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									HUMAN GENETICS COMMISSION AND NATIONAL SCREENING COMMITTEE Meeting on ‘Profiling Babies at Birth’ 13 November 2003 10am – 2pm Rm 137B Skipton House, 80 London Road London SE1 6LH Agenda 1. Chair‟s introduction

2. Background: HGC, NSC and Genetics White Paper commitments

3. Draft work programme

4. Working Arrangements

5. HGC: Update on Working Group Genetics and Reproductive Decision Making

6. NSC: Issues of Consent

7. Any other business

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Human Genetics Commission and National Screening Committee Minutes of the first joint meeting 13 November 2003 Present: Representing HGC Mr Philip Webb – Chair Dr Bill Albert Professor Brenda Almond Professor Elizabeth Anionwu Dr Frances Flinter Dr Hilary Harris Professor Peter Harper Ms Hilary Newiss Mrs Christine Patch Professor Martin Richards Mr Peter Sayers Dr Ros Skinner Dr John Sulston

Representing NSC Professor Carol Dezateux Dr David Elliman Professor Neva Haites Professor Theresa Marteau Professor Martin Whittle Dr Ron Zimmern

Secretariat Dr Mark Bale (HGC) Dr Jennie Carpenter (DH) Sir Charles Nightingale (NSC) Dr Sophie Taysom (HGC)

Apologies: Dr Jane Collins, Professor John Harris Item 1 - Introductions 1.1 The Chair welcomed everyone to the first joint meeting of the Human Genetics Commission (HGC) and the National Screening Committee (NSC) to discuss the request in the recent Genetics White Paper for the two committees to make an initial assessment of the case for genetically profiling babies at birth. 1.2 The Chair explained that it had been agreed that the HGC‟s Genetic Services Sub-group should lead on this work for the Commission, but that members of the Working Group on Genetics and Reproductive Decision Making would attend to consider the relevant aspects of current and planned new-born screening programmes. Members of the HGC and NSC then introduced themselves and Dr Elliman and Professor Whittle briefly outlined their respective responsibilities as chairs of the NSC Child Health Subgroup and the Antenatal Screening Subgroup. 1.3 The Chair explained that it was general HGC policy to publish attributable minutes of meetings on their website and all agreed that this was acceptable. The Chair also reminded members of the need to declare any personal or business interests connected with any of the agenda items. Items 2 and 3 – Background 2.1 The Chair introduced the main business of the meeting which was to cover some of the background and relevant issues around the case for having
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genetic profiles of babies from birth. The background to this request from Ministers was set out in Annex A of the meeting papers. The Chair emphasised that the White Paper request was to conduct an initial analysis of the ethical, legal, social and practical considerations by the end of 2004. There was also a question of whether the technology was going to be available to make this a practical reality in the foreseeable future. 2.2 Dr Sulston reminded the meeting that Paul Nurse had outlined this scenario as a possibility by 2023 in setting the scene for a recent Royal Society public forum. It was easy to envisage this being technically do-able and for the costs to be within the range accepted for individual health care. Whether it would be possible to sequence an individual genome for the $1000 quoted was debatable. But the possibility of scanning for key gene sequence variations that are envisaged in the Single Nucleotide Polymorphisms (SNP-) and Haplotype (HAP-) mapping programmes was entirely feasible. It seems unlikely that the whole sequence would in any case be necessary, but the ability to genotype would be possible. Dr Sulston offered to consult with others and to produce a paper which could give a „best guess‟ of the technological progress. Action: Dr Sulston will produce a brief report outlining future technological scenarios in relation to genetic profiling. 2.3 Professor Dezateux asked what was meant by “profiling” and suggested changing the terminology to emphasise looking at medically significant information. This, it was suggested, may help avoid comparisons being drawn in the public mind with other sorts of profiling, such as criminal identifications. Dr Sulston agreed that certain aspects of the profile might be medically significant. In contrast, the DNA profile taken for forensic purposes was said not to include areas with medical significance, but this perception might change as more is understood about the function of the genome. 2.4 Professor Whittle suggested that any profile could identify unintended medical information, in a similar way that ultrasound scanning in pregnancy could identify a number of unanticipated findings. Professor Haites felt that the importance of somatic and mosaic factors that were known to be important in the development of, for instance, childhood leukaemia. Dr Sulston felt that the UK Biobank would begin to identify these factors and would also act as a pilot to help show where the technology might be. 2.5 Dr Zimmern agreed that a consideration of technology was necessary, but that this would be insufficient if the genotype could not be related to disease risk. The need for well-designed epidemiological studies was emphasised by the enclosed paper (Haga et al 2003). Dr Zimmern also queried whether this was meant to be considered as a bolt-on to existing screening – i.e. that it would be made available and up to individual choice. 2.6 Professor Marteau raised the fact that if genotype were only responsible for a small proportion of increase disease risk there could be much more effective public health measures that could improve the health of children. Professor Dezateux supported this point, adding that it was important to take into account broader socio-economic issues. Dr Sulston felt that the work was not just about child health, but a possible life-time improvement of health. In

