Transparency data

UK NSC minutes March 2021

Updated 20 October 2021

These minutes are final.

The meeting was held online from 9:30am to 2pm on 5 March 2021.

1. Attendees

1.1 Members

• Professor Bob Steele – Chair
• Professor Roger Brownsword – School of Law, Kings College London
• Professor Louise Bryant – Associate Professor in Medical Psychology, University of Leeds
• Eleanor Cozens – patient and public voice (PPV)
• Dr Paul Cross – Consultant Cellular Pathologist, Queen Elizabeth Hospital Gateshead Health NHS Foundation Trust
• Professor Stephen Duffy – Director of the Policy Research Unit in Cancer Awareness, Screening and Early diagnosis and Professor of Cancer Screening, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine
• Professor Gareth Evans – Consultant in Genetics Medicine, St Mary’s Hospital, Manchester
• Jane Fisher – patient and public voice (PPV)
• Hilary Goodman – Midwife, Hampshire Hospitals NHS Foundation
• Professor Alastair Gray – Director at the Health Economics Research Centre, Nuffield Department of Population Health and Professor of Health Economics at the University of Oxford
• Professor Chris Hyde – Public Health Specialist, University of Exeter
• Dr Jim McMorran – GP, Coventry
• Margaret Ann Powell – patient and public voice
• Dr Graham Shortland – Consultant Paediatrician, Cardiff and Vale University Health Board, Noah’s Ark Children’s Hospital for Wales (Vice-Chair)
• Dr Anne-Marie Slowther – Reader in Ethics, University of Warwick

1.2 Observers

• Daniel Gascoigne – Head of Screening Policy, Department of Health and Social Care
• Nimisha De Souza – Department of Health and Social Care, Screening Policy Team, Global and Public Health Group
• Lucjan Kaliniecki – Department of Health and Social Care, Screening Policy Team, Global and Public Health Group
• Dr Heather Payne – Senior Medical Officer for Maternal and Child Health, Welsh Government
• Sheila Devlin – Scottish Government
• Tasmin Sommerfield – Scottish Government
• Dr Carol Beattie – Northern Ireland
• Professor Niall O’Higgins – Chair of the National Screening Advisory Committee, Ireland
• Dr Alan Smith – Deputy CMO, Department of Health – Ireland Invitees
• Dr David Elliman – Clinical lead for Newborn Infant Physical Examination and Newborn Blood Spot, PHE
• Catherine Joynson – Nuffield Bioethics on secondment to the UK NSC/PHE
• Dr Nick Hicks – National Co-ordinating Centre for HTA
• Dr Ros Given-Wilson – Chair of the Adult Reference Group (ARG)
• Dr Sharon Hillier – Chair of the Fetal, Maternal and Child Health Group (FMCH)

1.3 Presenters

• Professor Jim Bonham – Laboratory Lead, Newborn Screening Blood Spot Programme
• Professor James Leonard – Paediatric metabolic disease, Institute of Child Health, London

1.4 Secretariat

• Professor Anne Mackie – Director of Programmes, UK National Screening Committee
• John Marshall – UK NSC Evidence Lead
• Dr Farah Seedat – UK NSC Evidence Review Manager
• Dr Cristina Visintin – UK NSC Evidence Review Manager
• Paula Coles – UK NSC Evidence Review Manager
• Silvia Lombardo – UK NSC Evidence Review Manager
• Goda Kijauskaite – UK NSC Evidence Review Manager
• Zeenat Mauthoor – Secretariat
• Fabrice Lafronte – UK NSC Secretariat officer
• Joanne Harcombe – National Lead for Stakeholder Information and Professional Education and Training
• Nick Johnstone-Waddell – Public and professional information lead

1.5 Apologies from members

• Claire Bailey – Lead Clinical Nurse Specialist in breast screening, SW London
• Dr John Holden – Joint Head of Medical Division, Medical and Dental Defence Union of Scotland

1.6 Other apologies

• Caroline Vass – Public Health Consultant
• Deborah Tomalin – NHS England and Improvement (NHSEI)

2. Welcome and introductions

The chair, Professor Steele, welcomed all to the first meeting of 2021.

The chair reminded attendees of the confidential nature of the discussions, presentations and papers for the meeting.

Members were asked to provide an update on any new declarations of interest which may be relevant to this meeting. No new conflicts were raised.

Apologies were noted from 2 members. The chair confirmed that the meeting was quorate with 14 members in attendance.

3. Minutes of the last meeting

The committee approved the minutes from the 28 October 2020 meeting as a true and accurate record of the meeting.

The committee acknowledged the December chair’s action taken for a final recommendation on newborn hearing. It was recommended that auditory neuropathy spectrum disorder (ANSD) should not be added to the screening programme using the automated auditory brainstem response (AABR) test. The chair confirmed that the outcome had been reported back to the newborn hearing screening programme lead.

