-effectiveness of CRC screening in the DR, but the practical and logistical steps necessary to implement such a program nationwide are numerous, and difficult to assess using modeling studies alone. Multiple studies, including several meta-analyses, have described the current landscape of CRC screening in low- and middle-income countries, consistently showing that screening in these settings is typically either unavailable or opportunistic in delivery and that most CRC cases globally are diagnosed when patients become symptomatic, as is currently the case in the DR. In MICs that do have CRC screening programs, FIT-based programs are the most common.11 Specifically, a systematic review and meta-analysis of CRC screening programs in Latin America identified CRC screening programs in only seven upper-middle or high-income countries in Latin America, with no programs in lower-middle income countries and no programs in Caribbean countries.12 Of the 17 identified programs, 13 were FIT-based, while only 4 were colonoscopy-based without prior FIT, likely reflecting the higher cost and resources needed for colonoscopy-based programs. The overall pooled adherence rate to FIT in this study was 85.8% and the follow up colonoscopy rate was 79.6%. These real-world data lend credibility to our base model inputs, which included 60.6% FIT adherence rate and 100% follow-up colonoscopy adherence rate. However studies from Uruguay and Cuba report much lower adherence to FIT (< 20% uptake in both countries),27, 28 and local data from a pilot CRC screening program in a private sector hospital in Santo Domingo, DR (Hospital General de la Plaza de la Salud) also suggest low adherence to screening FIT (< 20%) and low follow-up colonoscopy completion rates of 22% (Pumpalova, unpublished data). To address this limitation, we performed a sensitivity analysis comparing the impact of CRC screening at various adherence rates of the two top-performing strategies (Colo and FIT). Our results show that a 20% reduction in CRC incidence could be achieved with any of the following: 25% adherence to Colo; 40% adherence to FIT and 100% adherence to follow-up colonoscopy; 55% adherence to FIT with 60% follow-up; or 70% adherence to FIT with 40% follow-up. This may be particularly relevant, given evidence that FIT typically has higher uptake than Colo, and emphasizes the importance of patient navigation to ensure adherence to follow-up colonoscopy.29
While ours is the first study to evaluate the cost-effectiveness of CRC screening in the DR or any country in the Caribbean region, our findings are consistent with similar analyses done in other middle and upper-middle income countries. In 2012, Pinzon Florez et al published a Markov model evaluating the health and economic impact of six CRC screening strategies in Colombia and in 2015 a similar analysis was published for Argentina.30, 31 Both models recommended stool-based testing based on costs and cost-effectiveness thresholds, although colonoscopy-based screening strategies were more effective. In October 2024, Lu et al published a microsimulation model using Chinese epidemiological data to evaluate the clinical and economic impact of four CRC screening strategies at various national adherence rates.32 Like our study, the authors found that all strategies reduce CRC incidence and mortality compared to no screening, with colonoscopy outperforming FIT-based strategies at the same invitation rates. However, CRC screening using colonoscopy was associated with higher costs and a greater number of lifetime colonoscopies and like us, the authors conclude that biennial FIT-based screening strategies are the preferred strategy for China.
In MICs, colonoscopy capacity is often limited by lack of trained personnel, including gastroenterologists, anesthetists, and pathologists, as well as lack of infrastructure such as endoscopy suites. These limitations mean that endoscopy-based one-step CRC screening is unrealistic for much of the world. Our model outputs therefore account not only for cost-effectiveness, but also for feasibility in terms of lifetime colonoscopy demand. In the DR, the Sociedad Domincana de Gastroenterologia has 539 active members, roughly equating to 4.5 practicing gastroenterologists per 100,000 people in the general population, or 4.5 practicing gastroenterologists per 25,640 people within the CRC screening age.33 In our model, biennial FIT would require 371 lifetime colonoscopies per 1,000 people screened, equating to 9,275 colonoscopies per 25,640 people screened, or 2,113 lifetime screening colonoscopies per endoscopist, which is well within average expectations for gastroenterologists. By contrast, colonoscopy every 10 years would require 1,953 lifetime colonoscopies per 1,000 people screened, resulting in 11,127 lifetime screening colonoscopies per endoscopist. Additionally, these crude workforce estimates likely overstate true capacity, as both gastroenterologists and endoscopy infrastructure are disproportionately concentrated in larger cities such as the capital, Santo Domingo, leaving much of the country with severely limited access. Implementing a colonoscopy-based strategy will therefore require not only an increase in the number of trained specialists and endoscopy suites, but also a more equitable distribution of services, both of which will take time to achieve. Our model predicts that CRC screening using colonoscopy becomes increasingly cost-effective as CRC incidence increases in the DR, highlighting the importance of beginning investments in endoscopy capacity now to prepare the healthcare system for the growing demand as CRC incidence increases.
