Cost effectiveness analysis of colorectal cancer screening modalities in Kuwait: Comparison of Three Alternative Screening Strategies

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Tolma, Mahmoud Annaka, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4654485/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Mar, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Colorectal cancer (CRC) poses a significant health challenge in Kuwait, ranking as the second most common cancer with a 2019 incidence rate of 13.2 cases per 100,000 people. This study evaluates the cost-effectiveness (CEA) of CRC screening methods from the perspective of Kuwait's healthcare providers. Using a Decision Tree Analysis Model, the study compared three screening modalities: Fecal Occult Blood Test (FOBT) followed by colonoscopy or sigmoidoscopy, colonoscopy alone, sigmoidoscopy alone and alongside no screening. Over a 10-year period post-diagnosis, the model tracked costs and outcomes based on CRC patients' life expectancy, expressing results using Incremental Cost Effectiveness Ratios (ICERs). Result: FOBT followed by colonoscopy or sigmoidoscopy emerged as the most cost-effective option, costing USD 3,573.00 and yielding 7.7 Quality-Adjusted Life Years (QALYs). In comparison, no screening resulted in 7.2 QALYs at USD 4,084.00, while sigmoidoscopy and colonoscopy alone provided 6.8 QALYs each, costing USD 4,905.00 and USD 5,002.00, respectively. Sensitivity analyses explored uncertainties in cost and outcome estimates. Conclusion: FOBT followed by colonoscopy or sigmoidoscopy could efficiently utilize healthcare resources compared to other modalities or no screening. This approach offers critical guidance for healthcare policymakers in Kuwait, advocating for the adoption of combined FOBT and colonoscopy or sigmoidoscopy strategies to enhance CRC screening effectiveness and economic efficiency. Biological sciences/Cancer Health sciences/Health care Health sciences/Oncology Cost-effectiveness Colorectal cancer Fecal occult blood testing Colonoscopy Sigmoidoscopy Figures Figure 1 Figure 2 Figure 3 Introduction According to a recent study on the Global Burden of Diseases, CRC stands as the second most prevalent cause of cancer-related mortality globally, claiming approximately 1.1 million lives annually and constituting 9.7% of all cancer-related Disability-Adjusted Life Years 1 . This underscores the significance of CRC as a pressing public health concern globally 2,3 . In Kuwait, CRC is the second most common cancer after breast cancer 4 . Data from the Kuwait Cancer Registry shows that between January 2010 and December 2019, there were 2,710 cases of CRC, accounting for approximately 10.2% of all cancer cases in the country. During this period, the age-standardized incidence rate of CRC in Kuwait was 13.2 per 100,000 people, which is lower than the global estimated rate of 19.7 per 100,000 4 . Early detection of colorectal cancer allows for treatment before it becomes incurable, potentially lowering cancer mortality. Preventive cancer screening aims to identify and remove precursor lesions, like colorectal adenomas, to prevent cancer development. Consequently, preventive screening can reduce both the incidence of cancer and the associated mortality 5 . In the United States of America (USA), US Preventive Services Task Forces recommends screening for colorectal cancer in all adults aged 50 to 75 years to select from a number of suggested screening strategies such as FOBT, colonoscopy, sigmoidoscopy 6 , meanwhile European Union (European Guide for Quality National Cancer Control Programmes) recommends CRC screening with a Guaiac Fecal Occult Blood Test (gFOBT) or immunochemical Fecal Occult Blood Test (iFOBT) for the age group 50–74 years, for all adult’s women and men 7 . In Kuwait, only one pilot program for CRC screening targeting asymptomatic average‑risk individuals aged 45–75 years has been launched in mid‑2015. The most widely utilized screening technique for early CRC detection in Kuwait's public hospitals is colonoscopy. Sigmoidoscopy and FOBT are two others widely used CRC screening methods 8 . Economic evaluation is a systematic and formal way of assessing the costs and benefits of screening interventions. There are a number of methods for screening for CRC; colonoscopy, one of the most widely used interventions, has been associated with relatively high accuracy performance 9 . In contrast, the FOBT is easier to use and less expensive than colonoscopy 10,11 . Until recently, gFOBT was the only test for which there was strong evidence of efficacy from randomized controlled trials (RCTs). The choice to base UK colorectal cancer screening programs on gFOBT was supported by data of a 16% mortality decrease following repeated screening with gFOBT 12 . FOBT screening has been shown to be beneficial in lowering the annual incidence eand death of CRC 13 . Alternative methods for CRC screening include colonoscopy and flexible sigmoidoscopy 14 , while US population-based case control studies have demonstrated a respectable decrease in yearly mortality with colonoscopy screening 15,16 . A randomized controlled trial (RCT) should ideally offer concrete empirical proof of the relative efficacy of different CRC screening techniques. Prior RCTs were intended to randomly assign participants into a regular FOBT screening group in order to capture such long-term CRC risk; however, no screening group persisted for at least ten years 17–21 . One-time colonoscopy and FOBT are being compared for effectiveness in a randomized controlled trial (RCT), which is anticipated to be finished in 2021 22 . Cost-effectiveness analysis (CEA) offers decision-making and rationale for effective resource allocation under a set budget restriction, aiming to strike a balance between costs and effectiveness incurred by CRC screening. The most cost-effective procedures in terms of live years (LYs) gained for an average-risk population are annual FOBT plus 5-yearly sigmoidoscopy under full compliance rate 23 and colonoscopy every 10 years 24 , according to cost-effectiveness modeling conducted on the U.S. population. According to a study conducted on a population in Hong Kong, the incremental costs of colonoscopy and FOBT compared to no screening were US $ 7,211 and US $ 6,222 per life year gained, respectively 25 . According to UK research studies, the most economical screening approach was to use only biennial FOBT since it was projected to have an incremental cost of less than £3,000 per QALY when compared to no screening 26,27 . Despite Kuwait's population having a lower incidence of CRC than developed nations, there is currently no established strategy for CRC screening for Kuwaitis. There has never been a cost effectiveness analysis (CEA) of CRC screening on Kuwaiti populations in terms of the gain in QALYs. Thus, this study's objective was to evaluate the relative cost-effectiveness of the three main CRC screening methods: sigmoidoscopy, colonoscopy, and FOBT followed by either sigmoidoscopy or colonoscopy. Methodology Study population A population-based statewide program for CRC screening was compared to no screening in a cost-effectiveness analysis, with adults in Kuwait between the ages of 50 and 80 being identified as being at risk for colorectal cancer. Three screening options were taken into consideration: yearly FOBT followed by sigmoidoscopy or colonoscopy, sigmoidoscopy every five or ten years, and colonoscopy every ten years (Table 1 ). CRC screening strategy: Table 1 CRC Screening strategies used in this study Strategies Interval (Years) Time Horizon Age at Screening (Years) Outcome Measures Incremental Cost-Effectiveness Ratio (ICER) No Screening - Lifetime 50–80 QALYs Cost/QALYs FOBT 1 Lifetime 50–80 QALYs Cost/QALYs Sigmoidoscopy 5 Lifetime 50–80 QALYs Cost/QALYs Sigmoidoscopy 10 Lifetime 50–80 QALYs Cost/QALYs Colonoscopy 10 Lifetime 50–80 QALYs Cost/QALYs Development of an economic model A decision tree analytic model was developed to conduct a cost-effectiveness analysis of various CRC screening modalities compared to no screening option. The model compared costs and outcomes of three major screening modalities for CRC which are (i) colonoscopy, (ii) sigmoidoscopy and (iii) Fecal Occult Blood Test (FOBT) followed by colonoscopy or sigmoidoscopy compared to no screening option. The model is presented in the supplementary document (Fig. 1 and Appendix A). This model adopted the third-party payer's perspective, in this case, the Kuwait Ministry of Health, to examine costs and outcomes associated with colorectal cancer screenings. This model tracks costs and outcomes for 10 years post-diagnosis based on the documented life expectancy of patients with colorectal cancer. All cost estimates were adjusted for inflation to the year 2023. For the cost-effectiveness analysis, a willingness to pay (WTP) threshold of 1 GDP per capita was used. The final output of the model was expressed in terms of Incremental Cost Effectiveness Ratio (ICER) comparing those alternatives. ICER was calculated between two alternatives to determine the magnitude of the cost-effectiveness of the various CRC screening modalities. For the ICER, a standard WHO threshold of cost-effectiveness wereused 28,29 . The uncertainties were assessed for any parameters estimated through deterministic and probabilistic sensitivity analyses. The findings were presented in an ICER table and diagrams accordingly. Model parameters including probabilities, costs, and outcomes were derived from primary data collection, expert’s opinions and published sources. Sensitivity analyses were used to account for uncertainty in these estimates. (1) Cost Information All cost information used in this model from the healthcare provider perspective, included screening cost and management cost of CRC patient. Indirect cost that are incurred by the patients such as transportation, meal, caregiver and loss of productivity were not included. The cost of FOBT, Colonoscopy and Sigmoidoscopy were extracted from existing Kuwait MOH charges 30 . The management cost of CRC patient by stage level was computed by multiplying the length of stay (LOS) of each CRC patient with the existing average unit cost per day of stay in the Kuwait government hospital 31 . The existing unit cost was computed in the year 2017. The adjusted inflation with multiple years was made for the year 2023. Local costs evaluated in Kuwaiti Dinar in year 2023 were converted to US dollar (USD) which exchange rate of 1 Kuwaiti Dinar = 3.254 USD. Refer to the Table 2 for the list of cost information. Table 2 List of cost information Costs information Cost (USD) Source Cost of screening with colonoscopy 293.00 [ 30 ] Cost of screening with sigmoidoscopy 195.00 [ 30 ] Cost of screening with Fecal Occult Blood Test (FOBT) 6.50 [ 30 ] The cost of managing a patient is stage 1 cancer 839.50 [ 31 ] The cost of managing a patient is stage 2 cancer 1,682.00 [ 31 ] The cost of managing a patient is stage 3 cancer 5,955.00 [ 31 ] The cost of managing a patient is stage 4 cancer 7,159.00 [ 31 ] Cost of death/cancer-free 0.00 NA (2) Effectiveness of health outcome To measure the health outcomes of the various screening alternatives, the values of QALYs were used. The QALY was imputed to the model by incorporating utility values from published studies multiplied by the duration of the time spent in the disease state, which in this study was 10 years. The 10-year cut-off point was used based on the reported life expectancy of CRC patients 32 . The utility values are described in Table 3 . Table 3 List of utility value of CRC patient by stages from published studies Utility Utility value Source Well patient (cancer-free) 1 [ 32 ] Patient with stage 1 cancer 0.8 [ 32 ] Patient with stage 2 cancer 0.8 [ 32 ] Patient with stage 3 cancer 0.7 [ 32 ] Patient with stage 4 cancer 0.6 [ 32 ] Death 0 [ 32 ] (3) Probability data All the probabilities that were incorporated in the cost-effectiveness model were obtained from published literature and expert’s inputs. The values used are described in Table 4 : Table 4 List of CRC probability detection rate by various CRC screening modalities and probability of CRC by stages, cancer free and death from published studies. Probability Value Source Positive detection rate with colonoscopy 0.93 [ 33 ] Positive detection rate with sigmoidoscopy 0.93 [ 33 ] Positive detection rate with Fecal Occult Blood Test (FOBT) 0.72 [ 33 ] Remain at stage 1 0.001 [ 34 , 35 , 36 ] Stage 1 to Stage 2 0.016 [ 34 , 35 , 36 ] Stage 1 to stage 3 0.018 [ 34 , 35 , 36 ] Stage 1 to stage 4 0.023 [ 34 , 35 , 36 ] Stage 1 to cancer-free 0.908 [ 34 , 35 , 36 ] Stage 1 to Death 0.034 [ 34 , 37 ] Remain at stage 2 0.029 [ 34 , 35 , 36 ] Stage 2 to stage 3 0.033 [ 34 , 35 , 36 ] Stage 2 to stage 4 0.044 [ 34 , 35 , 36 ] Stage 2 to cancer-free 0.781 [ 34 , 35 , 36 ] Stage 2 to Death 0.113 [ 34 , 37 ] Remain at stage 3 0.08743 [ 34 , 35 , 36 ] Stage 3 to Stage 4 0.11528 [ 34 , 35 , 36 ] Stage 3 to cancer-free 0.49629 [ 34 , 35 , 36 ] Stage 3 to Death 0.30100 [ 34 , 37 ] Remain at stage 4 0.343 [ 34 , 35 , 36 ] Stage 4 to Death 0.657 [ 34 , 37 ] (4) Assumptions In the model, several assumptions were made given the unavailability of the data. Firstly, it was assumed that, following the screening and disease staging, the probability of patients diagnosed at various stages of colorectal cancer (stage 1 to 4) is the same, and therefore probability of 0.25 was applied for each stage. Secondly, following FOBT, the probability of disease confirmation through colonoscopy and sigmoidoscopy is also the same and a probability of 0.5 was applied for each alternative. In the no-screening option, the number of patients with colorectal cancer was based on the information of the under-reported cases which was 63%. Therefore, the probability of 0.63 was applied 33 . Following that the distribution of patients in each stage of CRC was based on data from published studies 38,39,40 . Regarding the probability of patients at various stages of cancer, mathematical calculations were imputed in which the probabilities were first determined through the survival rate to determine the probability of death. Subsequently, the remaining probabilities were further distributed according to the weightage for each stage of cancer. The weights used were based on published literature 38,39 . Results Using base-case estimates, it was found that the screening modality with the FOBT followed by colonoscopy or sigmoidoscopy was the only undominated option. The other two modalities, which are colonoscopy and sigmoidoscopy, as well as the alternative with no screening, were all dominated by the FOBT followed by colonoscopy and sigmoidoscopy. It was found that CRC screening with FOBT followed by colonoscopy or sigmoidoscopy would cost USD 3573.00 compared to USD 4084.00, USD 4905.00, and USD 5002.00 for no screening option, screening with sigmoidoscopy and screening with colonoscopy, respectively. Regarding the QALYs, CRC screening with FOBT followed by colonoscopy or sigmoidoscopy would result in 7.7 compared to 7.2, 6.8 and 6.8 QALYs for no screening option, screening with sigmoidoscopy and screening with colonoscopy, respectively. In comparison to the CRC screening with the FOBT followed by colonoscopy or sigmoidoscopy, no screening option would result in an ICER of -1010.00. Also, compared to the same alternative, sigmoidoscopy