RIPCORD 2 Trial: HES data for outcome analyses.

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Objective for processing

On 1 February 2023, NHS Digital merged with NHS England. NHS England has assumed responsibility for all activities previously undertaken by NHS Digital. The merger was completed by a statute change. Any reference made to NHS Digital within this Data Sharing Agreement is in reference to the merged organisation known as NHS England. University Hospital Southampton NHS Foundation Trust (UHS) and Liverpool Heart & Chest Hospital NHS Foundation Trust (LHCH) require access to NHS England data for the purpose of the following research project: 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. RIPCORD 2 Trial: HES data for outcome analyses. 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. RIPCORD 2 was 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. 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). The project is now complete. UHS and LHCH would like to retain this Data to ensure reconstruction of the study analysis is possible if required. 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. No additional data will be requested from NHS England. Full Research Ethics Committee and local site approvals were gained. This Data Sharing Agreement (DSA) permits processing of the Data for the purpose of secure storage and back up. 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. This DSA does not permit any further processing that involves analysis or linkage other than for the purpose of verifying findings in line with the original objectives of the study by repeating previous analyses described in this DSA. Study Outcome measures are as follows: Following publication of the study findings, it is possible that the findings will be questioned or challenged by third parties through direct contact with UHS or LHCH, contact via the publishing journal or an open letter. In such circumstances, LHCH may repeat the previously analyses undertaken to verify that the published results were accurate and may write a response to be issued directly to the challenger or published. - Primary Economic Outcome Measure: UHS and LHCH may not undertake different analyses to those undertaken during the original analysis. 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). This DSA does not permit any onward sharing of the Data. - Primary Quality of Life Outcome Measure: This DSA permits the necessary processing of the Data for the purposes of permanently destroying, deleting or erasing the Data once it is no longer required for the purpose for which it was collected. Once destroyed/deleted or erased, LHCH must confirm destruction to NHS England. If any further data processing is required in addition to the above purposes or if the data needs to be moved to a different location/organisation UHS or LHCH must submit an Amendment request to NHS England before Data is accessed. 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). The following NHS England Data will be retained: - Secondary Outcomes: Clinical Events • Diagnostic Imaging Dataset (DIDS) Clinical event rates at one year derived from HES; • Civil Registration Mortality • All-cause mortality • Hospital Episode Statistics • Number of hospitalisation events and total hospital days - Admitted Patient Care • Hospitalisation events coded as: - Accident & Emergency - Cerebro-vascular accident (CVA) - Critical Care - Myocardial infarction Outpatients Coronary revascularisation. This analysis will involve a pre-specified subgroup analysis of: The level of the Data being retained is identifiable – necessary because although the data supplied by NHS England under previous iterations of this DSA was pseudonymised, the data contains a unique study-ID to enable linkage with study data collected by the controllers. Participant identifiers are held in a separate database in a different secure location on a different server owned by LHCH, with access restricted to individuals who were not involved in analysis of the pseudonymised linked dataset. • Planned revascularisation - if declared as the index strategy The data is minimised as follows: • All additional revascularisation events • Limited to data between 2016/17 to 2019/20. 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. • Limited to data for a study cohort of 1,100 participants identified by LHCH – The cohort consists of participants in the initial RIPCORD 2 study (who have not subsequently withdrawn from the trial). Participants are patients with stable angina or stabilised NSTEMI ACS scheduled for angiography at the time of recruitment to the trial in 2018. Participants gave informed consent at one of 24 Percutaneous Coronary Intervention (PCI) centres within the UK. 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. University Hospital Southampton NHS Foundation Trust (UHS) is the research sponsor and a joint Controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above. 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. UHS commissioned Liverpool Heart and Chest Hospital NHS Foundation Trust (LHCH) to undertake the work and LHCH is involved in decisions about the processing of the Data. As such, LHCH is a joint controller. 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 lawful basis for processing personal data under the UK GDPR is: 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. Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller. 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. The lawful basis for processing special category data under the UK GDPR is: Mortality data will provide cause of death details which will also contribute to the overall cost analysis. Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. 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 funding is provided by UHS. The funding is specifically for the study described. The study requires a one-off extract of data for patients for a 12 month period from the date of randomisation. The funder will have no ability to suppress or otherwise limit the publication of findings. 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. Arrow Business Communications Ltd provides IT back up services to LHCH and will store copies of the data as contracted by LHCH. Arrow Business Communications provides storage only. They host the rack space for LHCH server storage and cannot access data stored on the LHCH backup server. 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.

Processing activities

Description of the data flow: No data will flow to NHS England for the purposes of this Data Sharing Agreement (DSA). 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. Liverpool Heart and Chest Hospital NHS Foundation Trust (LHCH) hold the relevant records from the Diagnostic Imaging Data Set; Mortality; Hospital Episode Statistics Admitted Patient Care, Critical Care, Outpatients, and Accident & Emergency datasets. The Data contains no direct identifying data items but will contain a unique person ID which can be used to link the Data with other record level data already held by the recipient. 2) NHS Digital will link the cohort to HES, DIDs and mortality data using NHS Number, date of birth and gender. No additional data will be disseminated by NHS England for the purposes of this DSA. 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. This DSA permits processing of the Data for the purpose of secure storage and back up. 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. This DSA does not permit any further processing that involves analysis or linkage other than for the purpose of verifying findings in line with the original objectives of the study by repeating previous analyses described in this DSA. 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: This DSA does not permit any onward sharing of the Data with the exception that the Data may be viewed for the purpose of an audit by a regulator such as the Medicines and Healthcare products Regulatory Agency (MHRA). 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 Data will be stored on servers at LHCH. 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. LHCH uses offsite back-up services provided by Arrow Business Communications. Arrow Business Communications provide only the physical storage facility and are not permitted to access the NHSE data. 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). Trust data storage is replicated to an off site facility hosted by AIMES management services Ltd, for resilience purposes. There is a contractual arrangement in place. Although this party hosts the rack space for server storage, they do not have any access to data or any access to the servers.

