Renewal request for ‘Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease ALL-HEART’ study
University of Dundee · Academic
Expired The latest version ended on 14 March 2026. The September 2026 register still lists the agreement, but its term has passed.
- Reference
- DARS-NIC-369348-H6H8B
- Latest version
- v6.3
- Term of latest version
- 15 March 2024 to 14 March 2026
- Start date
- Before 1 June 2019
- Data controller
- Sole Data Controller
- Commercial purposes
- No
- Sublicensing
- No
- Files released to date
- 21
Why the data was released
Objective for processing
Under GDPR, the lawful basis on which processing of data from NHS England concerning participants in the ALL-HEART study is laid out by Articles 6(1)(e) and 9(2)(j) namely that processing is necessary for the performance of a task carried out in the exercise of official authority, such authority to make provision for research being vested in the University by virtue of the Royal Charter establishing the University dated 20 July 1967, and, that in respect of special category personal data, processing is necessary for research purposes carried out in accordance with Article 89(1) of the GDPR. University of Dundee are a public authority and the outcomes of this research are for the benefit of public interest.
The ALL-HEART (Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease) study was a multi-centre, controlled, Prospective Randomised Open-label Blinded Endpoint (PROBE) trial.
This study aimed to improve the treatment of patients with Ischaemic Heart Disease (IHD). The research team were investigating whether adding allopurinol up to 600mg daily to these patients' usual medications would 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 were randomly allocated to receive allopurinol or no treatment in addition to their usual medications and were then followed up for a period of around 4 years to count the number of heart attacks, strokes and cardiovascular deaths that occurred. The numbers of these events that occurred in the different treatment groups were compared to see if there was a benefit of adding allopurinol to their other treatment. Most of the follow-up data was collected electronically by accessing centrally held electronic records of hospital admissions and deaths which made the study easier for patients and more cost-efficient. The research team also measured quality of life and whether there was an economic benefit of using allopurinol in patients with IHD. Patients completed quality of life questionnaires at the screening visit, after 1 year and at the end of the trial. The questionnaires assessed general health outcomes and coronary artery disease-specific quality of life. Analysis measured five clinically important dimensions of health in patients with coronary artery disease (anginal stability, anginal frequency, physical limitation, treatment satisfaction, quality of life) and was sensitive to clinical change over time. The patients were asked to report the number of visits they had made to a GP, practice nurse, physiotherapist, and hospital outpatient clinics over the last year. The number of hospitalisations was collected via the electronic record-linkage system along with other outcome data.
Allopurinol is a xanthine oxidase inhibitor that lowers uric acid and is currently licensed for the prevention of gout and hyperuricaemia. Allopurinol has several positive effects on the cardiovascular system and is already widely used in patients by 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 (angina or heart attack) is one of the most common causes 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. Ischaemic heart disease currently costs the NHS billions of pounds each year. 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 which could easily be implemented into routine care, would result in significant cost adjustments for the NHS. If allopurinol improved 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. This economic analysis quantified the health economic benefits. Follow-up was primarily by electronic record-linkage using unique identifiers to collect data on hospitalisations and mortality centrally, without the need for study follow-up visits. This approach significantly reduced the cost of the trial and was a less intrusive way of collecting data.
The study population consisted of patients aged 60 years and over with IHD (angina or myocardial infarction). 5,215 participants were recruited across the UK of which 3,460 patients were recruited from England and Wales for which this Agreement applies. Recruitment started in June 2014 and ended in September 2017. The study ended on 31st March 2022 with the draft final report to NIHR due on 30th June 2022 and the results expected to be published in August 2022.
The University of Dundee and NHS Tayside were co-sponsors of the ALL-HEART study. The University of Dundee is the sole Data Controller. The Chief Investigator is based at the University of Dundee and designed the study. Any input of others, including individuals based at University of Nottingham and University of Glasgow, was strictly advisory to the decision-making of the Chief Investigator (University of Dundee). NHS Tayside had no say in determining the manner in which the data was processed for the purposes of the study conduct as described in the application.
As is the requirement for clinical trials, several local principal investigators (PI) were based around the country with local responsibilities for aspects of the study e.g., patient recruitment, as delegated by the University of Dundee. A professor at the University of Nottingham was one of these local PIs. This person acted as local PI in their region on the instruction of the University of Dundee for study activities. The University of Nottingham did not form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement was processed. The University of Nottingham is not a data controller. Patient Information Sheets and Consent Forms for clinical trials were required to be localised with the contact details of the local team and local PI and this is why some versions of the consent materials used in English sites featured the logo of the University of Nottingham. It did not imply any role of the University of Nottingham as a data controller.
The University of Nottingham were involved in a couple of ways. Firstly, the University of Nottingham played a role in the recruitment of GP practices, and then patients, to the trial (the English part of the cohort). Secondly, three key people from Nottingham provided expertise relating to the running of clinical trials (particularly where primary care was involved) and a focus on cardiovascular research within primary care.
The University of Glasgow is the Data Processor. The University of Glasgow acts on the instruction of the University of Dundee and with no discretion as to how the data is analysed. The University of Glasgow does not form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement is processed. The University of Glasgow is strictly a data processor. The University of Glasgow is not a data controller.
No other universities formed part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement were processed. No other universities or organisations other than the University of Dundee are data controllers.
No other universities are involved in the processing of NHS England supplied study data in any other way.
In its role as a data processor, the Robertson Centre for Biostatistics (RCB) at the University of Glasgow will upload patient’s surname, forename, gender, date of birth, NHS number and date of consent along with their unique study number to NHS England for matching and subsequent linkage. Data are returned using the unique study number only, minimising the use of identifying data.
NHS England supplied the University of Glasgow with linked data on inpatient Hospital Episode Statistics (HES), mortality, demographic and national cancer registrations. These data complemented the information collected directly from participants. Under the previous Agreement, the University of Dundee received an update to the latest demographic, mortality and cancer registrations linked to HES records up to the latest available and then subsequent quarterly reports thereafter. Under this Agreement, the University of Dundee received quarterly reports for demographic, mortality and cancer registrations linked to HES records until 31st March 2022. Data were required quarterly as the study entered its final phase to ensure that the study's independent data monitoring committee received data in a timely fashion to assess study safety and to enable the research team to assess the number of study endpoints that had accrued in order to manage planning for the end of this event-driven study. The objectives of the study remain the same as stated in previous iterations of this Agreement. The primary objective of the study was to determine whether the addition of allopurinol to usual therapy improved cardiovascular outcomes. Secondary objectives were to determine the cost-effectiveness of adding allopurinol to usual therapy and to determine whether the addition of allopurinol to usual therapy improved quality of life.
The University of Dundee required data on Hospital Episode Statistics (HES), namely HES Admitted Patient Care, linked to demographic, mortality and cancer registrations. Data were returned from NHS England containing no directly identifying details with a unique study ID being used to distinguish individuals. National linkage was required in order to comprehensively map hospital activity and cancer occurrence during and after treatment with allopurinol. Likewise, national linkage to deaths was required in order to examine survival.
The study only required data from the date participants gave consent. The Patient Information Sheets provided to participants when they gave consent explained: "Every year, we will receive information from centralised electronic databases in Scotland and England for all patients taking part in the ALL-HEART study on any hospital admissions that have occurred during the year" and the study's website states: "We receive data from centralised electronic databases regarding any hospital admissions, new cancers and deaths that occur in participants during the study." The study only requires information on new reportable events since the previous report. The date each participant consented was supplied to NHS England so that the linked data could be filtered to exclude events which occurred before consent was given. However, in some instances it was not technically feasible for NHS England to filter out all events before the date of consent or events that were previously reported. This did not apply for HES or Mortality data but may impact details of Cancer Registrations. In the event that the University of Glasgow received events which occurred before the date of consent or received duplicate events which had been previously reported, the University must destroy such data. The University of Glasgow was required to review all reports received from NHS England to ensure that only the minimum amount of data required to achieve successful analysis is retained and used in subsequent analyses.
Only the variables necessary to perform the analyses required to address the purpose were requested. Researchers needed to identify hospitalisations for patients (cardio-vascular, stroke) who were being treated with allopurinol. Additionally, analysis of HES data helped to determine cost-effectiveness of the medication. Using the cost perspective of the NHS took account of medicines cost, costs of monitoring and impact on hospital admissions.
Cancer registration data was requested in order to evaluate any side-effects of allopurinol and to determine any co-morbidities within the cohort that may affect the results of the study. Mortality data was used to determine any deaths associated with the medication and also to help researchers keep records for the cohort up-to-date. Demographic data assisted in the same way, so researchers could:
i) track any patients lost to follow-up, and
ii) lower the risk of researchers trying to contact participants who had died therefore reducing the risk of causing
upset to their family/next of kin
The data requested under this Agreement was linked to trial data at the Robertson Centre for Biostatistics at University of Glasgow. The trial data consisted of information on whether the patient is receiving allopurinol or not, and questionnaires on (i) health service usage, (ii) general health outcomes (EQ-5D), and (iii) quality of life (Seattle Angina Questionnaire)). The University of Glasgow is responsible for carrying out a data management role and are therefore listed as data processor within this agreement. A processing agreement is in place between University of Dundee and University of Glasgow which defines the precise activities. University of Dundee will access the data via a remote network access to the Robertson Centre for Biostatistic's server in order to process the data. University of Glasgow only process the data under instruction from University of Dundee. University of Dundee and University of Glasgow are both data processors under this Agreement. No data will be shared outside of these two organisations.
The University of Dundee is leading the trial and is sole data controller under this Agreement. The Chief Investigator is employed by the University of Dundee and the protocol is authored by University of Dundee. The trial project manager is employed by the University of Dundee and the funding is provided to University of Dundee.
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 Dundee and the University of Glasgow. The University of Nottingham will only have access to aggregated data (with small numbers suppressed in line with the HES Analysis Guide).
The study website states that the study is run by the University of Dundee and describes what research is carried out and what outputs are produced is determined by the University of Dundee (notwithstanding that the University of Dundee may have received expert advice from the University of Nottingham – the decision rested with the University of Dundee).
Funding was provided from the National Institute of Health Research (NIHR) and has been secured until 31st March 2022. An extension for production of the draft study report to NIHR was confirmed until 30th June 2022.
The research team 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. The patients 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.
Processing activities
The data controller provided identifiers of 3,460 participants to NHS England. The following fields were provided:
- Study ID
- NHS Number
- Postcode
- Gender
- Date of Birth
- Date of Consent
NHS England will link the identifying details with the following data sets:
• HES Admitted Patient Care (in-patient data)
• Personal Demographics Service (PDS)
• Mortality
• Cancer Registration
Death Details required:
• Fact of Death
• Date of Death
• ICD 10th Revision Coded Cause(s) of Death
• Cause(s) of Death (text)
GP Practice Code was requested by the data controller in order to help trace patients that were lost to follow-up. The consent and patient information materials state that the study will contact the GP to inform them of the patient's participation in the study and capture consent to use "information held by the NHS... to contact [participants] and follow up [their] health status where relevant to this study". Researchers would contact the GP of participant's who had not replied to recent correspondence from the research team. Researchers checked with the registered GP that the address they had for a participant is up-to-date. The addition of this field is compatible with the consent.
Based on the information provided to participants, the request for GP Practice code in order to contact participants is deemed compatible with the consent.
Once the linkage had been performed, the cohort was held on NHS England's system and data was returned to University of Glasgow along with the study ID but no other identifying details were returned. The Robertson Centre for Biostatics at the University of Glasgow (acting as Data Processor) provided:
- 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
Once data from NHS England was held by the University of Glasgow, NHS England data was linked to data collected from participants during the trial. Processing of data was performed within the Robertson Centre of Biostatistcs at University of Glasgow, University of Dundee also processed the data by accessing the data via a remote network access to the Robertson Centre for Biostatistics. Data held within RCB is used for large meta-analysis of trial data.
