Using National Congenital Heart Diseases Audit data to explore the impact of non-medical risk factors on late post-operative outcomes for children with complex congenital heart defects.

University College London (UCL) requires pseudonymised data of life status and age at life status for use in a new study that uses National Congenital Heart Diseases Audit (NCHDA) data, to explore the impact of nonmedical risk factors on late, post-operative outcomes for children with complex congenital heart defects. This research is referred to as the Long Term Outcome (LTO) project.

UCL are the sole data controller who also process the data.

Operative mortality for paediatric cardiac surgery represents the predominant outcome measure for service evaluations and registry-based research. This is now very low (2.5%) in the UK despite an increasingly large and complex congenital heart disease (CHD) population, which undermines its relevance as an outcome measure. Late mortalities occur in CHD, particularly during infancy and in complex conditions that require a series of operations and life-long multi-disciplinary care. However, these later events such as deaths and unplanned re operations are not currently analysed and reported given there is focus on early 30-day mortality rates post-operations. This situation needs to change and move forwards.

Population based studies of longer-term CHD outcomes are scarce and single centre or historic data lack relevance given the rapid evolutions in management. Apart from pilot work undertaken by the research group, there are no recent population-based analyses of longer-term outcome for complex CHDs from the UK.

Using routinely collected National Congenital Heart Diseases Audit (NCHDA) data representing procedures undertaken in the last 18 years, the proposed research will characterise longer-term outcome, in terms of survival and re-interventions, for selected individual complex CHDs.

For individual, complex CHDs, the research will then use survival models to explore the relationship between the longer-term outcomes of survival and unintended re-operations, and key non-medical risk factors of ethnic group and socio-economic deprivation, as well as the key service delivery factors of centre case volume and access to antenatal diagnosis. A greater understanding of these issues is required in order to leverage future care improvements for this growing population of children and young people with complex health needs.

The proposed research will use survival models to explore whether children from minority communities or deprived backgrounds experience worse outcomes than other children. This is important to understand since both children from a South Asian background and those living in addresses represented by the most deprived quintile are overrepresented amongst congenital heart patients. Further, the research intends to explore whether service provision in terms of antenatal diagnosis and case volume within children’s specialist cardiac centres (hospitals) are linked to improvements in these specified outcomes for complex congenital heart conditions.

The activity is compliant with the principles of General Data Protection Regulations (GDPR). Based on guidance, as this is for University research, the lawful basis for processing data is GDPR article 6(1)(e): Processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller, also referred to as Public Task. As the research involves health data, which is included in the definition of special categories of personal data, it requires an additional condition for processing. Based on guidance, for health research this is GDPR article 9(2)(j), which details that processing is necessary for scientific and research purposes, subject to appropriate safeguards.

At the time of planning this research study and applying for ethical and CAG approval, it was estimated that there would be around 120,000 records of procedures involved in the study. As analysis of the NCHDA data has commenced related to procedures that meet the inclusion criteria, it has been ascertained that the total number is 155,281 records corresponding to procedures between 1 April 2000 and 31 March, 2018, and these procedures are recorded for 102,056 individual patients. These figures might change slightly over the course of the analyses, as a small number could be of poor data quality and cannot be used.

To minimise data use, included will be patients who have had at least one intervention for congenital heart disease that has generated at least one entry in NCHDA after a first appearance in the dataset after the year 2000, with final data capture in 2018 according to UCL's agreement held with the Health Quality Improvement Partnership (HQIP) for the NCHDA dataset (the most recent data available). The year 2000 is the first year in which capture of interventions was reliably undertaken by NCHDA (as known from previous research on data quality and capture). Therefore, the study will capture interventions and outcomes between infancy with a maximum span of up to 18 years of age. Although limited to capturing interventions and outcomes for patients when they are babies, children, and young people, this still goes much further than any previous studies and provides much more insight than what is offered at present which is up to 30 days post operation. National data is required to enable a population-based analysis that will be more generalised to future patients in any of the UK's heart centres.

