NHS Digital Data Release Register - reformatted

Erasmus University Rotterdam projects

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

Synergy between PCI with TAXUS and Cardiac Surgery: SYNTAX Extended Survival (SYNTAXES) — DARS-NIC-230360-H3Y3C

Type of data: information not disclosed for TRE projects

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

Legal basis: Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii), Health and Social Care Act 2012 – s261(1) and s261(2)(b)(ii), Health and Social Care Act 2012 – s261(2)(b)(ii)

Purposes: No (Academic)

Sensitive: Sensitive

When:DSA runs 2019-05-09 — 2020-05-08 2019.06 — 2019.06.

Access method: One-Off

Data-controller type: ERASMUS UNIVERSITY MEDICAL CENTRE

Sublicensing allowed: No

Datasets:

  1. Civil Registration - Deaths
  2. Civil Registration (Deaths) - Secondary Care Cut
  3. Civil Registrations of Death - Secondary Care Cut

Objectives:

Ischemic heart disease remains the number one cause of death in Western countries.

Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Grafting (CABG) are excellent treatment options for patients with coronary artery disease (CAD) requiring myocardial revascularization. Randomized comparisons between PCI and CABG are extremely costly and challenging to set-up and therefore limited studies have been performed to determine the best treatment. The SYNTAX trial was the first large-scale randomized trial that randomly assigned patients with coronary artery disease to CABG versus PCI with drug-eluting stents and is currently considered to be the most important trial of CABG versus PCI.

The primary endpoint of the trial showed that PCI was equivalent to CABG in terms of the rates of death and myocardial infarction at one year. Follow-up to 5 years demonstrated that survival curves continued to diverge between PCI and CABG (without statistical difference) with significantly lower rates of cardiac death, myocardial infarction and repeat revascularization in favour of CABG. Findings from subgroup analyses have been crucial in determining the most appropriate treatment strategy according to baseline characteristics. Outcomes showed to differ substantially between patients with three vessel disease (3VD) or left main (LM) disease; those with LM disease had similar outcomes with PCI and CABG, while those with 3VD had significantly better outcomes with CABG. In addition, the SYNTAX score, an angiographically based risk model, showed to be a useful tool to stratify which patients should undergo PCI or CABG, with CABG being the preferred strategy especially in patients with more complex lesions. For patients with less complex (low SYNTAX score) 1 or 2 vessel coronary artery disease; including left main coronary artery disease, without having medically treated diabetes, PCI showed to be a suitable treatment option with equivalent 5-year outcomes compared to CABG.

Based on these 1- and 5-year results, both European and North American Myocardial Revascularisation guidelines on PCI and CABG have been strongly influenced by the results from the SYNTAX trial. The SYNTAX trial completed successful planned follow-up at 5-years. Other previous trials on PCI versus CABG have also not extended follow-up beyond 5 years, with the exception of the older GABI and BARI trials. Therefore, numerous questions on the debate of CABG versus PCI remain unanswered which focus on long-term follow-up. Particularly subgroup analyses, which have more limited statistical power because of smaller groups, could significantly benefit from extended follow-up. The key objective of the current SYNTAX Extended Survivavl (SYNTAXES) study is to provide long-term survival data on PCI with drug-eluting stents versus CABG for complex coronary artery disease and identify key factors for decision making between both therapies.

The aim of the SYNTAXES study is to assess long-term (>10 year) survival of patients that were enrolled in the SYNTAX trail and who underwent CABG or PCI. The first patients have reached their 10-year follow-up mark in July 2015. Therefore, the time frame beholds: May 2015 – March 2019.

Data minimization:
Datasets:
The number of data items that the SYNTAXES study requires is limited to: i) a patients name, ii) a patients date of birth, iii) gender and iv) a patients NHS personal identifier. With these determinants, the correct patients enrolled in the SYNTAX study can be tracked and their accurate survival data (dead or alive, exact date of death) i.e. Civil Registration/Mortality Data) can be collated. With help of these determinants, all relevant data can be adequately linked to each patient's correct and unique study identifier, in order to ensure pseudonymisation of all patients. The data processor will ensure this process is done efficiently, safely and concisely. This ensures that the sponsor (i.e. data controller, Erasmus MC) will never obtain identifiable data.

