MR1485 - Development of a linked, de-identified database resource for research into the health, mortality and educational outcomes of children with a congenital anomaly

The British and Irish Network of Congenital Anomaly Researchers (BINOCAR) is a collaboration of congenital anomaly registries which had been involved in the surveillance of congenital anomalies from as early as 1985 until 2015. This agreement seeks to create a linked de-identified research database through a one-off linkage of previously collected case data from five regional registers in England to subsets of Hospital Episode Statistics (HES) and civil registrations deaths. The historical BINOCAR data will also be independently linked to the National Pupil Database (NPD) under a separate data sharing agreement with the Department of Education (DfE) for a different study looking into educational outcomes associated with congenital anomalies. This will not involve the use of or linkage to NHS Digital data. However together these linked datasets will enable future, approved outcomes-research into the long-term survival, health and educational achievement of children with congenital anomalies to be conducted without the need or expense of re-linking the historical data. These proposed linkages are funded by a European Commission Horizon2020 project grant (EUROlinkCAT: Establishing a linked European Cohort of Children with Congenital Anomalies – grant reference 733001).

The legal basis for processing personal data for scientific research conducted in universities and NHS organisations fall under Article 6(1)(e), (“necessary for the performance of a task carried out in the public interest”) of the General Data Protection Regulation (GDPR). Additionally, Article 9(2)(j), (“necessary for archiving purposes in the public interest, scientific or historical research purposes”) provides the legal basis for processing special category data including clinical and health outcomes data; this project meets the requirement as it aims to examine the associations between congenital anomalies and outcomes such as infant and childhood mortality, frequency and duration of hospitalisation, diagnoses of chronic diseases and surgical interventions, whilst ethnicity, region and socio-economic indicators act as potential risk factors for health and survival. Only the minimum amount of data needed to fulfil research objectives will be processed and pseudonymised or anonymised data will be used wherever possible.

This one-time linkage of historically collected congenital anomaly registration data to HES data and civil registration deaths will create a valuable research dataset that can support the study of longer-term health and survival outcomes of children with congenital anomalies. The public benefit of this work will be helping parents understand the needs, prospects and life chances of their children. Additionally it will provide information to parents who may be considering termination of an pregnancy.

It will help optimise personalised care decisions during the school age and social support structures to ensure that children reach their full potential in society. Once the linked database has been created and validated, all personal identifiers including names, NHS numbers and addresses will be deleted to pseudonymise all records and prevent re-identification of individuals.

Congenital anomalies are developmental disorders of the embryo and foetus. Between 3-5% of babies born have a congenital anomaly; this equates to about 28,000 babies each year in England and Wales.

Following the thalidomide tragedy where thalidomide was prescribed to pregnant women for the treatment of morning sickness and proved to be a teratogen causing phocomelia (extreme limb reduction/absence defects), national surveillance of congenital anomalies was instituted in England and Wales. Regional Congenital Anomaly Registers (CARs) were established in different areas at different times across England and nationally in Wales. All had two main purposes: first, population surveillance of congenital anomalies and second, as a platform for research into the causes, consequences and management of congenital anomalies including evaluation of the newly emerging field of prenatal screening and diagnosis. The National Down Syndrome Cytogenetic Register (NDSCR), covering both England and Wales, was established in 1989 and has been used to evaluate many aspects of Down Syndrome and other common chromosomal disorders, but in particular the efficacy and impact of prenatal population screening for chromosomal disorders.

The British Isles Network of Congenital Anomaly Registers (BINOCAR) was established as a self-governing collaboration in the late 1990s to enable the regional registers to standardise the operations of the individual registers; establish an agreed dataset for collection; provide training and standardisation of anomaly data coding; apply as a group for research ethics and subsequently PIAG/NIGB/CAG approvals; develop information materials for patients and parents; work with relevant 3rd sector parent/patient representative organisations; and to conduct collaborative research by pooling data thereby maximising the number of cases of individual anomalies in any one study thus increasing the statistical power of any individual study given the relative rarity of both individual and groups of anomalies.

