Guidance

UK NSC previous annual call submissions

Updated 15 August 2023

2021 annual call topic proposals

The UK NSC received 4 proposals in 2021:

Metachromatic leukodystrophy (MLD)

UK NSC decision: commission more work and add MLD to list of conditions the committee regularly reviews

The UK NSC received a proposal for the introduction of newborn screening for MLD and the evaluation group agreed it fell within the UK NSC remit.

An evidence map was commissioned and its findings were promising. The evidence map recommended further work:

• to evaluate all available screening strategies
• to look in more depth at evidence related to the benefits and/or harms of treatments in presymptomatic patients with MLD
• on the question of cost-effectiveness

Chair’s action was taken to prevent delay to this further work and MLD will be added to the UK NSC’s recommendation list kept under regular review.

Anorectal malformations

UK NSC decision: evidence map commissioned, no further work

The UK NSC received a proposal to add anorectal malformations (ARMs) to the newborn and infant physical examination screening programme.

The evaluation group agreed that the topic fell within the remit of the UK NSC and an evidence map was commissioned.

The evidence map found no suitable studies that reported a screening test used to triage consecutive or randomly selected populations of all newborns and/or infants for ARMs.

Both the fetal, maternal and child health (FMCH) group and the UK NSC noted the findings of the evidence map for ARMs and agreed no further work should be commissioned at this time.

Neonatal diabetes

UK NSC decision: evidence map commissioned, no further work

The UK NSC received a proposal to screen for neonatal diabetes (NDM) in newborns.

The evaluation group agreed that the topic fell within the remit of the UK NSC and an evidence map was commissioned.

The evidence map concluded that the volume and type of evidence related to screening for NDM was insufficient to justify an evidence summary and no further work on screening for NDM should be commissioned at this time.

Craniosynostosis

UK NSC decision: evidence map commissioned, no further work

The UK NSC received a proposal to screen for craniosynostosis as part of the Newborn and Infant Physical Examination (NIPE) population screening programme.

The evaluation group agreed that the topic fell within the remit of the UK NSC and an evidence map was commissioned.

The evidence map concluded that the volume and type of evidence related to screening for craniosynostosis was insufficient to justify an evidence summary and no further work on screening for craniosynostosis should be commissioned at this time.

2020 annual call topic proposals

The UK NSC received 4 proposals in 2020:

Biliary atresia

UK NSC decision: include proposed methodology in next review of topic

The UK NSC received a proposal to introduce screening for biliary atresia using stool colour cards. These are cards that explain the colour of stools, ranging from those that are healthy to those that may require further investigation. Biliary atresia was already on the UK NSC list, so was not a new topic.

However, as work was being commissioned to look at biliary atresia in the regular UK NSC review cycle, it was agreed that additional questions on the use of stool coloured cards could be added to the commissioning document.

Klinefelter syndrome

UK NSC decision: submission declined

The 2020 submission on screening for Klinefelter syndrome sought the UK NSC’s input as to whether more work should be commissioned following the previous annual call proposal in 2018.

The UK NSC decided a further review was not justified.

Neuronal ceroid lipofuscinosis type 2 (CLN2)

UK NSC decision: evidence map commissioned, no further work

This was a new topic which the UK NSC had not reviewed before.

An evidence map was commissioned to look at 3 important questions covering:

• test accuracy
• treatment
• whether there are any national or international guidelines on population screening

The evidence map concluded that the volume and type of evidence relating to screening for CLN2 did not justify an evidence summary at this stage and no further work on screening for CLN2 should be commissioned. This was because:

• there were no international recommendations on population screening to detect CLN2 in newborns
• there was no direct evidence on how good screening tests were in a setting comparable to a population screening
• there were no studies on the benefits of treatment in screen-detected patients, and very limited evidence on the effectiveness of treatment in pre-symptomatic patients

Pressure reducing carotid stenosis in adults over 50

UK NSC decision: submission declined

It was noted that the 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.

2019 annual call topic proposals

The UK NSC received 5 proposals in 2019:

Dyslexia in school-age children

UK NSC decision: evidence map commissioned, no further work

This proposal suggested that children of school age should be screened for dyslexia.

The evaluation group agreed that it fell within the UK NSC’s remit and had not been considered before.

It was decided that an evidence map should be commissioned.

This evidence map concluded that the volume and type of studies available about the accuracy of screening tests specifically for dyslexia is insufficient to justify a further review of the evidence.

