Setting The setting was primary care. The economic study was carried out in the UK.

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1 The use of brain natriuretic peptide as a screening test for left ventricular systolic dysfunction: cost-effectiveness in relation to open access echocardiography Sim V, Hampton D, Phillips C, Lo S N, Vasishta S, Davies J, Penney M 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 plasma brain natriuretic peptide (BNP) measurement as a pre-screening test for left ventricular systolic dysfunction (LVSD). The intervention was used to select those patients requiring further diagnostic assessment with echocardiography (ECHO). Type of intervention Screening. Economic study type Cost-effectiveness analysis. Study population The study population comprised patients with symptoms of breathlessness. Those with symptoms of both breathlessness and heart murmur were excluded. Setting The setting was primary care. The economic study was carried out in the UK. Dates to which data relate The effectiveness and resource use data were gathered in 1997 and The price year was not explicitly reported. Source of effectiveness data The effectiveness evidence was derived from a single study. Link between effectiveness and cost data The costing was conducted prospectively on the same sample of patients as that used in the effectiveness study. Study sample A single group of patients was identified at the authors' centre in 1997 and A sample of 83 patients (43 female and 40 male) was included in the analysis. The mean age of the patients was 72 years (age range: 37-87). Statistical tests, to determine the most appropriate sample size, were not conducted. Study design This was a diagnostic study that was conducted at a single centre in New Port, covering an area of 110 general Page: 1 / 5

2 practitioners. The patients were not followed after ECHO was performed. Two independent echocardiographers assessed the outcomes, while a third observer adjudicated any disagreement. Analysis of effectiveness All the patients considered in the initial study sample were accounted for in the effectiveness analysis. The outcomes were: the prevalence of LVSD; and the rates of sensitivity, specificity, and positive predictive values associated with BNP measurement, using two thresholds (19 or 20 pg/ml to give negative predictive values for LVSD of greater than 98%). ECHO was considered the 'gold' standard, with an accuracy of 100%. Effectiveness results Of the 83 patients included in the analysis, 26 had LVSD (prevalence of 31%). Using the threshold of 19 pg/ml, the sensitivity associated with BNP measurement was 100%, the specificity was 49.1%, and the positive predictive value was 46.9%. At a threshold of 19 pg/ml, the number of patients assessed as requiring ECHO was 55. Of these, 26 were assessed as having LVSD. At a threshold of 20 pg/ml, the number of patients assessed as requiring ECHO was 49. Of these, 25 were assessed as having LVSD (one less than with ECHO). Clinical conclusions The effectiveness analysis showed that a pre-screen of BNP using a threshold of 19 pg/ml led to the accurate identification of patients with LVSD, as ECHO showed. Measure of benefits used in the economic analysis The health outcomes were left disaggregated and no summary benefit measure was used in the economic analysis. In effect, a cost-consequences analysis was conducted. Direct costs The unit costs were presented separately from the quantities of resources used. The health services included in the economic evaluation were BNP testing (consumables and labour) and ECHO (labour and equipment). The cost/resource boundary of the local third-party payer was presumably adopted. A staff grade doctor, who performed 1,400 investigations per year, performed ECHO. The costs of plasma BNP were based on standard laboratory costing package. The source of the data was not implicitly stated, but it appears to have been the authors' centre. The purchasing price of an echocardiograph was obtained from a published study and included upgrading and technical life of the machine. Discounting of the ECHO machine, to account for equipment depreciation, was applied, as recommended in the UK. The price year could have been 1999, although it was not stated clearly. Statistical analysis of costs The costs were treated deterministically in the base-case. Indirect Costs The indirect costs were not considered. Page: 2 / 5

