Draft Genetic Test Review

---

Cystic Fibrosis
Clinical Utility

(347KB)

---

CLINICAL UTILITY

Question 26: What is the natural history of the disorder?
Question 27: What is the impact of a positive (or negative) test on patient care?
Question 28: If applicable, are diagnostic tests available?
Question 29: Is there an effective remedy or acceptable action, or other measurable benefit?
Question 30: Is there general access to that remedy or action?
Question 31: Is the test being offered to a socially vulnerable population?
Question 32: What quality assurance measures are in place?
Question 33: What are the results of pilot trials?
Question 34: What health risks can be identified for follow-up testing and/or intervention?
Question 35: What are the financial costs associated with testing?
Question 36: What are the economic benefits associated with actions resulting from testing?
Question 37: What facilities/personnel are available or easily put in place?
Question 38: What educational materials have been developed and validated, and which of these are available?
Question 39: Are there informed consent requirements?
Question 40: What methods exist for long term monitoring?
Question 41: What guidelines have been developed for evaluating program performance?

---

CLINICAL UTILITY

Question 36: What are the economic benefits associated with actions resulting from testing?

Summary According to the majority of studies done in the early 1990's , the annual direct medical care costs for an average individual with cystic fibrosis are $15,000 to $20,000 (1996 dollars). Based on realistic annual direct medical care costs, expected lifetimes and recommended discount rates, the discounted lifetime medical care costs for an average individual with cystic fibrosis are between $300,000 and $500,000. The outcome of a cost effectiveness analysis can help guide program decision-making but should not be used as a single deciding factor in offering screening. In the non-Hispanic Caucasian and Ashkenazi Jewish populations, about half of the screening costs can be accounted for by averted direct medical care costs In other populations, less than 10 percent of screening costs can be accounted for by averted direct medical care costs. The actual cost-effectiveness is likely to be better than presented here since many subsequent pregnancies would not need testing. This reduction would only be possible with reliable record-keeping.

Introduction

Published estimates of direct medical costs of care for people with cystic fibrosis may be reported in terms of annual costs of care, and/or discounted lifetime total costs. To convert annual cost of care to lifetime cost (or vice versa), it is necessary to multiply the annual costs times the expected lifetime, while applying a discount rate. The discount rate is the return on investments possible above inflation over that lifetime. For example, assume that an annual bill of $100 must be paid each year for 10 years and the inflation rate is zero. It is not necessary to have all $1000 at the beginning of the time period, if the remaining money is invested and earns interest. This smaller ‘discounted' amount is all that is necessary. If, for example, the discount rate were 3percent, only $879 would be needed. If the discount rate were 5 percent, only $811 would be needed. Two studies with the same annual direct costs of care can have different lifetime discounted costs because of differences in life expectancies and/or discount rates. For example, assume that the annual direct care costs of an individual are $20,000. If one study assumed a life expectancy of 35 years with a 3 percent discount rate, the total lifetime costs would be $442,000. Another study assuming an average life expectancy of 25 years with a 5 percent discount rate would report total lifetime costs of $296,000.

To the extent possible, the following annual cost estimates only include direct costs of care excluding, for example, costs of the family's time for treatment and travel. Studies differ in what is included as costs of care. One area of difference is paid home health care. According to one estimate, 20 percent of all direct care costs are home care (Wildhagen et al., 1996a). Using a broader definition of costs of care that includes indirect costs, the same investigators report that 50 percent of the total cost of care for cystic fibrosis is incurred outside the formal medical system (Wildhagen et al., 1996b).

Annual cost of care

Table 4-22 contains a summary of published annual direct costs of care. All costs are adjusted 1996 dollars using the medical care component of the Consumer Price Index. Each study is then summarized after the table.