In 2010 BINOCAR was funded by the Department of Health to establish a hub at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, to enable pooling of de-identified regional data to provide the national anomaly surveillance function. In March 2015 Public Health England (PHE) transferred the existing regional register data and staff into a new national congenital anomaly registration system called “The National Congenital Anomaly and Rare Disease Registration Service” (NCARDRS) and the data collection function in the regional congenital anomalies registers ceased. NCARDRS does not have funding for research. Since the BINOCAR register leads are no longer responsible for congenital anomaly registration and surveillance from 1st April 2015 BINOCAR continued with a solely research role and re-adopted their own acronym to be the “British and Irish Network of Congenital Anomaly Researchers” (BINOCAR).

SGUL have received CAG approval (Ref: 19CAG0220) to hold named identifiable congenital anomaly information collected by the below-listed historical congenital anomaly registers until June 2021 to enable a one-off linkage to HES, Mortality and NPD datasets to create a de-identified BINOCAR Research Database (BINOCARD). Only substantive employees of the data controller and data processors named in this application will access BINOCARD for projects aiming to investigate the survival and physical health outcomes, receipt of health care, as well as the educational needs and achievements of children with congenital anomalies.

(Register--Organisations--Registry Lead--Start of Data Collection*)

1. Congenital Anomaly Register for Oxfordshire, Berkshire and Buckinghamshire (CAROBB)--University of Oxford--Prof Jenny Kurinczuk--1991

2. East Midlands and South Yorkshire Congenital Anomaly Register (EMSYCAR)--University of Leicester--Prof Elizabeth Draper--1997

3. South West Congenital Anomaly Register (SWCAR)--University Hospitals Bristol and Weston NHS Foundation Trust--Dr Karen Luyt--2002

4. Northern Congenital Abnormality Survey (NorCAS)--University of Newcastle Upon Tyne--Prof Judith Rankin--1985

5. Wessex Antenatally Detected Anomalies Register (WANDA)--University Hospital Southampton NHS Foundation Trust--Dr Diana Wellesley--1994

*all registers ended data collection on 31 March 2015

St George’s University of London (SGUL) is the project sponsor and data controller who also process data for the BINOCAR database and will act on behalf of all BINOCAR registers to coordinate the linkages, including consolidating the historical case data, transferring identifiers to NHS Digital for linkage and storing the final de-identified linked research database for future access. The above-named organisations are to be joint data processors for the project.

Each registry lead is a member of The BINOCAR Management Committee (BMC). The BMC also includes three representatives from: (1) a relevant patients’ organisation (Antenatal Results and Choices); (2) The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) at Public Health England. All research projects are subject to individual approval by SGUL with advice from the BMC. Full Terms of Reference for the BMC can be downloaded using this link: http://binocar.org/aboutus/managementcommittee

This agreement is for the creation of BINOCARD through a one-time linkage of historical BINOCAR congenital anomaly data to HES and Civil Registration Deaths data, and for BINOCARD. As two separate linkages are planned (HES and NPD), the cohort personal identifiers will be deleted when both linkages have been successfully completed and SGUL have received the linked data.

This agreement is also for SGUL to have the authority to approve requests from applicants who are substantive employees of the named Data Processors at the named data processing locations within this agreement for access to appropriately minimised subsets of HES and Civil Registration Deaths data linked to congenital anomaly data, for the purpose of conducting research into congenital anomalies (as evidenced by a study protocol with clearly defined objectives and methods). Some exemplars of such studies are given below. It is understood that for requests involving processing in other locations or by other organisations, the SGUL will not have the authority to approve such requests, and that the SGUL would need to request an amendment to the Data Sharing Agreement with NHS Digital and secure the latter’s approval to enable such sharing to take place.

The BMC is responsible (only SGUL will make decisions on how the data will be processed and other BMC members have an advisory role) for ensuring all research applications comply with ethical and legal requirements. It will review, monitor and audit applications to access BINOCARD data and the analyses subsequently carried out. For an application to gain approval applicants must:

1. Demonstrate the existence of underlying scientific merit and potential measurable benefits to health and social care in England.

2. Obtain approval (if required) from a formally constituted and recognised Ethics Committee.

3. Be carrying out research into congenital anomalies; using subsets of other variables in the dataset for research unrelated to congenital anomalies is prohibited.

4. Undertake that they will not make an attempt to deduce the identity of the individuals to which the BINOCARD data relate.

5. Have disclosure control measures in place to ensure that any reports of the findings do not make statements which may lead to individuals being identified.