The study team analysed the data to define the date and the nature of disease events for each participant. Researchers linked the list of processed disease outcomes with existing data-sets of baseline data, and the occurrence of disease events within trial. Data linkage took place within the RCB ISO/IEC 21007/2013 compliant environment. The data used in analyses were effectively pseudonymised - i.e. directly identifying details were removed and a study ID was used to distinguish individuals. The study ID could be used to reidentify individuals but there was no requirement to do this for this purpose.
No linkage to publicly available data was proposed. The data was processed by both University of Dundee and University of Glasgow. The University of Glasgow only processed the data under instruction from the University of Dundee. The University of Dundee and the University of Glasgow both processed the data under this Agreement. No record-level (pseudonymised or identifying) data will be shared outside of these two organisations.
Only substantive employees of the University of Dundee and the University of Glasgow will have access to the data under this Agreement. These individuals have been appropriately trained in data protection and confidentiality (they have completed the Medical Research Council (MRC) Research, GDPR and confidentiality e-learning modules and quiz). Any data shared outside of these two organisations 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 were made to the Medicines and Healthcare products Regulatory Agency (MHRA) in line with clinical trials requirements. A fully encrypted offsite back-up of study data is held with Iron Mountain, who cannot access any of these data.
The cohort was randomised to give 80% statistical power to detect a 20% reduction in the primary cardiovascular endpoint for the intervention (allowing for 4% dropout for withdrawal of consent to follow up and for non-cardiovascular deaths). The study ended when 631 adjudicated primary endpoints had occurred.
Record-linkage for events was carried out bi-annually then quarterly and potential endpoints were investigated further by obtaining information from medical records. Endpoint packages were adjudicated by an endpoint committee blinded to treatment allocation. No further dissemination of NHS England data is required as the study ended on 31/3/2022. The extension is required to allow ongoing analysis of the study results.
Data analysis was carried out according to a pre-determined data analysis plan. The primary analysis was intention-to-treat. The primary outcome and its individual components (cardiovascular death, non-fatal stroke and non-fatal myocardial infarction) will be analysed as cause-specific time to event outcomes using appropriate statistical models. Treatment effects were 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 statistical models. Pre-specified subgroups included splitting patients into three groups by urate at baseline, patients age <70 years versus those aged ≥70 years. Results for other cardiovascular outcomes and mortality were analysed in a similar manner. Time to discontinuation of allopurinol treatment was described. Serious adverse events were coded using MedDRA (Medical Dictionary for Regulatory Activities) and tabulated according to system organ class and preferred term.
The economic evaluation estimated costs and benefits over a lifetime horizon using a statistical analysis. Using the cost perspective of the NHS and social services, it took account of medicines cost, costs of monitoring, impact on hospital admissions (and associated costs after discharge). The research team compared 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.
A fully encrypted (i.e. not accessible to those storing it) back-up copy of the study data was made by the Robertson Centre for Biostatistics and held securely at Iron Mountain, Glasgow.
All organisations party to this agreement must 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).
Expected output
The main results paper was published in the Lancet in Oct 2022 (https://doi.org/10.1016/S0140-6736(22)01657-9) and presented as at the European Society of Cardiology annual meeting in Barcelona August 2022. A final report of the main study results was submitted to the study funder (NIHR) in January 2023. This report has been accepted for publication in NIHR Journals (expected
publication date Spring 2024). Further publications on aspects of the results are still being prepared. This will require ongoing analysis of the data to ensure that all aspects of the study data
are fully explored to yield any potential benefits for patients with ischaemic heart disease. The research team produced a non-technical summary of the results which the research team sent to
patients who participated in the trial, and other stakeholders in September 2022.
Outputs may also be shared with funders, but ownership and control of the outputs rests with the University of Dundee. There will be no data linkage undertaken with NHS England data provided under this Agreement that is not already noted in the Agreement. No further data dissemination is required under this Agreement. All outputs will only contain results in highly aggregated format with small numbers suppressed and as statistical summaries and measures of association. Small numbers will be suppressed in line with the HES Analysis Guide. Record level information will not be released to any third party.
Expected measurable benefits
This research has answered the main research question of whether the administration of allopurinol to patients with ischaemic heart disease (IHD) improves cardiovascular outcomes (stroke, myocardial infarction and cardiovascular death). Findings have been presented and published at international meetings and in the Lancet, which is a major international journal. The study found that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared with usual care in patients with ischaemic heart disease. Based on the results of the ALL-HEART study, allopurinol should not be recommended for secondary prevention of cardiovascular events in patients with ischaemic heart disease. This finding has influenced patient care worldwide and has informed future scientific and clinical studies in this area. Ongoing detailed analyses of the study data will further inform the medical and scientific community about any potential benefits or risks of allopurinol in patients with ischaemic heart disease. University of Dundee have requested a 2-year extension of the DARS so that these analyses can be completed over the next two years, to maximise the benefit of the study findings for the benefit of patients and guiding patient care internationally. Ischaemic heart disease is a very common condition and is one of the most common causes of death in the UK. Patients with ischaemic heart disease have many comorbidities so detailed analysis of the study data is important to inform future care of these patients. Many patients with ischaemic heart disease receive allopurinol and other xanthine oxidase inhibitors to treat gout, which is one of the common co-existing conditions, so achieving a full understanding of the potential benefits or adverse effects of allopurinol in these patients is important.
Benefits reported so far
The study has been completed and data analysis of the main study results has taken place. The main study results were presented as a hotline session at the European Society of Cardiology meeting in Barcelona in August 2022 and published in the Lancet (https://doi.org/10.1016/S0140-6736(22)01657-9). They were also presented at the Global Clinical Trials Summit in September 2022 to an international audience. A manuscript describing the study and the health economic analysis results is accepted in press at the NIHR HTA Journal. Further analyses of the data collected during the study are ongoing to fully understand the effects of allopurinol in patients with ischaemic heart disease.
Datasets on the latest version
Legal basis for provision: Health and Social Care Act 2012 – s261(2)(c)
| Dataset | Type of data | Sensitivity | Frequency | Confidential data |
|---|---|---|---|---|
| Cancer Registration Data | Identifiable | Sensitive | Ongoing | Consent (Reasonable Expectation) |
| Civil Registrations of Death | Identifiable | Sensitive | Ongoing | Consent (Reasonable Expectation) |
| Demographics | Identifiable | Sensitive | Ongoing | Consent (Reasonable Expectation) |
| Hospital Episode Statistics Admitted Patient Care (HES APC) | Identifiable | Non-Sensitive | Ongoing | Consent (Reasonable Expectation) |
| MRIS - Cause of Death Report | Identifiable | Sensitive | One-Off | Consent (Reasonable Expectation) |
| MRIS - Cohort Event Notification Report | Identifiable | Sensitive | One-Off | Consent (Reasonable Expectation) |
| MRIS - Flagging Current Status Report | Identifiable | Sensitive | One-Off | Consent (Reasonable Expectation) |
Files released
Files released counts only files released externally by DARS. Access granted in NHS England's own systems, such as its Secure Data Environment, is not included.
Patient opt-outs were not applied to any of the 21 files released under this agreement, across every version. About opt-outs
No files recorded as released under the latest version. 21 were released under earlier versions, shown in the version history.
Version history
The register lists each renewal of this agreement as a separate row. This site has 5 versions — earlier versions existed before this site's records begin.
DARS-NIC-369348-H6H8B-v6.3 15 March 2024 to 14 March 2026
- Title
- Renewal request for ‘Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease ALL-HEART’ study
- Commercial
- No
- Sublicensing
- No
- Datasets
- 7
- Files released
- 0
Datasets: Cancer Registration Data; Civil Registrations of Death; Demographics; Hospital Episode Statistics Admitted Patient Care (HES APC); MRIS - Cause of Death Report; MRIS - Cohort Event Notification Report; MRIS - Flagging Current Status Report
What changed from DARS-NIC-369348-H6H8B-v5.2
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2024-03-15 | |
| End date | 2026-03-14 | |
| Cancer Registration Data: legal basis | Health and Social Care Act 2012 – s261(2)(c) | |
| Civil Registrations of Death: legal basis | Health and Social Care Act 2012 – s261(2)(c) | |
| Demographics: legal basis | Health and Social Care Act 2012 – s261(2)(c) | |
| Hospital Episode Statistics Admitted Patient Care (HES APC): legal basis | Health and Social Care Act 2012 – s261(2)(c) | |
| MRIS - Cause of Death Report: legal basis | Health and Social Care Act 2012 – s261(2)(c) | |
| MRIS - Cohort Event Notification Report: legal basis | Health and Social Care Act 2012 – s261(2)(c) | |
| MRIS - Flagging Current Status Report: legal basis | Health and Social Care Act 2012 – s261(2)(c) |
Objective for processing
Under GDPR, the lawful basis on which processing of data from NHS
Digital
England
concerning participants in the ALL-HEART study is laid out by Articles 6(1)(e)
[72 words unchanged]
of Dundee are a public authority and the outcomes of this research
is
are
for the benefit of public interest.
[1 paragraph unchanged]
This study aimed to improve the treatment of patients with Ischaemic Heart
[243 words unchanged]
the number of visits they had made to a GP, practice nurse,
physiotherapist
physiotherapist,
and hospital outpatient clinics over the last year. The number of hospitalisations was collected via the electronic record-linkage system along with other outcome data.
[8 paragraphs unchanged]
No other universities are involved in the processing of NHS
Digital
England
supplied study data in any other way.
In its role as a data processor, the Robertson Centre for Biostatistics
[17 words unchanged]
and date of consent along with their unique study number to NHS
Digital
England
for matching and subsequent linkage. Data are returned using the unique study number only, minimising the use of identifying data.
NHS
Digital
England
supplied the University of Glasgow with linked data on inpatient Hospital Episode
[185 words unchanged]
whether the addition of allopurinol to usual therapy improved quality of life.
The University of Dundee required data on Hospital Episode Statistics (HES), namely HES Admitted Patient Care, linked to demographic, mortality and cancer registrations. Data were returned from NHS
Digital
England
containing no directly identifying details with a unique study ID being used
[23 words unchanged]
Likewise, national linkage to deaths was required in order to examine survival.
The study only required data from the date participants gave consent. The
[81 words unchanged]
the previous report. The date each participant consented was supplied to NHS
Digital
England
so that the linked data could be filtered to exclude events which occurred before consent was given. However, in some instances it was not technically feasible for NHS
Digital
England
to filter out all events before the date of consent or events
[53 words unchanged]
University of Glasgow was required to review all reports received from NHS
Digital
England
to ensure that only the minimum amount of data required to achieve successful analysis is retained and used in subsequent analyses.
[13 paragraphs unchanged]
Processing activities
The data controller provided identifiers of 3,460 participants to NHS
Digital.
England.
The following fields were provided:
[6 paragraphs unchanged]
NHS
Digital
England
will link the identifying details with the following data sets:
[11 paragraphs unchanged]
Once the linkage had been performed, the cohort was held on NHS
Digital's
England's
system and data was returned to University of Glasgow along with the
[12 words unchanged]
for Biostatics at the University of Glasgow (acting as Data Processor) provided:
[6 paragraphs unchanged]
Once data from NHS
Digital
England
was held by the University of Glasgow, NHS
Digital
England
data was linked to data collected from participants during the trial. Processing
[36 words unchanged]
Data held within RCB is used for large meta-analysis of trial data.
[4 paragraphs unchanged]
Record-linkage for events was carried out bi-annually then quarterly and potential endpoints
[14 words unchanged]
an endpoint committee blinded to treatment allocation. No further dissemination of NHS
Digital
England
data is required as the study ended on 31/3/2022. The extension is required to allow ongoing analysis of the study results.