and colonoscopy would result in ICERs of -1498.06 and − 1607.16 respectively. Based on these results, it shows that alternatives other than the CRC screening with FOBT followed by colonoscopy or sigmoidoscopy are less effective and will also increase cost. Therefore, it is obvious that the FOBT followed by colonoscopy or sigmoidoscopy option is dominant compared to other alternatives. Table 5 describes the ICERs of all four alternatives. Table 5 Cost, Incremental cost, QALYs per person (Effectiveness of health outcome) for each screening strategy, incremental effectiveness, and ICER compared with FOBT followed by colonoscopy or sigmoidoscopy. Alternatives Cost (USD) Incremental cost (*comparison with the undominated alternative) Effectiveness (Outcomes) Incremental effectiveness ICER FOBT followed by colonoscopy or sigmoidoscopy 3573 7.7 No screening 4084 511 7.2 -0.5 -1010.00 Sigmoidoscopy 4905 1332 6.8 -0.9 -1498.06 Colonoscopy 5002 1429 6.8 -0.9 -1607.16 Sensitivity analysis To test the effect of single variables on the overall economic conclusion from this model, multiple one-way sensitivity analyses were conducted. The tornado diagram (Fig. 2 ) was used to visually demonstrate the resulting Incremental Cost Effectiveness Ratios (ICERs) when one variable is changed to become either the maximum or minimum value of the range provided. It is used to identify the relative importance of a variable since it can demonstrate if the economic conclusion changes based on changing the variable. In an ICER tornado diagram, the importance of each variable on the economic conclusion is presented from top to bottom. The tails of each bar indicate the maximum and minimum ICER for each variable. The dashed line represents the ICER from the reference case to provide a reference for the changes in ICERs. In this study, 14 parameters were used in the multiple-1-way sensitivity analyses. All the included parameters with the lower value and upper value used are presented in the table below. The values were taken from the published studies and also expert input as shown in Table 6 . Table 6 14 parameters were used in the multiple-1-way sensitivity analyses Parameters Lower value Upper value Source 1 Positive detection rate with colonoscopy 0.75 0.95 [ 40 ] [ 43 – 46 ] 2 Positive detection rate with sigmoidoscopy 0.75 0.95 [ 40 ] [ 43 – 46 ] 3 Positive detection rate with Fecal Occult Blood Test (FOBT) 0.5 0.85 [ 40 – 42 ] 4 Cost of screening with colonoscopy 276 309 [ 30 ] 5 Cost of screening with sigmoidoscopy 179 211 [ 30 ] 6 Cost of screening with Fecal Occult Blood Test (FOBT) 4.9 8.2 [ 30 ] 7 Cost of managing a patient with Stage 1 cancer 420.50 6300.50 [ 31 ] 8 Cost of managing a patient with Stage 2 cancer 841.00 12601.00 [ 31 ] 9 Cost of managing a patient with Stage 3 cancer 841.00 32762.00 [ 31 ] 10 Cost of managing patients in stage 4 of cancer 841.00 127689.00 [ 31 ] 11 Utility for patients with stage 1 cancer 0.3 1 [ 32 ] 12 Utility for patients with stage 2 cancer 0.3 1 [ 32 ] 13 Utility for patients with stage 3 cancer -0.594 1 [ 32 ] 14 Utility for patients with stage 4 cancer -0.594 1 [ 32 ] To conduct the sensitivity analysis, two alternatives were chosen which are the FOBT followed by colonoscopy or sigmoidoscopy. The results of the multiple-1-way sensitivity analyses demonstrated that this CEA model was most sensitive to the cost of managing patients in stages 4, 3 and 2 of the cancer as illustrated Fig. 2 . Based on the results of the multiple-1-way sensitivity analyses, the parameters tested for sensitivity analysis changed the magnitude of ICER. The tornado diagram shows that all the parameters tested resulted in further negative ICERs when a higher value was set. Subsequently, a Probabilistic Sensitivity Analysis (PSA) was done for multivariate analysis using TreeAge Pro software. In the PSA, instead of changing one parameter value at a time, all variables were changed at once according to their plausible values by random sampling from their distributions. The model was simulated 10,000 times in the PSA from the probability distribution of each parameter. All cost data were assigned to a gamma distribution. Utility data followed a beta distribution. The cost-effectiveness scatterplot was used to test the stability of the model results. Based on the multiple-1-way sensitivity analyses, parameters that were sensitive to the changes of ICER were identified and applied for the PSA. The parameters included the cost of disease management for all the stages of colorectal cancer and utility value for stage 4 of the cancer. In this study, when the ICERs from the PSA are plotted onto the cost-effectiveness plane, comparing sigmoidoscopy and FOBT followed by colonoscopy or sigmoidoscopy, it demonstrates that more than 95% of the outcomes are located to the right (dominant) of the willingness to yay (WTP) lines. Based on the 10000 iterations, all negatives ICERs were obtained. This finding demonstrated that the sigmoidoscopy is a dominated alternative compared to FOBT followed by colonoscopy or sigmoidoscopy. The result of the PSA is illustrated in Fig. 3 . Discussion The decision tree model analysis conducted in this study aimed to assess the cost-effectiveness of various screening strategies for CRC detection. The findings from the analysis provide valuable insights into the economic implications and health outcomes associated with different screening modalities. The results of the decision tree analysis indicate that CRC screening with FOBT followed by colonoscopy or sigmoidoscopy would cost USD 3573.00 compared to USD 4084.00, USD 4905.00, and USD 5002.00 for no screening option, screening with sigmoidoscopy and screening with colonoscopy, respectively. Regarding the QALYs, colorectal cancer screening with FOBT followed by colonoscopy or sigmoidoscopy would result in 7.7 compared to 7.2, 6.8 and 6.8 QALYs for no screening option, screening with sigmoidoscopy and screening with colonoscopy respectively. This suggests that implementing FOBT-based screening programs could potentially lead to significant cost savings while effectively detecting and preventing CRC. This study findings in lines with several meta-analyses spanning from 1998 to 2016 have assessed the efficacy of CRC screening with gFOBT. While some varied in the trials they included, overall, they consistently showed a modest but significant reduction in CRC mortality. The relative risks for CRC mortality ranged from 0.82 to 0.87. A pooled estimate from the Minnesota and Nottingham trials, involving over 220,000 individuals with a median follow-up of 14.25 years, indicated an 8% reduction in late-stage CRC incidence with gFOBT screening 47–49 . Regarding the cost saving, this study finding also in lines with the majority study across the world. The cost-effectiveness of gFOBT screening for CRC has been assessed in several studies over the years. Helm et al. (2000) estimated the cost-effectiveness of gFOBT based on trials conducted in Minnesota, Nottingham, and Funen, was acceptable 50 . Whynes et al. (2004) followed up on the Nottingham trial, reaffirming the cost-effectiveness of gFOBT screening 51 . Three systematic reviews by Pignone et al. (2002), Lansdorp-Vogelaar et al. (2011), and Patel & Kilgore (2015) evaluated the cost-effectiveness of gFOBT or FIT compared to no screening 52–54 . These reviews consistently found gFOBT screening to be cost-effective, with costs per life year gained ranging from USD 5691 to USD 17,805 in Pignone et al. (2002) and from cost savings to USD 56,300 per life year gained in Lansdorp-Vogelaar et al. (2011). Patel & Kilgore (2015) included additional studies and confirmed the cost-effectiveness of gFOBT CRC screening strategies and cost savings compared to no screening 54 . Ladabaum & Mannalithara (2016) updated their model with new CEA results of CRC screening using gFOBT, showing cost savings 58 . These studies support the findings of Patel & Kilgore (2015) and assess both gFOBT and the fecal immunochemical test (FIT). Kingsley et al. (2016) and Barzi et al. (2017), along with a study in the Republic of Korea by Lee & Park (2016), found cost savings for annual FIT and gFOBT 55–57 . Outside the USA, 14 new studies have been published since Lansdorp-Vogelaar et al.'s review in 2011, evaluating the cost-effectiveness of gFOBT or FIT screening. These studies, conducted in Canada, Europe, and Asia (including the Middle East), predominantly show that FOBT screening is cost-saving 59–71 . Furthermore, the individual screening modalities of sigmoidoscopy and colonoscopy, while demonstrating similar effectiveness scores of 6.8, incur significantly higher costs compared to the FOBT-based strategy. Sigmoidoscopy incurs an incremental cost of USD 1332 and an ICER of USD 1498.06, while colonoscopy incurs an incremental cost of USD 1429 and an ICER of - USD 1607. These findings highlight the economic trade-offs associated with more invasive screening procedures. To date, only two methods have been assessed in RCTs to investigate reductions in CRC incidence or mortality: gFOBT and sigmoidoscopy. This section deals with comparisons between major endoscopic and stool-based CRC screening methods (i.e.,sigmoidoscopy or colonoscopy vs gFOBT or FIT) in terms of mortality or incidence outcomes, ADRs, and cost–effectiveness. No RCT is available that directly compares two or more CRC screening tests. Evidence comes from indirect comparisons of observational studies and from indirect meta-analyses, so-called network meta-analyses using Bayesian statistics 72 . Combining FOBT with colonoscopy or sigmoidoscopy in this study was a cost-effective screening strategy. This finding is also consistent with several studies that have been published, showing significant results. In the study by Littlejohn et al. (2012), which reviewed six studies comparing sigmoidoscopy with FOBT for detecting advanced adenoma and colorectal cancer (CRC), it was found that sigmoidoscopy, either alone or combined with FOBT, was more effective in detecting advanced adenoma compared to FOBT alone 73 . Similar results were observed for the detection of CRC. In a trial conducted in Norway by Holme et al. (2014), involving approximately 100,000 participants, the detection rates of advanced adenoma and CRC were similar between sigmoidoscopy alone and a combination of FIT with sigmoidoscopy. Both methods showed increases in detection rates compared to no screening 74 . The study in the United Kingdom by Berry et al. (1997) found that the screening strategy combining gFOBT with flexible sigmoidoscopy had a detection rate of 0.8% for advanced adenoma and 0.1% for colorectal cancer 75 . A similar study was also conducted by Verne et al. (1998), which found detection rates of 0.1% for advanced adenoma and 0.1% for colorectal cancer 76 . Another study by Holme et al. (2014) found that flexible sigmoidoscopy combined with FIT had detection rates of 4.5% for advanced adenoma and 0.3% for colorectal cancer patients. Another similar study by Sekiguchi et al. (2016), using a screening strategy of colonoscopy combined with annual FIT, found that the combination of colonoscopy and annual FIT was superior to annual FIT alone 77 . Sensitivity analyses were used to account for uncertainty in these estimates. To test the effect of single variables on the overall economic conclusion from this model, multiple one-way sensitivity analyses and a PSA has been used to evaluate the impact of varying parameters on ICERs. The tornado diagram highlighted the sensitivity of economic conclusions to individual parameter changes, with the cost of managing patients in advanced cancer stages having the most significant influence on ICERs. All parameters tested resulted in increasingly negative ICERs with higher values. The PSA, involving simultaneous changes to all variables, revealed that sigmoidoscopy was dominated compared to gFOBT followed by colonoscopy or sigmoidoscopy, with more than 95% of outcomes positioned to the right of the willingness-to-pay lines on the cost-effectiveness plane. In conclusion, our model were robust in sensitivity analyses as relevant variables such as costs of screening tests (FOBT, Sigmoidoscopy and colonoscopy), CRC management cost by stages, different FOBT cut-offs, changes in stages of the detected cancers and performance of the screening tests did not change the conclusions of the model, favoring FOBT followed by colonoscopy or sigmoidoscopy screening, as this programme remained cost-effective. Limitations and Future Directions It is important to acknowledge certain limitations of this study. First, the costs of CRC screening were calculated from the healthcare provider perspective (Kuwait MOH). The cost of lost productivity, meal, cost of transportation and caregiver is not included. Second, the model did not incorporate the potentially high cost of establishing a national screening program in Kuwait, including the costs of addressing adherence, public health campaigns to change attitudes toward CRC screening or other methods at the provider level to increase adherence as a reference the other paper that we just published 78 . Third, the utility data were measured by cross-sectional study rather than randomized controlled trial with sufficient follow-up periods, which involves the consideration of time-dependent utility data in the short and long term. To our knowledge this is the first cost-effectiveness analysis focusing on screening strategies for colorectal cancer in Kuwait and has the potential to contribute significantly to the knowledge base guiding rational decision making with respect to clinical practice and health care resource allocation. If acted upon, the findings of our study may substantially improve CRC care in Kuwait and can be used to concentrate efforts on developing a national screening program The decision tree analysis model relies on various assumptions (14 parameters) regarding the accuracy of screening tests, the effectiveness of treatment interventions, the probability of each CRC screening positive etc. Future research could address these limitations by incorporating real-world data and conducting sensitivity analyses to validate the robustness of the findings. Implications for Practice and Policy FOBT CRC screening presents a non-invasive, safe, and easily implementable alternative to colonoscopy screening. In contrast to the invasive nature of colonoscopy, FOBT involves minimal discomfort and presents considerably lower risks to patients. Not only does FOBT mitigate the risks inherent in invasive procedures like colonoscopy, including the potential for bleeding due to perforation, pain, and the arduous preparation process, but it also serves as a convenient and accessible means for early detection of colorectal cancer. Therefore, advocating for the widespread adoption and promotion of FOBT screening can significantly bolster public health initiatives aimed at reducing colorectal cancer incidence and mortality rates Despite the limitations, we believe that the study can contribute to the design of better and more efficient CRC screening policies in Kuwait. Our results, strong suggest, that the combination of CRC screening strategy such as Fecal Occult Blood Test (FOBT) followed by colonoscopy or sigmoidoscopy, can be considered replacing the colonoscopy screening alone or sigmoidoscopy screening alone. Finally, the implementation of an organized screening strategy