There are currently 2 specific research projects planned, but it is envisaged that this resource will be used for other projects in the future. Brief descriptions of exemplars are given below:

Project 1: EUROlinkCAT - Establishing a linked European Cohort of Children with Congenital Anomalies (Duration: January 2017 – December 2021; Chief Investigator at St George’s University of London).

EUROlinkCAT is funded by Horizon 2020 to support 22 EUROCAT registries in 14 European countries to link their congenital anomaly data to mortality, hospital discharge, prescription and educational databases. The project is comprised of different work packages (sub-studies) which separately investigate topics in mortality, morbidity and education. Each registry will send standard aggregate tables and analytical results (e.g. regression coefficients) to a Central Results Repository (CRR), thus respecting data security issues surrounding sensitive data, as individual case data will not be transferred. SGUL is a participant in this research and it is planned that all tables and results will be derived directly from the linked BINOCARD data at SGUL, and then sent to the CRR at Ulster University. Tables/results from the European registries will be subsequently aggregated and used in meta-analyses, with appropriate suppression rules being applied prior to the publication of findings. Approximately 52,000 cases from BINOCARD will be analysed, consisting of livebirths with a congenital anomaly from 1995 to 2014, followed up for 10 years or until 2015, whichever is earlier. The variables to be linked to, by work packages, are:

1. Mortality variables – date of death, ICD codes for underlying cause of death, multiple causes of death, place of death

2. Morbidity variables – dates of hospital admission and discharge, diagnoses at discharge, dates/days in intensive care, dates/days on ventilator, codes for surgery

3. Risk factors (both studies) – gestational age, prenatal diagnoses of congenital anomaly, maternal age, ethnicity and socio-economic status (index of multiple deprivation).

Project 2: The impact of congenital anomalies on educational performance and future potential (Duration: November 2017 – February 2021; Chief Investigator at NorCAS, Newcastle University).

The overall aim of this project is to ascertain the educational attainment of children born with a congenital anomaly. The specific objectives are to: describe educational attainment by congenital anomaly group and sub-type; investigate if educational attainment has changed over time; investigate what factors influence educational attainment.

It is envisaged that analysis will be performed on the BINOCAR cases who can be successfully linked to the National Pupil Database by DfE. Their results will be compared with those of children from the background population of the same age and geographical regions; this comparison group will be provided by DfE.

In 2012, the BINOCAR registers together covered about 36% of the total births in England and Wales. Data collection began as early as 1985 in one register (NorCAS), and the number of cases reported increased progressively as more regional registers became established over time. The total cohort to be linked is estimated to be ~75,000 livebirths between 1985 and 2015. The follow-up period is until the latest available data year. The linkage of high-quality clinical registry data collected at birth to long-term survival, health and educational outcomes will constitute an invaluable research resource for enhancing our understanding of the development and needs of children with congenital anomalies throughout their lives.

Subsets of mortality and HES data are requested for linkage from 1997/98 (or earliest available) until the end of calendar year 2015. These will enable the investigation of health outcomes of babies with congenital anomalies as they reach adolescence and young adulthood. Longitudinal trends will be explored, particularly in survival rates and treatment outcomes, which are expected to have improved over time. Moreover, their association with major contributing factors could be ascertained – e.g., prenatal diagnoses, advances in surgical interventions, socioeconomic status, evolution of better support networks for parents/children etc. Project 2 will study the educational achievements and needs of children with congenital anomalies; this would require following them up for several years spanning key educational milestones, as their health and morbidity could be important risk factors for school performance.

The data requested are of individuals from the catchment areas of the five historical congenital anomaly registers. Only outcomes, events, clinical information and risk factors relevant for the evaluation of mortality and morbidity (hospitalisations, surgical interventions, days in intensive care or supported by ventilation) will be requested for linkage; organisational, administrative and systems data would generally be excluded. In order for the database to be utilisable for future research projects ranging over different topics, initial variable selection and data years requested have not been restricted to only those needed for the current exemplar projects; instead, the BMC will apply project-based minimisation filters to any future data releases similar to those illustrated above. For example, only births from 1995-2014 and outcomes until 31 December 2015 will be extracted for researchers to analyse in EUROlinkCAT, as per study inclusion criteria.

Only the data controller and data processors who are listed in this agreement will have access to the subsets of linked data.