Table 4-22. Reported Annual Direct Medical Care Costs for an Individual with Cystic Fibrosis

Author	Year Pub	Year Collected	Site	Annual Costs	Comments
Lieu	1999	1996	NCA	$13,650	No home health costs included
Rowley	1998	1989	US	$43,083	Charge? Biased toward severe disease
Wildhagen	1996	1991	Neth	$18,226	Excludes $4,556 in home health costs
Lieu	1994	Pre- 1994	US	$18,233	From the OTA (1992)
OTA	1992	Pre- 1989	US	$16,637	Direct medical costs only

 

• Lieu and colleagues (1999) estimate the average annual direct medical cost of care based on 1996 health service utilization data from Northern California Kaiser Permanente for 136 patients who were continuously enrolled in the health plan for the whole year. Patients ranged in age from 9 months to 56 years. They were classified as mild (41 percent), moderate (31 percent) and severe (15 percent). This estimate includes hospital, laboratory, radiology, outpatient, and pharmaceutical services. It does not include any home health care services. The estimated annual cost of care is $13,650. Cost of care averaged $6,300 for mild, $11,400 for moderate, and $43,300 for severe cases of CF. For the US population, 56 percent have mild, 28 percent have moderate, and 16 percent have severe disease.

• Rowley and colleagues (1998) cite unpublished data from the Cystic Fibrosis Foundation that the direct cost of medical care amounted to $43,083 per year, in 1996 dollars. They do not provide information on how the CF Foundation came up with this estimate. Lieu et al. (1999) state that it was based on an inflation-adjusted 1991 estimate derived from 1989 data on hospital charges for a group of cystic fibrosis patients that may not have been representative of all patients. According to Lieu et al. (1999), the lower magnitude of their estimate results in part from changes over time in patterns of care, changes in costs, use of costs rather than charges, and a representative inclusion of mild and moderate cases. They do not mention the possibility that other direct costs such as home care may have been included in the CF Foundation estimate but excluded from their own analysis.

• Wildhagen and colleagues (1996) collected data on the direct costs of hospital care, hospital and non-hospital medication, and home care from a survey of medical records and a patient questionnaire. On average the annual cost of a patient with cystic fibrosis in 1991 was 10,908 pounds (hospital care 42 percent, medication 37 percent, home care 20 percent). Converted to 1996 US dollars using the medical care CPI, this is $22,782. This estimate differs from the Lieu et al. (1999) estimate by including the cost of home care. If home care were excluded, the Dutch estimate would be $18,226.

• Lieu and colleagues (1994) state that they took a published estimate from a study by the U.S. Congress's Office of Technology Assessment (1992), although the original figure is not mentioned. Adjusted for inflation, this is stated to be $16,092 in 1993 dollars. In 1996 dollars, this is equivalent to $18,233.

• The OTA (1992) report reveals a set of estimates, based on a contract document prepared by M.V. Pauly. First, data were collected by the Wilkerson Group from interviews with cystic fibrosis patients, their families, and clinicians. Three groups of patients were defined, with average annual cost of medical care of $8,500 for ‘mild', $24,500 for ‘moderate', and $46,500 for ‘severe' cases. Only patients with hospitalizations were included in the survey. The OTA analysis adjusted these estimates to take into account ‘submild' cases with no hospitalizations in a given year and came up with a weighted average of $10,885 in annual medical expenses. This was based on an arbitrary assumption that medical care costs were $2,000 for ‘submild' cases. These estimates are given in 1989 dollars. Adjusted for inflation on the basis of the medical care component of the CPI, the estimate is $16,637 in 1996 dollars.

Discounted lifetime cost of care

A number of estimates of discounted lifetime costs of care for cystic fibrosis patients have also been published. One of these (Ginsberg et al., 1994), contains no estimate of annual cost of care. The other studies all calculate lifetime estimates based on annual costs of care included either in the same publication or an earlier publication that is cited (Table 4-23). To the extent possible, the following estimates relate specifically to the direct cost of care. Some estimates include both medical and non-medical costs, others relate only to medical costs. The definition of medical costs varies across studies, notably in whether home health care costs are included. Published estimates have been converted to 1996 dollars, as needed. The U.S. Public Health Service Panel on Cost-Effectiveness in Health and Medicine recommends that studies conducted from the societal perspective publish estimates using both 3 percent and 5 percent discount rates. None of the prenatal cystic fibrosis screening evaluations has followed that practice. The choice of a 3 percent discount rate is appropriate from the societal perspective. From the health system perspective, a higher discount rate may be more appropriate. Most studies have used current estimates of historical survivorship, reflected in median age at death of affected patients (typically, 30 years). The cost estimates from the Netherlands assume a life expectancy of 35 years, which raises their cost estimates relative to the others. The Israel study assumed a life expectancy of 45 years.

