Published online September 1, 2006
PEDIATRICS Vol. 118 No. 3 September 2006, pp. 896-905 (doi:10.1542/peds.2005-2782)
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ARTICLE

Cost-effectiveness of 4 Neonatal Screening Strategies for Cystic Fibrosis

M. Elske van den Akker-van Marle, PhDa, Hinke M. Dankert, BSca, Paul H. Verkerk, PhDa and Jeannette E. Dankert-Roelse, MD, PhDb

a Netherlands Organization for Applied Scientific Research, Quality of Life, Leiden, Netherlands
b Department of Pediatrics, Atrium Medical Centre, Heerlen, Netherlands


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVES. The purpose of this work was to assess the costs of 4 neonatal screening strategies for cystic fibrosis in relation to health effects. In each strategy, the first test was the measurement of serum concentration of immunoreactive trypsin. The second step consisted of either a second immunoreactive trypsin test (strategy 1) or a multiple mutation analysis (strategy 2). In strategies 3 and 4, a third step was added to strategy 2: a second immunoreactive trypsin test (strategy 3) or an extended mutation analysis of the cystic fibrosis gene, that is, a denaturing gradient gel electrophoresis analysis (strategy 4).

METHODS. We conducted an economic-modeling exercise in the Netherlands based on published data and expert opinions. Subjects were a hypothetical cohort of 200 000 neonates, the approximate number of children born annually in the Netherlands, and we assessed the costs and number of life-years gained as a result of neonatal screening for cystic fibrosis. The costs and effects of changes in reproductive decisions because of neonatal screening were also assessed.

RESULTS. Immunoreactive trypsin + immunoreactive trypsin had the most favorable cost-effectiveness ratio of {euro}24800 per life-year gained. Immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis achieved more health effects than immunoreactive trypsin + DNA + immunoreactive trypsin at lower cost. The incremental costs per life-year gained of the immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis strategy compared with the immunoreactive trypsin + immunoreactive trypsin strategy were {euro}130700, whereas the incremental costs of the immunoreactive trypsin + DNA strategy compared with the immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis strategy were {euro}2154300. When changes in reproductive decisions as a result of neonatal screening are also taken into account, neonatal screening for cystic fibrosis may lead to financial savings of approximately {euro}1.8 million annually, depending on the screening strategy used.

CONCLUSIONS. Cystic fibrosis screening for neonates is a good economic option, and positive health effects can also be expected. Immunoreactive trypsin + immunoreactive trypsin and immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis are the most cost-effective strategies.

Key Words: cost-effectiveness • economic evaluation • neonatal • screening-newborn

Abbreviations: CF—cystic fibrosis • IRT—immunoreactive trypsin • DGGE—denaturing gradient gel electrophoresis

Cystic fibrosis (CF) is 1 of the most common autosomal recessively inherited disorders in white populations. It is a life-threatening multiorgan disease. The pancreas and the respiratory tract are affected in practically all patients, resulting in pancreatic insufficiency and lower respiratory infections. The present therapeutic strategies have dramatically improved the quality of life and life expectancy of patients with CF.

The aim of early detection of patients with CF by neonatal screening is to initiate treatment as early as possible. Early diagnosis of CF also enables timely genetic counseling about the risk of CF in a subsequent pregnancy.

Neonatal screening for CF has been implemented in several parts of the world.1–7 In other countries, the debate about the implementation of neonatal screening is still going on.8 Health-related, psychosocial, ethical, legal, and economic aspects are involved in the discussion. However, there is a scarcity of publications about the cost/cost-effectiveness of neonatal CF screening as support for the discussion. Existing publications focus on some aspects of cost-effectiveness9,10 or limit analysis to one of the available screening methods.11

The aim of this study was to assess the economic aspects of neonatal screening for CF in relation to health effects for 4 different neonatal screening strategies and to explore the effects and costs of neonatal screening on reproductive decisions of parents who are identified by screening as CF carriers.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
We developed a decision analysis model to compare the costs and effects of neonatal screening for CF with a situation without screening in the Netherlands. The comparison was made for a cohort of 200000 neonates, the approximate annual number of births in the Netherlands.12

The model parameters were based on the results of extensive literature review and on expert opinions. There was also primary data collection for some parameters.

