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Fetal nuchal translucency test for Down's syndrome
THE LANCET
start, the programme has been subject to frank open discussion and debate. The Malarone-donation programme offers a unique opportunity to evaluate the effective introduction of a new antimalarial and the monitoring of its use with the specific goal of keeping to a minimum the development of resistance. Because the issues in developing such a programme are complex, we have solicited input from international public-health and malaria experts and from official bodies, including WHO, all of whom have given thoughtful comment and constructive advice. Some of these experts met in London, in February, 1997, to discuss the issues related to developing and implementing such a programme. They concluded that, with a commitment to detailed monitoring and evaluation, we should begin a pilot programme of controlled distribution in Kenya, beginning in August, 1997, and expand it soon thereafter to southeast Asia. Most importantly, they emphasised the need for controls to prevent the indiscriminate use of Malarone in any setting. The target population will be patients who meet a rigorous definition of drug resistance. Treatment will be by direct observation only. Use in pregnancy is specifically excluded in the current licence indications, and no donated drug will be used for prophylaxis in travellers. There is some debate as to whether Africa or southeast Asia is the more appropriate site for the pilot programme. From detailed discussion with experts about geographical patterns of resistance, we feel that both sites are important. We plan to initiate well-controlled pilot programmes in both regions in 1998. We will also consider how best to include pilot programmes in Latin America. In all cases, the programmes will proceed with care. The success of the programme will not be the number of tablets distributed (we expect the number to be quite small in any given location). Rather, success will be evidence that the programme is being operated in a responsible way, with careful monitoring and ongoing evaluation, and that distribution is to an appropriate target population to keep to a minimum development of resistance. We are pleased to be a partner and play a role with Glaxo Wellcome in the Malarone-donation programme. This programme has great potential and positive implications for malaria control, as well as for establishing a model for public-private partnerships to address other international public-
Vol 350 • November 29, 1997
health problems. Most importantly, it will provide access to an otherwise unaffordable, effective antimalarial to people who need it most. William H Foege The Task Force for Child Survival and Development, One Copenhill, Atlanta, CA 30307, USA 1
Bloland PB, Kazembe PN, Watkins WM, Doumbo OK, Nwanyanwn OC, Ruebush TK. Malarone-donation programme in Africa. Lancet 1997; 350: 1624–25.
Fetal nuchal translucency test for Down’s syndrome SIR—We agree with James Neilson (Sept 13, p 754)1 about the importance of achieving a mature, evidence-based health-care system, but believe that the introduction of first-trimester nuchal translucency screening has contributed to that principle. Nuchal translucency screening was introduced into good clinical practice after the peer-reviewed publication of data from a multicentre, prospective study of more than 20 000 completed pregnancies.2 The study design ensured that all the sonographers involved in the project underwent both theoretical and practical training, and that data were regularly reviewed from each centre by a specially written computer program prospectively collecting all the relevant information. Nuchal translucency screening identified about 75% of pregnancies with trisomy 21 for a positive rate of 5%.2 Other obvious benefits included better management of miscarriage, early detection of gross malformations, very accurate dating, and detection of chorionicity in twins,3 which were achieved at little extra cost in those units that previously offered dating scans. Despite these clear data, strict policies of sonographer training and regular centre audit have been continued and so the study now has information on 100 000 completed pregnancies and is currently examining how the test’s performance can be further improved. It is true that the availability of screening imposes on parents the need to make decisions and that a proportion of affected pregnancies are destined to end in spontaneous miscarriage. However, anxiety can be induced by screening at any stage of pregnancy, and although 40% of trisomy 21 pregnancies miscarry after 12 weeks, 75% of these losses are after 16 weeks,4 so this issue also applies to previous screening policies at 16 weeks. Pregnant women want to be given the option of screening
