NHS Digital Data Release Register - reformatted

Norfolk And Norwich University Hospitals NHS Foundation Trust projects

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


Outcomes of Percutaneous Coronary Intervention at Norfolk & Norwich University Hospital — DARS-NIC-303785-L3K3Z

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

Legal basis: Health and Social Care Act 2012 - s261 - 'Other dissemination of information',

Purposes: (NHS Trust)

Sensitive: Sensitive, and Non-Sensitive

When:2021.10 — 2021.11. DSA runs 2021-02-25 — 2024-02-24

Access method: One-Off

Data-controller type: NORFOLK AND NORWICH UNIVERSITY HOSPITALS NHS FOUNDATION TRUST

Sublicensing allowed: No

Datasets:

  1. Civil Registration (Deaths) - Secondary Care Cut
  2. HES:Civil Registration (Deaths) bridge
  3. Hospital Episode Statistics Admitted Patient Care
  4. Hospital Episode Statistics Outpatients

Objectives:

BACKGROUND
According to the World Health Organisation, 7.4 million people died worldwide (13.1% of all deaths) of coronary artery disease in the year 2012. It remains the leading cause of mortality worldwide and the death rate continues to increase despite novel treatment strategies. Coronary artery disease refers to the “furring up” of the inside of the coronary arteries (the arteries that supply heart muscle with blood). Coronary artery disease occurs by a process of atherosclerosis and whilst there are drugs to help prevent and slow the progression of this disease, it is due to this underlying process that people may present to hospital with symptoms of angina or heart attacks.

Patients may present to Cardiology with symptoms of chest pain, breathlessness or collapse and subsequently be identified as having a problem relating to disease of the coronary arteries. Specifically these problems can be defined as "angina" or variants of "ischaemic heart disease" which is a spectrum including "myocardial infarction" or generally regarded as "heart attacks" and refers to the process of furring or blockages of coronary arteries. Heart attacks vary in severity and occur on a spectrum known as “Acute Coronary Syndrome” (ACS). ACS is further subdivided according to various clinical parameters. The first clinical criteria involve the presence of an Electrocardiogram (ECG) appearance known as “ST elevation”. ECGs are an investigational technique performed by attaching electrodes to a patient's chest and measuring electrical activity within the heart, generating a pain-free and quick way of assessing the heart. Heart attacks with the "ST elevation ECG finding" are known as ST Elevated Myocardial Infarctions (STEMI). Other acute coronary syndromes include Non-ST elevation Myocardial Infarctions (NSTEMI) and their clinical criteria is usually based on a clinical triad of certain other ECG appearances, blood marker sampling and symptoms. Identification of Stable angina as a clinical syndrome is based on clinical symptoms and certain cardiovascular investigations.

Invasive treatments of coronary artery disease are known as “coronary revascularisation” and there are two methods available to date which are percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG). PCI is a medical intervention technique that forms the cornerstone of the treatment of coronary artery disease. During PCI a wire is passed through a tube usually in the artery of the wrist or top of the leg. Using this wire, it is possible to advance a balloon to stretch the artery open. Subsequently there are two main treatments; either implantation of a stent (metal alloy scaffold that keeps the artery open) or usage of a drug coated balloon - DCB (balloon coated with medication that gets absorbed by the blood vessel and reduces the chance of the narrowing reappearing).

According to the national PCI audit in 2015, the number of PCIs has been steadily increasing over the last few years. Drug eluting stent (DES) implantation is considered the standard of care but DCB is an emerging technique with increasingly supportive evidence.

According to the 2015 BCIS data, 2.4% of the PCI procedures were undertaken for stent thrombosis (blocked coronary stents) while about 5% of the PCI procedures were undertaken for stent restenosis (a re-narrowing within a stent). A total therefore of 1 in 13 patients receiving Drug Eluting Stents (DES) will have significant complications relating to it needing further coronary intervention/cardiac procedures. This is a limitation to which treating with a drug coated balloon (DCB) would be advantageous in that it does not require the placement of a stent prosthesis. DCB are an alternative PCI technology where no permanent stent is left behind in the coronary artery. The absence of a permanent stent reduces significantly stent related complications, which contribute to the repeated PCI procedures many patients undergo. Therefore, there is clear public interest into the patient outcomes of alternative PCI technologies (such as DCB) and how they compare with the current standard of care which is DES.
There are mostly small randomised clinical trials to date showing non-inferiority between DES and DCB.