The study research dataset will be generated by linking pseudonymised NCHDA data (English and Welsh centres) to the Death registrations (Civil Registration, Deaths). UCL has received authorisation from HQIP to transfer personal identifiers (from patients of English and Welsh centres) from NICOR (which collects the NCHDA dataset) to NHS England. UCL has received authorisation from HQIP to receive the pseudonymised clinical information at University College London, from NHS England. UCL has Ethics (18/LO/1688) and CAG (18/CAG/0184) approval for the study to process the data and to link the datasets.

The final pseudonymised dataset containing record level clinical data from NCHDA and life status information from NHS England will be stored within UCL's secure data safe haven.

Amazon Web Services (AWS) is a processor acting under the instructions of UCL. AWS’ role is limited to secure back-up of data stored in UCL’s Data Safe Haven. UCL uses offsite data centre services provided by VIRTUS data centre. VIRTUS does not have access to the data.

Receiving the data about civil registration deaths is vital for this study, providing insight about which patients have died later on after they were discharged home following an operation. This unfortunately can happen, and it will not be possible to work out accurate survival figures for the different types of complex CHD without taking these later deaths into account.

The LTO study was instigated and is led by the Principal Investigator based at the Institute of Cardiovascular Science at UCL and co investigators at the Clinical Operational Research Unit (CORU) at UCL. University College London will be the only organisation to require access to the record level data supplied from NHS England.

The principal investigator of the study is an employee of Great Ormond Street Hospital (GOSH) and holds an honorary contract with UCL as associate professor: they will be working on this study entirely within their UCL role.

This is a standalone study funded by the British Heart Foundation and this study commenced in July 2019. The sole funder, The British Heart Foundation, are involved in the study only to provide the award, as grant-funding. They will also oversee progress of the project through annual reports and award meetings. The British Heart Foundation have no ability to suppress any of the study findings or the outputs produced. They are not permitted to access any record level NHS England data.

The Long-Term Outcome project has the necessary research ethics and section 251 approvals. A favourable opinion has been obtained from a Research Ethics Committee, reference number (18/LO/1688). Section 251 support has been received to ensure that the accessing, linking, and processing of the datasets is in line with the common law duty of confidence (Ref:18/CAG/0184). Data will not be handled by any additional third-party organisations. Data will not be accessed outside England and Wales.

Patient identifiers, as approved by the Confidentiality Advisory Group (CAG), will be sent to NHS England from the NCHDA database (NHS number, hospital ID, date of birth, ethnicity, and postcode). UCL are requesting that NHS England match the identifiers from the NCHDA dataset to Civil Registration Deaths and extract the requested fields. NCHDA will provide a record level LTO ID which should be transferred to each pseudonymised Civil Registration Deaths record that matches. UCL are requesting that NHS England includes the study patient’s age at death where any patient has died. For cohort patients that are alive, UCL are requesting that NHS England lists these as ‘alive’ and records the study patient’s age at the time of verifying their life status as alive.

The reason that age at life status (whether living or deceased) is required is to fulfil the main objective of assessing long-term survival in children who were born with complex heart disease. To assess long-term survival, the method of analysis employed is called survival analysis. To undertake this type of analysis, for statistical reasons, an age is needed at last known status for patients who are alive, as well as the age for deceased patients. Both sets of ages are inputted for analysis. All the survival times, considering both deceased and living children are used to make estimates of overall survival within a group, for example, a group of children with the same heart conditions. The survival analysis cannot be done without both living and deceased children’s data, based on inaccuracies and biases.

UCL are requesting age at life status (alive/deceased) to four decimal places for statistical accuracy and consistent. However, it is integral to note that UCL will not be receiving the dates that NHS England ran the extract for life status (for those alive and deceased) or date of death (for those deceased), so that date of birth cannot be calculated.

