Newborn Screening Programmes in the United Kingdom This paper has been developed to increase awareness with Ministers, Members of Parliament and the Department of Health of the issues surrounding the serious lack of funding for all the necessary work including research, literature review, economic evaluation and pilot studies, which is preventing NHS England and Public Health England timously adding appropriate disorders onto the UK newborn screening programme. We are asking Government Ministers, Members of Parliament and the Department of Health to consider the issues and recommendations outlined in this paper, with a view to requesting and supporting discussions between the Department of Health, NHS England, Public Health England and the National Institute for Health Research (NIHR) on how these issues can be addressed. There are currently a number of disorders that are being considered by the UK National Screening Committee (UK NSC) and some appropriate disorders waiting in line which are not being progressed due to these challenges. This has a direct impact on our ability to save children's lives. 1. Background to Newborn Screening in the United Kingdom In the United Kingdom (UK) we screen newborn babies for 9 congenital disorders. Screening newborns in the UK commenced with PKU in 1969. The most recent group of 4 disorders was added to the programme in England in early 2015. Early identification of babies at risk from rare disorders can offer the opportunity of immediate life saving or life enhancing treatment. Without early identification and treatment, children with inherited disorders will lead a life of disability or may die. It is a hard fact that many children in the UK do die from conditions that are not diagnosed sufficiently early. The UK Rare Disease Strategy also outlines the importance of early diagnosis for those who will subsequently present with rare disorders in early adulthood or later in life. Early identification of rare disorders can subsequently reduce costs to the NHS. Many other countries screen for more disorders than we do in the United Kingdom. Developments in medicines and new therapies enables the treatment of newborns with inherited disorders more viable. However accepting new disorders onto the UK newborn screening programme unfortunately remains a very lengthy process. In the UK we have added only 8 additional disorders to the programme since 1969. It took over 5 years to get the latest 4 disorders added to the UK programme in 2015. A comparative table of the screening position in Europe as at 2015 is attached at Annex 1. Public Health England, the UK National Screening Committee (UK NSC) and NHS England, along with most countries, have accepted the World Health Organization (WHO) criteria for determining whether a condition is suitable for adding onto the UK Newborn Screening programme. The list of criteria is outlined at the end of this document at Annex.2 The issues and recommendations contained in this paper are a result of conferences and meetings held during 2016 between the UK Patient Advocates for Newborn Screening Collaborative Group, clinicians, scientists, UK NSC representatives and other patient organisations, to address the challenges in securing more appropriate disorders onto the UK newborn screening programme. 1
2. UK National Screening Committee Quality Improvements During 2014, the House of Commons, Parliamentary Science and Technology Committee conducted an inquiry into health screening in the UK. Following a wide consultation exercise, including verbal submissions, a number of recommendations were made. In response to these recommendations, Public Health England and the UK NSC have made some quality improvements. Improvements include the development of new guidance for those proposing new disorders, the introduction of an annual stakeholder conference and, from September 2016, an annual open call for proposals for suitable new disorders to be considered for inclusion in the UK newborn screening programme. Anyone can submit a proposal to the UK NSC, although understandably it is unlikely to succeed without the support of expert health professionals with a knowledge of the particular disorder or group of disorders. The UK NSC has also introduced a more robust process for reviewing conditions that have previously been considered and rejected. 3. Meeting the criteria for disorders in the UK In order to meet the criteria for acceptance of a disorder onto the UK newborn screening programme and in considering a disorder, there are some key areas of work that do need to be commissioned by NHS England or Public Health England, UKNSC: Commissioning work to review the evidence presented by those submitting proposals. Also to support those submitting proposals throughout the process. Where the evidence is not available or appears insufficiently robust for the UK to identify the research questions, to commission the necessary research required to secure the required evidence or to communicate research priorities to the NIHR so it can be considered and prioritised. To undertake the necessary economic evaluation to ensure that evidence on the cost benefit and/or cost effectiveness analyses of newborn screening for a disorder has been balanced, i.e. at a reasonable cost and in relation to expenditure on medical care as a whole. This should incorporate both medical and social economic evaluation. When good quality evidence exists, to introduce pilot programmes to ensure all the newborn screening process works together. This is to ensure that all the required criteria in respect of the robustness of the test, the wider benefits of screening, the effectiveness of the screening, that screening brings positive health outcomes and the acceptability of the screening to both public and health professionals, can be determined prior to the introduction of a National screening programme. Pilot programmes are therefore crucial when introducing new disorders onto a newborn screening programme. 2
