NHS Digital Data Release Register - reformatted

St George's, University Of London projects

• A Phase II, randomised, single-blind, platform trial to assess safety, reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women in the United Kingdom (Preg-CoV)
• Spatio-Temporal Exposure Assessment Methods for estimating the health effects of air pollution
• MR515 - Randomised Prevention Trial of H. Pylori Screening
• Pre-participation screening: Clinical outcomes of a large UK cohort
• MR1485 - Development of a linked, de-identified database resource for research into the health, mortality and educational outcomes of children with a congenital anomaly
• Project 6
• MR39 - SMOKING STUDY - MEN ATTENDING BUPA MEDICAL CENTRE

93 data files in total were disseminated unsafely (information about files used safely is missing for TRE/"system access" projects).

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A Phase II, randomised, single-blind, platform trial to assess safety, reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women in the United Kingdom (Preg-CoV) — DARS-NIC-526384-M3T5R

Type of data: information not disclosed for TRE projects

Opt outs honoured: Identifiable (Consent (Reasonable Expectation))

Legal basis: Health and Social Care Act 2012 – s261(2)(c)

Purposes: No (Academic)

Sensitive: Non-Sensitive

When:DSA runs 2021-07-20 — 2022-07-19

Access method: One-Off

Data-controller type: ST GEORGE'S HOSPITAL MEDICAL SCHOOL

Sublicensing allowed: No

Datasets:

1. Permission to Contact

Objectives:

This Data Sharing Agreement authorises the use of information voluntarily provided to NHS Digital by individuals who have given permission to be contacted about potential participation in COVID-19 vaccine clinical trials. The data will be processed on behalf of the data controller, St George’s University of London, by NHS Digital as a data processor for the purpose of supporting recruitment to participate in a COVID-19 vaccine trial being run by St George’s University of London.

The following provides background to the Permission to Contact (PtC) Service:

NHS Digital has agreed to work in partnership with the National Institute of Health Research (NIHR) to build and host a first of type online Permission to Contact (PtC) Service on nhs.uk where members of the public can register their details and give their permission to be contacted by researchers working on NIHR approved UK coronavirus vaccine trials about participating in those trials. This PtC Service, which is called “Sign Up to be Contacted about Coronavirus Vaccine Studies” on the nhs.uk website was launched as a national service on 20th July 2020.

This Service enables participants to:
• Provide permission for NHS Digital to share an individual’s details provided through the Service with the researchers undertaking COVID-19 UK vaccine trials for the purposes of researchers contacting that individual about taking part in those trials.
• Provide their permission to be contacted by NHS Digital about progress and outcomes from CV19 vaccine studies and in relation to the development of the PtC Service, including to inform them of opportunities to participate in other types of health research.

The data collected from individuals who sign up includes sufficient information to achieve the following purposes:
• Matching potentially eligible participants to eligibility criteria provided by the vaccine trials for their specific studies. This data will comprise of age, sex, geographic locations, type of employment, and a number health question e.g. about whether they have long-term health conditions.
• Providing relevant details of potentially eligible participants which have been obtained through the Service to researchers. This will allow the researchers to contact the participants with a view to discussing their taking part in a trial and if so, to obtain their further permission to take part in the trial.
• NHS Digital will provide access to the information obtained from individuals through the Service via the existing Data Access Request Service (DARS) process available to researchers working on UK COVID-19 vaccine trials sponsored by the National Institute of Health Research. The Service will only provide researchers with the data collected directly from individuals themselves through the Service.

The contact details will be used to invite potentially eligible individuals to undertake an eligibility assessment and, if eligible, to give informed consent to participate in this trial. NHS Digital, as data processor acting on behalf of St George’s University of London, will be sending the email to eligible participants.

This request relates specifically to a vaccine trial. This is A Phase II, randomised, single-blind, platform trial to assess safety, reactogenicity and immunogenicity of COVID-19 vaccines in pregnant women in the United Kingdom

Pregnant women should be provided with a balanced and clear assessment of their risk of COVID-19 in pregnancy, taking into account their individual circumstances, local practices and available evidence. They should also be counselled with a balanced summary of the potential direct and indirect benefits of COVID-19 vaccines, and the current lack of safety data should be acknowledged. COVID-19 vaccination should not be withheld from women who have received adequate counselling and understand the uncertainties, potential harms, and potential benefits of these vaccines. However, there are important unanswered questions regarding the reactogenicity, safety, immunogenicity, and persistence of immunity in the mother and infant, as well as the efficiency of placental transfer of antibodies and the optimal schedule for pregnant women, it is important that such data are gathered in a systematic and controlled manner. In doing so, evidence based guidelines can be developed which will then benefit all pregnant women. There is a widespread call to gather such evidence for use of COVID-19 vaccines in pregnant women; however, it is possible that the window of opportunity for doing this is closing as more women receive vaccines routinely. A number of advantages therefore exist in recruiting pregnant women into a pragmatic clinical trial in which they all receive a COVID-19 vaccine (rather than a placebo). Using a platform design Preg-CoV will allow inclusion of new COVID-19 vaccines as they become licensed, as well as rapidly address new questions of relevance to the vaccine programme as they arise (different intervals, one dose schedules etc).

The aim is to recruit 900 participants for the trial. The initial mailout will aim for around four / five times the number of potential participants to be recruited and therefore the estimate is for around 4,500 individuals to be contacted.

The applicant has met with representatives of organisations such as The Miscarriage Association and SANDS to ensure that the content for the approved communication to members of the NHS Digital COVID-19 Vaccine Research Registry has been suitable worded to take account of the potential sensitivities around recruiting participants for a trial of this nature.

Although this application relates to the use of commercial vaccines, there is no commercial element specifically attached to this application itself, the purpose of which is about influencing national vaccine rollout strategy. Although results may influence the manner in which the commercial firms role out vaccines in future, this application relates solely to an academic exercise.

Although AstraZeneca, Pfeizer and Moderna have allowed the use of their vaccines for this trial, they have no responsibilities as to how the trial is conducted and therefore St. George’s University of London remain the sole Data Controller for this application. This also applies to any other commercial vaccine manufacturers that make their vaccines available for use in this trial in future.

Expected Benefits:

The primary benefit of using the data will be to recruit participants for the clinical study/trial in a manner which:
• Enables individuals to volunteer in advance to participate in COVID-19 vaccine trials as an alternative to other potentially more intrusive mechanisms, e.g. sharing data with researchers about individuals under section 251 consents or COPI notices, which although lawful is initially less transparent.
• Allows researchers to identify a suitable cohort and recruit them quickly into the vaccine trials – thus reducing the overall time to recruit into the trials and to accelerate the delivery of an effective vaccine to treat individuals to manage the COVID-19 outbreak and to save lives.
• Reduces burden on research staff in identifying and contacting potential clinical trial participants.
• Supports the Vaccines Taskforce objectives to drive forward, expedite and coordinate efforts to research and then produce a coronavirus vaccine and make sure one is made available to the public as quickly as possible.

Outputs:

The information from NHS Digital will be used to facilitate contact with individuals who are potentially eligible and who have indicated willingness to potentially participate in studies/trials of COVID-19 vaccines.