Years:
In the SYNTAX study, 85 sites enrolled patients from all over the world. Currently, the SYNTAXES study is in its final phase and only 7 remaining sites (all based in the UK). are finalising data collection. Therefore, the database will remain unlocked until all sites have obtained their patient survival data and this is expected to be finalised in the upcoming year. In case the remaining sites provide their survival data any sooner, the database will of course be locked accordingly.
Once the UK survival data (Civil Registration/Mortality Data) comes back from DARS (NHS Digital) and the data processor (UHS) collates all the survival data, then the database in Southampton (which contains NHS patient identifiers etc.) will be erased/destroyed.
Therefore NHS Digital and UHS will delete/destroy the patients identifiers as soon as mortality data has been provided (Summer 2019).

Filtering:
The data that is requested under this agreement is carefully selected and already filtered. Erasmus University Medical Centre only request data from patients who were enrolled in the SYNTAX study and which were alive at the last follow-up moment (e.g. 5 year after CABG or PCI patients were originally enrolled). All patients that died during the first 5 year follow-up, will not be followed-up again for this stage of the study and subsequent application process. In order to ensure completeness of follow-up Erasmus University Medical Centre request the survival data of the randomised and registry cohorts of patients who underwent CABG or PCI, in order to analyse potential survival differences among patients. No further filtering or minimisation is possible in this case.

Episodes:
Not all patients episodes are required in this specific SYNTAXES follow-up. As an example, Erasmus University Medical Centre chose not to pursue the cause of death of patients, in order to keep the data as robust as possible. Furthermore, there is no request for any data on the place of death. The only elective episodes required are: exact date of death (day-month-year) contained within the Civil Registration Mortality Dataset.

Expected Benefits:

Obtaining long-term survival data after undergoing coronary artery revascularization due to coronary artery disease is of interest to the public since cardiovascular diseases are the number one cause of death in Western countries. The number of patients with coronary artery disease rises each year and with increasing life-expectancy of the overall population, one could expect a rise in patients who will need to undergo coronary artery revascularization, by either percutaneous coronary intervention (PCI) or surgical coronary artery bypass grafting (CABG).

Currently available scientific data is limited to relative short to mid-term clinical outcomes (e.g. 1 to 5 years), however long-term outcomes for this specific group of patients is of utmost importance. Therefore the SYNTAXES study aims to provide this long-term follow-up in patients with coronary artery disease who underwent coronary artery revascularization, by either PCI or CABG.

By collecting survival (a patient being dead or alive) data on all UK patients that have been previously enrolled in the original SYNTAX trial and underwent either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), the SYNTAXES study can accurately assess the long-term effect of both revascularization strategies. The data of all UK patients will be combined into the general SYNTAXES database, and in total the study will collect survival data (dead or alive) of 1800 patients, from 85 different sites in 18 countries worldwide.

All survival data will be analysed and eventually published (anonymously) in scientific medical peer-reviewed journals (i.e. the output). Furthermore, the data will be presented at (inter)national medical meetings for cardiologists and cardiothoracic surgeons. Current SYNTAXES study can make a significant contribution to how patients with coronary artery disease will be treated, in the UK, but also in Europe and the United States. Ideally, by publishing the study results in high-impact peer-reviewed medical journal, all clinicians worldwide can critically appraise the data and thereby incorporate the findings in their daily clinical-decision making process.

The original SYNTAX trial generated numerous (>50) scientific publications and has contributed substantially to international (European and North-American) guidelines on myocardial revascularization. These guidelines inform clinicians (cardiologists, cardiothoracic surgeons) on the optimal revascularization strategies in specific patients with coronary artery disease. These myocardial revascularization guidelines form the basis of multidisciplinary clinical-decision making and enable discussing the optimal treatment strategy for patients with coronary artery disease. Also clinicians in the UK use these clinical guidelines to determine the best treatment for their patients.