and those who choose screening want the earliest and most accurate result possible. Sadly, we concur with Neilson’s comment that it made little sense for the Health Technology Assessment Programme to invest substantial funding in the evaluation of nuchal translucency screening while many parts of the National Health Service already provided the service. We believe that good observational data are not being given sufficient importance by some workers, especially since useful randomised trials are often impossible to undertake in complex clinical areas and meta-analysis has many possible flaws.5 For example, the protocol of the funded study includes not revealing the results of nuchal translucency screening to pregnant women despite the fact that a high measurement gives an increased risk not only for chromosome defects but also for cardiac abnormalities and several genetic syndromes. Inevitably, many health-care workers and pregnant women will not find it acceptable to join a study in which important information is not communicated. We expect those clinicians and health purchasers who wish to support the controlled, evidenced-based, and audited introduction of medical advances will wish to follow the example of the introduction of nuchal translucency screening which we believe has achieved all three. *Peter Soothill, Phillipa Kyle Fetal Medicine Research Unit, University of Bristol, St Michael’s Hospital, Bristol BS2 8EG, UK 1
2
3
4
5
Neilson JP. Assessment of fetal nuchal translucency test for Down’s syndrome. Lancet 1997; 350: 754–55. Pandya PP, Snijders RJM, Johnson SP, Brizot ML, Nicolaides KH. Screening for fetal trisomies by maternal age and fetal nuchal translucency thickness at 10–14 weeks of gestation. Br J Obstet Gynaecol 1995; 102: 957–62. Nicolaides KH, Snijders RJM, Noble PL, Brizot M, Sebire NJ. First trimester ultrasound screening for chromosomal defects. In: Gudzinkas JG, Ward RHT, eds. Screening for Down syndrome in the first trimester. London: Royal College of Obstetricians and Gynaecologists, 1997: 197–212. Snijders RJM, Sebire NJ, Nicolaides KH. Maternal age and gestational age specific risk for chromosomal defects. Fetal Diagn Ther 1995; 10: 3456–67. Grant JM. Multicentre trials in obstetrics and gynaecology. Br J Obstet Gynaecol 1996; 103: 599–602.
SIR—James Neilson1 is incorrect to assert that a randomised trial is required before ultrasound nuchal translucency screening can be introduced into the National Health Service. Many of the practical issues he
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start, the programme has been subject to frank open discussion and debate. The Malarone-donation programme offers a unique opportunity to evaluate the effective introduction of a new antimalarial and the monitoring of its use with the specific goal of keeping to a minimum the development of resistance. Because the issues in developing such a programme are complex, we have solicited input from international public-health and malaria experts and from official bodies, including WHO, all of whom have given thoughtful comment and constructive advice. Some of these experts met in London, in February, 1997, to discuss the issues related to developing and implementing such a programme. They concluded that, with a commitment to detailed monitoring and evaluation, we should begin a pilot programme of controlled distribution in Kenya, beginning in August, 1997, and expand it soon thereafter to southeast Asia. Most importantly, they emphasised the need for controls to prevent the indiscriminate use of Malarone in any setting. The target population will be patients who meet a rigorous definition of drug resistance. Treatment will be by direct observation only. Use in pregnancy is specifically excluded in the current licence indications, and no donated drug will be used for prophylaxis in travellers. There is some debate as to whether Africa or southeast Asia is the more appropriate site for the pilot programme. From detailed discussion with experts about geographical patterns of resistance, we feel that both sites are important. We plan to initiate well-controlled pilot programmes in both regions in 1998. We will also consider how best to include pilot programmes in Latin America. In all cases, the programmes will proceed with care. The success of the programme will not be the number of tablets distributed (we expect the number to be quite small in any given location). Rather, success will be evidence that the programme is being operated in a responsible way, with careful monitoring and ongoing evaluation, and that distribution is to an appropriate target population to keep to a minimum development of resistance. We are pleased to be a partner and play a role with Glaxo Wellcome in the Malarone-donation programme. This programme has great potential and positive implications for malaria control, as well as for establishing a model for public-private partnerships to address other international public-
Vol 350 • November 29, 1997
health problems. Most importantly, it will provide access to an otherwise unaffordable, effective antimalarial to people who need it most. William H Foege The Task Force for Child Survival and Development, One Copenhill, Atlanta, CA 30307, USA 1
Bloland PB, Kazembe PN, Watkins WM, Doumbo OK, Nwanyanwn OC, Ruebush TK. Malarone-donation programme in Africa. Lancet 1997; 350: 1624–25.
