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An economic viewpoint on alternative strategies for identifying persons with hereditary nonpolyposis colorectal cancer |
Ramsey S D, Burke W, Clarke L |
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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. Health technology The use of screening to identify persons with hereditary nonpolyposis colorectal cancer (HNPCC). Four screening strategies were considered.
Strategy 1 followed the Bethesda guidelines and involved microsatellite instability (MSI) testing for those with clinical and family history of the disease, followed by mutation analysis for those with MSI high tumours. Strategy 2 involved MSI testing for all individuals, irrespective of family or personal history. For both strategies 1 and 2, persons found to have MSI high tumours were offered DNA testing for mismatch repair (MMR) mutations.
Strategy 3 involved DNA MMR mutation testing for those who satisfied the conditions regarding clinical and family history outlined in the Bethesda guidelines).
Strategy 4 entailed all individuals undergoing MMR mutation testing, irrespective of personal or family history.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised individuals with recently diagnosed colorectal cancer.
Setting The setting was not explicitly stated. The economic study was carried out in the USA.
Dates to which data relate The effectiveness data were obtained from studies published between 1983 and 2001. The dates to which the resource data related were not reported. The price year was 2002.
Source of effectiveness data The effectiveness data were derived from a review of completed studies and from estimates of effectiveness based on opinion.
Modelling A decision model was developed to estimate the costs and benefits of the alternative screening strategies for identifying HNPCC mutation carriers among those with recently diagnosed colorectal cancer. The model was designed and run in Microsoft Excel and @RISK 4.0 Pro.
Outcomes assessed in the review The outcomes assessed included:
the prevalence of HNPCC in colorectal cancer probands,
the probability of a second diagnosis for HNPCC-positive probands with no treatment, and
the mean time to a second diagnosis in the absence of intervention for probands.
For first-degree relatives, the parameters included were:
the probability of a first diagnosis given an HNPCC-positive result,
the mean number of years until a first diagnosis for HNPCC-positive patients, and
the relative mortality risk for increased surveillance in HNPCC-positive patients.
Other parameters related to the sensitivity and specificity of the various screening strategies and compliance rates.
Study designs and other criteria for inclusion in the review Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Twenty-four primary studies were included in the review.
Methods of combining primary studies It was unclear whether the results of individual primary studies were combined.
Investigation of differences between primary studies The authors did not investigate differences between the primary studies.
Results of the review For probands:
the prevalence of HNPCC in colorectal cancer was 0.02,
the probability of a second diagnosis for HNPCC-positive patients with no treatment was 0.95, and
the mean time to a second diagnosis in the absence of intervention was 5.
For first-degree relatives:
the probability of a first diagnosis given an HNPCC-positive result was 0.8,
the mean number of years until a first diagnosis for HNPCC-positive patients was 2, and
the relative mortality risk for increased surveillance in HNPCC-positive patients was 0.348.
The sensitivity of the Bethesda guidelines was 0.7 and the specificity was 0.85.
The sensitivity of the MSI test was 0.91 and the specificity was 0.93.
Methods used to derive estimates of effectiveness Expert opinion was used to derive other model parameters.
Estimates of effectiveness and key assumptions According to expert opinion, the probability that probands would agree to the guideline assessment was 1, the probability of locating siblings was 0.65, and the probability of locating a child was 0.75.
Measure of benefits used in the economic analysis The measure of benefits used was the years of life gained.
Direct costs Discounting was performed at an annual rate of 3%. The quantities and the costs were not analysed separately. The direct costs of medical care were included in the analysis, as were the nonmedical costs of care (e.g. patient transportation costs). The costs were estimated from actual data. The costs of MSI assays, genetic testing and counselling were derived from national surveys. The lifetime costs related to colorectal cancer treatment, while the costs of prophylactic colectomy were based on published estimates using the SEER-Medicare database. The price year was 2002.
Statistical analysis of costs No statistical analysis of the costs was undertaken.
Indirect Costs The indirect costs were not reported.
Sensitivity analysis One-way and multi-way sensitivity analyses were undertaken to investigate uncertainty in the data used to populate the model. The parameter ranges used in the sensitivity analysis were based on 95% confidence intervals (CIs) where this information was available. Alternatively, the ranges were selected on the basis of expert opinion.
Estimated benefits used in the economic analysis For persons with newly diagnosed colorectal cancer (probands), the number of years of life gained (undiscounted) was 833 under strategy 1, 886 under strategy 2, 915 under strategy 3 and 973 under strategy 4.
When probands and their relatives were included, the years of life gained (undiscounted) were 7,615 under strategy 1, 8,111 under strategy 2, 8,390 under strategy 3 and 9,059 under strategy 4.
The duration of benefits to the patient was not reported. In addition, it was unclear if the side effects of treatment were considered in the economic analysis.