In summary the potential advantages (over a potential survival benefit), include a shorter period of mandated prescription of anti-platelet drugs (DES requires between a month and a year of uninterrupted anti platelet drugs to prevent thrombi developing within the stent scaffold), reduced complexity in their application over DES which means shorter procedures and they are more favourable for the attachment of subsequent bypass grafts.

AIM OF STUDY
The main aim of the research is to compare the outcomes of patients treated with drug coated balloons (DCB) and drug eluting stents (DES) at the Norfolk and Norwich Hospital. The Norfolk and Norwich University Hospital (NNUH) has one of the largest DCB implantation cohorts in the UK and the results of the study will be in the public interest for the consideration of the potential advantages of DCB over DES. The Norfolk and Norwich University Hospital has been an early adopter of drug coated balloon angioplasty and it was first introduced more than 10 years ago. Currently, all interventional cardiologists have been trained and are skilled in using drug coated balloons. In addition, the volume of coronary intervention in Norwich is very large (representing a large catchment area of patients at risk of coronary disease with an elderly population), therefore the combination of both the large numbers of intervention undertaken together with the early adoption of the drug coated balloons now mean Norwich in one of the largest users in the UK. Other centres e.g. In Germany or Finland undertake even more drug coated balloon angioplasty than Norwich.

This study is retrospective and non-randomised but will be the largest study published to date. It will be an important study with significant impact for DES and DCB usage. The study will compare DCB and DES as two PCI techniques. The comparison will be based on three main patient outcomes, which are:
+ cause of death
+ rehospitalisation
+ cause for rehospitalisation after the PCI.

These are important patient outcomes frequently used in studies to assess the effectiveness of various PCI techniques. Patients will be divided into two groups (groups 1 and 2). Group 1 will involve patients treated with drug coated balloon and Group 2 will involve patients treated with drug eluting stent, both subdivided according to indication for treatment (STEMI, NSTEMI or Stable angina). The study focuses on patients treated with DCB as NNUH has a vast clinical experience and a large cohort of patients treated with DCB. At present the utilisation of either DCB or DES is about 60%/40% in favour of DES at NNUH. These patients will be compared with patients treated with DES (at NNUH) which is the standard of care in the UK. The study team will use statistical analysis using regression models and propensity matching where appropriate and will take into consideration the baseline patients' characteristics including DCB or DES implantation. The study team will only know once the data have been analysed which (DCB or DES) is more suitable.

Previous NNUH studies and other published studies
There has been a precedence set for retrospective analysis of patients treated with percutaneous coronary intervention with an emphasis on drug coated balloon angioplasty which started in 2014 at the NNUH. NNUH has published research based on cardiovascular outcomes of percutaneous coronary intervention previously in conjunction with data obtained from the National Institute for Cardiovascular Outcomes Research (NICOR) group. There have been a series papers published on the safety of DCB, these papers can be found here https://pubmed.ncbi.nlm.nih.gov/29588716/ and here https://pubmed.ncbi.nlm.nih.gov/27858114/ as well as notably for the use of DCB in the treatment of large heart attacks – ST elevation Myocardial Infarction (STEMI) https://pubmed.ncbi.nlm.nih.gov/31314432/.

Since the work started, there has been a significant increase in the number of patients treated with drug coated balloons, which will increase the robustness of the results.

Wider review and publication of patient outcomes treated with DCB and DES became more prominent in 2016 and further since the recently entitled "BASKET-Small" trial that was published in the Lancet journal, this was a randomised trial which compared the utilisation of DES versus DCB in small coronary arteries and demonstrated DCB to at least be non-inferior to DES. This trial has no link to the project described in the application. Over the last few years there has been a great increase in the number of patients treated with DCB at NNUH. The larger number of patients will increase the power of the results, which will build on the published work from with the research group. So far to date there is a lack of “real world” data and the efficacy of DCBs. In particular there remain important subgroups of coronary artery disease whereby DCB provides a conceivable advantage and therefore would benefit from robust data scrutiny to establish whether it is in fact beneficial, namely the treatment of Left Main Stem Coronary disease (which refers to a location of coronary disease that poses challenges to traditional stent techniques and is often as a result referred for Coronary Artery Bypass surgery instead), bifurcational disease (treatment at junctions of coronary artery that tend to lead to complicated stent related techniques) and those with high bleeding risk such as the elderly population. Closer examination of these groups may establish that in certain situations, DCB is advantageous over DES, which at present a significant number of centres feels hesitant to use DCB without what they have regarded as the robust evidence to support it.