Nine action points were identified from the October meeting. All actions were in hand and/or completed:

3.1 Introductions and apologies

A valedictory letter to be issued to Prof Cameron for his time on the committee – completed.

3.2 Ethics and engagement at the UK NSC

Ethics to be added as an item to the March agenda – completed.

3.3 ARG report

Zeenat to share to the UK NSC statement on artificial intelligence (AI) accelerated access collaboration statement with the committee for comments – completed.

Zeenat to share the draft manuscript on the UK NSC ’s approach to reviewing evidence on AI in breast cancer screening. Members were invited to comment on the paper before it was submitted to the BMJ for publication. Deadline for comments was 11 November – completed.

3.4 Prostate cancer

For the plain English summary of the prostate cancer review to amend the word ‘benign’ to an alternative term such as ‘slow growing’, ‘low risk’ or ‘low grade’ – completed.

3.5 Antenatal screening for asymptomatic bacteriuria (ASB)

UK NSC secretariat to contact and discuss possible NIHR research into ASB with the developments being fed back to FMCH – ongoing.

3.6 Screening for galactosaemia

Reporting on outcomes for inherited metabolic diseases (IMD) to be added as a presentation item for the March UK NSC meeting. David Elliman to share details with Zeenat – completed and is on the agenda.

3.7 2019 annual call for topic: screening for dyslexia in school age children

The UK NSC to issue a formal outcome letter on the 2019 annual call for topics to screen for dyslexia to be send to the submitter – completed.

4. Matters arising – director’s update

Professor Mackie gave a verbal update on the following topics:

4.1 Creation of the National Institute of Health Protection

On 1 April the new National Institute for Health Protection (NIHP) will be established. The new organisation will have a primary focus on public health protection and infectious diseases. It will bring together various Public Health England (PHE) teams as well as NHS Test and Trace and the Joint Biosecurity Centre (JBC) to be under one leadership.

Post meeting note. It is to be known as the UK Health Security Agency.

Arrangements for the remaining PHE teams were under discussion, however PHE would continue to operate until October 2021.

The location for where screening would be held was still under active discussion. The chair informed the committee that a letter had been sent to England’s CMO expressing concern over the UK NSC’s future and stressed the importance to have the committee’s independence upheld.

4.2 CMO single body advisory committee – targeted screening definitions

The task and finish group led by CMOs to create a new advisory group in response to the independent review of adult screening programmes in England (2019) met for the final time at the start of March. The group had been given the opportunity to test the various criteria developed for the different types of screening and were content with developments made so far.

Further work was to be led by the DHSC secretariat to develop the workings of the new body in more detail, which included an agreed set of terms of reference and next steps.

4.3 Lung cancer

Initial work to look at the cost effectiveness of lung cancer screening was underway. Two task and finish groups had been set up to look at the modelling and pathway perspectives. An internal workshop would be held in the summer which would then present the outcomes of the various inputs of the cost effectiveness work. Further work may then be required before the UK NSC seeks wider stakeholder engagement.

4.4 Roll out of non-invasive prenatal testing (NIPT) in the NHS Fetal Anomaly Screening Programme (NHS FASP)

The evaluative roll out for NIPT is due to start on 1 June 2021.

NIPT however is an additional option and will be added to the FASP screening pathway for women with single or twin pregnancies who receive a higher chance result from either a combined or quadruple test.

Once the roll out has commenced the UK NSC will see the data and intelligence and will be able to review and amend the programme if necessary. Data will be collected on what women choose to do which was an area of uncertainty when initially recommended.

4.5 Ethics and engagement at the UK NSC

Ethics task group on child-parent screening for familial hypercholesterolemia (FH)

The UK NSC reviewed the confidential proposal. Part of UK NSC’s engagement on the proposal would be to test how the ethical principles developed could be applied. Information about this as part of the NHS long term plan is available at lipid management and FH/AHSN network.

Ethical principles to inform the restoration of adult screening pathways in the context of COVID-19

The committee had commissioned this report which looked to describe and explore the ethical issues relating to over inviting to population screening programmes in the context of COVID-19.

The report aims to provide a framework to think about both practical and ethical dilemmas both from a service provider perspective as well as concerns the public may have.

Catherine Joynson stated that this would be published in the coming weeks.

The committee expressed their gratitude for the development of the report and acknowledged that it had already been used as a springboard to help kick start discussions in Scotland.

Public dialogue on the implications of whole generation sequencing (WGS) in newborn screening

The UK NSC has taken part in various workshops which looked at how WGS could be used in the future. The UK NSC were working closely with various bodies to ensure a joint collaborative and acceptable approach was taken to using WGS in screening. More information about this would be discussed at a future meeting.

UK NSC stakeholder engagement review – preliminary results

The UK NSC undertook a stakeholder engagement exercise at the end of 2020 which sought to understand how the UK NSC currently engages with the public and stakeholders and how it might be improved. The UK NSC wanted to gather their views on the engagement processes and identify areas for improvement.

