Newborn screening Dr Jim Bonham Clinical Director Sheffield Children’s NHS FT 1

Outline What is screening and why is it different? The organisation of screening MCAD deficiency Expanded newborn screening Outcome data Who chooses and why? What are the tasks ahead? What about other disorders and what about the future? What is the role of CLIMB? The IMD App 2

Why is it different? The patients/families believe themselves to be well and this gives us a particular burden of responsibility The initial test does not in itself give a definitive answer. It simply separates those who are more likely to have the condition (and require follow-up) from those who are less likely to have it “All screening programmes do harm; some do good as well, and, of these, some do more good than harm….” Gray, BMJ (2008) 336:480 3

How do we organise screening in the UK? It is organised and supported as part of the NHS There are 16 screening labs testing 30,000 – 130,000 babies per year Samples are collected at home by midwives on day 5-8 They are transported by mail to the laboratory Analysed on the following day Reported by post to Child Health Record departments Patient referrals made by the Lab to relevant physicians for treatment The process is governed by agreed national targets

The History of Newborn Screening in the UK PKU began in 1969, around 60 babies detected each year, would otherwise be severely mentally disabled, can develop normally on a low phenylalanine diet. A total of approximately 2300 detected so far. Annual cost of residential care would be £ 60m pa Annual cost of treatment + screening program = £8m Typically 60 cases per year detected in 750k annual births

So what about the other disorders? MCAD deficiency introduced in 2004 MCAD deficiency A life threatening condition Difficult to detect clinically Good screening test C8 Reliable confirmation in most cases Safe effective and simple treatment Approx 70 cases pa

What about other IMD’s ? A growing clinical recognition that early detection improves outcome in IMD’s The widespread international adoption of expanded newborn screening, with ten countries in Europe screening for ten or more disorders Concern to identify potential dysbenefits of screening for IMDs Funding from CLAHRC in 2008 for five years to implement research findings into widespread practice Selection of a limited number (five disorders) of conditions that appeared on most lists and gained a consensus within the UK: GA1, MSUD, IVA, Hcys, LCHADD 7

The consultation and the decision The responses Organisations Number Trusts 10 Professional groups 6 Parent groups 2 Overseas Individuals 1 Other - PHG, CRG All except one suggested all five should be included and the start date was 5th January 2015

2014-2016 data – 1.235m births Prevalence True positives Condition Prevalence True positives False positives PPV% Expected at outset Actual 14-16 data Expected MSUD 1:140k 1:176k 9 7 4 50 64 HCU 1:204k 1:308k 6 5 38 44 GA1 1:96k 1:309k 13 40 IVA 1:123k 1:137k 10 3+6 20 30 60 Total 1:27k 1:51k 24 39 21 53

2012-2016 data – Sensitivity - provisional Disorder Screen detected Prospective testing Clinically detected Sensitivity (%) MSUD 14 6 70 HCU 9 1 100 GA1 15 3 83 IVA 13 4

Who chooses and why? It varies in different countries In the USA it is the ACMG In many countries in Europe it is government working with health insurers and health professionals In the UK, the National Screening Committee advises ministers, there is a strong representation from Public Health Standards are set and monitored by Public Health England and the services are commissioned by NHS England So - how do they choose? the condition screened for should be an important one there should be an acceptable treatment for patients with the disease the facilities for diagnosis and treatment should be available there should be a recognised latent or early symptomatic stage there should be a suitable test or examination which has few false positives – specificity and few false negatives – sensitivity the test or examination should be acceptable to the population the cost, including diagnosis and subsequent treatment, should be economically balanced in relation to expenditure on medical care as a whole 11

The tasks ahead Gathering longer term data on progress Identifying the cases UKNSPC data collection MetBioNet data collection on clinically identified cases Involving the clinicians to make an assessment Reducing the side effects Preparing materials to support families with screen positive cases, the App that Oliver will talk about Getting communication and consent right before screening, recent HTA study, Fiona Ulph Organising referral in the best possible way, current HS&DR study, Jane Chudleigh Using IT to speed up the system The e-red book project 12

What about other disorders and the future ? Other disorders under consideration Severe Combined Immune Deficiency X-linked adrenoleukodystrophy Tyrosinaemia type 1 mucopolysacchariodoses Different approaches Using genetic techniques In addition to the current screening As an alternative Health Innovation Challenge Fund

Health Innovation Challenge Fund The role of CLIMB Helping to think about and design research questions Helping to design the research study Taking part in the research As subjects As researchers Funding research Helping in dissemination The current newborn App Researching the literature Networking with other patient groups and being the voice of the patient on committees Lobbying and working with the National Screening Committee Health Innovation Challenge Fund