The ROMIO Study. Randomised Oesophagectomy: Minimally Invasive or Open (ODR1718_315)

Patients with gullet (oesophageal) cancer are often offered surgery to remove part of the gullet (oesophagectomy), usually following up-front chemotherapy and/or radiotherapy. It is unclear whether patients recover, and survive better following combined open and keyhole surgery (called 'combined' surgery) or standard open surgery.

Surgery improves survival rates but there is a reduction in quality of life. Minimally invasive, or "keyhole" surgery is technically demanding for a procedure as complex as oesophagectomy, but its use in the treatment of other cancers suggests that there may be benefits in terms of faster recovery. Open surgery is complex with large incisions made to the abdomen, chest and, sometimes, neck. Unfortunately, 30% of patients experience complications, and about 3% of patients die soon afterwards.

The Randomised Oesophagectomy: Minimally Invasive or Open (ROMIO) study compares 'combined' surgery (laparoscopic abdominal surgery and thoracotomy) with open surgery (open oesophagectomy), to find out whether 'combined' surgery allows faster recovery than open surgery, without changing the survival benefit of having surgery. The study also compares open and 'combined' surgery in terms of health-related quality of life, complications experienced by patients after surgery and cost-effectiveness.

The study is a pragmatic randomised controlled trial (randomising patients 1:1 between 'combined’ and standard 'open' surgery) at 9 participating major UK cancer centres. A sub-study run at 2 of the centres also randomly allocated participants to receive a fully minimally invasive ‘keyhole’ oesophagectomy (TMIO) as a sub-study. The sub-study will provide descriptive data on 'keyhole' TMIO surgery which is only undertaken at about 10% of UK cancer centres. The main trial was developed and seamlessly followed an internal pilot ROMIO study.

Participants have been recruited across seven participating centres. All those being considered for oesophagectomy were screened for trial eligibility by the multidisciplinary team caring for the patient. Where the individual is found to be eligible for the study the research nurse would give the patient information about the trial, and if the patient was content to participate informed consent would be obtained prior.

To support this work the study requires pseudonymised subsets of the following National Cancer Registration and Analysis Service (NCRAS) datasets:

• NDRS Cancer Registrations

• NDRS Systemic Anti-Cancer Dataset

• NDRS Radiotherapy Dataset (RTDS)

• NDRS Linked Hospital Episode Statistics (HES)- inclusive of the Admitted Patient Care, Outpatient and Accident and Emergency subsets

To address the GDPR Principle of Data Minimisation this request is limited to ~300 individuals that have consented to take part in the trial. Further to this, the NHS Digital Data Production team have had an extensive discussion with the study team to ensure that only the minimum amount of data necessary for achieving the purposes outlined within this Data Sharing Agreement (DSA) is being requested.

The study has determined that there is no alternative, less intrusive means of achieving the purpose of the study.

The lawful basis for processing personal data is General Data Protection Regulation (GDPR) Article 6(1)(e) ‘Public Task’, the processing is necessary for the performance of a task in the public interest. The exemption for processing special category data is GDPR Article 9(2)(j) ‘Archiving, research, and statistics (with a basis in law)’, the processing is necessary for scientific research purposes that are in the public interest.

University of Bristol and University Hospitals Bristol and Weston NHS Foundation Trust (the study sponsor) have been determined to be joint Data Controllers. The University of Bristol processes data for the purposes outlined within this DSA. The study receives funding from the National Institute of Health and Care Research (NIHR) Health Technology Assessment (HTA), beyond funding the project the NIHR play no role in the study.

University Hospitals Bristol and Weston NHS Trust will securely provide NHS Digital with the following identifiers to facilitate linkage to the study cohort:

• Study ID

• NHS Number

• Date of Birth

• Postcode

The NHS Digital Data Production team will identify cohort members in the NDRS Cancer Registrations Dataset, NDRS Systemic Anti-Cancer Dataset, NDRS Radiotherapy Dataset (RTDS) and NDRS Linked Hospital Episode Statistics (HES)- inclusive of the Admitted Patient Care, Outpatient and Accident and Emergency subsets. Before data is transferred securely to the University of Bristol, the NHS Digital Data Production Team will remove all personal identifiers. However, the data released will be inclusive of the Study ID (a pseudo-identifier). All data released under this Agreement is pseudonymised.

Once the study team receive the data, it will be linked to data generated by the trial to complete the study database. All data contained within the study database will be pseudonymised, there is no requirement to re-identify individuals whose data is contained within the study database. The study team will perform statistical analyses on the data to test the study's experimental hypotheses.

All data will be processed by substantive employees of the University of Bristol, all of whom have received appropriate training in data protection and confidentiality.

Data will be stored in the University of Bristol encapsulated Virtual Machine (eVM) which will be set up by the University of Bristol’s IT specialists before receiving the data. The ‘encapsulated virtual machine’ (eVM) is a purpose-built secure research server. It provides a secure way for approved University of Bristol substantive employees who are part of the research team to access the data from approved University of Bristol computers. The University of Bristol eVM is compliant with the existing University of Bristol organisational Data Security and Protection Toolkit (DSPT).

The University of Bristol have taken the following steps/actions to meet its Data Sharing and Protection Toolkit:

1. Detailed information of the researchers (including name, department, building and computer IT system number) accessing, processing and handling data has been provided to the Information Governance Team at the University of Bristol and has met the eligibility criteria for the DSPT.

2. Named Researchers accessing, processing and handling data have completed the "GDPR Information Security Training" and "Medical Research Council Research, GDPR and Confidentiality Training" scoring 80% or higher.

3. Once the data is obtained and stored in the respective eVM, the University of Bristol Information Governance Team will carry out a Data Quality Audit.

Virtus and AQL Leeds provide secure buildings within which University of Bristol equipment is hosted and maintained. Virtus and AQL Leeds do not access data held under this agreement as they only supply the building and are therefore not listed as a Data Processor. Therefore, any access to the data stored under this agreement would be considered a breach of the agreement. This includes granting access to the database containing the data.

It is anticipated that the study findings will be published in peer-reviewed journals and will also be presented at relevant conferences.

Should the opportunity arise, the study may publish findings on the University webpages, hold open lectures or engage with the press, this will aid the dissemination of the findings and will reach interested groups in civil society.

The study team are also required to provide NIHR, the study funder, with a final report that outlines the study's findings.

Following the publication of the study results, the contract with the funder requires that the study makes data available for further research projects. The study team have confirmed that, while they will not be sharing any data during the length of this Data Sharing Agreement, they anticipate that data shared following publication will be aggregated with appropriate suppressions rules applied and/or derived data. Before the study looks to share any data, they will submit a specification of the variables they wish to share to NHS Digital. NHS Digital will then assess the specification and confirm whether they are content that the specification aligns with the definition of derived data contained within the University’s Data Sharing Framework Contract (DSFC).

This study aims to determine whether there are differences in patient recovery, readmissions, cost, survival, and clinical effectiveness between ‘open’ and ‘combined’ keyhole surgery to remove the oesophagus. Carrying out research in this area may help inform optimal clinical practice in the future, ultimately this benefits the provision of health and social care in England and can be deemed to be in the public interest.

Should the study shed light on ways to optimise current clinical practice, and should these findings be incorporated into clinical guidelines, the study findings may:

• Contribute to a reduction in patient recovery times

• Contribute to a reduction in readmissions

• Allow more cost-effective practices

• Increase survival rates in oesophagectomy patients

• Lessen the impact on Quality of Life following oesophagectomy

Yielded Benefits is not a requirement for new applications.