Bioethics and the Impact of Human Genome Research in the 21st Century

6.5. Economics Issues of Genetics
pp. 95-101 in Bioethics and the Impact of Human Genome Research in the 21st Century

Author: Xin Mao (Eurasia Millenium, UK)

Editors: Norio Fujiki, Masakatu Sudo, and Darryl R. J. Macer
Eubios Ethics Institute

Copyright 2001, Eubios Ethics Institute All commercial rights reserved. This publication may be reproduced for limited educational or academic use, however please enquire with the author.

Ten years ago at the 59^th Annual Meeting of Japanese Society of Human Genetics, which was also organised by Professor Fujiki and held here, I was very luck to meet Professor Dorothy Wertz who is the world's leading sociologist in the field of genetic ethics. Since then Professor Wertz has given me a very good chance to participate the International survey on ethics and genetics conducted in 37nations, and to review the international guidelines on ethical issues in genetic services sponsored by the World Health Organization. The published survey data and the WHO documents provide a basis for international discussion on the ethical, legal and social issues of human genetics (Mao 1998a, 1998b, 1997a, 1997b; Mao and Wertz 1997; Mao 1996; WHO 1998).

It is true that the scientific side of human genetics appears to be less diversity or controversial than social side, in which cultural and political differences are always reflected although there have been certain universal principles on the basic human values that transcend these differences. Perhaps, this is one explanation why the social side of human genetics is much more attractive. It is thought that more knowledge people have about human genetics more views they will express. Therefore I believe that facilitating public debate on ethical, legal and social issues of human genetics and establishing an evidence-based health policy-making system worldwide would be tough issues for the international genetic and ethical communities in the new millennium (Mao 1999).

Introduction

On 26 June 2000 President Bill Clinton, Prime Minister Tony Blair and other world leaders simultaneously announced the completion of the working drafts of the human genome (Macilwain 2000). As the short history of the human genome project shows, this big day came 3-year earlier than expected. One of the driving forces behind this tremendous breakthrough in genetic science was the competition between publicly and privately funded teams related to the ownership of the completed human genome databases, which are thought to have a huge commercial potential (Pennisi 2000; Editorial of Nature Genetics 2000).

Economic factors have contributed a lot to the development of genetic-pharmaceutical industry, seeking for patenting the newly discovered disease-related genes, commercialisation of genetic services, and attracting huge funds from the national and international investors into genetic sectors (Caulfield and Gold 2000; Caulfield 1998; Triendl 2000; Li 2000). Obviously the interests of insurance companies in genetics are simply due to the economic considerations (Ostrer et al., 1993).

Although economic issues of genetics (EIG) are big issues, they are quite less discussed comparing with genetic ethics. One explanation for such phenomenon may be that historically social economy had a large impact on Western eugenic movement, and cost-effectiveness appeared to be one of major issues concerning eugenicists (Allen 1997, 1989; Stamp 1968). For example, in order to justify the expense of building enough institutions to house and separate all mentally retarded people the American Eugenics Society stated in 1923 that the US$25,000 spent on segregating the original mentally retarded persons for life would have saved the state more than US$2,000,000 in later costs. It also suggested that sterilising the mentally retarded people would have cost less than US$150 (Larson 1995). Similar voices could also been heard in many other nations including China in the past (Dikotter 1997). It is therefore uneasy to simply discuss economic issues of genetics beyond ethics. However, it is an undisputed fact that people can do nothing without money today. Furthermore, there is an argument about whether or not economic power would reshape the people's attitudes towards ethical issues in the future (Wertz 1997). Although the principles or formulas of economic calculation remain unchanged, it is unthinkable for planning of genetic services, allocation of health resources and management of budget without cost-effective analysis (Turner 1999; Torgerson and Spencer 1996). In this talk, I would like to discuss the cost-effective analysis of prenatal diagnosis, testing and screening of genetic diseases and the relevant issues.