Fetal nuchal translucency test for Down’s syndrome SIR—We agree with James Neilson (Sept 13, p 754)1 about the importance of achieving a mature, evidence-based health-care system, but believe that the introduction of first-trimester nuchal translucency screening has contributed to that principle. Nuchal translucency screening was introduced into good clinical practice after the peer-reviewed publication of data from a multicentre, prospective study of more than 20 000 completed pregnancies.2 The study design ensured that all the sonographers involved in the project underwent both theoretical and practical training, and that data were regularly reviewed from each centre by a specially written computer program prospectively collecting all the relevant information. Nuchal translucency screening identified about 75% of pregnancies with trisomy 21 for a positive rate of 5%.2 Other obvious benefits included better management of miscarriage, early detection of gross malformations, very accurate dating, and detection of chorionicity in twins,3 which were achieved at little extra cost in those units that previously offered dating scans. Despite these clear data, strict policies of sonographer training and regular centre audit have been continued and so the study now has information on 100 000 completed pregnancies and is currently examining how the test’s performance can be further improved. It is true that the availability of screening imposes on parents the need to make decisions and that a proportion of affected pregnancies are destined to end in spontaneous miscarriage. However, anxiety can be induced by screening at any stage of pregnancy, and although 40% of trisomy 21 pregnancies miscarry after 12 weeks, 75% of these losses are after 16 weeks,4 so this issue also applies to previous screening policies at 16 weeks. Pregnant women want to be given the option of screening
and those who choose screening want the earliest and most accurate result possible. Sadly, we concur with Neilson’s comment that it made little sense for the Health Technology Assessment Programme to invest substantial funding in the evaluation of nuchal translucency screening while many parts of the National Health Service already provided the service. We believe that good observational data are not being given sufficient importance by some workers, especially since useful randomised trials are often impossible to undertake in complex clinical areas and meta-analysis has many possible flaws.5 For example, the protocol of the funded study includes not revealing the results of nuchal translucency screening to pregnant women despite the fact that a high measurement gives an increased risk not only for chromosome defects but also for cardiac abnormalities and several genetic syndromes. Inevitably, many health-care workers and pregnant women will not find it acceptable to join a study in which important information is not communicated. We expect those clinicians and health purchasers who wish to support the controlled, evidenced-based, and audited introduction of medical advances will wish to follow the example of the introduction of nuchal translucency screening which we believe has achieved all three. *Peter Soothill, Phillipa Kyle Fetal Medicine Research Unit, University of Bristol, St Michael’s Hospital, Bristol BS2 8EG, UK 1
2
3
4
5
Neilson JP. Assessment of fetal nuchal translucency test for Down’s syndrome. Lancet 1997; 350: 754–55. Pandya PP, Snijders RJM, Johnson SP, Brizot ML, Nicolaides KH. Screening for fetal trisomies by maternal age and fetal nuchal translucency thickness at 10–14 weeks of gestation. Br J Obstet Gynaecol 1995; 102: 957–62. Nicolaides KH, Snijders RJM, Noble PL, Brizot M, Sebire NJ. First trimester ultrasound screening for chromosomal defects. In: Gudzinkas JG, Ward RHT, eds. Screening for Down syndrome in the first trimester. London: Royal College of Obstetricians and Gynaecologists, 1997: 197–212. Snijders RJM, Sebire NJ, Nicolaides KH. Maternal age and gestational age specific risk for chromosomal defects. Fetal Diagn Ther 1995; 10: 3456–67. Grant JM. Multicentre trials in obstetrics and gynaecology. Br J Obstet Gynaecol 1996; 103: 599–602.
SIR—James Neilson1 is incorrect to assert that a randomised trial is required before ultrasound nuchal translucency screening can be introduced into the National Health Service. Many of the practical issues he
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