Cognitive Behavioural Therapy for Dissociative (Non-Epileptic) Seizures: A Randomised Controlled Trial (CODES Study) (LREC LO/13/1595)

King’s College London (KCL) and South London and Maudsley (SLaM) NHS Foundation Trust requires HES data for the purpose of a research study called The Cognitive Behavioural Therapy for Dissociative (Non-Epileptic) Seizures (CODES).

About 12-20% of patients who attend neurology or specialist epilepsy clinics because of seizures do not in fact have epilepsy but instead have dissociative (non-epileptic) seizures (DS). A high percentage of people with dissociative seizures will have other psychological or psychiatric problems and may have other symptoms. It is generally thought that people with dissociative seizures will benefit from psychological treatments. However, studies on this have been small or have not compared the psychological therapy with the treatment people normally receive (there is no standardised medical care (SMC)). There is some evidence that cognitive behavioural therapy (CBT) may lead to a reduction in how often people have dissociative seizures. CBT is a widely accepted psychology therapy that focuses on the person's thoughts, emotions and behaviour, and considers the physical reactions and sensations that may occur in their body.

KCL has previously developed a CBT package for people with dissociative seizures. In a relatively small previous study, people receiving CBT overall showed greater reduction in how often they had their seizures. KCL is now leading on a larger study across several different hospitals, to obtain more definite results. The data processed by KCL is processed under Articles 6(1)(e) and 9(2)(j) as necessary for scientific research that is in the public interest. This is in line with KCL’s charter as an institution carrying out research in the public interest.

KCL and SLaM do not consider there to be any moral or ethical issues raised by the dissemination of the data. The processing of personal data was clearly explained to participants who provided written consent for the research team to have access to health related records including records held by the Information Centre, the General Register Officer and other health related databases. At the time of recruitment, NHS Digital was known as the NHS Information Centre. Therefore, KCL/SLaM feel that participants have given them permission to access their data for the purpose described in this Agreement.

The CODES study is a large multi-site study being funded by the National Institute of Health Research Health Technology Assessment programme (NIHR HTA). The study was submitted in response to a call from the NIHR HTA in 2012 to create a study to examine a treatment for this condition and to examine the health care costs to individuals and the NHS. The study is ‘co-sponsored’ by South London and Maudsley NHS Foundation Trust (SLaM) but SLaM does not determine any purposes of the study. The project is managed by staff at KCL and all patient data remains vested in KCL when the project completes. SLaM is provided with a small amount of research capability funding to facilitate the research because it requires NHS sponsorship. The only roles SLaM has is to process the grant funding and also an individual employed at SLaM is a co-investigator in the trial.

Individuals from SLaM, the University of Sheffield, the University of Edinburgh and Royal Edinburgh Hospital are named as co-investigators in the study protocol. These individuals are part of the trial management group meaning they are equally responsible for the grant and collectively form one of the decision-making bodies of the trial. However, within the clinical trial there are different levels of decision-making. The decision to process HES data from NHS Digital was taken solely by the Chief Investigator from KCL and the decisions about how that data is analysed are taken by the Professor of Health Economics, also of KCL. The co-investigators are not data controllers.

As co-sponsors for the trial, KCL and SLaM are joint data controllers for the purpose of this Data Sharing Agreement.

The trial has 3 significant centres where organisations have contributed materially to the trial but are not processing the data: The University of Edinburgh, NHS Lothian and the University of Sheffield. They were recruitment sites but had dedicated trial staff who managed recruitment at the many trusts around these institutions. 45 NHS trusts took part in recruiting participants, a smaller number of these, 19, were treatment centres as well. Recruitment began in July 2014 and continued until May 2018 with 368 total participants consenting to be randomised across the UK. Of these, 284 participants consented in England and were not withdrawn at the end of the study. The data requested is for these participants only.

All participants in the trial have provided a significant amount of data about their condition, how it impacts their lives and the lives of those who care for them, how their general health is, how they feel about their emotions, if they avoid things because of their seizures and many other facets of their lives. They did this up to three times during the trial period (baseline, 6-month follow up and 12-month follow up). 30 participants, just under 10% of the 368 who were randomised, also provided qualitative data by participating in a semi-structured interview with one of the researchers exploring their treatment, medical history, and experiences on the trial. The data KCL is requesting from NHS Digital contributes to a small part of the outcomes listed in the protocol.

One of the trial's outcome measures, per the protocol, is to examine and cost participants' service use and KCL originally intended that this would come only from participants. However, in addition to the self-report, the funder (NIHR HTA) advised including a more objective measure of service use and identified centrally-recorded data on hospital admissions, routine attendances and emergency department attendances as the best measure of this service use from a non self-report measure.

Participants who consented to the study were randomised to one of the two treatments. Service use for 6 months prior to each participant’s randomization will be requested and used as a baseline and the data from the 6 months prior to the end of each participant’s follow up period will be also be requested. In effect this means 6 months of data ending on the day of randomisation, followed by a six-month gap during which no data is requested from NHS Digital, and then another 6 months of data ending on the day the participant finished in the study. The dates for most participants will differ depending upon what day they were randomised.

The primary outcomes for the trial are all measured 1 year after randomisation representing the beginning of treatment. The data will provide an objective measure of service use, without relying on the participant's memory. Furthermore, participants who suffer from dissociative seizures tend to have costly and inappropriate medical use, especially before a diagnosis is made (Mellers, 2005). Therefore, the use of this data will allow KCL to see whether diagnosis and treatment of dissociative seizures reduces service use - a question very important to answer when the NHS services and resources are stretched. Furthermore, health economics analysis will be carried out to assess the cost of service use in KCL’s sample, and to see if this cost is reduced during the study.

