NHS Digital Data Release Register - reformatted

Liverpool Heart And Chest Hospital NHS Foundation Trust projects

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

FFRCT In Stable Heart disease & CTA Helps Improve Patient care and Societal costs (FISH & CHIPS) — DARS-NIC-460711-S8W6S

Type of data: information not disclosed for TRE projects

Opt outs honoured: Identifiable, Yes (Section 251 NHS Act 2006)

Legal basis: Health and Social Care Act 2012 – s261(7); National Health Service Act 2006 - s251 - 'Control of patient information'., Health and Social Care Act 2012 - s261(5)(d); National Health Service Act 2006 - s251 - 'Control of patient information'.

Purposes: Yes (NHS Trust)

Sensitive: Sensitive, and Non-Sensitive

When:DSA runs 2022-04-25 — 2023-04-24 2022.09 — 2023.07.

Access method: One-Off

Data-controller type: LIVERPOOL HEART AND CHEST HOSPITAL NHS FOUNDATION TRUST

Sublicensing allowed: No

Datasets:

  1. Civil Registration - Deaths
  2. Diagnostic Imaging Dataset
  3. Emergency Care Data Set (ECDS)
  4. Hospital Episode Statistics Accident and Emergency
  5. Hospital Episode Statistics Admitted Patient Care
  6. Hospital Episode Statistics Critical Care
  7. Hospital Episode Statistics Outpatients
  8. Civil Registrations of Death
  9. Diagnostic Imaging Data Set (DID)
  10. Hospital Episode Statistics Accident and Emergency (HES A and E)
  11. Hospital Episode Statistics Admitted Patient Care (HES APC)
  12. Hospital Episode Statistics Critical Care (HES Critical Care)
  13. Hospital Episode Statistics Outpatients (HES OP)
  14. Medicines dispensed in Primary Care (NHSBSA data)

Objectives:

The Liverpool Heart and Chest Hospital (LHCH) requires access to NHS Digital data for the purpose of the following research project: "Fractional Flow Reserve derived from Computed Tomography In Stable Heart disease and Coronary Computed Tomography Angiography Helps Improve Patient care and Societal costs (FISH and CHIPS)".

Rapid, early and accurate diagnosis of coronary artery disease (CAD) is essential to allow the appropriate diagnosis and treatment of patients. Coronary Computed Tomography Angiography (CCTA) is now the most used test for investigating patients with suspected CAD. For the two thirds of patients who have CAD, CCTA cannot tell whether the CAD is responsible for the patients' symptoms. This results in patients requiring further tests and sometimes unnecessary invasive tests (angiograms) with an increased risk to the patient and cost to the NHS.

A company called HeartFlow Inc, have developed new technology called computed tomography-derived fractional flow reserve (FFRCT) which uses the CCTA images to make a 3D model of the heart blood vessels that shows whether there is a limitation in the blood flow to the heart which is causing the symptoms. The National Institute for Health and Care Excellence (NICE) recommends the use of FFRCT in a chest pain pathway. However, use of this new technology remains limited due to funding restrictions and uncertainty as to its benefit in the NHS.

Between 2018-2020, several hospitals utilised FFRCT as part of an NHS Innovation and Technology Payment the NHS Innovation and Technology Payment (ITP) programme (henceforth 'the FFRCT programme'). LHCH requests use of data collected by NHS Digital on all patients who had a CCTA during the period of the FFRCT programme. The study aims to identify whether the use of FFRCT in population of patients with chest pain (angina) is safe, reduces the time to diagnosis, reduces the need for unnecessary tests and is thus cost effective. As a national programme it will also be able to identify any potential regional variations and health care discrepancies.

This pragmatic ‘real-world’ trial is designed to utilise big data to answer practical health questions and determine clinical outcomes in a timely fashion. The aim is to use information that is already collected by the NHS to determine whether the introduction of a new health care technology, FFRCT, has improved patient care and reduced costs to the NHS. No patient will be required to have any additional hospital visits or tests, as the study will be looking back to see how their care was impacted.

The study will be comparing individuals’ care who had the FFRCT (n=9700) to those that did not (n=100,000-110,000). Both the FFRCT and non-FFRCT group cohorts will be provided to NHS Digital. The time period for the data request corresponds to the time of the FFRCT programme (2018-2020), one year prior as a control period (2017-2018), and a follow-up period. 2017-2020 reflects the full time period for recruitment to the study. Patient data will be collected at 12 weeks, 12 months and 24 months post-CCTA. Longer-term follow-up (~5-10 years) is ultimately intended to provide a true long-term perspective of health care resource use in a stable angina population.

