FFRCT In Stable Heart disease & CTA Helps Improve Patient care and Societal costs (FISH & CHIPS)

The Liverpool Heart and Chest Hospital (LHCH) requires access to NHS England 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 England 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 a FFRCT (n=9700) to those that did not (n=80,000). Both the FFRCT and non-FFRCT group cohorts will be provided to NHS England. 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 2 year follow-up period (31st March 2022). The Health Technology (FFRCT) was introduced into the health system during 2018. Patient data will be collected at 90 days, 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.

The following dataset are requested to achieve the study’s aims:

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, NHS Business Services Authority (NHS BSA) and Civil Registrations (Deaths). 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.

Level of data: Record level, pseudonymised, patient information (such as age group, gender and ethnicity) and information on where patients are treated and the area where they live will be requested. This demographic information is required to assess whether there are any variations in care or outcomes relating to these factors. NHSBSA data is required to ensure that any changes in clinical outcomes observed over time following the health technology intervention are a result of the technology itself rather than variations in medical treatments. To be certain of this LHCH require the strength and number of medications taken over the study time period.

Item costs within the NHSBSA dataset are required as it is to determine the overall cost effectiveness of health treatments, including the medicines data as the study is estimating total NHS costs which includes hospital visits, tests etc. To have an accurate assessment of total healthcare costs this requires linkage to the medicines costs. LHCH can then determine the clinical effectiveness and cost effectiveness of the health intervention and medicines.

The linkage of the NHSBSA medicines data to the existing data from NHS England will allow LHCH to provide information relating to the:

1. Safety of medicines: LHCH have adverse clinical events data including heart attacks, cardiovascular death, all cause death, stroke etc. The medicines dispensed, dose and number of tablets will be used to look at relations to adverse events and thus safety.

2. Effectiveness of medicines: A key component to this study is to determine the effectiveness of the medicines (in particular aspirin and statins) on reducing the risk of the adverse clinical events (heart attacks, cardiovascular death, all cause death, stroke). This will be assessed simultaneously as the impact of the health technology. Without both sets of data LHCH will not be able to determine the impact of medications or health technology, nor their inter-relationship or independence.

The study needs to determine what medications patients were on during the study period in order to identify whether this impacted clinical outcomes. Data requested is minimised to the British National Formulary (BNF) name of the medication, whether the medication was dispensed (i.e. did the patient collect the medication), the item cost, strength and quantity of medications (level of medication). The identifier is the patient's NHS number. NHS England will provide the data of matched patients who have not registered a national data opt-out back to the Liverpool Heart and Chest Hospital CTU for the period 2016/17-2021/22. The data provided back to the CTU will be in the form of the unique study ID that has been supplied to NHS England in order to minimise identifiable data processing.

Justification for geographical spread of data requested: The geographical spread of the data requested 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.

The study is investigating the potential benefits of introducing a new health technology (CTFFR) on a national scale. 25 NHS England Hospital Trusts were involved in this programme for NHS England. They represent a geographical spread across England. Sites identified eligible patients who had a CCTA during the study time period using their radiology information system. These sites sent 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 England data. As a research organisation, Liverpool Heart and Chest Hospital’s lawful basis under the UK General Data Protection Regulations (GDPR) supporting the processing of personal data is Public Task – Article 6(1)(e). The additional UK 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 England 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 England 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 England 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 England 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.

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. They are a commercial industrial partner with UK and international presence. An assessment had been undertaken that the commercial benefit accruing to the commercial organisation is proportionate to the benefit to health and social care.

The project parties (including NHS Trusts, University, Funder (MRC) and HeartFlow Inc,) are subject to a collaboration agreement and head of terms which includes the use of research data for internal research and external publicity. The management of the study and all data is handled by the Liverpool clinical trials team with no access available to other parties in accordance with the principles of medical confidentiality in relation to Project Participants.

HeartFlow Inc, cannot influence the management of the trial nor its results.

No NHS England data will be shared with HeartFlow Inc,. This means the data or any subset of the data provided by NHS England under this Data Sharing Agreement including manipulated data, as defined in the Data Sharing Framework Contract. Only aggregated results with small number suppression that has been derived through the processing of NHS Digital data may be shared with HeartFlow Inc,. All academically generated Foreground IP (“Academic Foreground IP”) shall belong to Liverpool Heart and Chest Hospital. HeartFlow Inc, has given royalty-free, non-exclusive licence for the duration of the Project to use its Background IP for the sole purpose of carrying out the Project.

Publication and announcements of the results are in accordance with the publication agreement and independent publication committee. Regarding LHCH and its other collaboration parties, no Party will issue any information or statement to the press or public relating to the Project, without, where appropriate, review and the delivery of a favourable opinion by the Project Publication Committee.

The other parties may request a confidentiality notice where they can request a delay of the proposed Publication for a maximum of 3 months in order to seek patent or other protection for any of the Intellectual Property Rights in any of the Results or to prevent any of its background IP which is Confidential Information and which, in each case, cannot be protected by patent or other Intellectual Property Right registration.

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 2023

2. Publication in Peer review journal: Simultaneous ESC publication August 2023 (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.

There are currently no Yielded Benefits to date as LHCH only received the data in September 2022 and it has not yet been processed.