The creation of BINOCARD will involve a one-off linkage of historical registry data to subsets of HES and Civil Registration Deaths and National Pupil Database (to be negotiated separately with Department for Education) datasets. Nonetheless, the scope for further linkages does exist, as the children whose records are contained in BINOCARD grow and develop. Subsequent phases will involve appending future outcomes to children born in more recent years, for whom follow-up data beyond infancy and early childhood are not presently available. This will increase the sample of cases available for evaluating long-term outcomes more accurately, such as estimating 20-year survival rates and teenage and adult morbidity. By periodically updating an already established cohort, the usefulness and quality of the dataset can be maximised; the completion of the aforementioned exemplar projects will provide further insights into the scope and timing of potential future linkages.

1. Data transfer and linkage to outcome data

Personal identifiers (NHS number, name, address, date of birth) and a pseudonymised register-specific identification number for each anomaly case will be transferred by SGUL to NHS Digital for data linkage (record-matching and Demographics extract). Clinical data and other demographic data relating to the anomalies will not be transferred for linkage purposes. NHS Digital will provide the Demographics extract for the cohort back to SGUL. The identifiable Demographics extract dataset will be used to help improve the linkage of the applicants cohort to the National Pupil Database. The Demographic data will not be used in the research element of this application or for contacting the cohort.

2. Linkage of outcomes to register clinical data at SGUL & validation checks

Once the outcomes linkage is complete the requested subsets of HES and mortality data will be transferred by NHS Digital to SGUL together with the register-specific identification number and HES pseudonymised record keys. CAG approval (Section 251 support) provides the legal basis for transfer of corrected/updated personal identifiers back to SGUL to ensure we hold correct cohort information. The outcome data will be merged with the congenital anomaly clinical data using the register-specific identification numbers (cases). Given that it will not be possible to directly validate the linkages the linkages will be “sense checked” using logical cross checks. For example, in general higher rates of admissions and mortality are seen in children with major anomalies compared with the rates in children with minor anomalies and control children and children with major chromosomal anomalies (e.g. Down Syndrome) in general have lower educational attainment compared with other children.

3. De-identification of the linked data: creation of a de-identified research resource for future congenital anomaly outcomes research

Once the linkages as described above have been carried out and the linked data have been “sense checked” as described, area based measures of deprivation will derived from the postcode information. Date of birth and date of death (as appropriate) will be used to create date independent variables, e.g. time from birth to hospital admission. The linked dataset will then be de-identified. This will be carried out by deleting the NHS number of child, name of child, date of birth of child, date of death of child (if relevant), NHS number of mother, name of mother, date of birth of mother, all known postcodes and addresses. Month and year of birth and death will be retained, as these are not regarded as identifiers and will enable the possibility of seasonal and temporal trends to be explored. Thus the linked, de-identified research database for congenital anomaly outcomes named BINOCARD will be created. Data processing will be carried out at the Population Health Research Institute within SGUL and by substantive employees of SGUL only. BINOCARD will be securely held at SGUL to enable research datasets, once approved, to be extracted in a standard format. Once the BINOCARD has been created SGUL and the regional registers will delete all identifiers from their source register data.

4. Use of the BINOCARD for research into long term outcomes associated with congenital anomalies

Applicants for the BINOCAR data must be substantive employees of one of the named Data Processors at a named data processing location. The BINOCAR management committee developed a series of standard operating procedures and application processes to enable receipt and assessment of applications for access to the register’s data for research purposes. Effectively the same application and assessment processes will be used to enable access by bona fide researchers to BINOCARD. All research projects wishing to use the data must have the relevant ethics approvals. The costs of producing the data may be charged to the researchers applying for the data; such charges will be kept to a minimum. All researchers requesting data will be required to confirm that their outputs will be only aggregate level data with small numbers suppressed in line with the HES analysis guide. Research staff (all of whom are substantive employees of SGUL) will assemble appropriately minimised subsets of the BINOCARD data for the approved research studies. The minimised data subsets will be securely transferred to the applicant’s approved data processing location, which will be one of the locations named in this Data Sharing Agreement (DSA). All data processor organisations will have a published Data Security and Protection Toolkit. Data will not be shared with other organisations or processed at other locations without an amendment to this DSA.