should include a cost-effectiveness analysis of the different screening modalities so that the governments can take more rational decisions and better allocate resources in healthcare. Conclusions FOBT followed by colonoscopy or sigmoidoscopy screening for CRC is more cost effective than colonoscopy screening alone and sigmoidoscopy screening alone, presenting as a screening strategy affordable to the society, robust for a wide range of relevant clinical and cost variables and not requiring an extraordinary demand in extra capacity. This further supports the progressive implementation of FOBT followed by colonoscopy or sigmoidoscopy-based programmes in Kuwait. Future studies in other countries using realistic adherence rates are needed, to corroborate our conclusions. Declarations Ethics approval and consent to participate The study adhered to the principles of the Declaration of Helsinki and was approved (approval# 2017/694) by the Kuwait Ministry of Health Standing Committee for the Coordination of Health and Medical Research (Ethics Committee). All participants filled out a written informed consent for participation in the study. Competing interests The authors declare that they have no competing interests. Funding This research was conducted with Kuwait Foundation for the Advancement of Sciences (KFAS). Funding [No: PN19-13BH-01]. Author Contribution SMA, ELT, AMN, MA, RA, AE were involved in the design of the study. AMN and SMA were involved in data analysis, interpretation, and critical revision of the manuscript. MA, RA, AE, ELT, WQA, SMA were involved in data validation. AMN wrote the manuscript. AMN was involved in project administration. All authors reviewed and approved the final draft of the manuscript. Acknowledgement We would like to acknowledge the financial support we received from Kuwait Foundation for the Advancement of Sciences (KFAS) to undertake this study. We would also like to extend our gratitude to Kuwait University’s Health Sciences Center Ethical Committee and the Standing Committee for Coordination of Health and Medical Research, Ministry of Health, Kuwait, for providing ethical approval to conduct this research. We would also like to acknowledge Dr. Mahmoud Annaka and Dr. Rihab Al Wotayan (Department of International Health Relations, Kuwait MOH), Dr. Amani Elbasmi (Unit of epidemiology and cancer registry, Kuwait Cancer Control Centre, Ministry of Health Kuwait), and Mrs. Maryam (Head of Medical Records of KCCC) for their valuable input in this study. Data Availability The data that support the findings of this study are available from the Kuwait Cancer Control Centre (KCCC) and Kuwait Ministry of Health, but restrictions apply to the availability of these data, and so are not publicly available. Data are however available from Dr. Amrizal Nur upon reasonable request and with permission of the Kuwait Ministry of Health. References Jonathan MK et al . Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019. A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncology . 8 (3):420-444. doi:10.1001/ jamaoncol.2021.6987 (2022). Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin . 68 (6):394–424. doi:10.3322/caac.21492 (2018). Vekic B, Dragojevic-Simic V, Jakovljevic M, et al . A correlation study of the colorectal cancer statistics and economic indicators in selected Balkan countries. Front Public Health . 8 :29. doi:10.3389/ fpubh.2020.00029 (2020). El-Basmy, A., Kuwait Cancer Registry: Annual Report 2019 Kuwait Cancer Control Center Kuwait p. 122 (2019). Jodal HC, Helsingen LM, Anderson JC, et al . Colorectal cancer screening with faecal testing, sigmoidoscopy or colonoscopy: a systematic review and network meta-analysis. BMJ Open . 9 : e032773. doi:10.1136/ bmjopen-2019-032773 (2019). https://www.uspreventiveservicestaskforce.org/home/getfilebytoken/2Wc3FRHpVDPX2jT_WzjEXX (Accessed, June 14, 2024) Albreht T, Conroy F, Dalmas M, et al. European Guide for Quality National Cancer Control Programmes. Ljubljana, Slovenia: National Institute of Public Health (2015). Fadhil I, Al Hammod S. Colorectal screening programs in gulf countries: The role of primary care. J Glob Oncol . 4 : Supplement 2,36s–36s (2018) Schoenfeld P. Quality in colorectal cancer screening with colonoscopy. Gastrointest Endosc Clin N Am . 30 (3):541–551. doi: 10.1016/j.giec.2020.02.014 (2020) Ouyang DL, Getzenberg RH, Schoen RE. Noninvasive testing for colorectal cancer: a review. Am J Gastroenterol . 100 (6):1393–1403. doi:10.1111/j.1572-0241.2005.41427 (2005) Redwood D, Asay E, Roberts D, et al . Comparison of fecal occult blood tests for colorectal cancer screening in an Alaska Native population with high prevalence of Helicobacter pylori infection, 2008–2012. Prev Chronic Dis . 11 . doi:10.5888/pcd11.130281 (2014) Hewitson P, Glasziou P, Irwig L, Towler B, Watson E. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst Rev . ( 1 ): CD001216 2007) Shaukat A, Mongin SJ, Geisser MS, Lederle FA, Bond JH, Mandel JS, et al. Long-Term Mortality after Screening for Colorectal Cancer. N Engl J Med . 369 (12):1106–14 (2013) Rex DK, Johnson DA, Anderson JC, Schoenfeld PS, Burke CA, Inadomi JM. American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008. Am J Gastroenterol . 104 (3):739–50 (2009) Muller AD, Sonnenberg A. Protection by Endoscopy Against Death from Colorectal Cancer: A Case–control Study Among Veterans. Arch Intern Med . 155 (16):1741–8 (1995) Baxter NN, Goldwasser MA, Paszat LF, Saskin R, Urbach DR, Rabeneck L. Association of Colonoscopy and Death from Colorectal Cancer. Ann Intern Med . 150 (1):1–8 (2009) Mandel JS, Church TR, Bond JH, Ederer F, Geisser MS, Mongin SJ, et al. The Effect of Fecal Occult-Blood Screening on the Incidence of Colorectal Cancer. N Engl J Med . 343 (22):1603–7 (2000) Mandel JS, Church TR, Ederer F, Bond JH. Colorectal Cancer Mortality: Effectiveness of Biennial Screening for Fecal Occult Blood. J Natl Cancer Inst . 91 (5):434–7 (1999) Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet. 348 (9040):1467–71 (1996) Hardcastle JD, Chamberlain JO, Robinson MHE, Moss SM, Amar SS, Balfour TW, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet. 348 (9040):1472–7 (1996). Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, et al. Reducing Mortality from Colorectal Cancer by Screening for Fecal Occult Blood. N Engl J Med . 328 (19):1365–71 (1993). Quintero E, Castells A, Bujnda L, Cubiella J, Salas D, Lanas Á, et al. Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening. N Engl J Med . 366 (8):697–706 (2012). Frazier AL, Colditz GA, Fuchs CS, Kuntz KM. Cost-effectiveness of Screening for Colorectal Cancer in the General Population. JAMA . 284 (15):1954–61 (2000). Zauber AG, Lansdorp-Vogelaar I, Knudsen AB, Wilschut J, van Ballegooijen M, Kuntz KM. Evaluating Test Strategies for Colorectal Cancer Screening: A Decision Analysis for the U.S. Preventive Services Task Force. Ann Intern Med . 149 (9):659–69 (2008). Tsoi KKF, Ng SSM, Leung MCM, Sung JJY. Cost-effectiveness analysis on screening for colorectal neoplasm and management of colorectal cancer in Asia. Aliment Pharmacol Ther . 28 (3):353–63 (2008). Tappenden P, Chilcott J, Eggington S, Sakai H, Karnon J, Patnick J. Option appraisal of population-based colorectal cancer screening programmes in England. Gut . 56 (5):677–84 (2007). Whynes DK, Neilson AR, Walker AR, Hardcastle JD. Faecal occult blood screening for colorectal cancer: is it cost-effective? Health Econ . 7 (1):21–9 (1998) WHO Cost–effectiveness thresholds: pros and cons. Available from: https:// www.who.int/ bulletin /volumes/94/12/15-164418/en/. [cited Nov 2020]. Woods B, Revill P, Sculpher M, Claxton K. Country-Level Cost-Effectiveness Thresholds: Initial Estimates and the Need for Further Research. Value Health . 19 (8):929–935. doi: 10.1016/j.jval.2016.02.017 (2016). Ministry of Health Kuwait, Financial Affairs, Budget and Control Department, Cost Accounting Section. " Cost Analysis and Performance Evaluation for Government Health Services, 2016/2017, 39th Book Edition, page 81. Ministry of Health Kuwait, Financial Affairs, Budget and Control Department. “Cost of services Resolution” (2019). Soerjomataram I, Thong MSY, Ezzati M, Lamont EB, Nusselder WJ, Van De Poll-Franse L V. Most colorectal cancer survivors live a large proportion of their remaining life in good health. Cancer Causes Control . 23 (9):1421–8 (2012). Haley WE, Freeman. Colorectal Cancer Deaths Attributable to Nonuse of Screening in the United States. Physiol Behav . 176 (1):139–48 (2018). Masau Sekiguchi, Ataru Igarashi, Takahisa Matsuda, et.al. Optimal use of colonoscopy and fecal immunochemical test for population-based colorectal cancer screening: a cost-effectiveness analysis using Japanese data. Japanese Journal of Clinical Oncology . 46 (2) 116–125 (2016). Tappenden P, Chilcott J, Eggington S, Patnick J, Sakai H, Karnon J. Option appraisal of population-based colorectal cancer screening programmes in England. Gut . 56 :677–84 (2007). Sweet A, Lee D, Gairy K, Phiri D, Reason T, Lock K. The impact of CT colonography for colorectal cancer screening on the UK NHS: costs, healthcare resources and health outcomes. Appl Health Econ Health Policy . 9 :51–64 (2011). Japanese Society for Cancer of the Colon and Rectum. JSCCR Guidelines 2014 for the Treatment of Colorectal Cancer. Tokyo, Japan: Kanehara & Co., Ltd., (2014). Pang X, Xu B, Lian J, Wang R, Wang X, Shao J, et al. Real-world survival of colon cancer after radical surgery: A single-institutional retrospective analysis. Front Oncol . 12 (September):1-12 (2022). Van den Berg I, Coebergh van den Braak RRJ, van Vugt JLA, Ijzermans JNM, Buettner S. Correction to: Actual survival after resection of primary colorectal cancer: results from a prospective multicenter study (World Journal of Surgical Oncology, 19 , 1, (96), 10.1186/s12957-021-02207-4). World J Surg Oncol . 2021;19(1):1–10 (2021). Nelya Melnitchouk , Djora. Soeteman, Jennifer S. Davids, Adam Fields, Joshua Cohen, Farzad Noubary, Andrey Lukashenko, Olena O. Kolesnik and Karen. Freund. Cost‑effectiveness of colorectal cancer screening in Ukraine. Cost Eff Resour Alloc . 16 :20 https://doi.org/10.1186/s12962-018-0104-0 (2018). Greenberg PD, et al . A prospective multicenter evaluation of new fecal occult blood tests in patients undergoing colonoscopy. Am J Gastroenterol . 95 (5):1331–8 (2000). Imperiale TF, et al. Fecal DNA versus fecal occult blood for colorectalcancer screening in an average-risk population. N Engl J Med . 351 (26):2704–14 (2004). Collins JF, et al. Accuracy of screening for fecal occult blood on a single stool sample obtained by digital rectal examination: a comparison with recommended sampling practice. Ann Intern Med. 142 (2):81–5 (2005). Pickhardt PJ, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med . 349 (23):2191–200 (2003). Cotton PB, et al. Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia. JAMA. 291 (14):1713–9 (2004) Irvine EJ, et al. Prospective comparison of double contrast barium enema plus flexible sigmoidoscopy v colonoscopy in rectal bleeding: barium enema v colonoscopy in rectal bleeding. Gut . 29 (9):1188–93 (1988). Fitzpatrick-Lewis D, Ali MU, Warren R, Kenny M, Sherifali D, Raina P. Screening for colorectal cancer: a systematic review and meta-analysis. Clin Colorectal Cancer , 15 (4): 298–313. doi: 10.1016/j.clcc.2016.03.003 PMID:27133893 (2016). Hewitson P, Glasziou P, Watson E, Towler B, Irwig L. Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (Hemoccult): an update. Am J Gastroenterol , 103 (6):1541–9. doi:10.1111/j.1572-0241.2008. 01875.x PMID:18479499 (2008). Moayyedi P, Achkar E. Does fecal occult blood testing really reduce mortality? A reanalysis of systematic review data. Am J Gastroenterol . 101 (2):380–4. doi:10.1111/ j. 1572-0241.2006.00537.x PMID:16454847 (2006). Helm JF, Russo MW, Biddle AK, Simpson KN, Ransohoff DF, Sandler RS. Effectiveness and economic impact of screening for colorectal cancer by mass fecal occult blood testing . Am J Gastroenterol. 95 (11):3250–8. doi:10.1111/j.1572-0241.2000.03261.x PMID: 11095350 (2000). Whynes DK; Nottingham FOB Screening Trial. Cost-effectiveness of screening for colorectal cancer: evidence from the Nottingham faecal occult blood trial. J Med Screen , 11 (1):11–5. doi:10.1177/096914130301100104 PMID:15006108 (2004). Pignone M, Saha S, Hoerger T, Mandelblatt J. Cost-effectiveness analyses of colorectal cancer screening: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med , 137 (2):96–104. doi:10.7326/0003-4819-137-2-200207160-00007 PMID:12118964 (2002). Lansdorp-Vogelaar I, Knudsen AB, Brenner H. Cost-effectiveness of colorectal cancer screening. Epidemiol Rev , 33 (1):88–100. doi:10.1093/epirev/mxr004 PMID:21633092 (2011). Patel SS, Kilgore ML. Cost effectiveness of colorectal cancer screening strategies. Cancer Contr. 22 (2):248–58. doi:10.1177/107327481502200219 PMID:26068773 (2015). Kingsley J, Karanth S, Revere FL, Agrawal D. Cost effectiveness of screening colonoscopy depends on adequate bowel preparation rates – a modeling study. PLoS One. 11 (12):e0167452. doi: 10.1371/journal.pone.0167452 PMID:27936028 (2016). Barzi A, Lenz H-J, Quinn DI, Sadeghi S. Comparative effectiveness of screening strategies for colorectal cancer. Cancer . 123 (9):1516–27. doi:10.1002/cncr.30518 PMID:28117881 (2017). Lee KS, Park EC. Cost effectiveness of colorectal cancer screening interventions with their effects on health disparity being considered. Cancer Res Treat . 48 (3):1010–9. doi:10.4143/crt.2015.279 PMID:26727714 (2016). Ladabaum U, Mannalithara A. Comparative effectiveness and cost effectiveness of a multitarget stool DNA test to screen for colorectal neoplasia. Gastroenterology . 151 (3):427–439.e6. doi: 10.1053/j.gastro.2016.06.003 PMID:27311556 (2016). Heitman SJ, Hilsden RJ, Au F, Dowden S, Manns BJ. Colorectal cancer screening for average-risk North Americans: an economic evaluation. PLoS Med. 7 (11):e1000370. doi: 10.1371/journal.pmed.1000370 PMID:21124887 (2010). Telford JJ, Levy AR, Sambrook JC, Zou D, Enns RA. The cost-effectiveness of screening for colorectal cancer. CMAJ . 182 (12):1307–13. doi:10.1503/cmaj.090845 PMID:20624866 (2010). Goede SL, Rabeneck L, van Ballegooijen M, Zauber AG, Paszat LF, Hoch JS, et al . Harms, benefits and costs of fecal immunochemical testing versus guaiac fecal occult blood testing for colorectal cancer screening. PLoS One , 12 (3):e0172864. doi: 10.1371 /journal.pone. 0172864 PMID:28296927 (2017). Sharp L, Tilson L, Whyte S, O’Ceilleachair A, Walsh C, Usher C, et al. Cost-effectiveness of population-based screening for colorectal cancer: a comparison of guaiac-based faecal occult blood testing, faecal immunochemical testing and flexible sigmoidoscopy. Br J Cancer , 106 (5):805–16. doi:10.1038/bjc.2011.580 PMID:22343624 (2012). Whyte S, Chilcott J, Halloran S. Reappraisal of the options for colorectal cancer screening in England. Colorectal Dis . 14 (9):e547–61. doi:10.1111/j.1463-1318.2012. 