In principle, cost of illness studies subtract the cost of care for unaffected individuals from that of affected persons in order to calculate the incremental cost of care. Only one of the studies in this table (Ginsberg et al., 1994) has explicitly done so. The remaining estimates likely include some degree of overestimation of the cost of cystic fibrosis by failing to present net costs of care.

Table 4-23. Reported Lifetime Direct Medical Costs for an Individual with Cystic Fibrosis

Author	Year Pub	Site	Discount Rate (%)	Life Expectancy	Lifetime Costs ($1,000)
Lieu	1999	US	5	30	220
Lieu	1994	US	5	30	276
Lieu	1999	US	3	30	276
Van der Riet	1997	Neth	5	30	324
Ginsberg	1994	Israel	5	45	329
Asch	1998	US	5	30	364
Wildhagen	1996	Neth	5	35	388
Vintzileos	1998	US	3	30	778
Rowley	1998	US	3	30	844

• Rowley et al. (1998) report that the annual direct cost of care, in 1996 dollars, is $43,083 per year and the "indirect" (parental) care is $9,380 per year, based on parental time of 938 hours per year valued at $10 per hour. Assuming that costs are invariant with age, they sum up the total cost, direct plus indirect, over a life expectancy of 30 years. The undiscounted total is $1,573,890. Discounted at 3 percent, the total is $1,028,298. Although the authors do not report the discounted total medical cost of care, it is possible to calculate this by multiplying $1,028,298 by the ratio of $43,083 to $52,463. The resulting total for discounted total medical costs is $844,446.

• Vintzileos et al. (1998) cite the 1997 NIH Consensus Development Conference Statement (1999) as stating that the lifetime cost of care is $800,000, which supposedly includes both direct medical and indirect costs. The NIH appears to have relied, without attribution, on the same CF Foundation estimates (over $40,000 per year in direct costs and over $9,000 per year in indirect costs) as did Rowley et al. (1998). The NIH statement that the discounted total for direct and indirect costs is approximately $800,000 was in error. Based on an annual cost of $49,000 per year for 30 years and a 3 percent discount rate, the discounted total is close to $1 million; the discounted total for direct costs alone was approximately $800,000. In any case, the $800,000 figure in 1997 dollars is adjusted for inflation to $778,166 in 1996 dollars.

• Wildhagen et al. (1998) report that the lifetime cost of care for a CF patient in the Netherlands is 238,634 pounds sterling, calculated using a 5 percent discount rate and assuming a life expectancy of 35 years. This estimate is equivalent to $387,586 in 1996 dollars. This estimate is based on an examination of medical records for 81 CF patients complemented by additional information on use of health services obtained through a questionnaire filled out by 73 CF patients. Further details of the methods are provided in two other publications (Wildhagen et al., 1996a; 1996b). The original estimate, in 1991 currency, was a discounted total of 164,365 pounds, which implies a 45 percent adjustment for inflation between 1991 and 1996. This ratio is high, compared to a 29 percent increase in the medical care CPI in the United States during the same period.

• Van der Riet et al. (1997) rely on an unpublished version of the Wildhagen et al. (1996a) estimate of cost of care. They express this as 545,968 Dfl, in 1994 currency, and provide an exchange rate of 1.82 Dfl to 1 US$. This converts to $299,982 in 1994 dollars, or $324,436 in 1996 dollars.

• Asch et al. (1998) report lifetime medical and nonmedical direct cost of care for CF of $351,278 in 1995 dollars. This is taken from the OTA study, adjusted for inflation at an arbitrary rate of 4 percent per year. They also report that the OTA estimate has two components, $181,258 in direct medical costs and $170,020 in direct nonmedical costs. In 1996 dollars, the total estimate is $363,545.