All of the costs and effects were discounted at a rate of 3% to convert future costs and effects to their present value, as recommended by the Panel on Cost-Effectiveness in Health and Medicine.13 The costs and consequences of each strategy were assessed from a societal perspective, which means that all costs and consequences are incorporated regardless of who incurs the costs and who obtains the effects. Costs are stated in 2004 euros.

Epidemiology
The birth prevalence of CF in the Netherlands is 1 in 3600.14 Of an annual birth cohort of 200000 newborns, ~55 children are born with CF. Meconium ileus is the presenting sign in 10% to 20% of newborns with CF.15,16

The survival of CF patients has improved significantly over recent decades, mainly because of improved treatment for CF patients. Frederiksen et al reported a survival probability of 80% at the age of 45.17 Approximately 6%18 of patients with CF die of the disease during childhood. Simpson et al11 assumed a life expectancy of 45.8 years.

Neonatal Screening
The percentage of children covered by the existing neonatal screening program in the Netherlands is 99.5%.19 Several tests can be used for neonatal screening for CF. Tests differ with respect to sensitivity, specificity, and costs. To achieve optimal sensitivity and specificity and to limit costs generally, neonatal screening programs use a combination of tests. In this study, we address 4 different strategies.

In each screening strategy, the first test consists of measuring serum concentrations of immunoreactive trypsin (IRT).3 The second step is either a second IRT test (IRT + IRT strategy)3 or a single/multiple mutation analysis (IRT + DNA strategy).10,20–22 A third step can be added to strategy 2: a second IRT test (IRT + DNA + IRT strategy)22 or an extended mutation analysis of the CF gene, that is, a denaturing gradient gel electrophoresis (DGGE) analysis23 (IRT + DNA + DGGE analysis). In all of the strategies, infants with a positive screening test are referred for sweat testing to confirm or to exclude the CF diagnosis (Table 1).


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  		TABLE 1 Strategies for Neonatal Screening for CF Addressed in This Study

 
In the IRT + IRT strategy the screening test result is considered positive when the serum concentration of IRT from the second IRT measurement is above the cutoff level.24 In the IRT + DNA strategy, the test result is considered positive when 1 or 2 CF mutations are detected.24 When a multiple mutation analysis is used instead of a single mutation analysis, sensitivity increases, but specificity diminishes.21 In the IRT + DNA + IRT strategy, the test result is considered positive either when 2 CF mutations are found or when the second IRT test is above the cutoff level.22 In the IRT + DNA + DGGE strategy, the test result is only considered positive when 2 CF mutations are identified, either by multiple mutation analysis or by the extensive gene analysis.23 Carrier identification is, therefore, virtually unnecessary. Sensitivity and specificity are both high in the IRT + DNA + DGGE strategy.

A considerable number of studies have reported sensitivity and specificity estimates for the various screening strategies under consideration.2–5,7,20,21,25–31 For our analyses, to calculate the number of tests needed, we used the estimates from studies in which it was possible to derive the sensitivity and specificity of the individual tests. The sensitivity and specificity of the first IRT were reported to be between 86% and 100% and 98.4% and 100%, respectively.2,3,7,21,26–28,30 The sensitivity of a second IRT test varied between 88.5% and 95%, and the specificity range was between 88.3% and 98%.3,30 These differences were partly caused by differences in the cutoff levels used for the IRT test. In our study, we assumed that the first IRT test screen was positive when IRT values were in the top 1% daily.

