As a method of diagnosis neonatal screening is relatively expensive. At £5,387 per diagnosed infant, our estimate of the cost of diagnosis is similar to a previous (1997) estimate of £6,400 . Compared to no screening, neonatal screening for cystic fibrosis (under base case assumptions) produces an incremental cost-effectiveness of £6,864 per QALY gained.
There are a number of key assumptions and potential limitations to this study. Firstly, in relation to the model structure, we have simplified the representation of cystic fibrosis. However our representation of the disease – as three health states within a Markov model – makes best use of available knowledge. Also, we have assumed that the effect of early diagnosis is a delay in the emergence of respiratory symptoms after prophylactic treatment (but, with the subsequent treatment cost and quality of life in those states being the same for screened and unscreened infants). This choice was made in the absence of evidence to suggest other ways of modelling the effect of early diagnosis. Unfortunately, while recent trials or observational studies have shown that early (neonatal) diagnosis and treatment results in improvements in nutritional status, height and weight, and cognitive functioning, evidence about the long-term impact of early diagnosis on lung function (and therefore mortality) remains uncertain [24–28].
The model assumes that cystic fibrosis in infants is a relatively homogeneous condition. However, the spectrum of cases ranges from neonates that are severely affected, to cases who live a normal life undiagnosed until adulthood. It is possible that the more severe but asymptomatic cases would benefit most from early diagnosis. Those with milder forms of the disease would be diagnosed later under the no-screening strategy and would have their age at diagnosis advanced most under screening. The data in existing population-based data sets are insufficient to investigate this issue (PL – author), so this point has been ignored.
Our survival estimates are based on the most recent and reliable age-specific survival data. As yet there is a limited understanding of the interactions of cystic fibrosis with the normal ageing process. Recent clinical experience indicates that potentially life-shortening complications such as diabetes mellitis and liver disease may become more frequent with advancing age, so projections based on experience of younger people may be inaccurate [2, 29]. Although it is possible that recent improvements in survival may be confounded by the introduction of neonatal screening in some areas in the 1970s and 1980s, regional variations in mortality do not show this (PL – author). Further, using Quality of Well-Being (QWB) scores as a basis for weighting the quality of extra years survived may not provide a true indicator of relative preferences for being in these different health states. However, it remains the only health-related quality of life instrument that has been used widely in people with cystic fibrosis .
Overall, as far as presently available data allow, the model structure and data inputs would satisfy most of the criteria that are recommended in current guidelines for good practice in decision analytic modelling . External validation of the model is more problematic since valid data about either the long-term health effects of screening or the future survival of people with cystic fibrosis does not yet exist. Due to the absence of published data on the distributions underlying the means of most parameters our sensitivity analysis is restricted to one-way and two-way sensitivity analysis. Future modelling of these policy choices should attempt to use data that allow more probabilistic sensitivity analysis to be conducted, but with the proviso that model structure (or methodological) uncertainty can only be explored using traditional 'non-probabilistic' methods.
A number of costs, which may in theory are important have been omitted, either because of the complexity of deriving estimates, or their probable minimal effect on the main findings. The omitted costs are; the potential effects of distress or reassurance related to screening , self- and lay-care costs (for example, therapy provided by parents or by the patients themselves), unrelated health care costs and savings resulting from increasing life expectancy (for example, additional years of economically productive life); the costs of genetic counselling (generated by the identification of carriers); and the treatment option of heart-lung transplantation.
The omission of genetic counselling costs was partly because the benefits of such counselling would be difficult to quantify. Existing evidence also shows that, of the small number of carriers that will be identified, only a minority take up counselling and the cost of providing this counselling is small in relation to total screening costs [33, 34]. With regard to heart-lung transplantation, this treatment option is currently only available to a relatively small proportion of people with cystic fibrosis. Even if this changes there is no reason to assume that the costs, benefits or availability would be different for those diagnosed at birth by screening and those diagnosed later symptomatically [35–39].
With regard to the generalisability of the findings, this study has most relevance to the UK context: it employs cost estimates based on NHS care and the survival estimates are derived from the UK National Cystic Fibrosis Survey . Although comparisons with other studies are difficult; the costs of care at the Leeds unit (average annual cost of £10,567 ) from which our data are derived were comparable with another UK study .
Although a number of alternative screening protocols are being used in the UK and world-wide, they all employ an IRT test as the initial screening stage for all neonates. Our analysis shows that it is the cost of this initial stage, carried out on all infants, which most affects the cost-effectiveness ratio, and also that differences in the performance of the screening protocol produce only minor changes. Therefore, it is unlikely that substantially different results would be obtained with alternative protocols.
We have shown that, in the absence of antenatal screening, neonatal screening costs of £6,864 per QALY gained, based on an assumed benefit of six months average delay in the onset of symptoms, and that it would be less costly and more beneficial if the benefit were shown to be 11 months or more. As further evidence becomes available it will be clearer if this threshold can be realised. The model used here could be adapted to reflect new effectiveness data, associations between genotype and phenotype, new treatments for cystic fibrosis as they become available; and local information concerning populations or services.
Comparisons of cost per affected pregnancy identified by antenatal screening with averted treatment costs are generally favourable . However, these studies give no value to a life lived with cystic fibrosis. They also assume around 90% uptake of prenatal diagnosis and effectively universal termination of affected pregnancies. This contrasts with surveys of affected individuals and close family members which suggest that only about half find termination of an affected pregnancy acceptable [41–43]. Changes in public attitudes about prenatal diagnosis and termination might further affect the economic value of antenatal screening.
In the UK policy context Murray et al. recommended both that antenatal screening should be offered routinely and that health authorities 'could consider' introducing neonatal screening. They also suggest that routine antenatal screening would reduce the birth prevalence of cystic fibrosis by between 43% and 49% . According to our analysis, by halving the birth prevalence of the disease, the cost per QALY gained for neonatal screening would increase to £19,543. With this lower prevalence at birth, early diagnosis would have to delay the emergence of symptoms on average by 20 months or more for neonatal screening to be less costly and more beneficial.
In 1998 in the UK, up to a quarter of the population were covered by six regional programmes of neonatal screening for cystic fibrosis and we are aware of only one scheme which provides routine antenatal screening (in Edinburgh) . Any economic evaluation of antenatal screening compared with neonatal screening is impossible as the strategies have such different aims. Fundamentally, the benefits are not comparable: in antenatal screening the aim is to allow reproductive choice, including the option to terminate affected pregnancies, whereas neonatal screening primarily aims to improve the length and quality of life of sufferers. Economic evaluations of antenatal screening have therefore tended to give no value to a life with cystic fibrosis, and instead attribute financial savings to lives with cystic fibrosis avoided.
In conclusion, according to the scenarios explored here, as long as the birth incidence of cystic fibrosis remains stable, there is no reason for existing neonatal screening programmes to be discontinued on cost-effectiveness grounds. Although UK Health Authorities wanting to introduce neonatal screening may want to see more reliable evidence of the health benefits of early diagnosis before making a decision, this evidence is now beginning to emerge, especially from the Wisconsin trial . It has prompted the (UK) NHS National Screening Committee to implement a national neonatal screening programme for England (Scotland introduced theirs in 2003). As this programme is rolled out to different regions from April 2005 (see http://www.newbornscreening-bloodspot.org.uk) more reliable data on how early diagnosis alters lung function and long-term survival will become available, and could be used to update this cost-effectiveness analysis.