• Lieu et al. (1994) also derived their lifetime cost of care from the OTA report, but only for the medical cost of care component. This estimate is $243,650 in 1993 dollars, or $276,072, in 1996 dollars.

• Ginsberg et al. (1994) report a lifetime CF cost estimate of $328,431 in 1993 dollars, discounted to present value with a 5 percent discount rate. This total consists of $290,528 in medical costs, $6,938 in extra food, $18,845 in earnings losses, $1,806 in transport costs, and $10,316 in mortality cost. For physiotherapy, only the one sixth of sessions that are delivered by paid professionals are included in the medical care component; home care provided by family members is excluded. The medical care cost estimate when adjusted for inflation is equivalent to $329,188 in 1996 dollars. The medical cost estimates in this are based on a projection of future care standards, not current care. It was assumed that all patients would receive heart-lung transplants and that this would prolong survival by an average of 15 years. Offsetting these assumptions, which inflate costs quite substantially compared to other studies, is the lower cost of health care in Israel because of lower wage levels. The authors acknowledge that assuming a life expectancy of 45 years raises their cost estimates. They also report a cost estimate to age 25 of $192,000, which they note is more comparable to other estimates.

A unifying analysis of the lifetime direct medical costs of cystic fobrosis

The three components of the lifetime direct medical costs of cystic fibrosis are the annual costs of direct medical care, the expected lifetime, and the discount rate. From the literature, the annual costs of direct medical care in the early to mid 1990's are between $15,000 and $20,000 per year for the average patient. Given the increasing use of lung transplants and drugs, the costs in the near future are likely to be even higher. Thus, a third annual cost of $25,000 will also be included. Guidelines for economic analyses like these suggest using discount rates of both 3 and 5 percent. Both will be utilized. The average lifetime of an individual with cystic fibrosis had not increased significantly in the last decade and, therefore, the current lifetime of 30 years is a reasonable estimate. For purposes of sensitivity analysis, an additional lifetime of 35 years will also be included. Figure 4-2 shows the total costs for annual costs varying from $15,000 to $25,000, discount rates of 3 percent and 5 percent, and lifetime of 30 and 35 years. Overall, nearly all lifetime direct medical costs are between $250,000 and $500,000.

Figure 4-2. Total Lifetime Direct Medical Costs for an Individual with Cystic Fibrosis. This cost analysis considers annual direct medical expenses from between $15,000 and $25,000 dollars (x-axis) and total lifetime direct medical costs (y-axis). The analysis is performed at two life expectancies (labeled 30 and 35 years) and at two discount rates (solid lines 3 percent and dashed lines 5 percent).

Balance of costs and benefits of prenatal cystic fibrosis screening

Definitions: A cost-effectiveness analysis estimates the net cost of an intervention (defined as the cost of delivering the intervention minus averted costs), divided by the number of desired outcomes achieved. Although not addressed in this report, a cost-benefit analysis places a monetary value on the desired outcome (the denominator in a cost-effectiveness analysis), which is then subtracted from the other costs to derive the net cost or benefit of the intervention.

Cost effectiveness evaluations of prenatal screening for cystic fibrosis

Two different outcomes can be evaluated. The first is the number of affected fetuses detected and the second is the number of births of affected children averted. For the first outcome, the cost-effectiveness ratio is the screening cost per case identified. This type of cost-effectiveness analysis is non-directive in terms of what is done with the information, which is assumed to be of some value to the couples involved. Question 35 concludes that the cost per case detected is $500,000 in non-Hispanic Caucasians. For the second outcome the cost-effectiveness ratio is the cost per case averted. Analyses of this type find that the higher the rate of pregnancy termination, the more cost-effective screening appears. For either of these outcomes, two questions can be asked: 1) Is prenatal screening a cost-effective option to offer? and 2) Which prenatal screening protocol is the most cost-effective? Studies focusing on the first question typically analyze a single prenatal screening strategy and overall cost-effectiveness is closely tied to magnitude of averted cost of care from terminated pregnancies. The cost comparison of screening strategies does not depend on this, since the relevant outcome is minimizing the cost per case detected.

