|Probabilistic cost-effectiveness analysis of cascade screening for familial hypercholesterolaemia using alternative diagnostic and identification strategies
|Nherera L, Marks D, Minhas R, Thorogood M, Humphries SE
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.
This study assessed the cost-effectiveness of different methods of cascade screening for familial hypercholesterolaemia. The authors concluded that cascade screening was cost-effective when deoxyribonucleic acid (DNA) testing was used for the relatives of patients with an identified mutation and low-density lipoprotein cholesterol testing was used for relatives of possible or definite patients without the mutation. The methods and reporting of the results were good, but the effectiveness data were not well reported, making it difficult to assess the authors' conclusions.
Type of economic evaluation
Cost-effectiveness analysis, cost-utility analysis
The objective was to assess the cost-effectiveness of different methods of cascade screening for familial hypercholesterolaemia (FH).
Four cascade screening strategies were compared. The first option was to screen the patients' deoxyribonucleic acid (DNA) for the mutation related to FH, and then to DNA test the first-degree relatives of those patients who had the mutation. The second option was the same as the first, with low-density lipoprotein (LDL) cholesterol testing for the relatives of definite FH patients, who did not have the mutation. The third option was the same as the second, with LDL cholesterol testing for the relatives of possible FH patients, who did not have the mutation. The fourth option was standard clinical diagnosis, using LDL cholesterol, and testing of the relatives of patients with definite or possible FH.
The authors used a decision tree to combine published evidence, to simulate the diagnosis of FH using the four cascade screening methods. The decision tree identified patients with a diagnosis of true-positive FH, false-positive FH, true-negative FH, or false-negative FH. These outcomes were then fed into a Markov model to simulate the treatment for each diagnosis. The authors stated that the perspective was that of the UK NHS. The time horizon was the lifetime of the patients.
The evidence for diagnosis came from two published studies, and the evidence for the treatment effect came from a meta-analysis of four trials of statin treatment. The main clinical parameters were the diagnosis of FH and the effects of statin treatment.
Monetary benefit and utility valuations:
The utility estimates were from a published study and age-adjusted values from a national survey. The time trade-off technique was used to derive these estimates.
Measure of benefit:
The measure of benefit was quality-adjusted life-years (QALYs) gained, and these were discounted at an annual rate of 3.5%.
The direct costs included those of the drugs, cholesterol testing, and cardiovascular disease events. The drug unit costs were from the British National Formulary (2011) and NHS Reference Costs. All costs were presented in 2010 to 2011 UK pounds sterling (£) and discounted at an annual rate of 3.5%.
Analysis of uncertainty:
The effect of uncertainty on the results was tested in a probabilistic sensitivity analysis. The results were presented in a cost-effectiveness acceptability curve. One-way sensitivity analyses were performed on the costs of cholesterol testing, the costs of statins, the effects of side-effects on QALYs, and the costs of DNA testing.
The combined total cost of standard cholesterol testing was £44,576, compared with £50,918 for DNA testing, £52,670 for DNA with definite FH testing, and £54,799 for DNA with definite and possible FH testing.
The QALY gain for cholesterol testing was 10.89, compared with 24.12 for DNA, 24.28 for DNA with definite FH, and 25.18 for DNA with definite and possible FH testing.
DNA with definite FH testing was extendedly dominated, as its incremental cost-effectiveness ratio (ICER) was higher than that of a more effective comparator. Compared with cholesterol testing, the ICER for DNA testing was £479 per QALY gained, and, compared with DNA testing, the ICER for DNA with definite and possible FH testing was £3,666 per QALY gained.
The one-way sensitivity analysis found that the model results were robust to the changes in assumptions. The probabilistic sensitivity analysis found that DNA with definite and possible FH testing was cost-effective at the accepted threshold of £20,000 per QALY gained.
The authors concluded that cascade testing, with DNA testing for the relatives of patients with identified FH mutations and LDL-cholesterol testing for the relatives of patients with definite or possible FH without the mutation, was cost-effective.
All interventions were described, appear to have been appropriate comparators. The analysis included the usual practice in the study setting, which was testing for elevated LDL-cholesterol levels in index patients and their first-degree relatives.
The effectiveness data were from several published studies. These studies were not described, but their references were provided and these should be consulted to assess their quality. It was unclear if a systematic review was undertaken, making it impossible to ascertain if all the best available evidence was included. Details of the sources for the utility estimates were given, but it was not clear if the time trade-off method was used by both sources. QALYs were an appropriate benefit measure, as they incorporate both mortality and morbidity. They were appropriately discounted.
The authors reported the perspective and they appear to have included all those costs relevant to the health care system. The cost data were not fully described and were provided only in aggregate form for each screening method, which makes it difficult to replicate the study, but supplementary details were available online. The cost estimates were relevant to the study population and setting, and the costs were appropriately discounted and adjusted for inflation.
Analysis and results:
: The analytic approach was satisfactorily reported; the model structure was described and a diagram was presented. The results were reported clearly and in full. One-way sensitivity analyses and a probabilistic sensitivity analysis were performed to assess the parameter uncertainty. The reporting was generally good; the base-case estimates of the effectiveness, utility, and costs were given. The authors acknowledged and highlighted the limitations of their study.
: The methods and reporting of the results were good, but the effectiveness data were not well reported, making it difficult to assess the authors' conclusions.
Funding received from the National Institute for Health and Clinical Excellence (NICE), UK, and the British Heart Foundation.
Nherera L, Marks D, Minhas R, Thorogood M, Humphries SE. Probabilistic cost-effectiveness analysis of cascade screening for familial hypercholesterolaemia using alternative diagnostic and identification strategies. Heart 2011; 97(14): 1175-1181
Subject indexing assigned by NLM
Adult; Biomarkers /blood; Cardiovascular Diseases /economics /etiology /prevention & Cholesterol, LDL /blood; Cost-Benefit Analysis; Drug Costs; False Negative Reactions; False Positive Reactions; Genetic Predisposition to Disease; Genetic Testing /economics; Great Britain; Health Care Costs; Heredity; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors /economics /therapeutic use; Hyperlipoproteinemia Type II /blood /complications /diagnosis /drug therapy /economics /genetics; Markov Chains; Mass Screening /economics /methods; Middle Aged; Models, Economic; Mutation; Pedigree; Predictive Value of Tests; Probability; Prognosis; Quality-Adjusted Life Years; State Medicine /economics; Time Factors; control
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Date abstract record published