Cost-Effective Analysis In Genetics
Basically, the term of cost-effective analysis is defined as an economic tool which attempts to evaluate the particular programme under consideration by measuring and comparing all its effects; advantageous effects being measured as benefits and adverse effects being measured as costs. In addition, in the field of health-care, cost-effectiveness analysis is also based on the principles of decision analysis. Decision analysis is a systematic quantitative approach for assessing the relative value of one or more decision options and allows clinicians to make decisions on how to manage individual patients.

The aim of genetics services is "to help people with a genetic disadvantage to live and reproduce as normally as possible" (WHO 1985). Unlike other traditionally medical services such as internal medicine, surgery, gynaecology, paediatrician, etc, at moment genetics services are only capable of offering prenatal diagnosis, testing and screening of people with genetic conditions. Therefore evaluation of the costs-effectiveness of genetics services is naturally focused on these aspects (Modell et al., 1993).

Down's syndrome (DS)
DS occurs in 0.99 per 1000 births, and the risk increases with maternal age. About 10%-20% of infants with DS die in the first year, predominantly due to heart defects. The remaining DS children can survive about 40-50 years. Special education, the move away from institutionalisation, and more employment opportunities have improved the outlook for these persons.

As I mentioned earlier, in the past eugenicists and social reformers put much weight on the social costs of caring mental handicapped people including DS. Now medical professionals and economists pay more attention to the evaluation of the cost-effectiveness of different diagnostic techniques and screening programmes for DS (Cate and Ball 1999). For example, a study reported that if the uptake of a proposed screening programme for DS by using maternal age and serum alpha fetoprotein concentrations is maximal, the replacement rate is zero and a discount rate of 5% is used, the benefit cost ratio is 23.6. If the uptake of the programme is 50%, the replacement rate is 100% and a discount rate of 7% is used, the benefit cost ratio is 12.2 (Gill et al., 1987).

Another study investigated the cost-effectiveness of 5 different screening programs using maternal age, triple screening (TS), and ultrasound (U/S) for fetal markers of DS. These include (1) <35 years, no screening; > or = 35 years, AM; (2) <35 years, TS with AM for screen-positive subjects; > or = 35 years, AM; (3) all patients, TS with AM for screen-positive subjects; (4) <35 years, TS followed by U/S for screen-positive women, AM for women with fetal markers of DS on U/S; > or = 35 years TS with AM for screen-positive subjects; (5) all women, TS followed by U/S for screen-positive women, AM for women with fetal markers of DS on U/S. In this study sensitivities used were TS: 55% <35 years, 80% > or = 35 years; U/S: 70%, and average regional fees used were TS: US$80, U/S: US$200, amniocentesis (AM): US$1,000. The results showed that based on an estimation that 260 cases of DS would occur in the population of 167,654 women (8.4% > or = 35 years at delivery), sensitivity for programs 1-5 was 30, 69, 62, 51, and 36 percent, respectively, and cost/DS was 181,000, 203,000, 162,000, 151,000, and 194,000 US dollars, respectively. These data suggested that DS screening incorporating TS in all patients with program #4 and without program #3 selective U/S in women <35 years yield the best combination of sensitivity and cost effectiveness while minimizing the number of AM-related losses (Cusick and Vintzileos 1999).

The cost-effectiveness of prenatal diagnosis for DS by using the British and American approaches seemed to be different . The British strategy included screening by a first-trimester ultrasound at 10-14 weeks for nuchal translucency thickness, and the American strategy included only second-trimester screening by using maternal age and maternal serum screening. As compared with do-nothing, the American strategy allows savings of approximately US$96 million per year and the best scenario for the British strategy was savings of approximately US$5 million per year. The financial costs of the British and American strategies would be comparable only if the first-trimester ultrasound had a sensitivity of 80% and a false-positive rate of 5% in detecting DS. Therefore the British strategy does not appear to be economically beneficial in the United States even under the most ideal scenarios of ultrasound accuracy (Vintzileos et al., 2000).

