The protocol of this systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P 2015)  guidelines (see Additional file 1). The protocol is also registered in the PROSPERO database, the International prospective register of systematic reviews (CRD42022296113).
The PRISMA  guidance recommendations have been used to design the systematic review. The systematic review will apply the Consolidated Health Economic Evaluation Reporting Standards (CHEERS)  statement to extract relevant data from studies retrieved.
Decision Problem Review Question
The objective of this review is to identify the modelling methods and assumptions used for colorectal cancer screening globally and to derive cost-effective analysis / cost-utility analysis / cost-benefit analysis outcomes. The following specific questions will be addressed in the review.
1. What is the model structure (for example, Markov, Semi-Markov, Discrete event simulation) used in a particular colorectal cancer screening programme?
2. What are the model assumptions for each model structure e.g., time horizons, LYGs, QALYs, costs and other parameters?
3. What is the associated background mortality with the population used for the building of this model? Are other model parameters included, such as efficiency parameters?
Defining inclusion criteria
• Participants - Individuals eligible to receive a colorectal cancer screening invitation.
• Interventions - Interventions for screening for colorectal cancer, for example, faecal immunochemical test (FIT), faecal occult blood test (FOBT), flexible sigmoidoscopy, colonoscopy, computed tomography colonography (CTC), double-contrast barium enema, or any other screening methods, which are not included in this list.
• Comparators - Age range of the screening population and thresholds associated with quantitative FIT testing and FOBT testing.
• Outcomes - incremental cost-effectiveness ratio (ICER), net-benefit, life-years gained (LYGs), quality-adjusted life-years (QALYs), costs, colonoscopy utilisation or any other unit of health gain and screening harm.
• Study Designs - All economic evaluation academic papers which are published and discuss an economic evaluation model are eligible for inclusion in the review.
Defining exclusion criteria
• Participants - Only human patients to be included in the papers and not animals.
• Interventions - Interventions used outside of the interventions listed above.
• Study Designs - To avoid potentially high bias, case reports and case series are excluded from this review. Randomised controlled trials and cohort studies are needed for the quality evaluation of models but are not directly necessary for this review.
• Time frame - Academic papers published between January 2011 and December 2021.
Identifying research evidence
The search strategy was optimised from advice by the Specialist Medical Librarian at the host institution, who suggested using several databases to meet the needs of the review. The databases used for the planned strategy were MEDLINE, EMBASE, Web Of Science and Scopus. Searches were conducted in December 2021 using the
MESH search terms (see Additional File 2), and updated in January 2022 for the following:
1. Colorectal Neoplasms OR colorectal cancer OR bowel cancer OR colorectal
2. screen* OR Mass Screening
3. Cost-Benefit Analysis OR cost-effective* OR cost-utility OR quality-adjusted life-years OR life-year* gain* OR economic evaluat* OR health technology assessment OR incremental cost-effective* ratio* OR ICER* OR cost analys* OR qaly* OR lyg*
Searches 1, 2 and 3 are then combined by AND. Only English papers were included in this review since there was no funding to translate non-English language papers. The studies which fulfil this criterion were then screened for inclusion by the PICOS criteria.
There will be three stages in the study selection process.
1. All results found from the initial search will be downloaded into COVIDENCE systematic review manager  to facilitate the review management, including the removal of duplicated articles before starting the title and abstract review.
2. The titles and abstracts of the papers will be screened by two reviewers following the PICOS criteria.
3. The full text of the eligible papers will be reviewed to further confirm their eligibility.
If the two reviewers disagree on papers, a third reviewer will be introduced and a consensus of the three reviewers will be made. Also, in the case that multiple papers report the same model/method, the most recent paper with the overall model structure will be included, thus resulting in other papers with this model being discarded. The papers excluded will be deemed ineligible according to the PICOS criteria.
A sample of papers will be used to pilot the selection process using the inclusion criteria, to determine whether papers are being selected appropriately. If any noticeable or fundamental changes need to be addressed to the inclusion criteria, they can be iteratively improved by the reviewers to support the objectives.
The data extraction process will apply the CHEERS checklist for quality reporting of economic evaluations, as recommended by the EQUATOR Network . The extracted data will mirror the expected format of this standard for reporting and use this to benchmark and guide the collation of data. The data extraction focuses on the model design, parameter selection, modelling methods - to examine best practices and understand the sources of variation in methods, the likely impact on study quality, and therefore its appropriateness for future application.
Papers eligible to move on from the initial screening of the searches will undergo quality assessment, where detailed information on study characteristics will be collected, based on the CHEERS guidelines checklist.
To document the study selection process, a PRISMA flow chart showing the number of papers remaining at each stage will be presented.
As the purpose of this review was to examine the modelling methods used to evaluate the health economics of colorectal cancer screening, the results will be presented qualitatively. The studies included in the final review will be tabulated by the CHEERS checklist. Some key features will include the type of study, outcome measure and the interventions included. Thus, methodological study quality will be addressed, for example, the economic model choice, effectiveness measure, and cost measures. Examination of the results will also collate to any sensitivity analyses performed in the studies to help identify if there are any changes to the study conclusions due to the susceptibility of cost-effectiveness to key model parameters.
Results found from this systematic review will be published in a peer-reviewed journal and disseminated at international conferences and institutional academic workshops.