Economics of tandem mass spectrometry screening of neonatal inherited disorders Pandor A, Eastham J, Chilcott J, Paisley S, Beverley C

Transcription

1 Economics of tandem mass spectrometry screening of neonatal inherited disorders Pandor A, Eastham J, Chilcott J, Paisley S, Beverley C 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 authors studied the use of tandem mass spectrometry (MS) for the screening of phenylketonuria (PKU) and medium-chain acyl-coa dehydrogenase (MCAD) in newborn infants. Type of intervention Screening of neonates. Economic study type Cost-effectiveness analysis. Study population The study population comprised newborn infants. There were no further inclusion or exclusion criteria. Setting The setting was primary care. The economic study was carried out in the UK. Dates to which data relate The effectiveness data related to papers published between 1994 and The costing data related to papers and reports published between 1999 and The authors reported using current prices and, where necessary, the unit costs were reflated to 2001 prices. Source of effectiveness data The effectiveness data were derived from a review and synthesis of studies, supplemented with some authors' assumptions. Modelling The authors used a probabilistic model to estimate and compare the marginal costs and life-years gained (LYG) for the two technologies of interest. Outcomes assessed in the review The authors reported that a paper published in the Health Technology Assessment (HTA) series provided further details of the methods and underlying assumptions of the effectiveness analysis (Pandor et al. 2004, see 'Other Publications of Related Interest' below for bibliographic details). The outcomes assessed in the review were: Page: 1 / 6

2 the incidence of PKU, the false-positive rate of existing technologies for PKU, the false-positive rate of tandem MS for PKU, the false-negative rate of existing technologies and tandem MS for PKU (assumed to be the same for both technologies). For additional screening for MCAD deficiency using tandem MS, the authors also assessed: the incidence of MCAD, the false-positive and false-negative rates for MCAD deficiency screening, the proportion of cases that remained asymptomatic, the proportion of screening cases who developed significant disability and the proportion of symptomatic cases who developed significant disability, the life expectancy of those with and without significant disability, and the mortality proportion in screened and unscreened cases. Study designs and other criteria for inclusion in the review The authors reported that the effectiveness evidence was obtained from systematic reviews reported elsewhere (Pandor et al. 2004, Pollitt et al and Seymour et al. 1997, see 'Other Publications of Related Interest' below for bibliographic details). The authors included studies that "provided data on the sensitivity, specificity, or positive predictive value of neonatal screening using tandem MS for PKU and/or MCAD deficiency". Studies published until June 2003 were included. Sources searched to identify primary studies Not reported. Criteria used to ensure the validity of primary studies Not reported. Methods used to judge relevance and validity, and for extracting data Not reported. Number of primary studies included Nine studies provided data relevant to the study. Methods of combining primary studies Where the authors used systematic reviews within their own review, these were often used alone to provide data on a point estimate and range. Where data were combined, this seemed to be for the purposes of defining a parameter distribution or range. Narrative methods were used to combine the studies. Investigation of differences between primary studies Page: 2 / 6

3 Not reported. Results of the review The incidence of PKU was 9 per 100,000. The false-positive rate for PKU was 0.050% with existing technologies and 0.029% with tandem MS. The false-negative rate for PKU was 0.020% with existing technologies and 0.020% with tandem MS (assumed to be identical for both technologies, based on information available in the review). The incidence of MCAD was 8.3 per 100,000. The false-positive rate for MCAD deficiency screening was 0.023%, and the false-negative rate was %. The proportion of cases that remain asymptomatic was 0.3. Based on the available information, the proportion of screening cases that develop significant disability was assumed to be zero. The proportion of symptomatic cases that develop significant disability was Life expectancy was 55 years for those with significant disability and 75 years for those without significant disability (or who are asymptomatic). Based on the available evidence, the mortality proportion in screened cases was assumed to be zero. The mortality proportion in unscreened cases was 0.2. Methods used to derive estimates of effectiveness The authors used some assumptions to support their review of the literature. Estimates of effectiveness and key assumptions The repeat sampling rate required because of poor-quality samples was assumed to be 1% for both technologies. The authors assumed that the false-negative rates were the same for both technologies, although this assumption was backed up by evidence from the literature. Measure of benefits used in the economic analysis The authors used the LYG as a summary measure of health outcome. This was based on life expectancy observed from the available literature and from Government Actuaries Department Life Tables for The LYG were discounted at a rate of 1.5%. Direct costs The costs were estimated from the perspective of the UK NHS. The authors reported that the costs for all existing technologies were obtained from an HTA report (Pollitt et al. 1997). Costs from this report were reflated to 2001 prices using the Health Services Cost Index. The authors also reported that the costs for MS were based on current capital and operating costs. The analysis focused on the mean cost per specimen examined by both the existing technology and MS, and estimated the costs of sample collection, laboratory costs per sample, the costs of obtaining repeat specimens, confirmation cost per positive case, treatment costs, incremental costs of tandem MS for PKU, and acute presentation episode costs. The costs were discounted at a rate of 6% in conjunction with a time horizon for the analysis that extended to the life expectancy of the patient. The unit costs were reported separately from the quantities, which were Page: 3 / 6