The data is to be securely transferred with the record level study numbers to University College London.

The planned data flows are as follows:

1) Data flows to NHS England

National Institute for Cardiovascular Outcomes Research (NICOR) will securely transfer a file to the NHS England. This file will contain patient identifiable information as shown on the section 251 support (NHS Number, postcode, date of birth, local hospital patient ID) for all patients in the study cohort from National Congenital Heart Disease Audit (NCHDA), and unique study ID (NCHDA record-level LTO Study ID).

2) NHS England will identify common records between NCHDA data and Civil Registration Deaths data, including the requested derived fields.

3) The linkage strategy is that NICOR will provide the personal identifiers NHS number, hospital number, date of birth and postcode to NHS England, from the NCHDA data. NHS England will identify in their dataset which records pertain to those CHD individuals and return to UCL the requested data they hold on the matched individuals (UCL will not receive data for patients that do not match), pseudonymised with the LTO ID record level ID (which also is held by NICOR and the research team).

4) Data flows from NHS England. Civil Registration Deaths derived fields for all individuals in the NCHDA cohort will be returned to University College London. The unique study ID (LTO record level study number) will be appended to the end of every record.

The research team will only receive the pseudonymised clinical data of the NCHDA dataset with the LTO ID and pseudonymised life status from NHS England will not receive any personal identifiers. UCL will use the record level LTO study ID in case of any queries about specific records with NHS England.

The data is stored and processed within the UCL Identifiable Data Handling Solution (IDHS) called the Data Safe Haven (DSH). The data will be held within a secure environment where all statistical analyses will be undertaken. Access to this record level data will be limited to only specific members of the LTO team, who are substantive employees at UCL and the Principal Investigator (PI) who is a permanent associate professor of UCL, holding an honorary contract, and an employee of Great Ormond Street Hospital, and will be working on this study entirely within their UCL role. Staff accessing the UCL data safe haven attend training in its use and security procedures. Staff are also required to complete mandatory annual Information Governance and GDPR training. Each study working on the data safe haven has what is known as its own share where the study specific data is kept. Access to this share is granted only by the UCL data share owner who is a substantive employee of UCL, and who requests access for each user. Any team member leaving the study has their access revoked. The storage location is not in any physical location: the storage location is a cloud based secure data haven that is run following strict guidelines and access is only possible for approved authorised users who can access using three separate security checks.

Amazon Web Services provides cloud hosting services to UCL and will store the data as contracted by UCL.

UCL uses offsite data centre services provided by VIRTUS data centre.

Re-identification is not permitted under this data sharing agreement. Any linkage that could identify an individual is not permitted under this agreement. No linkage, other than that described within the agreement is permitted and no further data linkage will be undertaken.

As is common in many studies now, there are a number of collaborators providing an advisory role. Only UCL substantive employees and the PI work with the data. The organisations involved given that study advisors are their employees are Royal Brompton NHS Foundation Trust, Great Ormond Street Hospital NHS Trust, Leeds Teaching Hospitals NHS Foundation Trust, University of Southampton NHS Hospital Trust. These organisations / advisors will not have access to the data. UCL researchers make all the final decisions as data controllers. The remit of these organisations is that they employ clinicians: these clinicians are experts in congenital heart disease (surgeons and cardiologists) and they will provide clinical advice about operative treatments of congenital heart disease such as descriptions of best practice or descriptions of unplanned re-operations. These clinicians will have no control or influence on the means by which the data are being processed. Specifically, they will not have access to or see any of the data involved in the study.

The requested Civil Registration Deaths derived fields of life status, age at life status to four decimal places and place of occurrence of death (home/hospice/hospital/care home/other communal establishment/elsewhere), are vital to complete the patient trajectories.

Methods of analysis for the study will include:

1. Data cleaning and descriptive analysis of the dataset. This is required in order to detect any records that are unusable due to major errors.

2. Develop and update clinical coding maps. Coding maps are used to identify patients who have the various types of complex CHD and also to ascertain what types of heart operation patients have had.

