A randomised controlled trial of Specialist Physiotherapy for Functional Motor Disorder (Physio4FMD)

AIM AND PURPOSE OF THE APPLICATION

The Data Controller for this study is St George’s University Hospital Medical School. Whilst the Data Controller is legally named St George’s University Hospital Medical School, they are also known as St George's, University Hospital of London (SGUL).

SGUL requires Hospital Episode Statistic data for the purpose of a research study called ‘A randomised controlled trial of Specialist Physiotherapy for Functional Motor Disorder (Physio4FMD).’ The study is funded by the National Institute for Health Research (NIHR), Health Technology Assessment grant. The trial commenced in May 2018. Priment Clinical Trials Unit (CTU) - part of University College London (UCL) are a data processor within the Agreement and will process in accordance to SGUL’s instructions.

JUSTIFICATION

The lawful justification for processing this data is under Articles 6(1)(e) and 9(2)(j), as this data is necessary for research that is in the public interest.

This study is in the interest of the public because this research may benefit the public by determining if specialist physiotherapy is effective at reducing mobility related disability and health care costs associated with functional motor disorder. If effectiveness is demonstrated, the intervention can be rolled out across the NHS to help improve the health and quality of life in a large group of patients. If the intervention proves to be cost effective, there is potential for reducing NHS costs associated with this diagnosis. SGUL have obtained participants consent to process their HES personal data, which the study need for statistical purposes. SGUL are only requesting the minimum amount of data in accordance with Article 89(1).

The processing of personal data was clearly explained to participants who provided written informed consent for the research team to have access to health-related records through NHS England. Therefore, SGUL feel that participants have given their permission to access their data for the purpose described in this agreement.

BACKGROUND TO RESEARCH

Functional motor disorder (FMD), also known as conversion disorder, is a common and disabling condition at the intersection between neurology and neuropsychiatry. Patients experience symptoms affecting movement, such as weakness, tremor and dystonia. The symptoms of FMD cause distress and disability equivalent to or greater than those caused by neurological disease. The incidence is reported to be in the range of 4 to 12 per 100,000, making it similar in incidence to multiple sclerosis and Parkinson’s disease. The long-term outcome is generally considered to be poor. The economic burden of FMD is high due to extensive health and social care utilisation, high rates of unemployment and receipt of disability benefits.

Physiotherapy is generally considered a useful intervention for people with FMD, but evidence from large controlled trials is lacking. Additionally, there are few studies specifically assessing the costs associated with FMD.

The current research trial is based on a feasibility study of a specialist physiotherapy intervention, conducted by the trial team. This study found that the intervention, when compared to treatment as usual, was associated with improved measures of disability at 6 months. A preliminary health economic analysis suggested a high probability that the intervention was cost effective. SGUL is now leading the current study associated with this request with NHS England, which is a larger (powered), multicentre randomised controlled trial of the specialist physiotherapy intervention. The trial is being conducted in 10 hospitals across England. The primary objective is to evaluate the clinical and cost effectiveness of the specialist physiotherapy for FMD.

SGUL have recruited 272 participants with FMD from 9 hospitals in England. Prior to consenting to take part, all participants received a Patient Information Sheet (PIS) with information about the trial. There were four versions of the PIS. The amendments between version 1.0 and 2.0 related to new mandatory requirements associated with the General Data Protection Regulation. No participants were consented under version 1.0 of the PIS. There were 32 participants consented under version 2.0. With version 3.0, the trial website was added to the PIS. There were 174 participants consented under version 3.0. Version 4.0 of the PIS included information about precautions for COVID-19. There were 66 participants consented under version 4.0.