4. Financial and Funding Issues There are a number of financial issues that are creating a significant barrier to the consideration of new and appropriate disorders being submitted for inclusion in the UK newborn screening programme. There are complexities and concerns around the interpretation by NHS England, Public Health England and the National Institute for Health Research (NIHR) of what is 'research' and what is the 'implementation' component when considering a newborn screening pilot study. These definitions do impact how newborn screening pilot studies are funded. Although 'research' components of a pilot programme may be funded, the 'implementation' aspects of a pilot programme are considered not to be 'research'. Therefore those funding streams for research projects are not considered to be available for the 'implementation' elements of newborn screening pilots. It remains unclear what exactly the NIHR will fund and where the funding streams are to provide for the rest of the work. You will appreciate that this is certainly creating some confusion, particularly as we understand that in other areas of health the NIHR does fund 'implementation'. There is consequently a lack of clarity on who is responsible within the Department of Health for funding all the necessary work, including economic evaluation and the necessary pilot programme work. There is no tariff for newborn screening and no ring-fenced funding. There is no sense of direction on where the funding streams actually sit to move forward necessary work on newly proposed conditions. We also understand that some previously utilised funding streams for newborn screening are unavailable. We are unclear as to whether this is because newborn pilot implementation studies are not considered 'research'. Examples are the National Institute for Health Research schemes; the Collaboration for Leadership in Applied Health Research and Care (CLHARC) and Research for Patient Benefit (RfpB). Some funding streams, their scope and whether these could be utilised for newborn screening are outlined at Annex 3. Clarification is particularly critical for patients and patient organisations who are proposing new appropriate disorders for screening. It will inform what funding is available for all work, where there is a lack of funding within Public Health England or NHS England and inform whether there is a funding gap that needs to be filled from other sources. The burden of undertaking the required economic evaluation to support a proposal for newborn screening is currently resting with the proposer, i.e. the patient organisation or the charity who can ill afford what is a significant cost. Research based projects require a higher level of consent on part of participating subjects which in reality would add additional costs. In addition there are costs associated with ethical issues in consideration of appropriateness of newborn screening programmes. Recommendation 1: There needs to be in place greater clarity in definitions of all the component parts of the work required within the process of proposing and securing a new disorder onto the 3
UK NBS programme. There should be clarity and guidance for the proposer and other stakeholders on where the funding streams are to support each of these parts of the process. Recommendation 2: Economic evaluation should be considered to be a research question and funding for this work should within NHS England, NIHR which is the research evaluation arm of the NHS and not with proposers who are generally patient organisations supported by clinical and scientific experts. 5. Responsibilities and Guidance There is some confusion within the process on who is responsible i.e. Public Health England or NHS England, for commissioning the necessary work required, including from the National Institute for Health Research (NIHR) or elsewhere. We understand that the NIHR has competing priorities and do not have sufficient funding to do all of the NHS projects that are required. We accept that prioritisation in health is required, however there is a danger that newborn screening programmes may not being given the necessary priority. The UK Strategy for Rare Diseases in England, published in 2013 and to be implemented by 2020, contains a recommendation under 'Identifying and preventing rare diseases', that the Department of Health will continue to work with the UKNSC to ensure that the potential role of screening in achieving earlier diagnosis is appropriately considered in the assessment of all potential new national screening programmes and proposed extensions to existing programmes. Recommendation 3: The issues raised in this paper in relation to clarification and funding is a barrier to implementing the UK Strategy for Rare Diseases and therefore needs to be addressed as a matter of urgency. Stakeholders would welcome improved support and guidance when making new proposals to the UK NSC. However Public Health England (UKNSC) appear not have sufficient resources to do more to engage with, assist and support those proposing new conditions. This engagement and support becomes even more important in light of annual calls for proposals. There should be greater clarity on what support UK NSC are able to offer those submitting proposals. Recommendation 4: The UK NSC Programme Director should be sufficiently resourced to deliver necessary guidance and support services to proposers throughout the process as defined by Public Health England. This will enable them to be in a position to work alongside those proposing disorders for the newborn screening programme, ensuring that all considerations are met and work done in a collaborative manner. 6. The unreasonable burden on patients and organizations representing patients In light of the funding issues outlined, an increased burden is being put on patients and particularly organisations representing patients to secure money to commission the work that the NHS England 4