03014.x PMID:22390210 (2012). Pil L, Fobelets M, Putman K, Trybou J, Annemans L. Cost-effectiveness and budget impact analysis of a population-based screening program for colorectal cancer. Eur J Intern Med , 32 :72–8. doi: 10.1016/j.ejim.2016.03.031 PMID:27157827 (2016). Aronsson M, Carlsson P, Levin L-Å, Hager J, Hultcrantz R. Cost-effectiveness of high-sensitivity faecal immunochemical test and colonoscopy screening for colorectal cancer. Br J Surg. 104 (8):1078–86. doi:10.1002/bjs.10536 PMID:28561259 (2017). Barouni M, Larizadeh MH, Sabermahani A, Ghaderi H. Markov’s modeling for screening strategies for colorectal cancer. Asian Pac J Cancer Prev , 13 (10):5125–9. doi:10.7314/APJCP.2012.13.10.5125 PMID:23244122 (2012). Dan YY, Chuah BYS, Koh DCS, Yeoh KG. Screening based on risk for colorectal cancer is the most cost-effective approach. Clin Gastroenterol Hepatol, 10 :3: 266–71.e1, 6. doi:10.1016/j.cgh.2011.11.011 PMID:22100624 (2012). Wang ZH, Gao Q-Y, Fang J-Y. Repeat colonoscopy every 10 years or single colonoscopy for colorectal neoplasm screening in average-risk Chinese: a cost-effectiveness analysis. Asian Pac J Cancer Prev . 13 (5):1761–6. doi:10.7314/APJCP.2012.13.5.1761 PMID:22901118 (2012). Lam CL, Law WL, Poon JT, Chan P, Wong CK, McGhee SM, et al . Health-related quality of life in patients with colorectal neoplasm and cost-effectiveness of colorectal cancer screening in Hong Kong. Hong Kong Med J , 21 (Suppl 6):4–8. PMID:26645874 (2015). Wong MC, Ching JYL, Chan VCW, Sung JJY. The comparative cost-effectiveness of colorectal cancer screening using faecal immunochemical test vs. colonoscopy. Sci Rep , 5 (1):13568. doi:10.1038/srep13568 PMID:26338314 (2015). Sekiguchi M, Igarashi A, Matsuda T, Matsumoto M, Sakamoto T, Nakajima T, et al. Optimal use of colonoscopy and fecal immunochemical test for population-based colorectal cancer screening: a cost-effectiveness analysis using Japanese data. Jpn J Clin Oncol . 46 (2):116–25. doi:10.1093/jjco/hyv186 PMID:26685321 (2016). WHO, IARC (2019), Colorectal cancer screening. IARC Handb Cancer Prev. 17:1–300. Available from: http://publications.iarc.fr/573. (Accessed 18.6.2024). Littlejohn C, Hilton S, Macfarlane GJ, Phull P. Systematic review and meta-analysis of the evidence for flexible sigmoidoscopy as a screening method for the prevention of colorectal cancer. Br J Surg , 99 (11):1488–500. doi:10.1002/bjs.8882 PMID:23001715 (2012). Holme , Loberg M, Kalager M, Bretthauer M, Hernán MA, Aas E, et al . Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA , 312 (6):606–15. doi:10.1001/jama.2014.8266 PMID:25117129 (2014). Berry DP, Clarke P, Hardcastle JD, Vellacott KD. Randomized trial of the addition of flexible sigmoidoscopy to faecal occult blood testing for colorectal neoplasia population screening. Br J Surg , 84 (9):1274–6. doi:10.1002/bjs.1800840922 PMID:9313712 (1997). Verne JECW, Aubrey R, Love SB, Talbot IC, Northover JM. Population based randomized study of uptake and yield of screening by flexible sigmoidoscopy compared with screening by fecal occult blood testing. BMJ , 317 (7152):182–5. doi:10.1136/bmj.317.7152.182 (1998). Sekiguchi M, Igarashi A, Matsuda T, Matsumoto M, Sakamoto T, Nakajima T, et al. Optimal use of colonoscopy and fecal immunochemical test for population-based colorectal cancer screening: a cost-effectiveness analysis using Japanese data. Jpn J Clin Oncol , 46 (2):116–25. doi:10.1093/jjco/hyv186 PMID:26685321 (2016). Amrizal Muhammad Nur, Eleni L. Tolma, Syed Mohamed Aljunid, Joseph C. Longenecker, Dina Zein, Mahmoud Annaka, Rihab Alwotayan, Amani Elbasmi. 2024. Practices, Attitudes, and Perceived Barriers in Colorectal Cancer Screening Among Primary Care Physicians in Kuwait: Insight from A Cross Sectional Study. Malaysian Journal of Public Health (2024) Vol. 24(1):268-279. Additional Declarations No competing interests reported. Supplementary Files AppendixADecisiontreeforcolorectalcancerscreeningoptions.pdf Additional Information Appendix A: Figure-1: Decision tree for colorectal cancer screening options with high resolution in the PDF format. Cite Share Download PDF Status: Published Journal Publication published 01 Mar, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 19 Nov, 2024 Reviews received at journal 18 Nov, 2024 Reviews received at journal 25 Sep, 2024 Reviewers agreed at journal 24 Sep, 2024 Reviewers agreed at journal 19 Sep, 2024 Reviewers invited by journal 18 Aug, 2024 Editor assigned by journal 18 Aug, 2024 Editor invited by journal 28 Jul, 2024 Submission checks completed at journal 25 Jul, 2024 First submitted to journal 28 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4654485","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":342884423,"identity":"9628d937-d108-48d9-af88-bdc309d5bc52","order_by":0,"name":"Amrizal Muhammad Nur","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYJCCAwwMFnL27Q1ApoEF0VokjA14DoC0SBBtkUSigUQCmEFYLf+0sw8P/qiRSDCXfH51w48CCQb+9u4E/MbfTjc4IHFMIs9ydk7ZzR6gwyTOnN2A35rbaQwHDNgkihlu56Td4AFqMZDIxa9FHqQl4Z9EYsPNM2k3/xCjxQCk5WCbROKGG+zHbhNliyFQy8HGPgljyZ4cttsyBhI8BP0idzuN+eOPbzZy/OzHn9188wfIaO8l4H0E4DEAk8QqBwH2B6SoHgWjYBSMghEEAJVWSSUo8WK3AAAAAElFTkSuQmCC","orcid":"","institution":"Kuwait University","correspondingAuthor":true,"prefix":"","firstName":"Amrizal","middleName":"Muhammad","lastName":"Nur","suffix":""},{"id":342884425,"identity":"43e38ed6-0886-4a90-893a-7b46a03d0d38","order_by":1,"name":"Syed Mohamed Aljunid","email":"","orcid":"","institution":"International Medical University","correspondingAuthor":false,"prefix":"","firstName":"Syed","middleName":"Mohamed","lastName":"Aljunid","suffix":""},{"id":342884428,"identity":"c8b4cc70-3d32-4cab-9634-cd5dc0f3317d","order_by":2,"name":"Eleni L. 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Alali","email":"","orcid":"","institution":"East Tennessee State University","correspondingAuthor":false,"prefix":"","firstName":"Walid","middleName":"Q.","lastName":"Alali","suffix":""}],"badges":[],"createdAt":"2024-06-28 11:32:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4654485/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4654485/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-91119-4","type":"published","date":"2025-03-01T15:57:59+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":63313183,"identity":"b6e11c71-55f7-4953-8565-8fa51ce030f1","added_by":"auto","created_at":"2024-08-26 20:50:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":650097,"visible":true,"origin":"","legend":"\u003cp\u003eDecision tree for colorectal cancer screening options\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4654485/v1/02f52b03e375d4f6c12bcf85.png"},{"id":63313592,"identity":"fe16d68c-aa56-4d16-995e-961d865409b7","added_by":"auto","created_at":"2024-08-26 20:58:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":107917,"visible":true,"origin":"","legend":"\u003cp\u003eTornado diagram between ICER Sigmoidoscopy and FOBT\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4654485/v1/8680f797b94c522584cde33f.png"},{"id":63313179,"identity":"366718aa-6373-48d1-a318-3b2c654b4b9a","added_by":"auto","created_at":"2024-08-26 20:50:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":603887,"visible":true,"origin":"","legend":"\u003cp\u003eIncremental Cost Effectiveness Between FOBT and Sigmoidoscopy\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-4654485/v1/f8222ec0df4fb9707faf7ea5.png"},{"id":77622704,"identity":"1bf68dfa-8eb0-40f2-ad1b-050e4be395bb","added_by":"auto","created_at":"2025-03-03 16:09:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2378785,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4654485/v1/5d4367f2-6597-4097-9cd5-581ad9387a4d.pdf"},{"id":63313163,"identity":"f7426aee-a467-4cef-b842-ea946412dc7d","added_by":"auto","created_at":"2024-08-26 20:50:16","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2989957,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdditional Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAppendix A: Figure-1: Decision tree for colorectal cancer screening options with high resolution in the PDF format.\u003c/p\u003e","description":"","filename":"AppendixADecisiontreeforcolorectalcancerscreeningoptions.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4654485/v1/834a41e88e88d2748675d749.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cost effectiveness analysis of colorectal cancer screening modalities in Kuwait: Comparison of Three Alternative Screening Strategies","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAccording to a recent study on the Global Burden of Diseases, CRC stands as the second most prevalent cause of cancer-related mortality globally, claiming approximately 1.1\u0026nbsp;million lives annually and constituting 9.7% of all cancer-related Disability-Adjusted Life Years\u003csup\u003e1\u003c/sup\u003e. This underscores the significance of CRC as a pressing public health concern globally\u003csup\u003e2,3\u003c/sup\u003e. In Kuwait, CRC is the second most common cancer after breast cancer\u003csup\u003e4\u003c/sup\u003e. Data from the Kuwait Cancer Registry shows that between January 2010 and December 2019, there were 2,710 cases of CRC, accounting for approximately 10.2% of all cancer cases in the country. During this period, the age-standardized incidence rate of CRC in Kuwait was 13.2 per 100,000 people, which is lower than the global estimated rate of 19.7 per 100,000\u003csup\u003e4\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eEarly detection of colorectal cancer allows for treatment before it becomes incurable, potentially lowering cancer mortality. Preventive cancer screening aims to identify and remove precursor lesions, like colorectal adenomas, to prevent cancer development. Consequently, preventive screening can reduce both the incidence of cancer and the associated mortality\u003csup\u003e5\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the United States of America (USA), US Preventive Services Task Forces recommends screening for colorectal cancer in all adults aged 50 to 75 years to select from a number of suggested screening strategies such as FOBT, colonoscopy, sigmoidoscopy\u003csup\u003e6\u003c/sup\u003e, meanwhile European Union (European Guide for Quality National Cancer Control Programmes) recommends CRC screening with a Guaiac Fecal Occult Blood Test (gFOBT) or immunochemical Fecal Occult Blood Test (iFOBT) for the age group 50\u0026ndash;74 years, for all adult\u0026rsquo;s women and men\u003csup\u003e7\u003c/sup\u003e. In Kuwait, only one pilot program for CRC screening targeting asymptomatic average‑risk individuals aged 45\u0026ndash;75 years has been launched in mid‑2015. The most widely utilized screening technique for early CRC detection in Kuwait's public hospitals is colonoscopy. Sigmoidoscopy and FOBT are two others widely used CRC screening methods\u003csup\u003e8\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eEconomic evaluation is a systematic and formal way of assessing the costs and benefits of screening interventions. There are a number of methods for screening for CRC; colonoscopy, one of the most widely used interventions, has been associated with relatively high accuracy performance\u003csup\u003e9\u003c/sup\u003e. In contrast, the FOBT is easier to use and less expensive than colonoscopy\u003csup\u003e10,11\u003c/sup\u003e. Until recently, gFOBT was the only test for which there was strong evidence of efficacy from randomized controlled trials (RCTs). The choice to base UK colorectal cancer screening programs on gFOBT was supported by data of a 16% mortality decrease following repeated screening with gFOBT\u003csup\u003e12\u003c/sup\u003e. FOBT screening has been shown to be beneficial in lowering the annual incidence eand death of CRC\u003csup\u003e13\u003c/sup\u003e. Alternative methods for CRC screening include colonoscopy and flexible sigmoidoscopy\u003csup\u003e14\u003c/sup\u003e, while US population-based case control studies have demonstrated a respectable decrease in yearly mortality with colonoscopy screening\u003csup\u003e15,16\u003c/sup\u003e. A randomized controlled trial (RCT) should ideally offer concrete empirical proof of the relative efficacy of different CRC screening techniques. Prior RCTs were intended to randomly assign participants into a regular FOBT screening group in order to capture such long-term CRC risk; however, no screening group persisted for at least ten years\u003csup\u003e17\u0026ndash;21\u003c/sup\u003e. One-time colonoscopy and FOBT are being compared for effectiveness in a randomized controlled trial (RCT), which is anticipated to be finished in 2021\u003csup\u003e22\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCost-effectiveness analysis (CEA) offers decision-making and rationale for effective resource allocation under a set budget restriction, aiming to strike a balance between costs and effectiveness incurred by CRC screening. The most cost-effective procedures in terms of live years (LYs) gained for an average-risk population are annual FOBT plus 5-yearly sigmoidoscopy under full compliance rate\u003csup\u003e23\u003c/sup\u003e and colonoscopy every 10 years\u003csup\u003e24\u003c/sup\u003e, according to cost-effectiveness modeling conducted on the U.S. population. According to a study conducted on a population in Hong Kong, the incremental costs of colonoscopy and FOBT compared to no screening were US \u003cspan\u003e$\u003c/span\u003e7,211 and US \u003cspan\u003e$\u003c/span\u003e6,222 per life year gained, respectively\u003csup\u003e25\u003c/sup\u003e. According to UK research studies, the most economical screening approach was to use only biennial FOBT since it was projected to have an incremental cost of less than \u0026pound;3,000 per QALY when compared to no screening\u003csup\u003e26,27\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite Kuwait's population having a lower incidence of CRC than developed nations, there is currently no established strategy for CRC screening for Kuwaitis. There has never been a cost effectiveness analysis (CEA) of CRC screening on Kuwaiti populations in terms of the gain in QALYs. Thus, this study's objective was to evaluate the relative cost-effectiveness of the three main CRC screening methods: sigmoidoscopy, colonoscopy, and FOBT followed by either sigmoidoscopy or colonoscopy.