3 Currency UK pounds sterling (). Sensitivity analysis A univariate sensitivity analysis was conducted to assess the robustness of the cost-difference to variations in the cost of ECHO, as performed by a trained full-time technician rather than a staff grade doctor. Estimated benefits used in the economic analysis See the 'Effectiveness Results' section. Cost results When a threshold of 19 pg/ml was used, the estimated total cost of BNP measurement in the whole sample was 3,517.80, while ECHO cost 4,482. The cost-difference was When a threshold of 20 pg/ml was used, the estimated total cost of BNP measurement in the whole sample was 3,193.80, while ECHO cost the same as before (i.e. 4,482). The cost-difference was 1, When a trained full-time technician performed ECHO, the cost-difference was when using a threshold of 19 pg/ml and when using a threshold of 20 pg/ml. Synthesis of costs and benefits A synthesis of the costs and benefits was not relevant since a cost-consequences analysis was conducted. Authors' conclusions The use of brain natriuretic protein (BNP) measurement, at a threshold of 19 to 20 pg/ml, as a pre-screen for ECHO was a cost-effective strategy since the costs were reduced without compromising screening accuracy. CRD COMMENTARY - Selection of comparators The choice of the comparator appears to have been appropriate since ECHO represented the 'gold' standard for the detection of LVSD. You should decide whether this is a valid comparator in your own setting. Validity of estimate of measure of effectiveness The analysis of the effectiveness was based on evidence coming from a single group of patients who underwent both screening strategies. This design has several advantages, such as the lack of a similar comparison group. Further, two independent individuals evaluated all outcomes and a third investigator adjudicated any disagreements. It was not stated whether the echocardiographers were blinded to the screening results. There was no statistical evidence that the sample size was appropriate. The patients were recruited from a single centre with a large catchment area. Therefore, it would appear that the sample size was representative of the patient population. The outcome measures assessed in the effectiveness analysis were used to estimate the costs of the two screening strategies. Validity of estimate of measure of benefit No summary benefit measure was used in the analysis because a cost-consequences analysis was conducted. Validity of estimate of costs The perspective adopted in the study was not explicitly stated, although it is clear that costs relevant to the local health Page: 3 / 5

4 care payer were considered. Details of the cost calculation were satisfactorily reported, which enhances the possibility of replicating the study in other settings. The price year was not explicitly reported. No statistical analyses of the costs were performed and the cost estimates were specific to the study setting. Only the cost of the technician was varied in the sensitivity analysis. Other issues The authors compared their findings with those from other studies that reported quite consistent results. The authors also provided possible explanations for differences observed in some of the accuracy rates in their series and those estimated in the literature. The issue of the generalisability of the study results to other settings was not addressed and sensitivity analyses were not carried out extensively. This reduced the external validity of the analysis. The authors stressed that the analysis was carried out in a "real world" setting. This represents a strength of their study. Implications of the study The authors suggested that a study with a larger cohort should be conducted to corroborate the findings of the current analysis, which supported the use of plasma BNP measurement for the appropriate stratification of patients undergoing ECHO screening for LVSD. Source of funding Funded by the NHS R&D HTA programme. Bibliographic details Sim V, Hampton D, Phillips C, Lo S N, Vasishta S, Davies J, Penney M. The use of brain natriuretic peptide as a screening test for left ventricular systolic dysfunction: cost-effectiveness in relation to open access echocardiography. Family Practice 2003; 20(5): PubMedID Other publications of related interest Cowie MR, Struthers AD, Wood DA, Coat AJ, Thompson SG, Poole-Wilson PA. Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet 1997;350: McDonagh TA, Robb SD, Murdoch DR, et al. Biochemical detection of left ventricular systolic dysfunction. Lancet 1998;351:9-13. Indexing Status Subject indexing assigned by NLM MeSH Adult; Aged; Aged, 80 and over; Biomarkers /blood; Cost-Benefit Analysis; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain /blood; Predictive Value of Tests; Sensitivity and Specificity; Ventricular Dysfunction, Left /blood /ultrasonography AccessionNumber Date bibliographic record published 28/02/2005 Date abstract record published Page: 4 / 5

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