Hospital Episode Statistics (HES) Admitted Patient Care (APC), Critical Care (CC), Accident & Emergency (A&E) and Outpatient (OP) databases, Emergency Care Dataset (ECDS), Diagnostic Imaging Data (DID) set and Civil Registrations (Deaths) data is requested to achieve the study’s aims. These datasets will provide information on all hospital admissions and outpatient appointments at NHS hospitals in England. They will also provide information on any diagnostic tests performed. Record level patient information (such as age group, gender and ethnicity) and information on where patients are treated and the area where they live will be acquired from NHS Digital HES data. This demographic information is required to assess whether there are any variations in care or outcomes relating to these factors.

The geographical spread of the datasets represents all NHS England hospitals participating in the FFRCT programme. This allows the study team to assess the real impact of implementing a new health technology programme nationally from a centrally funded system. It also allows the study team to see whether this policy and health technology helps reduce geographical variations in health care. There is no alternative less intrusive method of achieving the study purpose. Data requested will only reflect the data that is required to answer the study questions.

28 NHS England research sites were involved in identifying eligible patients who had a CCTA during the study time period using their radiology information system. These sites send these patients’ personally identifiable information (NHS number, CT study date, CT study type, and hospital number) to the Clinical Trials Unit (CTU) at Liverpool Heart and Chest Hospital.

Liverpool Heart and Chest Hospital is the sponsor of the study and sole data controller who also processes the NHS Digital data. As a research organisation, Liverpool Heart and Chest Hospital’s lawful basis under the General Data Protection Regulations (GDPR) supporting the processing of personal data is Public Task - Article 6(1)(e). The additional GDPR lawful basis supporting the processing of special category data is Article 9(2)(j) - Scientific Research. These legal bases are applicable as the data will allow the Liverpool Heart and Chest Hospital to assess whether the introduction of a new technology into the NHS on a national scale helps improve patient management and clinical outcomes, and reduce regional variations in care and costs to the NHS. This study will have significant public interest in determining whether this health technology has patient benefits (reduced tests, reduced waiting time) and will have interest to the NHS in determining whether the technology is cost effective.

Liverpool Heart and Chest Hospital have section 251 support from the Confidentiality Advisory Group for this project. A specific condition of this support is that all staff involved in processing data under this section 251 support must have successfully completed local security awareness training before processing any data.

The University of Liverpool, University of Cambridge and the Royal Brompton Hospital are named on the study grant. None of these collaborators are handling NHS Digital data. The role of these collaborators is support of the grant application, study recruitment process and providing intellectual advisory input through their representative principal investigator. These collaborators do not determine the purpose or the means of the data processing. The principal investigators also support the study by providing their local cohort datasets.

HeartFlow Inc, (Redwood City, US) are also named on the study grant. HeartFlow Inc, are the private company who perform the FFRCT analysis for the NHS Trusts. They have National Institute for Health and Care Excellence (NICE) Medical Technologies Guidance (MTG32) approval and were funded by NHS England as part of the Innovation and Technologies payment programme. They provide the FFRCT data (per patient and per vessel lowest FFRCT values) to Liverpool Heart and Chest Hospital CTU. HeartFlow Inc, have no access to the NHS Digital data and do not determine the purpose or the means of the data processing. There may be a commercial benefit to HeartFlow Inc, depending upon the study results as the only current provider of FFRCT in the NHS. Should the study results be favourable for the impact of FFRCT HeartFlow Inc, could use this for their own internal research or commercial benefit. The FISH and CHIPS study results may be of commercial interest to the industrial partner- HeartFlow Inc,. Whilst there is no direct financial benefit from the study, if the results are favourable for the use of HeartFlow Inc,'s FFRCT in the management of coronary artery disease there will be indirect commercial benefit. HeartFlow Inc, holds the US Food and Drug Administration (FDA) and European CE mark patents for the technology and have substantial intellectual property (IP) invested in the technology.

NHS England's accelerated access collaborative (AAC) have been involved in the concept of this study and are supportive of its design. Aggregated results data with small number suppression applied will be made available to them for commissioning and health policy decisions. NHS England do not determine the purpose or the means of the data processing and do not process NHS Digital data.

The Innovation Agency and West Midlands Academic Health and Science Networks (AHSNs) have been involved in improving the uptake of the FFRCT programme and will promote the small numbers suppressed aggregated study results amongst local networks. The listed AHSNs do not determine the purpose or the means of the data processing and do not process NHS Digital data.

