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The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer |
Mvundura M, Grosse SD, Hampel H, Palomaki GE |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. CRD summary This study examined the cost-effectiveness of genetic testing strategies to identify Lynch syndrome among patients newly diagnosed with colorectal cancer and their first-degree relatives. Strategies that included immunohistochemistry were more likely to be cost-effective than those using microsatellite instability testing. The most cost-effective strategy was universal immunohistochemistry, followed by BRAF V600E mutation testing, and targeted mismatch repair gene sequencing. The methods were valid and should ensure the validity of the authors’ conclusions. Type of economic evaluation Cost-effectiveness analysis, cost-utility analysis Study objective This study examined the cost-effectiveness of genetic testing strategies for identifying Lynch syndrome among patients, who were newly diagnosed with colorectal cancer, and their first-degree relatives. Interventions There were four testing strategies; three of them included a genetic tumour test, by immunohistochemistry or microsatellite instability, and they all included sequencing of mismatch repair genes. These strategies were applied universally to all patients who were newly diagnosed with colorectal cancer and their first-degree relatives or for only those under 50 years old, and they were compared with no testing.
Strategy one was immunohistochemistry, with testing for the BRAF V600E mutation for those where the MLH1 protein stain was absent and mismatch repair for those where the MSH2, MSH6, or PMS2 stain was absent or the BRAF mutation was not found. Strategy two was immunohistochemistry, with mismatch repair for all those with an absent stain (MLH1, MSH2, MSH6, or PMS2). Strategy three was a microsatellite instability test, with mismatch repair for those with high instability. Strategy four was mismatch repair for all. Methods Analytical approach:The analysis was based on a decision-tree model, with a lifetime horizon. The authors stated that the perspective of the health care system was adopted.
Effectiveness data:Most of the clinical evidence came from a selection of relevant published studies, the main one being the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) evidence review. The colorectal cancer mortality data were from the Surveillance, Epidemiology and End Results (SEER) statistics. Some model inputs, such as the number of relatives per individual and the level of agreement to tests in relatives, were based on expert opinion and assumptions. The prevalence of Lynch syndrome was the key input and this was from the EGAPP study.
Monetary benefit and utility valuations:The utility values were from published studies that used the European Quality of life (EQ-5D) instrument with the general US population.
Measure of benefit:Life-years (LYs) were the summary benefit measure and they were discounted at an annual rate of 3%. Quality-adjusted life-years (QALYs) were also used as a benefit measure in the sensitivity analysis.
Cost data:The economic analysis included the costs of screening (offering tests, performing the tests, and genetic counselling for both patients and their relatives), surveillance for colorectal cancer among relatives with Lynch syndrome (including the costs of treating complications associated with colonoscopies), and health care associated with colorectal cancer. In the base case, costs were derived from the EGAPP review, which included Medicare reimbursement data, expert opinion, and data from published sources. The patterns of resource consumption were from published sources and reflected international guidelines. All costs were in US dollars ($) and were discounted yearly at a rate of 3%. The price year was 2007.
Analysis of uncertainty:A deterministic one-way sensitivity analysis was undertaken, using confidence intervals derived from the literature or based on authors’ opinions. Alternative scenarios considered the list prices from three large, commercial laboratories without discounts, and varied the number of relatives tested. Results Compared with no testing, the costs associated with universal testing ranged from $82,617,000 with strategy one to $439,971,000 with strategy four and the LYs gained ranged from 2,346 with strategy one to 2,833 with strategy four. The costs associated with age-targeted testing ranged from $23,026,000 with strategy one to $79,651,000 with strategy four and the LYs gained ranged from 1,162 with strategy one to 1,399 with strategy four.
The incremental cost-effectiveness ratio (ICER) of universal testing was $22,552 with strategy one, $23,321 with strategy two, $41,511 with strategy three, and $142,289 with strategies four. The ICER of age-targeted testing was $7,832 with strategy one, $7,944 with strategy two, $11,680 with strategy three, and $44,902 with strategies four.
Compared with age-targeted testing, the ICER of universal testing was $37,010 with strategy one, $38,411 with strategy two, $70,792 with strategy three, and $237,278 with strategies four.
Considering the most influential model inputs, more favourable ICERs for universal testing strategies were associated with a greater risk of colorectal cancer among relatives, a greater number of relatives per proband, a greater proportion of relatives accepting counselling and testing for the family mutation, and a higher proportion of new colorectal cancer patients with Lynch syndrome. The price of the laboratory test was also an influential input and the scenario analysis using cost data from three large commercial laboratories resulted in higher cost-effectiveness ratios for the universal screening strategies.
The preliminary cost-utility analysis showed that the number of QALYs gained was about 15% less than the number of LYs gained, with each strategy. This meant the incremental cost-utility ratios were 18% higher than the ICERs. Authors' conclusions The authors concluded that the strategies that included immunohistochemistry were more likely to be cost-effective than those using microsatellite instability testing. The most cost-effective strategy was universal immunohistochemistry followed by BRAF V600E mutation testing and targeted mismatch repair gene sequencing. CRD commentary Interventions:The rationale for the selection of the comparators was clear as a range of screening strategies were considered. Comparisons also considered the non-availability of some testing strategies in some laboratories. A clear description of each screening strategy was provided.
Effectiveness/benefits:: No systematic review was reported for identifying the relevant sources of evidence and it is not possible to fully judge the validity of these sources with the information on their methods that was provided. The EGAPP review should have ensured a high quality of evidence and the other data were from well-known published sources. Expert opinions were necessary for some model inputs, but these were extensively varied in the sensitivity analysis. The primary benefit measure, namely LYs, was appropriate as survival was a key outcome of the screening programme. They also allow comparisons with the benefits of other health care programmes. The assessment of health-related quality-of-life and the subsequent calculation of QALYs were also valid despite the limited reporting of their derivation.
Costs:The cost categories reflected the viewpoint stated. The sources of data also reflected the health care payer perspective, and a scenario analysis used data from commercial laboratories. The unit costs and quantities of resources were generally not reported separately, but the total cost of each strategy or of each stage of colorectal cancer was clearly reported. The price year and the discount rate were reported. In general the economic analysis was satisfactorily conducted.
Analysis and results:The analytic approach for the cost-effectiveness analysis was appropriate. The results were extensively presented in tables and graphs, with all the findings from multiple comparisons. The issue of uncertainty was investigated in a deterministic analysis that focused on variations in individual inputs. A more comprehensive approach would have been useful. The authors acknowledged some limitations of their analysis, such as the exclusion of Amsterdam and Bethesda family history-based criteria for targeted testing, the exclusion of cut-off ages other than 50 years, and the exclusion of other potential benefits of screening (e.g. the identification of other gynaecologic cancers). In general, it appears that the analysis was conservative against the universal strategies.
Concluding remarks:The methods were valid and should ensure the validity of the authors’ conclusions. Bibliographic details Mvundura M, Grosse SD, Hampel H, Palomaki GE. The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer. Genetics in Medicine 2010; 12(2): 93-104 Indexing Status Subject indexing assigned by NLM MeSH Colorectal Neoplasms /diagnosis; Colorectal Neoplasms, Hereditary Nonpolyposis /diagnosis; Cost-Benefit Analysis; Female; Genetic Testing /economics /methods; Humans; Male AccessionNumber 22010000625 Date bibliographic record published 23/06/2010 Date abstract record published 06/10/2010 |
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