Fetal presentation in pregnancy (to check on the baby’s position at 36 weeks)

UK NSC decision: evidence map commissioned and fetal presentation added to list of conditions the committee regularly reviews

The proposal is to screen all pregnant women for fetal presentation using a handheld ultrasound device during routine antenatal appointments at around 36 weeks of gestation.

The aim would be to detect the position of the baby to see if the baby is head-down (cephalic) rather than bottom or feet first (breech position) or lying sideways (transverse position). Screening would aim to detect those babies who were not head-down and to offer options to help manipulate the baby’s position to become head-down or offer a planned caesarean delivery to minimise harm to mother and baby.

The evaluation group agreed that this proposal had not been considered before and fell within a defined whole population group. It was agreed that an evidence map would be commissioned to scope the volume and type of published peer reviewed evidence available on this condition. The UK NSC agreed to this approach.

The evidence map recommended that the topic 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.

Liver cirrhosis in high risk groups

UK NSC decision: submission declined

The proposal calls to screen high risk groups of the condition using transient elastography. Liver cirrhosis is scarring of the liver caused by long-term liver damage which then prevents the liver from working properly. This can lead to liver failure. There is no cure for cirrhosis but it is possible to manage symptoms through lifestyle changes.

The evaluation group agreed that this proposal fell outside the UK NSC’s remit at the time because it related to high risk groups. It was proposed that no further work should be conducted. The UK NSC agreed.

Pressure reducing carotid stenosis in adults over 50

UK NSC decision: submission declined

It was noted that the 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.

5q spinal muscular atrophy (SMA) in newborns

UK NSC decision: submission considered as early topic update

The proposal called for newborn screening for 5q SMA.

The evaluation group agreed that the proposal did not meet the inclusion criteria for the annual call for new topics, as SMA screening in newborns is included in the list of conditions that the UK NSC regularly reviews. However, it was agreed to consider this submission as an early topic update given that new evidence submitted by the stakeholder may impact the UK NSC’s 2018 recommendation not to offer antenatal or newborn screening for SMA.

The UK NSC evidence team assessed if the new evidence would have an impact on the conclusions of the 2018 UK NSC evidence review and presented its conclusion to this meeting.

The proposal drew attention to developments relating to treatment. The evidence presented by the NURTURE study showed promising results in relation to the efficacy of the drug nusinersen in asymptomatic individuals with SMA type I to II. It is important to note that these are preliminary results and the study is due to report its conclusion in 2025.

The recent change in the National Institute for Health and Care Excellence (NICE) guidance on the use of nusinersen as a treatment option in 5q SMA in individuals with pre-symptomatic SMA, or SMA types 1, 2 or 3 is also a significant development and focuses attention on screening. However, the information provided in the proposal did not include new evidence in relation to other criteria that were not met in the 2018 review, such as the screening test.

There were also concerns about the cost-effectiveness of the treatment. An estimate is difficult because of lack of evidence about long-term benefits and the possibility of regression. Therefore, an early update would be unlikely to change the conclusion of the review overall.

The UK NSC organised a workshop with a wide range of stakeholders to plan the next steps to review the case for screening for SMA. A proposal for a scoping exercise to inform a decision analytic model and cost effectiveness evaluation of newborn screening for SMA was drafted following the stakeholder workshop. This work is in the process of being commissioned.

2018 annual call topic proposals

The UK NSC received 10 proposals:

All cancers in 30 to 75-year-olds

UK NSC decision: submission declined

The evaluation group agreed that this did not meet the criteria for formal consideration due to lack of evidence on outcomes.

Cutaneous melanoma in adults

UK NSC decision: evidence map commissioned, no further work

Following a submission to the 2018 annual call, an evidence map was commissioned to find out if there was any evidence available on the accuracy of using ocular/iris photography to detect iris nevi/iris pigmented lesions to screen for risk of cutaneous melanoma.

No studies examining the accuracy of this test were found and the UK NSC recommended that:

• no further work should be carried out due to lack of evidence
• cutaneous melanoma in adults should not be added to the UK NSC’s list of topics

Neurofibromatosis type 1 (NF1) in newborns

UK NSC decision: evidence map commissioned, no further work

An evidence map for NF1 was commissioned following the 2018 annual call. It addressed 3 questions:

1. Are there any guidelines and/or recommendations for systematic population screening?
2. Is there evidence on the diagnostic accuracy of physical examination of the child’s skin as a screening test?
3. Is there any evidence of the benefits of early detection of NF1?