The study is funded by the Medical Research Council (MR/T024933/1) and has ethical approval from the Health Research Authority and support from the Confidentiality Advisory Group under regulation 5, section 251 (IRAS project ID: 285996). The Medical Research Council do not determine the purpose or the means of the data processing. For the reasons stated, none of the above listed organisations excusing LHCH are considered either a data controller or a data processor under this Data Sharing Agreement.

Expected Benefits:

This research is expected to answer whether an NHS FFRCT pathway is better for the patients in terms of safety, reducing unnecessary alternative tests, time to treatment and reduce costs compared to previous diagnostic pathways. The impact on the NHS and global health policy for chest pain management is anticipated to be substantial. It could influence the way that health policy makers decide to introduce new technologies or interventions into the health care system by promoting a more centralised funding approach. There is the potential that this national approach has quicker and more effective health benefits and importantly reduces the possibility of a post code lottery or differing outcomes dependent upon social deprivation indices.

The results of this study are intended to aid NICE in their updating of the chest pain clinical guidance (CG95) and medical technologies guidance (MTG 32). All results will be made available to NICE for independent scrutiny and assessment for inclusion in future guidance.

The data dissemination has the potential to impact NHS England's health policy. All results will be made available to NHS England. Publication and communication of the results will be co-ordinated with NHS England to maximise impact.

The study have engaged extensively with patients and the public. A patient and public involvement event was held with the opportunity for the patient group to inform the research questions, influence the design of the study and highlight important factors for the study team to include. A lay public representative was involved in the design of the study and writing of the protocol. The study protocol and lay summary were reviewed by a National Institute for Health Research (NIHR) research design service lay representative. A member of the public is also on the trial steering committee. The study team will continue to engage with the study patient and public engagement group with regards to the conduct, results and publication of the study over its lifecourse.

It is hoped that initial data analysis will be able to commence in summer 2022, with publications and sharing of study results with NICE and NHS England intended in autumn/winter 2022.

Outputs:

The results of this study are intended to be shared with NHS England's Accelerated Access Collaborative (AAC), submitted to peer reviewed journals (European Heart Journal, British Medical Journal) and presented at conferences. Specific target dates:

1. First report - Conference presentation: European Society Cardiology (ESC) Congress 26-29th August 2022
2. Publication in Peer review journal: Simultaneous ESC publication August 2022 (European Heart Journal)
3. Subsequent data analysis (2 year data) and conferences/publications will be subject to the publication committee review

All outputs will be aggregated with small numbers suppressed in line with the HES Analysis Guide.

There will be continued support and active involvement from all interested parties (study collaborators, HeartFlow Inc, NHS England accelerated access collaborative (AAC), NICE) for the lifetime of the research. Any results available to these parties will be aggregated with small numbers suppressed. HeartFlow Inc, have appointed a UK lead for engagement and advocacy who is working closely with NHS England and the AAC. The company have agreed to support the research by providing the FFRCT data for the duration of the programme. The results of this study will be of paramount importance to NICE in their updating of the chest pain clinical guidance (CG95) and medical technologies guidance (MTG 32). All results will be made available to NICE and the AAC for independent scrutiny and assessment for inclusion in future guidance. The study principal investigator has advised NICE for their MTG implementation and sits on the NICE technology adoption panel.

The Innovation Agency Academic Health and Science Network (AHSN) have worked extensively with the lead investigators, HeartFlow Inc, and NHS England to improve the uptake of the FFRCT programme. This AHSN has agreed to continue this national and regional engagement, informing health policy makers (local commissioning groups and hospitals) in order to communicate the research results. The study team will also use social media (Twitter - @LHCHFT (Liverpool Heart and Chest Hospital); @LiverpoolCCS (Liverpool Centre for Cardiovascular Science); @NIHRCRN_nwcoast (NIHR North West)) and the national Cardiac and Cardiac CT Societies to communicate the study results.

Processing:

HeartFlow Inc, will provide FFRCT data to Liverpool Heart and Chest Hospital (LHCH) Clinical Trials Unit (CTU). Participating hospital sites will provide radiology information (date of CT scan and referral to treatment time) to LHCH CTU, for all patients who had a CCTA for chest pain in England between 2017-2020.

The LHCH CTU will provide NHS number and unique study ID to NHS Digital for all eligible cohort members of the FISH and CHIPS study who have not registered a type 2 opt out. No HeartFlow Inc, data will be provided to NHS Digital.