Catherine Joynson and Nick Johnstone-Waddell shared the preliminary results with the committee and explored the themes in detail.

The committee thanked both Catherine and Nick J-W for this important piece of work and looked forward to receiving the final results in order to have an informed discussion on areas of improvement.

Action 1A: Dr Elliman to share contacts of Immunisation colleagues to discuss the impact of the FH proposal with Prof Brownsword.

Action 1B: Invitation to a show and tell event to UK NSC members about the digital project should be arranged for the end of the March.

5. 2020 annual call for topic submissions

This item was presented by Paula Coles and sought the UK NSC’s input on the fourth submission (Klinefelter syndrome) received from the 2020 annual call for topics.

Decisions on next steps for 3 of the submissions had been made by the UK NSC’s evaluation group, who had met in January and was supported by the respective reference groups.

5.1 Neuronal ceroid lipofuscinosis type 2 (CLN2)

This was a new topic which the UK NSC had not reviewed before and met the initial triage step.

It was agreed that an evidence map should be commissioned which looked at 3 important questions on test accuracy, treatment and whether there are any national or international guidelines on population screening.

5.2 Biliary atresia using the stool colour card

This was already on the UK NSC list therefore was not a new topic. However, as work was being commissioned to look at biliary atresia as per its regular review cycle it was agreed that additional questions could be added to the commissioning document which looked at the use of stool coloured cards.

5.3 Pressure reducing carotid stenosis in adults over 50

It was noted that UK NSC had looked at this topic following a 2019 annual call for topic submission and an evidence map had been commissioned. The recommendation of the 2019 evidence map was that further work should not be commissioned. Given the recent work undertaken on this topic and that no new evidence was submitted with the new proposal, it was agreed that no further work should be commissioned at this time.

5.4 Klinefelter syndrome

This submission sought the UK NSC’s input as to whether further work should be commissioned.

The UK NSC received a proposal to look at this in 2018. An evidence map was commissioned to scope the volume and direction of the evidence for this condition since it had not been previously considered. At the UK NSC November 2019 meeting the outcome of the evidence map for Klinefelter which looked at 3 important questions only found 5 potential references which related to the incidence and prevalence of the condition and no evidence on the 2 other questions which looked at any type of screening test in the newborns, children or adolescents and any national or international guidelines or recommendations on screening for Klinefelter syndrome.

Due to the limited evidence it was recommended that further work should not be commissioned. The UK NSC was now being asked whether the second submission warranted further assessment or if the current work undertaken had sufficiently addressed this.

The UK NSC reviewed the proposal and acknowledged the frustration of the submitter as well as the unfortunate outcomes individuals with this condition with this condition faced. However, as the evidence base was limited it does not meet the UK NSC’s criteria for a population screening programme. The suggested use of non-invasive prenatal testing (NIPT) had not been explored widely but the UK NSC did suggest that the use of whole generation sequencing (WGS) may be a possible area where this condition could benefit from consideration. Furthermore, the UK NSC stated that having recently considered this condition it would not be good use of public money or resources to review this condition again so soon.

It was agreed that further work should not be commissioned, and that the submitter be informed of the outcome.

Action 2: UK NSC secretariat to report the outcome of the 2020 annual call submission for Klinefelter to submitter.

6. IMDs in newborn screening

Prof Jim Bonham had been invited to present his findings on the outcomes from the introduction of the 4 inherited metabolic disorders into newborn screening. These are:

• maple syrup urine disease (MSUD)
• homocystinuria – pyridoxine unresponsive (HCU)
• isovaleric acidaemia (IVA)
• glutaric aciduria type 1 (GA1)

The confidential presentation outlined how the conditions had been added to the newborn blood spot programme and presented confidential data on follow up and outcomes for the period of 2012 to 2016. The committee were informed that a second analysis of data up between 2016 to 2020 was due to be completed and would then be published later in the year.

7. Adult screening

Dr Given-Wilson presented the report from the adult reference group (ARG) which provided the committee with a summary of developments following the ARG meeting held on the 27 January 2021, as well as an update on the work from the artificial intelligence (AI) task group. Conditions discussed at the ARG meeting in January had been tabled for a final recommendation at today’s UK NSC meeting.

8. Stomach cancer

Dr Cristina Visintin presented this item. Detailed information is provided in the coversheet and should be read in conjunction with the evidence review report.

Stomach cancer is an important health problem. In 2017 it was the 5th most common cancer globally and the 17th most common in the UK. There are a number of factors which are known to increase the risk of developing stomach cancer. One of the main risk factors is a stomach infection caused by a bacterium called heliobactoer pylori.

The UK NSC last reviewed the evidence to screen for stomach cancer in 2016 and recommended that screening should not be introduced as there was too little evidence that population screening would be beneficial. At the time a screening and treatment strategy was not found to be appropriate for use in population screening in the UK. The review also noted that there was evidence that the epidemiology of the condition was changing in the UK, and that this needed to be taken into consideration in future review of the evidence.