Cost results For probands, the cost per carrier detected was $20,313 under strategy 1, $57,027 under strategy 2, $63,980 under strategy 3 and $336,475 under strategy 4.
When relatives were included, the cost per carrier detected fell to $15,787 under strategy 1, $43,737 under strategy 2, $49,020 under strategy 3 and $255,160 under strategy 4.
The duration of costs in the economic analysis was not reported. It was unclear if the costs of any adverse events were included.
Synthesis of costs and benefits The estimated benefits and costs were combined to calculate the added cost per life-year gained (LYG) relative to a strategy of no screening.
When both the costs and benefits were discounted at an annual rate of 3%, the added cost per LYG for probands only was $73,711 under strategy 1, $213,290 under strategy 2, $296,793 under strategy 3 and $1,625,687 under strategy 4.
With the inclusion of probands and their relatives, the added cost per LYG was $11,865 (90% CI: 8,005 - 80,226) under strategy 1, $35,617 (90% CI: 15,091 - 180,056) under strategy 2, $49,702 (90% CI: 19,100 - 252,151) under strategy 3 and $267,548 (90% CI: 68,328 - 637,007) under strategy 4.
The authors found that the results were sensitive to the survival benefits from aggressive surveillance in mutation carriers without cancer and the prevalence of HNPCC in the population. For example, if HPNCC were present in 0.5% of newly diagnosed cases, the Bethesda guidelines under strategy 1 resulted in additional costs of $21,478 per LYG, while DNA analysis for MMR mutations for all new cases under strategy 4 led to additional costs of $552,880 per LYG.
The authors also found that changing the cost of the DNA analysis had a lower impact on the results under strategy 1 compared with the other strategies, because fewer individuals were offered DNA analysis under the former. The results from confidence ellipses showed that it was not possible to distinguish between strategies 1, 2 or 3 with certainty. Moreover, strategy 4 was less cost-effective than the alternative strategies.
Authors' conclusions The most cost-effective strategy for detecting carriers of hereditary nonpolyposis colorectal cancer (HNPCC) in those recently diagnosed with colorectal cancer was following the Bethesda guidelines (strategy 1).
CRD COMMENTARY - Selection of comparators No explicit justification for the choice of the comparator was given. It would appear that no screening was chosen so that the full benefits and costs attributable to active screening strategies could be evaluated in comparison with a do-nothing strategy. The authors also carried out comparisons across the screening strategies.
Validity of estimate of measure of effectiveness The authors did not state that a systematic review of the literature had been undertaken. They did not report the method used to combine estimates of effectiveness from the primary studies, and they did not consider the impact of differences between the primary studies when estimating the effectiveness.
Validity of estimate of measure of benefit The estimation of benefits was modelled. The instrument used to derive a measure of health benefit, a decision model, was appropriate.
Validity of estimate of costs The perspective adopted for the economic evaluation was not explicitly stated. As such, it was unclear whether all the categories of cost relevant to the perspective adopted were included in the analysis. The costs and the quantities were not reported separately. A sensitivity analysis of the quantities was not conducted, which may limit the interpretation of the study findings. However, a sensitivity analysis of the prices was conducted.
Other issues The authors did not make appropriate comparisons of their findings with those from other studies. They also did not address the issue of generalisability to other settings. Since this study concentrated on newly diagnosed cancer cases, it is difficult to draw any conclusions about the implementation of these screening strategies in the wider population. The authors do not appear to have presented their results selectively. Persons with recently diagnosed colorectal cancer were modelled in this study and this was reflected in the authors' conclusions. The authors did not report the size of the cohort modelled or the time horizon of the model. Therefore, it is difficult to assess the validity of the results.
The authors reported a number of further limitations to their study. First, some model parameters were based on expert opinion. However, the robustness of the results to these parameters was tested in a sensitivity analysis. Second, the authors did not allow for correlation between variables, which may have reduced the predictive regions for the estimates of costs and benefits. Finally, the indirect costs were omitted from the analysis, although the authors argued that their omission was unlikely to influence the ranking of the strategies.
Implications of the study The authors argued that their study provides evidence to support the use of MSI testing in detecting HPNCC carriers.
Source of funding Supported by a Howard Temin Career Development Award from the National Cancer Institute (K01 CA76189) and by a grant from the National Human Genome Research (RO1-HG02263).
Bibliographic details Ramsey S D, Burke W, Clarke L. An economic viewpoint on alternative strategies for identifying persons with hereditary nonpolyposis colorectal cancer. Genetics in Medicine 2003; 5(5): 353-336 Indexing Status Subject indexing assigned by NLM MeSH Colorectal Neoplasms, Hereditary Nonpolyposis /diagnosis; DNA Mutational Analysis /economics; Genetic Testing /economics; Humans; Microsatellite Repeats AccessionNumber 22003009942 Date bibliographic record published 30/11/2004 Date abstract record published 30/11/2004 |
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