NHS Digital will provide Hospital Episode Statistics (HES) Admitted Patient Care (APC), Critical Care (CC), Accident & Emergency (A&E) and Outpatient (OP) data, Emergency Care Dataset (ECDS), diagnostic imaging data (DID) and Civil Registrations (Deaths) data of matched patients who have not registered a type 2 opt out back to the Liverpool Heart and Chest Hospital CTU for the period 2016/17 – 2021/22.

LHCH CTU will link the NHS Digital data with patient specific FFRCT data by the unique hospital identifier. HeartFlow Inc, only have a unique hospital identifier associated with the data they are providing to LHCH. The hospital trusts providing LHCH with patient data provide both NHS number and the hospital identifier, allowing trust referral to treatment time to be linked with HeartFlow Inc, data. The LHCH will link the NHS Digital data with ‘referral to treatment time’ data provided by the recruitment sites.

All analysis will be performed on the linked data by LHCH CTU. HeartFlow Inc, will have no access to any NHS Digital data and are not processing the data. Only aggregated results with small number suppression that has been derived through the processing of NHS Digital data may be shared with HeartFlow Inc,.

LHCH CTU will store patient identifiable information (NHS number and hospital number) separately to the study data on which analysis will be undertaken. LHCH would only identify an individual within the study dataset in the event that an individual requests that their data is no longer used in the study, or in the rare event that this is required as part of the audit of the study. There will be no other requirement or attempt to identify individuals.

LLHCH CTU will undertake an analysis of the safety of FFRCT based on the rate of adverse events (MACE) as a composite of all-cause death, heart attack and invasive coronary procedures to restore blood flow and oxygen to the heart. Number of investigations post CCTA will be compared between FFRCT and control groups. Cost analyses will include total patient pathway costs at 12 months, with comparison between the two groups.

Only substantive employees of LHCH who have been appropriately trained in data protection and are part of the research project will have access to the NHS Digital data. Study staff will comply with the Data Protection Act 2018 with regards to collection, storage, processing and disclosure of data. Data access and analysis will be performed onsite. All data will be stored within the NHS trust secure research framework with password protection and external server backup. Publication of the study results will not include any patient identifiable data. All outputs will be aggregated with small numbers suppressed in line with the HES Analysis Guide.

RIPCORD 2 Trial: HES data for outcome analyses. — DARS-NIC-303379-H4C8H

Type of data: information not disclosed for TRE projects

Opt outs honoured: No - consent provided by participants of research study, Identifiable, No (Consent (Reasonable Expectation))

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

Purposes: No (NHS Trust)

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

When:DSA runs 2019-12-01 — 2022-11-30 2020.05 — 2020.11.

Access method: One-Off

Data-controller type: LIVERPOOL HEART AND CHEST HOSPITAL NHS FOUNDATION TRUST, UNIVERSITY HOSPITAL SOUTHAMPTON NHS FOUNDATION TRUST

Sublicensing allowed: No

Datasets:

  1. Hospital Episode Statistics Outpatients
  2. Hospital Episode Statistics Critical Care
  3. Civil Registration - Deaths
  4. HES:Civil Registration (Deaths) bridge
  5. Hospital Episode Statistics Accident and Emergency
  6. Hospital Episode Statistics Admitted Patient Care
  7. Bridge file: Hospital Episode Statistics to Diagnostic Imaging Dataset
  8. Diagnostic Imaging Dataset
  9. Civil Registration (Deaths) - Secondary Care Cut
  10. Civil Registrations of Death - Secondary Care Cut
  11. Diagnostic Imaging Data Set (DID)
  12. Hospital Episode Statistics Accident and Emergency (HES A and E)
  13. Hospital Episode Statistics Admitted Patient Care (HES APC)
  14. Hospital Episode Statistics Critical Care (HES Critical Care)
  15. Hospital Episode Statistics Outpatients (HES OP)

Objectives:

RIPCORD (Does routine pressure wire assessment influence management strategy at coronary angiography for diagnosis of chest pain?) was a proof of concept study designed to assess the feasibility and management impact of routine assessment of fractional flow reserve (FFR) in patients undergoing angiography for diagnosis and management of stable chest pain.