and Public Health England is responsible for. In some instances funding is being secured from overseas or from their own members. A recent quote to a UK patient organisation from an appropriate UK research institution to do the necessary economic evaluation work for newborn screening for a disorder affecting UK children is between 60,000 and 90,000. Patient organisations should not be 'propping up' the NHS where proposals for new disorders are being submitted. This is wholly unacceptable This situation can also present inequitable treatment for children affected by different rare conditions. A larger and better resourced patient organisation with access to international funding can sometimes find a way to financially support the commissioning of the necessary work required to move forward a proposal to the UK National Screening Committee. Others who cannot access the same funding sources are unable to progress their proposal for newborn screening. Recommendation 5: Department of Health, NHS England and Public Health England to issue clear guidelines on how screening research is funded. To publish clear avenues for funding that proposers might consider when considering submitting a proposal. Public Health England and NHS England to give clarity on what a proposer might anticipate having to fund themselves as part of the process and offer guidance on what institutions or research establishments within the UK that proposers might approach. Recommendation 6: Although we welcome the introduction of the Annual Stakeholder Conference this conference covers stakeholders from every area of public health screening in the UK. It is not sufficiently focused on or engaged with newborn screening, including engagement with stakeholders with, or representing those, with the rare disorders. We suggest that a separate dialogue and conference should be introduced for newborn screening stakeholders. Patricia A Roberts Chair of the UK Patient Advocates for Newborn Screening Group (PANS) and Director of Save Babies Through Screening Foundation UK. 30th January 2017 This paper is submitted on behalf of the PANS Group and has the support of the British Inherited Metabolic Disease Group (BIMDG). The PANS Group is a collaborative of rare disease patient organisations, all with an interest in advocating for the extension of the newborn screening programme in the UK for appropriate disorders, i.e.(agsd UK, Save Babies UK, Children Living with Inherited Metabolic Disorders (Climb), ALD Life, the MPS Society, Archangel Trust. The group is supported by relevant scientists and other health professionals. 5
Annex 1 Table of the position Newborn screening position in Europe has been taken from the report 'Current Status of Newborn Screening worldwide 2015. https://www.ncbi.nlm.nih.gov/pubmed/25979780 6
Annex 2 The screening criteria is outlined below and can be accessed at the GOV.UK website. at https://www.gov.uk/government/publications/evidence-review-criteria-national-screeningprogrammes/criteria-for-appraising-the-viability-effectiveness-and-appropriateness-of-a-screeningprogramme. Criteria for appraising the viability, effectiveness and appropriateness of a screening programme. 1.The condition 1. The condition should be an important health problem as judged by its frequency and/or severity. The epidemiology, incidence, prevalence and natural history of the condition should be understood, including development from latent to declared disease and/or there should be robust evidence about the association between the risk or disease marker and serious or treatable disease. 2. All the cost-effective primary prevention interventions should have been implemented as far as practicable. 3. If the carriers of a mutation are identified as a result of screening the natural history of people with this status should be understood, including the psychological implications. 2.The test 4. There should be a simple, safe, precise and validated screening test. 5. The distribution of test values in the target population should be known and a suitable cut-off level defined and agreed. 6. The test, from sample collection to delivery of results, should be acceptable to the target population. 7. There should be an agreed policy on the further diagnostic investigation of individuals with a positive test result and on the choices available to those individuals. 8. If the test is for a particular mutation or set of genetic variants the method for their selection and the means through which these will be kept under review in the programme should be clearly set out. 3.The intervention 9. There should be an effective intervention for patients identified through screening, with evidence that intervention at a pre-symptomatic phase leads to better outcomes for the screened individual compared with usual care. Evidence relating to wider benefits of screening, for example those relating to family members, should be taken into account where available. However, where there is no prospect of benefit for the individual screened then the screening programme shouldn t be further considered. 7