There was only one version of the consent form, which explicitly asked for consent to use data held by NHS Digital (point 6 on the consent form). NHS Digital is the predecessor of NHS England following a merge on 01/02/2023. Concerted efforts were made to ensure all participants understood the process of how the linkage to NHS England data works. All participants were consented by trained and experienced researchers and clinicians. Participants were informed of all sections of the consent form and had all their questions answered before the initialled each box when in agreement. They were also informed that, on top of the information on the PIS, further information about the trial could be found on the trial’s website: www.physio4fmd.org

Once consented, participants were randomised on a 1:1 ratio to either the trial intervention (specialist physiotherapy), or to the control group (treatment as usual [TAU]). Participants will be providing data at three time points in the study: baseline, 6 months, and 12 months (primary outcome). The trial intervention (specialist physiotherapy) is a novel, protocolised physiotherapy treatment that has been designed based on a contemporary biopsychosocial understanding of FMD. There are 9 sessions, which are delivered over a 3-week period. TAU is a referral to a community physiotherapy service suitable for people with neurological symptoms. The primary outcome measure is the Physical Function domain of the Short Form 36 questionnaire, which is collected blindly. Through the trial outcome measures, the participants have provided a significant amount of data about their condition. This includes how symptoms affect their quality of life, physical health and mental health. Participants are also reporting on the economic and social impact of their symptoms and how they affect the people who care for them and the wider society. Data from NHS England are an additional important trial outcome.

TRIAL STATUS AND PROJECTED TIMELINES

Participant Recruitment began on 15 November 2018. Trial activity was temporarily suspended in March 2020 due to the COVID-19 pandemic. Trial recruitment recommenced in July 2021 and concluded on 31 January 2022. Participants are followed up for 12 months, the last recruited participant followed up in January 2023.

There are currently no other works or planned follow ups associated with his project and its collaborators . The collaborators (namely SGUL, UCL, University of Edinburgh, University of Sheffield, King’s College London and the University of Plymouth) are specified in the ‘organisations involved’ sub section part of this purpose.

AIMS OF RESEARCH AND HOW HES DATA WILL HELP TO ACHIEVE THE RESEARCH AIMS

The overall aim of the study is to evaluate the clinical and cost-effectiveness of the specialist physiotherapy intervention compared to TAU for participants with FMD, over 12 months. Cost-effectiveness will be assessed through a comprehensive health economic evaluation to determine the cost impact of the specialist physiotherapy intervention compared to TAU. HES data will be important for this analysis. It provides an objective measure of health service use that does not rely on patient report. People with FMD tend to have high and often inappropriate health service utilisation. HES data will help to determine if the trial intervention is associated with a reduction in health care use.

The HES data will provide the number of hospital contacts (outpatient, critical care, admitted patient care and A&E/Emergency Care Data Set (ECDS)) made by each trial participant for a six year period, with the study team focusing on the 12 months pre- and post-randomisation, totalling a 24-month period for each participant. The dates analysed for each participant will vary depending on the date they were randomised.

The HES data will also be used to validate the subjectively reported health economic data which is collected using the Client Service Receipt Inventory (CSRI) questionnaire. This will be achieved by applying more specific costs to service used based on reason for attendance; checking the reliability of patient reporting; and investigating the implications of missing data or loss to follow up on the cost effectiveness analysis. The trial data includes both objective (HES/ECDS data) and subjective (CSRI) measures of health service use. This is on request from the funder (NIHR-HTA) who advised that SGUL should include objective, non-participant reported measures as well as subjective participant reported measures. Having two corroborating sources will make the findings more robust. If there are differences between HES data and subjective report, the findings will be presented objectively and SGUL will attempt to account for differences.

The fields requested are minimised to ensure that SGUL are adequately able to determine the service received by the individual, as well as what investigations and interventions were performed in order to calculate the cost of the hospital episode. Fields that do not contribute to these investigations and interventions are not requested.

DATA ANALYSIS AND REPORTING

The data will be pseudonymised and reported at the level of randomised group. The data will not be compared at individual participant level. SGUL will report descriptive statistics for each service type (outpatient, inpatient, A&E) separately. Suitable descriptive statistics and statistical tests will be selected for each service type depending on the distribution of the data (i.e. non-parametric tests for highly skewed data). A statistician will analyse the data to determine whether there is a statistically significant difference between the intervention and treatment as usual (TAU) groups. The specific statistical test that will be used is called general linear model (GLM).

ORGANISATIONS INVOLVED

SGUL, as sponsor for the trial, are the data controller for the purpose of this Data Sharing Agreement. SGUL contract with UCL as a data processor to carry out a number of trial responsibilities on their behalf. The study is managed by staff at SGUL.

UCL (Priment CTU) will act as the data processor for the purpose of this Data Sharing Agreement.