Therefore, the SYNTAXES study will substantially contribute to the knowledge on what the optimal treatment strategy is for patients with coronary artery disease in the UK and around the world. Consequently, patients will eventually benefit from the publication of current SYNTAXES study data. Furthermore, once the data has been published, the research team of the SYNTAXES study will update the British Heart Foundation with the main findings from the study. This was, the SYNTAXES study ensures that also UK patients and the UK public can access the data and will be informed on the main outcomes.

Many studies have been published on the first 5 year SYNTAX follow-up and consequently European and North American guidelines on myocardial revascularization have been influenced substantially by the evidence provided by the first 5-year SYNTAX follow-up. References, some but not all, to these papers are as follows:

• Current percutaneous coronary intervention and coronary artery bypass grafting practices for three-vessel and left main coronary artery disease. Insights from the SYNTAX run-in phase.
Kappetein AP, Dawkins KD, Mohr FW, Morice MC, Mack MJ, Russell ME, Pomar J, Serruys PW.
Eur J Cardiothorac Surg. 2006 Apr;29(4):486-91.

• Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease.
Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, Ståhle E, Feldman TE, van den Brand M, Bass EJ, Van Dyck N, Leadley K, Dawkins KD, Mohr FW; SYNTAX Investigators.
N Engl J Med. 2009 Mar 5;360(10):961-72.

• The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) study: design, rationale, and run-in phase.
Ong AT, Serruys PW, Mohr FW, Morice MC, Kappetein AP, Holmes DR Jr, Mack MJ, van den Brand M, Morel MA, van Es GA, Kleijne J, Koglin J, Russell ME.
Am Heart J. 2006 Jun;151(6):1194-204.

• Outcomes in patients with de novo left main disease treated with either percutaneous coronary intervention using paclitaxel-eluting stents or coronary artery bypass graft treatment in the Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) trial.
Morice MC, Serruys PW, Kappetein AP, Feldman TE, Ståhle E, Colombo A, Mack MJ, Holmes DR, Torracca L, van Es GA, Leadley K, Dawkins KD, Mohr F.

• Economic outcomes of percutaneous coronary intervention with drug-eluting stents versus bypass surgery for patients with left main or three-vessel coronary artery disease: one-year results from the SYNTAX trial.
Cohen DJ, Lavelle TA, Van Hout B, Li H, Lei Y, Robertus K, Pinto D, Magnuson EA, Mcgarry TF, Lucas SK, Horwitz PA, Henry CA, Serruys PW, Mohr FW, Kappetein AP.
Catheter Cardiovasc Interv. 2012 Feb 1;79(2):198-209.

• Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial.
Mohr FW, Morice MC, Kappetein AP, Feldman TE, Ståhle E, Colombo A, Mack MJ, Holmes DR Jr, Morel MA, Van Dyck N, Houle VM, Dawkins KD, Serruys PW.
Lancet. 2013 Feb 23;381(9867):629-38.

• Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the 40 guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and 45 Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2014;64:1929–49.

• Kolh P, Windecker S, Alfonso F, Collet JP, Cremer J, Falk V et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology 50 (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur J Cardiothorac Surg 2014;46:517–92

Outputs:

When the data of all UK patients has been obtained, the SYNTAXES study can lock its database and start analysing all data (this includes all other survival status data of patients enrolled in sites across the world, n=1800). The goal of the SYNTAXES study completion is expected to be reached in July 2019. Then all patient data will be analysed and writing of the manuscript will start.

All survival data will be analysed and eventually published as aggregated data with small number suppression, in scientific medical peer-reviewed journals (i.e. the output). Furthermore, the data will be presented at (inter)national medical meetings for cardiologists and cardiothoracic surgeons. The target date to be finished with all analyses, manuscript preparations, (inter)national scientific medical conference presentations and peer-reviewed journal submission is expected to be in September 2019.

Results will also be used to inform patient and practitioner guidelines, as indicated in the benefits section below.