This is expected to result in individuals entering the trials screening process with a view to them participating in the trial with fully informed consent.

The main results from this trial are expected to inform development of a safe and effective multiple vaccine combination against COVID 19.

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Spatio-Temporal Exposure Assessment Methods for estimating the health effects of air pollution — DARS-NIC-127189-R2K8F

Type of data: information not disclosed for TRE projects

Opt outs honoured: Anonymised - ICO Code Compliant (Does not include the flow of confidential data)

Legal basis: Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii), Health and Social Care Act 2012 - s261 - 'Other dissemination of information', Health and Social Care Act 2012 – s261(2)(b)(ii)

Purposes: No (Academic)

Sensitive: Non-Sensitive

When:DSA runs 2019-12-20 — 2020-07-19

Access method: One-Off

Data-controller type: KING'S COLLEGE LONDON, ST GEORGE'S, UNIVERSITY OF LONDON, KING'S COLLEGE LONDON, ST. GEORGE’S HOSPITAL MEDICAL SCHOOL

Sublicensing allowed: No

Datasets:

1. Hospital Episode Statistics Admitted Patient Care
2. Hospital Episode Statistics Admitted Patient Care (HES APC)

Objectives:

Exposure to outdoor air pollution has been associated with increased risks of admission to hospital and death. These risks are thought to be related to both long-term exposure to air pollution measured over many months/years and to short-term changes in pollution concentrations on a day-today basis. Cohort studies use long-term pollution measurements at different geographical locations to assess the risk to health whereas time-series studies use daily average concentrations in a city related to daily counts of health events (e.g. hospital admissions for respiratory disease) in the city. As the public are exposed to air pollution over days/weeks/months/years, the extent to which estimates of the associations between long-term average and short-term variations in pollutant concentrations and health overlap is an important issue with implications for the development of policies to control pollution. To date, this issue has not been investigated in the UK.

In the past, both cohort and time-series studies have been limited by the availability of data from pollution monitors. In recent years, statistical models have been developed that incorporate data on land use, pollution emissions, and/or predictions derived from satellite data to estimate daily pollutant concentrations in small geographical areas. The objective of this study is to evaluate, and integrate, the different models and use the resulting predicted pollution concentration in a joint analyses of long- and short-term exposures for a limited number of health endpoints as a ‘proof of concept’.

King’s College London (KCL) and St George’s University of London (SGUL) have come together as a collaboration in order to carry out this work. The results of this study will be in the interests of the public and therefore the data will be processed under GDPR Article 6(1)(e) and GDPR Article 9(2)(j).

To achieve this objective, both annual and daily estimates of concentrations of particles and gaseous pollutants for lower super output areas (LSOA) within the south east of England will be derived from daily pollutant measurements at fixed site monitors, remote sensing (satellite) data and daily estimates from different modelling methods for the period 2004 to 2013. The performance of each approach in estimating the health effects associated with short and long-term exposures will be assessed using newly developed simulation methods. To demonstrate proof of concept in estimating simultaneously the health effects of both long- and short-term exposure to air pollution, estimates of pollutant concentrations from the method(s) showing the best performance will be used in separate analyses of primary care data, counts of hospital admissions for respiratory and cardiovascular disease and counts of deaths for a 5-year period (2009-2013).

The study has been funded by the Medical Research Council. The lead Principal Investigator is a senior investigator from KCL, and the co-Principal Investigator is a senior investigator at SGUL. Both KCL and SGUL have responsibility for the Hospital Episode Statistics (HES) analysis aspect of the project including the purposes and therefore KCL and SGUL are joint Data Controllers. Other collaborators for the wider project (i.e. outside this agreement) are Imperial College London, University of Athens and University of Harvard. The project includes modules undertaken at each of the institutions, the HES analysis aspect being one of these modules. SGUL and KCL are responsible for the analysis of the hospital admissions and mortality data. This application relates only to the provision of hospital admissions data provided by means of a tabulation from NHS Digital. An unsuppressed tabulation is required to ensure the data is in a comparable format to the pollution data from other sources. A separate application to the UK Data Service for access to Civil Registrations (Deaths) data was made by SGUL. There will be no linkage of the Civil Registration Data with the data provided by NHS Digital. Only the SGUL and KCL investigators will have access to the hospital admissions data under this Agreement.

The data received by St. George’s University of London or King’s College London will not be used for any purpose other than to meet objectives as stated in this Data Sharing Agreement and will not be shared with any other third party or organisation.

The Data Controllers should ensure appropriate data processing agreements with all data processors contracted to undertaking work referenced within this agreement.

Yielded Benefits:

None to date. The agreement start date was December 2018. The data were produced in July 2019 therefore additional time is needed in order to complete the analysis.

Expected Benefits:

National and international governmental agencies are responsible for the evaluation and development of policies to regulate air pollution. Part of this process is an assessment of the impact of air pollution on health. Whilst the proposed analyses of the admissions data is for ‘proof of concept’, the results from this study will provide policy makers in the UK including Defra, the Department of Health, Public Health England and Local Authorities with useful information to assess health impacts and so help plan local and national air pollution mitigation strategies in both the long- and short-term.

Outputs:

Results from the analyses of the hospital admissions counts will be risk estimates, associating long- and short-term exposure to outdoor air pollution and admission to hospital. Summary statistics will be produced for the whole study area and study period only, not for individual LSOA or day so eliminating any small cell reporting. All outputs with be aggregated with small numbers suppressed in line with the HES Analysis Guide. Study results will be available to the project team prior to the completion date of the analysis (June 2020). The results from the study will be written up and submitted to a peer review journal for publication. It is also anticipated that the study findings will be presented at scientific conferences such as the International Society for Environmental Epidemiology.

The evidence from this study will be considered by the UK Government advisory committee on air pollution (COMEAP) when formulating advice to policy makers and ministers. COMEAP maintains a watching brief on air pollution research particularly from the UK as well as undertaking targeted work in response to specific requests for advice from Government departments. Similarly, other institutions such as WHO and the US Health Effects Institute undertake periodic reviews of the literature as part as its ongoing assessments of the health effects of air pollution. The published outputs from this study will therefore be included in such assessments.

Processing:

The hospital admissions data extract will be stored in the data safe haven (DASH) at SGUL. The data will be accessed only by substantive employees of SGUL and KCL, and in accordance with SGUL’s DASH IT security policies and procedures. Members of the research team from KCL will only access the data via the SGUL data safe haven. No data will be stored, accessed or processed on KCL premises. The lead and co-Principal Investigators at KCL and SGUL respectively are responsible for the data processing, management and statistical analyses of the HES data. Only details of the statistical method and the interpretation of the output from the analyses will be discussed with other investigators. The admissions data will not be shared with any other institution/organisation and other collaborators within the study will not have access to the data.

