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Most bowel cancers are initially treated with surgery, but around 17% spread to the liver. When this happens, sometimes the liver tumour can be treated surgically, or chemotherapy may be used to shrink the tumour to make surgery possible. Kirsten rat sarcoma viral oncogene (<jats:italic>KRAS<\/jats:italic>) mutations make some tumours less responsive to treatment with biological therapies such as cetuximab. There are a variety of tests available to detect these mutations. These vary in the specific mutations that they detect, the amount of mutation they detect, the amount of tumour cells needed, the time to give a result, the error rate and cost.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-2\"><jats:title>Objectives<\/jats:title><jats:p>To compare the performance and cost-effectiveness of<jats:italic>KRAS<\/jats:italic>mutation tests in differentiating adults with metastatic colorectal cancer whose metastases are confined to the liver and are unresectable and who may benefit from first-line treatment with cetuximab in combination with standard chemotherapy from those who should receive standard chemotherapy alone.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-3\"><jats:title>Data sources<\/jats:title><jats:p>Thirteen databases, including MEDLINE and EMBASE, research registers and conference proceedings were searched to January 2013. Additional data were obtained from an online survey of laboratories participating in the UK National External Quality Assurance Scheme pilot for<jats:italic>KRAS<\/jats:italic>mutation testing.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-4\"><jats:title>Methods<\/jats:title><jats:p>A systematic review of the evidence was carried out using standard methods. Randomised controlled trials were assessed for quality using the Cochrane risk of bias tool. Diagnostic accuracy studies were assessed using the QUADAS-2 tool. There were insufficient data for meta-analysis. For accuracy studies we calculated sensitivity and specificity together with 95% confidence intervals (CIs). Survival data were summarised as hazard ratios and tumour response data were summarised as relative risks, with 95% CIs. The health economic analysis considered the long-term costs and quality-adjusted life-years associated with different tests followed by treatment with standard chemotherapy or cetuximab plus standard chemotherapy. The analysis took a \u2018no comparator\u2019 approach, which implies that the cost-effectiveness of each strategy will be presented only compared with the next most cost-effective strategy. The de novo model consisted of a decision tree and Markov model.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-5\"><jats:title>Results<\/jats:title><jats:p>The online survey indicated no differences between tests in batch size, turnaround time, number of failed samples or cost. The literature searches identified 7903 references, of which seven publications of five studies were included in the review. Two studies provided data on the accuracy of<jats:italic>KRAS<\/jats:italic>mutation testing for predicting response to treatment in patients treated with cetuximab plus standard chemotherapy. Four RCTs provided data on the clinical effectiveness of cetuximab plus standard chemotherapy compared with that of standard chemotherapy in patients with<jats:italic>KRAS<\/jats:italic>wild-type tumours. There were no clear differences in the treatment effects reported by different studies, regardless of which<jats:italic>KRAS<\/jats:italic>mutation test was used to select patients. In the \u2018linked evidence\u2019 analysis the Therascreen<jats:sup>\u00ae<\/jats:sup><jats:italic>KRAS<\/jats:italic>RGQ PCR Kit (QIAGEN) was more expensive but also more effective than pyrosequencing or direct sequencing, with an incremental cost-effectiveness ratio of \u00a317,019 per quality-adjusted life-year gained. In the \u2018assumption of equal prognostic value\u2019 analysis the total costs associated with the various testing strategies were similar.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-6\"><jats:title>Limitations<\/jats:title><jats:p>The results assume that the differences in outcomes between the trials were solely the result of the different mutation tests used to distinguish between patients; this assumption ignores other factors that might explain this variation.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-7\"><jats:title>Conclusions<\/jats:title><jats:p>There was no strong evidence that any one<jats:italic>KRAS<\/jats:italic>mutation test was more effective or cost-effective than any other test.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-8\"><jats:title>Study registration<\/jats:title><jats:p>PROSPERO CRD42013003663.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-9\"><jats:title>Funding<\/jats:title><jats:p>The National Institute for Health Research Health Technology Assessment programme.<\/jats:p><\/jats:sec>","DOI":"10.3310\/hta18620","type":"journal-article","created":{"date-parts":[[2014,10,16]],"date-time":"2014-10-16T07:02:50Z","timestamp":1413442970000},"page":"1-132","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":64,"title":["KRAS mutation testing of tumours in adults with metastatic colorectal cancer: a systematic review and cost-effectiveness analysis"],"prefix":"10.3310","volume":"18","author":[{"given":"Marie","family":"Westwood","sequence":"first","affiliation":[{"name":"Kleijnen Systematic Reviews Ltd, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thea","family":"van Asselt","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, the 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caro","family":"Noake","sequence":"additional","affiliation":[{"name":"Kleijnen Systematic Reviews Ltd, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Ross","sequence":"additional","affiliation":[{"name":"Kleijnen Systematic Reviews Ltd, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Severens","sequence":"additional","affiliation":[{"name":"Institute of Health Policy and Management, Erasmus University, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos","family":"Kleijnen","sequence":"additional","affiliation":[{"name":"School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, the 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