FFR is an invasive measure of the change in pressure across any given narrowing (or ‘stenosis’) of a coronary artery, acquired using a pressure wire placed in the vessel. It has been shown that using this measurement to determine whether a stenosis is clinically significant, and requires treatment, results in improved clinical outcomes for patients. Despite this weight of evidence, FFR is still not routinely used in many centres across the UK and the world. There are multiple reasons for this, including: cost implications, extra procedural time/complexity and lack of expertise.

In RIPCORD (compromising a total of 200 patients) when FFR data were available to cardiologists who had previously only had angiographic data, there was a change of the management plan (between options: optimal medical therapy (i.e. tablet treatment), Percutaneous coronary intervention (i.e. balloons/stents) or coronary artery bypass graft surgery (CABG)) in 26%. This was the result of a change in the classification as to whether coronary arteries had a “significant” stenosis in 32% between angiographic assessment alone versus FFR data. These data suggest that routine FFR measurement in such patients at the stage of diagnostic angiography would have profound impact on improving the management strategy by tailoring therapy. It is likely that a strategy of systematic FFR-guided assessment of coronary artery disease will be associated with more effective resource utilisation, improved patient-reported quality of life and better clinical outcome when compared with angiographic guidance alone. Based upon this hypothesis, a large scale and definitive randomised trial of this strategy was designed (RIPCORD 2).

RIPCORD 2 is an open-label, prospective, dual-arm, multi-centre, randomised controlled trial across 17 percutaneous coronary intervention (PCI) centres in the UK (16 in England/Wales and 1 in Scotland). These are all specialised local or regional tertiary cardiac centres where patients with heart attacks or angina can undergo invasive coronary angiography and, if necessary, treatment using balloon/stent type technology.

Full Research Ethics Committee and local site approvals were gained.

Patients were screened for inclusion/exclusion criteria at two time points (before, and again at the time of angiography). Patients eligible and willing to participate underwent a formal informed consent process before the point of angiography. Patient information sheets and consent forms were approved by NRES and local hospital process prior to implementation. The consent process included gaining permission to access subsequent data from Hospital Episode Statistics (HES) for follow up purposes. Eligible patients were randomised 1:1 to either conventional angiography alone or routine pressure wire assessment (FFR) in all main vessels.

Study Outcome measures are as follows:

- Primary Economic Outcome Measure:

The primary economic outcome measure will be a comparison of health care costs, observed over the 12 month follow-up period. The case record form will be designed to capture key elements of resource utilisation during the index procedure and up to the confirmation of the initial management strategy. Costs for each patient will then be calculated for hospitalisation events, reported by the UK Hospital Episode Statistics. The study will capture details of the index and all subsequent hospitalisation events, elective procedures, outpatient appointments and investigations. A standardised UK cost model will be applied for reported diagnostic and procedural codes. The primary analysis will describe the range of observed total costs and compare the mean total costs incurred in the two groups created at randomisation (or median, depending on the distribution of observations).

- Primary Quality of Life Outcome Measure:

This analysis will compare the mean (or median), patient reported quality of life scores using the EQ-5D-5L health questionnaire. Patients will complete the questionnaire at 12 months from randomisation (plus or minus one month).

- Secondary Outcomes: Clinical Events
Clinical event rates at one year derived from HES;
• All-cause mortality
• Number of hospitalisation events and total hospital days
• Hospitalisation events coded as:
- Cerebro-vascular accident (CVA)
- Myocardial infarction

Coronary revascularisation. This analysis will involve a pre-specified subgroup analysis of:
• Planned revascularisation - if declared as the index strategy
• All additional revascularisation events

Additional descriptive statistics will be provided (for the two randomised groups) in terms of the overall pattern of hospitalisation events in terms of diagnostic classification and procedures performed.

A total of 1100 patients were recruited into the study (1062 in England/Wales, 38 in Scotland). The study is now at the end of the 12 month follow up period for the last of those 1100 patients. As such the study team now intend to request the HES data for 12 month follow up of the complete cohort, which all the participants consented to. Given the primary and secondary outcome measures of the study, researchers clearly require a complete set of pseudonymised HES data relating to all hospital admissions anywhere in the UK with related codes, as well as mortality data (both dates and causes of death) for the 12 month follow up period.