SGUL/KCL are requesting daily counts of respiratory and cardiovascular emergency hospital admissions in subjects aged 35+ for each LSOA for a defined area of the south east of England (9811 LSOAs). The LSOAs will be provided to NHS Digital by SGUL. Estimated pollution concentrations for each LSOA for each day between 2009-2013 will be supplied by KCL and stored in SGUL DASH. The daily pollution concentrations will be combined with the daily counts of admissions by date and LSOA for statistical analyses by one of the SGUL investigators. The counts of admissions derived from the admissions records will not be shared with any other institution/organisation or other collaborators. No other collaborators will have access to the admission data.

The statistical analysis will consist of a regression model to assess associations between pollution concentrations and counts of admissions controlling for other factors that vary over time such as daily temperature and holiday periods. The analyses will produce risk estimates for changes in pollution levels for spatial and temporal variation in pollutant concentrations. The analysis of the admissions data is part of the final module of the Spatio-Temporal Exposure Assessment Methods Project (proof of concept) and therefore the output does not feed into other work within the project.

All organisations party to this agreement must 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 i.e.: employees, agents and contractors of the Data Recipient who may have access to that data).

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MR515 - Randomised Prevention Trial of H. Pylori Screening — DARS-NIC-147843-8NKTW

Type of data: information not disclosed for TRE projects

Opt outs honoured: Yes - patient objections upheld, Y, Identifiable, Yes (Section 251, Section 251 NHS Act 2006)

Legal basis: Health and Social Care Act 2012 – s261(7), Section 251 approval is in place for the flow of identifiable data, Health and Social Care Act 2012 – s261(7), Health and Social Care Act 2012 – s261(7); National Health Service Act 2006 - s251 - 'Control of patient information'.

Purposes: No (Academic)

Sensitive: Sensitive

When:DSA runs 2018-12-01 — 2021-11-30 2019.03 — 2023.10.

Access method: Ongoing, One-Off

Data-controller type: QUEEN MARY UNIVERSITY OF LONDON, ST GEORGE'S, UNIVERSITY OF LONDON, ST. GEORGE’S HOSPITAL MEDICAL SCHOOL

Sublicensing allowed: No

Datasets:

1. MRIS - Cause of Death Report
2. MRIS - Cohort Event Notification Report
3. MRIS - Scottish NHS / Registration
4. Civil Registration - Deaths
5. Demographics
6. Cancer Registration Data
7. MRIS - Flagging Current Status Report
8. MRIS - Members and Postings Report
9. Civil Registrations of Death

Objectives:

Helicobacter pylori infection of the stomach accounts for most cases of stomach cancer worldwide. The risk of stomach cancer is about five times greater in infected than in uninfected persons. While the association is accepted as causal, it is not known whether screening and treatment of the infection in middle age can reverse this excess risk. This trial aims to determine if screening for and treating H Pylori infection in middle age reduces the risk of stomach cancer

The Wolfson Institute, QMUL requires cancer notification and death certificates for use in Follow Up of Participants in the Randomised Trial of Helicobacter Pylori Screening (HPSS)

a) Researchers at the Wolfson Institute, QMUL instigated the trial
b) BUPA Wellness Centres were approached to recruit patients
c) Only the named researchers at the Wolfson Institute, QMUL will have access to the record level data supplied by NHS digital.

Researchers at the Wolfson Institute are concerned with screening and decided that a large scale screening trial was needed to establish if population screening for HPylori and treating the infection would reduce the risk of stomach cancer .

A randomised controlled trial was set up to answer this question. Recruitment for the trial was from 1997 to 2006 during which 62,454 people attending ten BUPA Wellness Centres for a medical examination were randomly allocated into screened and control groups. Those screened were offered serological testing for H pylori and, if they were positive, a one week course of eradication treatment. Blood was collected and stored from all participants (screened and control). All participants were flagged with NHS Digital and information on their deaths and cancer notifications has been supplied to the PI since 1997. It was expected that the length of follow-up would be a minimum of 20 years.

When a sufficient number of participants have developed stomach cancer for the results of the trial to have sufficient statistical power the serum samples from all persons who developed stomach cancer and a random sample of those who did not will be retrieved from freezers in the Wolfson Institute and tested for H. pylori. The final comparison will be between the incidence of stomach cancer in the screened and control groups among H pylori positive persons only (rather than all persons). This design, a “nested randomised trial”, maximizes statistical power and substantially reduces cost.

Yielded Benefits:

No outputs have been produced as the data analysis plan was designed such that no analysis would be undertaken until sufficient numbers of stomach cancers had occurred. The numbers reported are not sufficient yet.

Expected Benefits:

If the trial determines that screening and subsequent eradication of H Pylori reduces the incidence of stomach cancer this will have an enormous benefit to the whole population in the UK and worldwide. Both screening and eradication (a 1 week course of antibiotics) are simple and cheap. Around 40% of people have H Pylori infection. In 2015 6740 people developed stomach cancer. If screening does work and prevents 20% of stomach cancers then this will mean that over 1,300 stomach cancers will be prevented. With 4 out of 10 people in the UK thought to have H Pylori infection potentially 40% of the population could have their risk of stomach cancer reduced. The extension of our data sharing agreement will allow us to obtain enough cases of stomach cancer to provide the information needed on the value of screening.

This trial will provide evidence concerning whether screening for HPylori infection is worthwhile. If the results from the trial are positive then we would be in a position to contact PHE to discuss implementing a population screening programme.

Outputs:

The following outputs will be produced :
A peer review paper analysing the results from the trial will be submitted to an open-access peer reviewed journal within one year after sufficient stomach cancers have occurred.This paper should be influential in deciding whether to screen for H Pylori infection . The final report of results will be submitted to CRUK. This will cover all findings of the study.

For each paper published, a short presentation may be developed to summarise the findings for a range of stakeholders, including healthcare professionals and patient groups.
The study website will provide links to the open access papers and will offer free downloads of accessible summaries of findings.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide/compliant with the MHSDS disclosure control rules including suppression and rounding.

Processing:

All 62,454 participants in the HPSS have been flagged at NHS Digital. Information on deaths and cancer registrations is requested to be received every 6 months electronically. The electronic information will be downloaded onto a secure server, protected by a fire-wall, based in the Wolfson Institute of Preventive Medicine. The data are then merged with the HPSS study database by the database manager in the Wolfson Institute. The data are stored on the server, with any identifiers stored separately from the clinical information. The database manager provides the study statistician with pseudonymised information on the numbers of deaths and cancer registrations that have occurred since the start of the trial.

Data will only be accessed by individuals within the Centre for Environmental and Preventive Medicine who have authorisation from the PI (Sir Nicholas Wald) to access the data for the purpose described, all of whom are substantive employees of QMUL.

The core dataset will only be accessed by the data manager within the Wolfson Institute. They will produce subsets of the data that will be accessed by the study statistician. Any other person seeking access toi a subset of the data will have to submit a formal reuest to the PI (Sir Nicholas Wald) and justify from a scientific basis all requested information.

All organisations party to this agreement must 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 i.e.: employees of QMUL situated in the Centre for Environmental and Preventive medicine who may have access to that data).

No further linkage will be performed.
The data will not be made available to any third parties other than those specified except in the form of aggregated outputs with small numbers suppressed in line with the HES Analysis Guide.