3. Establish and examine variations in longitudinal patient outcomes. Survival rates will be worked out for the different important complex CHD along with unplanned re operations within different subtypes of complex CHD.

4. Explore non-medical risk factors for adverse outcomes including deprivation, ethnicity, and centre volume. This is needed to find out whether children who are less well off or are from certain ethnic minority communities do worse than others. It also helps to explore whether getting a defect diagnosed before birth or whether being treated at a hospital that cares for larger numbers of similar types of patients helps children do better.

The results of all analyses will be published in aggregate form, with small numbers suppressed in line with HES analysis guidelines.

No identifiable data will be held by University College London as no identifiable data will be released by NHS England.

All outputs produced will have small numbers suppressed in line with the HES Analysis guide.

The results of the study have been and will be disseminated in all cases using aggregated non identifiable data.

The research team has strong links with the Congenital Heart Services Clinical Reference Group, The National Audit, NHS England, and clinical bodies including the British Congenital Cardiac Association, the Society for Cardiothoracic Surgery, and the Royal College of Surgeons of Edinburgh. Given that UCL already hold strong links with these organisations and have worked with them before to introduce methods of monitoring and auditing clinical practice, it is expected that this will help UCL to put into practice any learning that comes from the current study. For example, UCL hope it will be possible to introduce new ways to monitor the rates of unplanned reoperations using the current project’s work. If rates of unplanned reoperations are monitored in future within reports issued each year by the National Audit, this might help clinical practice to improve. UCL has kept the National Congenital Heart Diseases Audit up to date on the progress of the study at annual domain expert group meetings including in 2023.

UCL also have strong links with CHD charities including The Children’s Heart Federation, The British Heart Foundation (the funder of the project) and Little Hearts Matter (a patient user organisation which supports parents of children with complex CHD). The project team is working with Little Hearts Matter, working together to find ways to present the study outputs in the most accessible format for parents of children with CHD. As of January 2023, the patient user organisation Little Hearts Matter, are already using the results of this study regarding the outcomes of children with single ventricle disease for their patient information leaflets. These leaflets are read and used by parents who are expecting a baby with CHD who want information about the condition, and by parents of babies and children who are born with CHD and by clinicians undertaking consultations. The first such parent - patient outcome report was completed in 2021 and has been included in the Little Hearts Matter patient information leaflet for hypoplastic left heart syndrome that was published in Feb 2022. The research team met with patient user groups including Little Hearts Matter on 25 Nov 2022 and planned the addition of -2-3 further outcome reports on additional complex single ventricle heart conditions for 2023. These will be produced jointly between the research team, clinicians and the relevant patient group experts who will obtain parent and patient feedback on the reports as part of this process.

Outputs will involve between five publications in peer-reviewed Medical and Scientific Journals by study end, as well as oral and written presentations at national and international conferences such as the British Congenital Cardiac Association annual conference and the American Heart Association Conference. The final outputs will only contain aggregate results with small number suppression, in line with the HES Analysis Guidelines.

To date UCL have published these two papers

Cohort study of intervened functionally univentricular heart in England and Wales (2000-2018).

Hadjicosta E, Franklin R, Seale A, Stumper O, Tsang V, Anderson DR, Pagel C, Crowe S, Espuny Pujol F, Ridout D, Brown KL.

Heart. 2022 Jun 10;108(13):1046-1054. doi: 10.1136/heartjnl-2021-319677.

PMID: 34706904 Free PMC article.

Long-term survival and center volume for functionally single-ventricle congenital heart disease in England and Wales.

Brown KL, Huang Q, Hadjicosta E, Seale AN, Tsang V, Anderson D, Barron D, Bellsham-Revell H, Pagel C, Crowe S, Espuny-Pujol F, Franklin R, Ridout D.