Data on all hospital admissions for any purpose are required because ultimately it is very hard to define what is 'cardiovascular' or 'non-cardiovascular' when it comes to admissions for various reasons. There are some cases that are obvious: e.g. an admission with a severe heart attack, or at the opposite end of the spectrum an admission with a stubbed toe. The reality is however is that life is not always that black and white. Frequently people are admitted with multiple issues, some may be related to cardiac causes and others not. Similarly trying to define exact causality is not always that obvious. An extreme example would be someone who gets dizzy and blacks out in the middle of the road, hit by a bus and breaks their leg. The cause for admission might seem to be orthopaedic but actually it all can be traced back to the heart medication they received that gave them low blood pressure. Another example would be if one patient in a particular arm of the study gets inferior heart treatment that might mean they get depression because they have much worse angina, as a result they could be admitted with depression or even pneumonia because they are less active, etc. Additionally the nature of the study means that the group a participant is in would make it more or less likely that they underwent a coronary bypass operation. It is very common to get non-cardiac complications after these operations (e.g. mobility problems, wound infections etc) which are also very important to identify. There is a lot of 'grayscale' so trying to distinguish accurately between those admissions that will be directly related to activity in the trial and those that are not is essentially impossible. By far the cleaner and more scientifically sound methodology is to compare all healthcare costs incurred in both groups. This is the only method free of any potential confounders or error. This would be the best and only good way of assessing for differing financial implications of the two treatment strategies in the study. Secondly, a reduction in total healthcare costs is much more meaningful as a study outcome as it translates into real world cost savings that can be interpreted by the scientific community and related to daily practice.

Due to the all encompassing nature of the primary health economic outcome measure and the requirement for all hospital admissions and certain outpatient activities (including procedures/investigations) the study will require the following datasets: HES Admitted Patient Care, Civil Registration (mortality), HES Accident and Emergency, HES Critical Care, HES Outpatients, Diagnostic Imaging.

The trial resource utilisation model requires researchers to take into account any patient hospital contact that relates to their heart health: defining this requires a broad knowledge of their outpatient and inpatient contact with the NHS and tests generated. All admission and outpatient appointments will therefore be components of the economic model, since the resource utilisation model the study has chosen does not pre-specify specific datapoints that trigger costs, but takes account of complete NHS interactions. Further, admissions including revascularisation, angiograms, heart attack, heart assessment, etc not only go into overall cost analysis, but are part of pre-specified secondary endpoints for the trial, and these will be identified in HES Accident and Emergency, HES Critical Care and HES Outpatients.

Digital Imaging Dataset (DIDs) will provide valuable resource data for investigations including MRI and CT, etc many of which will be referred via Outpatients. DIDs data are required in order to inform the uptake of all the digital imaging tests (most commonly MRI/CT) by patients in the randomised trial. This is completely consistent with the trial primary outcome which is complete resource utilisation within the NHS. Thus, imaging utilisation is as important as any other aspect of interaction with the NHS to feed into the model. The nature of the imaging test is not specifically important, because the resource model (one of several options for resource models commonly employed in research trials) requires information on all DID.

Mortality data will provide cause of death details which will also contribute to the overall cost analysis.

The admission related codes for each patient will be used in conjunction with UK tariffs to calculate the overall incurred healthcare costs for the primary outcome measure. This is not achievable by any other means than access of the HES coded data. The nature of each admission (i.e. specific codes) is required for this costing exercise and also to calculate the incidence of other clinical secondary outcome measures. Mortality data is also required as an outcome measure and is integral to understanding any important differences observed in the two groups.

The study requires a one-off extract of data for patients for a 12 month period from the date of randomisation.

The study team will minimise the data requested to that which is necessary to calculate outcome measures; datasets not relevant to this will not be asked for. For example, the study is not requesting maternity or mental health datasets. Within the requested datasets the fields requested have been limited to essential items. For instance, within the APC dataset, the study has not requested patient level, geographical, socio-economic or psychiatric data.

The organisation involved is primarily the ICECAP research group based at Liverpool Heart and Chest Hospital NHS Foundation Trust. The study had 17 recruitment sites in the UK, but the recruitment sites are not involved in the processing of the data being requested. The chief investigator and sponsor for the study are based at University Hospital Southampton, however the ICECAP research group at Liverpool Heart and Chest Hospital (where the co-principal investigator resides) is the designated site/agent responsible for collection, storage and analysis of the study data. This is the only site where data returned from NHS Digital will be stored or accessed.

Liverpool Heart and Chest Hospital NHS Foundation Trust and University Hospital Southampton NHS Foundation Trust are joint data controllers and both organisations will process the data. However, Liverpool Heart and Chest Hospital will be the only site where data will be accessed or processed. No work on this study has or will be undertaken outside the UK. The study was funded by the Sponsor- the University Hospital of Southampton.