Data is only requested for those participants in the HPSS study.
Some identifiers are necessary to ensure that the correct match with the study participant is made. The BUPA identifiers which were used in this study were not totally unique, causing manual checks to be made when any linkage is performed.

No outputs have been produced as the data analysis plan was designed such that no analysis would be undertaken until sufficient numbers of stomach cancers had occurred. The numbers reported are not sufficient yet.

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Pre-participation screening: Clinical outcomes of a large UK cohort — DARS-NIC-190086-F5Z7B

Type of data: information not disclosed for TRE projects

Opt outs honoured: Yes - patient objections upheld, Anonymised - ICO Code Compliant, Yes (Section 251 NHS Act 2006)

Legal basis: Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii), Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii), Health and Social Care Act 2012 – s261(7), Health and Social Care Act 2012 - s261 - 'Other dissemination of information'; National Health Service Act 2006 - s251 - 'Control of patient information'., Health and Social Care Act 2012 – s261(2)(b)(ii)

Purposes: No (Academic)

Sensitive: Non Sensitive, and Sensitive, and Non-Sensitive

When:DSA runs 2019-10-01 — 2022-09-30 2020.04 — 2021.07.

Access method: One-Off

Data-controller type: ST GEORGE'S, UNIVERSITY OF LONDON, ST. GEORGE’S HOSPITAL MEDICAL SCHOOL

Sublicensing allowed: No

Datasets:

1. Hospital Episode Statistics Accident and Emergency
2. Hospital Episode Statistics Outpatients
3. Hospital Episode Statistics Admitted Patient Care
4. Civil Registration - Deaths
5. Civil Registration (Deaths) - Secondary Care Cut
6. MRIS - List Cleaning Report
7. Civil Registrations of Death - Secondary Care Cut
8. Hospital Episode Statistics Accident and Emergency (HES A and E)
9. Hospital Episode Statistics Admitted Patient Care (HES APC)
10. Hospital Episode Statistics Outpatients (HES OP)

Objectives:

The UK National Screening Committee (UK NSC) does not recommend a national sponsored screening program for cardiac disease in young asymptomatic individuals with no relevant family history. In the most recent UK NSC review the authors highlight the low incidence of sudden cardiac death (SCD) in young adults and raised concerns regarding the performance of the proposed screening tools and in particular the 12-lead ECG. The 12-lead ECG is a representation of the heart's electrical activity recorded from electrodes on the body surface.

The true incidence of sudden cardiac death (SCD) in children and young adults is widely debated. Accurate calculation of the incidence requires a precise numerator (number of deaths per year) and an exact denominator (number of participants per year) in the population studied. The reported incidence of SCD in young adults (age 14-35 years) varies widely depending on the group studied and the methodology used and has been reported as low as 1:300,000. In the absence of systematic registries, collection methods using retrospective review of media reports, electronic databases and insurance claims in these early studies, are limited by ascertainment and selection bias which underestimate calculations of incidence. Gauging the effect of preventative strategies such as preparticipation cardiovascular screening (PPS) is limited by unreliable estimates of SCD incidence.

Cardiac Risk in the Young (CRY) has provided a voluntary cardiac screening program to children and young individuals since 1996. In this time CRY have screened in excess of 150,000 individuals for conditions associated with SCD. This has formed the largest database of its kind with a well-defined denominator. Up till now research on screening outcomes has primarily focussed on individuals that were flagged as positive by the screening and proceeded to further evaluation. As such they have been able to define the positive predictive value as well as the false discovery rate of the screening programme and in particular the 12-lead ECG. For the first time, this project will explore outcomes in the entire population and in particular individuals whose screening tests were considered normal and were reassured that they did not have any cardiac condition predisposing them to sudden cardiac death. These individuals comprise >90% of the screened population.

The organisation requests mortality data for approximately 120,000 consecutive individuals screened over a decade, from 2007 till 2018. These individuals were screened across England, Wales, Scotland and Northern Ireland. Individuals were aged between 14 and 34 years of age at the time of data acquisition. Outcomes will not be compared to an un-screened population and for that reason no control group exists.

The following steps have been taken to minimise the data requested:

1. The data request only relates to those individuals in the cohort. Data outcomes from individuals who have undergone cardiac evaluation by other screening providers (not Cardiac Risk in the Young) will not be included.

2. There is no requirement for data which was stored prior to the screening period of the cohort. For this reason, data stored earlier than 2007 is not requested.

3. This study aims to ascertain the prevalence of conditions which are associated with sudden cardiac death. For that reason, the ICD-10 codes have been filtered to reflect these conditions only.

4. This study aims to ascertain the frequency of cardiac interventions which are performed in order to reduce the individual's risk of sudden cardiac death. The OPCS4 codes have been filtered to include these procedures only.

5. This study aims to ascertain the incidence of sudden cardiac death. The timing and location of an individual's collapse/sudden cardiac arrest prior to death can disguise the cause of death. The clinical experience from a dedicated sudden arrhythmic death syndrome service has highlighted this fact. Examples include: Cardiac rarest with resuscitation and survival to hospital admission but died with hypoxic brain injury (stated as cause of death), drowning where circumstances are not clear or appear unusual (without struggle), road traffic accident where circumstances indicate the driver may have collapsed before the trauma related impact (no brake marks, or driver found dead at the hand-wheel of a car that is stationary). Indeed, familial evaluation of such cases has, from experience and others, identified familial forms of the Long QT syndrome, Brugada syndrome and catecholaminergic polymorphic tachycardia which are then attributed to the cause of death retrospectively. These outcomes reflected in the available medical literature. For this reason, the request for all-cause mortality to evaluate the possible number of additional cardiac deaths which manifest atypically and are then incorrectly coded.

From these datasets the aim is to identify any individual with: A) sudden cardiac death, B) Sudden Cardiac Arrest (SCA) and C) a diagnosis of a cardiac condition associated with sudden cardiac death. The data will be securely returned to the storage location in the pseudonymised form for outcome analysis.

Pilot data from a cohort of 5,000 individuals from the same research group supported by CRY looking at the outcomes of a specific ECG index (early repolarisation) indicates that through this process the study will be able to obtain outcomes in excess of 95% of the individuals screened.

This study will be the most comprehensive study on cardiac screening of children and young individuals yet and will be able to define the: 1. The exact incidence of sudden cardiac death in a screened population of young individuals and compare it to reported rates in the UK, 2. Assess the sensitivity, specificity, positive and negative predictive value of cardiac screening overall as well as the individual tests used (12-lead ECG and health questionnaire) of identifying individuals with conditions predisposing to sudden cardiac death, 3. Assess the effectiveness of screening in terms of detecting different conditions predisposing to sudden cardiac death.

This study has the potential to define the future approach to PPS not only in the UK, but worldwide. Accurate assessment of SCD incidence, as well as insight into the true performance of commonly used screening tools, will guide the outcome of PPS policies including that of the UK NSC. As a result, the Primary Investigator (PI) and the organisation, believes the processing of such data is justified on legal grounds - GDPR Article 6(1)(e). Data processing is also necessary for reasons of substantial public interest under Article 9(2)(j).
This project has the potential to form the basis for a number of other projects including 1. Comparison of mortality rates in a screened compared to a well-defined non-screened population, 2. Assessment of true screening costs, 3. Assess the predictive value of identifying cardiac disease of different ECG indices.

