Optimising Prescription of Treatment In older patients with Mild hypertension at Increased risk of Serious adverse Events - OPTIMISE2: Consultee Advice Cohort

The University of Oxford requires access to NHS England data for the purpose of the following research project:

Optimising Prescription of Treatment In older patients with Mild hypertension at Increased risk of Serious adverse Events - OPTIMISE2

The following is a summary of the aims of the research project provided by the University of Oxford:

High blood pressure is the leading modifiable risk factor for cardiovascular disease and the most common co-morbid condition in older people with multi-morbidity. Antihypertensive treatment has been shown to be effective at preventing stroke and cardiovascular disease in older high-risk patients and 52% of those aged 80 years and above are prescribed two or more antihypertensive medications. However, antihypertensive medications are also associated with adverse events, such as syncope, falls and acute kidney injury, particularly in older people and those with frailty.

Clinical guidelines therefore recommend using clinical judgement when prescribing in older patients with frailty, emphasising a personalised approach to care which might include attempts to improve quality of life through deprescribing. They state that drugs which are used to prevent future events (e.g. antihypertensives) should be considered for withdrawal, taking into account an individual’s personal goals and the likelihood of benefit and harm from continued treatment. However, these guidelines are largely based on expert opinion and currently there are no trials examining the long-term effects of antihypertensive deprescribing. The previous OPTIMISE trial showed that antihypertensive deprescribing could be achieved without affecting NICE recommended systolic blood pressure control at 12-weeks follow-up but the long-term effects of deprescribing remain unknown.

Therefore, the OPTIMISE2 trial aims to examine the effect of antihypertensive deprescribing on serious adverse events, health-related quality of life, and value for money for the NHS. It is hoped that the findings of this work will establish the longer-term impact of antihypertensive deprescribing and inform clinical guidelines on the treatment of high blood pressure in older adults.

The following NHS England Data will be accessed:

• Hospital Episode Statistics Admitted Patient Care (APC), and Emergency Care Data Set (ECDS)– necessary for the the primary endpoint of the trial. OPTIMISE2 aims to determine the difference in All Cause Emergency Hospital admissions between randomised groups.

• Civil Registration Mortality – necessary for the primary endpoint of the trial. OPTIMSIE2 aims to determine the difference in all cause death between randomised groups.

The level of the Data will be:

• Identifiable

Date of death is a sensitive field required in order to determine the primary endpoint. DOD is not a direct identifier, however in combination with other data items DOD could make an individual identifiable.

The Data will be minimised as follows

• Limited to a study cohort identified by the University of Oxford – the cohort consists of a maximum of 50 participants, aged 75 years or older who are taking blood pressure lowering drugs, but do not have raised blood pressure readings, who lack capacity to give informed patient consent and have been recruited under Consultee Advice (Mental Capacity Act 2005) from 16th November 2023 and onwards (recruitment expected to end 30th December 2025).

• Limited to data between 2023/24 to 2026/27. For each individual patient, data will only be provided from the date of their randomisation.

The University of Oxford is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is Article 6(1)(e) - processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller. As a higher education establishment, the University of Oxford, as the Data Controller who is also processing the data, conduct research to improve health care and service and the data requested is necessary for the performance of a task carried out in the public interest.

The lawful basis for processing special category data under the UK GDPR is Article 9(2)(j) - processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. Data minimisation process is being followed and only data that is required specifically for the purposes of this study has been requested, to protect the rights of the data subjects.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care. The OPTIMISE2 Trial aims to determine whether deprescribing common drugs that lower blood pressure is safe in older people, whether this affects health-related quality of life, and offers value for money for the NHS.

The funding is provided by the National Institute for Health Research (NIHR). The funding is specifically for the trial described. Funding is in place until April 2027 .

The funder will have no ability to suppress or otherwise limit the publication of findings.

Data will be accessed by:

An individual with an honorary contract with the University of Oxford – This individual is the Chief Investigator (CI) for the OPTIMISE2 trial, whom was previously a substantive employee at the University of Oxford. This individual has now transferred employment to Brighton and Sussex Medical School, but retains an honorary contract at the University of Oxford and remains as the CI for the OPTIMISE2 trial.

A Trial Steering Committee (TSC) is convened at 6-Month intervals to provide supervision of the trial and to ensure it is conducted in accordance with the principles of good clinical practice.

The TSC have agreed the trial protocol and provide advice to the investigators on all aspects of the trial. The TSC includes at least 75% of members, who are independent of the investigators, including an independent chairperson.

An independent Data Monitoring and Ethics Committee (DMEC), meets at 6 monthly intervals, for the duration of the trial. The DMEC report and advise the TSC.