Explicit written informed consent was given by trial participants for the access to their electronic healthcare records. The study cites GDPR Articles 6(1)(e) and Article 9 (2)(j) as lawful bases to process the data. The study requires this data on one occasion, at one time point. The purposes of the study are clearly outlined and were explained to participants during the consent process. These have not, and will not, change during the study. All patients were given contact information should they wish to withdraw from the study. To date, no participants have withdrawn their consent.

The study has already received equivalent datasets from NHS Wales Informatics Service in Wales. The HES data from England/Wales etc will be processed separately. The key outcome data (e.g. healthcare spell costs and specific clinical outcomes e.g. MI codes) will then be extracted into a master pseudonymised database. This is the point at which data from different sources will be linked; this therefore does not involve the entirety of the HES datasets, just the key information required to achieve the study results. The study team take measures to ensure there is no data protection breach including pseudonymising the data, by removal of patient identifying information other than the study ID.

Expected Benefits:

The results of this study could have a profound impact on recommended practice in cardiology. This has the potential for significant clinical improvements for patients in the future, in both prognostic terms and with regards to overall quality of life. It is therefore important for patients that the data and results are disseminated to enable a change in practice. Patients gave their consent for use of this data and it is therefore the obligation of the investigative team to complete the trial and publish its findings for the betterment of evidence based clinical practice in the future. Findings have the potential to change clinical practice guidelines on a national and international level; if positive the trial may lead to the recommendation of routine pressure wire usage in patients undergoing coronary angiography. Given the high prevalence of coronary artery disease and the large numbers of patients undergoing invasive procedures worldwide, this would potentially impact the care of thousands of patients. Demonstration of a clinical benefit to patients could substantially increase the use of pressure wire technology on an international level.

There are also potentially large health economic implications. If the study's hypothesis is proven to be true then a switch to a routine FFR guided approach in the investigation of coronary artery disease could lead to significant savings in healthcare costs. This is of particular importance in a constrained health care system of limited resources and funding such as that in the UK. The potential health economic benefits are hard to quantify until the results of the study are available. However, if a significant cost saving per patient is proven, given the huge number of patients treated for coronary artery disease worldwide, the potential overall benefits would be large. For example, in 2016 there were over 260,000 invasive coronary angiograms and over 100,000 PCI (percutaneous coronary intervention) procedures performed in the UK alone. Therefore, even a small cost saving per patient will equate to a large cost reduction overall. This could financially benefit health care systems locally and nationally.

Given the frequency of guideline production with cardiology, any alterations as a result of this trial's results may have the potential to significantly change practice within a short space of time (e.g. within 5 years).

Although not the primary purpose of this study, the formulation of results will also contribute towards a post graduate MD thesis for one of the main researchers.

Outputs:

The output expected would be at least one, or potentially multiple, high-quality scientific papers on the results of RIPCORD 2. As there are different types of outcomes in the trial (traditional clinical event end points compared to health economic analyses) this may lend itself to multiple different publications of results. The expectation is for the primary publication of the randomised control trial results to be in a high impact journal. As a reference example, the original RIPCORD study was published in Circulation: Cardiovascular Interventions. Due to the larger nature of this second study with potentially greater clinical impact the study anticipate publication in an equivalent or even higher impact journal. Due to the large amount of ancillary data captured the study may aim for additional smaller papers on specific aspects e.g. relating to procedural details. The target data for the primary paper would be April 2020 but depends on the speed at which the data can be extracted and subsequently analysed. The final article will not include any patient identifiable information. The final article will be reviewed by the research team prior to submission. As stated, it is not yet clear which journal will be targeted for publication as this will depend on circumstances nearer the time of publication. The data in outputs will be anonymised, aggregate level data with small numbers suppressed in line with HES analysis guide.

It is also likely, given the potential large clinical impact, that results will be presented during at least one large international cardiology conference, either ahead of or in conjunction with publication. Depending on timing of our final results, the study will most likely target the American College of Cardiology (ACC), or European Society Cardiology (ESC) conferences in 2020. In this aspect the results may be cited on cardiology related websites/social media/news platforms surrounding those conferences. The research may be cited in future publications by other authors. Again, no patient identifiable information will be included in the results presented in this domain. Results of the study will be available to the public and presented in appropriate forums. This may include presentation to patient groups (such as the SURE group in Merseyside), public news reports and on websites such as clinicaltrials.gov.