10. There should be agreed evidence based policies covering which individuals should be offered interventions and the appropriate intervention to be offered. 4.The screening programme 11. There should be evidence from high quality randomised controlled trials that the screening programme is effective in reducing mortality or morbidity. Where screening is aimed solely at providing information to allow the person being screened to make an informed choice (such as Down s syndrome or cystic fibrosis carrier screening), there must be evidence from high quality trials that the test accurately measures risk. The information that is provided about the test and its outcome must be of value and readily understood by the individual being screened. 12. There should be evidence that the complete screening programme (test, diagnostic procedures, treatment/ intervention) is clinically, socially and ethically acceptable to health professionals and the public. 13. The benefit gained by individuals from the screening programme should outweigh any harms for example from over diagnosis, overtreatment, false positives, false reassurance, uncertain findings and complications. 14. The opportunity cost of the screening programme (including testing, diagnosis and treatment, administration, training and quality assurance) should be economically balanced in relation to expenditure on medical care as a whole (value for money). Assessment against this criteria should have regard to evidence from cost benefit and/or cost effectiveness analyses and have regard to the effective use of available resource. 5.Implementation criteria 15. Clinical management of the condition and patient outcomes should be optimised in all health care providers prior to participation in a screening programme. 16. All other options for managing the condition should have been considered (such as improving treatment or providing other services), to ensure that no more cost effective intervention could be introduced or current interventions increased within the resources available. 17. There should be a plan for managing and monitoring the screening programme and an agreed set of quality assurance standards. 18. Adequate staffing and facilities for testing, diagnosis, treatment and programme management should be available prior to the commencement of the screening programme. 19. Evidence-based information, explaining the purpose and potential consequences of screening, investigation and preventative intervention or treatment, should be made available to potential participants to assist them in making an informed choice. 20. Public pressure for widening the eligibility criteria for reducing the screening interval, and for increasing the sensitivity of the testing process, should be anticipated. Decisions about these parameters should be scientifically justifiable to the public. 8
Annex 3: Funding streams within NHS England which could support Newborn Screening introduction: (Information current as at January 2017). Funding Source Type of Funding What it covers Can NBS work fit within this initiative or has this funding stream supported NBS initiatives in the past National Institute for Health Research NIHR Health Technology Assessment Programme HTA The HTA Programme is the largest of the NIHR programmes. HTA will fund independent research about the effectiveness, costs and broader impact of healthcare treatments and tests for those who plan, provide or receive care in the NHS. We fund our studies via a number of routes including commissioned and researcher led work streams. http://www.nets.nihr.ac.uk/programmes /hta The HTA Programme funds research about the clinical and cost effectiveness and broader impact of healthcare treatments and tests for those who plan, provide or receive care in the NHS. HTA research is undertaken where some evidence already exists to show that a technology can be effective and this needs to be compared to the current standard NHS intervention to see which works best. The term health technology can cover any intervention used in the treatment, prevention or diagnosis of disease. This could mean research evaluating for example, devices, procedures, drugs, settings of care or screening, provided the study outcomes lead to findings that have the potential to be of direct benefit to NHS patients.the HTA Programme has two main work streams: researcherled and commissioned. The researcher-led work stream, Clinical Evaluation and Trials (CET), offers researchers the opportunity to submit proposals on topics or research questions within the programme s remit. There are three cut-off dates a year when applications will be considered. YES. This funding stream is relevant to newborn screening. 9 The commissioned work stream invites applications in
EME Efficacy and Mechanisms Evaluation (EME) response to calls for research on specific questions which have been identified and prioritised for their importance to the NHS and patients. Proposals may include primary research, evidence synthesis, or feasibility and pilot studies. The programme supports clinical trials and evaluative studies in patients which evaluate clinical efficacy of interventions where proof of concept in humans has already been achieved, add significantly to our understanding of biological or behavioural mechanisms and processes, or explore new scientific or clinical principles; and include the development or testing of new methodologies. This can be used to fund research on new diagnostic tests or new treatments for a disorder. It is generally for the research stage before the HTA. There are two work streams, researcher-led and commissioned. Both work streams fund large projects with clear stages and milestones. Proposals may include pilot and feasibility studies and late development of technologies. The programme welcomes collaborations with industry and charities. RfPB Research for Patient Benefit (RfPB) The Research for Patient Benefit Programme (RfPB) funds NHS research covering a wide range of health service challenges. The aim of the programme is to fund topics and research methodologies that increase the effectiveness of NHS services, provide value for money and benefit patients. Research topics for funding are researcher-led. YES. This funding source is relevant to newborn screening and it has been used in the past. The projects funded are for regionally-derived applied research in health services and social care. The programme s strong regional element is unique within the NIHR s research programmes. 10