Individuals from University of Edinburgh, University of Sheffield, King’s College London and the University of Plymouth are named as co-investigators in the study protocol. These individuals are part of the trial management group that provided preliminary input during the design phase of the trial. Though these individuals have played an advisory role, they are not (and have not been) involved in decision making in the trial. They will not be involved in the processing or analysis of the data, and do not have access to any data received from NHS England.

Patient and Public Involvement (PPI) representatives have been involved in the proposal/project from the early planning stages and are still involved now that the project is running. SGUL have worked closely with the patient charity FND Hope UK (Functional Neurological Disorder Hope UK) for SGUL's PPI work.

The aims of SGUL's PPI in the current project was/are to ensure the research question and intervention is meaningful to patients and relevant to their needs; to ensure the methodology is acceptable; to ensure SGUL are measuring meaningful outcomes; to support and provide advice on the conduct and management of the trial; to provide input into interpretation of results; and to support and oversee dissemination of results to relevant stakeholders.

In the design stage of the study, SGUL initially disseminated a short questionnaire to FND charity forums, where the public could comment on their problematic symptoms, priorities for treatment, important considerations for physiotherapy and dissemination targets. Following this, a Facebook discussion group was initiated to engage an active dialogue regarding important issues to consider with treatment, treatment outcome and dissemination of research outcomes.

The conclusions from these social media projects was that an improved ability to walk is the most important treatment outcome for most of the public consulted with the condition. These findings support the primary outcome of this study, which measures walking problems (Short Form 36*), as do some of the secondary outcome measures.

*The 36-Item Short Form Survey (SF-36) is an outcome measure instrument that is often used, well-researched, self-reported measure of health.

SGUL also held a workshop with some previous service users, who reviewed each of the proposed outcome measures of the study, and deemed them to be important and acceptable to patients.

The trial has been running since May 2018, and SGUL have active patient and public involvement throughout. SGUL have PPI representatives in both SGUL's internal Trial Management Group and SGUL's independent Trial Steering Committee. Their role is to input into development of patient facing trial materials, input into project management, input into analysis of the results to consider what is a meaningful change for patients and support with dissemination of the results.

PPI influenced the trial protocol in a number of important ways, this includes:

1. SGUL included a number of different ways for participants to complete their outcome assessments (online forms, over the telephone, paper).

2. SGUL's PPI group helped to select relevant and suitable outcome measures and advised ways to minimise the burden of outcome assessment by reducing the number of assessment tools.

3. PPI influenced decisions regarding reimbursement of travel, to ensure SGUL 's participants were not left out of pocket.

4. PPI were heavily involved in the planning and decisions regarding restarting the trial after pausing due to COVID-19. This included safety considerations and strategies to ensure participants concerns were considered and addressed.

FLOW OF DATA INTO NHS ENGLAND

SGUL will submit the NHS number, study ID, and date of birth (DOB) to NHS England for each participant. The information SGUL is requesting has also been requested from the participants through a subjective self-report outcome measure. However the HES data will provide an independent objective measure.

The HES data will only be sent to UCL – the data processor. Only aggregate data with small numbers suppressed (in line with the HES analysis guide) will leave the UCL Data Safe Haven. The data controller – SGUL, will only receive aggregate data with small numbers suppressed (in line with the HES analysis guide). SGUL has a Data Processing Agreement in place with UCL.

FLOW OF DATA OUT OF NHS ENGLAND

Using the NHS Number, study ID, and DOB, NHS England will extract and provide the HES data requested for each participant. The data requested relates to HES outpatient, inpatient, critical care and A&E/ECDS visits only. The returned data (to UCL) will contain no directly identifying details but will include the participants unique study ID. The linked data will be provided by NHS England to the study team at UCL and downloaded into the UCL Data Safe Haven. It will be stored, processed and linked only through this safe haven hosted by UCL which can only be accessed by substantive employees of UCL: namely the trial Lead Health Economist and Junior Health Economist and the trial Lead Statistician and Junior Statistician. All processing activities will take place within the UCL Data Safe Haven only.