DNA analysis can be limited to testing for the {Delta}F508 mutation, which detects 95% of CF patients in most Western European countries. To detect 99% of the patients in the Netherlands, DNA analysis can be extended to include the 31 most common mutations. Reports indicate that this approach detects 97% of CF patients in the United States.21 In our study, we assumed use of the extended test. In 75% of patients, 2 CF mutations will be identified, but 25% of the patients will be detected by the identification of only 1 CF mutation.21 Assuming a carrier frequency of CF in the Netherlands of 1 in 30, it can be expected that 3% of carriers will be detected by screening. The frequency of carriers has been found to be twice as high in newborns with increased IRT concentrations.32

In a randomized, controlled trial, Doull et al25 observed a significant decrease in nonmeconium ileus mortality early in life in screened patients (0 of 78) compared with nonscreened patients (4 of 71). This study, together with a number of observational studies, indicates that there is level 2 evidence of a reduction ≥50% in mortality rates in children with CF diagnosed by newborn screening compared with children with a clinical diagnosis of CF.6,16,18,25,33 However, the difference between the screened group and the clinical diagnosis group was not statistically significant in all of these studies.

In this study, we assumed a gain of 40 life-years per CF death prevented by neonatal screening. No gain in life expectancy was assumed for CF patients with meconium ileus, because practically all of these infants are diagnosed shortly after birth, and they do not, therefore, benefit from neonatal screening. The number of quality-adjusted life-years gained is the preferred effect measure in cost-effectiveness analyses. However, no adequate estimates are available for health-related quality of life in CF patients identified by screening compared with clinically detected patients.18 We, therefore, used the number of life-years gained as the effect measure in this study.

Reproductive Decisions
Newborn screening allows couples with a child with CF to make early informed reproductive choices about future pregnancies. As a result of neonatal screening, a drop in the birth rate of ~10% was observed for children with CF in Australia.34 In ~50% of cases, this was a result of the parents' decision to have no further children. In the other cases, parents opted for prenatal diagnosis; 69% of these parents decided to terminate or indicated that they would have terminated a pregnancy with an affected fetus.35 Similarly, in Brittany, France, it was found that prenatal diagnosis followed by abortion was responsible for an overall decrease in CF prevalence at birth of 30.5% over the period 1992–2001.36 A calculated reduction of 15.7%, ~50% of the observed decrease, was attributed to newborn screening for CF.

Costs
An IRT test in the Netherlands costs {euro}4.79 (J. G. Loeber, PhD, written communication, 2005). A second IRT test costs {euro}18.47, assuming that a new blood spot has to be collected by the district nurse at the child health clinic. This figure includes the cost of the laboratory, the cost of the district nurse (15 minutes), and travel and time (30 minutes) for one of the parents.37

Multiple mutation tests and DGGE tests cost {euro}100 (G. Pals, written communication, 2005) and {euro}500 (G. Pals, written communication, 2005), respectively. These costs include the cost of DNA extraction, DNA analysis, laboratory space, equipment, reagents, supplies, licenses, technical and administrative personnel, and new technical advances.

In the IRT + DNA strategy, all infants with 1 CF mutation and a normal sweat test are considered to be healthy carriers. When the parents of these infants are informed about the results of the sweat test, genetic counseling is also offered to them and accepted by 90%.38 After genetic counseling, ~50%38 of the parents ask for CF carrier testing for themselves. We assumed that, in the IRT + DNA + IRT strategy, parents are also informed about the carrier status of their child when a second IRT test is necessary. These parents will also be offered genetic counseling, and we assumed the same acceptance rates as in the IRT + DNA strategy.

Genetic counseling costs {euro}449 per couple,39 and testing parents for carrier status costs an additional {euro}66439 per person. Both amounts include parents' traveling expenses and time (60 minutes).37

The costs of including neonatal screening for CF in the existing neonatal screening program are based on the costs of adding screening for congenital adrenal hyperplasia to the neonatal screening program in the Netherlands. These costs amount to {euro}133116 per year40 and consist of the costs of a medical consultant, administration costs, and evaluation costs. In addition, changes are required to the information leaflet to include new information. Assuming that the information leaflet is updated regularly, adding new information about CF screening can be included in this process, resulting in negligible costs for adding information about neonatal screening for CF.

