- Email: [email protected]
Cost utility of prenatal diagnosis
CORRESPONDENCE
burdens resulting from the birth of a child with trisomy 21 and whether these concerns would be shared by women in other health-care systems. Finally, the comparator chosen by the authors of no screening test is inappropriate. To illustrate, if diagnostic testing were applied to a typical population of 100 000, it would identify around 125 Down’s syndrome pregnancies and lead to procedural losses in about 1000 unaffected fetuses. Screening with the integrated test followed by diagnostic testing would identify about 106 of the 125 Down’s syndrome pregnancies and lead to around 12 fetal losses. Compared with screening, routine application of diagnostic testing would identify 19 additional Down’s syndrome fetuses for the price of 988 unaffected fetal losses, thus sacrificing more than 50 unaffected fetuses for every additional Down’s syndrome fetus detected. In conclusion, we do not share the authors’ confidence that this study provides clear, generalisable evidence that “diagnostic testing should be offered to pregnant women irrespective of maternal age or risk”. We also suggest that such a policy would require very clear and careful explanation of the potential risks and benefits, and would like to know how the authors suggest that such information should be conveyed to pregnant women. Ian Bradbury, Dave Wright, Jim Slattery, *Karen Ritchie University of Ulster, Coleraine, UK (IB); University of Plymouth, Plymouth, UK (DW); and *NHS Quality Improvement Scotland, Delta House, 50 West Nile Street, Glasgow G1 2NP, UK (JS, KR) (e-mail: [email protected]) 1
Harris RA, Washington AE, Nease FR Jr, Kuppermann M. Cost utility of prenatal diagnosis and the risk-based threshold. Lancet 2004; 363: 276–82.
Authors’ reply Sir—The utilities used in our analysis were obtained from a diverse sample of 534 Spanish-speaking, Chinesespeaking, or English-speaking women aged 16–47 years. 62% had previously given birth. The fact that the mean utility for miscarriage without a future birth was higher than that of no testing followed by the birth of an infant with Down’s syndrome simply suggests that, on average, these women preferred not having a child to having one with Down’s syndrome. As we have there is previously reported,1,2 substantial variation in these preferences, so many women will prefer a child with Down’s syndrome to no child at all. Whether these preferences
are “strange” or reflect a “relaxed view” of procedure-related miscarriage is not a judgment we are prepared to make. We believe that we have provided evidence that, on average, women do not equate procedure-related miscarriage with Down’s-syndromeaffected birth, and that incorporating these and other preferences into testing decisions is cost effective. We agree that these preferences might vary depending on the health-care system in which care is obtained. Women participating in the study were recruited from 23 different clinics and practices in the San Francisco Bay area, including private practices, community clinics, and health maintenance organisations, and therefore represent the range of systems available in the USA. Whether women in other countries value these outcomes similarly is not known. However, we included wide ranges of utilities in our sensitivity analyses, and found that the outcome of the analysis was most sensitive to the degree of reassurance brought about by definitive negative results. We appreciate the important role of screening as a precursor to diagnostic testing, and we agree that future analyses that account for individual preference in the cost-effectiveness of prenatal screening are warranted. However, most prenatal screening tests use the risk of an untested 35-year-old woman as the cutoff (ie, the screen is defined as positive if the post-test probability of Down’s syndrome is at least as great as that of an unscreened 35-year-old). This approach implicitly assumes that diagnostic testing is not cost effective at lower risks—an assumption that is at odds with our findings. On the contrary, our study suggests that, for some women who currently screen negative (ie, those who derive a gain in perceived health benefit even at reduced risk of carrying an affected fetus), diagnostic testing remains cost effective. Finally, we agree that making informed decisions requires understanding of the risks and benefits of the different testing options. Developing tools to help inform patients of all types make health-care decisions that are reflective of their underlying preferences is a growing need and should be given high priority. *Miriam Kuppermann, Robert F Nease Jr, Ryan Harris, A E Washington *Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA 94143, USA (MK, RH, AEW); and Laboratory for Medical Decision Sciences, Division of General Medical Sciences, Department of Internal Medicine, Washington University Medical School and Express Scripts, St Louis, MO, USA (RFN) (e-mail: [email protected])
THE LANCET • Vol 363 • April 3, 2004 • www.thelancet.com
1
2
Kuppermann M, Feeny D, Gates, E, Posner S, Blumberg B, Washington AE. Preferences of women facing a prenatal diagnostic choice: long-term outcomes matter most. Prenat Diagn 1999; 19: 711–16. Kuppermann M, Nease RF, Learman LA, Gates E, Blumberg B, Washington AE. Procedure-related miscarriages and Down syndrome-affected births: implications for prenatal testing. Obstet Gynecol 2000; 96: 511–16.