Processing:

SYNTAXES is a multinational study based upon collecting 10 year mortality on the original SYNTAX population. The data is unique and will offer important outcomes to inform the decision-making and counselling for patients who have a choice between surgery or stenting for complex coronary disease. Given the multinational nature of this project, the most effective way to ensure robust data collection for the UK is to use a coordinating site to collate data and
submit a single application on behalf of the English sites to NHS Digital for the 245 UK
patients, rather than separate applications and data collection across participating Trusts.
This is more likely to ensure accurate and secure transmission of data to establish survival status. The research team at Southampton will coordinate the UK data collection in a structured and safe manner, so that the patient data is handled appropriately.

Patients will only be followed-up for the pre-specified primary endpoint: survival status (i.e. dead or alive and the exact date of death (Civil Registration/Mortality Data). None of the patients will undergo any intervention, nor any consultation. There will be no patient contact for this part of the trial.

Each of the 7 participating centre/site in the U.K. will be contacted by email or telephone by the Chief Investigators research team (UHS) to gather the identifiable data needed for linkage on the CABG and PCI patients already included at that particular centre. This is in line with the appropriate approvals. The identifiable data items for linkage will be collected by each individual participating UK sites (eight sites in total, of which one is in Glasgow - so only 7 in England and Wales). The seven sites (Glasgow will not be included; due to different ethical and lawful regulations that are in place there) will send the requested data (i.e. DOB, gender, NHS number, patient name) for each participant, coupled with a unique study ID to the chief investigator in Southampton. The eighth site in Scotland will retrieve mortality data from their local database as the NHS database excludes non-English hospitals and in Glasgow ethical approval has already been obtained separately. Patient name will not be transferred to NHS Digital for the purposes of linkage - but the other identifiers will.

Data from the 7 remaining sites will be collated safely, efficiently and securely, according to latest GDPR and UK regulations, by medically-ethically trained personnel. The identifiers (excluding patient name) will be sent to NHS Digital by University of Southampton. NHS Digital will link the Civil Registration/Mortality data to the individuals, NHS Digital will then send back the collected pseudonymised survival data (identifiers removed and only using Study ID) to the Chief Investigator in University Hospital Southampton. This data will include fact and full date of death.

Finally, the pseudonymised survival data (patients are now only identifiable by unique SYNTAX study IDs without any NHS or personal patient identifiers) for all sites (7 in England and Wales who are the subject of the linkage with NHS Digital, and one in Glasgow who's linkage will be done by the relevant Scottish body) will be sent to the sponsor (Erasmus University Medical Centre, Rotterdam, The Netherlands). The data controller (Erasmus Medical Centre - also the sponsor) will never have access to patient identifiers such as names and NHS number - and will not make an attempt at any stage to re-identify patients in the cohort. There will be no attempts to re-link the pseudyonymised clinical data disseminated by NHS Digital to University of Southampton to the identifiable data relating to each patient also held at University of Southampton. They will be kept in separate locations.

An anonymous database of patients enrolled in the SYNTAX trial is already available with baseline characteristics, procedural characteristics, and outcome data, which has been used for multiple publications. All patients included in the database have been assigned a unique study number - kept seperate from the PID. Local UK investigators will send pseudonymised data only identifiable per unique study number, to the chief investigator (CI) of the study and University Hospital Southampton. The CI will then transfer all pseudonymised data in an encrypted way to the sponsor and data controller. (Erasmus MC, Rotterdam, The Netherlands). A central database will be stored at the Department of Cardio-thoracic Surgery, Erasmus MC in Rotterdam, The Netherlands. This database, in comparison to the already existing database, will be edited only by changing the duration of follow-up, (e.g. date of death if a patient has died). The remainder of the database will not be changed.

All survival data will be analysed and eventually published as aggregated data with small number suppression (in line with the HES Analysis Guide), in scientific medical peer-reviewed journals (i.e. the output). Furthermore, the data will be presented at (inter)national medical meetings for cardiologists and cardiothoracic surgeons. The target date to be finished with all analyses, manuscript preparations, (inter)national scientific medical conference presentations and peer-reviewed journal submission is expected to be in September 2019.