A sweat test costs {euro}109.56. These costs include the following: pediatric consultation, laboratory costs, and parents' traveling expenses and time (60 minutes).37,39

In a situation without screening, several diagnostic tests are generally performed before the diagnosis of CF is established. We reviewed the case histories before the diagnosis of CF in 36 patients. This yielded information about the number of hospital days and the medical procedures performed in the diagnostic process. These numbers were multiplied by hospitalization costs37 and the costs of medical procedures.37,39 This resulted in an average diagnostic cost of {euro}9096 per patient diagnosed with CF. CF can also be suspected in patients without the disease. For each clinical CF patient diagnosed, ~100 sweat tests are performed in patients without CF.9 This number was confirmed by primary data research in the VU Medical Centre.

The lifetime costs of care for a CF patient are estimated at {euro}406266 (3% discounting).41 Costs incurred during life-years gained because of neonatal CF screening are not included in the analysis.13 Prenatal diagnostics cost {euro}1648; pregnancy termination costs {euro}690.39

Base-Case Analysis and Sensitivity Analysis
Table 2 shows the values of the model parameters used in the base-case model. Base-case values are in the range for the model parameters described above.


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  		TABLE 2 Model Parameters: Base-Case Values and Lower and Upper Values in Sensitivity Analysis

 
Sensitivity analyses were performed in which the values of the model parameters were varied. This made it possible to study how much influence each parameter had on cost-effectiveness, and crucial parameters determining the cost-effectiveness of neonatal CF screening were identified. In the sensitivity analyses, we used the lower and upper values of the parameters as shown in Table 2.

Both univariate and multivariate sensitivity analyses were performed. In univariate sensitivity analyses, 1 model parameter at a time was varied. Univariate sensitivity analyses are useful in understanding how model parameters influence cost-effectiveness. However, looking at 1 source of uncertainty at a time provides an incomplete estimate of how uncertain the estimated overall cost-effectiveness ratio actually is, because the cost-effectiveness ratio depends on multiple parameters. The interaction of these parameters may imply that the total effect can be something quite different from the simple sum of individual contributions. We, therefore, also performed multivariate sensitivity analyses in which all of the model parameters were varied together. We assumed that all of the model parameters mentioned in Table 2 are independent from each other, and constructed a set of extreme parameter values that yield the highest and the lowest cost-effectiveness ratios. Furthermore, we performed a probabilistic multivariate sensitivity analysis. This consisted of taking 100000 random draws from the probability distributions defined for the model parameters for each model parameter, and the resulting cost-effectiveness ratio for these parameter values was calculated using Crystal Ball, Version 4.0 (Microsoft Corporation, Redmond, WA). In this way, information was derived about the influence of the uncertainty relating to individual parameters on the uncertainty in the cost-effectiveness ratio. Furthermore, acceptability curves were constructed showing the proportion of random draws for which a screening strategy is optimal as a function of the willingness to pay ({lambda}). In this case, an intervention is optimal for a particular random draw when it is associated with the maximum net benefit (net benefit = [{lambda} x life-year gained] – cost). In the probabilistic multivariate sensitivity analysis, we assumed a uniform distribution for the parameters between the lower and upper value presented in Table 2.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
The expected results of neonatal screening for CF are presented in Table 3. In a situation without screening, it is expected that 46 children with CF without meconium ileus will be born each year. The vast majority of these children would be detected by newborn screening. The IRT + IRT strategy would detect 41 of these children, the IRT + DNA + IRT strategy would detect 44, and the other screening strategies were expected to miss only 1 of the children with CF.


