The CIPHER study - UK Cohort study to Investigate the prevention of Parastomal Hernia

The Royal Devon University Healthcare NHS Foundation Trust (RDUH) and the University of Bristol require access to the Data for the purpose of the following research project: The CIPHER study – UK Cohort study to Investigate the prevention of Parastomal Hernia (PSH).

The following is a summary of the aims of the research project provided on behalf of RDUH and the University of Bristol:

“The CIPHER study is an ethically approved study with patients providing consent to participate. Participants understand how their data will be used and why. This study collected data about key technical surgical steps used during stoma formation and followed up the participants to establish the incidence of symptomatic and radiologically confirmed PSH.

“The formation of a stoma can be associated with future complications, including the risk of developing a PSH. PSH are relatively common and affect approximately 40% of patients within 2 years of their bowel surgery. Complications of PSH can be severe and are known to negatively influence patients’ quality of life. Both patient and surgical factors are believed to influence the development of PSH. However, the way in which surgeons create stomata is very varied and research is needed to investigate whether these factors influence the risk of developing a PSH. Modification of the technical aspects of surgery may reduce the incidence of PSH and could lead to improvements in the health of patients, better quality of life, a reduction in direct stoma appliance and accessory costs and fewer PSH repairs. The modifications offer the potential for significant savings for the NHS as well as benefit for individual patients. Unfortunately, existing studies on surgical technique relating to stoma formation are limited by poor design and generalisability and, consequently, further high-quality research is urgently needed.

“In 2014, the NIHR released a commissioned funding call for the “Prevention of Parastomal Hernia Formation”. The Royal Devon University Healthcare NHS Foundation Trust responded to this call with the support of the Bristol Trials Centre (BTC, University of Bristol) with an application for funding for the CIPHER study. To date, Phase A of the study has been completed. The aim of Phase A was to undertake feasibility work to inform the design of Phase B. This included identifying the surgical steps and other factors relevant to PSH development and developing a Patient Reported Outcome Measure to use in Phase B to identify symptomatic PSH.”

During the conception of this project study representatives met with patients, representatives of patient organisations (Colostomy, Ileostomy & Urostomy Associations) and professionals to garner feedback on the proposed study and to continue to engage with the PSH community. Patients have been involved in the design of the study and two patient representatives are on the Study Steering Committee.

"The CIPHER study (Phase B; CIPHER-B) aims to establish the incidence of symptomatic and radiologically confirmed PSH during a minimum of 2 years follow up. Additionally, CIPHER aims to evaluate the effects of key technical surgical steps during index stoma formation on the risk of subsequent PSH formation.

“Specific objectives of CIPHER-B are:

1. To describe the incidence of PSH formation within 2 years of formation of all types of stomata;

2. To describe the risk of PSH for different types of stoma;

3. To describe the risk of PSH according to how the stoma trephine is created;

4. To describe the relative risk of PSH following index stoma creation with or without mesh;

5. To describe the relative risk of PSH following index stoma creation with prophylactic mesh according to mesh position;

6. To describe the relative risk of PSH with different trephine shapes in the mesh;

7. To estimate the cost effectiveness of commonly used types of mesh in prevention PSH and improving health related quality of life.”

For Phase B of the project, the following NHS England data will be accessed:

• Hospital Episode Statistics Admitted Patient Care, Critical Care, Accident & Emergency, Outpatients – necessary to calculate the incidence of PSH, describe the specific risks of PSH for different types of stoma, describe hospital resource use of patients who develop PSH, and enable the study team to estimate the cost effectiveness of modifying surgical techniques.

• Emergency Care Data Set (ECDS) – necessary because this dataset replaced HES Accident & Emergency data

• Diagnostic Imaging Dataset (DIDS) – necessary to identify patients who develop a PSH

• Civil Registration Mortality – necessary to identify patients who die during follow up and describe the specific risks of PSH for different types of stoma

The level of the data will be:

• Identifiable – necessary to ensure that the data linkage has been successful

The data will be minimised as follows :

• Limited to data for a study cohort of participants that consented to take part in the CIPHER study

• Limited to data between 2017/18 – 2022/23. For each individual patient, data will only be provided from the date 6 months prior to the date of their index surgery and until the date of withdrawal or end of follow-up period. End of follow-up is defined as 3 months after a patient's last follow up questionnaire. Questionnaires were sent bi-annually with the last questionnaires sent on 01/09/2022. End of follow-up period is therefore between June 2022 and December 2022 for patients who have not withdrawn.

Royal Devon University Healthcare NHS Foundation Trust (RDUH) as the research sponsor, and the University of Bristol as the main collaborator, are joint data controllers as the organisations responsible for ensuring that the data will only be processed for the purpose described above.

The statisticians in the Bristol Trials Centre (BTC, University of Bristol) will make the decision about how the data will be analysed and RDUH will have oversight of the processes in their role of Sponsor. At no point will RDUH have access to any NHS England data – they will only see the aggregated outputs with small numbers suppressed in line with the NHS England analysis guidelines.

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;

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.

This processing is in the public interest because the study has the potential to significantly benefit society by addressing an important area of clinical uncertainty for patients at risk of developing PSH. This research priority was supported by a recent survey of The Association of Coloproctology of Great Britain and Ireland (ACPGBI) that ranked optimisation of methods to prevent and repair PSH as the second most important research question not related to cancer. For these reasons, the processing also meets the conditions of Schedule 1 Part 1 paragraph 4 of the Data Protection Act 2018.

The funding is provided by the National Institute for Health and Care Research (NIHR) (14/166/01) under the NIHR Health Technology Assessment award. The funding is specifically for the study described. Funding is in place until April 2023.