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principle this was an exciting prospect, but he was concerned that sociallyspeaking it was not safe. 2.7 Professor Dezateux noted that there were significant differences between biobank and any potential newborn profiling. She added that the Newborn Screening programme had discussed similar matters in detail. She went on to outline the arrangements for collecting and storing the „Guthrie‟ cards. There were several active strands of work to introduce a more robust governance framework and several consultations were planned. The retention of samples for research was different from the UK Biobank because there were different consent arrangements. Practical experience showed that parents found it very difficult to grasp the information they were presented with. There was also still some debate about the implications of a „screen-positive‟ result, as well as the inevitable sub-categorisation of disease categories as more information became available. She also raised the point of the need to ensure that public trust in the screening process is maintained. Professor Anionwu felt that this highlighted the important role for health professionals who were in direct contact with the family. It emphasised the important work on raising genetic competencies among health professionals. 2.8 In response to the comments about the health aspects of genetic profiling, Professor Richards felt that there was a need to consider parallel debates about identity cards, biometric data and forensic uses of DNA. It was agreed that it would be impossible to keep these considerations separate from any debate on the topic. The Chair felt that forensic uses of the birth profiles should only be allowed in the most exceptional of circumstances. 2.9 Professor Whittle noted that the discussion centred around new-born screening, but felt that advances in methods for detecting foetal cells in maternal blood might cause pressure to conduct antenatal profiling. Professor Almond felt that the central issue was one of consent, and that there might need to be practical arrangements to ensure that parental consent was given for information relevant to childhood health and that testing or disclosure of other genetic risk factors might be delayed until adulthood. It was agreed that the practical considerations could be informed by the experiences of new-born screening, and that some testing or disclosure might be postponed. 2.10 Dr Harris echoed concerns about the information given before and after any profiling. There would inevitably be increased pressures on primary care, and even now GPs did not always know the outcome of screening. 2.11 Dr Sulston felt that it was pointless envisaging universal genotyping until the social dimension is properly addressed. Aspects such as consent and intellectual property rights will block any such schemes. There would also need to be improvements to ensure that society trusted Government to use such information responsibly. There would need to be a whole-scale revolution in several areas to ensure social safeguards. It was also stressed at this point that it needs to be taken on board that the NHS and other health services do not operate in a vacuum given the private sector and the implications this may have for patient demand.