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  		TABLE 3 Overview of the Predicted Costs ({euro}) and Effects of Neonatal Screening for CF in the Netherlands for a Cohort of 200 000 Children (3% Discounting)

 
The number of false-positives after the first IRT test would be 1945. With the IRT + IRT strategy, the second IRT test would result in false-positives for 117 of these patients. In the IRT + IRT strategy, no carriers would be detected. In the IRT + DNA and IRT + DNA + IRT strategies, 117 children who are carriers of a CF mutation would be detected, but in the IRT + DNA + DGGE strategy, the number of carriers detected is negligible. In the IRT + DNA + DGGE strategy, information about carrier status remains within the screening laboratory.

The IRT + IRT strategy was the cheapest. The other strategies were more expensive because of the higher costs of screening and diagnostics, and the costs of genetic counseling when carriers are detected by the IRT + DNA or the IRT + DNA + IRT strategies.

When comparing the costs and the effects, 3 strategies (IRT + IRT, IRT + DNA, and IRT + DNA + DGGE) seemed to be efficient. However, the IRT + DNA + IRT strategy was dominated, because more effects could be obtained for lower costs with the IRT + DNA and IRT + DNA + DGGE strategy. The IRT + IRT strategy had the most favorable cost-effectiveness ratio of {euro}24800 per life-year gained. Additional life-years could be saved by the IRT + DNA + DGGE strategy. Linking these additional life-years to the additional costs of the IRT + DNA + DGGE strategy compared with the IRT + IRT strategy resulted in incremental costs of {euro}130700 per life-year gained for the IRT + DNA + DGGE strategy compared with the IRT + IRT strategy. The IRT + DNA strategy actually results in a slight increase in the number of life-years compared with the IRT + DNA + DGGE strategy. The costs of the IRT + DNA strategy are also higher, despite the extra test in the IRT + DNA + DGGE strategy for blood samples, in which 1 mutation was identified by the DNA test. These additional costs for screening in the IRT + DNA + DGGE strategy are outweighed by the savings in cost of genetic counseling, because, in contrast to the IRT + DNA strategy, this strategy does not include genetic counseling (see Table 3). Linking the additional costs of the IRT + DNA strategy and the additional effects results in an incremental cost for the IRT + DNA strategy compared with the IRT + DNA + DGGE strategy of {euro}2 154 300 per life-year gained.

The results of the univariate sensitivity analyses are shown in Table 4. Changes in the lifelong costs for clinically diagnosed patients did not affect the cost-effectiveness ratio of screening if the lifelong costs of patients identified by screening changed accordingly. Assuming that the lifelong costs of patients detected by screening are 10% lower than the lifelong cost of clinically diagnosed patients, neonatal screening for CF would result in financial savings, as well as life-years gained.


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  		TABLE 4 Univariate Sensitivity Analysis: Cost-effectiveness Ratios for Lower and Upper Values of Model Parameters Included in Sensitivity Analysis

 
Constructing 2 sets of extreme parameter values that generate highest and lowest cost-effectiveness showed that the cost-effectiveness ratio of adding screening for CF to the Dutch neonatal screening program ranged from {euro}220000 per life-year gained for the IRT + IRT strategy and {euro}306900 for the IRT + DNA + DGGE strategy in the least favorable situation to financial savings (range: {euro}1.8–1.9 million) and life-years gained for all strategies (range: 52–54 life-years) in the most favorable situation.

The uncertainty about whether screening for CF will lead to savings in lifelong costs of treatment determines ~85% of the variance in the cost-effectiveness ratio. This parameter is, therefore, the most important in determining variance in cost-effectiveness. Other parameters that influence variance in the cost-effectiveness are the lifelong costs of treatment of clinically diagnosed patients, mortality in early childhood because of CF in a situation without screening, and the reduction in childhood mortality as a result of screening for CF.

Figure 1 shows the cost-effectiveness acceptability curves for the different neonatal screening strategies, including the current situation of no neonatal screening. At lower values for willingness to pay (less than {euro}25000 per life-year gained), the IRT-IRT strategy is better. At willingness-to-pay values between {euro}25000 and {euro}800000 per life-year gained, the IRT + DGGE + DNA strategy is optimal, with the IRT + DNA strategy being preferred at willingness-to-pay values above {euro}800000 per life-year gained.