Open neural tube defects (NTD)
NTD is very different from other genetic diseases discussed here, as it can be prevented by means of prenatal screening and periconceptional administration of folic acid. For instances, in 1988, the incidence of NTD was 25.3 / 1,000 in China, while in 1992, it reduced to 18.0 / 1,000 (Wang et al., 1998). In 1993, a public health campaign was launched in two areas of China, one with high rates of neural-tube defects (the northern region) and another with low rates (the southern region). In this programme women at their reproductive age were asked to take a pill containing 400 m g of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. The results showed a further reduction of incidence of NTD from 4.8 per 1000 pregnancies of at least 20 weeks' gestation to 1.0 per 1000 in the northern region, and 1.0 per 1000 to 0.6 per 1000 (Berry et al., 1999).

It appears that the evaluation of cost-effectiveness of NTD has also been changing. In the early 1980, health economists augured about the cost-effectiveness of screening and monitoring NTD in order to bid for the public funds to support such programme (Henderson 1982a, 1982b; Chan et al., 1993). Now medical professionals are talking about how to fairly re-allocate resources to allow those prospectively pregnant women to access folic acid treatment on the routine basis.

Inherited disorders of haemoglobin
Collectively sickle cell disease (SCD) and thalassaemia are the most commonly inherited single-gene defects world-wide and were the first group of diseases for which DNA-based detection strategies were utilized. Although genotypically distinct, these two groups of diseases exhibit several common clinical features: moderate-to-severe haemolytic anaemia, acute and progressive tissue damage, disease- or treatment-related organ failure and premature death. Within the last two decades, a striking improvement in life expectancy in the two patient populations has been observed, by dint of primary and secondary prevention strategies (Davies et al., 2000; Rodgers 1998; Modell and Kuliev 1991).

The undiscounted lifetime cost of treating a beta-thalassaemia major patient in UK was estimated to be __803,002, although when the costs were discounted at a rate of 6%, the lifetime cost was reduced to __ 219,068. Within sensitivity analyses, the discounted cost ranged from approximately __188,000 to __ 226,000 (Karnon et al., 1999). In addition, the costs of identifying abnormal haemoglobin in mother were __l209, identifying at-risk fetus before confirmation by prenatal diagnosis __l2,455, providing genetic information and counselling to mother with abnormal haemoglobin __l109, programme savings from cases averted __l61,000 (Eugenia et al., 2000).

In 1994 47,948 babies were screened at a diagnostic laboratory in UK by using isoelectric focusing (IEF) / high power liquid chromatography (HPLC). Among them 25 babies with clinically significant haemoglobinopathies and 704 with haemoglobinopathy traits had identified. The average cost per baby tested was (IEF / HPLC) __3.51 / __3.83. The cost per case of sickle cell disease identified was __6738 / __7355. The cost per trait identified was __234 / __255. There was no significant difference between IEF and HPLC in terms of average cost per test. Therefore the cost-effective screening services should aim to cover a screened population which will generate a workload over 25,000 births a year, and preferably over 40,000 (Cronin et al., 2000, 1998).

Cystic fibrosis (CF)
CF causes a relatively high medical consumption. For examples, in the Netherlands the annuall average cost of a patient with cystic fibrosis in 1991 was __10,908 (hospital care 42%, medication 37%, home care 20%). The cost of care of cystic fibrosis in the Netherlands, with approximately 1000 patients, is estimated at __10.9 million per year, which is 0.07% of the total health care budget. The cost of care of a patient up to the age of 35 is estimated at __614,587. When year-to-year survival is taken into account and future costs are discounted to the year of birth with a yearly discount rate of 5%, the cost of care of a patient with cystic fibrosis is estimated at __164,365 for 1991(Wildhagen et al., 1996a).