Applicants need to demonstrate the regional benefits of the proposed research, although studies with national benefit will also be considered. Members of the regional panels, including members of the public and service users, that assess the applications are drawn from local academic institutions and health organisations. All researchers in the NHS in England can apply, and joint applications with academic partners are encouraged. RfPB funds up to 350,000 per project for up to 36 months in duration. The programme supports: studies of the provision and use of NHS services evaluations of the effectiveness and cost effectiveness of interventions examination of the resource utilisation of alternative means for healthcare delivery scrutinising innovations and developments feasibility studies to help reach the next step of a definitive trial. CLHARC Collaboration for Leadership in Applied Health Research and Care (CLHARC) Collaborations for Leadership in Applied Health Research and Care (CLAHRCs) are funded by the National Institute for Health Research and undertake high-quality applied health research focused on the needs of patients and support the translation of research evidence into YES. This funding source is relevant to newborn screening and has been used in the past. 11
practice in the NHS. PGfAR Programme Grants for Applied Research (PGfAR) CLAHRCs are collaborative partnerships between a university and the surrounding NHS organisations, focused on improving patient outcomes through the conduct and application of applied health research. They create and embed approaches to research and its dissemination that are specifically designed to take account of the way that health care is increasingly delivered across sectors and a wide geographical area. There are currently 13 CLHARC's in the UK. Programme Grants for Applied Research (PGfAR) fund research studies requiring a multidisciplinary approach that will have practical application for the benefit of patients and the NHS, typically through improved healthcare or better healthcare delivery in the relatively near future (within three to five years of a programme s end). Topics for funding are researcher-led and particular emphasis is given to conditions causing significant disease burden. The programmes funded are interrelated research projects requiring input from, for example, clinical, health economics, statistics, qualitative and behavioural sciences backgrounds to ensure that research objectives can be met. This is as relevant as RfPB. If a number of pieces of screening evidence need generating around a single condition, the PGfAR would be a good vehicle. This is providing we can achieve the answers to our research questions within the 2+ million limit. The programme supports applied health research (including health services research), public health research, behavioural research, economic evaluations and 12
modelling. Applicants should be balanced teams of leading researchers from the NHS and academia working together, who can demonstrate an impressive track record of achievement in applied health research. SR Programme Systematic Reviews (SR) Programme The amount awarded and the length of the funding period depends on the nature of the proposed work, in particular whether or not the proposal includes a substantial powered trial, although funding in excess of 2.5m over more than six years will be unusual. The Systematic Reviews Programme consists of a number of initiatives including the Cochrane Review Groups, the UK Cochrane Centre and the Health Technology Assessment Reviews, which provide high-quality research evidence to support decision-making. Systematic reviews identify, evaluate, combine and summarise the findings of all relevant individual studies, to provide decision makers with the best possible information about the effects of tests, treatments and other interventions used in health and social care. This funding stream is relevant to newborn screening. There will be questions around a treatment, test or disease prevalence that may be answered by a systematic review. The SR Programme supports the production and updates of systematic reviews both by core infrastructure funding and open competition via two funding streams: the Cochrane Collaborations Programme Grant Scheme and the Cochrane Incentive Awards. The Cochrane Collaborations Programme Grant Scheme supports high quality systematic reviews that are of direct benefit to users of the NHS in England. This call runs every 13
three years. The Cochrane Incentive Awards are available to Cochrane Review Groups to facilitate, and possibly accelerate, activity that is already planned or is underway. This call runs annually. PHR Programme Public Health Research Programme The PHR Programme funds research that evaluates public health interventions, providing new knowledge on the benefits, costs, acceptability and wider impacts of non-nhs interventions intended to improve the health of the public and reduce inequalities in health. The scope of the PHR Programme is multidisciplinary and broad, covering a range of public health interventions. Examples include examining whether regeneration programmes improve public health and reduce health inequalities, evaluating employer schemes to encourage walking or cycling to work and assessing interventions that encourage healthy eating among school children. This funding stream has been included for completeness however we are not certain if it is relevant to newborn screening research or pilot studies. Even though screening is a public health activity, the presence or absence of the condition we are looking to consider may not have a wide public health impact in the same way as e.g. cancer screening programmes. 14