The Liverpool Heart and Chest Hospital (LHCH) requires access to NHS England 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 England 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 a FFRCT (n=9700) to those that did not (n=80,000). Both the FFRCT and non-FFRCT group cohorts will be provided to NHS England. 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 2 year follow-up period (31st March 2022). The Health Technology (FFRCT) was introduced into the health system during 2018. Patient data will be collected at 90 days, 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.

The following dataset are requested to achieve the study’s aims:

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, NHS Business Services Authority (NHS BSA) and Civil Registrations (Deaths). 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.

Level of data: Record level, pseudonymised, patient information (such as age group, gender and ethnicity) and information on where patients are treated and the area where they live will be requested. This demographic information is required to assess whether there are any variations in care or outcomes relating to these factors. NHSBSA data is required to ensure that any changes in clinical outcomes observed over time following the health technology intervention are a result of the technology itself rather than variations in medical treatments. To be certain of this LHCH require the strength and number of medications taken over the study time period.

Item costs within the NHSBSA dataset are required as it is to determine the overall cost effectiveness of health treatments, including the medicines data as the study is estimating total NHS costs which includes hospital visits, tests etc. To have an accurate assessment of total healthcare costs this requires linkage to the medicines costs. LHCH can then determine the clinical effectiveness and cost effectiveness of the health intervention and medicines.

The linkage of the NHSBSA medicines data to the existing data from NHS England will allow LHCH to provide information relating to the:

1. Safety of medicines: LHCH have adverse clinical events data including heart attacks, cardiovascular death, all cause death, stroke etc. The medicines dispensed, dose and number of tablets will be used to look at relations to adverse events and thus safety.

2. Effectiveness of medicines: A key component to this study is to determine the effectiveness of the medicines (in particular aspirin and statins) on reducing the risk of the adverse clinical events (heart attacks, cardiovascular death, all cause death, stroke). This will be assessed simultaneously as the impact of the health technology. Without both sets of data LHCH will not be able to determine the impact of medications or health technology, nor their inter-relationship or independence.

The study needs to determine what medications patients were on during the study period in order to identify whether this impacted clinical outcomes. Data requested is minimised to the British National Formulary (BNF) name of the medication, whether the medication was dispensed (i.e. did the patient collect the medication), the item cost, strength and quantity of medications (level of medication). The identifier is the patient's NHS number. NHS England will provide the data of matched patients who have not registered a national data opt-out back to the Liverpool Heart and Chest Hospital CTU for the period 2016/17-2021/22. The data provided back to the CTU will be in the form of the unique study ID that has been supplied to NHS England in order to minimise identifiable data processing.

Justification for geographical spread of data requested: The geographical spread of the data requested 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.

The study is investigating the potential benefits of introducing a new health technology (CTFFR) on a national scale. 25 NHS England Hospital Trusts were involved in this programme for NHS England. They represent a geographical spread across England. Sites identified eligible patients who had a CCTA during the study time period using their radiology information system. These sites sent 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 England data. As a research organisation, Liverpool Heart and Chest Hospital’s lawful basis under the UK General Data Protection Regulations (GDPR) supporting the processing of personal data is Public Task – Article 6(1)(e). The additional UK 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 England 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 England 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 England 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 England 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.

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. They are a commercial industrial partner with UK and international presence. An assessment had been undertaken that the commercial benefit accruing to the commercial organisation is proportionate to the benefit to health and social care.

The project parties (including NHS Trusts, University, Funder (MRC) and HeartFlow Inc,) are subject to a collaboration agreement and head of terms which includes the use of research data for internal research and external publicity. The management of the study and all data is handled by the Liverpool clinical trials team with no access available to other parties in accordance with the principles of medical confidentiality in relation to Project Participants.

HeartFlow Inc, cannot influence the management of the trial nor its results.

No NHS England data will be shared with HeartFlow Inc,. This means the data or any subset of the data provided by NHS England under this Data Sharing Agreement including manipulated data, as defined in the Data Sharing Framework Contract. Only aggregated results with small number suppression that has been derived through the processing of NHS Digital data may be shared with HeartFlow Inc,. All academically generated Foreground IP (“Academic Foreground IP”) shall belong to Liverpool Heart and Chest Hospital. HeartFlow Inc, has given royalty-free, non-exclusive licence for the duration of the Project to use its Background IP for the sole purpose of carrying out the Project.

Publication and announcements of the results are in accordance with the publication agreement and independent publication committee. Regarding LHCH and its other collaboration parties, no Party will issue any information or statement to the press or public relating to the Project, without, where appropriate, review and the delivery of a favourable opinion by the Project Publication Committee.

The other parties may request a confidentiality notice where they can request a delay of the proposed Publication for a maximum of 3 months in order to seek patent or other protection for any of the Intellectual Property Rights in any of the Results or to prevent any of its background IP which is Confidential Information and which, in each case, cannot be protected by patent or other Intellectual Property Right registration.

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 2023

2. Publication in Peer review journal: Simultaneous ESC publication August 2023 (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.

There are currently no Yielded Benefits to date as LHCH only received the data in September 2022 and it has not yet been processed.

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.

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.

Yielded Benefits is not a requirement for new applications.