A survey about the costs of care of patients with CF outside the hospital in the Netherlands using six categories, e.g. nonhospital medical care, domestic help, diet, travelling because of CF, medication, devices and special facilities at home, work or school showed that the average nonhospital costs of care were about __4,641 per child per year and __10,242 per adult. Nonhospital medical care for children and adults accounted for, respectively, 8 and 5% of these costs, domestic help for 15 and 9%, diet for 10 and 7%, travelling because of CF for 4 and 8%, medication for 63 and 67%, and devices and special facilities at home, work or school for 1 and 4%. Nonhospital costs of care of cystic fibrosis are very high and amount to 50% of the total (medical and nonmedical) lifetime costs of cystic fibrosis (Wildhagen et al., 1996b).

In USA, the cost per screening test for CF was assumed to be US$50-150, patient screening acceptance rates was 25-100%, and therapeutic abortion rates was 50-100%. The net savings per prenatally diagnosed case of cystic fibrosis are US$58,369-$382,369 among whites assuming therapeutic abortion rates of 50-100%. Given the patient screening acceptance rates of 50-78%, the overall annual cost savings in the United States for whites are US$161-251 million. However, the screening program was not found to be cost-effective for blacks, Asians, or Hispanics (Vintzileos et al., 1998).

Regarding the cost-effectiveness of different screening strategies such as prenatal, preconceptional, school, and neonatal carrier screening for CF gene carrier, a Dutch report revealed that neonatal carrier screening gives most carrier couples an informed choice concerning reproduction. If the parents of carrier newborns would not be tested however, prenatal screening detects most carrier couples. Prenatal and single entry preconceptional screening programmes have a favourable cost-savings balance in the Netherlands under a wide range of assumptions. For double entry preconceptional screening and neonatal screening, high enough values of uptake of screening, prenatal diagnosis, and induced abortion are necessary. School carrier screening does not have a favourable cost-savings balance. The authors concluded that if a CF screening programme is judged to be useful on individual and social grounds, costs considerations are no obstacle for prenatal and single entry preconceptional (Wildhagen et al., 1998).

A similar study in UK showed that couple screening for CF at antenatal hospital clinics was the least expensive per carrier couple detected, amounting to __35,700 (__142,900 for each potential cystic fibrosis fetus detected). The costs of the reagents (__25 per test) accounted for over 60% of this total. The results indicated that antenatal screening, in addition to being the most cost effective method of screening, is also medically the screening method of choice as it provides information at the latest time when effective preventive action can be taken and at a time when all people to be screened are likely to be accessible. If the costs of the reagents could be reduced to __5 (still higher than the costs of most diagnostic reagents) the cost for each pregnant carrier couple offered screening would be reduced by 50% to about __18,000 pounds, and the cost of offering screening to 684,000 pregnant couples in England and Wales would be about __9 1/2 million instead of __19 million (Morris and Oppenheimer 1995).

Other monogenic diseases
The costs of DNA diagnosis of people who are at risk of having a child with a monogenic disease such as Duchenne muscular dystrophy (DMD), congenital myotonic dystrophy (CMD), and fragile X syndrome (FraX) in the Netherlands were estimated to be US$1200, delivery US$3916, abortion (13 weeks) US$987 and curettage US$668. The undiscounted life time costs of DMD was about US$747,173, CMD US$1,187,919, and FraX US$4,107,920. The costs minus savings within the health care sector depend on the prior risks and on the future burden of the monogenic illness under consideration. Basically, DNA diagnosis for these three diseases produces considerable savings (van der Riet et al., 1997).

Endocrine diseases
The cost of screening tests in endocrine diseases, e.g. multiple endocrine neoplasia type I and II (MEN-I and -II) can be determined in a number of ways, including the charge or billed cost, the production cost, or most appropriately the cost to achieve the intended aim of the test (cost-effectiveness). Cost-effectiveness analysis allows clinicians to determine whether an added benefit of a test comes at an acceptable cost for patients with endocrine diseases. For example, analysis of the cost-effectiveness of routine thyroid function tests prior to surgery in elderly patients with nodular thyroid disease shows that the cost per life saved is only US$405, making the tests clearly cost-effective. Cost-effectiveness does not always equate with affordability, however, especially in developing countries. Thyroid function testing prior to surgery represents only 0.8% of the average household income in Australia and is therefore both cost-effective and affordable, whereas in Sri Lanka the same screening test represents up to 50% of the average monthly income (Delbridge and Robinson 1998).