Studies of the value of information – willingness to pay

Estimates of the average cost of prenatal screening for cystic fibrosis have been calculated in terms of both cost per couple screened and cost per affected fetus detected (Question 35). The average cost is at least $120 per couple screened and $500,000 to $800,000 per case detected. The cost of obtaining this information (which fetus would develop cystic fibrosis) can be directly compared to the perceived value of the information. A few of these willingness to pay (WTP) analyses have been conducted.

The only willingness to pay analysis conducted in the United States (summarized by Rowley et al., 1998) was based on responses to a single question that elicited from respondents how much they would have been willing to pay for screening that was provided free of charge in the context of a research protocol. Most (77 percent) of the respondents were willing to pay less than $25. Only 6 percent of the respondents were willing to pay more than $50 for the test. The average cost of screening in this study was calculated to be almost $200. The perceived value of information from cystic fibrosis screening did not come close to justifying the cost of the screening, as carried out in Rochester, New York in the mid-1990s.

A more sophisticated willingness to pay study was conducted earlier in Great Britain (Donaldson et al., 1995). In Aberdeen, a group of pregnant women who had undergone cystic fibrosis screening in a randomized trial were surveyed regarding their willingness to pay. Overall, 51 percent responded. The median response was 20.5 pounds ($34), higher than was the case for the respondents in the Rochester survey. One difference was where the information was obtained. Median response in the Aberdeen survey was 24 pounds for those who filled out the survey at home, compared to 14 pounds for those who answered the questions at the clinic. Further, respondents who were given prompts had a mean response of 22 pounds, compared to 11 pounds for those who were asked an open-ended question. The main predictors of willingness to pay were found to be the willingness to terminate an affected pregnancy, higher social class, and greater knowledge about cystic fibrosis.

The open-ended version of the Aberdeen survey was repeated in a group of women attending prenatal care who indicated that they would accept cystic fibrosis screening if it were offered (Donaldson et al., 1997). The median estimate from this survey was 19 pounds (or $32). Like the other surveys cited, the WTP estimates exclude women who do not consider screening to be of value and are unwilling to be tested. It is possible than many of the non-respondents did not place a high value on the information. One limitation of the WTP estimates from Aberdeen is that many of the respondents appear to have based their estimates on their perceptions of the cost of screening, not their actual willingness to pay. That is, when asked how much people are willing to pay for a service, many people may give a response based on their idea of what a reasonable price is for the service.

Cost effectiveness analyses that include averted costs

Differences between cost-effectiveness analyses hinge on the proportion of affected fetuses that are selectively terminated. The following sections summarize and critically evaluate the four cost-effectiveness and cost-benefit studies published since 1994.

• Lieu and colleagues (1994) concluded that providing screening to one million white women in the United States would cost $83 million. The base line assumptions of the model are that 72.3 percent would accept screening, 80 percent of those who accept screening would accept prenatal diagnosis, and 30 percent of those whose fetuses test positive would be selectively terminated. Under these assumptions, screening would save $12 million in averted lifetime direct medical costs from 50 selective terminations, resulting in a net cost of $71 million (83-12). The net cost per affected birth averted is $1,420,000 ($71 million/50). This study has been criticized for assuming that only 30 percent of affected fetus would be selectively terminated (Petrou et al., 2000). Pilot trials (Question 33) have shown that at least 80 percent of couples who pursue fetal testing and are found to have an affected fetus will make that choice. If this higher number were used, 133 termination (compared to 50) would occur and reduce the net cost per affected birth averted to $383,000 (compared to $1,420,000).