[4 paragraphs unchanged]
Expected output
Results will be reported in a peer-reviewed journal and at major scientific and clinical meetings. The timescale for this is expected to be in summer 2022. The research team aim to submit the main results paper to the Lancet and present the results at a major meeting, probably the European Society of Cardiology annual meeting in Barcelona August 2022. The research team will organise press releases to coincide with the publication to promote knowledge mobilisation of the study results. Further publications on aspects of the results may be prepared over the next few months. This will require ongoing analysis of the data to ensure that all aspects of the study data are fully explored to yield any potential benefits for patients with ischaemic heart disease.
The main results paper was published in the Lancet in Oct 2022 (https://doi.org/10.1016/S0140-6736(22)01657-9) and presented as at the European Society of Cardiology annual meeting in Barcelona August 2022. A final report of the main study results was submitted to the study funder (NIHR) in January 2023. This report has been accepted for publication in NIHR Journals (expected
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 Summer 2022.
publication date Spring 2024). Further publications on aspects of the results are still being prepared. This will require ongoing analysis of the data to ensure that all aspects of the study data
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 Summer 2022.
are fully explored to yield any potential benefits for patients with ischaemic heart disease. The research team produced a non-technical summary of the results which the research team sent to
Outputs may also be shared with funders, but ownership and control of the outputs rests with the University of Dundee.
patients who participated in the trial, and other stakeholders in September 2022.
Outputs may also be shared with funders, but ownership and control of the outputs rests with the University of Dundee.
There will be no data linkage undertaken with NHS
Digital
England
data provided under this Agreement that is not already noted in the Agreement. No further data dissemination is required under this Agreement.
All outputs will only contain results in highly aggregated format with small numbers suppressed and as statistical summaries and measures of association. Small numbers will be suppressed in line with the HES Analysis Guide. Record level information will not be released to any third party.
All outputs will only contain results in highly aggregated format with small numbers suppressed and as statistical summaries and measures of association. Small numbers will be suppressed in line with the HES Analysis Guide. Record level information will not be released to any third party.
Expected measurable benefits
This research will establish whether the administration of allopurinol to patients with ischaemic heart disease (IHD) improves cardiovascular outcomes (stroke, myocardial infarction and cardiovascular death).
This research has answered the main research question of whether the administration of allopurinol to patients with ischaemic heart disease (IHD) improves cardiovascular outcomes (stroke, myocardial infarction and cardiovascular death). Findings have been presented and published at international meetings and in the Lancet, which is a major international journal. The study found that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared with usual care in patients with ischaemic heart disease. Based on the results of the ALL-HEART study, allopurinol should not be recommended for secondary prevention of cardiovascular events in patients with ischaemic heart disease. This finding has influenced patient care worldwide and has informed future scientific and clinical studies in this area. Ongoing detailed analyses of the study data will further inform the medical and scientific community about any potential benefits or risks of allopurinol in patients with ischaemic heart disease. University of Dundee have requested a 2-year extension of the DARS so that these analyses can be completed over the next two years, to maximise the benefit of the study findings for the benefit of patients and guiding patient care internationally. Ischaemic heart disease is a very common condition and is one of the most common causes of death in the UK. Patients with ischaemic heart disease have many comorbidities so detailed analysis of the study data is important to inform future care of these patients. Many patients with ischaemic heart disease receive allopurinol and other xanthine oxidase inhibitors to treat gout, which is one of the common co-existing conditions, so achieving a full understanding of the potential benefits or adverse effects of allopurinol in these patients is important.
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 adjustments for the NHS in terms of admissions with major events and acute coronary syndrome or coronary revascularisations. The health economic analysis might 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.
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.
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 adjustments 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.
Benefits reported
There are no yielded benefits to date. The ALL-HEART study is near completion and data analysis will take place over the next few weeks; in order to yield the expected benefits, the study results need to be analysed and published. Database lock is expected in April 2022 and until then the results are not available.
The study has been completed and data analysis of the main study results has taken place. The main study results were presented as a hotline session at the European Society of Cardiology meeting in Barcelona in August 2022 and published in the Lancet (https://doi.org/10.1016/S0140-6736(22)01657-9). They were also presented at the Global Clinical Trials Summit in September 2022 to an international audience. A manuscript describing the study and the health economic analysis results is accepted in press at the NIHR HTA Journal. Further analyses of the data collected during the study are ongoing to fully understand the effects of allopurinol in patients with ischaemic heart disease.
DARS-NIC-369348-H6H8B-v5.2 1 April 2022 to 31 March 2024
- Title
- Renewal request for ‘Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease ALL-HEART’ study
- Commercial
- No
- Sublicensing
- No
- Datasets
- 7
- Files released
- 0
Datasets: Cancer Registration Data; Civil Registrations of Death; Demographics; Hospital Episode Statistics Admitted Patient Care (HES APC); MRIS - Cause of Death Report; MRIS - Cohort Event Notification Report; MRIS - Flagging Current Status Report
What changed from DARS-NIC-369348-H6H8B-v4.3
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2022-04-01 | |
| End date | 2024-03-31 | |
| Cancer Registration Data: legal basis | 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 | |
| Civil Registrations of Death: legal basis | Health and Social Care Act 2012 – s261(2)(c); Informed Patient consent to permit the receipt, processing and release of data by NHS Digital | |
| Demographics: legal basis | Health and Social Care Act 2012 – s261(2)(c); Informed Patient consent to permit the receipt, processing and release of data by NHS Digital | |
| Hospital Episode Statistics Admitted Patient Care (HES APC): legal basis | Health and Social Care Act 2012 – s261(2)(c); Informed Patient consent to permit the receipt, processing and release of data by NHS Digital | |
| MRIS - Cause of Death Report: legal basis | Health and Social Care Act 2012 – s261(2)(c); Informed Patient consent to permit the receipt, processing and release of data by NHS Digital | |
| MRIS - Cohort Event Notification Report: legal basis | Health and Social Care Act 2012 – s261(2)(c); Informed Patient consent to permit the receipt, processing and release of data by NHS Digital | |
| MRIS - Flagging Current Status Report: legal basis | 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 |
Objective for processing
[1 paragraph unchanged]
The ALL-HEART (Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease) study
is
was
a multi-centre, controlled, Prospective Randomised Open-label Blinded Endpoint (PROBE) trial.
This study
aims
aimed
to improve the treatment of patients with Ischaemic Heart Disease (IHD). The research team
are
were
investigating whether adding allopurinol up to 600mg daily to these patients' usual medications
will
would
reduce their risk of having a stroke, heart attack or of dying
[8 words unchanged]
primary care centre (general practice) to take part in the study. Patients
have been
were
randomly allocated to receive allopurinol or no treatment in addition to their usual medications and
are
were
then followed up for a period of around 4 years to count the number of heart attacks, strokes and cardiovascular deaths that
occur.
occurred.
The numbers of these events that
occur
occurred
in the different treatment groups
will be
were
compared to see if there
is
was
a benefit of adding allopurinol to their other treatment. Most of the follow-up data
is
was
collected electronically by accessing centrally held electronic records of hospital admissions and deaths which
will make
made
the study easier for patients and more cost-efficient. The research team
will
also
measure
measured
quality of life and whether there
is
was
an economic benefit of using allopurinol in patients with IHD. Patients
will complete
completed
quality of life questionnaires at the screening visit, after 1 year and at the end of the trial. The questionnaires
will assess
assessed
general health outcomes and coronary artery disease-specific quality of life. Analysis
will measure
measured
five clinically important dimensions of health in patients with coronary artery disease (anginal stability, anginal frequency, physical limitation, treatment satisfaction, quality of life) and
is
was
sensitive to clinical change over time. The
patient will be
patients were
asked to report the number of visits they
have
had
made to a GP, practice nurse, physiotherapist and hospital outpatient clinics over the last year. The number of hospitalisations
will be
was
collected via the electronic record-linkage system along with other outcome data.
[1 paragraph unchanged]
lschaemic heart disease (angina or heart attack) is one of the most
[154 words unchanged]
care, would result in significant cost adjustments for the NHS. If allopurinol
improves
improved
cardiovascular outcomes and were to be prescribed more widely based on the
[19 words unchanged]
savings of reductions in IHD morbidity for the NHS. This economic analysis
will quantify
quantified
the health economic benefits. Follow-up
will
was
primarily
be
by electronic record-linkage using unique identifiers to collect data on hospitalisations and mortality centrally, without the need for study follow-up visits. This approach significantly
reduces
reduced
the cost of the trial and
is
was
a less intrusive way of collecting data.
The study population
consists
consisted
of patients aged 60 years and over with IHD (angina or myocardial
[21 words unchanged]
Agreement applies. Recruitment started in June 2014 and ended in September 2017.
The study ended on 31st March 2022 with the draft final report to NIHR due on 30th June 2022 and the results expected to be published in August 2022.
The University of Dundee and NHS Tayside
are
were
co-sponsors of the ALL-HEART study. The University of Dundee is the sole
[34 words unchanged]
to the decision-making of the Chief Investigator (University of Dundee). NHS Tayside
has
had
no say in determining the manner in which the data
is
was
processed for the purposes of the study conduct as described in the application.
As is the requirement for clinical trials, several local principal investigators (PI)
are
were
based around the country with local responsibilities for aspects of the study
[5 words unchanged]
by the University of Dundee. A professor at the University of Nottingham
is
was
one of these local PIs. This person
acts
acted
as local PI in their region on the instruction of the University of Dundee for study activities. The University of Nottingham
does
did
not form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement
will be
was
processed. The University of Nottingham is not a data controller. Patient Information Sheets and Consent Forms for clinical trials
are
were
required to be localised with the contact details of the local team
[5 words unchanged]
is why some versions of the consent materials used in English sites
feature
featured
the logo of the University of Nottingham. It
does
did
not imply any role of the University of Nottingham as a data controller.
The University of Nottingham
are
were
involved in a couple of ways. Firstly, the University of Nottingham
has
played a role in the recruitment of GP practices, and then patients, to the trial (the English part of the cohort). Secondly, three key people from Nottingham
are providing
provided
expertise relating to the running of clinical trials (particularly where primary care
is
was
involved) and a focus on cardiovascular research within primary care.
The University of Glasgow is the Data Processor. The University of Glasgow
[36 words unchanged]
purposes for, or the manner in which, the data under this Agreement
will be
is
processed. The University of Glasgow is strictly a data processor. The University of Glasgow is not a data controller.
No other universities
form
formed
part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement
will be
were
processed. No other universities or organisations other than the University of Dundee are data controllers.
[2 paragraphs unchanged]
NHS Digital
supply
supplied
the University of Glasgow with linked data on inpatient Hospital Episode Statistics (HES), mortality, demographic and national cancer registrations. These data
complement
complemented
the information collected directly from participants. Under the previous Agreement, the University
[23 words unchanged]
then subsequent quarterly reports thereafter. Under this Agreement, the University of Dundee
will continue to receive
received
quarterly reports for demographic, mortality and cancer registrations linked to HES records
for the duration of this Agreement.
until 31st March 2022.
Data
are
were
required quarterly as the study
enters
entered
its final phase to ensure that the study's independent data monitoring committee
receive
received
data in a timely fashion to assess study safety and to enable the research team to assess the number of study endpoints that
have
had
accrued in order to manage planning for the end of this event-driven
[11 words unchanged]
in previous iterations of this Agreement. The primary objective of the study
is
was
to determine whether the addition of allopurinol to usual therapy
improves
improved
cardiovascular outcomes. Secondary objectives
are
were
to determine the cost-effectiveness of adding allopurinol to usual therapy and to determine whether the addition of allopurinol to usual therapy
improves
improved
quality of life.
The University of Dundee
requires
required
data on Hospital Episode Statistics (HES), namely HES Admitted Patient Care, linked to demographic, mortality and cancer registrations. Data
are
were
returned from NHS Digital containing no directly identifying details with a unique study ID being used to distinguish individuals. National linkage
is
was
required in order to comprehensively map hospital activity and cancer occurrence during and after treatment with allopurinol. Likewise, national linkage to deaths
is
was
required in order to examine survival.