Study Rationale
A government sponsored screening program, mandated by Italian law, has demonstrated a fall in rates of sudden cardiac death by 89%. Currently no equivalent UK state sponsored program exists. Concerns in part relate to the perceived low incidence of sudden cardiac death (SCD) and sudden cardiac arrest (SCA) in young individuals. This study will provide the most reliable estimate for the incidence rate for SCD and SCA in the literature. Only once a reliable estimate of SCD and SCA is calculated, can the screening community gauge the need for preventative strategies such as cardiac screening.

Primary Objectives

1. To define the incidence of sudden cardiac death in a screened population of children and young individuals.

2. To assess the value of cardiac screening overall, individual tests used (12-lead ECG and health questionnaire), as well as specific indices of these tests (specific questions or ECG indices) of identifying individuals with conditions predisposing to sudden cardiac death or sudden cardiac arrest.

3. Assess the effectiveness of screening of detecting different conditions predisposing to sudden cardiac death.

Primary aim:

• The primary aim is to estimate the incidence of sudden cardiac death and sudden cardiac arrest in a population of individuals who had previously undergone assessment with pre-participation screening over a ten-year period.

Secondary aims:
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To assess the value of cardiac screening overall, individual tests used (12-lead ECG and health questionnaire), as well as specific indices of these tests (specific questions or ECG indices) of identifying individuals with conditions predisposing to sudden cardiac death or adverse outcomes (sudden cardiac death, sudden cardiac arrest).

• Assess the effectiveness of screening of detecting different conditions predisposing to sudden cardiac death.

The following organisations are involved:

• St George’s, University of London
Role: Sole data controller and sole data processor
Organisation Type: Academic

• Cardiac Risk in the Young
Role: Source of funding for study. Owners of source data.
Organisation Type: Charity

The Principal Investigator is substantively employed at St Georges, University of London but holds an honorary contract at Cardiac Risk in the Young (CRY), so they can access the identifiers from the database. However, no linkage of the NHS Digital data disseminated under this agreement is permitted to the identifiers held at CRY. St George’s, University of London are not permitted to re-identify any members in the cohort.

There are no other organisations/commissioners involved in this or wider anticipated projects.

Expected Benefits:

The incidence of sudden cardiac death is widely debated. Previous studies evaluating this figure have used heterogenous passive collection methods with poorly defined population demographics leading to unreliable estimates. The methodological strengths of this study in a large cohort will provide the most reliable estimate of SCD in young individuals in the literature to date. The effectiveness of preventative strategies for SCD can only be evaluated once a reliable estimate of incidence is agreed. This study has the potential to influence the decision on whether there should be a government driven screening programme for SCD which affects at least 400 people a year.

Publication of the research in high impact medical journals will allow it's wide international circulation. Future studies in this area will also reference the work in subsequent investigations. Through academic publication and presentation it is expected that the findings of the research, if significant, will inform future national and international guidelines on the assessment and management on individuals at risk of sudden death and regarding pre-participation cardiac screening of athletes. Such guideline documents are widely circulated and advertised within clinical service. They inform the basis of clinical practice of cardiologists, sports physicians and general practitioners looking after such individuals. In many cases, guidelines are adopted or endorsed by the National Institute for Clinical Excellence (NICE) and therefore effectively become mandatory for NHS physicians.

Outputs:

The research output will be submitted to peer-reviewed cardiology and/or general medical journals in the form of an original research article. It is expected that the work will be accepted for publication in a high-impact cardiology-specific journal, such as Circulation, the Journal of the American College of Cardiology (JACC) or the European Heart Journal (EHJ). These journals are widely read amongst the clinical and academic cardiology community worldwide. Articles published in these journals therefore frequently inform clinical practice are often cited in national and international guideline documents.

CRY hold 6 monthly ‘Heart Group Meetings’. The meetings are advertised on the CRY website. The Primary Investigator presented the study to 80 attendees which included individuals within the study cohort. Feedback was positive and there were no concerns about the methodology expressed. Further clarity has been sought by sending emails to the cohort requesting their feedback, this process has begun and was confirmed in a call with the applicant on 13/09/2019, at each screening event questionnaires are given out, each event is attended by approx. 200 people

Only aggregated data, with small numbers suppressed in line with HES analysis guidance, will be included in any research output. No patient level data will be included. It is expected that the research article will be submitted for peer review within 3 months of receipt of the data from NHS digital.

In addition to the written outputs, the research data will be submitted for oral presentation at national and international cardiology conferences such as the British Cardiac Society annual conference, British Heart Rhythm Congress, European Heart Rhythm Association conference and Heart Rhythm Congress in the USA. Similarly to the journal listed above, these conferences serve to dissipate cutting edge clinical research findings to leading clinical and academic cardiologists. Through this network of academic research presentations the findings, if significant, will lead to changes in national and international guidance on the assessment and management of young adults at apparent risk of sudden cardiac death or undergoing pre- participation ECG screening in the context of elite or amateur sport. Such guideline documents are widely circulated and advertised within clinical service. They inform the basis of clinical practice of cardiologists, sports physicians and general practitioners looking after such individuals. Summaries of the research findings will also be published by Cardiac Risk in the Young including on their website, via twitter and at the annual CRY International Conference on Sports Cardiology.

Processing:

The organisation must 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).

Completion of the medical questionnaire and acquisition of the ECG were performed by CRY at various sites throughout England and Wales at the time of cardiac screening events. All participants gave written informed consent themselves or via parental consent where applicable for their data to be stored and used for research purposes by CRY.

Primary source data (i.e. medical questionnaire responses and ECG) were used to construct two databases. The first containing the participants demographic details and the second containing data from the medical questionnaire and ECG. The databases are linked by unique ID numbers and are password protected. These databases are stored securely on the local network at the central office of Cardiac Risk in the Young. Access to the local network is via a unique login ID and password protected. It cannot be accessed remotely.

Identifiers of individuals who participated in the screening and consented to using their data for research will be transferred securely to NHS Digital. The identifiers are required in order for NHS Digital to match each individual to their NHS number. Subsequently, NHS numbers will be matched against a pre-defined set of codes (ICD for diagnosis, OPCS for procedures) on various national databases (Civil Registration Mortality data, Hospital Episode Statistics and Primary Care Mortality).

Identifiers will be provided to NHS Digital from St George’s, University of London who will have received them via Cardiac Risk in the Young (CRY). The linked data will flow from NHS Digital to St George’s, University of London via Secure Electronic File Transfer (SEFT).

The data-set sent to NHS Digital will include the following demographics for each individual of the cohort:

• Name
• GP Registration
• Date of Birth
• Date of Death (if applicable)
• Postcode (Unit level)
• Gender
• Ethnicity

These demographics will enhance the linkage rate to each individual’s NHS number. This service will be provided by the Medical Research Information Service (operated by NHS Digital).