J Thorac Cardiovasc Surg. 2022 Nov 25:S0022-5223(22)01259-4. doi: 10.1016/j.jtcvs.2022.11.018. Online ahead of print.

PMID: 36535820 Free article.

UCL have written two papers that are under consideration with journals / under peer review:

Ethnic group and deprivation related to long term survival in functionally single ventricle heart disease

How often do unplanned re interventions occur in single ventricle heart disease and what are the risk factors?

The principal investigator presented highlight aggregated study findings at a session on 'Transparency' at the Pediatric Cardiac Critical Care Society Conference in Miami USA in December 2022.

The principal investigator of the study presented the study findings so far at the Society of Cardiothoracic Surgery meeting in March 2023.

The project team will continue to disseminate to key stakeholders including national audit bodies, the Care Quality Commission, HQIP, commissioners and local hospitals through meetings and short briefing documents. UCL will disseminate via social media (Twitter @UCL_CORU) and blogs. UCL will ensure that lay summaries are provided (reviewed in collaboration with patients and parents on their Advisory Committee). The patients and parents on the advisory committee attend annual advisory group meetings will receive updates and can provide feedback on any aspect of the study.

The goal of the proposed research is to use information collected about every heart operation undertaken in the UK in the form of national audit data. This will help to better understand what happens over childhood, in terms of longer-term survival and operations that were not part of the planned treatment pathway, for babies born with specific complex heart conditions. This represents a novel use of the procedure based on national audit dataset and represents a complex undertaking since records will need to be linked together and patient trajectories mapped out over time based on individual diagnostic and surgical codes.

The proposed research will use survival models to explore whether children from minority communities or deprived backgrounds experience worse outcomes than other children. This is important to understand since both children from a South Asian background and those living in addresses represented by the most deprived quintile are overrepresented amongst congenital heart patients. Further, the research intends to explore whether service provision in terms of antenatal diagnosis and case volume within children’s specialist cardiac centres (hospitals) are linked to improvements in these specified outcomes for complex congenital heart conditions.

The information generated will be of value to a range of stakeholders including most importantly the parents of children born with complex heart disease who make decisions for their child, since it will form the basis of accurate data driven information about meaningful and important clinical outcomes over childhood. UCL are already working with the main user group for parents of children with complex CHD and have a plan in place to work with them to use the study findings to generate parent information leaflets. These would be read and used by parents who are expecting a baby with CHD who want information about the condition, by parents of babies and children who are born with CHD and, they might be used by clinicians undertaking consultations. These data are not yet available, and they are very much needed.

The findings of the research, in terms of any emerging links between ethnic origin, deprivation, and service provision factors of antenatal diagnosis and centre case volume, could help hospitals to organise their services to provide better treatment for patients. For example, if it were found that children from a particular ethnic group had a greater chance of experiencing late mortality after discharge to home, this might mean these children need extra surveillance and checks on their wellbeing. Or, if it were found that hospitals that treated very few patients with complex CHD had worse survival rates than hospitals that treated larger numbers of patients with complex CHD this knowledge might help NHS England to review where they recommend children are treated. Such longer-term data are currently lacking from service reviews despite being widely sought, and one reason for this is that the analyses required are complex and to date have not been undertaken.

UCL analysed and published the survival and re operation rates for children born with a group of conditions called 'Functionally univentricular heart (FUH)'. These conditions are extremely complex and managed with staged surgical palliation developed for these conditions (Fontan pathway). Population based data reporting longer term outcomes of FUH reflecting current practice are scarce.

UCL found that

• Interventional treatment pathways followed for FUH are complex and highly variable.

• Patients of South Asian ethnicity and those living in the most deprived quintile areas are overrepresented amongst those with this very complex heart condition.

• The 10-year survival was 77.2% and 34.0% of children who underwent initial palliation had an additional cardiac intervention over and above their planned staged treatment.

