CHIEF-PD (Cholinesterase Inhibitor to prEvent Falls in Parkinson’s Disease): A phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson’s disease.

University of Bristol Medical School (UOB-BMS) requires access to NHS England data for the CHIEF-PD (CHolinesterase Inhibitor to prEvent Falls in Parkinson’s Disease) trial. CHIEF-PD is a large NIHR-funded phase 3 trial which will establish whether cholinesterase inhibitor (ChEi) treatment, compared to placebo, prevents people with Parkinson’s Disease (PD) from falling and is cost-effective. This will be achieved through a multi-centre randomised controlled clinical trial.

The primary objective is to determine the difference in fall rate over 12 months between people with PD treated for 12 months with a ChEi and those treated with a placebo. Data from NHS England will be used to extract data on the hospital-based care received by CHIEF-PD study participants and used to identify hospitalisations due to falls and estimate whether ChEi treatment has any impact on the costs of NHS hospital care. When combined with other data collected in the CHIEF-PD trial, the aim is to calculate whether ChEi treatment is effective for patients and cost-effective for the NHS.

The following NHS England Data will be accessed: Hospital Episode Statistics (HES) Admitted Patient Care (APC), Outpatients (OP) and Emergency Care Data Set (ECDS) necessary to calculate the cumulative cost of hospital care.

The level of the Data will be identifiable.

The Data will be minimised as follows:

• Limited to a study cohort of approximately 600 patients who consented to the CHIEF-PD trial from various secondary care settings across >20 sites in the United Kingdom recruited between January 2020-April 2023.

• Limited to Data from recruitment to up to 12 months post recruitment date for each participant.

• Data that will identify cause of hospitalisations (to enable the trial team to identify those due to falls) and to describe and cost hospital care for trial participants.

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. Research is a task that University of Bristol performs in the public interest, as part of their core function as a university.

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.

The work is in the public interest because it aims to improve public health by providing evidence to help NHS decision-makers identify effective and cost-effective healthcare for patients with Parkinson’s Disease.

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.

Funding is provided by the National Institute for Health and Care Research (NIHR). The funding is specifically for the CHIEF-PD trial. The funder will have no ability to suppress or otherwise limit the publication of findings.

Only approved University of Bristol substantive employees who are part of the CHIEF-PD research team will have access to the data from approved University of Bristol computers.

In relation to Public and Patient Involvement and Engagement group, those with Parkinson’s Disease have helped to refine the purpose of the research and will be involved in every phase of the research trial. This will involve group meetings, specific roles on the trial management group, review of the protocol, participant information, consent and data collection forms and informing dissemination of the research findings to participants. The group strongly supported the collection of the data for the purposes described above.

Commercial benefit:

Luye Pharma AG is a manufacturer of a cholinesterase inhibitor and supply this for the study.

There is a potential commercial benefit where NHS Trusts or clinicians are influenced by the findings of this study and might choose to use the Luye Pharma AG manufactured cholinesterase inhibitor at the end of the intervention phase where participants require continuation of treatment with a cholinesterase inhibitor or if the results of the study demonstrate that cholinesterase inhibitor is effective and is adopted into clinical practice.

Luye Pharma AG have not had any role in the study design, data collection or funding. They will not have any role in analysis or presentation of the research findings.

The University of Bristol will transfer data to NHS England. The data will consist of identifying details (specifically Participant ID, NHS Number and Date of Birth) for the cohort to be linked with NHS England Data. The University of Bristol will also provide the participant 'Recruitment Date' to the study date to NHS England.

NHS England will provide the relevant records from the HES APC, HES OP and ECDS datasets to The University of Bristol.

The Data will contain no direct identifying 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 stored on servers at the University of Bristol.

In the event that Data will be accessed via remote access, the Controller(s) 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.

- 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 agreement) 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).

The Data will not leave England.

Access will be restricted to employees of the University of Bristol who have authorisation from the CHIEF-PD Chief Investigator. All such individuals are substantive employees of the University of Bristol.

