Comprehensive cost-utility analysis of newborn screening strategies Carroll A E, Downs S M

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1 Comprehensive cost-utility analysis of newborn screening strategies Carroll A E, Downs S 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 component tests of a multi-test newborn screening programme, either alone or in combination with diseases detectable by tandem mass spectrometry (MS/MS) methods, were compared. The screening component tests included screening for phenylketonuria (PKU), congenital adrenal hyperplasia (CAH), congenital hypothyroidism (CH), biotinidase deficiency (BIOT), maple syrup urine disease (MSUD), galactodemia (GAL), homocystinuria (HCY) and medium-chain acyl-coa dehydrogenase deficiency (MCAD). Type of intervention Screening. Economic study type Cost-utility analysis. Study population The study population comprised hypothetical newborn babies. Setting The setting was not explicitly stated. The economic study was carried out in the USA. Dates to which data relate The model data were derived from studies published between 1982 and The price year was Source of effectiveness data The effectiveness data were derived from a systematic review of the literature and expert opinion. Modelling A decision-analytical model (using decision analysis software DATA 4.0; TreeAge software) was used to compare the various strategies. The structure of the model was described in full and a diagram presented. Outcomes assessed in the review The following outcomes were assessed: the test characteristics (i.e. sensitivity and specificity) of all component screening tests; disease prevalence for all eight conditions; the probability of these diseases causing sequelae; and Page: 1 / 6

2 the effectiveness of early screening in preventing sequelae. Study designs and other criteria for inclusion in the review Sources searched to identify primary studies MEDLINE (from January 1980 to November 2002) and online (unspecified) internet databases were searched for relevant studies. The bibliographies of studies identified through the electronic searches were also handsearched for further 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 Approximately 14 primary studies were included in the review. Methods of combining primary studies Investigation of differences between primary studies Results of the review The sensitivity of newborn screening tests for all conditions was 1. The specificity of the component tests ranged from to Disease prevalence ranged from 0.4 to 39.6 per 100,000 infants. The probability of disease sequelae ranged from to 1. The effectiveness of early screening in preventing sequelae ranged from 0 to 1. Methods used to derive estimates of effectiveness Expert opinion was used to derive some of the estimates of effectiveness. Estimates of effectiveness and key assumptions The parameters assumed were the risk of death from CAH in the first 5 years (0.10) and the effectiveness of early screening in preventing CAH death from crisis (0.8). Measure of benefits used in the economic analysis Page: 2 / 6

3 The measure of benefit used was the quality-adjusted life-years (QALYs) gained. Utilities for most disabilities were drawn from a study of parents' utilities using the standard gamble technique. Utilities for blindness were taken from a study that developed an equation for estimating utility on the basis of visual acuity. Direct costs The direct costs included the cost of the screening tests, cost of caring for the disease and cost of sequelae. Costs for specific screening tests were derived from a Price Waterhouse Coopers analysis of newborn screening costs and from a review of the literature. Both amortised start-up costs and operating costs were included. The costs of treating selected diseases over the course of a lifetime were estimated using data from the Office of Technology Assessment analysis for newborn screening, data from Washington State and, in one case, from expert opinion. The costs were reported separately. All costs were discounted at an annual rate of 3%. The price year was The costs were adjusted to 2004 US dollars using the General Consumer Price Index. The estimations of the quantities and costs were derived by modelling. Statistical analysis of costs The costs were treated deterministically. Indirect Costs The authors reported that they adopted a societal perspective, although any indirect costs included in the analysis were not explicitly stated. Currency US dollars ($). Sensitivity analysis A one-way sensitivity analysis was used to test areas of uncertainty. All probabilities were tested across the full range from 0 to 1. The costs were analysed from $0 to $1 million. A threshold analysis was carried out on all variables to determine at what levels the tests were no longer cost-saving. A multi-way sensitivity analysis was also performed by examining a pessimistic analysis that biased the model against newborn screening. Indirect costs were excluded from the estimated costs of developmental delay and CP, and the cost of developmental delay from outcomes that included CP. The cost of MS/MS was increased to $20, the high end of published results. The cost of evaluating false-positive cases was increased to $1,000. The low-end estimates for prevalence of MCAD and PKU and risk of death from CAH were used in the pessimistic case analysis. Estimated benefits used in the economic analysis When all component tests were compared with the "no-test strategy", the incremental benefits were: QALYs for MS/MS testing; QALYs PKU testing; QALYs for BIOT testing; QALYs for CH testing; QALYs for HYC testing; QALYs for MSUD testing; QALYs for GAL testing; and Page: 3 / 6