The study only
requires
required
data from the date participants gave consent. The Patient Information Sheets provided
[73 words unchanged]
new reportable events since the previous report. The date each participant consented
will be
was
supplied to NHS Digital so that the linked data
can
could
be filtered to exclude events which occurred before consent was given. However, in some instances it
will
was
not
be
technically feasible for NHS Digital to filter out all events before the date of consent or events that were previously reported. This
will
did
not apply for HES or Mortality data but may impact details of Cancer Registrations. In the event that the University of Glasgow
receives
received
events which occurred before the date of consent or
receives
received
duplicate events which
have
had
been previously reported, the University must destroy such data. The University of Glasgow
is
was
required to review all reports received from NHS Digital to ensure that
[6 words unchanged]
required to achieve successful analysis is retained and used in subsequent analyses.
Only the variables necessary to perform the analyses required to address the purpose
are
were
requested. Researchers
need
needed
to identify hospitalisations for patients (cardio-vascular, stroke) who
are
were
being treated with allopurinol. Additionally, analysis of HES data
will help
helped
to determine cost-effectiveness of the medication. Using the cost perspective of the NHS
will take
took
account of medicines cost, costs of monitoring and impact on hospital admissions.
Cancer registration data
is
was
requested in order to evaluate any side-effects of allopurinol and to determine any co-morbidities within the cohort that may affect the results of the study. Mortality data
will be
was
used to determine any deaths
resulting from
associated with
the medication and also to help researchers keep records for the cohort up-to-date. Demographic data
will assist
assisted
in the same way, so researchers
can:
could:
[1 paragraph unchanged]
ii) lower the risk of researchers trying to contact participants who
have
had
died therefore reducing the risk of causing
[1 paragraph unchanged]
The data requested under this Agreement
will be
was
linked to trial data at the Robertson Centre for Biostatistics at University of Glasgow. The trial data
consists
consisted
of information on whether the patient is receiving allopurinol or not, and
[111 words unchanged]
this Agreement. No data will be shared outside of these two organisations.
[2 paragraphs unchanged]
The study website states that the study is run by the University
[16 words unchanged]
by the University of Dundee (notwithstanding that the University of Dundee may
receive
have received
expert advice from the University of Nottingham – the decision
rests
rested
with the University of Dundee).
Funding
is
was
provided from the National Institute of Health
research
Research
(NIHR) and has been secured until 31st March
2021. This is currently in
2022. An extension for production of
the
process of being extended
draft study report to NIHR was confirmed
until
31/03/2022.
30th June 2022.
The research team
have
discussed the research topic with three patients with heart disease and engaged
[16 words unchanged]
contribute to the success of research studies within the NHS and beyond.
They have
The patients
advised on patient perceptions of the research question and practicalities of delivering the trial.
[2 paragraphs unchanged]
Processing activities
[17 paragraphs unchanged]
GP Practice Code
has been
was
requested by the data controller in order to help trace patients that
have been
were
lost to follow-up. The consent and patient information materials state that the
[28 words unchanged]
and follow up [their] health status where relevant to this study". Researchers
will
would
contact the GP of participant's who
have
had
not replied to recent correspondence from the research team. Researchers
will check
checked
with the registered GP that the address they
have
had
for a participant is up-to-date. The addition of this field is compatible with the consent.
[1 paragraph unchanged]
Once the linkage
has
had
been performed, the cohort
will be
was
held on NHS Digital's system and data
will be
was
returned to University of Glasgow along with the study ID but no other identifying details
will be
were
returned. The Robertson Centre for Biostatics at the University of Glasgow (acting as Data Processor)
will provide:
provided:
[6 paragraphs unchanged]
Once data from NHS Digital
is
was
held by the University of Glasgow, NHS Digital data
will be
was
linked to data collected from participants during the trial. Processing of data
will be
was
performed within the Robertson Centre of Biostatistcs at University of Glasgow, University of Dundee
will
also
process
processed
the data by accessing the data via a remote network access to
[5 words unchanged]
Data held within RCB is used for large meta-analysis of trial data.
The study team
will analyse
analysed
the data to define the date and the nature of disease events for each participant. Researchers
will link
linked
the list of processed disease outcomes with existing data-sets of baseline data, and the occurrence of disease events within trial. Data linkage
takes
took
place within the RCB ISO/IEC 21007/2013 compliant environment. The data used in analyses
are
were
effectively pseudonymised - i.e. directly identifying details
are
were
removed and a study ID
is
was
used to distinguish individuals. The study ID could be used to reidentify individuals but there
is
was
no requirement to do this for this purpose.
No linkage to publicly available data
is
was
proposed. The data
will be
was
processed by both University of Dundee and University of Glasgow. The University of Glasgow only
process
processed
the data under instruction from the University of Dundee. The University of Dundee and the University of Glasgow both
process
processed
the data under this Agreement. No record-level (pseudonymised or identifying) data will be shared outside of these two organisations.
Only substantive employees of the University of Dundee and the University of
[64 words unchanged]
reports of serious adverse events and suspected unexpected serious adverse reaction reports
are
were
made to the Medicines and Healthcare products Regulatory Agency (MHRA) in line
[12 words unchanged]
is held with Iron Mountain, who cannot access any of these data.
The cohort
will be
was
randomised to give 80% statistical power to detect a 20% reduction in
[12 words unchanged]
withdrawal of consent to follow up and for non-cardiovascular deaths). The study
will end
ended
when 631 adjudicated primary endpoints
have
had
occurred.
Record-linkage for events
will be
was
carried out bi-annually
then quarterly
and potential endpoints
will be
were
investigated further by obtaining information from medical records. Endpoint packages
will be
were
adjudicated by an endpoint committee blinded to treatment allocation.
No further dissemination of NHS Digital data is required as the study ended on 31/3/2022. The extension is required to allow ongoing analysis of the study results.
Data analysis
will be
was
carried out according to a pre-determined data analysis plan. The primary analysis
will be
was
intention-to-treat. The primary outcome and its individual components (cardiovascular death, non-fatal stroke
[7 words unchanged]
as cause-specific time to event outcomes using appropriate statistical models. Treatment effects
will be
were
estimated in the form of hazard ratios (allopurinol vs. no treatment). Results
[17 words unchanged]
assessed by fitting interaction terms to the overall statistical models. Pre-specified subgroups
will include
included
splitting patients into three groups by urate at baseline, patients age <70 years versus those aged ≥70 years. Results for other cardiovascular outcomes and mortality
will be
were
analysed in a similar manner. Time to discontinuation of allopurinol treatment
will be
was
described. Serious adverse events
will be
were
coded using MedDRA (Medical Dictionary for Regulatory Activities) and tabulated according to system organ class and preferred term.
The economic evaluation
will estimate
estimated
costs and benefits over a lifetime horizon using a statistical analysis. Using the cost perspective of the NHS and social services, it
will take
took
account of medicines cost, costs of monitoring, impact on hospital admissions (and associated costs after discharge). The research team
will compare
compared
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.
A fully encrypted (i.e. not accessible to those storing it) back-up copy of the study data
is
was
made by the Robertson Centre for Biostatistics and held securely at Iron Mountain, Glasgow.
[1 paragraph unchanged]
Expected output
Results will be reported in a peer-reviewed journal and at major scientific and clinical meetings. The timescale for this is expected to be in 2022. A contract variation request to extend the duration of the study until 31st March 2022 has been submitted to NIHR. An IRAS amendment extending the study to 31st March 2022 has been implemented.
Results will be reported in a peer-reviewed journal and at major scientific and clinical meetings. The timescale for this is expected to be in summer 2022. The research team aim to submit the main results paper to the Lancet and present the results at a major meeting, probably the European Society of Cardiology annual meeting in Barcelona August 2022. The research team will organise press releases to coincide with the publication to promote knowledge mobilisation of the study results. Further publications on aspects of the results may be prepared over the next few months. This will require ongoing analysis of the data to ensure that all aspects of the study data are fully explored to yield any potential benefits for patients with ischaemic heart disease.
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 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 Summer 2022.
The research team will also present the findings at major cardiovascular and rheumatology scientific and clinical meetings. Target date 2022 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 Summer 2022.
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 2022 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 2022 as above.
[1 paragraph unchanged]
There will be no data linkage undertaken with NHS Digital data provided under this Agreement that is not already noted in the Agreement.
No further data dissemination is required under this Agreement.
All outputs will only contain results in highly aggregated format
with small numbers suppressed
and as statistical summaries and measures of association. Small numbers will be
[7 words unchanged]
Guide. Record level information will not be released to any third party.
Expected measurable benefits
This research
is hoped to
will
establish whether the administration of allopurinol to patients with ischaemic heart disease (IHD) improves cardiovascular outcomes (stroke, myocardial infarction and cardiovascular death).
[4 paragraphs unchanged]
Benefits reported
There are no yielded benefits to date. The ALL-HEART study is
ongoing;
near completion and data analysis will take place over the next few weeks;
in order to yield the expected benefits, the study
needs
results need
to
run to completion.
be analysed and published. Database lock is expected in April 2022 and until then the results are not available.
Objective for processing
Under GDPR, the lawful basis on which processing of data from NHS Digital concerning participants in the ALL-HEART study is laid out by Articles 6(1)(e) and 9(2)(j) namely that processing is necessary for the performance of a task carried out in the exercise of official authority, such authority to make provision for research being vested in the University by virtue of the Royal Charter establishing the University dated 20 July 1967, and, that in respect of special category personal data, processing is necessary for research purposes carried out in accordance with Article 89(1) of the GDPR. University of Dundee are a public authority and the outcomes of this research is for the benefit of public interest.
The ALL-HEART (Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease) study was a multi-centre, controlled, Prospective Randomised Open-label Blinded Endpoint (PROBE) trial.
This study aimed to improve the treatment of patients with Ischaemic Heart Disease (IHD). The research team were investigating whether adding allopurinol up to 600mg daily to these patients' usual medications would 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 were randomly allocated to receive allopurinol or no treatment in addition to their usual medications and were then followed up for a period of around 4 years to count the number of heart attacks, strokes and cardiovascular deaths that occurred. The numbers of these events that occurred in the different treatment groups were compared to see if there was a benefit of adding allopurinol to their other treatment. Most of the follow-up data was collected electronically by accessing centrally held electronic records of hospital admissions and deaths which made the study easier for patients and more cost-efficient. The research team also measured quality of life and whether there was an economic benefit of using allopurinol in patients with IHD. Patients completed quality of life questionnaires at the screening visit, after 1 year and at the end of the trial. The questionnaires assessed general health outcomes and coronary artery disease-specific quality of life. Analysis measured five clinically important dimensions of health in patients with coronary artery disease (anginal stability, anginal frequency, physical limitation, treatment satisfaction, quality of life) and was sensitive to clinical change over time. The patients were asked to report the number of visits they had made to a GP, practice nurse, physiotherapist and hospital outpatient clinics over the last year. The number of hospitalisations was collected via the electronic record-linkage system along with other outcome data.
Allopurinol is a xanthine oxidase inhibitor that lowers uric acid and is currently licensed for the prevention of gout and hyperuricaemia. Allopurinol has several positive effects on the cardiovascular system and is already widely used in patients by 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 (angina or heart attack) is one of the most common causes 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. Ischaemic heart disease currently costs the NHS billions of pounds each year. 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 which could easily be implemented into routine care, would result in significant cost adjustments for the NHS. If allopurinol improved 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. This economic analysis quantified the health economic benefits. Follow-up was primarily by electronic record-linkage using unique identifiers to collect data on hospitalisations and mortality centrally, without the need for study follow-up visits. This approach significantly reduced the cost of the trial and was a less intrusive way of collecting data.
The study population consisted of patients aged 60 years and over with IHD (angina or myocardial infarction). 5,215 participants were recruited across the UK of which 3,460 patients were recruited from England and Wales for which this Agreement applies. Recruitment started in June 2014 and ended in September 2017. The study ended on 31st March 2022 with the draft final report to NIHR due on 30th June 2022 and the results expected to be published in August 2022.