The 2021 evidence review for stomach cancer was divided into 2 parts (an evidence summary and an evidence map) looking at 2 important questions. The evidence summary looked at the epidemiology and natural history of stomach cancer. Whilst the evidence map looked at the performance of screening tests for the detection of stomach cancer following the conclusion of the epidemiology review. This was to ensure that the tests considered by the evidence map were specific to the type of cancer relevant to the UK population.

The evidence summary on natural history found sufficient high-quality evidence drawn from 5 peer reviewed studies and 2 data reports that meet UK NSC criterion 1. The conclusions were similar to the 2016 evidence review with the majority of stomach cancers caused by h.Pylori. However, the review noted that over the coming decades there would be a rise in stomach cancer cases due to e other risk factors such as overweight and obesity. Furthermore, another important change identified was the age of presentation. Previously stomach cancer was more prevalent in people over the age of 50; however, in recent years there has been acceleration of people under 50 developing the condition. Therefore, it is important that such changes are factored into future UK NSC reviews of the evidence.

Question 2 looked at the test accuracy of screening tests for the detection of stomach cancer. The evidence map identified a single small prospective screening study that was carried out in elderly Chinese men. Due to the limited evidence found it was suggested that no further work should be commissioned at this time.

The UK NSC held a 3-month public consultation from 4 December 2020 to 24 February 2021 and contacted 29 UK NSC stakeholders directly.

The UK NSC received 3 consultation comments from the:

• British Society of Gastroenterology (BSG)
• Royal College of Nursing
• Royal College of Physicians

All comments received supported the recommendation that population screening should not be offered, recognising that there had not been significant changes in the literature base. The BSG noted the fall in incidence as well as the increase in cases among the younger age group and agreed that this was important to monitor in the future. The committee supported the public consultation comments made and raised no further queries.

The UK NSC approved the recommendation that a systematic population screening for stomach cancer should not be recommended in the UK.

9. Hearing loss in adults

Goda Kijauskaite presented this item to the committee. Detailed information is provided in the coversheet and should be read in conjunction with the evidence review report.

Hearing loss is a major public health problem and common among adults as they age. People with hearing problems may feel isolated, depressed and have difficulties in their relationships and may often live with a hearing impairment for some time before seeking help.

The UK NSC’s 2021 evidence review looked to see whether there had been any developments since the last review in 2015. The review looked at 4 important areas: the accuracy of screening tests for hearing loss in adults, the acceptability of treatment for hearing loss, whether screening helps improve health outcomes for adults with hearing loss and to see how well clinical detection and management were implemented currently in the UK.

The review identified 12 publications and found that overall, these did not change the evidence base to screen for hearing loss in adults.

None of the criteria were considered to have been met. While the review found there had been technological advancement with the use of smart phone applications being used as a screening tool these were still unreliable for use at a national level.

The applicability on the use of hearing aids was also unclear because the studies used different ways of measuring acceptability of hearing aids to the user therefore it was not possible to determine whether there were any changes since the last review. Also, the applicability to the UK context is unclear.

No new evidence had been identified to support the theory that earlier interventions, for example, as a result of screening, would improve health outcomes. In addition, the review found that there was insufficient evidence to determine the current implementation and clinical management of people with hearing loss in the UK.

Since the last review however the committee were informed that work to look at hearing loss services had been completed. In 2016, NHSE published commissioning guidance on hearing loss services and in 2018 NICE published evidence-based guidance about the referral, diagnosis, interventions and management for adults with hearing loss.

A 3-month consultation took place from the 3 August to the 26 October 2020 and 24 UK NSC stakeholders were contacted directly. Seven stakeholders submitted comments, 3 of which supported the recommendation whilst the remaining 4 did not provide a direct statement. Detailed responses to the main themes were provided in the coversheet.

The main themes which emerged from the 2021 review were focussed on:

9.1 Ongoing research and new evidence

The UK NSC were made aware of an ongoing systematic review and a planned RCT. Studies that were already published fell outside the period of the UK NSC’s literature search. The UK NSC members recognised the amount of work ongoing in this area and asked the Secretariat to carefully monitor this as part of its existing horizon scanning function.

9.2 Acceptability and uptake of treatment and effectiveness of screening on health outcomes

The committee agreed that patient’s views along the whole clinical pathway were important however this evidence summary and UK NSC’s recommendations relate to studies that included asymptomatic individuals who were screen detected. The members agreed that data relating to acceptability of hearing aids which was shared with the UK NSC via the consultation did not meet the UK NSC’s quality / criteria of evidence to be included. The committee noted that there was ongoing research in this area which hopefully prove useful in time for the next UK NSC’s review.

9.3 Proposed age of screening to commence at 55 years

The UK NSC noted that on PROSPERO (CRD42020222125), McMahon et al published a protocol for a systematic review to look at optimal age for screening in adults and looked forward to reviewing the outcomes by the next UK NSC review.