Expected output

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. The outputs of the processing were communicated to stakeholders through publication of the primary RIPCORD 2 trial paper in a leading cardiology journal, Circulation on 10th August 2022: 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. Routine Pressure Wire Assessment Versus Conventional Angiography in the Management of Patients With Coronary Artery Disease: The RIPCORD 2 Trial - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.057793 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. The outputs do not contain NHS England Data and only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived. October 2022 (v1.2) Update: The primary paper has been published in Circulation and well received within the scientific community. It has been discussed/referenced in several medical conferences/forums and will help guide future practice in the use of pressure wire technology. It is likely that it would serve as a reference for future guidelines for use of this type of technology. There are no specific expected additional outputs thus far, but as above we may look to perform secondary analyses for ancillary publications in due course. In addition, the novel methodology for outcome ascertainment via HEs that was employed in this trial has gained interest. The applicant has presented the methodology at a national meeting (British cardiac society) and has been asked to join a British Heart foundation data sciences centre working group looking to standardise clinical outcome definitions. The methods for using HES for this purpose have been suggested as a framework/starting point for potential consensus guideline type publications. LHCH are reproducing these methods in a much larger scale study being undertaken out of LHCH using HES data. The experience from this study has therefore been very important in enabling future research.

Expected measurable 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. The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study. 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. It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients. 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.

Benefits reported

The primary paper has been published in Circulation, a major cardiac journal.- Routine Pressure Wire Assessment Versus Conventional Angiography in the Management of Patients With Coronary Artery Disease: The RIPCORD 2 Trial (ahajournals.org) The main findings of the trial found that systematically using Fractional Flow Reserve (FFR) with a pressure wire during diagnostic angiography for stable angina or NSTEMI patients wasn't better than standard angiography for 1-year costs or quality of life, with similar clinical events but longer procedures and more contrast/radiation use. While FFR-guided care usually reduces unnecessary stenting (PCI), in RIPCORD 2, the FFR group actually had more PCI, though fewer stents were used, suggesting it improved treatment accuracy by guiding revascularization, but didn't save resources or boost QoL overall at one year. The results of the study should help guide clinicians in the appropriate use of this technology and therefore have the potential to potentially benefit the care of thousands of patients undergoing these types of procedures every year. The development of the novel research methodology, will enable more cost effective research studies to be conducted in the future, which may of course be of benefit to the NHS. The findings have helped guide clinicians on the appropriate use of pressure wire technology, with the potential to benefit thousands of patients undergoing coronary angiography and revascularisation procedures each year. Additionally, the innovative methodology developed for outcome ascertainment using linked Hospital Episode Statistics (HES) and mortality data has contributed to development of more efficient and cost-effective cardiovascular research studies within the NHS and beyond. In 2025, University Hospital Southampton NHS Foundation Trust (UHS) received support from the NHSE Confidentiality Advisory Group (CAG) to access RIPCORD-2 health data for the purpose of conducting a remote extended follow-up of RIPCORD-2 participants at 5-years to further enhance understanding of the long-term clinical impact of FFR-guided management, supporting improvements in patient care and informing future clinical guidelines. The Data supplied under previous iterations of this DSA are archived at LHCH and will not be used by UHS for the purposes of the 5-year follow-up study.

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Objective for processing

On 1 February 2023, NHS Digital merged with NHS England. NHS England has assumed responsibility for all activities previously undertaken by NHS Digital. The merger was completed by a statute change. Any reference made to NHS Digital within this Data Sharing Agreement is in reference to the merged organisation known as NHS England. [35 paragraphs unchanged]

Processing activities

[11 paragraphs unchanged] 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). Trust data storage is replicated to an off site facility hosted by AIMES management services Ltd, for resilience purposes. There is a contractual arrangement in place. Although this party hosts the rack space for server storage, they do not have any access to data or any access to the servers.

Expected output

[3 paragraphs unchanged] October 2022 (v1.2) Update: The primary paper has been published in Circulation and well received within the scientific community. It has been discussed/referenced in several medical conferences/forums and will help guide future practice in the use of pressure wire technology. It is likely that it would serve as a reference for future guidelines for use of this type of technology. There are no specific expected additional outputs thus far, but as above we may look to perform secondary analyses for ancillary publications in due course. In addition, the novel methodology for outcome ascertainment via HEs that was employed in this trial has gained interest. The applicant has presented the methodology at a national meeting (British cardiac society) and has been asked to join a British Heart foundation data sciences centre working group looking to standardise clinical outcome definitions. The methods for using HES for this purpose have been suggested as a framework/starting point for potential consensus guideline type publications. LHCH are reproducing these methods in a much larger scale study being undertaken out of LHCH using HES data. The experience from this study has therefore been very important in enabling future research.

Benefits reported

Yielded Benefits is not a requirement for new applications. The primary paper has been published in Circulation, a major cardiac journal.- Routine Pressure Wire Assessment Versus Conventional Angiography in the Management of Patients With Coronary Artery Disease: The RIPCORD 2 Trial (ahajournals.org) The results of the study should help guide clinicians in the appropriate use of this technology and therefore have the potential to potentially benefit the care of thousands of patients undergoing these types of procedures every year. The development of the novel research methodology, will enable more cost effective research studies to be conducted in the future, which may of course be of benefit to the NHS.

Unchanged: Expected measurable benefits.