Sir—Ryan Harris and colleagues’ costutility analysis of chorionic villous sampling (CVS) for Down’s syndrome1 raises numerous issues. By contrast with serum screening allied with nuchal fold lucency measurement by ultrasonography, CVS offers the opportunity for definitive diagnosis of Down’s syndrome or other karyotypic abnormalities. Screening methods that involve biochemistry and nuchal folds are subject to biological and analytical variation,2 mathematical and statistical test interactions,2 and operator variation, and do not detect 20–30% of cases of Down’s syndrome, mostly in pregnancies in young mothers.3 CVS also offers significant benefits to individuals—the majority— who have false-positive screening tests. As technology improves and samplesize requirements fall, the chances of CVS-induced miscarriage are likely to decrease further. The UK National Health Service is about to enforce standardised screening protocols for Down’s syndrome on a large scale.4 We suggest doing a health technology assessment of CVS as an alternative to the current complicated, mixed biochemical and radiological protocols, on the grounds that CVS is better placed to deliver definitive information to prospective mothers while minimising psychological distress caused by the inadequate predictive power of current tests. *Anthony S Wierzbicki, Timothy M Reynolds *St Thomas’ Hospital, London SE1 7EH, UK (ASW); Queen’s Hospital, Burton-on-Trent, UK (TMR) (e-mail: [email protected]) 1
2
3
4
Harris RA, Washington AE, Nease RF Jr, Kuppermann M. Cost utility of prenatal diagnosis and the risk-based threshold. Lancet 2004; 363: 276–82. Reynolds TM. Practical problems in Down syndrome screening: what should we do about gestation dating? What is the effect of laboratory imprecision? Commun Lab Med 1992; 1: 31–38. Reynolds TM, Nix B, Dunstan F, Dawson A. Age-specific detection and falsepositive rates: an aid to counselling in Down syndrome risk screening. Obstet Gynecol 1993; 81: 447–50. National Screening Committee: standards for Down’s syndrome screening. http:// www.nelh.nhs.uk/screening/dssp/downbest practice.pdf (accessed Feb 2, 2004).
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burdens resulting from the birth of a child with trisomy 21 and whether these concerns would be shared by women in other health-care systems. Finally, the comparator chosen by the authors of no screening test is inappropriate. To illustrate, if diagnostic testing were applied to a typical population of 100 000, it would identify around 125 Down’s syndrome pregnancies and lead to procedural losses in about 1000 unaffected fetuses. Screening with the integrated test followed by diagnostic testing would identify about 106 of the 125 Down’s syndrome pregnancies and lead to around 12 fetal losses. Compared with screening, routine application of diagnostic testing would identify 19 additional Down’s syndrome fetuses for the price of 988 unaffected fetal losses, thus sacrificing more than 50 unaffected fetuses for every additional Down’s syndrome fetus detected. In conclusion, we do not share the authors’ confidence that this study provides clear, generalisable evidence that “diagnostic testing should be offered to pregnant women irrespective of maternal age or risk”. We also suggest that such a policy would require very clear and careful explanation of the potential risks and benefits, and would like to know how the authors suggest that such information should be conveyed to pregnant women. Ian Bradbury, Dave Wright, Jim Slattery, *Karen Ritchie University of Ulster, Coleraine, UK (IB); University of Plymouth, Plymouth, UK (DW); and *NHS Quality Improvement Scotland, Delta House, 50 West Nile Street, Glasgow G1 2NP, UK (JS, KR) (e-mail: [email protected]) 1
Harris RA, Washington AE, Nease FR Jr, Kuppermann M. Cost utility of prenatal diagnosis and the risk-based threshold. Lancet 2004; 363: 276–82.