9.4 Effectiveness of screening on health outcome

The committee agreed that treatment for hearing loss is effective, however, the effects on health outcomes are not to be found in the literature. The UK NSC noted that on PROSPERO (CRD42020222125), McMahon et al published a protocol for a systematic review to look at the impact of hearing loss. screening programmes on the quality of life and looked forward to reviewing the outcomes by the next UK NSC review.

The committee expressed its gratitude for the constructive comments submitted during the consultation. The committee recognised that the stakeholders had engaged with the issues identified previously and this engagement had led to research being undertaken to help bridge the evidence gaps. Although there were no international screening programmes for hearing loss in adults the UK NSC was encouraged by the active work undertaken and looked forward to reviewing this again.

The UK NSC recommended, based on the evidence presented and comments submitted, that a systematic population screening for hearing loss in adults should not be recommended in the UK.

The UK NSC noted that the active research agenda meant that the UK NSC should actively monitor this condition as part of its horizon scanning function.

10. Hereditary haemochromatosis in adults

This item was presented by Silvia Lombardo. Detailed information is provided in the coversheet and should be read in conjunction with the evidence review product.

Haemochromatosis is a condition where iron levels build up in the body over time. Deposits of iron begin to increase around various organs, including the heart and liver. This can cause uncomfortable symptoms, such as nausea, abdominal pain, constipation and joint pain. It can also lead to liver damage, heart failure and diabetes.

The UK NSC last looked at the evidence to screen for hereditary haemochromatosis (HH) in 2015. It was recommended at that time that screening should not be offered because:

• although a faulty human homeostatic iron regulator protein (HFE) gene is known to cause iron to build up, this does not necessarily happen to every person with a faulty gene (low penetrance)
• screening would identify people who may never experience symptoms
• there was no evidence to suggest that a screening programme would be effective
• there was insufficient evidence to draw conclusions on a suitable screening strategy (for example. test, intervals, age)

The 2020 evidence review carried out an extensive literature search from 1996 to December 2019 and focused on 4 important questions:

1. What is the penetrance of type 1 hereditary haemochromatosis (HH) in untreated adults who were positive for C282Y homozygosity, H63D homozygosity or C282Y/H63D compound heterozygosity? (UK NSC criterion 1). Based on the quality and heterogeneity of the studies, is a meta-analysis or a summary estimate possible?
2. What is the association between HH-related biochemical and clinical features and mutations in the HFE gene (C282Y homozygosity, H63D homozygosity or C282Y/H63D compound heterozygosity)? (UK NSC criterion 1). Based on the quality and heterogeneity of the studies, was a meta-analysis or a summary estimate possible?
3. Is there evidence that intervention at a pre-symptomatic phase leads to better outcomes compared to intervention following presentation of symptoms? (UK NSC criterion 9)
4. What is the effectiveness of screening to reduce HH-related morbidity and mortality? (UK NSC criteria 11 and 13)

The review concluded that the recommendation to not offer screening for HH should remain in place. This was because, even though there is clear evidence for an association between the 3 hereditary haemochromatosis genotypes and iron overload, these are biochemical outcomes, which may or may not have clinical implications for individuals. The proportion of people with clinical outcomes was generally low (low penetrance), and the evidence regarding clinical conditions generally does not support associations with type 1 HH genotypes. In addition, there was limited evidence on whether intervention at an earlier/asymptomatic stage leads to better outcomes compared to intervention at a later/symptomatic stage in individuals with hereditary haemochromatosis.

No eligible studies were identified which addressed the question on the benefits and harms of screening for hereditary haemochromatosis in adults. In relation to whether, based on the quality and heterogeneity of the studies, a meta-analysis or a summary estimate is possible, the review noted that pooling together prioritised and deprioritised studies in a systematic review and/or meta-analysis may help to provide more refined estimates of penetrance and associations between genotypes and iron overload.

The UK NSC held a public consultation from the 19 October 2020 to 15 January 2021. It contacted 14 stakeholders and received 5 comments, from:

• British Association for the Study of the Liver (BASL)
• Royal College of Nursing (RCN)
• Haemochromatosis UK
• Genetic Alliance UK
• a member of the public volunteering for Haemochromatosis UK

BASL and RCN agreed with the evidence review recommendation and expressed their appreciation of the in-depth report. BASL in particular stated that it was still premature to recommend a national screening programme and that the emphasis should remain on primary and secondary care clinician education to perform genetic testing and implementation of cascade screening after identification of index cases.

Haemochromatosis UK, Genetic Alliance UK (who endorsed the response of Haemochromatosis UK) and the member of the public disagreed with the conclusion of the evidence summary and advocated for the implementation of systematic genetic screening for haemochromatosis in adults across the UK. They noted that HH was not rare, but rarely diagnosed and so a population screening programme would be relevant to assist in early diagnosis. The comments also outlined that current diagnostic pathways are ineffective and that a screening pilot should instead be considered.