The UCL Data Safe Haven is an ISO27001 compliant and NHS IG toolkit approved facility used for storing sensitive data. It has been built using a walled garden approach, where the data are stored, processed and managed within the security of the system. The Data Safe Haven technical infrastructure is hosted on a thin client system with dual factor authentication. This is a multi-user system with permission-based access control. There is a standard process for granting and revoking access and system privileges are limited to those individuals referenced above who have received training in information security. Users access their data using a remote desktop technology, which has been hardened to prevent data from accidental or deliberate transfer to the endpoint device, including copy and paste, and connected storage. Whilst using the Data Safe Haven, accessing any external network resources (web sites, email, etc) is prevented.

SUBSEQUENT FLOWS OF DATA

Only aggregated analysed data (in line with the HES analysis guide) will leave the Data Safe Haven.

DATA PROCESSING AT EACH STAGE TO ACHIEVE PURPOSE

The data from HES will contribute to a comprehensive health economic evaluation. The data provided will be compared at randomised group level to determine the impact of treatment allocation on health service use and the costs associated with this. This will contribute to an understanding of whether the specialist physiotherapy intervention or TAU are related to a decreased use in services, and if so, the cost of the savings minus the cost of the treatment. All reports/outputs will be aggregated with small numbers suppressed in line with the HES analysis guide.

DATA LINKAGE AND RE-IDENTIFICATION RISK

The HES/ECDS data set will be stored in the UCL Data Safe Haven, which is in a separate institution to the location of the identifying details which are stored with the trial management team at SGUL. Therefore, there will be no risk of re-identification as UCL employees do not have and cannot have access to SGUL servers. There is also no requirement to re-identify participants. The HES data set will include the study ID and no other identifying details.

The HES data set will be linked to other pseudonymised (CSRI) study data in the Data Safe Haven. These datasets will be linked via the study ID only, the CSRI dataset contains no other identifiable information. The subjective CSRI study data will be imported into the Data Safe Haven to allow the necessary validation and analysis against the HES data set. Only the aggregated data of these analyses will leave the Data Safe Haven.

The HES data set will also be linked to a coded treatment allocation identifier (e.g. group 1 or 2 to correspond to whether the participant was allocated to intervention or control treatment). The data will be analysed blindly before the true treatment allocation is revealed.

The CSRI dataset and coded treatment allocation identifiers will be imported by substantively employed UCL employees, who have been permitted access to the Data Safe Haven.

SGUL will submit an end of trial report to the funder (NIHR-HTA) which is due 14 days after the completion of the trial. The trial is due to end on the 30 September 2023.

The main trial paper will be submitted for publication as soon as possible after the data has been analysed. It is SGUL's aim to publish this paper in October 2023, or before if possible. It is St George’s University of London’s policy to publish a peer reviewed manuscript within 180 days of completion of the trial.

Also in October 2023 (or before if possible), SGUL will complete a lay summary of the trial results and send to all trial participants. This same information will be added to the trial’s public-facing website. The website will also be updated with links to published trial reports. SGUL are committed to publishing trial reports open access.

SGUL's dissemination plan will include the presentation of findings to clinical commissioners for neurology and psychiatry services. SGUL will also promote the findings in national bodies within influence on service development such as the Association of British Neurologists and the Association of Chartered Physiotherapists in Neurology (ACPIN). SGUL's research team is involved in on-going meetings around the UK to support the planning of the care pathways for patients with FMD.

SGUL will disseminate research outputs to healthcare professionals such as physiotherapists, occupational therapists, neurologists, psychiatrists, and GPs through publication in high impact journals and presentations at scientific meetings (such as the Association of British Neurologists, Movement Disorders Society Congress, British Neuropsychiatry Association meeting, International Congress of the Royal College of Psychiatrists, and ACPIN Annual Conference).

SGUL's public engagement work has identified that patients consider that GPs require more information and support in helping patients with FMD. SGUL will target this group via GP-focussed general and academic publications and national scientific meetings (e.g. Society of Academic Primary Care and Royal College of General Practice conferences).

If the trial shows the intervention is clinically and cost effective, SGUL will use the data to support Specialist Physiotherapy provision as part of the NHS patient pathway. SGUL will present data to health service commissioners to support rolling out the intervention across the NHS. The treatment manual and physiotherapy education resources from the trial will be made publicly available. SGUL will develop a training package to support rolling out the intervention across the NHS. SGUL will share data and support physiotherapy departments setting up services for patients with FMD – an activity SGUL currently regularly engage in.