The University of Dundee and NHS Tayside were co-sponsors of the ALL-HEART study. The University of Dundee is the sole Data Controller. The Chief Investigator is based at the University of Dundee and designed the study. Any input of others, including individuals based at University of Nottingham and University of Glasgow, was strictly advisory to the decision-making of the Chief Investigator (University of Dundee). NHS Tayside had no say in determining the manner in which the data was processed for the purposes of the study conduct as described in the application.
As is the requirement for clinical trials, several local principal investigators (PI) were based around the country with local responsibilities for aspects of the study e.g., patient recruitment, as delegated by the University of Dundee. A professor at the University of Nottingham was one of these local PIs. This person acted as local PI in their region on the instruction of the University of Dundee for study activities. The University of Nottingham did not form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement was processed. The University of Nottingham is not a data controller. Patient Information Sheets and Consent Forms for clinical trials were required to be localised with the contact details of the local team and local PI and this is why some versions of the consent materials used in English sites featured the logo of the University of Nottingham. It did not imply any role of the University of Nottingham as a data controller.
The University of Nottingham were involved in a couple of ways. Firstly, the University of Nottingham played a role in the recruitment of GP practices, and then patients, to the trial (the English part of the cohort). Secondly, three key people from Nottingham provided expertise relating to the running of clinical trials (particularly where primary care was involved) and a focus on cardiovascular research within primary care.
The University of Glasgow is the Data Processor. The University of Glasgow acts on the instruction of the University of Dundee and with no discretion as to how the data is analysed. The University of Glasgow does not form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement is processed. The University of Glasgow is strictly a data processor. The University of Glasgow is not a data controller.
No other universities formed part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement were processed. No other universities or organisations other than the University of Dundee are data controllers.
No other universities are involved in the processing of NHS Digital supplied study data in any other way.
In its role as a data processor, the Robertson Centre for Biostatistics (RCB) at the University of Glasgow will upload patient’s surname, forename, gender, date of birth, NHS number and date of consent along with their unique study number to NHS Digital for matching and subsequent linkage. Data are returned using the unique study number only, minimising the use of identifying data.
NHS Digital supplied the University of Glasgow with linked data on inpatient Hospital Episode Statistics (HES), mortality, demographic and national cancer registrations. These data complemented the information collected directly from participants. Under the previous Agreement, the University of Dundee received an update to the latest demographic, mortality and cancer registrations linked to HES records up to the latest available and then subsequent quarterly reports thereafter. Under this Agreement, the University of Dundee received quarterly reports for demographic, mortality and cancer registrations linked to HES records until 31st March 2022. Data were required quarterly as the study entered its final phase to ensure that the study's independent data monitoring committee received data in a timely fashion to assess study safety and to enable the research team to assess the number of study endpoints that had accrued in order to manage planning for the end of this event-driven study. The objectives of the study remain the same as stated in previous iterations of this Agreement. The primary objective of the study was to determine whether the addition of allopurinol to usual therapy improved cardiovascular outcomes. Secondary objectives were to determine the cost-effectiveness of adding allopurinol to usual therapy and to determine whether the addition of allopurinol to usual therapy improved quality of life.
The University of Dundee required data on Hospital Episode Statistics (HES), namely HES Admitted Patient Care, linked to demographic, mortality and cancer registrations. Data were returned from NHS Digital containing no directly identifying details with a unique study ID being used to distinguish individuals. National linkage was required in order to comprehensively map hospital activity and cancer occurrence during and after treatment with allopurinol. Likewise, national linkage to deaths was required in order to examine survival.
The study only required data from the date participants gave consent. The Patient Information Sheets provided to participants when they gave consent explained: "Every year, we will receive information from centralised electronic databases in Scotland and England for all patients taking part in the ALL-HEART study on any hospital admissions that have occurred during the year" and the study's website states: "We receive data from centralised electronic databases regarding any hospital admissions, new cancers and deaths that occur in participants during the study." The study only requires information on new reportable events since the previous report. The date each participant consented was supplied to NHS Digital so that the linked data could be filtered to exclude events which occurred before consent was given. However, in some instances it was not technically feasible for NHS Digital to filter out all events before the date of consent or events that were previously reported. This did not apply for HES or Mortality data but may impact details of Cancer Registrations. In the event that the University of Glasgow received events which occurred before the date of consent or received duplicate events which had been previously reported, the University must destroy such data. The University of Glasgow was required to review all reports received from NHS Digital to ensure that only the minimum amount of data required to achieve successful analysis is retained and used in subsequent analyses.
Only the variables necessary to perform the analyses required to address the purpose were requested. Researchers needed to identify hospitalisations for patients (cardio-vascular, stroke) who were being treated with allopurinol. Additionally, analysis of HES data helped to determine cost-effectiveness of the medication. Using the cost perspective of the NHS took account of medicines cost, costs of monitoring and impact on hospital admissions.
Cancer registration data was requested in order to evaluate any side-effects of allopurinol and to determine any co-morbidities within the cohort that may affect the results of the study. Mortality data was used to determine any deaths associated with the medication and also to help researchers keep records for the cohort up-to-date. Demographic data assisted in the same way, so researchers could:
i) track any patients lost to follow-up, and
ii) lower the risk of researchers trying to contact participants who had died therefore reducing the risk of causing
upset to their family/next of kin
The data requested under this Agreement was linked to trial data at the Robertson Centre for Biostatistics at University of Glasgow. The trial data consisted of information on whether the patient is receiving allopurinol or not, and questionnaires on (i) health service usage, (ii) general health outcomes (EQ-5D), and (iii) quality of life (Seattle Angina Questionnaire)). The University of Glasgow is responsible for carrying out a data management role and are therefore listed as data processor within this agreement. A processing agreement is in place between University of Dundee and University of Glasgow which defines the precise activities. University of Dundee will access the data via a remote network access to the Robertson Centre for Biostatistic's server in order to process the data. University of Glasgow only process the data under instruction from University of Dundee. University of Dundee and University of Glasgow are both data processors under this Agreement. No data will be shared outside of these two organisations.
The University of Dundee is leading the trial and is sole data controller under this Agreement. The Chief Investigator is employed by the University of Dundee and the protocol is authored by University of Dundee. The trial project manager is employed by the University of Dundee and the funding is provided to University of Dundee.
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 Dundee and the University of Glasgow. The University of Nottingham will only have access to aggregated data (with small numbers suppressed in line with the HES Analysis Guide).
The study website states that the study is run by the University of Dundee and describes what research is carried out and what outputs are produced is determined by the University of Dundee (notwithstanding that the University of Dundee may have received expert advice from the University of Nottingham – the decision rested with the University of Dundee).
Funding was provided from the National Institute of Health Research (NIHR) and has been secured until 31st March 2022. An extension for production of the draft study report to NIHR was confirmed until 30th June 2022.
The research team 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. The patients 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.
Expected output
Results will be reported in a peer-reviewed journal and at major scientific and clinical meetings. The timescale for this is expected to be in summer 2022. The research team aim to submit the main results paper to the Lancet and present the results at a major meeting, probably the European Society of Cardiology annual meeting in Barcelona August 2022. The research team will organise press releases to coincide with the publication to promote knowledge mobilisation of the study results. Further publications on aspects of the results may be prepared over the next few months. This will require ongoing analysis of the data to ensure that all aspects of the study data are fully explored to yield any potential benefits for patients with ischaemic heart disease.
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 Summer 2022.
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 Summer 2022.
Outputs may also be shared with funders, but ownership and control of the outputs rests with the University of Dundee.
There will be no data linkage undertaken with NHS Digital data provided under this Agreement that is not already noted in the Agreement. No further data dissemination is required under this Agreement.
All outputs will only contain results in highly aggregated format with small numbers suppressed and as statistical summaries and measures of association. Small numbers will be suppressed in line with the HES Analysis Guide. Record level information will not be released to any third party.
Benefits reported
There are no yielded benefits to date. The ALL-HEART study is near completion and data analysis will take place over the next few weeks; in order to yield the expected benefits, the study results need to be analysed and published. Database lock is expected in April 2022 and until then the results are not available.
DARS-NIC-369348-H6H8B-v4.3 1 April 2021 to 31 March 2022
- Title
- Renewal request for ‘Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease ALL-HEART’ study
- Commercial
- No
- Sublicensing
- No
- Datasets
- 7
- Files released
- 8
Datasets: Cancer Registration Data; Civil Registrations of Death; Demographics; Hospital Episode Statistics Admitted Patient Care (HES APC); MRIS - Cause of Death Report; MRIS - Cohort Event Notification Report; MRIS - Flagging Current Status Report
What changed from DARS-NIC-369348-H6H8B-v3.2
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Title | Renewal request for ‘Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease ALL-HEART’ study | |
| Start date | 2021-04-01 | |
| End date | 2022-03-31 | |
| Civil Registrations of Death: type of data | Identifiable | |
| Demographics: type of data | Identifiable |
Objective for processing
Under GDPR, the lawful basis on which processing of data from NHS Digital concerning participants in the ALL-HEART study is laid out by Articles 6(1)(e) and 9(2)(j) namely that processing is necessary for the performance of a task carried out in the exercise of official authority, such authority to make provision for research being vested in the University by virtue of the Royal Charter establishing the University dated 20 July 1967, and, that in respect of special category personal data, processing is necessary for research purposes carried out in accordance with Article 89(1) of the GDPR. University of Dundee are a public authority and the outcomes of this research is for the benefit of public interest.
[1 paragraph unchanged]
This study aims to improve the treatment of patients with Ischaemic Heart
[6 words unchanged]
investigating whether adding allopurinol up to 600mg daily to these patients' usual
medications,
medications
will reduce their risk of having a stroke, heart attack or of
[132 words unchanged]
there is an economic benefit of using allopurinol in patients with IHD.
Patients will complete quality of life questionnaires at the screening visit, after 1 year and at the end of the trial. The questionnaires will assess general health outcomes and coronary artery disease-specific quality of life. Analysis will measure five clinically important dimensions of health in patients with coronary artery disease (anginal stability, anginal frequency, physical limitation, treatment satisfaction, quality of life) and is sensitive to clinical change over time. The patient will be asked to report the number of visits they have made to a GP, practice nurse, physiotherapist and hospital outpatient clinics over the last year. The number of hospitalisations will be collected via the electronic record-linkage system along with other outcome data.
[1 paragraph unchanged]
lschaemic heart disease (angina or heart attack) is one of the
commonest
most common
causes of death in both men and women in the UK (around
[135 words unchanged]
could easily be implemented into routine care, would result in significant cost
savings
adjustments
for the NHS. If allopurinol improves cardiovascular outcomes and were to be
[74 words unchanged]
of the trial and is a less intrusive way of collecting data.
[1 paragraph unchanged]
The University of Dundee
is the sponsor
and NHS Tayside are co-sponsors
of the ALL-HEART
study and
study. The University of Dundee
is the sole Data Controller. The Chief Investigator is based at the
[20 words unchanged]
of Glasgow, was strictly advisory to the decision-making of the Chief Investigator
and sponsor
(University of Dundee).
NHS Tayside has no say in determining the manner in which the data is processed for the purposes of the study conduct as described in the application.
As is the requirement for clinical trials, several local principal investigators
(PI)
are based around the country with local responsibilities for aspects of the study
e.g.
e.g.,
patient recruitment, as delegated by the University of Dundee. A professor at
[5 words unchanged]
one of these local PIs. This person acts as local PI in
his
their
region on the instruction of the University of Dundee for study activities.
[90 words unchanged]
imply any role of the University of Nottingham as a data controller.
[4 paragraphs unchanged]
In its role as a data processor, the Robertson Centre for Biostatistics
[17 words unchanged]
and date of consent along with their unique study number to NHS
Digital’s Data Exchange Service (DES)
Digital
for matching and subsequent linkage. Data are returned using the unique study number only, minimising the use of identifying data.