Detailed responses to the consultation comments made are provided in the coversheet.

The committee noted that following the end of the consultation the HH all-party parliamentary group (APPG) had emailed the Secretariat asking for an indicative timeline for the publication of the findings of the review and flagging up 3 papers they wished to be included. One was already included in the 2020 evidence summary. The other 2 papers fell outside the literature search dates of the evidence review. The papers would not be likely to change the recommendation, so they were not reviewed in detail as part of the review. The committee was satisfied that an extensive literature search had been undertaken dating back to 1996 when the HFE mutations were first identified. A response had since been issued to the submitter.

Following the significant consultation responses including submission of late papers, contact with the secretariat and suggestions made during the consultation, several members suggested that more could be done to clarify the UK NSC processes. In particular acknowledging that all recommendations are provisional and will be reviewed regularly or on the receipt of significant new evidence that might change the recommendation on screening. The committee agreed that more should be done. They noted the work already underway on stakeholder engagement.

The evidence review highlighted that further research was needed to demonstrate that screening is effective. Therefore, members of the committee proposed that the Secretariat should offer to facilitate discussions with stakeholders on how it might be possible to take research forward. It was emphasised that although commissioning and/or funding research was outside the UK NSC’s remit, the committee would be happy to have constructive conversations which would help bridge the gaps in the evidence base and move the discussion forwards for future reviews of screening for HH.

Based on the evidence presented and comments submitted, the UK NSC recommended that a population screening programme for HH should not be introduced at the current time.

Following publication of the recommendation, the UK NSC would facilitate a stakeholder workshop focusing on potential research questions which may help to move the discussion forward for future reviews of screening for haemochromatosis.

Action 3: UK NSC secretariat to engage with hereditary haemochromatosis stakeholders to take forward discussion on research and clarify UK NSC processes.

11. Thrombophilia in all ages

Dr Cristina Visintin presented this item. Detailed information is provided in the coversheet and should be read in conjunction with the evidence review product.

Thrombophilia is a condition where the blood has an increased tendency to form clots. This clotting is called thrombosis. There are many different causes, some of which are hereditary. Some people with thrombophilia have no problems, whereas others may need to take medication to prevent or treat blood clots.

The UK NSC last looked at screening for thrombophilia in 2016.

The 2021 evidence map of thrombophilia in all ages combined the 2 previous reviews which looked at screening for thrombophilia in pregnancy and newborns to include adults.

The evidence map looked at 4 important questions:

1. What is the accuracy of universal screening tests for thrombophilia in the general pregnant population?
2. What is the effectiveness and safety of thromboprophylaxis for preventing venous thromboembolism and adverse pregnancy outcomes in screen-detected women?
3. What is the accuracy of screening tests for detecting thrombophilia in neonates and the general adult population?
4. What is the reported effectiveness of thromboprophylaxis for preventing adverse outcomes in screen-detected neonates and adults?

The evidence map did not identify any new evidence. Therefore, it was proposed that no further work should be commissioned at this time, and that the UK NSC recommendation should be confirmed.

A public consultation was hosted for 3 months from the 16 October 2020 to 15 January 2021. The UK NSC contacted 12 stakeholders and received one response from the Royal College of Paediatrics and Child Health, which agreed with the conclusions of the evidence map.

The UK NSC made no further comment on the document or consultation comment and were content with the findings.

The UK NSC recommended that a systematic population screening programme for thrombophilia in all ages should not be recommended in the UK.

12. Fetal, maternal and child health screening

Dr Sharon Hillier provided the committee with a brief summary of developments following the fetal, maternal and child health (FMCH) meeting in January.

The UK NSC were informed that screening for gestational diabetes was currently open for consultation. Deadline for comments was 6 May 2021.

13. NHS FASP: programme modification

The UK NSC was asked to comment on the confidential evidence review and evidence map submitted as a programme modification proposal regarding quadruple testing for T18 in the fetal anomaly screening programme.

14. Fetal presentation

This item was presented by Silvia Lombardo.

Screening for fetal presentation came from the 2019 annual call for topic submission. By the late stages of pregnancy, most babies in singleton pregnancies are positioned with their heads down ready for the birth. However, approximately 3 to 4% of all pregnant women who reach full term will have a baby presenting in the breech position (bottom first). Breech presentation places the baby and the mother at increased risk of a complicated vaginal birth or caesarean section (C-section).

The proposal submitted suggested that all pregnant women, irrespective of risk status, should be offered screening using a handheld ultrasound device to detect fetal presentation during routine antenatal screening appointments at around 36 weeks gestation. It was proposed that the main purpose would be to reduce the rate of unexpected breech presentations and consequently the rate of emergency C-section or complicated vaginal birth.

Having met the initial triage step of the UK NSC annual call for topics process, it was agreed that an evidence map should be commissioned to gauge the volume and type of available published evidence on this topic.