• Rowley and colleagues (1998) report that the screening cost per cystic fibrosis birth averted is $1,322,376, assuming no replacement pregnancy. They report that the discounted lifetime cost of care is $1,028,298, and that averted costs of care amount to 78 percent of the cost of providing screening. This is a mixed-perspective analysis. The authors used the health care system perspective for calculating costs of screening and the societal perspective for calculating cost of care. The same perspective should have been used throughout the analysis. If only medical costs of care were included ($844,446), the cost offset ratio would fall from 78 percent to 64 percent. Even this cost of care estimate is based on unpublished data that refer to costs for relatively severe cases. Population-based data yield lower estimates of cost of care. If the estimate from Lieu et al. (1999) using a 3 percent discount rate ($275,572) is substituted, the cost-offset ratio declines to 21 percent. Some of the cost parameters in Rowley et al. (1998) appear surprisingly high. In particular, the pre-screening education cost of $20 likely reflects a research protocol rather than a routine screening protocol. The cost of DNA analysis is also high, at $150, and the cost of genetic counseling for carriers, at $150, is much higher than in other studies. With alternative estimates of $10 for pre-screening education, $100 for DNA analysis, and $30 for carrier counseling, the screening cost per case averted would fall to $826,556. On the other hand, it should be noted that the analysis excluded the cost of specimen collection and processing.

• Vintzileos and colleagues (1998) have published the least complete analysis of screening, but their report is the only U.S. study that concludes that screening for cystic fibrosis in pregnancy is likely to be cost saving. In particular, the study concluded that under most assumptions considered, screening is cost saving for Caucasians, although not for African Americans, Asians, or Hispanics. The authors maintain that, "Because the overwhelming majority of pregnant women are white, the savings from this group is more than enough to compensate for the small losses observed among the three other racial or ethnic minorities." This analysis includes only two costs of screening: DNA analysis and prenatal diagnosis. No costs are allowed for pre-screening education, sample acquisition, result notification, genetic counseling, fetal loss, or induced abortion. The model includes implausible assumptions about program uptake, including 100 percent partner testing and 100 percent use of prenatal diagnosis. Further, the authors arbitrarily reduced all screening costs by half, under the assumption that each affected pregnancy identified today would, without additional cost, avert an additional cystic fibrosis pregnancy in the future. Finally, this study used a relatively high estimate of cost of direct medical care care.

• Asch and colleagues (1998) report a relatively rigorous decision analysis of prenatal screening. The authors modeled three approaches: expanded one-step (couple screening with both partners tested termed "parallel parental sequence" in the report), one-step (couple screening with sequential testing termed "sequential parental sequence" in the report) and two-step (sequential screening with only female sample collected initially termed "sequential parental sequence" in the report). For each model, three types of DNA testing were modeled: a "standard" molecular test for 6 mutations, an "expanded" molecular test for 20-30 mutations, and "mixed" testing, with the standard test for the first partner and the expanded test used only if the first partner tests positive. The analysis was conducted from three perspectives: societal, patient, and payer. Societal perspective was based on resource costs, the individual perspective on out-of-pocket and opportunity costs, and the payer perspective on an assumption that payers would pay 80 percent of stated charges. The base-case analysis was conducted from the societal perspective. The average cost per cystic fibrosis birth avoided is calculated for three sequential screening strategies. According to the authors, it was $381,000 for standard (6-mutation) screening, $512,000 for expanded (20-30 mutation) screening, and $367,000 for mixed screening. The difference in results between the standard and expanded screening strategies reflects the difference in cost of $100 for the expanded mutation test and $50 for the 6-mutation test. The authors note that these estimates all assume 100 percent uptake of abortion in cases of affected fetuses. Unlike most other analyses, these authors did not subtract averted costs of care from screening costs to calculate net costs. Consequently, their results cannot be directly compared with the other estimates in this section.

A unifying analysis of cost effectiveness with averted costs

Screening costs are just over $500,000 per prenatal case of cystic fibrosis detected in a population of non-Hispanic Caucasians (Question 35, Table 4-21). Analysis of pilot trials (Question 34) show that about 80 percent of affected fetuses identified as part of screening programs are terminated. Lifetime direct medical care costs for the average individual with cystic fibrosis is between $250,000 and $500,000. Table 4-24 shows the cost effectiveness of prenatal cystic fibrosis screening for various racial/ethnic groups when averted costs are included. The analysis assumes one-million couples approached for screening (for a more complete discussion of the assumptions for this analysis, see Table 4-17, Question 35). In the non-Hispanic Caucasian and Ashkenazi Jewish population, about half, or more of the screening costs are covered by averted direct medical care costs. For the remaining racial/ethnic groups, less than 10 percent of screening costs are accounted for by averted direct medical care costs.

