NHS Digital Data Release Register - reformatted

University Of Dundee projects

Data linkage request for Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease ALL-HEART study
Data linkage request for (TIME) Treatment in Morning versus Evening Study

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

Data linkage request for Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease ALL-HEART study — DARS-NIC-369348-H6H8B

Type of data: information not disclosed for TRE projects

Opt outs honoured: No - consent provided by participants of research study, No - data flow is not identifiable, Identifiable, Anonymised - ICO Code Compliant, No (Reasonable Expectation, Consent (Reasonable Expectation))

Legal basis: Informed Patient consent to permit the receipt, processing and release of data by the HSCIC, Health and Social Care Act 2012 – s261(2)(c), Informed Patient consent to permit the receipt, processing and release of data by NHS Digital, Health and Social Care Act 2012 s261(2)(c), Health and Social Care Act 2012 s261(2)(c); Informed Patient consent to permit the receipt, processing and release of data by NHS Digital; Informed Patient consent to permit the receipt, processing and release of data by NHS Digital, Health and Social Care Act 2012 s261(2)(c); Informed Patient consent to permit the receipt, processing and release of data by NHS Digital

Purposes: No (Academic)

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

When:DSA runs 2019-06-01 — 2021-03-31 2017.09 — 2022.03.

Access method: Ongoing, One-Off

Data-controller type: UNIVERSITY OF DUNDEE

Sublicensing allowed: No

Datasets:

MRIS - Cause of Death Report
MRIS - Flagging Current Status Report
Hospital Episode Statistics Admitted Patient Care
Civil Registration - Deaths
MRIS - Cohort Event Notification Report
Demographics
Cancer Registration Data
Hospital Episode Statistics Admitted Patient Care (HES APC)
Civil Registrations of Death

Objectives:

The study is a multi-centre, controlled, prospective randomised open-label blinded endpoint (PROBE) trial. The study sponsor and co-ordinator and Data Controller is the University of Dundee (who have engaged the University of Glasgow as a Data Processor).

The "research team" includes those organisations involved in the ALL-HEART study (comprising the University of Dundee, the University of Glasgow, and the University of Nottingham). However, the record-level data will only be accessed by the University of Glasgow, and other organisations in the research team will only have access to aggregated data (with small numbers suppressed in line with the HES Analysis Guide).

In this study, the research team want to improve the treatment of patients with IHD. The research team are investigating whether adding allopurinol up to 600mg daily to these patients' usual medications will reduce their risk of having a stroke, heart attack or of dying due to cardiovascular disease. Patients attend their local primary care centre (general practice) to take part in the study. Patients have been randomly allocated to receive allopurinol or no treatment in addition to their usual medications, then are followed up for a period of around 4 years to count the number of heart attacks, strokes and cardiovascular deaths that occur. The numbers of these events that occur in the different treatment groups will be compared to see if there is a benefit of adding allopurinol to their other treatment. Most of the follow-up data is collected electronically by accessing centrally held electronic records of hospital admissions and deaths which will make the study easier for patients and more cost-efficient. The research team will also measure quality of life and whether there is an economic benefit of using allopurinol in patients with IHD.

The only record linkage permitted under this agreement is the linkage of data provided by NHS Digital to the other trial data (whether the patient is receiving allopurinol or not, questionnaires on (i) health service usage, (ii) general health outcomes (EQ-5D), and (iii) quality of life (Seattle Angina Questionnaire)).these records and treatments. No record-level data will be shared with any organisation, including funding organisations.

Patient/public involvement:
The research team have discussed the research topic with three patients with heart disease and engaged the help of the Angus Cardiac Group which is a patient group that is keen to contribute to the success of research studies within the NHS and beyond. They have advised on patient perceptions of the research question and practicalities of delivering the trial.

In 2013, two patients from the Angus Cardiac Group became members of the steering group of the trial. They have made invaluable contributions to this committee ever since.

In addition, the trial was discussed with the Public Involvement Co-ordinator at NHS Tayside, to help identify members of the public to help with reviewing trial documentation.

Allopurinol is a medication used to prevent gout. Allopurinol has several positive effects on the cardiovascular system, is inexpensive and is already widely used in patients. lschaemic heart disease (angina or heart attack) is one of the commonest causes of death in people in the UK and treatment of patients with ischaemic heart disease costs the NHS billions of pounds each year.

Allopurinol
Allopurinol is a xanthine oxidase inhibitor that lowers uric acid and is currently licensed for the prevention of gout and hyperuricaemia. Allopurinol is already widely prescribed in the NHS; 3,260,500 prescriptions for allopurinol were dispensed in England in 2008. The current British National Formulary price for a 28-day supply of allopurinol 300mg is £1.17 (allopurinol 600mg would be £2.34 for a 28-day supply). Therefore, this is an inexpensive drug therapy.

lschaemic heart disease (IHD)
IHD is one of the commonest cause of death in both men and women in the UK (around 1-in-5 men and 1-in-7 women die of IHD). Although death rates from IHD have fallen in the last 10 years, largely due to reductions in smoking and improvements in treatment and secondary prevention, morbidity from IHD
is increasing. IHD is more common in Scotland (4.6%) than in England (3.5%) and is more prevalent in lower socioeconomic groups and older age groups. Overall, 4% of men and 0.5% of women in the UK have a history of myocardial infarction while 14% of men and 8% of women aged 65-74 years have a history of angina.

Yielded Benefits:

There are no yielded benefits to date. The ALL-HEART study is ongoing; in order to yield the expected benefits the study needs to run to completion.