NHS Digital supply the University of Glasgow with linked data on inpatient
[8 words unchanged]
cancer registrations. These data complement the information collected directly from participants. Under
this Agreement
the previous Agreement,
the University of Dundee
will receive
received
an update to the latest demographic, mortality and cancer registrations linked to HES records up to the latest available and then subsequent
bi-annual
quarterly
reports
thereafter. Under this Agreement, the University of Dundee will continue to receive quarterly reports for demographic, mortality and cancer registrations linked to HES records
for the duration of this Agreement. Data are required
bi-annually
quarterly
as the study enters its final phase to ensure that the study's
[94 words unchanged]
whether the addition of allopurinol to usual therapy improves quality of life.
[7 paragraphs unchanged]
The data requested under this Agreement will be linked to trial data
[110 words unchanged]
the data. University of Glasgow only process the data under instruction from
Univeristy
University
of Dundee. University of Dundee and University of Glasgow are both data processors under this Agreement. No data will be shared outside of these two organisations.
[3 paragraphs unchanged]
Funding is provided from the National Institute of Health research (NIHR) and has been secured until 31st March 2021.
This is currently in the process of being extended until 31/03/2022.
[3 paragraphs unchanged]
Under GDPR, the lawful basis on which processing of data from NHS Digital concerning participants in the ALL-HEART study is laid out by Articles 6(1)(e) and 9(2)(j) namely that processing is necessary for the performance of a task carried out in the exercise of official authority, such authority to make provision for research being vested in the University by virtue of the Royal Charter establishing the University dated 20 July 1967, and, that in respect of special category personal data, processing is necessary for research purposes carried out in accordance with Article 89(1). University of Dundee are a public authority and the outcomes of this research is for the benefit of public interest.
Processing activities
The data controller
will provide
provided
identifiers of 3,460 participants to NHS Digital.
These were previously provided to NHS Digital but not flagged and will therefore need to be re-supplied under this Agreement.
The following fields
are
were
provided:
[18 paragraphs unchanged]
Once the linkage has been
performed
performed,
the cohort will be held on NHS Digital's system and data will
[23 words unchanged]
Biostatics at the University of Glasgow (acting as Data Processor) will provide:
[6 paragraphs unchanged]
Once data from NHS Digital is held by the University of Glasgow,
[10 words unchanged]
participants during the trial. Processing of data will be performed within the
Roberston
Robertson
Centre of Biostatistcs at University of Glasgow, University of Dundee will also
[18 words unchanged]
Data held within RCB is used for large meta-analysis of trial data.
[2 paragraphs unchanged]
Only substantive employees of the University of Dundee and the University of Glasgow will have access to the data under this Agreement.
These individuals have been appropriately trained in data protection and confidentiality (they have completed the Medical Research Council (MRC) Research, GDPR and confidentiality e-learning modules and quiz).
Any data shared outside of these two organisations will contain only data
[52 words unchanged]
is held with Iron Mountain, who cannot access any of these data.
[2 paragraphs unchanged]
Data analysis will be carried out according to a pre-determined data analysis
[20 words unchanged]
myocardial infarction) will be analysed as cause-specific time to event outcomes using
Cox proportional hazards
appropriate statistical
models. Treatment effects will be estimated in the form of hazard ratios
[18 words unchanged]
the effects of treatment assessed by fitting interaction terms to the overall
Cox
statistical
models. Pre-specified subgroups will include splitting patients into three groups by urate
[45 words unchanged]
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.
statistical analysis.
Using the cost perspective of the NHS and social services, it will
[38 words unchanged]
a net cost per QALY gained for adding allopurinol to usual care.
[2 paragraphs unchanged]
Expected output
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 2020 and 2021 depending on event rate within the study which is not yet known until data on outcomes is obtained via record-linkage. NIHR have agreed a
in 2022. A
contract variation request to extend the duration of the study until
31st
March
2021 and a protocol
2022 has been submitted to NIHR. An IRAS
amendment
extending the study to 31st March 2022
has
recently
been
approved by ethics detailing this extension to follow up.
implemented.
[1 paragraph unchanged]
The research team will also present the findings at major cardiovascular and rheumatology scientific and clinical meetings. Target date
2020-2021
2022
as above.
The research team will also send copies of the results to guideline
[20 words unchanged]
they are considered and incorporated appropriately into revisions of guidelines. Target date
2020-2021
2022
as above.
The research team will produce a non-technical summary of the results which
[28 words unchanged]
the study results and communicate these to the wider public. Target date
2020-2021
2022
as above.
[1 paragraph unchanged]
There will be
not
no
data linkage undertaken with NHS Digital data provided under this Agreement that is not already noted in the Agreement.
[1 paragraph unchanged]
Expected measurable benefits
This research
will
is hoped to
establish whether the administration of allopurinol to patients with ischaemic heart disease (IHD) improves cardiovascular outcomes (stroke, myocardial infarction and cardiovascular death).
[1 paragraph unchanged]
It could have a huge impact on reducing NHS costs if allopurinol,
[14 words unchanged]
It could lead to reductions in morbidity and mortality and huge cost
savings
adjustments
for the NHS in terms of admissions with major events and acute coronary syndrome or coronary revascularisations. The health economic analysis
will
might
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.
[1 paragraph unchanged]
IHD causes a significant cost burden on the NHS and costs are
[46 words unchanged]
could easily be implemented into routine care, would result in significant cost
savings
adjustments
for the NHS. If allopurinol improves cardiovascular outcomes and were to be
[31 words unchanged]
for the NHS. The economic analysis will quantify the health economic benefits.
Benefits reported
There are no yielded benefits to date. The ALL-HEART study is ongoing; in order to yield the expected
benefits
benefits,
the study needs to run to completion.
Objective for processing
Under GDPR, the lawful basis on which processing of data from NHS Digital concerning participants in the ALL-HEART study is laid out by Articles 6(1)(e) and 9(2)(j) namely that processing is necessary for the performance of a task carried out in the exercise of official authority, such authority to make provision for research being vested in the University by virtue of the Royal Charter establishing the University dated 20 July 1967, and, that in respect of special category personal data, processing is necessary for research purposes carried out in accordance with Article 89(1) of the GDPR. University of Dundee are a public authority and the outcomes of this research is for the benefit of public interest.
The ALL-HEART (Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease) study is a multi-centre, controlled, Prospective Randomised Open-label Blinded Endpoint (PROBE) trial.
This study aims to improve the treatment of patients with Ischaemic Heart Disease (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 and are then 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. Patients will complete quality of life questionnaires at the screening visit, after 1 year and at the end of the trial. The questionnaires will assess general health outcomes and coronary artery disease-specific quality of life. Analysis will measure five clinically important dimensions of health in patients with coronary artery disease (anginal stability, anginal frequency, physical limitation, treatment satisfaction, quality of life) and is sensitive to clinical change over time. The patient will be asked to report the number of visits they have made to a GP, practice nurse, physiotherapist and hospital outpatient clinics over the last year. The number of hospitalisations will be collected via the electronic record-linkage system along with other outcome data.
Allopurinol is a xanthine oxidase inhibitor that lowers uric acid and is currently licensed for the prevention of gout and hyperuricaemia. Allopurinol has several positive effects on the cardiovascular system and is already widely used in patients by 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 (angina or heart attack) is one of the most common causes 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. Ischaemic heart disease currently costs the NHS billions of pounds each year. 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 which could easily be implemented into routine care, would result in significant cost adjustments 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. This economic analysis will quantify the health economic benefits. Follow-up will primarily be by electronic record-linkage using unique identifiers to collect data on hospitalisations and mortality centrally, without the need for study follow-up visits. This approach significantly reduces the cost of the trial and is a less intrusive way of collecting data.
The study population consists of patients aged 60 years and over with IHD (angina or myocardial infarction). 5,215 participants were recruited across the UK of which 3,460 patients were recruited from England and Wales for which this Agreement applies. Recruitment started in June 2014 and ended in September 2017.
The University of Dundee and NHS Tayside are co-sponsors of the ALL-HEART study. The University of Dundee is the sole Data Controller. The Chief Investigator is based at the University of Dundee and designed the study. Any input of others, including individuals based at University of Nottingham and University of Glasgow, was strictly advisory to the decision-making of the Chief Investigator (University of Dundee). NHS Tayside has no say in determining the manner in which the data is processed for the purposes of the study conduct as described in the application.
As is the requirement for clinical trials, several local principal investigators (PI) are based around the country with local responsibilities for aspects of the study e.g., patient recruitment, as delegated by the University of Dundee. A professor at the University of Nottingham is one of these local PIs. This person acts as local PI in their region on the instruction of the University of Dundee for study activities. The University of Nottingham does not form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement will be processed. The University of Nottingham is not a data controller. Patient Information Sheets and Consent Forms for clinical trials are required to be localised with the contact details of the local team and local PI and this is why some versions of the consent materials used in English sites feature the logo of the University of Nottingham. It does not imply any role of the University of Nottingham as a data controller.
The University of Nottingham are involved in a couple of ways. Firstly, the University of Nottingham has played a role in the recruitment of GP practices, and then patients, to the trial (the English part of the cohort). Secondly, three key people from Nottingham are providing expertise relating to the running of clinical trials (particularly where primary care is involved) and a focus on cardiovascular research within primary care.
The University of Glasgow is the Data Processor. The University of Glasgow acts on the instruction of the University of Dundee and with no discretion as to how the data is analysed. The University of Glasgow does not form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement will be processed. The University of Glasgow is strictly a data processor. The University of Glasgow is not a data controller.
No other universities form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement will be processed. No other universities or organisations other than the University of Dundee are data controllers.
No other universities are involved in the processing of NHS Digital supplied study data in any other way.
In its role as a data processor, the Robertson Centre for Biostatistics (RCB) at the University of Glasgow will upload patient’s surname, forename, gender, date of birth, NHS number and date of consent along with their unique study number to NHS Digital for matching and subsequent linkage. Data are returned using the unique study number only, minimising the use of identifying data.
NHS Digital supply the University of Glasgow with linked data on inpatient Hospital Episode Statistics (HES), mortality, demographic and national cancer registrations. These data complement the information collected directly from participants. Under the previous Agreement, the University of Dundee received an update to the latest demographic, mortality and cancer registrations linked to HES records up to the latest available and then subsequent quarterly reports thereafter. Under this Agreement, the University of Dundee will continue to receive quarterly reports for demographic, mortality and cancer registrations linked to HES records for the duration of this Agreement. Data are required quarterly as the study enters its final phase to ensure that the study's independent data monitoring committee receive data in a timely fashion to assess study safety and to enable the research team to assess the number of study endpoints that have accrued in order to manage planning for the end of this event-driven study. The objectives of the study remain the same as stated in previous iterations of this Agreement. The primary objective of the study is to determine whether the addition of allopurinol to usual therapy improves cardiovascular outcomes. Secondary objectives are to determine the cost-effectiveness of adding allopurinol to usual therapy and to determine whether the addition of allopurinol to usual therapy improves quality of life.
The University of Dundee requires data on Hospital Episode Statistics (HES), namely HES Admitted Patient Care, linked to demographic, mortality and cancer registrations. Data are returned from NHS Digital containing no directly identifying details with a unique study ID being used to distinguish individuals. National linkage is required in order to comprehensively map hospital activity and cancer occurrence during and after treatment with allopurinol. Likewise, national linkage to deaths is required in order to examine survival.