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eA population-based statewide program for CRC screening was compared to no screening in a cost-effectiveness analysis, with adults in Kuwait between the ages of 50 and 80 being identified as being at risk for colorectal cancer. Three screening options were taken into consideration: yearly FOBT followed by sigmoidoscopy or colonoscopy, sigmoidoscopy every five or ten years, and colonoscopy every ten years (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eCRC screening strategy:\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCRC Screening strategies used in this study\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStrategies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInterval\u003c/p\u003e \u003cp\u003e(Years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003cp\u003eHorizon\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAge at Screening (Years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003cp\u003eMeasures\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIncremental Cost-Effectiveness Ratio (ICER)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo Screening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLifetime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u0026ndash;80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQALYs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCost/QALYs\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFOBT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLifetime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u0026ndash;80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQALYs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCost/QALYs\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSigmoidoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLifetime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u0026ndash;80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQALYs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCost/QALYs\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSigmoidoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLifetime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u0026ndash;80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQALYs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCost/QALYs\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColonoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLifetime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u0026ndash;80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQALYs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCost/QALYs\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eDevelopment of an economic model\u003c/h2\u003e \u003cp\u003eA decision tree analytic model was developed to conduct a cost-effectiveness analysis of various CRC screening modalities compared to no screening option. The model compared costs and outcomes of three major screening modalities for CRC which are (i) colonoscopy, (ii) sigmoidoscopy and (iii) Fecal Occult Blood Test (FOBT) followed by colonoscopy or sigmoidoscopy compared to no screening option. The model is presented in the supplementary document (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Appendix A).\u003c/p\u003e \u003cp\u003eThis model adopted the third-party payer's perspective, in this case, the Kuwait Ministry of Health, to examine costs and outcomes associated with colorectal cancer screenings. This model tracks costs and outcomes for 10 years post-diagnosis based on the documented life expectancy of patients with colorectal cancer. All cost estimates were adjusted for inflation to the year 2023. For the cost-effectiveness analysis, a willingness to pay (WTP) threshold of 1 GDP per capita was used.\u003c/p\u003e \u003cp\u003eThe final output of the model was expressed in terms of Incremental Cost Effectiveness Ratio (ICER) comparing those alternatives. ICER was calculated between two alternatives to determine the magnitude of the cost-effectiveness of the various CRC screening modalities. For the ICER, a standard WHO threshold of cost-effectiveness wereused\u003csup\u003e28,29\u003c/sup\u003e. The uncertainties were assessed for any parameters estimated through deterministic and probabilistic sensitivity analyses. The findings were presented in an ICER table and diagrams accordingly. Model parameters including probabilities, costs, and outcomes were derived from primary data collection, expert\u0026rsquo;s opinions and published sources. Sensitivity analyses were used to account for uncertainty in these estimates.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e(1) Cost Information\u003c/h2\u003e \u003cp\u003eAll cost information used in this model from the healthcare provider perspective, included screening cost and management cost of CRC patient. Indirect cost that are incurred by the patients such as transportation, meal, caregiver and loss of productivity were not included. The cost of FOBT, Colonoscopy and Sigmoidoscopy were extracted from existing Kuwait MOH charges\u003csup\u003e30\u003c/sup\u003e. The management cost of CRC patient by stage level was computed by multiplying the length of stay (LOS) of each CRC patient with the existing average unit cost per day of stay in the Kuwait government hospital\u003csup\u003e31\u003c/sup\u003e. The existing unit cost was computed in the year 2017. The adjusted inflation with multiple years was made for the year 2023. Local costs evaluated in Kuwaiti Dinar in year 2023 were converted to US dollar (USD) which exchange rate of 1 Kuwaiti Dinar\u0026thinsp;=\u0026thinsp;3.254 USD. Refer to the Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e for the list of cost information.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eList of cost information\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCosts information\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCost (USD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCost of screening with colonoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e293.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCost of screening with sigmoidoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e195.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCost of screening with Fecal Occult Blood Test (FOBT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe cost of managing a patient is stage 1 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e839.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe cost of managing a patient is stage 2 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,682.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe cost of managing a patient is stage 3 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5,955.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe cost of managing a patient is stage 4 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7,159.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCost of death/cancer-free\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e(2) Effectiveness of health outcome\u003c/h2\u003e \u003cp\u003eTo measure the health outcomes of the various screening alternatives, the values of QALYs were used. The QALY was imputed to the model by incorporating utility values from published studies multiplied by the duration of the time spent in the disease state, which in this study was 10 years. The 10-year cut-off point was used based on the reported life expectancy of CRC patients\u003csup\u003e32\u003c/sup\u003e. The utility values are described in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eList of utility value of CRC patient by stages from published studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUtility\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUtility value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWell patient (cancer-free)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient with stage 1 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient with stage 2 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient with stage 3 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient with stage 4 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e(3) Probability data\u003c/h2\u003e \u003cp\u003eAll the probabilities that were incorporated in the cost-effectiveness model were obtained from published literature and expert\u0026rsquo;s inputs. The values used are described in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e:\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eList of CRC probability detection rate by various CRC screening modalities and probability of CRC by stages, cancer free and death from published studies.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbability\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive detection rate with colonoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive detection rate with sigmoidoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive detection rate with Fecal Occult Blood Test (FOBT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemain at stage 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 1 to Stage 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 1 to stage 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 1 to stage 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 1 to cancer-free\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.908\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 1 to Death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemain at stage 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 2 to stage 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 2 to stage 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 2 to cancer-free\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.781\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 2 to Death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemain at stage 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.08743\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 3 to Stage 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.11528\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 3 to cancer-free\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.49629\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 3 to Death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.30100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemain at stage 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.343\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 4 to Death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.657\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e(4) Assumptions\u003c/h2\u003e \u003cp\u003eIn the model, several assumptions were made given the unavailability of the data. Firstly, it was assumed that, following the screening and disease staging, the probability of patients diagnosed at various stages of colorectal cancer (stage 1 to 4) is the same, and therefore probability of 0.25 was applied for each stage. Secondly, following FOBT, the probability of disease confirmation through colonoscopy and sigmoidoscopy is also the same and a probability of 0.5 was applied for each alternative. In the no-screening option, the number of patients with colorectal cancer was based on the information of the under-reported cases which was 63%. Therefore, the probability of 0.63 was applied\u003csup\u003e33\u003c/sup\u003e. Following that the distribution of patients in each stage of CRC was based on data from published studies\u003csup\u003e38,39,40\u003c/sup\u003e. Regarding the probability of patients at various stages of cancer, mathematical calculations were imputed in which the probabilities were first determined through the survival rate to determine the probability of death. Subsequently, the remaining probabilities were further distributed according to the weightage for each stage of cancer. The weights used were based on published literature\u003csup\u003e38,39\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eUsing base-case estimates, it was found that the screening modality with the FOBT followed by colonoscopy or sigmoidoscopy was the only undominated option. The other two modalities, which are colonoscopy and sigmoidoscopy, as well as the alternative with no screening, were all dominated by the FOBT followed by colonoscopy and sigmoidoscopy. It was found that CRC screening with FOBT followed by colonoscopy or sigmoidoscopy would cost USD 3573.00 compared to USD 4084.00, USD 4905.00, and USD 5002.00 for no screening option, screening with sigmoidoscopy and screening with colonoscopy, respectively. Regarding the QALYs, CRC screening with FOBT followed by colonoscopy or sigmoidoscopy would result in 7.7 compared to 7.2, 6.8 and 6.8 QALYs for no screening option, screening with sigmoidoscopy and screening with colonoscopy, respectively.\u003c/p\u003e \u003cp\u003eIn comparison to the CRC screening with the FOBT followed by colonoscopy or sigmoidoscopy, no screening option would result in an ICER of -1010.00. Also, compared to the same alternative, sigmoidoscopy and colonoscopy would result in ICERs of -1498.06 and \u0026minus;\u0026thinsp;1607.16 respectively. Based on these results, it shows that alternatives other than the CRC screening with FOBT followed by colonoscopy or sigmoidoscopy are less effective and will also increase cost. Therefore, it is obvious that the FOBT followed by colonoscopy or sigmoidoscopy option is dominant compared to other alternatives. Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e describes the ICERs of all four alternatives.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCost, Incremental cost, QALYs per person (Effectiveness of health outcome) for each screening strategy, incremental effectiveness, and ICER compared with FOBT followed by colonoscopy or sigmoidoscopy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlternatives\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCost (USD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIncremental cost (*comparison with the undominated alternative)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEffectiveness (Outcomes)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIncremental effectiveness\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eICER\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFOBT followed by colonoscopy or sigmoidoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo screening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4084\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e511\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-1010.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSigmoidoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4905\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-1498.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColonoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1429\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-1607.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analysis\u003c/h2\u003e \u003cp\u003eTo test the effect of single variables on the overall economic conclusion from this model, multiple one-way sensitivity analyses were conducted. The tornado diagram (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) was used to visually demonstrate the resulting Incremental Cost Effectiveness Ratios (ICERs) when one variable is changed to become either the maximum or minimum value of the range provided. It is used to identify the relative importance of a variable since it can demonstrate if the economic conclusion changes based on changing the variable. In an ICER tornado diagram, the importance of each variable on the economic conclusion is presented from top to bottom. The tails of each bar indicate the maximum and minimum ICER for each variable. The dashed line represents the ICER from the reference case to provide a reference for the changes in ICERs.\u003c/p\u003e \u003cp\u003eIn this study, 14 parameters were used in the multiple-1-way sensitivity analyses. All the included parameters with the lower value and upper value used are presented in the table below. The values were taken from the published studies and also expert input as shown in Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e14 parameters were used in the multiple-1-way sensitivity analyses\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLower value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUpper value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive detection rate with colonoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e] [\u003csup\u003e\u003cspan additionalcitationids=\"CR44 CR45\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive detection rate with sigmoidoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e] [\u003csup\u003e\u003cspan additionalcitationids=\"CR44 CR45\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive detection rate with Fecal Occult Blood Test (FOBT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCost of screening with colonoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e309\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCost of screening with sigmoidoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCost of screening with Fecal Occult Blood Test (FOBT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCost of managing a patient with Stage 1 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e420.