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      Personalized medicine in colorectal cancer diagnosis and treatment: a systematic review of health economic evaluations

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          Abstract

          Background

          Due to its epidemiological relevance, several studies have been performed to assess the cost-effectiveness of diagnostic tests and treatments in colorectal cancer (CRC) patients.

          Objective

          We reviewed economic evaluations on diagnosis of inherited CRC-syndromes and genetic tests for the detection of mutations associated with response to therapeutics.

          Methods

          A systematic literature review was performed by searching the main literature databases for relevant papers on the field, published in the last 5 years.

          Results

          20 studies were included in the final analysis: 14 investigating the cost-effectiveness of hereditary-CRC screening; 5 evaluating the cost-effectiveness of KRAS mutation assessment before treatment; and 1 study analysing the cost-effectiveness of genetic tests for early-stage CRC patients prognosis. Overall, we found that: (a) screening strategies among CRC patients were more effective than no screening; (b) all the evaluated interventions were cost-saving for certain willingness-to-pay (WTP) threshold; and (c) all new CRC patients diagnosed at age 70 or below should be screened. Regarding patients treatment, we found that KRAS testing is economically sustainable only if anticipated in patients with non-metastatic CRC (mCRC), while becoming unsustainable, due to an incremental cost-effectiveness ratio (ICER) beyond the levels of WTP-threshold, in all others evaluated scenarios.

          Conclusions

          The poor evidence in the field, combined to the number of assumptions done to perform the models, lead us to a high level of uncertainty on the cost-effectiveness of genetic evaluations in CRC, suggesting that major research is required in order to assess the best combination among detection tests, type of genetic test screening and targeted-therapy.

          Electronic supplementary material

          The online version of this article (10.1186/s12962-018-0085-z) contains supplementary material, which is available to authorized users.

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          Most cited references32

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          Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis.

          Testing has been advocated for all persons with newly diagnosed colorectal cancer to identify families with the Lynch syndrome, an autosomal dominant cancer-predisposition syndrome that is a paradigm for personalized medicine. To estimate the effectiveness and cost-effectiveness of strategies to identify the Lynch syndrome, with attention to sex, age at screening, and differential effects for probands and relatives. Markov model that incorporated risk for colorectal, endometrial, and ovarian cancers. Published literature. All persons with newly diagnosed colorectal cancer and their relatives. Lifetime. Third-party payer. Strategies based on clinical criteria, prediction algorithms, tumor testing, or up-front germline mutation testing, followed by tailored screening and risk-reducing surgery. Life-years, cancer cases and deaths, costs, and incremental cost-effectiveness ratios. The benefit of all strategies accrued primarily to relatives with a mutation associated with the Lynch syndrome, particularly women, whose life expectancy could increase by approximately 4 years with hysterectomy and salpingo-oophorectomy and adherence to colorectal cancer screening recommendations. At current rates of germline testing, screening, and prophylactic surgery, the strategies reduced deaths from colorectal cancer by 7% to 42% and deaths from endometrial and ovarian cancer by 1% to 6%. Among tumor-testing strategies, immunohistochemistry followed by BRAF mutation testing was preferred, with an incremental cost-effectiveness ratio of $36,200 per life-year gained. The number of relatives tested per proband was a critical determinant of both effectiveness and cost-effectiveness, with testing of 3 to 4 relatives required for most strategies to meet a threshold of $50,000 per life-year gained. Immunohistochemistry followed by BRAF mutation testing was preferred in 59% of iterations in probabilistic sensitivity analysis at a threshold of $100,000 per life-year gained. Screening for the Lynch syndrome with immunohistochemistry followed by BRAF mutation testing only up to age 70 years cost $44,000 per incremental life-year gained compared with screening only up to age 60 years, and screening without an upper age limit cost $88,700 per incremental life-year gained compared with screening only up to age 70 years. Other types of cancer, uncertain family pedigrees, and genetic variants of unknown significance were not considered. Widespread colorectal tumor testing to identify families with the Lynch syndrome could yield substantial benefits at acceptable costs, particularly for women with a mutation associated with the Lynch syndrome who begin regular screening and have risk-reducing surgery. The cost-effectiveness of such testing depends on the participation rate among relatives at risk for the Lynch syndrome. National Institutes of Health.
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            Modelling in economic evaluation: an unavoidable fact of life.

            The role of modelling in economic evaluation is explored by discussing, with examples, the uses of models. The expanded use of pragmatic clinical trials as an alternative to models is discussed. Some suggestions for good modelling practice are made.
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              Next-Generation Sequencing Panels for the Diagnosis of Colorectal Cancer and Polyposis Syndromes: A Cost-Effectiveness Analysis.

              To evaluate the cost effectiveness of next-generation sequencing (NGS) panels for the diagnosis of colorectal cancer and polyposis (CRCP) syndromes in patients referred to cancer genetics clinics.
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                Author and article information

                Contributors
                +39 0961 3694976 , guglielmo@unicz.it
                nicolettastaropoli@gmail.com
                mgiancotti@unicz.it
                mauro@unicz.it
                Journal
                Cost Eff Resour Alloc
                Cost Eff Resour Alloc
                Cost Effectiveness and Resource Allocation : C/E
                BioMed Central (London )
                1478-7547
                22 January 2018
                22 January 2018
                2018
                : 16
                : 2
                Affiliations
                ISNI 0000 0001 2168 2547, GRID grid.411489.1, Department of Clinical and Experimental Medicine, , “Magna Græcia” University, ; Viale Europa 88100, Catanzaro, Italy
                Author information
                http://orcid.org/0000-0001-9748-3974
                Article
                85
                10.1186/s12962-018-0085-z
                5778687
                29386984
                134626c4-76af-40c1-8e1c-d4bac3c8364b
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 September 2017
                : 3 January 2018
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Public health
                personalized medicine,economic evaluation,cost-effectiveness analysis,colorectal cancer,crc

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