NHS Digital will then match each individual's NHS number to a selected list of product codes using mortality data. This filtered list of ICD and OPCS-4 codes will be provided to NHS Digital by the organisation. This will include ICD-10 and OPCS-4 codes. These matched data-codes will provide the following outcomes:

1. Episode of death
2. Cause of death
3. Episode of sudden cardiac arrest
4. Diagnosis of cardiac condition associated with sudden cardiac death (e.g. hypertrophic cardiomyopathy)
5. Cardiac intervention to reduce risk of sudden cardiac death (e.g. implantable cardioverter defibrillator)

NHS Digital will then link these outcomes to each individual’s unique study number.

The linked mortality data will be transferred from NHS Digital to the data processor in the pseudonymised form. This data-set will be stored securely on an encrypted St George's Hospital University of London Data Safe Haven (DaSH) server. Those accessing the data are substantive employees of St George’s Hospital.

No attempts will be made to re-identify any individuals under this Data Sharing Agreement.
Data provided by the NHS Digital will be analysed at St. George s Hospital Medical School Research Department by the PI who is a substantive employee of St Georges Hospital Medical School and St George’s University London. Record level data will not be shared with any other individual. The data will not be converted back into the identifiable form at any stage.

Final data will be aggregated to prevent the identification of any individual within the study. All outputs will be aggregated with small numbers suppresses in line with HES analysis. No data will be shared with third parties. Data will not be accessed from outside the UK.

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MR1485 - Development of a linked, de-identified database resource for research into the health, mortality and educational outcomes of children with a congenital anomaly — DARS-NIC-64474-V4B2D

Type of data: information not disclosed for TRE projects

Opt outs honoured: Yes - patient objections upheld, Anonymised - ICO Code Compliant, Identifiable, Yes (Section 251 NHS Act 2006)

Legal basis: Health and Social Care Act 2012 – s261(7), Health and Social Care Act 2012 – s261(7)

Purposes: No (Academic)

Sensitive: Sensitive, and Non Sensitive, and Non-Sensitive

When:DSA runs 2020-05-15 — 2023-05-14 2020.10 — 2020.12.

Access method: One-Off

Data-controller type: ST GEORGE'S, UNIVERSITY OF LONDON, ST. GEORGE’S HOSPITAL MEDICAL SCHOOL

Sublicensing allowed: No

Datasets:

1. Demographics
2. HES:Civil Registration (Deaths) bridge
3. Civil Registration - Deaths
4. Hospital Episode Statistics Admitted Patient Care
5. Hospital Episode Statistics Critical Care
6. Civil Registration (Deaths) - Secondary Care Cut
7. Civil Registrations of Death - Secondary Care Cut
8. Hospital Episode Statistics Admitted Patient Care (HES APC)
9. Hospital Episode Statistics Critical Care (HES Critical Care)

Objectives:

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.

Expected Benefits:

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.

Outputs:

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).

Processing:

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.

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Project 6 — DARS-NIC-45477-B9W1L

Type of data: information not disclosed for TRE projects

Opt outs honoured: Yes - patient objections upheld (Section 251)

Legal basis: Health and Social Care Act 2012 – s261(7)

Purposes: ()

Sensitive: Sensitive

When:2018.10 — 2019.01.

Access method: One-Off

Data-controller type:

Sublicensing allowed:

Datasets:

1. MRIS - Flagging Current Status Report
2. MRIS - Cause of Death Report

Objectives:

Around 400 young people die from sudden cardiac death (SCD) each year in the UK. The majority of these events are due to inherited abnormalities of the heart muscle or electrical systems and are often silent until they present with a cardiac arrest. It was first reported in 2008 that individuals who suffered a cardiac arrest were more likely to have a particular pattern on their resting electrocardiogram (ECG); the Early Repolarisation Pattern (ERP). Subsequent large population cohort studies showed that individuals with the ERP had an increased risk of sudden cardiac death over long-follow up periods. The excess of sudden cardiac deaths occurred in the sixth decade of life and onwards. These studies led to great concern over the significance of the ERP in the general population.
Meanwhile the ERP is known to be common in young adults, particularly those who take part in high volumes of regular exercise. There have been no large-scale studies to date in cohorts of young adults with ERP.
The intention of this study was firstly to identify the prevalence of the ERP in a large cohort of physically active young adults and to identify whether those with ERP have an increased risk of sudden cardiac death in the short to medium-term. Central to answering this question is to reliably identify those who have suffered sudden cardiac death and correlate these deaths with the presence of the ERP on the ECG.
This study forms part of a larger research project, "EVALUATION OF THE 12 LEAD ECG AS A USEFUL TOOL IN IDENTIFYING YOUNG APPARENTLY HEALTHY INDIVIDUALS WITH CARDIAC DISEASE" (REC Ref MH532A) undertaken by clinical researchers at St. George’s Hospital Medical School Research Dept. who have published extensively in the field of ECG screening, sudden cardiac death risk and ECG patterns.

The purpose of this larger study is to identify a cost-effective screening method of identifying young individuals with cardiac disease who may be at risk of sudden cardiac death. As described above, sudden cardiac death may occur in individuals with previously asymptomatic heart muscle or electrical diseases. These diseases may be diagnosed with a 12-lead ECG which therefore may be considered as a potential screening tool. This particular application utilises the demographic and ECG data collected to assess the significance of the ERP as described above. Results from this study will then feed back in to the ongoing larger study by determining whether ERP constitutes a significant marker of risk that could be screened for with a 12 lead ECG.

This research analyses multiple features of an individuals ECG, looks for the prevalence of known abnormalities associated with conditions that may pose an increased risk of sudden cardiac death and also for novel features which may be associated independently with increased risk. The project has been funded by Cardiac Risk in the Young (CRY), a charitable organisation offering cardiac screening to athletes and young people with the aim of reducing rates of sudden deaths in the young. CRY funded the research for this project as well as providing the infrastructure for collection of data. This data will not form part of any other research project nor be shared with any outside parties. No part of the work is being carried out outside of the UK.

Expected Benefits:

The research output will help inform the cardiology community regarding the risk of the ERP in young adults. The hypothesis is that there will be no increased risk in young adults with ERP. If this is proven, the research will lead to a reduction of unnecessary investigations of asymptomatic individuals with ERP and reduce patient and family anxieties in individuals where ERP is found incidentally.

Based upon current knowledge there is confusion amongst practicing cardiologists, sports physicians and general practitioners as to the significance of the ERP in young adults. Consequently individuals can be restricted from physical activity and referred to specialist centres for further investigation. Such investigation uses health resources and can cause significant anxiety to the affected individual. Furthermore, restriction from physical activity can have a wide range of detrimental physical and psychological effects.

Publication of the research in high impact medical journals will allow it's wide international circulation. Future studies in this area will also reference the work in subsequent investigations. Through academic publication and presentation it is expected that the findings of the research, if significant, will inform future national and international guidelines on the assessment and management on individuals at risk of sudden death and regarding pre-participation cardiac screening of athletes. Such guideline documents are widely circulated and advertised within clinical service. They inform the basis of clinical practice of cardiologists, sports physicians and general practitioners looking after such individuals. In many cases, guidelines are adopted or endorsed by the National Institute for Clinical Excellence (NICE) and therefore effectively become mandatory for NHS physicians.