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6300.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCost of managing a patient with Stage 2 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e841.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12601.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCost of managing a patient with Stage 3 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e841.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32762.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCost of managing patients in stage 4 of cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e841.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e127689.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUtility for patients with stage 1 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUtility for patients with stage 2 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUtility for patients with stage 3 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.594\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUtility for patients with stage 4 cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.594\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTo conduct the sensitivity analysis, two alternatives were chosen which are the FOBT followed by colonoscopy or sigmoidoscopy. The results of the multiple-1-way sensitivity analyses demonstrated that this CEA model was most sensitive to the cost of managing patients in stages 4, 3 and 2 of the cancer as illustrated Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBased on the results of the multiple-1-way sensitivity analyses, the parameters tested for sensitivity analysis changed the magnitude of ICER. The tornado diagram shows that all the parameters tested resulted in further negative ICERs when a higher value was set. Subsequently, a Probabilistic Sensitivity Analysis (PSA) was done for multivariate analysis using TreeAge Pro software. In the PSA, instead of changing one parameter value at a time, all variables were changed at once according to their plausible values by random sampling from their distributions. The model was simulated 10,000 times in the PSA from the probability distribution of each parameter. All cost data were assigned to a gamma distribution. Utility data followed a beta distribution. The cost-effectiveness scatterplot was used to test the stability of the model results. Based on the multiple-1-way sensitivity analyses, parameters that were sensitive to the changes of ICER were identified and applied for the PSA. The parameters included the cost of disease management for all the stages of colorectal cancer and utility value for stage 4 of the cancer.\u003c/p\u003e \u003cp\u003eIn this study, when the ICERs from the PSA are plotted onto the cost-effectiveness plane, comparing sigmoidoscopy and FOBT followed by colonoscopy or sigmoidoscopy, it demonstrates that more than 95% of the outcomes are located to the right (dominant) of the willingness to yay (WTP) lines. Based on the 10000 iterations, all negatives ICERs were obtained. This finding demonstrated that the sigmoidoscopy is a dominated alternative compared to FOBT followed by colonoscopy or sigmoidoscopy. The result of the PSA is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe decision tree model analysis conducted in this study aimed to assess the cost-effectiveness of various screening strategies for CRC detection. The findings from the analysis provide valuable insights into the economic implications and health outcomes associated with different screening modalities.\u003c/p\u003e \u003cp\u003eThe results of the decision tree analysis indicate that CRC screening with FOBT followed by colonoscopy or sigmoidoscopy would cost USD 3573.00 compared to USD 4084.00, USD 4905.00, and USD 5002.00 for no screening option, screening with sigmoidoscopy and screening with colonoscopy, respectively. Regarding the QALYs, colorectal cancer screening with FOBT followed by colonoscopy or sigmoidoscopy would result in 7.7 compared to 7.2, 6.8 and 6.8 QALYs for no screening option, screening with sigmoidoscopy and screening with colonoscopy respectively. This suggests that implementing FOBT-based screening programs could potentially lead to significant cost savings while effectively detecting and preventing CRC. This study findings in lines with several meta-analyses spanning from 1998 to 2016 have assessed the efficacy of CRC screening with gFOBT. While some varied in the trials they included, overall, they consistently showed a modest but significant reduction in CRC mortality. The relative risks for CRC mortality ranged from 0.82 to 0.87. A pooled estimate from the Minnesota and Nottingham trials, involving over 220,000 individuals with a median follow-up of 14.25 years, indicated an 8% reduction in late-stage CRC incidence with gFOBT screening\u003csup\u003e47\u0026ndash;49\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRegarding the cost saving, this study finding also in lines with the majority study across the world. The cost-effectiveness of gFOBT screening for CRC has been assessed in several studies over the years. Helm et al. (2000) estimated the cost-effectiveness of gFOBT based on trials conducted in Minnesota, Nottingham, and Funen, was acceptable\u003csup\u003e50\u003c/sup\u003e. Whynes et al. (2004) followed up on the Nottingham trial, reaffirming the cost-effectiveness of gFOBT screening\u003csup\u003e51\u003c/sup\u003e. Three systematic reviews by Pignone et al. (2002), Lansdorp-Vogelaar et al. (2011), and Patel \u0026amp; Kilgore (2015) evaluated the cost-effectiveness of gFOBT or FIT compared to no screening\u003csup\u003e52\u0026ndash;54\u003c/sup\u003e. These reviews consistently found gFOBT screening to be cost-effective, with costs per life year gained ranging from USD 5691 to USD 17,805 in Pignone et al. (2002) and from cost savings to USD 56,300 per life year gained in Lansdorp-Vogelaar et al. (2011). Patel \u0026amp; Kilgore (2015) included additional studies and confirmed the cost-effectiveness of gFOBT CRC screening strategies and cost savings compared to no screening\u003csup\u003e54\u003c/sup\u003e. Ladabaum \u0026amp; Mannalithara (2016) updated their model with new CEA results of CRC screening using gFOBT, showing cost savings\u003csup\u003e58\u003c/sup\u003e. These studies support the findings of Patel \u0026amp; Kilgore (2015) and assess both gFOBT and the fecal immunochemical test (FIT). Kingsley et al. (2016) and Barzi et al. (2017), along with a study in the Republic of Korea by Lee \u0026amp; Park (2016), found cost savings for annual FIT and gFOBT\u003csup\u003e55\u0026ndash;57\u003c/sup\u003e. Outside the USA, 14 new studies have been published since Lansdorp-Vogelaar et al.'s review in 2011, evaluating the cost-effectiveness of gFOBT or FIT screening. These studies, conducted in Canada, Europe, and Asia (including the Middle East), predominantly show that FOBT screening is cost-saving\u003csup\u003e59\u0026ndash;71\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFurthermore, the individual screening modalities of sigmoidoscopy and colonoscopy, while demonstrating similar effectiveness scores of 6.8, incur significantly higher costs compared to the FOBT-based strategy. Sigmoidoscopy incurs an incremental cost of USD 1332 and an ICER of USD 1498.06, while colonoscopy incurs an incremental cost of USD 1429 and an ICER of - USD 1607. These findings highlight the economic trade-offs associated with more invasive screening procedures.\u003c/p\u003e \u003cp\u003eTo date, only two methods have been assessed in RCTs to investigate reductions in CRC incidence or mortality: gFOBT and sigmoidoscopy. This section deals with comparisons between major endoscopic and stool-based CRC screening methods (i.e.,sigmoidoscopy or colonoscopy vs gFOBT or FIT) in terms of mortality or incidence outcomes, ADRs, and cost\u0026ndash;effectiveness. No RCT is available that directly compares two or more CRC screening tests. Evidence comes from indirect comparisons of observational studies and from indirect meta-analyses, so-called network meta-analyses using Bayesian statistics\u003csup\u003e72\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCombining FOBT with colonoscopy or sigmoidoscopy in this study was a cost-effective screening strategy. This finding is also consistent with several studies that have been published, showing significant results. In the study by Littlejohn et al. (2012), which reviewed six studies comparing sigmoidoscopy with FOBT for detecting advanced adenoma and colorectal cancer (CRC), it was found that sigmoidoscopy, either alone or combined with FOBT, was more effective in detecting advanced adenoma compared to FOBT alone\u003csup\u003e73\u003c/sup\u003e. Similar results were observed for the detection of CRC. In a trial conducted in Norway by Holme et al. (2014), involving approximately 100,000 participants, the detection rates of advanced adenoma and CRC were similar between sigmoidoscopy alone and a combination of FIT with sigmoidoscopy. Both methods showed increases in detection rates compared to no screening\u003csup\u003e74\u003c/sup\u003e. The study in the United Kingdom by Berry et al. (1997) found that the screening strategy combining gFOBT with flexible sigmoidoscopy had a detection rate of 0.8% for advanced adenoma and 0.1% for colorectal cancer\u003csup\u003e75\u003c/sup\u003e. A similar study was also conducted by Verne et al. (1998), which found detection rates of 0.1% for advanced adenoma and 0.1% for colorectal cancer\u003csup\u003e76\u003c/sup\u003e. Another study by Holme et al. (2014) found that flexible sigmoidoscopy combined with FIT had detection rates of 4.5% for advanced adenoma and 0.3% for colorectal cancer patients. Another similar study by Sekiguchi et al. (2016), using a screening strategy of colonoscopy combined with annual FIT, found that the combination of colonoscopy and annual FIT was superior to annual FIT alone\u003csup\u003e77\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSensitivity analyses were used to account for uncertainty in these estimates. To test the effect of single variables on the overall economic conclusion from this model, multiple one-way sensitivity analyses and a PSA has been used to evaluate the impact of varying parameters on ICERs. The tornado diagram highlighted the sensitivity of economic conclusions to individual parameter changes, with the cost of managing patients in advanced cancer stages having the most significant influence on ICERs. All parameters tested resulted in increasingly negative ICERs with higher values. The PSA, involving simultaneous changes to all variables, revealed that sigmoidoscopy was dominated compared to gFOBT followed by colonoscopy or sigmoidoscopy, with more than 95% of outcomes positioned to the right of the willingness-to-pay lines on the cost-effectiveness plane. In conclusion, our model were robust in sensitivity analyses as relevant variables such as costs of screening tests (FOBT, Sigmoidoscopy and colonoscopy), CRC management cost by stages, different FOBT cut-offs, changes in stages of the detected cancers and performance of the screening tests did not change the conclusions of the model, favoring FOBT followed by colonoscopy or sigmoidoscopy screening, as this programme remained cost-effective.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eLimitations and Future Directions\u003c/h2\u003e \u003cp\u003eIt is important to acknowledge certain limitations of this study. First, the costs of CRC screening were calculated from the healthcare provider perspective (Kuwait MOH). The cost of lost productivity, meal, cost of transportation and caregiver is not included. Second, the model did not incorporate the potentially high cost of establishing a national screening program in Kuwait, including the costs of addressing adherence, public health campaigns to change attitudes toward CRC screening or other methods at the provider level to increase adherence as a reference the other paper that we just published\u003csup\u003e78\u003c/sup\u003e. Third, the utility data were measured by cross-sectional study rather than randomized controlled trial with sufficient follow-up periods, which involves the consideration of time-dependent utility data in the short and long term.\u003c/p\u003e \u003cp\u003eTo our knowledge this is the first cost-effectiveness analysis focusing on screening strategies for colorectal cancer in Kuwait and has the potential to contribute significantly to the knowledge base guiding rational decision making with respect to clinical practice and health care resource allocation. If acted upon, the findings of our study may substantially improve CRC care in Kuwait and can be used to concentrate efforts on developing a national screening program\u003c/p\u003e \u003cp\u003eThe decision tree analysis model relies on various assumptions (14 parameters) regarding the accuracy of screening tests, the effectiveness of treatment interventions, the probability of each CRC screening positive etc. Future research could address these limitations by incorporating real-world data and conducting sensitivity analyses to validate the robustness of the findings.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eImplications for Practice and Policy\u003c/h2\u003e \u003cp\u003eFOBT CRC screening presents a non-invasive, safe, and easily implementable alternative to colonoscopy screening. In contrast to the invasive nature of colonoscopy, FOBT involves minimal discomfort and presents considerably lower risks to patients. Not only does FOBT mitigate the risks inherent in invasive procedures like colonoscopy, including the potential for bleeding due to perforation, pain, and the arduous preparation process, but it also serves as a convenient and accessible means for early detection of colorectal cancer. Therefore, advocating for the widespread adoption and promotion of FOBT screening can significantly bolster public health initiatives aimed at reducing colorectal cancer incidence and mortality rates\u003c/p\u003e \u003cp\u003eDespite the limitations, we believe that the study can contribute to the design of better and more efficient CRC screening policies in Kuwait. Our results, strong suggest, that the combination of CRC screening strategy such as Fecal Occult Blood Test (FOBT) followed by colonoscopy or sigmoidoscopy, can be considered replacing the colonoscopy screening alone or sigmoidoscopy screening alone. Finally, the implementation of an organized screening strategy should include a cost-effectiveness analysis of the different screening modalities so that the governments can take more rational decisions and better allocate resources in healthcare.