A survey of membership of the International Association of Endocrine Surgeons worldwide showed that molecular genetic screening for endocrine disease is readily available in 67% of institutions, with all of those having facilities for the rearrangement during transfection (RET) proto-oncogene testing, and lesser numbers having access to the Menin gene, the von Hippel-Lindau syndrome (VHL) gene, or linkage analysis for familial pheochromocytoma. The median cost of screening for the RET proto-oncogene was US$290 (range US$100-3000). Cost-effectiveness analysis of molecular genetic screening for MEN-II syndrome demonstrates that the cost per life saved is only about US$5175. This compares favorably with reliance on screening based on annual pentagastrin testing, where the cost per life saved is as high as US$76,315. Molecular genetic screening for MEN-I and -II syndrome is not only cost-effective but the therapy required (total thyroidectomy) is both acceptable and well tolerated in the western nations (Delbridge and Robinson 1998).

Breast cancer (BRCA)
BRCA is the most common neoplasm in white women, with a cumulative lifetime breast cancer risk of about 1 in 10 (Wingo et al, 1995). Although most BRCA cases are sporadic, familial clustering is observed in ~ 20% of breast tumours and at least 5-10% of cases appear to be a result of the inheritance of an autosomal dominant gene (Stratton et al, 1996). Up to now several BRCA-related genes, e.g. BRCA1 and 2 have been identified (Miki et al, 1994; Wooster et al, 1995; Perou et al., 2000), which offer a molecular diagnostic means for testing and screening those women who are at high-risk of having BRCA.

There is one Norwegian study evaluating the cost-effectiveness of testing women predisposing BRCA. It reported that the annual cost of identifying the high-risk women through a traditional cancer family clinic was estimated at Euro 753. A strategy of identifying the high-risk families through genetic testing of all incident breast and ovarian cancers for founder mutations in BRCA1, will increase the cost to Euro 832. The number of relatives counseled to identify one healthy female mutation carrier is more important to cost-effectiveness than family size. Costs will vary depending upon the penetrance of the mutations detected and the prevalence of founder mutations in the population examined. Identification of high-risk families through founder mutation analysis of BRCA1 ensures that families with maximum risks are given first access to the limited resources of the high-risk clinics. This may be the greatest contribution to increased cost effectiveness of such a strategy. The conclusion is that inherited breast cancer may be managed effectively for the cost of Euro 750-1,600 per year earned (Heimdal et al., 1999).

Closing Remark
The examples I showed above may be boring, but they tell people how the cost-effective analysis in genetics works today. In the foreseeable future, most of genetic diseases could be tested and screened via molecular approach, and some of them could be cured by means of gene therapy or other advanced biomedical technologies. These techniques would be very expensive as research, development and application of these technologies need a huge investment. Therefore the cost-effective analysis would certainly play much more important role in planning genetics services, allocation of resources and management of health budget. Whether or not economic power would reshape the people's attitudes towards ethical issues in the future, let us wait and see.

References

Allen GE (1997) The social and economic origins of genetic determinism: a case history of the American Eugenics Movement, 1900-1940 and its lessons for today. Genetica 99(2-3):77-88.

Allen GE. (1989) Eugenics and American social history, 1880-1950. Genome 31(2):885-9.

Berry RJ, Li Z, Erickson JD, Li S, Moore CA, Wang H, Mulinare J, Zhao P, Wong LY, Gindler J, Hong SX, Correa A (1999) Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med 341(20):1485-90.