The BMC (only SGUL will make decisions on how the data will be processed and other BMC members have an advisory role) will review, monitor and audit applications with access to BINOCARD and the analyses subsequently carried out. At the completion of research projects, the applicants are responsible for securely destroying their copies of the data subsets from their data processing location (and providing confirmation to the BMC that they have done so); the original data subset created at SGUL will be archived for a period in line with the Data Sharing Agreement retention dates and then permanently destroyed, unless an application for extension is approved by NHS Digital.

The BINOCAR Management Committee will be responsible for providing an annual report of projects approved to use the data and updates on status of previous projects to NHS Digital.

5. Use of the database for proposed initial studies

There are currently two studies approved by the BINOCAR Management Committee:

Project 1: EUROlinkCAT: Establishing a linked European Cohort of Children with Congenital Anomalies. All analysis of individual case data will occur within SGUL by researchers who are substantive employees of SGUL as directed by Prof Morris. Only aggregate tables and analytical results (e.g. risk and odds ratios) will be released to Ulster University for inclusion in the Central Results Repository to be used subsequently in European meta-analyses.

Project 2: The impact of congenital anomalies on educational performance and future potential. Anonymised data on individual cases from the separate linked BINOCAR-NPD dataset will be released to Newcastle University for analysis by researchers. At the time of writing the study protocol it was thought possible that the separately linked HES/Mortality and NPD datasets could be combined at SGUL to enable study of the effect of health on educational outcomes. However, the team subsequently learnt that NPD data extracts can only be released to ONS secure labs for SGUL researchers to access. In consideration of the governance and logistical issues the creation of a combined health-education dataset would entail, it was decided that the education study will not involve any data provided by NHS Digital under this agreement. SGUL will attempt to link all congenital anomaly register cases to NPD (unless our own records show that they died before school age).

NHS Digital reminds all organisations party to this agreement of the need to comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: employees, agents and contractors of the Data Recipient who may have access to that data).

Data flowing to Ulster University for the wider EU project would be in aggregated form with small numbers suppressed in line with the HES analysis guide.

Only substantive employees of the Data Processors and Data Controller will have access to the data provided under, any change to this, would be subject to an amendment application submitted to NHS Digital.

The UK has one of the highest infant mortality rates (deaths in the first year after birth) in Europe. Congenital anomalies are the second commonest cause of deaths in the first month after birth (neonatal deaths) and the commonest cause of deaths from the end of the first month to the end of the first year after birth (postneonatal deaths). The capacity to conduct robust research is critical to improving the understanding of, and developing preventive measures to reduce, infant mortality rates.

The goal of creating the research database is to enable research to improve the knowledge and understanding of the consequences, and health and developmental outcomes for children born with a congenital anomaly (or anomalies). The importance of doing so is in order to: provide information to support parents in any decision making regarding the prevention of congenital anomalies; to improve treatment and thus the survival of children with anomalies; and to provide appropriate services to support their physical, medical and developmental needs, including educational needs which are integral to child development. The purpose of the creation of the research database, to which bonafide researchers will be able apply for data, is to enable the wider use of congenital anomaly data, collected over many years, to the maximum benefit of children and adults affected by congenital anomalies and their parents.

The primary output of the linkage is the creation of a research resource to be used for research projects aiming to investigate the survival, physical health outcomes and receipt of healthcare, as well as educational needs and achievements of children with congenital anomalies. Such research is expected to be submitted for publication in peer-reviewed journals and other standard routes of academic dissemination (e.g. conference presentations).

The data being requested will only be used for the purpose described. All secondary outputs will only include aggregated data with small numbers suppressed in line with the HES analysis guide. BINOCAR expects that around three research papers would be published per year using data from the database created through the proposed data linkages. Examples of planned publications in current projects include:

Project 1: EUROlinkCAT: Establishing a linked European Cohort of Children with Congenital Anomalies (Chief Investigator at St George’s University of London).

EUROlinkCAT is funded by Horizon 2020 to support 22 EUROCAT registries in 14 European countries to link their congenital anomaly data to mortality, hospital discharge, prescription and educational databases. Each registry will send standard aggregate tables and analysis results to a Central Results Repository (CRR) at Ulster University. SGUL is a participant in this research and it is planned that all aggregate tables and analyses on the historical BINOCAR cases will be obtained directly from the linked, de-identified research database at SGUL. Over 15 peer reviewed papers are planned before 2022. These include papers on ‘survival and risk factors for survival in children born with a congenital anomaly’, ‘hospitalisations and surgery during the first 5 years of life for children born with a congenital anomaly’ and ‘is there a relationship between prenatal diagnosis of congenital anomalies and lower morbidity?’, to name a few. Publication in peer-reviewed journals is planned to take place between June 2020 and December 2021.