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eFOBT followed by colonoscopy or sigmoidoscopy screening for CRC is more cost effective than colonoscopy screening alone and sigmoidoscopy screening alone, presenting as a screening strategy affordable to the society, robust for a wide range of relevant clinical and cost variables and not requiring an extraordinary demand in extra capacity. This further supports the progressive implementation of FOBT followed by colonoscopy or sigmoidoscopy-based programmes in Kuwait. Future studies in other countries using realistic adherence rates are needed, to corroborate our conclusions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003eThe study adhered to the principles of the Declaration of Helsinki and was approved (approval# 2017/694) by the Kuwait Ministry of Health Standing Committee for the Coordination of Health and Medical Research (Ethics Committee). All participants filled out a written informed consent for participation in the study.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research was conducted with Kuwait Foundation for the Advancement of Sciences (KFAS). Funding [No: PN19-13BH-01].\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eSMA, ELT, AMN, MA, RA, AE were involved in the design of the study. AMN and SMA were involved in data analysis, interpretation, and critical revision of the manuscript. MA, RA, AE, ELT, WQA, SMA were involved in data validation. AMN wrote the manuscript. AMN was involved in project administration. All authors reviewed and approved the final draft of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to acknowledge the financial support we received from Kuwait Foundation for the Advancement of Sciences (KFAS) to undertake this study. We would also like to extend our gratitude to Kuwait University\u0026rsquo;s Health Sciences Center Ethical Committee and the Standing Committee for Coordination of Health and Medical Research, Ministry of Health, Kuwait, for providing ethical approval to conduct this research. We would also like to acknowledge Dr. Mahmoud Annaka and Dr. Rihab Al Wotayan (Department of International Health Relations, Kuwait MOH), Dr. Amani Elbasmi (Unit of epidemiology and cancer registry, Kuwait Cancer Control Centre, Ministry of Health Kuwait), and Mrs. Maryam (Head of Medical Records of KCCC) for their valuable input in this study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available from the Kuwait Cancer Control Centre (KCCC) and Kuwait Ministry of Health, but restrictions apply to the availability of these data, and so are not publicly available. Data are however available from Dr. Amrizal Nur upon reasonable request and with permission of the Kuwait Ministry of Health.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eJonathan MK \u003cem\u003eet al\u003c/em\u003e. Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019. A Systematic Analysis for the Global Burden of Disease Study. \u003cem\u003eJAMA Oncology\u003c/em\u003e. \u003cstrong\u003e8\u003c/strong\u003e(3):420-444. doi:10.1001/ jamaoncol.2021.6987 (2022).\u003c/li\u003e\n \u003cli\u003eBray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. \u003cem\u003eCA Cancer J Clin\u003c/em\u003e. \u003cstrong\u003e68\u003c/strong\u003e(6):394\u0026ndash;424. doi:10.3322/caac.21492 (2018).\u003c/li\u003e\n \u003cli\u003eVekic B, Dragojevic-Simic V, Jakovljevic M, \u003cem\u003eet al\u003c/em\u003e. A correlation study of the colorectal cancer statistics and economic indicators in selected Balkan countries. \u003cem\u003eFront Public Health\u003c/em\u003e. \u003cstrong\u003e8\u003c/strong\u003e:29. doi:10.3389/ fpubh.2020.00029 (2020).\u003c/li\u003e\n \u003cli\u003eEl-Basmy, A., Kuwait Cancer Registry: \u003cem\u003eAnnual Report\u003c/em\u003e 2019 Kuwait Cancer Control Center Kuwait p. 122 (2019).\u003c/li\u003e\n \u003cli\u003eJodal HC, Helsingen LM, Anderson JC, \u003cem\u003eet al\u003c/em\u003e. Colorectal cancer screening with faecal testing, sigmoidoscopy or colonoscopy: a systematic review and network meta-analysis. \u003cem\u003eBMJ Open\u003c/em\u003e. \u003cstrong\u003e9\u003c/strong\u003e: e032773. doi:10.1136/ bmjopen-2019-032773 (2019).\u003c/li\u003e\n \u003cli\u003ehttps://www.uspreventiveservicestaskforce.org/home/getfilebytoken/2Wc3FRHpVDPX2jT_WzjEXX (Accessed, June 14, 2024)\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAlbreht T, Conroy F, Dalmas M, \u003cem\u003eet al.\u003c/em\u003e European Guide for Quality National Cancer Control Programmes. Ljubljana, Slovenia: \u003cem\u003eNational Institute of Public Health\u003c/em\u003e (2015).\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eFadhil I, Al Hammod S. Colorectal screening programs in gulf countries: The role of primary care. \u003cem\u003eJ Glob Oncol\u003c/em\u003e. \u003cstrong\u003e4\u003c/strong\u003e: Supplement 2,36s\u0026ndash;36s (2018)\u003c/li\u003e\n \u003cli\u003eSchoenfeld P. Quality in colorectal cancer screening with colonoscopy. \u003cem\u003eGastrointest Endosc Clin N Am\u003c/em\u003e. \u003cstrong\u003e30\u003c/strong\u003e(3):541\u0026ndash;551. doi: 10.1016/j.giec.2020.02.014 (2020)\u003c/li\u003e\n \u003cli\u003eOuyang DL, Getzenberg RH, Schoen RE. Noninvasive testing for colorectal cancer: a review. \u003cem\u003eAm J Gastroenterol\u003c/em\u003e. \u003cstrong\u003e100\u003c/strong\u003e (6):1393\u0026ndash;1403. doi:10.1111/j.1572-0241.2005.41427 (2005)\u003c/li\u003e\n \u003cli\u003eRedwood D, Asay E, Roberts D, \u003cem\u003eet al\u003c/em\u003e. Comparison of fecal occult blood tests for colorectal cancer screening in an Alaska Native population with high prevalence of Helicobacter pylori infection, 2008\u0026ndash;2012. \u003cem\u003ePrev Chronic Dis\u003c/em\u003e.\u003cstrong\u003e11\u003c/strong\u003e. doi:10.5888/pcd11.130281 (2014)\u003c/li\u003e\n \u003cli\u003eHewitson P, Glasziou P, Irwig L, Towler B, Watson E. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. \u003cem\u003eCochrane Database Syst Rev\u003c/em\u003e. (\u003cstrong\u003e1\u003c/strong\u003e): CD001216 2007)\u003c/li\u003e\n \u003cli\u003eShaukat A, Mongin SJ, Geisser MS, Lederle FA, Bond JH, Mandel JS, \u003cem\u003eet al.\u003c/em\u003e Long-Term Mortality after Screening for Colorectal Cancer. \u003cem\u003eN Engl J Med\u003c/em\u003e. \u003cstrong\u003e369\u003c/strong\u003e(12):1106\u0026ndash;14 (2013)\u003c/li\u003e\n \u003cli\u003eRex DK, Johnson DA, Anderson JC, Schoenfeld PS, Burke CA, Inadomi JM. American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008. \u003cem\u003eAm J Gastroenterol\u003c/em\u003e. \u003cstrong\u003e104\u0026nbsp;\u003c/strong\u003e(3):739\u0026ndash;50 (2009)\u003c/li\u003e\n \u003cli\u003eMuller AD, Sonnenberg A. Protection by Endoscopy Against Death from Colorectal Cancer: A Case\u0026ndash;control Study Among Veterans. \u003cem\u003eArch Intern Med\u003c/em\u003e. \u003cstrong\u003e155\u003c/strong\u003e(16):1741\u0026ndash;8 (1995)\u003c/li\u003e\n \u003cli\u003eBaxter NN, Goldwasser MA, Paszat LF, Saskin R, Urbach DR, Rabeneck L. Association of Colonoscopy and Death from Colorectal Cancer. \u003cem\u003eAnn Intern Med\u003c/em\u003e. \u003cstrong\u003e150\u003c/strong\u003e(1):1\u0026ndash;8 (2009)\u003c/li\u003e\n \u003cli\u003eMandel JS, Church TR, Bond JH, Ederer F, Geisser MS, Mongin SJ, et al. The Effect of Fecal Occult-Blood Screening on the Incidence of Colorectal Cancer. \u003cem\u003eN Engl J Med\u003c/em\u003e. \u003cstrong\u003e343\u003c/strong\u003e (22):1603\u0026ndash;7 (2000)\u003c/li\u003e\n \u003cli\u003eMandel JS, Church TR, Ederer F, Bond JH. Colorectal Cancer Mortality: Effectiveness of Biennial Screening for Fecal Occult Blood. \u003cem\u003eJ Natl Cancer Inst\u003c/em\u003e. \u003cstrong\u003e91\u003c/strong\u003e(5):434\u0026ndash;7 (1999)\u003c/li\u003e\n \u003cli\u003eKronborg O, Fenger C, Olsen J, J\u0026oslash;rgensen OD, S\u0026oslash;ndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. \u003cem\u003eLancet.\u003c/em\u003e\u003cstrong\u003e348\u003c/strong\u003e(9040):1467\u0026ndash;71 (1996)\u003c/li\u003e\n \u003cli\u003eHardcastle JD, Chamberlain JO, Robinson MHE, Moss SM, Amar SS, Balfour TW, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. \u003cem\u003eLancet.\u003c/em\u003e\u003cstrong\u003e348\u003c/strong\u003e(9040):1472\u0026ndash;7 (1996).\u003c/li\u003e\n \u003cli\u003eMandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, et al. Reducing Mortality from Colorectal Cancer by Screening for Fecal Occult Blood. \u003cem\u003eN Engl J Med\u003c/em\u003e. \u003cstrong\u003e328\u003c/strong\u003e(19):1365\u0026ndash;71 (1993).\u003c/li\u003e\n \u003cli\u003eQuintero E, Castells A, Bujnda L, Cubiella J, Salas D, Lanas \u0026Aacute;, et al. Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening. \u003cem\u003eN Engl J Med\u003c/em\u003e. \u003cstrong\u003e366\u003c/strong\u003e(8):697\u0026ndash;706 (2012).\u003c/li\u003e\n \u003cli\u003eFrazier AL, Colditz GA, Fuchs CS, Kuntz KM. Cost-effectiveness of Screening for Colorectal Cancer in the General Population. \u003cem\u003eJAMA\u003c/em\u003e. \u003cstrong\u003e284\u003c/strong\u003e(15):1954\u0026ndash;61 (2000).\u003c/li\u003e\n \u003cli\u003eZauber AG, Lansdorp-Vogelaar I, Knudsen AB, Wilschut J, van Ballegooijen M, Kuntz KM. Evaluating Test Strategies for Colorectal Cancer Screening: A Decision Analysis for the U.S. Preventive Services Task Force. \u003cem\u003eAnn Intern Med\u003c/em\u003e. \u003cstrong\u003e149\u003c/strong\u003e(9):659\u0026ndash;69 (2008).\u003c/li\u003e\n \u003cli\u003eTsoi KKF, Ng SSM, Leung MCM, Sung JJY. Cost-effectiveness analysis on screening for colorectal neoplasm and management of colorectal cancer in Asia. \u003cem\u003eAliment Pharmacol Ther\u003c/em\u003e. \u003cstrong\u003e28\u003c/strong\u003e(3):353\u0026ndash;63 (2008).\u003c/li\u003e\n \u003cli\u003eTappenden P, Chilcott J, Eggington S, Sakai H, Karnon J, Patnick J. Option appraisal of population-based colorectal cancer screening programmes in England. \u003cem\u003eGut\u003c/em\u003e. \u003cstrong\u003e56\u003c/strong\u003e(5):677\u0026ndash;84 (2007).\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWhynes DK, Neilson AR, Walker AR, Hardcastle JD. Faecal occult blood screening for colorectal cancer: is it cost-effective? \u003cem\u003eHealth Econ\u003c/em\u003e. \u003cstrong\u003e7\u003c/strong\u003e(1):21\u0026ndash;9 (1998)\u003c/li\u003e\n \u003cli\u003eWHO Cost\u0026ndash;effectiveness thresholds: pros and cons. Available from:\u0026nbsp;https:// www.who.int/ bulletin /volumes/94/12/15-164418/en/. [cited Nov 2020].\u003c/li\u003e\n \u003cli\u003eWoods B, Revill P, Sculpher M, Claxton K. Country-Level Cost-Effectiveness Thresholds: Initial Estimates and the Need for Further Research. \u003cem\u003eValue Health\u003c/em\u003e. \u003cstrong\u003e19\u003c/strong\u003e(8):929\u0026ndash;935. doi: 10.1016/j.jval.2016.02.017 (2016).\u003c/li\u003e\n \u003cli\u003eMinistry of Health Kuwait, Financial Affairs, Budget and Control Department, Cost Accounting Section. \u0026quot; Cost Analysis and Performance Evaluation for Government Health Services, 2016/2017, 39th Book Edition, page 81.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMinistry of Health Kuwait, Financial Affairs, Budget and Control Department. \u0026ldquo;Cost of services Resolution\u0026rdquo; (2019).\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSoerjomataram I, Thong MSY, Ezzati M, Lamont EB, Nusselder WJ, Van De Poll-Franse L V. Most colorectal cancer survivors live a large proportion of their remaining life in good health. \u003cem\u003eCancer Causes Control\u003c/em\u003e. \u003cstrong\u003e23\u003c/strong\u003e(9):1421\u0026ndash;8 (2012).\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHaley WE, Freeman. Colorectal Cancer Deaths Attributable to Nonuse of Screening in the United States. \u003cem\u003ePhysiol Behav\u003c/em\u003e. \u003cstrong\u003e176\u003c/strong\u003e(1):139\u0026ndash;48 (2018).\u003c/li\u003e\n \u003cli\u003eMasau Sekiguchi, Ataru Igarashi, Takahisa Matsuda, et.al. Optimal use of colonoscopy and fecal immunochemical test for population-based colorectal cancer screening: a cost-effectiveness analysis using Japanese data. \u003cem\u003eJapanese Journal of Clinical Oncology\u003c/em\u003e. \u003cstrong\u003e46\u003c/strong\u003e(2) 116\u0026ndash;125 (2016).\u003c/li\u003e\n \u003cli\u003eTappenden P, Chilcott J, Eggington S, Patnick J, Sakai H, Karnon J. Option appraisal of population-based colorectal cancer screening programmes in England. \u003cem\u003eGut\u003c/em\u003e. \u003cstrong\u003e56\u003c/strong\u003e:677\u0026ndash;84 (2007).\u003c/li\u003e\n \u003cli\u003eSweet A, Lee D, Gairy K, Phiri D, Reason T, Lock K. The impact of CT colonography for colorectal cancer screening on the UK NHS: costs, healthcare resources and health outcomes. \u003cem\u003eAppl Health Econ Health Policy\u003c/em\u003e. \u003cstrong\u003e9\u003c/strong\u003e:51\u0026ndash;64 (2011).\u003c/li\u003e\n \u003cli\u003eJapanese Society for Cancer of the Colon and Rectum. JSCCR Guidelines 2014 for the Treatment of Colorectal Cancer. Tokyo, Japan: Kanehara \u0026amp; Co., Ltd., (2014).\u003c/li\u003e\n \u003cli\u003ePang X, Xu B, Lian J, Wang R, Wang X, Shao J, et al. Real-world survival of colon cancer after radical surgery: A single-institutional retrospective analysis. \u003cem\u003eFront Oncol\u003c/em\u003e. \u003cstrong\u003e12\u003c/strong\u003e (September):1-12 (2022).\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eVan den Berg I, Coebergh van den Braak RRJ, van Vugt JLA, Ijzermans JNM, Buettner S. Correction to: Actual survival after resection of primary colorectal cancer: results from a prospective multicenter study (World Journal of Surgical Oncology, \u003cstrong\u003e19\u003c/strong\u003e, 1, (96), 10.1186/s12957-021-02207-4). \u003cem\u003eWorld J Surg Oncol\u003c/em\u003e. 2021;19(1):1\u0026ndash;10 (2021).\u003c/li\u003e\n \u003cli\u003eNelya Melnitchouk , Djora. Soeteman, Jennifer S. Davids, Adam Fields, Joshua Cohen, Farzad Noubary, Andrey Lukashenko, Olena O. Kolesnik and Karen. Freund. Cost‑effectiveness of colorectal cancer screening in Ukraine. \u003cem\u003eCost Eff Resour Alloc\u003c/em\u003e. \u003cstrong\u003e16\u003c/strong\u003e:20 https://doi.org/10.1186/s12962-018-0104-0 (2018).\u003c/li\u003e\n \u003cli\u003eGreenberg PD, \u003cem\u003eet al\u003c/em\u003e. A prospective multicenter evaluation of new fecal occult blood tests in patients undergoing colonoscopy. \u003cem\u003eAm J Gastroenterol\u003c/em\u003e. \u003cstrong\u003e95\u003c/strong\u003e(5):1331\u0026ndash;8 (2000).\u003c/li\u003e\n \u003cli\u003eImperiale TF, \u003cem\u003eet al.\u003c/em\u003e Fecal DNA versus fecal occult blood for colorectalcancer screening in an average-risk population. \u003cem\u003eN Engl J Med\u003c/em\u003e. \u003cstrong\u003e351\u003c/strong\u003e(26):2704\u0026ndash;14 (2004).\u003c/li\u003e\n \u003cli\u003eCollins JF, \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003eAccuracy of screening for fecal occult blood on a single stool sample obtained by digital rectal examination: a comparison with recommended sampling practice. \u003cem\u003eAnn Intern Med.\u003c/em\u003e \u003cstrong\u003e142\u003c/strong\u003e(2):81\u0026ndash;5 (2005).\u003c/li\u003e\n \u003cli\u003ePickhardt PJ, \u003cem\u003eet al.\u003c/em\u003e Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. \u003cem\u003eN Engl J Med\u003c/em\u003e. \u003cstrong\u003e349\u003c/strong\u003e(23):2191\u0026ndash;200 (2003).\u003c/li\u003e\n \u003cli\u003eCotton PB, \u003cem\u003eet al.