Caulfield TA, Gold ER. (2000) Genetic testing, ethical concerns, and the role of patent law. Clin Genet. May;57(5):370-5.

Caulfield T (1998) The commercialization of human genetics:profits and problems. Mol Med Today 4(4):148-50.

Cate S, Ball S (1999) Multiple marker screening for Down syndrome--whom should we screen? J Am Board Fam Pract 12(5):367-74.

Chan A, Robertson EF, Haan EA, Keane RJ, Ranieri E, Carney A (1993) Prevalence of neural tube defects in South Australia, 1966-91: effectiveness and impact of prenatal diagnosis. BMJ 18;307(6906):703-6.

Cronin EK, Normand C, Henthorn JS, Graham V, Davies SC (2000) Organisation and cost-effectiveness of antenatal haemoglobinopathy screening and follow up in a community-based programme. BJOG 107(4):486-91.

Cronin EK, Normand C, Henthorn JS, Hickman M, Davies SC (1998) Costing model for neonatal screening and diagnosis of haemoglobinopathies. Arch Dis Child Fetal Neonatal Ed 79(3):F161-7.

Davies SC, Cronin E, Gill M, Greengross P, Hickman M, Normand C (2000) Screening for sickle cell disease and thalassaemia: a systematic review with supplementary research. Health Technol Assess 4(3):1-150.

Delbridge L, Robinson B (1998) Genetic and biochemical screening for endocrine disease: III. Costs and logistics. World J Surg 22(12):1212-7.

Dikotter F (ed) (1997) Imperfect Conceptions: Medical Knowledge, Birth Defects and Eugenics in China. Hurst & Co, London.

Editorial (2000) The end of the beginning. Nat Genet 25:363-364.

Gill M, Murday V, Slack J (1987). An economic appraisal of screening for Down's syndrome in pregnancy using maternal age and serum alpha fetoprotein concentration.
Soc Sci Med.;24(9):725-31.

Henderson JB (1982a) Measuring the benefits of screening for open neural tube defects. J Epidemiol Community Health 36(3):214-9.

Henderson JB (1982b) An economic appraisal of the benefits of screening for open spina bifida.
Soc Sci Med 16(5):545-60.

Heimdal K, Maehle L, Moller P (1999) Costs and benefits of diagnosing familial breast cancer. Dis Markers. 15(1-3):167-73.

Karnon J, Zeuner D, Brown J, Ades AE, Wonke B, Modell B (1999) Lifetime treatment costs of beta-thalassaemia major. Clin Lab Haematol 21(6):377-85.

Larson EJ (ed) (1995) Sex, race, and science: eugenics in the deep South. Johns Hopkins University Press, Baltimore.

Li H (2000) Genomics. Money and machines fuel China's push in sequencing. Science 288(5467):795-8.

Macilwain C (2000) World leaders heap praise on human genome landmark. Nature 405(6790):983-4.

Mao X (1999) Reply to Guo and to Chen et al. Am J Hum Genet 65(4):1199-1201.

Mao X (1998a) Chinese geneticists' views of ethical issues in genetic testing and screening: evidence for eugenics in China. Am J Hum Genet 63(3):688-95.

Mao X (1998b) Chinese geneticists approach ethics. J Med Genet 35:83.

Mao X, Wertz DC (1997) China's genetic services providers' attitudes towards several ethical issues: a cross-cultural survey. Clin Genet 52(2):100-9.

Mao X (1997a) Ethics and genetics in China: an inside story. Nat Genet 17:20.

Mao X (1997b) Chinese eugenic legislation. Lancet 349:139.

Mao X (1996) Chinese ethics. Nature 384:404.

Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66-71

Modell B, Kuliev AM (1993) A scientific basis for cost-benefit analysis of genetics services. Trends Genet 9(2):46-52.

Modell B, Kuliev AM (1991) Services for thalassaemia as a model for cost-benefit analysis of genetics services. J Inherit Metab Dis 14(4):640-51.