The study only requires data from the date participants gave consent. The Patient Information Sheets provided to participants when they gave consent explained: "Every year, we will receive information from centralised electronic databases in Scotland and England for all patients taking part in the ALL-HEART study on any hospital admissions that have occurred during the year" and the study's website states: "We receive data from centralised electronic databases regarding any hospital admissions, new cancers and deaths that occur in participants during the study." The study only requires information on new reportable events since the previous report. The date each participant consented will be supplied to NHS Digital so that the linked data can be filtered to exclude events which occurred before consent was given. However, in some instances it will not be technically feasible for NHS Digital to filter out all events before the date of consent or events that were previously reported. This will not apply for HES or Mortality data but may impact details of Cancer Registrations. In the event that the University of Glasgow receives events which occurred before the date of consent or receives duplicate events which have been previously reported, the University must destroy such data. The University of Glasgow is required to review all reports received from NHS Digital to ensure that only the minimum amount of data required to achieve successful analysis is retained and used in subsequent analyses.
Only the variables necessary to perform the analyses required to address the purpose are requested. Researchers need to identify hospitalisations for patients (cardio-vascular, stroke) who are being treated with allopurinol. Additionally, analysis of HES data will help to determine cost-effectiveness of the medication. Using the cost perspective of the NHS will take account of medicines cost, costs of monitoring and impact on hospital admissions.
Cancer registration data is requested in order to evaluate any side-effects of allopurinol and to determine any co-morbidities within the cohort that may affect the results of the study. Mortality data will be used to determine any deaths resulting from the medication and also to help researchers keep records for the cohort up-to-date. Demographic data will assist in the same way, so researchers can:
i) track any patients lost to follow-up, and
ii) lower the risk of researchers trying to contact participants who have died therefore reducing the risk of causing
upset to their family/next of kin
The data requested under this Agreement will be linked to trial data at the Robertson Centre for Biostatistics at University of Glasgow. The trial data consists of information on whether the patient is receiving allopurinol or not, and questionnaires on (i) health service usage, (ii) general health outcomes (EQ-5D), and (iii) quality of life (Seattle Angina Questionnaire)). The University of Glasgow is responsible for carrying out a data management role and are therefore listed as data processor within this agreement. A processing agreement is in place between University of Dundee and University of Glasgow which defines the precise activities. University of Dundee will access the data via a remote network access to the Robertson Centre for Biostatistic's server in order to process the data. University of Glasgow only process the data under instruction from University of Dundee. University of Dundee and University of Glasgow are both data processors under this Agreement. No data will be shared outside of these two organisations.
The University of Dundee is leading the trial and is sole data controller under this Agreement. The Chief Investigator is employed by the University of Dundee and the protocol is authored by University of Dundee. The trial project manager is employed by the University of Dundee and the funding is provided to University of Dundee.
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 Dundee and the University of Glasgow. The University of Nottingham will only have access to aggregated data (with small numbers suppressed in line with the HES Analysis Guide).
The study website states that the study is run by the University of Dundee and describes what research is carried out and what outputs are produced is determined by the University of Dundee (notwithstanding that the University of Dundee may receive expert advice from the University of Nottingham – the decision rests with the University of Dundee).
Funding is provided from the National Institute of Health research (NIHR) and has been secured until 31st March 2021. This is currently in the process of being extended until 31/03/2022.
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.
Expected output
Results will be reported in a peer-reviewed journal and at major scientific and clinical meetings. The timescale for this is expected to be in 2022. A contract variation request to extend the duration of the study until 31st March 2022 has been submitted to NIHR. An IRAS amendment extending the study to 31st March 2022 has been implemented.
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 2022 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 2022 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 2022 as above.
Outputs may also be shared with funders, but ownership and control of the outputs rests with the University of Dundee.
There will be no data linkage undertaken with NHS Digital data provided under this Agreement that is not already noted in the Agreement.
All outputs will only contain results in highly aggregated format and as statistical summaries and measures of association. Small numbers will be suppressed in line with the HES Analysis Guide. Record level information will not be released to any third party.
Benefits reported
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.
DARS-NIC-369348-H6H8B-v3.2 21 May 2020 to 31 March 2021
- Title
- Data linkage request for ‘Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease ALL-HEART’ study
- Commercial
- No
- Sublicensing
- No
- Datasets
- 7
- Files released
- 8
Datasets: Cancer Registration Data; Civil Registrations of Death; Demographics; Hospital Episode Statistics Admitted Patient Care (HES APC); MRIS - Cause of Death Report; MRIS - Cohort Event Notification Report; MRIS - Flagging Current Status Report
What changed from DARS-NIC-369348-H6H8B-v2.15
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2020-05-21 |
Datasets: + Cancer Registration Data; + Civil Registrations of Death; + Demographics
Unchanged: Objective for processing, Processing activities, Expected output, Expected measurable benefits, Benefits reported.
Objective for processing
The ALL-HEART (Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease) study is a multi-centre, controlled, prospective randomised open-label blinded endpoint (PROBE) trial.
This study aims to improve the treatment of patients with Ischaemic Heart Disease (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 and are then 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.
Allopurinol is a xanthine oxidase inhibitor that lowers uric acid and is currently licensed for the prevention of gout and hyperuricaemia. Allopurinol has several positive effects on the cardiovascular system and is already widely used in patients by 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 (angina or heart attack) is one of the commonest causes 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. Ischaemic heart disease currently costs the NHS billions of pounds each year. 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 which 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. This economic analysis will quantify the health economic benefits. Follow-up will primarily be by electronic record-linkage using unique identifiers to collect data on hospitalisations and mortality centrally, without the need for study follow-up visits. This approach significantly reduces the cost of the trial and is a less intrusive way of collecting data.
The study population consists of patients aged 60 years and over with IHD (angina or myocardial infarction). 5,215 participants were recruited across the UK of which 3,460 patients were recruited from England and Wales for which this Agreement applies. Recruitment started in June 2014 and ended in September 2017.
The University of Dundee is the sponsor of the ALL-HEART study and is the sole Data Controller. The Chief Investigator is based at the University of Dundee and designed the study. Any input of others, including individuals based at University of Nottingham and University of Glasgow, was strictly advisory to the decision-making of the Chief Investigator and sponsor (University of Dundee).
As is the requirement for clinical trials, several local principal investigators are based around the country with local responsibilities for aspects of the study e.g. patient recruitment, as delegated by the University of Dundee. A professor at the University of Nottingham is one of these local PIs. This person acts as local PI in his region on the instruction of the University of Dundee for study activities. The University of Nottingham does not form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement will be processed. The University of Nottingham is not a data controller. Patient Information Sheets and Consent Forms for clinical trials are required to be localised with the contact details of the local team and local PI and this is why some versions of the consent materials used in English sites feature the logo of the University of Nottingham. It does not imply any role of the University of Nottingham as a data controller.
The University of Nottingham are involved in a couple of ways. Firstly, the University of Nottingham has played a role in the recruitment of GP practices, and then patients, to the trial (the English part of the cohort). Secondly, three key people from Nottingham are providing expertise relating to the running of clinical trials (particularly where primary care is involved) and a focus on cardiovascular research within primary care.
The University of Glasgow is the Data Processor. The University of Glasgow acts on the instruction of the University of Dundee and with no discretion as to how the data is analysed. The University of Glasgow does not form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement will be processed. The University of Glasgow is strictly a data processor. The University of Glasgow is not a data controller.
No other universities form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement will be processed. No other universities or organisations other than the University of Dundee are data controllers.
No other universities are involved in the processing of NHS Digital supplied study data in any other way.
In its role as a data processor, the Robertson Centre for Biostatistics (RCB) at the University of Glasgow will upload patient’s surname, forename, gender, date of birth, NHS number and date of consent along with their unique study number to NHS Digital’s Data Exchange Service (DES) for matching and subsequent linkage. Data are returned using the unique study number only, minimising the use of identifying data.
NHS Digital supply the University of Glasgow with linked data on inpatient Hospital Episode Statistics (HES), mortality, demographic and national cancer registrations. These data complement the information collected directly from participants. Under this Agreement the University of Dundee will receive an update to the latest demographic, mortality and cancer registrations linked to HES records up to the latest available and then subsequent bi-annual reports for the duration of this Agreement. Data are required bi-annually as the study enters its final phase to ensure that the study's independent data monitoring committee receive data in a timely fashion to assess study safety and to enable the research team to assess the number of study endpoints that have accrued in order to manage planning for the end of this event-driven study. The objectives of the study remain the same as stated in previous iterations of this Agreement. The primary objective of the study is to determine whether the addition of allopurinol to usual therapy improves cardiovascular outcomes. Secondary objectives are to determine the cost-effectiveness of adding allopurinol to usual therapy and to determine whether the addition of allopurinol to usual therapy improves quality of life.
The University of Dundee requires data on Hospital Episode Statistics (HES), namely HES Admitted Patient Care, linked to demographic, mortality and cancer registrations. Data are returned from NHS Digital containing no directly identifying details with a unique study ID being used to distinguish individuals. National linkage is required in order to comprehensively map hospital activity and cancer occurrence during and after treatment with allopurinol. Likewise, national linkage to deaths is required in order to examine survival.
The study only requires data from the date participants gave consent. The Patient Information Sheets provided to participants when they gave consent explained: "Every year, we will receive information from centralised electronic databases in Scotland and England for all patients taking part in the ALL-HEART study on any hospital admissions that have occurred during the year" and the study's website states: "We receive data from centralised electronic databases regarding any hospital admissions, new cancers and deaths that occur in participants during the study." The study only requires information on new reportable events since the previous report. The date each participant consented will be supplied to NHS Digital so that the linked data can be filtered to exclude events which occurred before consent was given. However, in some instances it will not be technically feasible for NHS Digital to filter out all events before the date of consent or events that were previously reported. This will not apply for HES or Mortality data but may impact details of Cancer Registrations. In the event that the University of Glasgow receives events which occurred before the date of consent or receives duplicate events which have been previously reported, the University must destroy such data. The University of Glasgow is required to review all reports received from NHS Digital to ensure that only the minimum amount of data required to achieve successful analysis is retained and used in subsequent analyses.
Only the variables necessary to perform the analyses required to address the purpose are requested. Researchers need to identify hospitalisations for patients (cardio-vascular, stroke) who are being treated with allopurinol. Additionally, analysis of HES data will help to determine cost-effectiveness of the medication. Using the cost perspective of the NHS will take account of medicines cost, costs of monitoring and impact on hospital admissions.
Cancer registration data is requested in order to evaluate any side-effects of allopurinol and to determine any co-morbidities within the cohort that may affect the results of the study. Mortality data will be used to determine any deaths resulting from the medication and also to help researchers keep records for the cohort up-to-date. Demographic data will assist in the same way, so researchers can:
i) track any patients lost to follow-up, and
ii) lower the risk of researchers trying to contact participants who have died therefore reducing the risk of causing
upset to their family/next of kin
The data requested under this Agreement will be linked to trial data at the Robertson Centre for Biostatistics at University of Glasgow. The trial data consists of information on whether the patient is receiving allopurinol or not, and questionnaires on (i) health service usage, (ii) general health outcomes (EQ-5D), and (iii) quality of life (Seattle Angina Questionnaire)). The University of Glasgow is responsible for carrying out a data management role and are therefore listed as data processor within this agreement. A processing agreement is in place between University of Dundee and University of Glasgow which defines the precise activities. University of Dundee will access the data via a remote network access to the Robertson Centre for Biostatistic's server in order to process the data. University of Glasgow only process the data under instruction from Univeristy of Dundee. University of Dundee and University of Glasgow are both data processors under this Agreement. No data will be shared outside of these two organisations.
The University of Dundee is leading the trial and is sole data controller under this Agreement. The Chief Investigator is employed by the University of Dundee and the protocol is authored by University of Dundee. The trial project manager is employed by the University of Dundee and the funding is provided to University of Dundee.
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 Dundee and the University of Glasgow. The University of Nottingham will only have access to aggregated data (with small numbers suppressed in line with the HES Analysis Guide).
The study website states that the study is run by the University of Dundee and describes what research is carried out and what outputs are produced is determined by the University of Dundee (notwithstanding that the University of Dundee may receive expert advice from the University of Nottingham – the decision rests with the University of Dundee).
