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

doi:10.21203/rs.3.rs-4654485/v1

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

https://doi.org/10.21203/rs.3.rs-4654485/v1

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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

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 Years¹. 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 cancer⁴. 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 100,000⁴.

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 mortality⁵.

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, sigmoidoscopy⁶, 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 men⁷. 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 methods⁸.

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 performance⁹. 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 gFOBT¹². FOBT screening has been shown to be beneficial in lowering the annual incidence eand death of CRC¹³. Alternative methods for CRC screening include colonoscopy and flexible sigmoidoscopy¹⁴, 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 2021²².

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 rate²³ and colonoscopy every 10 years²⁴, 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, respectively²⁵. 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.

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 charges³⁰. 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 hospital³¹. 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 patients³². 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 applied³³. 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.

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.

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 acceptable⁵⁰. Whynes et al. (2004) followed up on the Nottingham trial, reaffirming the cost-effectiveness of gFOBT screening⁵¹. 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 screening⁵⁴. Ladabaum & Mannalithara (2016) updated their model with new CEA results of CRC screening using gFOBT, showing cost savings⁵⁸. 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 statistics⁷².

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 alone⁷³. 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 screening⁷⁴. 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 cancer⁷⁵. 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 cancer⁷⁶. 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 alone⁷⁷.

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 published⁷⁸. 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.

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.

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.

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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.

No competing interests reported.

AppendixADecisiontreeforcolorectalcancerscreeningoptions.pdf
Additional Information Appendix A: Figure-1: Decision tree for colorectal cancer screening options with high resolution in the PDF format.

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

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Abstract

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Introduction

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Study population

CRC screening strategy:

Development of an economic model

(1) Cost Information

(2) Effectiveness of health outcome

(3) Probability data

(4) Assumptions

Results

Sensitivity analysis

Discussion

Limitations and Future Directions

Implications for Practice and Policy

Conclusions

Declarations

Ethics approval and consent to participate

Competing interests

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Author Contribution

Acknowledgement

Data Availability

References

Additional Declarations

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