Authors’ reply Sir—The utilities used in our analysis were obtained from a diverse sample of 534 Spanish-speaking, Chinesespeaking, or English-speaking women aged 16–47 years. 62% had previously given birth. The fact that the mean utility for miscarriage without a future birth was higher than that of no testing followed by the birth of an infant with Down’s syndrome simply suggests that, on average, these women preferred not having a child to having one with Down’s syndrome. As we have there is previously reported,1,2 substantial variation in these preferences, so many women will prefer a child with Down’s syndrome to no child at all. Whether these preferences
are “strange” or reflect a “relaxed view” of procedure-related miscarriage is not a judgment we are prepared to make. We believe that we have provided evidence that, on average, women do not equate procedure-related miscarriage with Down’s-syndromeaffected birth, and that incorporating these and other preferences into testing decisions is cost effective. We agree that these preferences might vary depending on the health-care system in which care is obtained. Women participating in the study were recruited from 23 different clinics and practices in the San Francisco Bay area, including private practices, community clinics, and health maintenance organisations, and therefore represent the range of systems available in the USA. Whether women in other countries value these outcomes similarly is not known. However, we included wide ranges of utilities in our sensitivity analyses, and found that the outcome of the analysis was most sensitive to the degree of reassurance brought about by definitive negative results. We appreciate the important role of screening as a precursor to diagnostic testing, and we agree that future analyses that account for individual preference in the cost-effectiveness of prenatal screening are warranted. However, most prenatal screening tests use the risk of an untested 35-year-old woman as the cutoff (ie, the screen is defined as positive if the post-test probability of Down’s syndrome is at least as great as that of an unscreened 35-year-old). This approach implicitly assumes that diagnostic testing is not cost effective at lower risks—an assumption that is at odds with our findings. On the contrary, our study suggests that, for some women who currently screen negative (ie, those who derive a gain in perceived health benefit even at reduced risk of carrying an affected fetus), diagnostic testing remains cost effective. Finally, we agree that making informed decisions requires understanding of the risks and benefits of the different testing options. Developing tools to help inform patients of all types make health-care decisions that are reflective of their underlying preferences is a growing need and should be given high priority. *Miriam Kuppermann, Robert F Nease Jr, Ryan Harris, A E Washington *Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA 94143, USA (MK, RH, AEW); and Laboratory for Medical Decision Sciences, Division of General Medical Sciences, Department of Internal Medicine, Washington University Medical School and Express Scripts, St Louis, MO, USA (RFN) (e-mail: [email protected])
THE LANCET • Vol 363 • April 3, 2004 • www.thelancet.com
1
2
Kuppermann M, Feeny D, Gates, E, Posner S, Blumberg B, Washington AE. Preferences of women facing a prenatal diagnostic choice: long-term outcomes matter most. Prenat Diagn 1999; 19: 711–16. Kuppermann M, Nease RF, Learman LA, Gates E, Blumberg B, Washington AE. Procedure-related miscarriages and Down syndrome-affected births: implications for prenatal testing. Obstet Gynecol 2000; 96: 511–16.
Sir—Ryan Harris and colleagues’ costutility analysis of chorionic villous sampling (CVS) for Down’s syndrome1 raises numerous issues. By contrast with serum screening allied with nuchal fold lucency measurement by ultrasonography, CVS offers the opportunity for definitive diagnosis of Down’s syndrome or other karyotypic abnormalities. Screening methods that involve biochemistry and nuchal folds are subject to biological and analytical variation,2 mathematical and statistical test interactions,2 and operator variation, and do not detect 20–30% of cases of Down’s syndrome, mostly in pregnancies in young mothers.3 CVS also offers significant benefits to individuals—the majority— who have false-positive screening tests. As technology improves and samplesize requirements fall, the chances of CVS-induced miscarriage are likely to decrease further. The UK National Health Service is about to enforce standardised screening protocols for Down’s syndrome on a large scale.4 We suggest doing a health technology assessment of CVS as an alternative to the current complicated, mixed biochemical and radiological protocols, on the grounds that CVS is better placed to deliver definitive information to prospective mothers while minimising psychological distress caused by the inadequate predictive power of current tests. *Anthony S Wierzbicki, Timothy M Reynolds *St Thomas’ Hospital, London SE1 7EH, UK (ASW); Queen’s Hospital, Burton-on-Trent, UK (TMR) (e-mail: [email protected]) 1
2
3
4
Harris RA, Washington AE, Nease RF Jr, Kuppermann M. Cost utility of prenatal diagnosis and the risk-based threshold. Lancet 2004; 363: 276–82. Reynolds TM. Practical problems in Down syndrome screening: what should we do about gestation dating? What is the effect of laboratory imprecision? Commun Lab Med 1992; 1: 31–38. Reynolds TM, Nix B, Dunstan F, Dawson A. Age-specific detection and falsepositive rates: an aid to counselling in Down syndrome risk screening. Obstet Gynecol 1993; 81: 447–50. National Screening Committee: standards for Down’s syndrome screening. http:// www.nelh.nhs.uk/screening/dssp/downbest practice.pdf (accessed Feb 2, 2004).
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