No guidelines or recommendations were found. There was some evidence on the test but none of this evidence assessed the diagnostic accuracy.

No studies were found that directly assessed the benefits of early detection. The UK NSC agreed that:

• there was not enough evidence to progress to the next step of the process and commission a more detailed assessment
• the condition should not be added to the UK NSC’s list of topics

Klinefelter syndrome

UK NSC decision: evidence map commissioned, no further work

An evidence map was commissioned to scope the volume and direction of the evidence for this condition since it had not been previously considered. The UK NSC considered the evidence map, which looked at 3 important questions, at its meeting in November 2019.

The evidence map only found 5 potential references which related to the incidence and prevalence of the condition. It found no evidence on the 2 other questions, which looked at any type of potential screening test in newborns, children or adolescents. There were no national or international guidelines or recommendations on screening for Klinefelter syndrome.

As the evidence base was limited, the committee agreed that it did not meet the UK NSC’s criteria for a population screening programme and further work should not be commissioned.

22q11 deletion syndrome in newborns

UK NSC decision: evidence map commissioned, no further work

22q11 deletion syndrome (also called DiGeorge syndrome) is a condition present from birth that can cause a range of lifelong problems, including heart defects and learning difficulties. The evaluation group agreed that the evidence team would do more work to check references to understand the volume of literature available.

The following questions were addressed in the evidence map:

1. What is the incidence/prevalence and severity of 22q11.2 Deletion Syndrome in the UK?
2. Is there a simple, safe, precise and validated screening test for 22q11.2 Deletion Syndrome?
3. Are there any national or international guidelines or recommendations on population screening for 22q11.2 Deletion Syndrome?

Six references were included in the final evidence map: one on prevalence in the UK and 5 on the diagnostic accuracy of potential screening tests. No guidance or recommendations on population screening for 22q11.2 Deletion Syndrome were found.

One study conducted in the UK was identified which reported prevalence. However, this study was conducted in 1994 to 1995 and was carried out in a high-risk population so it would not be comparable to the general population.

Five studies on diagnostic accuracy studies were found. However, these considered a range of different tests and were all small case-control studies, which restricted their usefulness in determining the accuracy of the test in a screening population.

It was concluded that the volume and type of evidence related to screening for 22q11.2 Deletion Syndrome was insufficient to justify an evidence summary.

Beta thalassaemia in newborns

UK NSC decision: evidence map commissioned, further research recommended

This was a proposal for beta thalassaemia major to be formally screened for rather than be reported as an incidental finding within the existing newborn screening programme for sickle cell disease. The evaluation group agreed to consider this proposal as a major programme modification.

An evidence summary was commissioned. It recommended further areas of research to consider before newborn screening for beta thalassaemia major might be included in the NHS Sickle Cell and Thalassaemia Screening Programme. For example, cost-effectiveness of formally screening for beta thalassaemia major was flagged as an area that would benefit from further research.

Lung cancer in adults

UK NSC decision: submission declined

This condition is already on the UK NSC’s list of conditions which is reviewed regularly as per its published process. No further action is required.

Risk of sudden cardiac death

UK NSC decision: submission declined

This condition is already on the UK NSC’s list of conditions which is reviewed regularly as per its published process. No further action is required.

Nonsyndromic thoracic aortic diseases (NS-TAD)

UK NSC decision: submission declined

The evaluation group agreed that no further action was needed because the proposal related to cascade testing, not population screening. Cascade testing is the systematic tracing and testing of family members of an affected patient for a genetic disease. The ‘index case’ is the first person in a family to be identified with the condition. Family members of the index patient are tested to find out if they also have the condition.

Carbon monoxide levels

UK NSC decision: evidence map commissioned, no further work

The evaluation group agreed that this proposal was within the remit of the UK NSC and that an evidence summary to look at screening for carbon monoxide levels in pregnancy should be commissioned. Based on the evidence summary, it was not possible to conclude whether screening would increase smoking cessation rates in pregnancy. It was agreed that further work on this topic should not be commissioned as it was unlikely to identify the evidence required to recommend a population screening programme.

2017 annual call topic proposals

The UK NSC received 4 proposals:

Keratoconus in children and young adults with Down’s syndrome

UK NSC decision: submission declined

The evaluation group agreed that this proposal falls outside the UK NSC’s remit of whole population screening programmes. Therefore the proposal was sent to the Down Syndrome Medical Interest Group and NICE to consider.