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2.12 Dr Skinner commented on the example of consent for new-born bloodspot screening, where in Scotland discussion has led to a different procedure for opting-in or –out of screening programmes. Instead of implicit consent, there were now comprehensive leaflets and consent forms which require consent for each screened condition and for retention of samples beyond 12 months or anonymised research. Of 41,000 newborns screened since the new policy was introduced, a small but increasing number refuse some screening tests and approximately 2% refuse retention of the residual blood spots for research. 2.13 Professor Dezateux noted that the refusals might have coincided with the introduction of screening for cystic fibrosis. The use of anonymous samples from the new-born screening programme for research and public health purposes involved stringent procedures to protect the identity of the subject and to prevent deductive reasoning. It was also noted that there are new arrangements for a unique NHS identity number from birth that might evolve into a project for a unique number for screening purposes. 2.14 Dr Zimmern cautioned against being too distracted by single-gene disorders as they are identified in bloodspot screening. It might be sensible to place blood-spot studies to one side. Professor Harper agreed that these were not actually genetic tests, all were done biochemically and the screen positive results needed to be examined further. He felt that the initial review should include consideration of:

     

definitions, particularly of profiling scientific feasibility all possible uses – health related and others what is tested now what might be tested in the future what effects new developments might have on current arrangements.

2.15 Dr Albert felt that these were important but were technical aspects of what was at heart a social issue. If there were to be a consultation on such a programme it would give a resounding “no”. Professor Anionwu pointed out that the framework was clearly set out in the Genetics White Paper, and this included the social and ethical aspects to be examined for any case of profiling babies at birth. Dr Sulston felt that both aspects were important, and that it was also necessary to consider what might happen in the private sector. However, he wanted to approach this in terms of needing a revolution, from a technical viewpoint, from the accepted principles of medical ethics and in the need for legislation to prevent discrimination. Professor Marteau agreed that there were social implications, but also stressed the importance of looking at social behaviour. 2.16 Dr Zimmern outlined the approach taken in the United States to the evaluation of genetic tests, this included the need for evidence on the analytical, clinical utility and the ethical / social implications. Dr Elliman felt that the UK screening criteria were highly relevant. Professor Dezateux suggested that the progress would not be linear, and on occasion screening programmes are progressed in response to pressure from the public or from patient groups.
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2.17 Dr Elliman also noted that past discussions of developments in tandem mass spectrometry (TMS) were relevant. After lengthy consideration, NSC felt that it was necessary to apply the standard principles to each test that might be conducted by TMS. This approach might not be possible for any future genotyping programme, but there was a need to avoid such programmes being technology driven. 2.18 In response to Dr Albert‟s question about the origins of the White Paper request, the Secretariat reminded the meeting of the background and public debate, especially that led by the Royal Society, that influenced Ministers in seeking HGC and NSC advice on the possibilities. Professor Almond noted that the effect of the technology would be to medicalise the population, something that the public reaction to the proposals, which had been largely positive, had failed to notice. It was also noted that some commercial companies might market DNA profiling as a consumer product, and encourage such information to be given to people as an 18th or 21st birthday present. Similar concerns had arisen in relation to companies that offered cord blood storage, and the Secretariat reminded the meeting of the conclusions of the Royal College of Obstetrics and Gynaecology report which had pointed out the remote possibility that such storage would benefit the health of the child. 2.19 Dr Sulston felt that genotyping at birth could not initially be endorsed as anything other than a research activity. Any company that promoted a commercial service would be misleading the public. He also felt that such a programme could only be seen in the context of the NHS as it did not fit within the normal private healthcare model. 2.20 Professor Dezateux agreed and felt that because mortality in childhood was low and largely unrelated to genetic factors it could only be seen as a research activity. She questioned whether genotyping at birth was appropriate – why not wait until adulthood when issues of consent become easier? Professor Richards responded that experience with birth cohorts showed that it was easier to collect samples at birth, and this was highly relevant to the debate about a universal forensic DNA database. Item 3 and 4 –Work Programme and Working Arrangements 3.1 The Chair asked the meeting to consider possible terms of reference for this work, based on the background discussions. He drew attention to the terms of reference for the HGC Working Group as an example. Action: Secretariat to draft Terms of Reference and circulate 3.2 Professor Harper sought clarification of the respective remits of the parent committees in the light of devolution. It was generally agreed that HGC and NSC would be providing advice to all UK countries, but any policy decision on local implementation would be taken in the respective Home Countries. 3.3 Professor Whittle suggested that the terms of reference should look at the disadvantages of any programme and where the harms might occur. Dr Albert suggested considering if profiling at birth would be consistent with international protocols on genetics and the collection of genetic information. He also suggested an evaluation in terms of narrow medical ethics and the broader