There is a clear and real potential for these results to affect clinical practice guidelines in cardiology, both on a national and international level. If significant the results could lead local, national and international policy making bodies e.g. National Institute of Clinical Excellence or European Society of Cardiology to update relevant clinical practice guidelines.

Processing:

Description of the data flow:
1) Liverpool Heart and Chest Hospital NHS Foundation Trust will securely transfer a file of identifying information (Study ID, NHS Number, Gender and date of birth) plus each participant's individual start and end dates to NHS Digital. For avoidance of doubt, participants' names will not be supplied to NHS Digital.
2) NHS Digital will link the cohort to HES, DIDs and mortality data using NHS Number, date of birth and gender.
3) NHS Digital will generate and transfer a file of linked data to the secure environment at Liverpool Heart and Chest Hospital NHS Foundation Trust.

The data will be securely linked and held within Liverpool Heart and Chest Hospital NHS Foundation Trust and will be available for access only by the research team. The dataset will be used to identify all hospital admissions, related codes and mortality data (including dates and cause of death) up to 12 months after recruitment date for each individual in the cohort.

Data management and analysis is to be conducted within the ICECAP research unit at the Liverpool Heart and Chest Hospital NHS Foundation Trust. The specific methodological activities involved in the processing of data are as follows:

The HES Admitted Patient Care, A&E, Critical Care, Outpatients and Civil Registration data will be requested for all trial participants who provided consent and who have not subsequently formally withdrawn from the trial. A one off request for data will be made for all applicable participants after the 12 month follow up period has ended for all 1100 in the cohort. Each participant has a unique start date for follow up (the day at which they were randomised in the trial). The study is requesting 366 days of follow up for each individual (for example from 1/5/2017 to 1/5/2018 inclusive); this is to allow for the fact that participants were randomised at different times of day into the study and thus ensures a full 365 days of follow up is captured in all cases. Hospital activity (particularly in Admitted Patient Care datasets) may cross the start and end dates of follow up in many patients; the study seeks to capture all this data. The primary data search will be performed using hospital episode/spell admission dates, so that any admission starting between day 0 up until before, or on, day 366 of the follow up period is collected. At the beginning of the follow up period for each participant NHS Digital will also have to search by discharge date to ensure any hospital spell with a discharge date after day 0 but an admission date preceding it, is still collected. (This will pick up HES data for the index hospital admissions in the study).

The research team will send Study ID, NHS Number, date of birth and gender to NHS Digital. The file will also contain the unique start and end dates for the follow up period for each participant (day 0 and day 366 respectively). Within the data file returned by NHS Digital, the research team need to know the study ID associated with each individual’s data within the time period of interest. No other identifiers other than the study ID are required in the returned file; the returned data will therefore be pseudonymised. The data file will be securely transferred back to the ICECAP research unit at the Liverpool Heart and Chest Hospital NHS Foundation Trust, again using NHS Digital’s Secure Electronic File Transfer SEFT system. The Study ID will be used to link the data received to that already recorded for each participant in the case record forms. Once the pseudonymised data has been downloaded and stored securely, there will be no further need to identify individuals.

Data will be stored electronically on a password protected ICECAP group drive on the Liverpool Heart and Chest Hospital NHS Foundation Trust central servers, located in an access-controlled server room and connected to the main trust network, located behind a firewall. Physical access is limited to Computer Services Department staff. Data will be encrypted using industry standard techniques meeting the Data Security and Protection Toolkit (RBQ). The data will not be transferred to an additional location.

Analyses will be completed using the pseudonymised data set and will be viewed in an encrypted Microsoft Excel/Access database on a network PC in the ICECAP research unit. Access will be limited to the research group involved in the study. All data will be stored and accessed at the Liverpool Heart and Chest Hospital NHS Foundation Trust at all times. All personal data in this trial is kept strictly confidential and is being handled, stored and destroyed in accordance with GDPR. The data in its pseudonymised form would not be identifiable alone. To be identifiable this study ID would have to be converted back to corresponding NHS numbers/identifiers- this information is kept in a completely separate database in a different secure location on a different server- again with limited access to certain individuals.

Only individuals who are part of the ICECAP research group and part of this study, will have access to the data. The Chief Investigator of the study, who is employed by University Hospital Southampton NHS Foundation Trust, may need and will have access to view the data but only at the LHCH site (the data will not be accessible from the Southampton site). There will be no external data flow of identifiable information outside of LHCH. No other collaborator of this study will have access to the data received from NHS Digital (that includes the sites involved in the data safety monitoring etc).

All organisations party to this Agreement will 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).