The evidence map looked at 2 questions:

1. What is the diagnostic accuracy of an ultrasound scan performed at point of care (for example using handheld scanners) at 36 weeks’ gestation to detect fetal presentation?
2. What is the effectiveness of ultrasound screening in preventing emergency caesarean section and adverse maternal and neonatal outcomes?

The evidence map found no studies between the period of 2010 to October 2020 which met the eligibility criteria on diagnostic accuracy for a point of care ultrasound (POCUS) scan performed at 36 weeks gestation to detect fetal presentation. It was not clear whether the accuracy of this test was established in studies published prior to the search dates. However, in the introduction the evidence map noted that a study by Nassar et al. (2006) used POCUS as the reference standard to confirm diagnosis of breech representation if suspected following clinical examination (index test). This suggests that the diagnostic accuracy of POCUS screening is expected to be high.

In relation to question 2 on the effectiveness of ultrasound screening in preventing adverse outcomes 3 studies were identified, a systematic review and 2 studies conducted in the UK.

The evidence map concluded that the volume and type of direct evidence related to ultrasound screening for breech presentation at 36 weeks’ gestation is currently insufficient to justify an evidence summary at this stage. Though limited, the evidence map pointed out that the current evidence appears promising and that the topic should therefore be added to the UK NSC recommendations list.

The UK NSC agreed that this condition looked promising and may be a suitable candidate for a screening programme once further research had been published in the coming years. An important research item would be the forthcoming Health Technology Assessment (HTA) on universal late ultrasound screening to predict adverse outcomes in pregnancy.

The UK NSC recommended that further work on screening for fetal presentation should not be commissioned at this time. But that the condition should be added to the UK NSC recommendations list, so that it can be reconsidered in 3 years’ time or sooner if significant evidence should be published before this time.

The submitter has been in touch with the UK NSC secretariat noting his interest in conducting research on this topic.

As this was an annual call submission, a public consultation was not held.

Action 5A: The outcome of the 2019 annual call for topic on fetal presentation should be fed back to the submitter.

Action 5B: Fetal presentation to be added to the UK NSC regular list of conditions.

15. Adolescent idiopathic scoliosis

Goda Kijauskaite presented this item on adolescent idiopathic scoliosis (AIS). Detailed information is provided in the coversheet and should be read in conjunction with the evidence review product.

Scoliosis is an abnormal curvature of the spine to one side. It most often affects children aged 10 to 15. It can cause back pain and lead to psychological effects such as stress, anxiety and lower self-esteem.

The UK NSC last looked at AIS in 2015 and recommended that population screening should not be offered. This was because the accuracy of the most commonly used test, the forward bend test, and its ability to predict progression to clinically significant scoliosis was questionable. As the test was unable to consistently identify a group of children who would progress in this way, screening could lead to unnecessary follow up procedures such as x-ray with which harm is associated. In addition, the treatment usually involves exercise, bracing and surgery or a combination of these approaches.

The 2020 evidence review was an evidence map which looked at the effectiveness of the screening for AIS in children on health outcomes.

Only one relevant publication was identified which was a systematic review commissioned by the US preventative task force in 2018, which identified no relevant studies. As a result, the findings of the evidence map were that due to the limited evidence base no further work should be commissioned at this time.

A public consultation was held from 11 June to 3 September 2020.

The consultation received only one comment from SWS Cymru Support with Scoliosis who disagreed with the recommendation.

The stakeholder replied to say there was missing evidence on the effectiveness of screening for AIS and on health outcomes. The suggested papers fell outside the literature search dates. The proposal to extend the search date was considered by FMCH. After careful discussion it was agreed that this should not be extended as the evidence would not have changed the conclusions of the evidence map.

The second point made by the stakeholder was about screening tests, they suggested that there was new evidence on the test called Scolioscan, which uses 3D ultrasound imaging. However, the test appeared to be a diagnostic rather than a screening tool. Another suggested test was Digital Moire topography, the committee agreed that there appeared to be little evidence on this test so it was agreed that an evidence map on screening tests should not be commissioned at this time.

The UK NSC noted the findings and made no further comments.

The UK NSC recommended that based on the findings of the evidence map no further work on AIS should be commissioned at this time.

The 2021 recommendation for screening for AIS is that a population screening programme should not be introduced at this time.

16. Adrenoleukodystrophy

This item on adrenoleukodystrophy (ALD) was presented by Silvia Lombardo. Detailed information is provided in the coversheet and should be read in conjunction with the evidence review product.

ALD was added to the UK NSC’s list of recommendations following a review of the evidence carried out in 2017 as part of the first run of the annual call for topics.

An evidence map was commissioned in 2020 addressing 4 important questions:

1. What is the incidence of ALD in the UK? What is the proportion of people with a mutation of the ABCD1 gene who will develop symptoms associated with any form of ALD? What are the age of onset and clinical prognosis of each of these forms?
2. Are there any factors that can predict the future ALD phenotype in the pre-symptomatic phase?
3. What is the evidence on the accuracy of currently available screening tests using dried blood spots to detect ALD?
4. Does early initiation of treatment following screening provide better outcomes for ALD compared to initiation of treatment following clinical detection?