Figure 1
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  		FIGURE 1 Cost-effectiveness acceptability curves of the different neonatal screening strategies for cystic fibrosis, including no neonatal screening.

 
Neonatal screening will also lead to changes in reproductive decisions. Parents may choose to refrain from further children or to opt for prenatal diagnosis and an abortion when the fetus is positive for CF. This will lead to additional costs for prenatal diagnosis and abortion of, respectively, {euro}26500 and {euro}1900 a year, but savings will also be obtained as a result of a fall in the birth rate of CF patients. These savings are expected to amount to {euro}2.3 million.

The additional costs of implementing neonatal screening for CF range from {euro}320000 to {euro}540000 per year depending on the screening strategy used (Table 3). However, when changes in reproductive decisions because of neonatal screening are also taken into account, implementing neonatal screening for CF may lead to financial savings of approximately {euro}1.8 million annually depending on the screening strategy used.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Our exploratory study shows that the cost-effectiveness of neonatal screening for CF in the Netherlands is acceptable. The IRT + IRT strategy had the best cost-effectiveness ratio of {euro}24800 per life-year gained. Additional life-years can be gained when screening strategies testing for specific DNA mutations are used. However, the incremental costs of the additional life-years vary from {euro}130700 per life-year gained for the IRT + DNA + DGGE strategy compared with the IRT + IRT strategy to {euro}2154300 per life-year gained for the IRT + DNA strategy compared with the IRT + DNA + DGGE strategy.

The nature of this exploratory study implies certain limitations. Parameter values have been assessed on the basis of literature review and expert opinions, which may be less appropriate than parameter estimates derived from primary data collected for the situation under study. However, this study was a starting point for priority setting in further research into the cost-effectiveness of neonatal screening for CF. Sensitivity analyses show that estimating lifelong costs of treatment after the early detection of CF should be given high priority in further research. Other priorities for further research are lifetime costs of treatment of clinically diagnosed CF patients, mortality in early childhood because of CF in a situation without screening, and the reduction in childhood mortality because of screening.

Some elements were not incorporated in the cost-effectiveness ratios presented. First, we used the number of life-years gained as the effect measure, whereas the preferred outcome measure would have been the number of quality-adjusted life-years gained. However, there are no adequate parameters available for quality of life in CF patients.18 There is level 1 evidence that newborn screening has a positive effect on growth and nutritional status.18 It is also very probable that newborn screening has a positive effect on lung function.42 Better quality of life can, therefore, be expected in CF patients detected by newborn screening compared with patients detected clinically. More research into quality of life parameters for CF patients is warranted to assess the potential qualitative benefits of newborn screening.

Second, the costs and effects of changes in reproductive decisions were not included in the cost-effectiveness ratios because of the methodologic problem of how to assess the health loss because of the abortion of an affected fetus. The abortion of an affected fetus can be assessed as not involving a loss in health, but it can also be argued that abortion accounts for a loss of 45 life-years (assumed mean life expectancy of CF patients). Implementing newborn screening for CF leads to financial savings of approximately {euro}1.8 million per year when the costs and savings of changes in reproductive decisions are included. Depending on the choice made, this may lead to a health gain compared with a situation without screening (if one assumes no health loss because of abortion) or an annual health loss of ~56 life-years (3% discounted) if abortion is considered to result in a loss of 45 life-years. Further research into this methodologic issue is warranted. This research should also include other methodologic issues relating to the quantification of the health consequences of changes in reproductive decisions. These may include the issue of potential replacement children and the quality of life of parents.

In this study, productivity gains because of improved health as a result of screening were not taken into account, because no information was available on this subject. Including these gains will result in more favorable cost-effectiveness ratios for neonatal CF screening. Productivity gains associated with life extension were also excluded for the same reason. Productivity gains may, however, be offset by the additional health care costs for CF, as well as the costs of unrelated diseases that may occur in the additional life-years.