For a full list of publications that have used data from the BINOCAR registries please see the BINOCAR website: http://binocar.org/ourresearch/papers. The EUROCAT website also includes relevant BINOCAR publications: http://www.eurocat-network.eu/aboutus/publications/publications. Often general medical and/or public health journals with a broad audience have been chosen, but for certain papers specialist genetic or paediatric journals have been more appropriate. Dissemination at national and international conferences will adopt a similar strategy of aiming for as broad a reach as possible.

A recent study (Morris JK , Rankin J, Draper ES, Kurinczuk JJ, Springett A, Tucker D, Wellesley D, Wreyford B, Wald NJ. Prevention of neural tube defects in the UK: a missed opportunity. Arch Dis Child. 2016;101:604-7) highlighted the lack of fortification of food with folic acid in the UK, which evoked some media interest including a brief interview in the BBC News.

In addition to these traditional routes of academic dissemination, the BINOCAR registries, as part of the EUROlinkCAT project, will be investigating using social media to involve parents of children with congenital anomalies in determining the research priorities of EUROlinkCAT and also in disseminating the results to parents. Any relevant findings from the EUROlinkCAT project will be made available to applicants using the BINOCARD data to help enhance their analysis strategy and interpretation of results.

Project 2: The impact of congenital anomalies on educational performance and future potential (Chief Investigator at NorCAS, Newcastle University).

The aim of this project is to ascertain the educational attainment of children born with a congenital anomaly. Papers are planned in order to investigate: (i) Describing the educational attainment by congenital anomaly group and sub-type; (ii) Investigating if educational attainment has changed over time and (iii) Investigate what factors influence educational attainment. The target for completion and submission for peer-review is January 2021 (subject to timelines for linkage to NPD data).

The unique linked de-identified database (BINOCARD) will be a valuable resource for research into the health, mortality and educational outcomes associated with congenital anomalies. It will be available to authorised researchers as soon as the linkage is completed. Below are the expected measurable benefits from the planned projects as examples of the measurable benefits which will be derived from the creation of BINOCARD; more projects will follow as present findings generate new hypotheses for future studies.

The public benefit of this work will be helping parents understand the needs, prospects and life chances of their children. Additionally it will provide information to parents who may be considering termination of a pregnancy.

Benefits from Project 1: EUROlinkCAT: Establishing a linked European Cohort of Children with Congenital Anomalies.

Participating in the EUROlinkCAT project provides the unique opportunity to collaborate with European researchers to:

• Identify potentially preventable and remedial causes and to understand the source of the variations in child death rates between the UK and the rest of Europe.

• Enable reliable information on rare anomalies and syndromes to be obtained.

• Enable results to be generalisable across Europe.

• Establish a method of standardisation of clinical and healthcare data across Europe that can be utilised for future research.

• Demonstrate that pan-European analysis of sensitive information can be performed safely.

Some of the benefits, such as development of standardisation methods, will be realised alongside the project’s execution. Findings and recommendations on the long-term survival and health outcomes associated with different congenital anomalies will be disseminated to academics, clinicians, policy-makers and the wider public; potential impact and benefits are expected to occur within 1-5 years after the end of the project.

Benefits from Project 2: The impact of congenital anomalies on educational performance and future potential

As the proportion of children born with a congenital anomaly surviving beyond infancy is increasing, how these children are performing in school is becoming increasingly important; there may be a growing population of children and young people with continuing special needs which are not being met. Local authorities need reliable data to be able to accurately predict the future need for education support for children born with a range of congenital anomalies. Increasing our understanding of educational attainment of children born with a congenital anomaly, as well as what factors influence attainment, has the potential to improve surveillance of this group of children. This could lead to the development of early intervention strategies which would have substantial positive effects on the children and young people’s health and wellbeing. It is hoped that the study’s findings and recommendations will contribute towards policy-changes within 2-4 years of publication.

Yielded Benefits is not a requirement for new applications.