Funding is provided from the National Institute of Health research (NIHR) and has been secured until 31st March 2021.
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.
Under GDPR, the lawful basis on which processing of data from NHS Digital concerning participants in the ALL-HEART study is laid out by Articles 6(1)(e) and 9(2)(j) namely that processing is necessary for the performance of a task carried out in the exercise of official authority, such authority to make provision for research being vested in the University by virtue of the Royal Charter establishing the University dated 20 July 1967, and, that in respect of special category personal data, processing is necessary for research purposes carried out in accordance with Article 89(1). University of Dundee are a public authority and the outcomes of this research is for the benefit of public interest.
Expected output
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 2020 and 2021 depending on event rate within the study which is not yet known until data on outcomes is obtained via record-linkage. NIHR have agreed a contract variation request to extend the duration of the study until March 2021 and a protocol amendment has recently been approved by ethics detailing this extension to follow up.
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 2020-2021 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 2020-2021 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 2020-2021 as above.
Outputs may also be shared with funders, but ownership and control of the outputs rests with the University of Dundee.
There will be not data linkage undertaken with NHS Digital data provided under this Agreement that is not already noted in the Agreement.
All outputs will only contain results in highly aggregated format and as statistical summaries and measures of association. Small numbers will be suppressed in line with the HES Analysis Guide. Record level information will not be released to any third party.
Benefits reported
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.
DARS-NIC-369348-H6H8B-v2.15 1 June 2019 to 31 March 2021
- Title
- Data linkage request for ‘Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease ALL-HEART’ study
- Commercial
- No
- Sublicensing
- No
- Datasets
- 4
- Files released
- 5
Datasets: Hospital Episode Statistics Admitted Patient Care (HES APC); MRIS - Cause of Death Report; MRIS - Cohort Event Notification Report; MRIS - Flagging Current Status Report
Objective for processing
The ALL-HEART (Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease) study is a multi-centre, controlled, prospective randomised open-label blinded endpoint (PROBE) trial.
This study aims to improve the treatment of patients with Ischaemic Heart Disease (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 and are then 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.
Allopurinol is a xanthine oxidase inhibitor that lowers uric acid and is currently licensed for the prevention of gout and hyperuricaemia. Allopurinol has several positive effects on the cardiovascular system and is already widely used in patients by 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 (angina or heart attack) is one of the commonest causes 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. Ischaemic heart disease currently costs the NHS billions of pounds each year. 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 which 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. This economic analysis will quantify the health economic benefits. Follow-up will primarily be by electronic record-linkage using unique identifiers to collect data on hospitalisations and mortality centrally, without the need for study follow-up visits. This approach significantly reduces the cost of the trial and is a less intrusive way of collecting data.
The study population consists of patients aged 60 years and over with IHD (angina or myocardial infarction). 5,215 participants were recruited across the UK of which 3,460 patients were recruited from England and Wales for which this Agreement applies. Recruitment started in June 2014 and ended in September 2017.
The University of Dundee is the sponsor of the ALL-HEART study and is the sole Data Controller. The Chief Investigator is based at the University of Dundee and designed the study. Any input of others, including individuals based at University of Nottingham and University of Glasgow, was strictly advisory to the decision-making of the Chief Investigator and sponsor (University of Dundee).
As is the requirement for clinical trials, several local principal investigators are based around the country with local responsibilities for aspects of the study e.g. patient recruitment, as delegated by the University of Dundee. A professor at the University of Nottingham is one of these local PIs. This person acts as local PI in his region on the instruction of the University of Dundee for study activities. The University of Nottingham does not form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement will be processed. The University of Nottingham is not a data controller. Patient Information Sheets and Consent Forms for clinical trials are required to be localised with the contact details of the local team and local PI and this is why some versions of the consent materials used in English sites feature the logo of the University of Nottingham. It does not imply any role of the University of Nottingham as a data controller.
The University of Nottingham are involved in a couple of ways. Firstly, the University of Nottingham has played a role in the recruitment of GP practices, and then patients, to the trial (the English part of the cohort). Secondly, three key people from Nottingham are providing expertise relating to the running of clinical trials (particularly where primary care is involved) and a focus on cardiovascular research within primary care.
The University of Glasgow is the Data Processor. The University of Glasgow acts on the instruction of the University of Dundee and with no discretion as to how the data is analysed. The University of Glasgow does not form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement will be processed. The University of Glasgow is strictly a data processor. The University of Glasgow is not a data controller.
No other universities form part of the ‘Study Team’ responsible for determining the purposes for, or the manner in which, the data under this Agreement will be processed. No other universities or organisations other than the University of Dundee are data controllers.
No other universities are involved in the processing of NHS Digital supplied study data in any other way.
In its role as a data processor, the Robertson Centre for Biostatistics (RCB) at the University of Glasgow will upload patient’s surname, forename, gender, date of birth, NHS number and date of consent along with their unique study number to NHS Digital’s Data Exchange Service (DES) for matching and subsequent linkage. Data are returned using the unique study number only, minimising the use of identifying data.
NHS Digital supply the University of Glasgow with linked data on inpatient Hospital Episode Statistics (HES), mortality, demographic and national cancer registrations. These data complement the information collected directly from participants. Under this Agreement the University of Dundee will receive an update to the latest demographic, mortality and cancer registrations linked to HES records up to the latest available and then subsequent bi-annual reports for the duration of this Agreement. Data are required bi-annually as the study enters its final phase to ensure that the study's independent data monitoring committee receive data in a timely fashion to assess study safety and to enable the research team to assess the number of study endpoints that have accrued in order to manage planning for the end of this event-driven study. The objectives of the study remain the same as stated in previous iterations of this Agreement. The primary objective of the study is to determine whether the addition of allopurinol to usual therapy improves cardiovascular outcomes. Secondary objectives are to determine the cost-effectiveness of adding allopurinol to usual therapy and to determine whether the addition of allopurinol to usual therapy improves quality of life.
The University of Dundee requires data on Hospital Episode Statistics (HES), namely HES Admitted Patient Care, linked to demographic, mortality and cancer registrations. Data are returned from NHS Digital containing no directly identifying details with a unique study ID being used to distinguish individuals. National linkage is required in order to comprehensively map hospital activity and cancer occurrence during and after treatment with allopurinol. Likewise, national linkage to deaths is required in order to examine survival.
The study only requires data from the date participants gave consent. The Patient Information Sheets provided to participants when they gave consent explained: "Every year, we will receive information from centralised electronic databases in Scotland and England for all patients taking part in the ALL-HEART study on any hospital admissions that have occurred during the year" and the study's website states: "We receive data from centralised electronic databases regarding any hospital admissions, new cancers and deaths that occur in participants during the study." The study only requires information on new reportable events since the previous report. The date each participant consented will be supplied to NHS Digital so that the linked data can be filtered to exclude events which occurred before consent was given. However, in some instances it will not be technically feasible for NHS Digital to filter out all events before the date of consent or events that were previously reported. This will not apply for HES or Mortality data but may impact details of Cancer Registrations. In the event that the University of Glasgow receives events which occurred before the date of consent or receives duplicate events which have been previously reported, the University must destroy such data. The University of Glasgow is required to review all reports received from NHS Digital to ensure that only the minimum amount of data required to achieve successful analysis is retained and used in subsequent analyses.
Only the variables necessary to perform the analyses required to address the purpose are requested. Researchers need to identify hospitalisations for patients (cardio-vascular, stroke) who are being treated with allopurinol. Additionally, analysis of HES data will help to determine cost-effectiveness of the medication. Using the cost perspective of the NHS will take account of medicines cost, costs of monitoring and impact on hospital admissions.
Cancer registration data is requested in order to evaluate any side-effects of allopurinol and to determine any co-morbidities within the cohort that may affect the results of the study. Mortality data will be used to determine any deaths resulting from the medication and also to help researchers keep records for the cohort up-to-date. Demographic data will assist in the same way, so researchers can:
i) track any patients lost to follow-up, and
ii) lower the risk of researchers trying to contact participants who have died therefore reducing the risk of causing
upset to their family/next of kin
The data requested under this Agreement will be linked to trial data at the Robertson Centre for Biostatistics at University of Glasgow. The trial data consists of information on whether the patient is receiving allopurinol or not, and questionnaires on (i) health service usage, (ii) general health outcomes (EQ-5D), and (iii) quality of life (Seattle Angina Questionnaire)). The University of Glasgow is responsible for carrying out a data management role and are therefore listed as data processor within this agreement. A processing agreement is in place between University of Dundee and University of Glasgow which defines the precise activities. University of Dundee will access the data via a remote network access to the Robertson Centre for Biostatistic's server in order to process the data. University of Glasgow only process the data under instruction from Univeristy of Dundee. University of Dundee and University of Glasgow are both data processors under this Agreement. No data will be shared outside of these two organisations.
The University of Dundee is leading the trial and is sole data controller under this Agreement. The Chief Investigator is employed by the University of Dundee and the protocol is authored by University of Dundee. The trial project manager is employed by the University of Dundee and the funding is provided to University of Dundee.
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 Dundee and the University of Glasgow. The University of Nottingham will only have access to aggregated data (with small numbers suppressed in line with the HES Analysis Guide).
The study website states that the study is run by the University of Dundee and describes what research is carried out and what outputs are produced is determined by the University of Dundee (notwithstanding that the University of Dundee may receive expert advice from the University of Nottingham – the decision rests with the University of Dundee).
Funding is provided from the National Institute of Health research (NIHR) and has been secured until 31st March 2021.
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.
Under GDPR, the lawful basis on which processing of data from NHS Digital concerning participants in the ALL-HEART study is laid out by Articles 6(1)(e) and 9(2)(j) namely that processing is necessary for the performance of a task carried out in the exercise of official authority, such authority to make provision for research being vested in the University by virtue of the Royal Charter establishing the University dated 20 July 1967, and, that in respect of special category personal data, processing is necessary for research purposes carried out in accordance with Article 89(1). University of Dundee are a public authority and the outcomes of this research is for the benefit of public interest.
Expected output
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 2020 and 2021 depending on event rate within the study which is not yet known until data on outcomes is obtained via record-linkage. NIHR have agreed a contract variation request to extend the duration of the study until March 2021 and a protocol amendment has recently been approved by ethics detailing this extension to follow up.
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 2020-2021 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 2020-2021 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 2020-2021 as above.
Outputs may also be shared with funders, but ownership and control of the outputs rests with the University of Dundee.
There will be not data linkage undertaken with NHS Digital data provided under this Agreement that is not already noted in the Agreement.
All outputs will only contain results in highly aggregated format and as statistical summaries and measures of association. Small numbers will be suppressed in line with the HES Analysis Guide. Record level information will not be released to any third party.
Benefits reported
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.
Register history
When this agreement appeared in, or was edited in, each monthly edition of the register. Built by comparing every edition this site holds, the earliest of which is July 2021.
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July 2021 —
already listed in the earliest edition this site holds, so it may be older. 3 versions: DARS-NIC-369348-H6H8B-v2.15, DARS-NIC-369348-H6H8B-v3.2, DARS-NIC-369348-H6H8B-v4.3
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June 2022
1 version added: DARS-NIC-369348-H6H8B-v5.2
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June 2024
1 version added: DARS-NIC-369348-H6H8B-v6.3
Cite this page
NHS England (2026) Data Uses Register, September 2026 edition, agreement DARS-NIC-369348-H6H8B, “Renewal request for ‘Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease ALL-HEART’ study”. Read via NHS Data Access Explorer (unofficial), https://healthdatauses.uk/agreements/dars-nic-369348-h6h8b/ (accessed [date]).
This address stays the same, but the page is rebuilt with each monthly edition, so the citation names the edition it shows. Every edition's data is kept in the facts store.
Source: datausesregister_september2026.xlsx, September 2026 edition of the NHS England Data Uses Register. Search that workbook for DARS-NIC-369348-H6H8B to see the original rows.