Outputs:

The research output will be submitted to peer-reviewed cardiology and/or general medical journals in the form of an original research article. It is expected that the work will be accepted for publication in a high-impact cardiology-specific journal, such as Circulation, the Journal of the American College of Cardiology (JACC) or the European Heart Journal (EHJ). These journals are widely read amongst the clinical and academic cardiology community worldwide. Articles published in these journal therefore frequently inform clinical practice and are often cited in national and international guideline documents.

Only aggregated data, with small number suppressed in line with HES guidance, will be included in any research output. No patient level data will be included. It is expected that the research article will be submitted for peer review within 3 months of receipt of the data from NHS digital.

In addition to the written outputs, the research data will be submitted for oral presentation at national and international cardiology conferences such as the British Cardiac Society annual conference, British Heart Rhythm Congress, Euoropean Heart Rhythm Association conference and Heart Rhythm Congress in the USA. Similarly to the journal listed above, these conferences serve to dissipate cutting edge clinical research findings to leading clinical and academic cardiologists. Through this network of academic research presentations the findings, if significant, will lead to changes in national and international guidance on the assessment and management of young adults at apparent risk of sudden cardiac death or undergoing pre-participation ECG screening in the context of elite or amateur sport. Such guideline documents are widely circulated and advertised within clinical service. They inform the basis of clinical practice of cardiologists, sports physicians and general practitioners looking after such individuals.

Summaries of the research findings will also be published by Cardiac Risk in the Young including on their website, via twitter and at the annual CRY International Conference on Sports Cardiology.

Processing:

Completion of the medical questionnaire and acquisition of the ECG were performed by CRY at various sites throughout England and Wales at the time of cardiac screening events. All participants gave written informed consent for their data to be stored and used for research purposes by CRY.

Researchers at St. George’s Hospital Medical School Research Dept used this primary source data (i.e. medical questionnaire responses and ECG) were used to construct two databases. The first containing the participants demographic details and the second containing data from the medical questionnaire and ECG. The databases are linked by unique ID numbers and are password protected. These databases are stored at St. George’s Hospital Medical School Research Dept. Access to the local network is via a unique login ID and password protected. St. George’s Hospital Medical School Research Dept. is IG toolkit compliant. Storage of data acquired from CRY medical questionnaires and ECGs at St. George's is covered by the original research protocol and consent process which were agreed by the local REC (ref MH532A)). These databases are not accessible to CRY staff.

Data in the demographic database will be provided to NHS Digital with the intention of identifying any member of the cohort who has died and to identify the cause of death in each case if applicable. Data provided will be organised in to three groups; those individuals with no ERP; those with low risk form of ERP and those with the high risk form of ERP. Data flow between St. George’s Hospital Medical School Research Dept. and NHS Digital is covered by section 251 and has been approved both by the local REC and by the confidential advisory group (CAG). St. George’s Hospital Medical School Research Dept. request the numbers of deaths within each group as well as the cause of death as per the death certificate for any deceased individual.

Mortality data will be analysed at St. George’s Hospital Medical School Research Dept by an ONS accredited researcher.

Final data will be aggregated to prevent the identification of any individual within the study. All research outputs will include aggregated data only suppressed in line with the HES analysis guide. Aggregated data small numbers will be suppressed in line with the HES analysis guidelines. No data will be shared with third parties. Data will not be accessed from outside the UK.

All organisations party to this agreement must 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).

ONS Terms and Conditions will be adhered to.

The data controller must ensure that there are appropriate contracts and controls in place between the organisation and all persons accessing NHS Digital disseminated data. NHS Digital have the right to audit the controls in place under the data sharing agreement.

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MR39 - SMOKING STUDY - MEN ATTENDING BUPA MEDICAL CENTRE — DARS-NIC-148331-5F2FS

Type of data: information not disclosed for TRE projects

Opt outs honoured: No - data flow is not identifiable, Y, Anonymised - ICO Code Compliant (Does not include the flow of confidential data)

Legal basis: Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii), Other - GDPR does not apply solely to the deceased, Section 251 approval is in place for the flow of identifiable data, Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii), Health and Social Care Act 2012 – s261(2)(b)(ii), Health and Social Care Act 2012 – s261(2)(a)

Purposes: No (Academic)

Sensitive: Sensitive

When:DSA runs 2019-09-26 — 2022-09-25 2019.03 — 2016.11.

Access method: One-Off, Ongoing

Data-controller type: ST GEORGE'S, UNIVERSITY OF LONDON, ST. GEORGE’S HOSPITAL MEDICAL SCHOOL

Sublicensing allowed: No

Datasets:

1. MRIS - Members and Postings Report
2. MRIS - Cause of Death Report
3. MRIS - Cohort Event Notification Report
4. MRIS - Scottish NHS / Registration
5. MRIS - Flagging Current Status Report

Objectives:

This BUPA cohort study was set up to look at risk factors for cancer and cause specific mortality, with an emphasis on the risks of smoking.

The purpose of this request is to continue to receive information on the deaths of men who are part of the BUPA research cohort. This cohort consisted of 22,000 men aged 35-64 years who attended the British United Provident Association (BUPA) medical centre in London for a comprehensive medical examination between 1975 and 1982. The data on mortality and cancers has been used to conduct both cohort and case control studies resulting in over 32 papers being published in peer review journals. The areas of research covered have included the health effects of active and passive smoking, screening, cancer and nutrition, cancer and infection, serum cholesterol in relation to Ischaemic Heart Disease (IHD) and cancer, apolipoproteins, blood pressure and stroke, cardiovascular screening and osteoporosis. Queen Mary University wish to continue to receive the mortality data in order to continue their research into risk factors for mortality, mainly from ischemic heart disease or cancer.

The original purposes of the study were:

1. To continue a prospective epidemiological study of the association between Carboxyhemoglobin (COHb) levels and mortality from Coronary Heart Disease (CHD) and lung cancer.

2. To investigate the interrelationships of COHb levels with risk factors of CHD, and estimate their value in predicting CHD.

3. To clarify some of the conflicting observations concerning the relationship between risk of lung cancer and coronary heart disease in relation to self-described inhaling habits.

4. To store serum and urine samples from men recruited into the study so that substances which may be markers of or aetiologically linked to lung cancer or coronary heart disease can be measured in these samples on a case-control basis after being notified of deaths.

The BUPA study was originally funded by the Medical Research Council and BUPA. Now that recruitment has ended data analysis is conducted by university funded staff without additional external funding.