Table 4-24. Cost Effectiveness of Prenatal Screening for Cystic Fibrosis when Averted Costs are Taken into Account

Racial/Ethnic Group	Total Costs of Screening (millions of $)	Cases Detected	Cases Averted	Direct Medical Costs Averted		Offset Ratio Range (%)
				$250k	$500k
Non Hispanic Caucasians	98	188	150	37	75	36 to 75
Ashkenazi Jewish	99	236	189	47	95	47 to 95
Hispanic Caucasians	96	23	18	5	9	5 to 9
African Americans	96	17	14	3	7	3 to 7
Asian Americans	96	5	4	1	2	1 to 2

 

Implications of ‘Steady State' Screening
In all of the discussions to this point, one underlying assumption has been implicitly made. That is, all pregnancies are tested for all couples regardless of test results from a previous pregnancy. Several studies have pointed out that the ‘steady state' of screening would actually result in reduced costs as most subsequent pregnancies would not need to be tested again. A couple would need to be tested in a subsequent pregnancy if 1) the partner has changed or 2) the test will detect a higher proportion of mutations. No formal estimate of the effect of ‘steady state' screening will be made, but it can be easily seen that a large proportion of the population would not need to be tested in a subsequent pregnancy, if reliable records of testing could be maintained.

 

References

Asch DA, Hershey JC, Dekay ML, Pauly MV, Patton JP, Jedrziewski MK, Frei F, Giardine R, Kant JA, Mennuti MT. 1998. Carrier screening for cystic fibrosis: costs and clinical outcomes. Med Dec Make 18:202-212.

Beech R, Bekker. 1996. Planning the development of cystic fibrosis gene carrier screening. J Health Serv Res Policy 1:81-92.

Cuckle HS, Richardson GA, Sheldon TA, Quirke P. 1994. Cost effectiveness of antenatal screening for cystic fibrosis. BMJ 311:1460-1464.

Donaldson C, Shackley P, Abdalla M, Miedzybrodzka Z. 1995. Willingness to pay for antenatal screening for cystic fibrosis. Health Econ 4:439-452.

Donaldson C, Shackley P, Abdalla M. 1997. Using willingness to pay to value close substitutes: carrier screening for cystic fibrosis revisited. Health Econ 6:145-159.

Ginsberg G, Blau H, Kerem E, et al. 1994. Cost-benefit analysis of a national screening programme for cystic fibrosis in an Israeli population. Health Econ 3:5-23.

Lieu TA, Watson SE, Washington AE. 1994. The cost-effectiveness of prenatal carrier screening for cystic fibrosis. Obstet Gynecol 84:903-912.

Morris JK, Oppenheimer PM. 1995. Cost comparison of different methods of screening for cystic fibrosis. J Med Screen 2:22-27.

Murray J, Cuckle H. 2001. Cystic fibrosis and fragile X syndrome: the arguments for antenatal screening. Comb Chem High Throughput Screen 4:265-272.

Petrou S, Henderson J, Roberts T, Martin MA. 2000. Recent economic evaluations of antenatal screening: a systematic review and critique. J Med Screen 7:59-73.

Rowley PT, Loader S, Kaplan RM. 1998. Prenatal screening for cystic fibrosis: An economic evaluation. Am J Hum Genet 63:1160-1174.

US Congress, Office of Technology Assessment, Cystic Fibrosis and DNA Tests: Implications of carrier screening. OTA-BA-532 (Washington, DC: US Government Printing Office, August 1992).

Vintzileos AM, Ananth CV, Smulian JC, Fisher AJ, Day-Salvatore D, Beazoglou T. 1998. A cost-effectiveness analysis of prenatal carrier screening for cystic fibrosis. Obstet Gynecol 91:529-534.

Wildhagen MF, Hilderink HB, Verzijl JG, Verheij JB, Kooij L, Tijmstra T, ten Kate LP, Habbema JD. 1998. Costs, effects, and savings of screening for cystic fibrosis gene carriers. J Epidemiol Comm Health 52:459-467.