Norfolk and Norwich University Hospital NHS Trust is the sole Controller and the sole Processor under this application. This application received a favourable ethical opinion from the Northwest Haydock Research Ethics committee (Reference 17/NW/0278) and approval from the Confidentiality Advisory Group 15/11/19. The funding body is the "Norfolk Heart Trust" which is a charitable organisation dedicated to improving cardiac care to people. Norfolk Heart Trust will have no influence on, involvement with or access to any of NHS Digital data in the study.

Data processed is as per GDPR Article 6 (1) (e) in the public interest as Norfolk and Norwich University Hospitals NHS Foundation Trust is a teaching hospital and is therefore considered a public authority. Processing of data is also justified as per GDPR Article 9 (2)(j) “processing is necessary for archiving purposes in the public interest, scientific 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”. NHS Digital data are required to investigate long terms outcomes of Drug Coated Balloon Angioplasty Treatment, a novel therapy as opposed to standard Drug Eluting Stent insertion, this research project could provide an important source of information for health professionals and patients to guide future clinical practice and research.

The aim pursued involves the greater scientific understanding of the efficacy of the treatment of coronary artery disease. Data will be stored securely and individual details will be anonymised with results demonstrating findings on a cohort-based scale and therefore rendering individuals impossible to identify from subsequent published data.

Expected Benefits:

At present, it would seem anecdotally from Cardiology meetings including with the British Cardiovascular Interventional Society that greater data is needed to demonstrate that drug coated balloon angioplasty is indeed non inferior to drug eluting stents in these various patient groups before wide scale practice is adopted. One of the potential drawbacks is the increased procedural familiarity required to insert drug coated balloons. They are applied in a different fashion and so there is a reticence to apply them over the current method of stenting which in some regards seen as easier as it is what most Cardiologist operators have been trained to do. The data obtained from the study could help this paradigm shift towards a technique that is different and potentially poses its own benefits.

The outputs received look at the complications of angioplasty and cardiovascular disease. Drug coated balloon treatments do not require the implantation of the scaffold (stent structure of the drug eluting stent techniques). This is a crucial difference as there is a risk of forming clots (“stent thrombosis”) within them which necessitates being treated with anti platelet medications (1-month with DCB vs 1 year for DES) that have been shown in a large volume of study to be associated with higher rates of bleeding and mortality especially within the elderly. The outputs received will include follow up data relating to whether patients had to re attend due to bleeding complications and to highlight the proportional difference between the two techniques. Research to date has focussed on the aim with drug eluting stents to reduce the duration with which a patient has to have mandated antiplatelet therapy. The research into outcomes of patients treated with drug coated balloons could help provide a shift in perspective regarding the way that angioplasty treatments are approached.

The presence of the scaffold structure is also thought (from various previous studies) to affect “endothelial function”. This refers to the inner wall of coronary arteries to which the stent scaffold adheres and can influence how the blood vessel moves. It is known that coronary arteries can dilate and expand and this response is controlled by the inner endothelial layer. Some previous studies in assessing coronary artery dilator responses have shown that the presence of the stent scaffold attenuates the way the vessel moves by way of physical restriction (presence of the rigid structure within the vessel) but also in a regulatory capacity (ie beyond where the stent is). There has also been research to suggest that this effect on blood vessel responses can have effects further “downstream” and therefore may elicit further complications (hence the output requested for other vascular complications including stroke).

There is increasing understanding that the mechanisms causing acute coronary syndrome are multiple rather than a singular process and individualised patient groups response differently to therapy. The data collected within NNUH includes subgroups with different comorbidities (for example whether the patient is diabetic, asthmatic, has had a previous stroke etc) and the outputs derived would help understanding as to how the different therapeutic changes affect these subgroups. This is also likely to have wider interest for publication.