\u003c/em\u003e Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia. \u003cem\u003eJAMA.\u003c/em\u003e \u003cstrong\u003e291\u003c/strong\u003e(14):1713\u0026ndash;9 (2004)\u003c/li\u003e\n \u003cli\u003eIrvine EJ, \u003cem\u003eet al.\u003c/em\u003e Prospective comparison of double contrast barium enema plus flexible sigmoidoscopy v colonoscopy in rectal bleeding: barium enema v colonoscopy in rectal bleeding. \u003cem\u003eGut\u003c/em\u003e. \u003cstrong\u003e29\u003c/strong\u003e(9):1188\u0026ndash;93 (1988).\u003c/li\u003e\n \u003cli\u003eFitzpatrick-Lewis D, Ali MU, Warren R, Kenny M, Sherifali D, Raina P. Screening for colorectal cancer: a systematic review and meta-analysis. \u003cem\u003eClin Colorectal Cancer\u003c/em\u003e, \u003cstrong\u003e15\u003c/strong\u003e(4): 298\u0026ndash;313. doi: 10.1016/j.clcc.2016.03.003 PMID:27133893 (2016).\u003c/li\u003e\n \u003cli\u003eHewitson P, Glasziou P, Watson E, Towler B, Irwig L. Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (Hemoccult): an update. \u003cem\u003eAm J Gastroenterol\u003c/em\u003e, \u003cstrong\u003e103\u003c/strong\u003e(6):1541\u0026ndash;9. doi:10.1111/j.1572-0241.2008. 01875.x PMID:18479499 (2008).\u003c/li\u003e\n \u003cli\u003eMoayyedi P, Achkar E. Does fecal occult blood testing really reduce mortality? A reanalysis of systematic review data. \u003cem\u003eAm J Gastroenterol\u003c/em\u003e. \u003cstrong\u003e101\u003c/strong\u003e(2):380\u0026ndash;4. doi:10.1111/ j. 1572-0241.2006.00537.x PMID:16454847 (2006).\u003c/li\u003e\n \u003cli\u003eHelm JF, Russo MW, Biddle AK, Simpson KN, Ransohoff DF, Sandler RS. Effectiveness and economic impact of screening for colorectal cancer by mass fecal occult blood testing\u003cem\u003e. Am J Gastroenterol.\u003c/em\u003e \u003cstrong\u003e95\u003c/strong\u003e(11):3250\u0026ndash;8. doi:10.1111/j.1572-0241.2000.03261.x PMID: 11095350 (2000).\u003c/li\u003e\n \u003cli\u003eWhynes DK; Nottingham FOB Screening Trial. Cost-effectiveness of screening for colorectal cancer: evidence from the Nottingham faecal occult blood trial. \u003cem\u003eJ Med Screen\u003c/em\u003e, \u003cstrong\u003e11\u003c/strong\u003e(1):11\u0026ndash;5. doi:10.1177/096914130301100104 PMID:15006108 (2004).\u003c/li\u003e\n \u003cli\u003ePignone M, Saha S, Hoerger T, Mandelblatt J. Cost-effectiveness analyses of colorectal cancer screening: a systematic review for the U.S. Preventive Services Task Force. \u003cem\u003eAnn Intern Med\u003c/em\u003e, \u003cstrong\u003e137\u003c/strong\u003e(2):96\u0026ndash;104. doi:10.7326/0003-4819-137-2-200207160-00007 PMID:12118964 (2002).\u003c/li\u003e\n \u003cli\u003eLansdorp-Vogelaar I, Knudsen AB, Brenner H. Cost-effectiveness of colorectal cancer screening. \u003cem\u003eEpidemiol Rev\u003c/em\u003e, \u003cstrong\u003e33\u003c/strong\u003e(1):88\u0026ndash;100. doi:10.1093/epirev/mxr004 PMID:21633092 (2011).\u003c/li\u003e\n \u003cli\u003ePatel SS, Kilgore ML. Cost effectiveness of colorectal cancer screening strategies. \u003cem\u003eCancer Contr.\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e(2):248\u0026ndash;58. doi:10.1177/107327481502200219 PMID:26068773 (2015).\u003c/li\u003e\n \u003cli\u003eKingsley J, Karanth S, Revere FL, Agrawal D. Cost effectiveness of screening colonoscopy depends on adequate bowel preparation rates \u0026ndash; a modeling study. \u003cem\u003ePLoS One.\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e11\u003c/strong\u003e(12):e0167452. doi: 10.1371/journal.pone.0167452 PMID:27936028 (2016).\u003c/li\u003e\n \u003cli\u003eBarzi A, Lenz H-J, Quinn DI, Sadeghi S. Comparative effectiveness of screening strategies for colorectal cancer. \u003cem\u003eCancer\u003c/em\u003e. \u003cstrong\u003e123\u003c/strong\u003e(9):1516\u0026ndash;27. doi:10.1002/cncr.30518 PMID:28117881 (2017).\u003c/li\u003e\n \u003cli\u003eLee KS, Park EC. Cost effectiveness of colorectal cancer screening interventions with their effects on health disparity being considered. \u003cem\u003eCancer Res Treat\u003c/em\u003e. \u003cstrong\u003e48\u003c/strong\u003e(3):1010\u0026ndash;9. doi:10.4143/crt.2015.279 PMID:26727714 (2016).\u003c/li\u003e\n \u003cli\u003eLadabaum U, Mannalithara A. Comparative effectiveness and cost effectiveness of a multitarget stool DNA test to screen for colorectal neoplasia. \u003cem\u003eGastroenterology\u003c/em\u003e. \u003cstrong\u003e151\u003c/strong\u003e(3):427\u0026ndash;439.e6. doi: 10.1053/j.gastro.2016.06.003 PMID:27311556 (2016).\u003c/li\u003e\n \u003cli\u003eHeitman SJ, Hilsden RJ, Au F, Dowden S, Manns BJ. Colorectal cancer screening for average-risk North Americans: an economic evaluation. \u003cem\u003ePLoS Med.\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e7\u003c/strong\u003e(11):e1000370. doi: 10.1371/journal.pmed.1000370 PMID:21124887 (2010).\u003c/li\u003e\n \u003cli\u003eTelford JJ, Levy AR, Sambrook JC, Zou D, Enns RA. The cost-effectiveness of screening for colorectal cancer. \u003cem\u003eCMAJ\u003c/em\u003e. \u003cstrong\u003e182\u003c/strong\u003e(12):1307\u0026ndash;13. doi:10.1503/cmaj.090845 PMID:20624866 (2010).\u003c/li\u003e\n \u003cli\u003eGoede SL, Rabeneck L, van Ballegooijen M, Zauber AG, Paszat LF, Hoch JS, \u003cem\u003eet al\u003c/em\u003e. Harms, benefits and costs of fecal immunochemical testing versus guaiac fecal occult blood testing for colorectal cancer screening. \u003cem\u003ePLoS One\u003c/em\u003e, \u003cstrong\u003e12\u003c/strong\u003e(3):e0172864. doi: 10.1371 /journal.pone. 0172864 PMID:28296927 (2017).\u003c/li\u003e\n \u003cli\u003eSharp L, Tilson L, Whyte S, O\u0026rsquo;Ceilleachair A, Walsh C, Usher C, \u003cem\u003eet al.\u003c/em\u003e Cost-effectiveness of population-based screening for colorectal cancer: a comparison of guaiac-based faecal occult blood testing, faecal immunochemical testing and flexible sigmoidoscopy. \u003cem\u003eBr J Cancer\u003c/em\u003e, \u003cstrong\u003e106\u003c/strong\u003e(5):805\u0026ndash;16. doi:10.1038/bjc.2011.580 PMID:22343624 (2012).\u003c/li\u003e\n \u003cli\u003eWhyte S, Chilcott J, Halloran S. Reappraisal of the options for colorectal cancer screening in England. \u003cem\u003eColorectal Dis\u003c/em\u003e. \u003cstrong\u003e14\u003c/strong\u003e(9):e547\u0026ndash;61. doi:10.1111/j.1463-1318.2012. 03014.x PMID:22390210 (2012).\u003c/li\u003e\n \u003cli\u003ePil L, Fobelets M, Putman K, Trybou J, Annemans L. Cost-effectiveness and budget impact analysis of a population-based screening program for colorectal cancer. \u003cem\u003eEur J Intern Med\u003c/em\u003e, \u003cstrong\u003e32\u003c/strong\u003e:72\u0026ndash;8. doi: 10.1016/j.ejim.2016.03.031 PMID:27157827 (2016).\u003c/li\u003e\n \u003cli\u003eAronsson M, Carlsson P, Levin L-\u0026Aring;, Hager J, Hultcrantz R. Cost-effectiveness of high-sensitivity faecal immunochemical test and colonoscopy screening for colorectal cancer. \u003cem\u003eBr J Surg.\u003c/em\u003e \u003cstrong\u003e104\u003c/strong\u003e(8):1078\u0026ndash;86. doi:10.1002/bjs.10536 PMID:28561259 (2017).\u003c/li\u003e\n \u003cli\u003eBarouni M, Larizadeh MH, Sabermahani A, Ghaderi H. Markov\u0026rsquo;s modeling for screening strategies for colorectal cancer. \u003cem\u003eAsian Pac J Cancer Prev\u003c/em\u003e, \u003cstrong\u003e13\u003c/strong\u003e(10):5125\u0026ndash;9. doi:10.7314/APJCP.2012.13.10.5125 PMID:23244122 (2012).\u003c/li\u003e\n \u003cli\u003eDan YY, Chuah BYS, Koh DCS, Yeoh KG. Screening based on risk for colorectal cancer is the most cost-effective approach. \u003cem\u003eClin Gastroenterol Hepatol,\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e:3: 266\u0026ndash;71.e1, 6. doi:10.1016/j.cgh.2011.11.011 PMID:22100624 (2012).\u003c/li\u003e\n \u003cli\u003eWang ZH, Gao Q-Y, Fang J-Y. Repeat colonoscopy every 10 years or single colonoscopy for colorectal neoplasm screening in average-risk Chinese: a cost-effectiveness analysis. \u003cem\u003eAsian Pac J Cancer Prev\u003c/em\u003e. \u003cstrong\u003e13\u003c/strong\u003e(5):1761\u0026ndash;6. doi:10.7314/APJCP.2012.13.5.1761 PMID:22901118 (2012).\u003c/li\u003e\n \u003cli\u003eLam CL, Law WL, Poon JT, Chan P, Wong CK, McGhee SM, \u003cem\u003eet al\u003c/em\u003e. Health-related quality of life in patients with colorectal neoplasm and cost-effectiveness of colorectal cancer screening in Hong Kong. \u003cem\u003eHong Kong Med J\u003c/em\u003e, \u003cstrong\u003e21\u003c/strong\u003e(Suppl 6):4\u0026ndash;8. PMID:26645874 (2015).\u003c/li\u003e\n \u003cli\u003eWong MC, Ching JYL, Chan VCW, Sung JJY. The comparative cost-effectiveness of colorectal cancer screening using faecal immunochemical test vs. colonoscopy. \u003cem\u003eSci Rep\u003c/em\u003e, \u003cstrong\u003e5\u003c/strong\u003e(1):13568. doi:10.1038/srep13568 PMID:26338314 (2015).\u003c/li\u003e\n \u003cli\u003eSekiguchi M, Igarashi A, Matsuda T, Matsumoto M, Sakamoto T, Nakajima T, et al. Optimal use of colonoscopy and fecal immunochemical test for population-based colorectal cancer screening: a cost-effectiveness analysis using Japanese data. \u003cem\u003eJpn J Clin Oncol\u003c/em\u003e. \u003cstrong\u003e46\u003c/strong\u003e(2):116\u0026ndash;25. doi:10.1093/jjco/hyv186 PMID:26685321 (2016).\u003c/li\u003e\n \u003cli\u003eWHO, IARC (2019), Colorectal cancer screening. IARC Handb Cancer Prev. 17:1\u0026ndash;300. Available from: http://publications.iarc.fr/573. (Accessed 18.6.2024).\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eLittlejohn C, Hilton S, Macfarlane GJ, Phull P. Systematic review and meta-analysis of the evidence for flexible sigmoidoscopy as a screening method for the prevention of colorectal cancer. \u003cem\u003eBr J Surg\u003c/em\u003e, \u003cstrong\u003e99\u003c/strong\u003e(11):1488\u0026ndash;500. doi:10.1002/bjs.8882 PMID:23001715 (2012).\u003c/li\u003e\n \u003cli\u003eHolme , Loberg M, Kalager M, Bretthauer M, Hern\u0026aacute;n MA, Aas E, \u003cem\u003eet al\u003c/em\u003e. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. \u003cem\u003eJAMA\u003c/em\u003e, \u003cstrong\u003e312\u003c/strong\u003e(6):606\u0026ndash;15. doi:10.1001/jama.2014.8266 PMID:25117129 (2014).\u003c/li\u003e\n \u003cli\u003eBerry DP, Clarke P, Hardcastle JD, Vellacott KD. Randomized trial of the addition of flexible sigmoidoscopy to faecal occult blood testing for colorectal neoplasia population screening. \u003cem\u003eBr J Surg\u003c/em\u003e, \u003cstrong\u003e84\u003c/strong\u003e(9):1274\u0026ndash;6. doi:10.1002/bjs.1800840922 PMID:9313712 (1997).\u003c/li\u003e\n \u003cli\u003eVerne JECW, Aubrey R, Love SB, Talbot IC, Northover JM. Population based randomized study of uptake and yield of screening by flexible sigmoidoscopy compared with screening by fecal occult blood testing. \u003cem\u003eBMJ\u003c/em\u003e, \u003cstrong\u003e317\u003c/strong\u003e(7152):182\u0026ndash;5. doi:10.1136/bmj.317.7152.182 (1998).\u003c/li\u003e\n \u003cli\u003eSekiguchi M, Igarashi A, Matsuda T, Matsumoto M, Sakamoto T, Nakajima T, \u003cem\u003eet al.\u003c/em\u003e Optimal use of colonoscopy and fecal immunochemical test for population-based colorectal cancer screening: a cost-effectiveness analysis using Japanese data. \u003cem\u003eJpn J Clin Oncol\u003c/em\u003e, \u003cstrong\u003e46\u003c/strong\u003e(2):116\u0026ndash;25. doi:10.1093/jjco/hyv186 PMID:26685321 (2016).\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eAmrizal Muhammad Nur,\u0026nbsp;\u003c/strong\u003eEleni L. Tolma, Syed Mohamed Aljunid, Joseph C. Longenecker, Dina Zein, Mahmoud Annaka, Rihab Alwotayan, Amani Elbasmi. 2024. Practices, Attitudes, and Perceived Barriers in Colorectal Cancer Screening Among Primary Care Physicians in Kuwait: Insight from A Cross Sectional Study. \u003cem\u003eMalaysian Journal of Public Health\u0026nbsp;\u003c/em\u003e(2024) Vol. 24(1):268-279.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cost-effectiveness, Colorectal cancer, Fecal occult blood testing, Colonoscopy, Sigmoidoscopy","lastPublishedDoi":"10.21203/rs.3.rs-4654485/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4654485/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eColorectal cancer (CRC) poses a significant health challenge in Kuwait, ranking as the second most common cancer with a 2019 incidence rate of 13.2 cases per 100,000 people. This study evaluates the cost-effectiveness (CEA) of CRC screening methods from the perspective of Kuwait's healthcare providers. Using a Decision Tree Analysis Model, the study compared three screening modalities: Fecal Occult Blood Test (FOBT) followed by colonoscopy or sigmoidoscopy, colonoscopy alone, sigmoidoscopy alone and alongside no screening. Over a 10-year period post-diagnosis, the model tracked costs and outcomes based on CRC patients' life expectancy, expressing results using Incremental Cost Effectiveness Ratios (ICERs). Result: FOBT followed by colonoscopy or sigmoidoscopy emerged as the most cost-effective option, costing USD 3,573.00 and yielding 7.7 Quality-Adjusted Life Years (QALYs). In comparison, no screening resulted in 7.2 QALYs at USD 4,084.00, while sigmoidoscopy and colonoscopy alone provided 6.8 QALYs each, costing USD 4,905.00 and USD 5,002.00, respectively. Sensitivity analyses explored uncertainties in cost and outcome estimates. Conclusion: FOBT followed by colonoscopy or sigmoidoscopy could efficiently utilize healthcare resources compared to other modalities or no screening. This approach offers critical guidance for healthcare policymakers in Kuwait, advocating for the adoption of combined FOBT and colonoscopy or sigmoidoscopy strategies to enhance CRC screening effectiveness and economic efficiency.\u003c/p\u003e","manuscriptTitle":"Cost effectiveness analysis of colorectal cancer screening modalities in Kuwait: Comparison of Three Alternative Screening Strategies","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 20:50:11","doi":"10.21203/rs.3.rs-4654485/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-19T05:24:29+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-18T15:12:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-25T07:10:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"328033517572816441769208744528307650403","date":"2024-09-24T08:15:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"250768521248500045699728056138706167509","date":"2024-09-19T08:13:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-18T22:57:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-18T22:54:47+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-29T01:51:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-25T04:10:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-06-28T11:29:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b2801768-7795-44ca-8c3c-3a68ccfba36f","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":36328681,"name":"Biological sciences/Cancer"},{"id":36328682,"name":"Health sciences/Health care"},{"id":36328683,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2025-03-03T16:05:30+00:00","versionOfRecord":{"articleIdentity":"rs-4654485","link":"https://doi.org/10.1038/s41598-025-91119-4","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-03-01 15:57:59","publishedOnDateReadable":"March 1st, 2025"},"versionCreatedAt":"2024-08-26 20:50:11","video":"","vorDoi":"10.1038/s41598-025-91119-4","vorDoiUrl":"https://doi.org/10.1038/s41598-025-91119-4","workflowStages":[]},"version":"v1","identity":"rs-4654485","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4654485","identity":"rs-4654485","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}