The University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) is a data processor acting under the instructions of the data controllers. UHBW’s role is limited to providing IT hosting services, sending and receiving data to and from NHS England and removing identifiable data before transfer to the University of Bristol. UHBW will store the Data as contracted by University of Bristol and RDUH.

University of Birmingham are a study collaborator on the funding application. They support the study in an advisory capacity and do not make any decisions determining the study purposes, determine the manner in which the data will be processed, nor have any access to NHS England data. This co-applicant is not considered by the CIPHER study team as Data Processor or Data Controller.

Identifiable data will be accessed by:

• Individuals employed by the University of Bristol with UHBW contracts.

Pseudonymised data will be accessed by:

• Individuals employed by the University of Bristol.

Data for ~2175 consenting patients will be transferred from University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) to NHS England . The data will consist of identifying details (specifically NHS Number, Date of Birth, start and end dates of study involvement, and a unique person ID) for the cohort to be linked with NHS England data. The start date will be a pre-calculated date per patient which is 6 months prior to their index stoma formation surgery. The end date for a patient will be either their withdrawal date or the end of the study follow-up period.

NHS England data will provide the relevant records from the HES, ECDS, Civil Registration Mortality and Diagnostic Imaging Datasets to UHBW. The data will contain directly identifying data items including NHS Number and Date of Birth which are required to ensure effective linkage of the data at record level with data already held by the recipient.

UHBW will pseudonymise the data and securely transfer this to the University of Bristol.

The data will be stored on servers at UHBW and the University of Bristol encapsulated Virtual Machine (EVM) – a secure purpose-built secure research server. The EVM provides a secure way for approved University of Bristol substantive employees who are part of the CIPHER research team to access the data from approved University of Bristol computers. The EVM is hosted in the Virtus Data Centre in Slough.

Patient identifiable data will be accessed remotely by substantive employees of the University of Bristol who hold an honorary contract with UHBW. Access is restricted to employees or agents of UHBW who have authorisation from the Chief Investigator.

Pseudonymised data will be accessed onsite at the premises of the University of Bristol. Access is restricted to employees or agents of University of Bristol who have authorisation from the Chief Investigator.

Personnel are prohibited from downloading or copying data to local devices.

The data will not leave the UK at any time.

Employees or agents of RDUH are only permitted to access anonymised data including information derived from NHS England data. Such datasets will adhere to the relevant suppression rules.

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

The data will be linked at person record level with health and questionnaire data obtained from research sites during the study.

The identifying details will be stored in a separate database to the NHS England linked dataset used for analysis. All analyses will use the pseudonymised dataset. Pseudonymised study data will be analysed by individuals with access to the patient identifiable data. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

Researchers from the University of Bristol with a UHBW honorary contract will process the data to send and receive data to and from NHS England, and remove identifiable data before transfer to the University of Bristol.

Researchers from University of Bristol will analyse the data as described in order to find out which surgical factors are linked with PSH.

The data from this study will be used to produce outputs including publications in peer-reviewed academic journals, professional media (e.g. to stoma care nurses) and presentation at national and international conferences. A simplified version of the findings will also be disseminated as newsletters to patients, in accordance with advice from the patient and public involvement (PPI) group about how best to do this effectively. The findings will also be reported as a report to the funder in the form of a Health Technology Assessment monograph, and to other health care stakeholders with an interest in research.

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.

A report to the funding body will be sent to the National Institute for Health and Care Research and will provide a summary of the work undertaken during the life of the study. The target journals for the main study paper and other related publications have not been identified, but these will be Open Access and should be completed by summer 2024. These will communicate the results of the primary and secondary outcomes of the study. A summary for stakeholders will be provided and will be aimed both externally (e.g. general public/patients, media) and internally (e.g. participating Trust stuff, operational staff).

All outputs will be reviewed by the Chief Investigator and other collaborators, as necessary.

Findings will be shared with the Association of Coloproctology of Great Britain & Ireland (ACPGBI), Colostomy Association (a patient support organisation) and the Association of Stoma Care Nurses. The Chief Investigator has close links with these groups who are already aware and supportive of the study and awaiting its results. The study team intend to make presentations to all of them. Presentations will be given at national and international conferences relevant to colorectal surgery. This is intended to occur in ~Autumn 2024.

Engagement with patient support groups (e.g. Colostomy UK; Ileostomy and Internal Pouch Association) and relevant surgical societies (ACPGBI, The Association of Stoma Care Nurses UK) will ensure the results are targeted to the relevant staff and patient groups.

The CIPHER study has the potential to significantly benefit society by addressing an important area of clinical uncertainty for patients at risk of developing PSH. This research priority was supported by a recent survey of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) that ranked optimisation of methods to prevent and repair PSH as the second most important research question not related to cancer. The ACPGBI Patient Consultation Exercise involved representatives of national inflammatory bowel disease, colorectal cancer, ileostomy and colostomy patient support groups who discussed and ranked 24 different research topics.

The use of the data could support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work), and advance understanding of regional and national trends in health and social care needs.

It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of knowledge that is considered by organisations who may wish to build upon this to pursue a randomised controlled trial (RCT).

The RCT would look to establish whether certain surgical techniques reduce the incidence of PSH. Subsequent changes in guidance could then benefit patients.

The primary analyses of the CIPHER cohort study have not yet been completed. This is the key reason for seeking an extension for the data extract; we need to be sure we have the data extract to address any queries raised by peer reviewers when we submit publications to journals. Main analyses are ongoing and the main reason for not having published the main findings is the illness over the last year and recent death of the chief investigator. “Measurable benefits” that the analyses will provide in due course are quantified risks for and protective factors against parastomal hernia associated with: (a) participants’ demographic characteristics and medical history, (b) operative details including variation in the way stomata were created and (c) post-operative events such as surgical or medical complications and surgical site infection. Quantifying these associations will allow clinical staff to customise their management of patients.