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

The team will aggregate the HES Data with small numbers suppressed, to patient-level summaries (for example, to calculate the total number and cost of hospital admissions for each patient). The primary analysis of NHS England Data will be a comparison of healthcare use and costs between patients randomised to receive ChEi treatment or placebo.

At no point will the research team at The University of Bristol link the NHS England Data back to direct patient identifiers (NHS number) in an attempt to re-identify individuals, or attempt to link to any other datasets collected outside of the auspices of the trial. Analysts/researchers from the University of Bristol will process/analyse the Data for the purposes described above. The Data will not be linked with any other data.

The expected plan for dissemination of the research findings will include:

• Presentations to participants. Many participants are frail and therefore the findings will be disseminated to them via post using large print summaries which will be designed with our PPI panel. The trial has partnered throughout with Parkinson’s UK – the main research charity supporting people with the condition who have supported PPI recruitment and dissemination activities.

• a comprehensive report of the trial findings will be submitted in approximately Autumn 2024 for publication in the NIHR journals library. It is expected that all project publications to be published within 12 months thereafter.

• submission to peer-reviewed scientific journals (e.g. British Medical Journal).

• Presentations at "The Movement Disorder Society" and "Parkinsonism International Congress" conferences.

• Summaries of results disseminated to the public and trial participants.

All papers will be published on the University of Bristol’s website.

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

- Postal updates to participants at the end of the trial. The demographics of the patients that participate are such that they tend to prefer paper updates as opposed to online material.

- Research newsletters hosted by Parkinson’s UK, such as ‘Progress’, will be utilised to reach people living with Parkinson's Disease.

A series of PPI workshops aimed at people with Parkinson’s from underrepresented groups including from BAME (Black, Asian and minority ethnic) and / or socioeconomically deprived backgrounds are planned to further inform the means by which are findings are disseminated.

The target date for production and dissemination of the outputs will be Autumn 2024.

The findings of the study will be provided to the NICE Committee that develops clinical guidelines for management of Parkinson’s disease to help inform decision-making within the NHS. Evidence will be provided on whether ChEi treatment is effective for patients with Parkinson’s disease and cost-effective for the NHS. If ChEi treatment is cost-effective, it could be made available to all patients with Parkinson’s disease in the UK. Its provision by the NHS has the potential to deliver substantial health gains for the large number of patients suffering from falling as a result of Parkinson’s disease.

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 populations

- lead to the identification or improvement of treatments or interventions, or health and care system design to improve health and care outcomes or experience.

- inform planning health services and programmes, for example to improve equity of access, experience, and outcomes.

- inform decisions on how to effectively allocate and evaluate funding according to health needs.

- provide a mechanism for checking the quality of care. This could include identifying areas of good practice to learn from, or areas of poorer practice which need to be addressed.

- support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

In looking at the specific benefits to patients, it is estimated that there are approximately 127,000 people living with Parkinson's Disease (PD) in the United Kingdom. People with PD who are admitted to hospital with a fall cost the NHS £29 million per year, with the estimated 3542 admissions/year for hip fracture, head injury and fractures costing £18 million. The devastating consequences of falls span the physical, mental and social domains of health. There is an urgent and unmet need to identify strategies to tackle falls in PD. The CHIEF-PD trial could therefore positively impact health and wellbeing.

These data are based on the following references.

The incidence and prevalence of Parkinson’s in the UK. Parkinson’s UK. (2017).

A link to the research ca be found here: https://www.parkinsons.org.uk/sites/default/files/2018-01/Prevalence%20%20Incidence%20Report%20Latest_Public_2.pdf

Low V, Ben-Shlomo Y, Coward E, Fletcher S, Walker R, Clarke CE. Measuring the burden and mortality of hospitalisation in Parkinson’s disease: A cross-sectional analysis of the English Hospital Episodes Statistics database 2009-2013. Parkinsonism Relat Disord. 2015 May;21(5):449–54.

Disproportionate growth in the older population will mean that the overall burden of PD will increase. The results of this research will therefore remain highly relevant and important to the NHS in the future.

It is hoped 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 patient.

Yielded Benefits is not a requirement for new applications.