UCL's findings might impact on clinical practice as follows:

• UCL's data on longer-term outcomes can be used to inform families during decision making for their child for example during foetal counselling. To this end UCL have worked with a patient user group on one condition and are working with them to report further conditions for the patient leaflets that produce.

• It is essential that long-term outcomes of conditions like FUH that require serial interventions are used for audit to provide a fuller picture and to inform quality assurance and improvement, and UCL's work will help to enable this.

(The study was published in the journal 'Heart', a BMJ Journal)

UCL undertook analysis to explore whether in the centralised service provided for children with functionally single ventricle (f-SV) hearts in England, where children receive their treatment in only ten centres. In UCL's analysis UCL found no evidence for a relationship between centre-volume and long-term survival after adjusting for case mix. The survival rate for patients with f-SV disease at one year and five years, was 76.8% (95%CI 75.3%,78.2%) and 72.1% (95%CI 70.6%,73.7%), respectively. After adjusting for risk factors, there was no evidence that centre-volume was associated with long term survival, i.e., HR 1.01 (95%CI 0.99,1.04) p=0.28. Higher volume centres tended to treat children with more complex disease (HLHS, Norwood pathway). This study supports the current service model for treating these complex children in ten centres and the data will help to inform future service planning.

The study is published in the journal 'Journal of Thoracic and Cardiovascular Surgery'.

UCL undertook an analysis of additional operations that occurred over and above the expected treatment pathway in children who have functionally single ventricle heart disease. These additional procedures are common, affecting nearly half of all children. UCL undertook an analysis to detect the characteristics of children who were more likely to need additional interventions over and above the treatment pathway and we published this in the journal 'Circulation'. UCL has taken the methods to identify the re-interventions and are developing these to use for the National Congenital Heart Diseases Audit, so that these rates can be routinely monitored for the purposes of quality assurance.

UCL noted that children who had early reinterventions as infants were severely affected and UCL undertook a specific analysis to look at this further. Of the children in the study, 27.5% had no follow up beyond one-year of age (most had sadly died), amongst whom 35.3% had one or more reinterventions in infancy; and 72.5% of children in the study had transplant-free survival beyond one-year of age, amongst whom 31.5% had one or more reinterventions in infancy. The 5-year transplant-free survival and cumulative incidence of Fontan, amongst those who survived infancy, were 93.4% and 79.3% respectively. Both survival and Fontan completion were similar for those with a single reintervention and those who had no reinterventions. Patients who had more than one additional surgery had higher adjusted risk of mortality. Patients who had more than one additional interventional catheter had lower likelihood of achieving Fontan. Amongst children with f-SV, the occurrence of more than one reintervention in the first year of life, especially surgical reinterventions, was associated with poorer prognosis later in childhood.

UCL's analysis of ethnicity and deprivation has been completed and is in peer review. UCL investigated the influence of key social determinants of health, specifically sex, race/ethnicity and neighbourhood socio-economic position (SEP), on childhood mortality and timing of completion of palliative Stage 3 Fontan-type surgery for a nationally representative cohort of children with functionally single ventricle hearts (f-SV). The optimal age to undergo Stage 3 Fontan-type surgery is dependent on multiple clinical factors. In this multi-centre study, female sex, Asian race/ethnicity and neighbourhood deprivation were associated with lower likelihood of completing Fontan-type surgery after adjustment for f-SV subtypes and associated comorbidities. In these subgroups, Fontan-type surgery was performed at a higher median age and lower weight z-score. Evidence that growth in patients with f-SV is modifiable suggests that additional effort could be focused on ensuring optimal inter-stage growth. It is unclear whether the observed disparities are associated with longer-term impacts such as mortality in adulthood, or broader outcomes such as exercise performance and neurodevelopment, and this merits further investigation. This report is in review with the journal 'Circulation' and the findings in terms of supporting babies with weight gain in order to achieve best outcomes will be discussed within clinical networks.

UCL is currently undertaking a report on the relationship between antenatal diagnosis and certain key events for children with very complex heart disease.