The final evidence map included 19 references, of which 9 studies met the inclusion criteria for the question on treatment. However, no studies were identified that directly compared the effectiveness of treatment for individuals identified pre-symptomatically with those presenting with clinical symptoms (this being critical to a screening programme).

The outcome of the evidence map was that, although there might be sufficient evidence to commission an evidence summary on the treatment, it is unlikely that a review of the available evidence in this area alone would lead to a change in the UK NSC’s position. The FMCH group agreed with the evidence map’s conclusion. The evidence relating to the other important questions about UK incidence, predicting ALD phenotype and the accuracy of screening tests was limited in relation to both volume and type.

The conclusion of the evidence map was that an evidence summary on newborn screening for ALD is not currently justified and that the topic should be re-considered in 3-years’ time.

A public consultation for ALD was held from 7 October 2020 to 5 January 2021. The UK NSC contacted 11 stakeholders and received 34 comments.

The Royal College of Paediatrics and Child Health supported the findings of the evidence map.

Comments were received from:

• Alex: the Leukodystrophy Charity
• Zellweger UK
• a board director of SwanBio Therapeutics

The majority of the comments were from members of the public who shared their very personal experiences of ALD and Zellweger Spectrum Disorder (ZSD). These submissions expressed support for screening for ALD, which would also help to identity ZSD. The personal accounts received spoke candidly about the physical, mental and financial impact that the progressive neurodegenerative or lethal nature of these conditions had not only to the affected individual but to their families. These included depression and feelings of guilt for either passing on the faulty gene or for having a better outcome than a sibling.

The UK NSC outlined how the personal stories submitted by the members of the public are an important statement of the effect that a diagnosis of ALD and ZSD has on individuals, their families and friends, and expressed its gratitude to stakeholders for having taken time to submit such personal comments and for their contribution to the consultation process.

Detailed responses to the main themes of stakeholder’s comments can be found in the coversheet.

Several themes came through supporting the call for screening. Respondents said that screening would:

• enable early diagnosis thereby avoiding a long diagnostic odyssey and enabling early treatment
• align the UK with other countries such as the US and the Netherlands where screening for ALD is offered
• provide early knowledge of carrier status which would help with families’ reproductive choices
• enable more research on potential treatments and provide better epidemiological data
• benefit also family members other than the individual immediately affected, such as women who are often misdiagnosed later in life with multiple sclerosis and offered inappropriate treatments

However, when looking at the evidence base for ALD more broadly, the UK NSC recognised that there was still uncertainty regarding the impact of receiving an early diagnosis of ALD, particularly for those who would not go on to develop childhood cerebral ALD (CCALD), but also for those diagnosed with other peroxisomal disorders. This is relevant because there are no established treatment options for non-CCALD patients and the same applies to many other peroxisomal disorders. Therefore, screening would be unlikely to improve clinical outcomes in these patients. Hence, the conclusion of the evidence map was that an evidence summary is not justified at the current time and so the topic should be re-considered in 3-years’ time or sooner if significant evidence is published before this time.

Given that several comments came in about ZSD, the committee discussed this. Dr Shortland informed the committee that ZSD was quite different to ALD. ZSD would usually be detected in the neonate period and be identified more swiftly when compared to ALD. Although identification may take weeks or months, it was recognised that, from a parent perspective, this in itself was a lengthy and worrying time. Identification and further testing and treatment for ALD overall is a lengthier process, as symptoms may not present during infancy but may do so later on in life. This means that the individual would need to be monitored over long periods of time to see whether they develop the cerebral childhood form.

Dr Shortland also stated that enabling reproductive choices and enabling pre-implantation genetic diagnosis was important but predicting the exact ALD phenotype with the current state of knowledge is difficult and requires further research. The committee agreed with the points made by Dr Shortland.

It was noted that the idea of reproductive choices and its benefits to others was being explored from an ethical perspective in familial hypercholesteraemia. The UK NSC had developed its ethical principles considering the impact screening has on others and was due to be published shortly. However, Prof Mackie stated that the point around impact in screening for others was not the primary focus with regard to the discussion on ALD. Ethical considerations would need to be considered in further details for ALD if it was to become a potential screening candidate.

The committee made no further comments on the evidence and expressed their appreciation for the informative submissions received during the consultation process.

Based on the findings of the evidence map, the UK NSC recommended that a systematic population screening programme for adrenoleukodystrophy (ALD) should not be introduced.

Action 6: Dr Shortland to verify lines on reproductive choice to be added in the final coversheet.

17. Updates – NIHR NETSCC

This was noted.

18. Any other business

There was no other business.

19. Next meeting

Friday 25 June 2021