Our study has several strengths and some key limitations.
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We used a validated modeling framework for cost-effectiveness analyses, consistent with prior approaches, and compared multiple guideline-supported CRC screening strategies. We included lifetime colonoscopy demand as a model output, providing insight into feasibility and resource utilization alongside cost-effectiveness. Although this does not fully capture the real-world costs of implementing CRC screening programs in MICs, where limitations in trained personnel, infrastructure, and equipment may pose significant challenges, it is a meaningful starting point for assessing feasibility.
A
We also tested the robustness of our base-case results using a wide range of scenario and sensitivity analyses, which consistently supported biennial FIT as the preferred strategy in the DR. We derived costs using local data from SeNaSa and HGPS; however, this approach does not capture out of pocket costs, as well as differences in costs between public and private sectors, which may limit generalizability. Nonetheless, extensive sensitivity analyses demonstrated that the ICER for biennial FIT remained below the GDP-derived WTP threshold in both one-way and probabilistic sensitivity analyses. Our model incorporated all available data on CRC incidence and stage distribution from the DR, but this data was not always nationally-representative.
A
Specifically, stage-distribution data was derived from just one institution - INCART, the national referral hospital for cancer care in the Dominican Republic. We were unable to obtain nationally representative or single-institution data on CRC mortality from the DR, thus our model used CRC mortality data from SEER 1975–1985 to reflect worse cancer-specific outcomes in MICs. To account for uncertainty in CRC incidence, stage distribution, and outcomes after diagnosis, we calibrated multiple natural history models reflecting a range of plausible assumptions. Despite these strategies, the limited availability of DR-specific data may affect the generalizability of our results and highlights the need for improved cancer data collection in the DR.
Data from high-income regions of the world that have implemented population-level CRC screening using FIT show that at least 50% adherence to initial testing is necessary to meaningfully decrease CRC incidence and mortality on a population level, and that this is best achieved with organized national CRC screening programs.9 These studies, local data from DR, and our model all underscore the need for further investigation in the DR to understand what the barriers and facilitators are to improve adherence to CRC screening using FIT, and what interventions are necessary to ensure acceptability of FIT. Such studies are needed before large-scale roll out of CRC screening using FIT should be implemented.
All authors had direct access to all the data, significantly contributed to the manuscript and agreed to submit it for publication.
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All costs and DALYs represent per-person estimates accumulated over the modeled time horizon. Strategies connected by the line (NH, FIT, and Colo) lie on the cost-effectiveness frontier, representing the most efficient options. Sig and FOBT are absolutely dominated, meaning they result in higher costs and fewer DALYs averted compared to other strategies.
Model parameters were independently varied across a set range while all other parameters were held constant at their base-case value. Model parameters for test performance characteristics and costs are shown; parameters with the largest effect on the ICER are shown at the top and those with smallest effect are shown at the bottom. High and low estimate indication on either side of the EV indicate the direction that an increase or decrease in the model parameter changes the ICER. The tornado diagram shown compares no screening with our next most optimal strategy, biennial FIT.
Probabilistic sensitivity analysis (PSA) was performed for 10,000 simulations, jointly sampling input parameters from predefined distributions. Figure 4A plots the average per-person cost and DALYs averted for each simulation relative to no screening (NH). Points in the bottom left represent simulations with lower costs and fewer DALYs averted, while points in the top right represent higher costs and DALYs averted. Figure 4B presents the cost-effectiveness acceptability curve, which shows the probability that each strategy is the most cost-effective option across a range of WTP thresholds. The dashed vertical line indicates the base-case WTP threshold of $11,694, at which FIT was the most cost-effective strategy in 66.9% of simulations.