Once NHS digital data has been analysed the aim will be for the research team to present this data to the British Cardiovascular Interventional Society (BCIS) at their national meetings in the form of formal written and visual presentations and further on an international scale with further collaboration. This has occurred informally involving previous data to the BCIS meeting in January 2020. The BCIS society would have no access to NHS digital data and only to findings following analysis of the small numbers suppressed in line with HES Analysis guidelines. Other planned meetings involve the Transcatheter Cardiovascular Therapeutics (TCT) conference in the USA and the European Percutaneous Cardiovascular Research Society (EuroPCR). Similarly, at TCT and EuroPCR the societies would have no access to NHS digital data and only to findings following analysis of the small numbers suppressed in line with HES Analysis guidelines.

The target date for initial publication and dissemination of findings would be from February 2021 onwards. At present an area of current interest is Left Main stem coronary disease which is a high-risk anatomical arrangement of coronary artery disease that is often treated with coronary artery bypass grafting. Insights into this subgroup could have far reaching effects on the wider patient community.

This study is not undertaken to support a PhD or post-graduate research.

Outputs:

The data used will be analysed to look at outcomes of patients who are treated with percutaneous coronary intervention. The main aim is to compare drug coated balloons with drug eluting stents. These treatments have different inherent potential advantages and disadvantages in both their usage but also to certain cohorts of patients. Areas of scientific and wider public interest would include consideration of various different subgroups of patients with coronary artery disease (for example people with heart attacks, people with high blood pressure, smokers, people who have had previous heart operations etc) and look to see the influence or associations with either treatment strategy.

The aim would be to produce publications to peer reviewed, scientific journals within the medical community and to disseminate the findings via presentations and posters at Medical conferences and other forums.

The data obtained will be presented as with small numbers suppressed in line with the HES Analysis guidelines as aggregate data so as to see if there are common associations between particular biometric traits. Data will be used to undertake statistical analysis to identify trends in the data (predictors of mortality, rehospitalisations etc).

The study statistician will only receive aggregated numbers with small numbers supressed.

The findings will be presented at meetings and conferences (such as the annual "British Cardiovascular Interventional Society" Conference or the Transcatheter Cardiovascular Therapeutics" conference) to encourage further research and utilisation of different treatment strategies.

Every attempt will be made to ensure that the findings are as widely available and open access if possible.

There is a relationship with the Charity “Norfolk Heart Trust” that has supported the research team at NNUH in the past purely from a funding standpoint. Norfolk Heart Trust have no influence nor involvement with studies and will therefore have no access to the data. Norfolk Heart Trust have provided a research grant which will support financing the NHS digital data application. Norfolk Heart Trust's donation is on the basis of an aim to further insight into cardiovascular disease treatment research. Norfolk Heart Trust will only disseminate final results (aggregate data) and will have no other involvement in this project.

Data collection is an ongoing process, with the aim currently to review patients up until April 2021. There is no involvement of EU funding in this research.

Processing:

DATA
The following data are requested from NHS digital:
Pseudonymised Hospital Episode Statistics Admitted Patient Care 2011/2012 -2019/2020 (latest available).
Pseudonymised Hospital episode statistics Outpatients 2011/2012 -2019/2020 (latest available).
Pseudonymised Civil registration (deaths) - linked to HES
HES (Civil registration deaths) bridge.

HES Data will allow analysis of future relevant complications relating to the cohort’s cardiovascular disease and treatments. Mortality data will provide insights into the crucial effects of the cohort’s conditions and the associated effects on prognosis.

COHORT
The cohort will be obtained from the Audit data collected as part of the daily practice within Cardiology departments throughout the UK in agreement with the British Cardiovascular intervention society whereby data is collected on all patients who receive PCI. Only patients from the NNUH registry of patients who have received PCI with either DES or DCB will be included in the project.

Some of the important considerations include subsequent diagnoses (listed as primary and secondary in the admissions products). This will provide insight into subsequent issues or medical problems that patients may have encountered following their procedure and relating to their condition. Cause of death, rehospitalisation and cause of re-hospitalisation after PCI (DES or DCB) are very important outcomes following a PCI indicating the long-term success of the PCI technique.