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social dimension of ethics. Ms Newiss reminded the meeting that the current legal position – perhaps a précis of the HGC‟s report on personal genetic information – would be instructive. 3.4 Professor Harper felt that the discussion so far had emphasised the importance of trust in a society. Profiling at birth might be more acceptable in a Scandinavian country, but in the UK the public does not trust Government. He also felt it instructive to recall the “Genetics Manifesto” issued in 1939 which was asked to consider what place genetics had in improving health. It covered all of the wider matters of social justice that would need to be addressed before genetics could play a proper role. In his view, the Government had put forward a scenario that was naïve, possibly with merit, but which might damage, or be damaged by, existing problems such as discrimination or forensic uses of DNA. 3.5 Dr Elliman felt that the Genetics White Paper essentially provided the terms of reference. In essence, this review was to be an initial study of the desirability and practicability of genotyping at birth in order to improve the health of children. However, he wondered if the review should be an examination of the principle of genotyping or the practical issues and likely benefits. 3.6 It was felt that a consideration of the special concerns about the use of unanticipated and difficult to evaluate technology in healthcare. HGC had previously considered how technology could drive services into making difficult ethical decisions, e.g. the use of DNA chips and multiple FISH technology. Furthermore, Professor Dezateux was concerned about the public reaction to the publication of „bad science‟ as exemplified by the MMR story. Mr Sayers suggested including the real, and perceived, examples of what might go wrong. Action: Dr Elliman, Professor Dezateux and Professor Whittle to produce a paper on possible principles. 3.7 Dr Zimmern offered to provide a short summary on the evaluation of epidemiological findings and how to link genetic variation to the risk of disease. It was also suggested that there was useful published material on genetic testing in childhood. Professor Marteau offered to provide some a summary of relevant issues from a behavioural science perspective. Action: Dr Zimmern and Professor Marteau to produce a brief paper on genetics and the risk of disease. 3.8 Professor Harper commented on the need to consider genetic, and partially genetic, factors that were relevant to adult and later-onset disorders. It would be useful to note what might be improved by being identified early in life and to allow prevention or early management. Action: Professor Harper to produce a brief paper on the reasons for genetic profiling at birth. 3.9 Professor Marteau felt that the review might ask whether and how genotyping at birth might contribute to major diseases like cancer and coronary heart disease, and hence to the delivery of the NHS plan. Dr Zimmern supported consideration of the possible role of genetic factors in major diseases and to be prepared to reject the notion of genotyping at birth if necessary. It was felt that there needed to be more information on the genetic aspects of birth cohort studies. Professor Dezateux said that the burden of disease in childhood
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tended to be obesity, death from injury and complex diseases like asthma and diabetes. It was difficult to envisage how DNA testing might be relevant, but some relevant information was available from Scandinavia. She offered to provide a contribution based on the studies done in support of the new-born screening programme. Action: Professor Dezateux to produce a brief paper on the burden of genetic disease in children 3.10 Dr Harris felt that the group lacked sufficient expertise on health economics. She was also concerned about the potential impact on GPs who have a major role in managing long-term disease. Ms Patch suggested raising this via the Royal College of GP‟s virtual genetics network. Dr Sulston accepted this point, but felt that any programme would need to be support by evaluation of individual findings via appropriate computer-based expert decision systems. He also noted that one important use of such data would be in optimising drug dosages (pharmacogenetics). Mr Sayers also agreed that the review needed to consider the possible risks from an informatics perspective. Members echoed this and noted the Genetics White Paper spoke of the ability to alter and correct health records, which was potentially difficult under the current legal framework. 3.11 Professor Richards and Dr Flinter noted the possible wider use of genotyping data by individuals to disclose information about relationships or genealogy. Dr Zimmern felt that it would be important to address the quality issues alongside a discussion of future technology. Professor Haites, Dr Skinner and Dr Sulston agreed that quality assurance and laboratory accreditation were being considered in high volume sequencing. 3.12 Dr Albert suggested approaching some of the key groups that had considered the wider social implications and legal concerns. He agreed to contact Liberty, GeneWatch and Privacy International to see if they wished to contribute short position papers. It was also suggested that the Nuffield Council on Bioethics could have a view in connection with their work on the ethics of public health. A number of centres in other countries would have useful information, including Professor Knoppers in Montreal, the Australasian Genetics Group and the Danish Council on Bioethics who oversaw the establishment of the Danish Biobank of newborn screening samples. Action: Dr Albert to contact key groups that may consider the wider and social implications of profiling at birth for short papers/statements. The Chair also noted that as part of the discussion on future terms of reference, the structure of the Joint Group and its Chair should be considered. He did not feel that he should chair the group because he would be standing down from the HGC in July 2004. It was agreed that the Secretariat would circulate draft Terms of Reference and that Members would consider who should be invited to chair the group. 3.14 In addition to circulating dated, the Chair suggested that part of HGC‟s meeting in May could be an information gathering session on this topic. It was suggested that the Secretariat look at initially contacting Paul Nurse to possibly address the group given his role in the Royal Society Report.