Morris JK, Oppenheimer PM (1995) Cost comparison of different methods of screening for cystic fibrosis. J Med Screen 2(1):22-7.

Ostrer H, Allen W, Crandall LA, Moseley RE, Dewar MA, Nye D, McCrary SV (1993) Insurance and genetic testing: where are we now? Am J Hum Genet 52(3):565-77

Pennisi E (2000) Human genome. Finally, the book of life and instructions for navigating it. Science 288(5475):2304-7.

Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams CF, Zhu SX, Lonning PE, Borresen-Dale A-L, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747-752.

Rodgers GP (1998) Pharmacological therapy. Baillieres Clin Haematol 11(1):239-55.

Stamp J (1968) Eugenic influences in economics. Eugen Rev 60(1):32-45.

Stratton MR, Wooster R (1996) Hereditary predisposition to breast cancer. Curr Opin Genet Dev 6:93-7

Torgerson DJ, Spencer A (1996) Marginal costs and benefits. BMJ 312(7022):35-6.

Triendl R (2000) Genomics forges ahead in East Asia. Nat Biotechnol 18(3):278-9.

Turner RD (1999) Economics of genetics from a health commissioning point of view. Dis Markers 15(1-3):175-6.

van der Riet AA, van Hout BA, Rutten FF (1997) Cost effectiveness of DNA diagnosis for four monogenic diseases. J Med Genet 34(9):741-5.

Vintzileos AM, Ananth CV, Smulian JC, Day-Salvatore DL, Beazoglou T, Knuppel RA. (2000) Cost-benefit analysis of prenatal diagnosis for Down syndrome using the British or the American approach. Obstet Gynecol 95(4):577-83.

Vintzileos AM, Ananth CV, Fisher AJ, Smulian JC, Day-Salvatore D, Beazoglou T. (1998a) An economic evaluation of first-trimester genetic sonography for prenatal detection of Down syndrome. Obstet Gynecol 91(4):535-9.

Vintzileos AM, Ananth CV, Smulian JC, Fisher AJ, Day-Salvatore D, Beazoglou T (1998b) A cost-effectiveness analysis of prenatal carrier screening for cystic fibrosis. Obstet Gynecol 91(4):529-34.

Wang Y, Zhu J, Wu Y (1998) Dynamic variation of incidence of neural tube defects during 1988 to 1992 in China. Chung Hua Yu Fang I Hsueh Tsa Chih (Chinese Medical Journal of Preventive Medicine) 32(6):369-71.

Wertz DC. (1997) Society and the not-so-new genetics: what are we afraid of? Some future predictions from a social scientist. J Contemp Health Law Policy 13:299-345.

WHO (1985) Document No. HMG/WG/85.10, The Hereditary Diseases Programme, WHO, Geneva, Switzland.

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 Community Health. 52(7):459-67.

Wildhagen MF, Verheij JB, Verzijl JG, Gerritsen J, Bakker W, Hilderink HB, ten Kate LP, Tijmstra T, Kooij L, Habbema JD (1996a) The nonhospital costs of care of patients with CF in The Netherlands: results of a questionnaire. Eur Respir J 9(11):2215-9.

Wildhagen MF, Verheij JB, Verzijl JG, Gerritsen J, Bakker W, Hilderink HB, ten Kate LP, Tijmstra T, Kooij L, Habbema JD (1996b) Cost of care of patients with cystic fibrosis in The Netherlands in 1990-1. Thorax. Mar;51(3):298-301.

Wingo PA, Tong T, Bolden S (1995) Cancer statistics, 1995. CA Cancer J Clin 45:8-30

Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G, et al (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378: 789-92

WHO (1998) Proposed international guidelines on ethical issues in medical genetics and the provision of genetics services. Report of a World Health Organization meeting on ethics issues in medical genetics, Geneva, December 15-16 1997.

Please send comments to Email < asianbioethics@yahoo.co.nz >.

To contents page
To Eubios book list
To Eubios Ethics Institute home page