The same analyses will be run on both the self-reported data and the data from NHS Digital. The findings of both analyses will be compared. The data will not be compared at individual participant level. Ideally, the analyses of both datasets should show the same levels of service use. If so, having two corroborating sources will make the findings more robust. If there are differences, the findings will be presented objectively and KCL will attempt to account for the differences. For example, there may be data entry bias in the HES data from NHS Digital or memory bias in the self-reported data. For the credibility of the study, it is important to present any differences and explain what they were attributed to.

The data will only be accessible to the CODES study team at King's College London. The CODES team involves the Trial Manager, and the Professor of Health Economics and Junior Health Economist. All have computers based at King's College London, and data will only be stored on these computers. No other organisation will have access to the data.

KCL will submit the NHS number, study ID (Participant Identification Number or PIN), and two dates to NHS Digital for each participant. The dates for each participant are the date six months prior to randomisation and the date six months prior to completion of follow up for each individual. All participants have consented to this information being passed to NHS Digital for this purpose. The information KCL is requesting has also been requested from the participants through a self-report measure but receiving the HES data from NHS Digital will provide an independent measure. The information KCL receives from NHS Digital is not going to be directly compared to the individual’s self-report. Instead both self-report and the data provided by NHS Digital are summarized and compared on an aggregate level.

Using the NHS Number, NHS Digital will extract and provide the HES data requested for each participant. The data requested relates to HES outpatient, admitted patient care and A&E visits only. The returned data will contain no directly identifying details but will include the participants unique study ID. The linked data will be provided by NHS Digital to the study team and downloaded by the Trial Manager onto the highly encrypted secure hosting environment provided through KCL’ s protected digital network storage. It will be stored, processed and linked only through the server hosted by KCL which can only be accessed by substantive employees of the university: the Trial Manager, Chief Investigator, Professor of Health Economics and the Junior Health Economist. All individuals with access to the data are substantive employees of King’s College London. All processing activities will take place within KCL.

The data set will be kept and stored separately to the identifying details and will include the study ID number. The data will not be linked to other data held by KCL, with the exception of a treatment identifier indicating whether the participant received CBT and SMC or SMC Alone. These are the two treatments the trial is comparing.

The data from HES will contribute to a health economics analysis which is interested in average costs and service use in patients. The data provided from HES will be compared at an individual level to see if participants’ service use (and the costs associated with this service use) changed during the study. This will contribute to an understanding of whether or not CBT and SMC or SMC alone are related to a decreased use of services, and if so how much savings that translates to taking into account the cost of the treatment. The HES data will not be directly compared to the self-report data on an individual level. Instead the aggregates of service use change within the HES data will be compared at aggregate level to the self-report data to see if they both show similar trends. All reports/outputs will be aggregated with small numbers suppressed in line with the HES analysis guide.

Findings for KCL’s baseline data, which would include data from HES, will be submitted by the middle of 2019, and KCL’s final outcome paper would come in late 2019 in a journal such as the Lancet or Journal of the American Medical Association. KCL will also publish results in the HTA's own journal which will include HES data. KCL are committed, as is KCL’s funder, to open access journals so that this information is available as freely as possible.

Findings from the study will be communicated back to CODES participants through a specially written document posted to them after KCL’s analysis is complete. KCL will also be including an alternative infographic version of the findings where possible to convey the information as succinctly and easily as possible to the participants.

The findings will also be reported on the trial website (http://www.codestrial.org/) which contains information for patients (not limited to trial participants) and health professionals (see: http://www.codestrial.org/information-booklets/4579871164).

As the CODES trial is a first trial of its kind and the largest ever done with people who have dissociative seizures, KCL’s work will be of interest to many conferences. KCL will submit presentations to the following conferences, which would include results from KCL’s analysis of the data provided by NHS Digital. British Neuropsychiatry Association, International League Against Epilepsy- British Chapter- annual conference, American Epilepsy Society annual conference, European Congress on Epileptology,

International Congress on Epileptology, Annual Conference of the British Association for Behavioural & Cognitive Psychotherapies, and the Annual meeting of Association of British Neurologists.

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

The overall aim of the CODES study is to determine whether being given a diagnosis of dissociative seizures and receiving one of two types of treatment reduces participants’ seizures, as well as their psychological distress symptoms and healthcare service use. The information KCL are requesting is in line with the information KCL have asked of the participants already, but this measure comes from system wide usage and will help avoid any forgotten, mis-remembered, or unreported data to provide an accurate and real reflection of cost and service usage. This use of this data from NHS Digital will enable KCL to conclude whether or not certain treatments reduces healthcare service use in patients with dissociative seizures. If it does, in the long term it will mean less money is being spent by the NHS which is very important as the NHS is currently financially strained. The outputs are expected in late 2019-20. The outcome of the health economics findings will be included in these outputs.

Policy makers, CCGs, and other materially interested parties will be invited to a conference about the results with any health economics outcomes being extremely important. These outcomes, if sufficiently robust, could form the basis of any recommended changes to the health care system around this diagnosis and the treatment of people who have it. For example a CCG might decide to fund CBT therapy treatments for the condition because it is associated with better outcomes for the patient and a reduction on unnecessary A&E visits. The most significant change to the health care system and to patients in general would be a recommended standard care pathway for patients with this diagnosis. These changes rely in part on the outcomes from HES about the service usage. These changes could be incorporated into the health care system within a few years.

Yielded Benefits is not a requirement for new applications.