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Item 5 – HGC update 5.1 Professor Richards introduced HGC‟s work on Genetics and Reproductive Decision-Making that was addressing a wide range of issues from worries about „designer babies‟ to practical and ethical aspects of pre-natal diagnosis and screening. The Commission had just discussed an outline that would form the basis of a consultation that was tabled for information. HGC had already noted the importance of working closely with the Human Fertilisation and Embryology Authority (HFEA) and the National Screening Committee. There were certainly some potential overlaps with the HFEA on pre-implantation genetic diagnosis. It had been agreed that HGC would not consider the specifics of the licensing decisions that HFEA must make, but would participate in discussions around other aspects of HFEA‟s remit. 5.2 Dr Albert noted his unease about the potential difficulty if HGC felt unable to comment on a particular issue. There was a potential for arguments that were valid in obvious medical cases being read across in less obvious scenarios such as sex-selection. Dr Harris agreed that HGC had brought useful genetics expertise into past HFEA discussions. Professor Anionwu also noted that patient groups were concerned with the way that β-thalassaemia was portrayed in the media as being invariably fatal in a recent decision on PGD combined with HLA tissue-typing. 5.3 In response to Dr Zimmern‟s comment that there were few links between neonatal screening and reproductive decision-making, Professor Richards disagreed and cited the example of Duchenne‟s Muscular Dystrophy (DMD) where the results were often relevant to making decisions about future pregnancy. Professor Marteau also felt that there were some useful parallels between genotyping at birth and the ethical dilemmas that occurred in genetics and reproduction. Dr Flinter echoed the earlier comment there might be pressure to introduce antenatal genotyping. Some useful pointers to this might be gained from the parallel implementation of antenatal and neonatal screening for cystic fibrosis. 5.4 Professor Harper also raised the example of Health Technology Assessment (HTA) reports. Dr Zimmern chairs the committee that oversees the HTA programme and commented that the recent report on Fragile-X screening illustrated the importance of a robust process to provide evidence for the National Screening Committee. Dr Zimmern felt that there was a clear distinction between DNA-based testing in diagnosis and treatment of disease and other tests for conditions that are inherited and it was important not to conflate the two ideas. Members agreed that it was valuable for committees with different perspectives to consider an issue and that a diversity of viewpoints was important in these controversial areas. 5.5 Professor Richards noted that the Working Group was still looking for an update on antenatal screening in England and Professor Whittle agreed to consider this. Professor Anionwu also felt that it was important to summarise the history of screening, especially to contrast the situation before and after the establishment of the NSC. Professor Dezateux noted that it was often easier not