SGUL will encourage and support SGUL's Patient and Public Involvement (PPI) representatives to present the research findings at scientific and lay meetings. SGUL will make the findings accessible to patients and the public via SGUL's longstanding collaboration with the charitable patient support organisations FNDHope.org and FNDAction.org.uk. These groups have written letters of support for SGUL's research and will support dissemination and promotion of the results. Both charities host websites that receive high volumes of internet traffic, and have user active discussion forums. SGUL will also disseminate results via the patient information website neurosymptoms.org, a website written and managed by a co-applicant. The website receives 60,000 hits a month globally. SGUL will also publicise SGUL's work to the wider public through national media and social media (e.g. Twitter). In addition, SGUL's PPI representatives will help to identify other important avenues for disseminating results.

The study findings will be reported on the trial website (www.physio4FMD.org), which was created for the public, trial participants and health professionals.

All outputs will be in aggregate form only with small numbers suppressed in line with the HES analysis guide.

The overall aim of the Physio4FMD study is to evaluate the clinical and cost-effectiveness of a specialist physiotherapy intervention compared to TAU in FMD. The HES/ECDS data SGUL are requesting hope to provide the objective measures of health service. This data hopes to complement what has and is being collected subjectively from participants, and will look to help avoid any forgotten, mis-remembered or unreported data to ensure SGUL have an accurate and real reflection of health service use and cost. The NHS England data aim to enable SGUL to conclude whether a specialist physiotherapy intervention or TAU reduce health service use in patients with FMD. If the specialist physiotherapy intervention is proven clinically and cost-effective, there could be a strong argument in support of commissioning specialist services for patients with FMD and rolling out the intervention across the NHS. Should the results be positive, rolling out a proven clinically and cost-effective intervention could improve health outcomes and reduced costs of a large group of people. Should the trial intervention be found not to be effective, health care resources can be more appropriately reallocated.

Public interest in dissemination relates to improved allocation/spending of health care resources. If proven clinically effective, dissemination could help improve access to members of the public who are affected by FMD to an effective treatment.

SGUL's interest in processing the data relates to developing and improving access to effective treatments for people with the disabling condition FMD. In order to change practice within the NHS and introduce treatment, evidence from high quality randomised controlled trials are needed; and the results of such trials need to be published in peer reviewed journals. This is SGUL's first objective and SGUL aim to publish the results of the Physio4FMD trial in or before October 2023. As described above, SGUL have additional dissemination activities to ensure the results from the trial reaches the necessary people (e.g. clinicians via clinical conferences; and commissioners via specific meetings). It is important that dissemination reaches patients and service users. In partnering with all the main patient support charities; and the most viewed patient information website (neurosymptoms.org); SGUL hopes to ensure maximum reach. Targeting clinicians, in particular physiotherapists with outputs could help physiotherapists to implement findings from this research into their clinical practice.

SGUL's dissemination plan was created in consultation with clinicians, researchers, and members of the public/service users; with the aim of creating maximum impact and reaching as wider audience as possible. The dissemination plan has been created with a mind towards optimising implementation of the trial intervention, should it be found to be cost effective.

The trial intervention is a novel approach to physiotherapy that can be easily implemented into clinical practice.

The results of this research relate to a large group of patients. The incidence of FMD is estimated to be in the range of 4 to 12 per 100,000 per year; making it similar in incidence to multiple sclerosis and Parkinson’s disease. The costs of FND have yet to be formally assessed, but are assumed to be very high due to high health care utilisation, the cost if investigations and acute hospital care.

Those who could potentially benefit include patients who may gain access to the trial interventions, should it be proven effective; physiotherapists who provide treatment for people with FMD could benefit by having access to evidence based interventions. Society may benefit from a reduced health and social cost of FMD.

Measurement of the effectiveness of the trial intervention is being measured in the current project (a randomised controlled trial). Future work should look at the pragmatic implementation of the intervention, though this is beyond the scope of the current project.

The results from this project is hoped to be published in or before October 2023 and should the intervention be proven effective, it could be implemented in the NHS immediately. Dissemination projects described could support that implementation.

No yielded benefits as of yet as the data has not been disseminated.