A Public and Patient Involvement and Engagement group helped refine the purpose of the research. The group supported the collection of the data for the purposes described above. The the TSC includes two PPI representatives who contributed to the trial design and support the proposed data use. OPTIMISE2 also have a PPI committee who contributed during trial set-up, including reviewing the Patient Information Sheet, and are consulted when changes are made to the trial.

The University of Oxford will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number, Date of Birth and a unique person ID) for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the HES/ECDS and Civil Registration Mortality datasets to the University of Oxford. The Data will:

• contain no direct identifying data items but will contain a unique person ID which can be used to link the Data with other record level data already held by the recipient.

The Data will not be transferred to any other location. The data will be imported into the trial database for analysis alongside the core trial data.

The Data will be stored on servers at the University of Oxford.

The Data will be accessed by authorised personnel via remote access.

The Controller must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract.

For remote access:

- Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA;

- Access controls granting users the minimum level of access required are in place;

- Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data;

- Multifactor authentication (MFA) is required for remote access;

- Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access;

- All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy.

The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose).

Remote processing will be from secure locations within England/Wales. The data will not leave: England/Wales at any time.

Data will be accessed by an individual with an honorary contract with the University of Oxford (the Chief Investigator of the OPTIMISE2 trial). The individual will act as an agent of the University of Oxford at all times under supervision from employees of the University of Oxford. Aside from this individual, access is restricted to employees or agents of the University of Oxford who have authorisation from the Co-Principal Investigator.

All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

The Data will be linked at person record level with the pseudonymised trial data obtained from the University of Oxford, by using the unique pseudonymised trial ID.

The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

Analysts from the Nuffield Department of Primary Care Health Sciences at the University of Oxford. will analyse the Data for the purposes described above.

The expected outputs of the processing will be:

• A final report of findings to MHRA and the Ethics Committee that provided approval for the trial, within 12 months of the end of the trial (which is expected to end in December 2025.

• Submissions to peer reviewed journals within one year of the end of the trial

• Presentations at national scientific meetings (e.g. of the British and Irish Hypertension Society, Society for Academic Primary Care, British Geriatrics Society) and international conferences (e.g., for the European Society of Cardiology, North American Primary Care Research Group).

• Publication of findings on the trial website (www.optimise2-trial.org).

The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Social media

• Newsletters

• Press/media engagement

• Participant newsletters

• Reports aimed at participants

The University of Oxford will aim to present the findings of their analysis using these data at conferences in 2027 and publish the final results in publications and online in within 12 months of the end of the trial.

The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study.

The use of the data could help the system to better understand the health and care needs of frail older adults who are prescribed multiple medications and lead to the identification or improvement of health and care system design to improve health and care outcomes or experience.

This trial aims to establish the longer-term impact of antihypertensive deprescription in older patients at risk of serious adverse events. This will be the largest trial to examine the impact on whether deprescribing common drugs that lower blood pressure is safe in older people, on hospital admissions and death, health-related quality of life, and value for money for the NHS. Such information could be incorporated into clinical guidelines soon after the publication of the trial results and is likely to affect a large number of older people. In England, approximately 1.5 million adults aged 75+ years are prescribed ≥5 medications and antihypertensives are the most frequently prescribed medication in patients with polypharmacy. If deprescribing is shown to be safe and cost-effective, it could lead to a reduction in inappropriate polypharmacy amongst older patients and improve their quality of life. Around 250,000 non-elective NHS hospital admissions (costing £530 million) are thought to be related to potentially avoidable Adverse Drug Reactions every year and if deprescribing is found to be beneficial the number of hospital admissions due to potentially avoidable adverse drug reactions could be reduced. The impact of this trial can be measured in the number of non-elective emergency NHS hospital admissions each year.

Furthermore, because there are limited data at present on optimal strategies for deprescribing in older patients, the results of this trial will likely inform future trials of medication reduction in other clinical conditions.

It is hoped that the findings of this trial will support better patient-centred management plans for the prevention of cardiovascular disease in older individuals and will be made available for the next iterations of the NICE hypertension and multi-morbidity guidelines.

It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients.

The results of the trial will be published in peer-reviewed journals and presented at national scientific meetings (e.g. of the British and Irish Hypertension Society, Society for Academic Primary Care, British Geriatrics Society) and inter-national conferences (e.g., for the European Society of Cardiology, North Ameri-can Primary Care Research Group). It is hoped that the findings of this trial will be made available for the next iterations of the NICE hypertension and multi-morbidity guidelines.

Yielded Benefits is not a requirement for new applications.