4 determined within the authors' model. Statistical analysis of costs The authors obtained probabilistic estimates of cost, defined a distribution or range for variables, and used this to inform their Monte Carlo simulation. A value of information study was also carried out, the results of which were stated to have been reported elsewhere (Pandor et al. 2004). Indirect Costs Indirect costs were not relevant to the perspective adopted and, therefore, were not estimated. Currency UK pounds sterling (). Sensitivity analysis A multivariate sensitivity analysis was carried out, using Monte Carlo simulation, to explore uncertainty associated with the random variables and parameter assumptions. Estimated benefits used in the economic analysis There was no additional health gain between PKU screening with existing methods and with tandem MS. Screening for MCAD in addition to PKU led to a mean incremental gain of 57.3 (28.0, 91.4) life-years per 100,000 neonates screened. Cost results For a cohort of 100,000 neonates screened and an operating volume of between 50,000 and 60,000 samples per year per tandem MS system, screening would cost 184,644 for PKU alone compared with 129,744 for existing methods. This represented an incremental change of 54,900 (23,738, 86,062). PKU and MCAD deficiency screening with tandem MS would cost 112,446, an incremental change of -17,298 (-129,174, 66,434). Synthesis of costs and benefits Operating at a capacity of between 50,000 and 60,000 samples per system at a threshold valuation of 1,000 per LYG, the probability that the use of tandem MS was cost-effective was At a threshold valuation of 5,000 per LYG, the probability that the use of tandem MS was cost-effective was Authors' conclusions The use of tandem mass spectrometry (MS) instead of existing technologies for the screening of phenylketonuria (PKU) alone could not be economically justified. However, "replacing the existing PKU screening program with a tandem MS-based PKU plus MCAD (medium-chain acyl-coa dehydrogenase) deficiency screening programme would be economically attractive". CRD COMMENTARY - Selection of comparators The authors assessed tandem MS and stated that this was compared with existing technologies. The readers understanding of the study and ability to generalise results to their own setting would have been improved had the authors specified the exact nature of the existing technology. Page: 4 / 6

5 Validity of estimate of measure of effectiveness The authors did not carry out a systematic review of the literature but reported that evidence on diagnostic test characteristics was obtained from published systematic reviews. The inclusion criteria for evidence were clearly set out, although the authors did not state which sources were searched for evidence. They also did not state how they ensured the validity of the primary studies, or how they judged the relevance of the data extracted. Although the authors specified that three systematic reviews were used in the review and a total of nine studies provided data for the study of effectiveness, the characteristics and validity of the remaining studies was unclear. Validity of estimate of measure of benefit The LYG were used as a summary measure of benefit. This measure enables broad comparison to be made with a range of other health care-related technologies. Validity of estimate of costs The economic analysis was carried out from the perspective of the UK NHS. A previous report was used to provide the costs of existing technologies (bibliographic details were given, thus the reader is referred to this additional study to judge the validity of this estimate). The cost of MS was reported to have been based on current capital and operating costs. However, the authors could have been more specific about which elements this included, for instance whether staffing costs were included. A full explanation of their inclusions and exclusions would have enabled the reader to understand the extent of the cost coverage and to judge whether the results are applicable to their own setting. The unit costs in terms of, for example, the laboratory cost per sample (rather than the component parts of this unit cost), were reported separately from the quantities, thus enabling a slightly more detailed understanding. The results were a little confusing in the sense that tandem MS for PKU and MCAD was cheaper than both tandem MS for PKU alone and existing technologies. This result seems counterintuitive and the authors did not explicitly acknowledge, explain or discuss it. Since all costs were incurred during a long time period, discounting was appropriately carried out. The price date was reported, which will aid any future inflation exercises. Other issues The authors did not make broad comparisons of their results. However, this seems to have been the first economic study of this nature, thus preventing comparisons. The issue of generalisability was not explicitly addressed; this has been mentioned above but it was generally improved by the inclusion of a range of systematic reviews within the effectiveness study. The authors provided a useful discussion of their results, highlighting the inability to quantify potential psychological "disbenefits" associated with false positives, and the absence of quality of life weights for MCAD deficiency as potential limitations. With respect to the latter, they argued that this limitation would have resulted in an underestimate of the health benefits of screening. However, not including quality weights would require the explicit assumption that all future years would be lived in the best imaginable health state (i.e. a weight of one), therefore, in actual fact, this likely implies an overestimate of potential benefits. Implications of the study The authors recommended additional research into screening for other neonatal conditions. Source of funding Funded by the UK National Coordinating Centre for Health Technology Assessment Programme. Bibliographic details Pandor A, Eastham J, Chilcott J, Paisley S, Beverley C. Economics of tandem mass spectrometry screening of neonatal inherited disorders. International Journal of Technology Assessment in Health Care 2006; 22(3): PubMedID Page: 5 / 6

6 Powered by TCPDF ( Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information. Pandor A, Eastham J, Beverley C, et al. Clinical effectiveness and cost-effectiveness of neonatal screening for inborn errors of metabolism using tandem mass spectrometry: a systematic review. Health Technol Assess 2004;8(12): Pollitt RJ, Green A, McCabe CJ, et al. Neonatal screening for inborn errors of metabolism: cost, yield and outcome. Health Technol Assess 1997;1(7): Seymour CA, Thomason MJ, Chalmers RA, et al. Newborn screening for inborn errors of metabolism: a systematic review. Health Technol Assess 1997;1(11):1-97. Indexing Status Subject indexing assigned by NLM MeSH Acyl-CoA Dehydrogenase /deficiency; Cost-Benefit Analysis; Great Britain; Humans; Infant, Newborn; Mass Spectrometry; Neonatal Screening /economics /instrumentation; Phenylketonurias /diagnosis; Technology Assessment, Biomedical AccessionNumber Date bibliographic record published 31/03/2007 Date abstract record published 31/03/2007 Page: 6 / 6