Yielded Benefits:

The BUPA study has been a very valuable research resource providing evidence to support a range of public health interventions. Early work providing evidence on the link between passive smoking and both lung cancer and heart disease was extremely influential in the government deciding to ban passive smoking from public places (The dose-response relationship between cigarette consumption, biochemical markers and risk of lung cancer,). Additional work on the effect of tar yield of cigarettes also influenced the move to low tar cigarettes. (Mortality in relation to tar yield of cigarettes: a prospective study of four cohorts, Relative intakes of tar, nicotine, and carbon monoxide from cigarettes of different yields.) The BUPA study was also one of the first studies to establish the link between serum cholesterol and subsequent heart disease (Systematic underestimation of association between serum cholesterol concentration and ischaemic heart disease in observational studies: data from the BUPA study) and the link between serum homocysteine and subsequent heart disease (Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention.) and between apolipoproteins and heart disease (Apolipoproteins and ischaemic heart disease: implications for screening.). All these findings have implications for screening for heart disease and will improve the prevention of the 73,000 deaths from heart disease that occur in the UK each year. The BUPA study has also provided information on screening for cancers, with the finding that Insulin-like growth factors are not useful in screening for cancer (Insulin-like growth factors and cancer: no role in screening. Evidence from the BUPA study and meta-analysis of prospective epidemiological studies.) and that PSA is useful in screening for prostate cancer (Prospective observational study to assess value of prostate specific antigen as screening test for prostate cancer.), but that free PSA is not (Adding free to total prostate-specific antigen levels in trials of prostate cancer screening).Prostate cancer is the second most commonest cause of death from cancer in men and therefore any improvements in screening will impact on the lives of large numbers of men. In summary data from the BUPA cohort have been of considerable importance in the field of epidemiology and preventive medicine; particularly in the field of cancer prevention and cardiovascular disease prevention. There have been over 50 publications, the last one as recently as April 2017 (Wald DS et al. Mortality from aortic stenosis: prospective study of serum calcium phosphate. J Int Med 2017;281:407-411).

Expected Benefits:

The Wolfson Institute's work on establishing the link between passive smoking and lung cancer and heart disease using the BUPA database was extremely influential in the government deciding to ban passive smoking from public places. This clearly affects the health of the whole population.

The BUPA study established the link between Prostate-Specific Antigen (PSA) and the risk of developing prostate cancer in men (Prospective observational study to assess value of prostate specific antigen as screening test for prostate cancer; Nov 1995.). The Wolfson Institute is currently collaborating with Professor Hans Lilja (Oxford University) and Dr Brian Shine trying to improve methods of screening for prostate cancer to avoid over-treating men with prostate cancer. This collaboration consists of Oxford providing the technical expertise on stored serum analysis, the Wolfson Institute analysing the results and discussing the interpretation of these with Oxford. Individual patient data is not released to Oxford. Prostate cancer is the most common male cancer and over 41,000 men in the UK are diagnosed with it each year. If a new screening test is developed this would improve the outlook not only for the 41,000 men diagnosed with prostate cancer every year in the UK , but also it would avoid large numbers of men becoming extremely anxious due to being told they are at a high risk of prostate cancer by less accurate screening tests.

Aortic stenosis is a serious heart condition with no known means of prevention. Death follows symptoms of heart failure in most cases unless the valve is surgically replaced. Aortic stenosis is caused by the build up of calcium (a mineral found in the blood) on the aortic valve (flaps of tissue which regulates blood flow) leading to obstruction of blood flow from the heart. Recent work on analysing data from the BUPA study on men with aortic stenosis suggests that lowering plasma phosphate or calcium could prevent calcium phosphate deposition on heart valves. (Mortality from aortic stenosis: prospective study of serum calcium and phosphate,2017). This work provided sufficient evidence for the MRC to fund a randomised trial as a pilot trial to determine whether the progression of aortic stenosis can be prevented using sevelamer. If this is successful it will radically change the management of patients with aortic stenosis, potentially removing the necessity of surgery.

Outputs:

The main aims of the study were:
1. To continue a prospective epidemiological study of the association between COHb levels and mortality from coronary heart disease and lung cancer. This was achieved with over 22,000 men being recruited into the BUPA cohort from 1975 to 1982.

2. To investigate the interrelationships of COHb levels with risk factors of CHD, and estimate their value in predicting CHD.
This was achieved with the following papers being published :
a.Carbon monoxide in breath in relation to smoking and carboxyhaemoglobin levels; May 1981.
b. Serum cotinine levels in pipe smokers: evidence against nicotine as cause of coronary heart disease; Oct 1981.

3. To clarify some of the conflicting observations concerning the relationship between risk of lung cancer and coronary heart disease in relation to self-described inhaling habits.
The following papers have been published:
a. Prospective study of effect of switching from cigarettes to pipes or cigars on mortality from three smoking related diseases; June 1997.
b. The dose-response relationship between cigarette consumption, biochemical markers and risk of lung cancer; 1997.

4. To store serum and urine samples from men recruited into the study so that substances which may be markers of or aetiologically linked to lung cancer or coronary heart disease can be measured in these samples on a case-control basis after being notified of deaths.
This has been achieved – the BUPA cohort information and blood samples have been securely stored for over 40 years (since 1976). Research on a case-control basis continues to be performed on these data , evidenced by the following 9 publications: -
a.Insulin-like growth factors and cancer: no role in screening. Evidence from the BUPA study and meta-analysis of prospective epidemiological studies; July 2006.
b.Chlamydia pneumoniae infection and mortality from ischaemic heart disease: large prospective study; July 2000.
c.Adding free to total prostate-specific antigen levels in trials of prostate cancer screening; Feb 2000.
d. Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention; April 1998.
e. Helicobacter pylori infection and mortality from ischaemic heart disease: negative result from a large, prospective study; Nov 1997.
f. Prospective observational study to assess value of prostate specific antigen as screening test for prostate cancer; Nov 1995.
g. Serum albumin and mortality in the BUPA study. British United Provident Association; Feb 1994.
h. Apolipoproteins and ischaemic heart disease: implications for screening; Jan 1994.
I. Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation; June 1991.

QMUL are currently analysing data concerning the prediction of the occurrence of clinically detected prostate cancer during the following 30 years. It is expected that the results from this study will be finalised in 2019. The value of the BUPA cohort is that any new hypothesis can be investigated extremely quickly as the data and serum samples are all stored at the Wolfson Institute of Preventive Medicine which is part of Queen Mary University London.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide

Processing:

NHS Digital supplied historically the date and cause of death to QMUL. This mortality data was linked to other clinical information on these men using the study ID numbers. QMUL used this information to create case-control data sets where cases include all men who have died from a specific cause and the controls are those men who have not died from that cause. Risk factors for the disease are then examined amongst these case control data sets. Dates of death and birth were not used – only age at death and age at time of collecting the clinical information.

This agreement will only flow pseudonymised data back to QMUL. The Study no longer hold any identifiers for the cohort. NHS Digital will share back to QMUL the following, BUPA unique member ID and month and year of DOB along with exits/re-entries, Cancer registration details (not registration number as this is identifiable) and fact/date/cause of death.

The data will not be linked to any other information about the participants. QMUL have already collected all information required about the cohort and will not be linking to any additional datasets.

The data on mortality received will be coded and stored in the BUPA cohort database on a secure fire-walled server at the Wolfson Institute of Preventive Medicine.

The data can be accessed only via passwords by three members of staff who are all substantive employees of the QMUL. No identifying information is released. The data will not be linked to any other information about the participants.

Data will only be accessed and processed by substantive employees of Queen Mary University London and one member of the team who is working under an honorary contract at QMUL.

All organisations party to this agreement must 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.

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