Expected Benefits:

This research will establish whether the administration of allopurinol to patients with IHD improves cardiovascular outcomes (stroke, myocardial infarction and cardiovascular death).

This study could result in a major change to treatment guidelines in the way patients with IHD are treated.

It could have a huge impact on reducing NHS costs if allopurinol, a cheap drug, is shown to reduce major cardiovascular events in patients with IHD. It could lead to reductions in morbidity and mortality and huge cost savings for the NHS in terms of admissions with major events and acute coronary syndrome or coronary revascularisations. The health economic analysis will help to quantify this. IHD is a very common disease in the aging population therefore the impact of the results of this study could be immense.

Benefits to patients
Patients with IHD often have reduced quality of life due to symptoms including chest pain, reduced exercise tolerance and limitation of activities. The diagnosis of IHD also causes a significant psychological impact on patients due to concerns about mortality and impairment of lifestyle. A simple intervention that could be prescribed easily on the NHS and could improve symptoms and reduce the risk of serious events such as myocardial infarctions, strokes and cardiovascular deaths in this patient group would be of great benefit to patients.

Benefits to the NHS
IHD causes a significant cost burden on the NHS and costs are likely to increase further as the population ages. In 2006, cardiovascular disease cost the NHS around £14.4 billion. Hospital care accounted for 72% of these costs and drug therapies accounted for 20%. Any simple inexpensive measure that could further reduce the morbidity associated with IHD, and could easily be implemented into routine care, would result in significant cost savings for the NHS. If allopurinol improves cardiovascular outcomes and were to be prescribed more widely based on the results of this study, the minimal cost of this generic medication would likely be greatly outweighed by the cost savings of reductions in IHD morbidity for the NHS. The economic analysis will quantify the health economic benefits.

Outputs:

Results will be reported in a peer-reviewed journal and at major scientific and clinical meetings. The timescale for this is expected to be between 2019 and 2021 depending on event rate within the study which is not yet known until data on outcomes is obtained via record-linkage.

The research team believe that the results of this study would be of interest to a high impact factor journal such as the Lancet or New England Journal of Medicine. The research team will organise press releases to coincide with the publication to promote knowledge mobilisation of the study results.

The research team will also present the findings at major cardiovascular and rheumatology scientific and clinical meetings. Target date 2019-2021 as above.

The research team will also send copies of the results to guideline groups such as NICE (National Institute for Health and Care Excellence) and SIGN (Scottish Intercollegiate Guidelines Network) and ask that they are considered and incorporated appropriately into revisions of guidelines. Target date 2019-2021 as above.

The research team will produce a non-technical summary of the results which the research team will send to patients who participated in the trial, patient groups and cardiovascular charities and the research team will work to generate media coverage of the study results and communicate these to the wider public. Target date 2019-2021 as above.

Outputs may also be shared with funders, but ownership and control of the outputs rests with the University of Dundee.

Processing:

Although the University of Dundee is the Data Controller, data will only be held and processed by the University of Glasgow. Only substantive employees of the University of Glasgow will have access to the data. Any data shared outside of the University of Glasgow will contain only data that is aggregated (with small numbers suppressed in line with the HES Analysis Guide). Summary reports of serious adverse events and suspected unexpected serious adverse reaction reports are made to the Medicines and Healthcare products Regulatory Agency (MHRA) in line with clinical trials requirements.

The Robertson Centre for Biostatics (part of the University of Glasgow, acting as Data Processor) will provide:
- Data management (including e-CRF design, database setup and management, data validation)
- Statistical analysis and reporting (final report, Independent Data Monitoring Committee reports)
- Data management and statistical support to record linkage
- provision of support for issues relating to data quality and use of endpoint adjudication system
- project management and quality assurance
- health economic analysis and reporting

Sample size
5,215 patients will be randomised to give 80% statistical power to detect a 20% reduction in the primary CV endpoint for the intervention (allowing for 4% dropout for withdrawal of consent to follow up and for non-cardiovascular deaths). The study will end when 631 adjudicated primary endpoints have occurred.

Record-linkage for events will be carried out annually and potential endpoints will be investigated further by obtaining information from medical records. Endpoint packages will be adjudicated by an endpoint committee blinded to treatment allocation.

Data analysis will be carried out according to a pre-determined data analysis plan. The primary analysis will be intention-to-treat.

The primary outcome and its individual components (CV death, non-fatal stroke and non-fatal myocardial infarction) will be analysed as cause-specific time to event outcomes using Cox proportional hazards models. Treatment effects will be estimated in the form of hazard ratios (allopurinol vs. no treatment). Results will be summarised graphically. Pre-specified sub-group analyses will be carried out by investigating the effects of treatment assessed by fitting interaction terms to the overall Cox models. Pre-specified subgroups will include patients with high or normal urate at baseline, patients with CV or any hospitalisation within the year prior to entry to the study, patients age <70 years versus those aged 70+ years. Results for other cardiovascular outcomes and mortality will be analysed in a similar manner. Time to discontinuation of allopurinol treatment will be described. Serious adverse events will be coded using MedDRA (Medical Dictionary for Regulatory Activities) and tabulated according to system organ class and preferred term.

The economic evaluation will estimate costs and benefits over a lifetime horizon using a Markov model approach. Using the cost perspective of the NHS and social services, it will take account of medicines cost, costs of monitoring, impact on hospital admissions (and associated costs after discharge). The research team will compare this to their estimate of the Quality Adjusted Life Years (QALY) gain from treatment to produce a net cost per QALY gained for adding allopurinol to usual care.

Data linkage request for (TIME) Treatment in Morning versus Evening Study — DARS-NIC-67135-G7D9V