4 QALYs for CAH testing. The time horizon was a lifetime. Cost results The cost of the test and average costs (per person screened) associated with all the treatments and outcomes for the diseases represented in the model were: $55 using MS/MS testing; $63 for PKU testing; $85 for BIOT testing; $93 for CH testing; $96 for HCY testing; $97 for MSUD testing; $98 for the "no-test strategy"; $102 for GAL testing; and $102 for CAH testing. Synthesis of costs and benefits Average and incremental cost-effectiveness ratios were calculated to combine the costs and benefits of the diagnostic strategies under evaluation. The average cost-effectiveness ratio was: 0.72 for MS/MS testing; 0.81 for PKU test; 1.1 for BIOT test; 1.21 for CH test; 1.24 for HCY test; 1.26 for MSUD test; 1.26 for no test; 1.32 for GAL test; and 1.34 for CAH test. The incremental cost-effectiveness analysis showed MS/MS testing, PKU testing, BIOT testing, CH testing, HYC testing and MSUD testing were dominant, that is, they saved money and improved outcomes relative to not testing. CAH testing cost slightly more than $20,000 per QALY gained and GAL testing approximately $94,000 per QALY. A panel of conventional tests (for PKU, BIOT, MSUD, GAL, HCY, MCAD) was compared with MS/MS testing. MS/MS was found to be dominant (less expensive and more effective). Page: 4 / 6

5 Threshold values for each variable (the value at which the corresponding screening strategy becomes more costly than not screening) were described in the paper. In sensitivity testing it was found that the dominant strategies remained dominant even when it was assumed that the test sensitivities were lower. When the specificity of he screening tests was lowered, a larger proportion of unaffected children had false-positive test results, which resulted in increased costs to rule out disease. When specificity was below a threshold value, some tests were no longer cost-saving. The cost-savings with the screening tests depended in some cases on the effectiveness of treatment in preventing specific sequelae. The results were relatively insensitive to the rates at which individual sequelae developed. The results were not sensitive to the cost of the screening test. The pessimistic case analysis biased the model against screening. Authors' conclusions Newborn screening is beneficial to patients and, with some assumptions, cost-saving. Over the long term, funding comprehensive newborn screening may save money for society. CRD COMMENTARY - Selection of comparators The reason for the choice of the comparator was clear. By choosing "no test" the authors could ascertain the relative effectiveness of each component test, either alone or in combination. You should determine if this is a relevant comparator for your own setting. Validity of estimate of measure of effectiveness The principal input parameters for the model were derived from a review of the literature, for which search strategies were provided. However, the primary studies were neither assessed for quality nor combined, and it is possible that data from the available studies might have been used selectively. The authors conducted several sensitivity analyses relating to the efficiency estimates and this helps improve the generalisability of their findings. However, given the limited reporting on the methods of the review (inclusion criteria, quality assessment, synthesis), it is difficult to assess the internal validity of the estimates used in the model. Validity of estimate of measure of benefit The measure of benefit used in the incremental cost-utility analysis was the QALYs gained. The authors provided a brief description of how the utilities for disabilities were estimated, but for full details the reader is referred elsewhere (Bernett et al. 2000, see 'Other Publications of Related Interest' below for bibliographic details). The use of QALYs allows the results of the study to be easily compared with the results from other interventions. Validity of estimate of costs The perspective was stated to have been societal. However, from the summary of costs under different headings in the base-case, it is difficulty to say whether all the costs relevant to the perspective adopted were included. A full breakdown of the costing was not provided, although the authors did acknowledge this limitation. Given this limitation it is difficult to comment on the validity of the estimate of costs. The costs were subjected to extensive sensitivity testing and the conclusions drawn were shown to be robust to changes in the cost estimates. Other issues The authors did not compare their findings with those from other studies. The issue of generalisability to other settings was partially addressed by performing a sensitivity analysis on the cost items. The authors acknowledged some further limitations to their study, for example changes in technology and care that may alter the lifetime cost estimates for disability. Implications of the study The authors suggested that newborn screening seems to be one of those rare health care interventions that are both beneficial to patients and, in many cases, cost-saving. Over the long term, funding comprehensive newborn screening Page: 5 / 6

6 Powered by TCPDF ( programmes is likely to save money for society. The authors suggested that the cost-effectiveness analysis will continue to be useful in deciding which test to consider. Source of funding Funded by the Maternal and Child Health Bureau, Health Resources and Services Administration, and the National Institutes of Health. Bibliographic details Carroll A E, Downs S M. Comprehensive cost-utility analysis of newborn screening strategies. Pediatrics 2006; 117(5 Part 2): S287-S295 PubMedID DOI /peds H 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. Bennett JE, Sumner W, Downs SM, Jaffe DM. Parents' utilities for outcomes of occult bacteremia. Arch Pediatr Adolesc Med 2000;154:43-8. Indexing Status Subject indexing assigned by NLM MeSH Cost-Benefit Analysis; Decision Support Techniques; Humans; Infant, Newborn; Mass Spectrometry; Metabolism, Inborn Errors /diagnosis; Neonatal Screening /economics; United States AccessionNumber Date bibliographic record published 28/02/2007 Date abstract record published 28/02/2007 Page: 6 / 6