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to start a programme than to stop something that had been started. This made it important to set clear parameters to guide any new programme. 5.6 Professor Marteau asked about the legal position on termination of pregnancy following screening for haemoglobinopathies. Professor Anionwu also noted the problem with the interpretation of „seriousness‟ within the current law and the differing belief systems of obstetricians. Dr Albert was concerned that the joint HGC and HFEA report on pre-implantation genetic diagnosis had fudged the question of seriousness. Professor Whittle commented that the law was clear, but clinicians often sought legal advice on the interpretation in differing circumstances. However, it needed to be recognised there were difficult personal decisions and that it often took time for the couple to make the decision that was right for them. The legal framework had therefore to allow termination of pregnancy up to 40 weeks in certain circumstances. Item 6: NSC and consent 6.1 Dr Elliman introduced some of the difficulties around consent in screening programmes. It is generally agreed that to remove the need for consent is unacceptably paternalistic. But in practical terms, the precise circumstances around when to obtain consent differ markedly. For example in antenatal diagnosis there is not always proper pre-consent for ultrasound scanning. In neonatal screening there is supposed to be informed consent, but most information is sparse or non-existent. The new literature being piloted will address this problem. Parents were not always given clear information about some conditions which are genetic and Mendelian and therefore of wider significance to future pregnancy. He felt that this would be improved, but in time the practicalities would make truly informed consent impossible. Dr Elliman noted the earlier example of Tandem Mass Spectrometry where the NSC decided to seek consent on each test for each condition. The alternative might be to take generic consent and then have to make a decision about what results should be fed back to the patient. 6.2 Members also noted that there was still a difficulty in interpreting the link between genotype and phenotype in providing information about the significance of a finding. Professor Harper felt that this raised the question of what was meant by disease? The simple answer was if a finding predicted a health problem – this was straightforward for Phenylketonuria (PKU), but in other conditions like cystic fibrosis was more complex. In other cases, particularly the example of haemochromatosis, it seemed that this was a rare disease with a common predisposing genotype. Furthermore, with truly polygenic disease it is not really a disease genotype at all. Dr Sulston asked whether Dr Zimmern‟s paper could take an optimistic and a pessimistic view of the possibility of linking DNA with the disease evidence base. Dr Zimmern felt that genotyping would not be like a screen, but could be a health predictor. However, the question would need to be addressed by some major cohort studies. 6.3 Professor Dezateux felt that this supported the NSC approach to clinical validity of a test, with the decision to screen being left to local implementation. There was also a different legal dimension to parental responsibility for

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screening. Parental consent is lawful because it is in the best interests of the health of the child. But screening for Duchenne Muscular Dystrophy (DMD) challenged that assumption. The joint HGC and NSC work stresses the importance of consent, but there are numerous instances of where people do not know why they are being screened. The new-born screening programme is also considering issues of consent to archive samples for research. 6.4 Professor Richards felt that the UK Biobank is showing how people are willing to consider general consent. Professor Harper agreed, but drew the distinction that the UK Biobank consent was based on the assumption that there would be no specific feedback to participants. It was noted that this was still being considered by the Biobank Ethics and Governance Framework. 6.5 Professor Richards felt that the current approach to consent could be safely adapted, as was illustrated by ultrasound screening. This was introduced for a very different purpose, for example to date a pregnancy. Professor Whittle said that only one-fifth of women knew why they were having an ultrasound scan. He added that first trimester screening was available in the United States, but that resources there allowed 45 minutes for a consultation, something that would be impracticable given normal NHS clinic sizes. 6.6 Dr Elliman added that new models of consent might be necessary, for example by individuals declining test or the disclosure of certain information, such as details of carrier status. 6.7 The Chair said that the discussions illustrated that consent was a central theme in the work of the two committees and that the HGC had hopefully provided a detailed analysis of the issues in their Inside Information report. He thanked Members for contributing to such an interesting discussion and said that the two Secretariat‟s would circulate minutes of the meeting and draft terms of reference as soon as possible. The next meeting would be decided once the composition of the group, and the chair, had been agreed, but it would be useful to meet towards the end of February. Action: Secretariat to circulate dates for a second meeting in late February.

HGC Secretariat November 2003

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