This study will provide the basis for the design of a future larger randomised controlled clinical trial comparing DES vs DCB. Such a large randomised control trial will be necessary to verify the results of the retrospective study before a change in policy takes place.

DATA MINIMISATION
The aim is to request the most minimal dataset possible to facilitate a scientific and robust comparison between the two treatment methods (DCB and DES) by examining the following fields:
1) cause of death
2) rehospitalisation
3) cause for rehospitalisation.

This data request would include data covering the whole period of practice (from 2012 till present) to increase patient number, minimise any bias and increase the robustness of the results. It would be advisable to include as many patients as possible to ensure a complete dataset not confounded by loss to follow up. Patients included will be from the NNUH registry of patients who have received PCI treatment with either DES or DCB.

Data will be narrowed by demographic by age in that patients under 24 will not be included and will be narrowed by certain clinical factors in that the only patients required are those treated for ACS or stable angina specifically with PCI with either DCB or DES.

Only relevant episodes outlined are within the scope of interest, therefore it is unlikely that all patient’s episode will be required to achieve the purposes of the study. Stable angina is often treated electively so it is likely that some of these episodes will be required. Furthermore, it is possible that some future clinics sought may be coded as “elective”. For example, some patients may present with symptoms after their PCI treatment consistent with a mini stroke or Transient Ischaemic Attack (TIA). These are often reviewed in ambulatory (i.e. “walk in”) clinics which may be considered elective. It is unlikely that all elective episodes will be required to achieve the purposes of the study. Maternity episodes, problems related to psychiatry or alcohol and specific location-based information will not be required for the purposes of the study.

To reduce loss to follow up, it would be important to include ALL patients who were treated and therefore would request that the data not be narrowed by geographical location. Most likely - these patients will receive further follow up or additional episodes within the East of England region however limiting it to this region will lose patients who moved out of region. Geographical spread would be contingent on patient location as some patients may have been visitors and have been from out of area.

The cohort focusses on patients who have received angioplasty treatment and the analysis of complications related to this and the sequelae of ischaemic heart disease. Therefore, the outpatient episode specialities of interest would be limited to Cardiology, Vascular, Stroke, Renal and Gastroenterology. The study team would only want episodes dated after the patients entry into the database and not historical data as this would not be a direct result of their procedure.

The study team has considered in depth the data requested and confirms that these are the minimal data required to make it possible to undertake the study and produce robust results.

PROCESSING
Data provided by Norfolk and Norwich University Hospital NHS Trust to NHS digital will be:
- NHS number,
- Date of Birth
- Sex (the absolute minimum required) for accurate data linkage.

The flow of these data items is covered by section 251 approval granted by the Health Research Authority (HRA).

Encrypted data that will be received back by Norfolk and Norwick University Hospital for the relevant patients will include cause of death, rehospitalisation admissions and causes for the readmissions which will be analysed using the pseudonymised format i.e. identified with research specific reference ID. This will be stored on NHS computers only and in an encrypted, password protected format. Transfer of data between NHS computers will also be only using NHS encrypted "iron key" USB transfer.

NHS digital data will only be processed by substantive employees of Norfolk and Norwich University NHS Trust and will not be accessed or processed by any other third parties not mentioned in this agreement.

Subgroups will be identified, and data aggregated (for example – all patients with left main stem coronary artery disease) and propensity matched) and the outcomes compared using Kaplan Meier analysis of DCB versus DES. 'Propensity matched scoring' is a statistical method that tries to estimate the effect of a treatment (DCB or DES for example) having taken into consideration some important baseline characteristics effectively mimicking some of the particular characteristics of a randomized controlled trial, as described in this landmark article” Austin PC Multivariate Behav Res 2011; 46(3): 399-424 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144483/). These may include outcomes such as post procedural bleeding complications (requiring endoscopy), major adverse cardiovascular adverse outcomes (such as further Myocardial infarctions or Strokes) or death. This will be submitted to a peer reviewed scientific journal for publication.

Only certain members of the NNUH Cardiology department will have access to NHS digital data.