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The reflex DNA method is an improvement on current antenatal screening in the UK

27 November 2017
By Jonathan Bestwick
Wolfson Institute of Preventive Medicine, Queen Mary University of London
Appeared in BioNews 928

Antenatal screening for Down's, Edwards' and Patau's syndromes with the reflex DNA method was shown in our recent study to have higher screening performance compared with the combined test alone, and compared with the proposed recall DNA method (see BioNews 926). In the reflex DNA method, part of the original blood sample from a woman is stored and a DNA test is automatically triggered by a combined test risk of 1 in 800 or higher – negating the need to recall women for an extra blood test.

Catherine Joynson at the Nuffield Council of Bioethics, in her comment article last week (see BioNews 927) gives unfounded general opinions and ignores the improvement in antenatal screening performance afforded by the reflex DNA method compared with the recall method in which women are recalled for a second screening test (DNA) following an initial positive test (combined test).

The reflex DNA method has a higher detection rate (95 versus 81 percent) and a lower false-positive rate (0.02 versus 2.3 percent) than the recall method.(1) Although most of the false-positives in the recall method are reclassified negative by the DNA test, this does not avoid the distress associated with being recalled on account of a positive screening test. Joynson seems to overlook the substantial advantages of the reflex DNA method.

My response to Joynson's specific comments are as follows:

1. There is no lack of informed choice. Women are informed of what is available and decide on the basis of the screening test regarded as a whole. Obtaining consent for reflex DNA screening is no different from obtaining consent for other established screening tests. The assertion that 'reproductive choice was not given high priority' is incorrect. Joynson raises the question as to whether reflex DNA screening is a test or a method. It is a test as well as a method because the women having the test are given a single test result. In contrast, with the recall method, women are given two test results. Reflex DNA screening was not presented as the invention of a new marker but as the application of a known maker in a way that achieves a more accurate and safer method of screening than existing tests.

2. The accusation that the authors of the reflex project (1) have ignored a 'swathe of research and public debate' with reference to the Nuffield Council report titled 'Non-invasive prenatal testing: ethical issues' (2) is unjustified. The reflex method is only referred to in one paragraph (4.25) of the 169-page Nuffield Council report, which does so incorrectly in a chapter titled 'NIPT in the private sector'. The reflex method was and is provided through the NHS. Policymakers have failed to recognise that the measurement of DNA in screening or diagnosis is not conceptually different from the measurement of proteins, steroids or ultrasound markers. The use of the term NIPT (non-invasive prenatal testing) disguises this fact and fails to recognise that the test is a screening test (not a diagnostic test). The term conceptually isolates the test as non-invasive when all screening tests are non-invasive. NIPT is a term that is best avoided. In practice the question is which of the markers, or combination of markers, achieves the best screening performance at an affordable cost.

3. Joynson argues that the RAPID study (3) using the recall method is better than the combined test alone, as is the reflex method, and implies that the recall method and the reflex method are similar in screening performance. This implication is incorrect as is apparent from the observation that of the 30,790 women screened in the RAPID study there were 118 false-positive results. By comparison in the reflex DNA project there were four false-positive results out of the 22,812 women screened, a rate over 20 times lower. Furthermore the recall screening method leads to women having unnecessary invasive diagnostic tests. In the RAPID study about two-thirds of women who opted for an invasive diagnostic test in the over one in 150 risk category (a category in which they had a choice of a DNA test or a diagnostic test) had an unaffected pregnancy, reflecting the anxiety caused by the initial positive combined test screening result. In the circumstances the women understandably wanted a definitive diagnostic result instead of another screening result.

4. Joynson suggests that an 'extended discussion' (ie counselling) is needed before a woman decides whether to be screened with the reflex DNA test. There is no reason why this process of obtaining consent need be more or less extended than with other tests. Women offered all screening tests are informed of the test in question and choose whether to be screened. They are not counselled at this stage. Counselling is needed once a woman has been identified as having a positive screening result.

5. In connection with the professional duty to 'reduce unnecessary anxiety', Joynson argues that contrary to what is said in our paper nothing is self-evident in this complicated area of medicine. My colleagues and I disagree. Regardless of whether the area of medicine is simple or complicated, causing unnecessary harm is always wrong and unethical.

6. Joynson suggests that reflex DNA screening may not be as good for women with true positive results as it is for those with false-positive results. This is a surprising proposition which has no basis in fact.

7. Joynson raises an issue that does not specifically affect reflex DNA screening, namely that the aim of prenatal screening for Down's syndrome may be to 'screen out' the disorder implying eugenics. There is no way in which an antenatal screening service has anything to do with eugenics. It provides women and their partners with a choice, without pressure to either accept or reject screening. The fact that such screening services are available does not mean that individuals with Down's syndrome are different from other members of society.

I believe that the points made by Joynson are neither correct nor relevant. What is of concern is that she, the Assistant Director of the Nuffield Council on Bioethics, is supporting a poorer method of screening when a better one could be made available at the same or similar cost. I believe that the Nuffield Council should review its position in this area. It should recommend the most effective and safe method of screening for those who consent to screening rather than support an inferior method. It should not recommend obtaining separate consent to individual components of a single screening test.

1) Prenatal reflex DNA screening for trisomies 21, 18, and 13
Genetics in Medicine |  9 November 2017
2) Non-invasive prenatal testing: ethical issues
Nuffield Bioethics Council |  2017
3) Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down’s syndrome into NHS maternity care
BMJ |  4 July 2016
1 June 2021 - by Michaela Chen 
A long-running court case over non-invasive prenatal testing patents has been settled...
20 November 2017 - by Catherine Joynson 
The new 'reflex' method of antenatal screening for Down's, Edwards' and Patau's syndromes was described last week as a 'transformational advance'. It might be cheaper than other approaches, but it could come at the cost of informed choice for pregnant women and couples...
13 November 2017 - by Dr Barbara Kramarz 
A new prenatal screening method for Down's syndrome, Edwards syndrome and Patau syndromes is safer, more reliable and cheaper than existing approaches, a study has found...
18 January 2016 - by Lone Hørlyck 
A new blood test for Down’s syndrome in high-risk women has been recommended for use on the NHS....
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