In our analysis, we assumed that parents will be informed that their child is a carrier of CF when 1 CF mutation is found using the IRT + DNA or the IRT + DNA + IRT strategies. Approximately 90% of parents will accept genetic counseling when this is offered to them.38 In ~50% of those who accept counseling, this is followed by testing to determine whether the parents themselves are CF carriers. In the IRT + DNA + DGGE strategy, parents will not be informed unless the screening test is positive, that is, only when 2 CF mutations are found. However, the number of infants identified as CF carriers in the screening laboratory is the same as in the IRT + DNA and IRT + DNA + IRT strategy. Whether or not to inform parents that their child is a CF carrier is an ethical issue. Other assumptions may change the cost-effectiveness and ranking of the strategies.

For the first IRT test, the IRT threshold used was the >99th daily percentile. Other thresholds are also used, for example the >95th daily percentile.21 Using this threshold in the Dutch situation will lead to less favorable cost-effectiveness ratios, varying from {euro}40400 per life-year gained for the IRT + IRT strategy to {euro}134500 per life-year gained for the IRT + DNA + IRT strategy (assuming constant sensitivity10).

The cost-effectiveness ratio for the IRT + DNA procedure presented by Simpson et al11 was more favorable. This is mainly caused by the higher cost estimates in our study. We included more cost elements (organization costs of CF screening and costs of genetic counseling). Furthermore, the cost estimates for the elements included were higher in our study. This is partly because of the fact that we performed the analysis from a societal perspective. Our cost estimates, therefore, included, in addition to the costs of health care, the costs for the parents, such as time and travel costs.

In addition to newborn screening for CF, there are alternatives, such as carrier screening and prenatal screening. Economic studies of these types of screening have shown that these methods may result in net cost savings,43,44 because the costs of screening may be outweighed by the health care savings resulting from CF prevention. None of these studies, however, attempt to quantify the methodologic dilemma of how to assess health loss because of the loss of an affected fetus. When we included the effects of reproductive decisions of parents in newborn screening for CF, we also found that newborn CF screening leads to net savings. This is because of the fact that fewer CF patients will be born. Furthermore, newborn screening leads to major benefits for children with CF, such as reductions in mortality early in life, better growth and nutritional status, and probably improved lung function. The early diagnosis also means that children will be less exposed to the burden of diagnostic procedures.

In this study, we addressed 4 strategies for newborn CF screening. New developments may lead to changes in the characteristics of the screening tests (sensitivity, specificity, and cost) or to new screening strategies. Sarles et al45 concluded that the use of pancreatitis-associated protein testing looks promising in terms of performance and costs. These developments should be closely followed and may require further investigation focusing on cost-effectiveness.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Newborn CF screening is economically beneficial, and positive health effects are expected as a result of the screening. This is important knowledge in the debate about whether, and which type of, screening should be introduced for CF.


   ACKNOWLEDGMENTS
 
Financial support for this study was provided by the Nederlandse Cystic Fibrosis Stichting.

We thank J. Gerard Loeber (Rijksinstituut voor Volksgezondheid en Milieu) and Gerard Pals (Vrije Universiteit Medical Centre) for their expert opinions.


   FOOTNOTES
 
Accepted Apr 18, 2006.

Address correspondence to M. Elske van den Akker-van Marle, TNO Quality of Life, PO Box 2215, 2301 CE Leiden, Netherlands. E-mail: elske.vandenakker{at}tno.nl

The authors have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Crossley JR, Elliott RB, Smith PA. Dried–blood spot screening for cystic fibrosis in the newborn. Lancet. 1979;1 :472 –474[Web of Science][Medline]
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L. F. Ross
Ethical and Policy Issues in Newborn Screening: Historical, Current, and Future Developments
NeoReviews, February 1, 2009; 10(2): e71 - e81.
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