Increased risk of stroke in children with sickle cell disease

UK NSC decision: submission declined

The evaluation group agreed that the proposal to diagnose children with sickle cell disease (SCD) who are at a higher risk of stroke and to offer early intervention was outside the remit of the UK NSC but was part of the care pathway for children diagnosed with SCD. Although no further action was required by the UK NSC it was agreed that the issue would be escalated to NHS England and NICE.

Auditory neuropathy spectrum disorder (ANSD) in newborns

UK NSC decision: evidence summary commissioned

ANSD represents a range of possible disorders and prognoses due to a problem with the hearing nerve and is defined by a pattern of test results.

The evaluation group agreed to review the proposal for ANSD to be added to the NHS Newborn Hearing Screening Programme (NHSP) as a programme modification.

The evidence summary concluded that ANSD should not be added to the NHSP. This was because:

• there was uncertainty as to the number of babies with the condition who are missed using the current screening strategy and who would benefit from the addition of ANSD to the programme
• only one small study looked at the test in the newborn general population and conclusions on the accuracy of the test could not be made
• there was no published information on the practicalities of implementing the test in the newborn general population

Endometrial cancer

UK NSC decision: scoping exercise commissioned

This submission was handled as a new topic as the UK NSC had not looked at the evidence to screen for endometrial cancer before. A scoping exercise was undertaken which revealed that screening is not recommended. It was therefore agreed that this would not to be added to the UK NSC list of conditions to screen for.

2016 annual call topic proposals

The UK NSC received 4 proposals:

Cerebral adrenoleukodystrophy (cCALD) in newborns

UK NSC decision: evidence map commissioned, cCALD added to list of conditions to be reviewed regularly

The evaluation group agreed that this proposal was within the remit of the UK NSC and that an evidence map on screening in newborns should be commissioned. The evidence map identified a number of issues. These included:

1. The screening test was still experimental. Case control type studies are the mainstay of accuracy estimates and its use in a population setting is currently being evaluated in the New York State newborn screening programme.
2. The test would identify a number of boys with the genetic mutation who would not develop cCALD. In addition, the test would identify babies with conditions, other than ALD, for which there are no interventions.
3. There was uncertainty on the ability of the diagnostic pathway to distinguish those requiring haematopoietic stem cell transplantation (HSCT) from those who do not.
4. There was uncertainty on the balance of long-term benefits and harms of treatment with HSCT.

Although further work was not justified, the UK NSC agreed to add adrenoleukodystrophy to the list of conditions to be reviewed as part of its regular update cycle.

Hypercholesterolaemia in children

UK NSC decision: early topic update not justified

The evaluation group felt this submission was more in keeping with an early update proposal because familial hypercholesterolaemia (FH) is already on the UK NSC’s list of conditions that it regularly reviews.

The submission was prompted by the publication of a study of screening in children aged 2.

The UK NSC commissioned 2 external assessments to summarise the evidence submitted and consider the impact on the previous review of the topic.  These assessments, and their recommendations on whether to bring the FH review forward, were considered by the chair and vice-chair of the UK NSC, the Fetal, Maternal and Child Health (FMCH) reference group and the Director of Screening. They agreed with the overall recommendation of these assessments that an early update was not justified.

The main reasons an early update was not justified were:

• an absence of information on the management of children with FH identified by screening
• that the acceptability of the strategy was only evaluated in those with positive results
• clinical and cost effectiveness compared with current practice was not addressed

As a result, the study did not alter the overall recommendation of the previous review.

Although the review of screening for FH in children aged between 1 and 2 was not brought forward, the evidence submitted was subsequently included in the 2019 evidence summary.

Prostate cancer

UK NSC decision: submission declined

Prostate cancer is already on the list of topics and was reviewed in 2016. The proposal is to add MRI as a risk refinement test following the identification of eligible men using a risk calculator. The risk calculator is based on the outcomes of the STHLM3 study. This study was considered in the last UK NSC review.

It is proposed further consideration of this approach should be deferred until the next review of prostate cancer screening. The proposed strategy should be considered in the scoping work at the beginning of the review project.

Anal cancer

UK NSC decision: submission declined

Anal cancer is already on the list of topics and is due for review in 2017 to 2018. A document is being prepared on whether the topic should be retained on the list. This is because the condition is confined to high risk groups and may not be within the remit of the UK NSC.

It is proposed that this topic should not be taken any further as it falls outside the UK NSC’s remit.