SCOPE 1: Study of Chemotherapy in Oesophageal cancer Plus or minus Erbitux

Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.

Datasets: − MRIS - Cohort Event Notification Report; − MRIS - Flagging Current Status Report; − MRIS - Members and Postings Report; − MRIS - Personal Demographics Service

Objective for processing

SCOPE 1 is a study in patients with cancer of the oesophagus for whom it has been decided the best form of treatment is chemo-radiation (treatment that involves giving radiotherapy together [or concurrently] with chemotherapy). The trial aims to identify whether the addition of the monoclonal antibody cetuximab (Erbitux™) to definitive chemo-radiation (CRT) shows evidence of enhanced overall survival, whether it is safe, and whether the treatment of patients with non-metastatic carcinoma of the oesophagus is feasible. If cetuximab is found to be active, safe and feasible then the trial will continue recruitment to accrue sufficient patients to establish whether the addition of cetuximab to the standard treatment improves overall survival. On 1 February 2023, NHS Digital merged with NHS England. NHS England has assumed responsibility for all activities previously undertaken by NHS Digital. The merger was completed by a statute change. Any reference made to NHS Digital within this Data Sharing Agreement is in reference to the merged organisation known as NHS England. Cardiff University requires on-going access to NHS Digital data for the purpose of the following research project: SCOPE 1: Study of Chemotherapy in Oesophageal cancer Plus or minus Erbitux. SCOPE 1 was a study in patients with cancer of the oesophagus for whom it had been decided the best form of treatment was chemo-radiation (treatment that involves giving radiotherapy together [or concurrently] with chemotherapy). The trial aimed to identify whether the addition of the monoclonal antibody cetuximab (Erbitux™) to definitive chemo-radiation (CRT) showed evidence of enhanced overall survival, whether it was safe, and whether the treatment of patients with non-metastatic carcinoma of the oesophagus was feasible. If cetuximab was found to be active, safe and feasible then the trial intended to continue recruitment to accrue sufficient patients to establish whether the addition of cetuximab to the standard treatment improves overall survival. The trial ended in 2015. However, Medical Health Research Authority guidance stipulates those clinical trials should retain data for 15 years post trial. Cardiff University would like to retain this data to enable reconstruction of the trial analysis and to support audits should this be required. No additional data will be requested from NHS Digital. This Agreement does not permit any further processing that involves analysis or linkage other than for the purpose of verifying findings in line with the original objectives of the study by repeating previous analyses. Following publication of study findings, it is possible that the findings will be questioned or challenged by third parties through direct contact with Cardiff University, contact via the publishing journal or an open letter. In such circumstances, Cardiff University may re-run previous analyses to verify that the published results were accurate and may publish or write a response directly to the challenger. Cardiff University are not permitted to undertake different analyses to those undertaken during the original analysis. This Agreement does not permit any onward sharing of the data with the exception that the data may be viewed for the purpose of an audit by a regulator such as the Medicines and Healthcare products Regulatory Agency (MHRA). The data controller themselves may exercise the right to audit. If any further data processing is required in addition to the above purposes, or if the data needs to be moved to a different location/organisation, the applicants must submit a request to amend this Agreement to NHS Digital before data is accessed or migrated. The following NHS Digital data will be retained: • Mortality Data obtained via the Medical Research Information Service (MRIS)– Death data was obtained from NHSD for participants in the SCOPE1 trial that had missing death data due to loss to follow up, for example if a participant moved location. Obtaining this information improved the accuracy of the data in the trial analysis. The level of the data will be: •Pseudonymised data only. The data will be minimised as follows • Limited to data for a study cohort of ~200 consented individuals • Limited to data disseminated between July 2011 and April 2015 Velindre NHS Trust was the research sponsor and the employer of the Chief Investigator for the study. They were not listed under previous iterations of this Agreement as a data controller however as study sponsor Velindre did undertake some duties of a joint data controller including obtaining trial authorisation and appropriate ethics committee opinion. However, for the purpose of the data being archived under this Agreement, Velindre NHS University Trust and its employees, including the former Chief Investigator, play no active roles, delegating this responsibility to the Centre for Trials Research at Cardiff University. All decisions concerning the retention and any potential reuse of the data are taken by Cardiff University. Cardiff University are therefore deemed to be sole data controller for the purpose of this Agreement. The data will be archived and will not be accessed by any individuals other than substantive employees of Cardiff University or employees of the auditing organisation and strictly for purposes described above.

Processing activities

Not stated in the previous version; added here.

Pseudonymised mortality data was supplied by NHS Digital to Cardiff University.

The study will retain identifiable information collected from participants by the trial; but this will be stored separately to the pseudonymised data provided by NHS Digital. There will be no requirement to link the data disseminated under this Agreement and the identifiable participant data collected by the trial.

The data will be securely stored at Cardiff University.

The data may be accessed for a purpose specified above only. In all such circumstances, the data must remain on Cardiff University servers, with access restricted to substantive employees of Cardiff University or substantive employees of the organisation auditing the study.

Previous processing activities pertaining to the original purpose of this Agreement are detailed below:

For the analyses it was important for the study to have accurate date and cause of death data for all patients. The study team used the Medical Record Information Service (MRIS) to obtain this information to corroborate the existing data and to find data on patients who have been lost to follow up. The study team performed the following process before each stage analysis:

i) For patients who specifically consented to use of their identifiable data for follow up through MRIS, the study team asked research nurses to collect their surname, forename, initials, date of birth, NHS number, postcode, and trial number (specific to this trial) on a Case Report Form. This was sent to Wales Clinical Trials Unit (WCTU) at Cardiff University.

ii) WCTU stored these forms in a locked cupboard

iii) When all required forms had been obtained, the above data was entered into a spreadsheet and sent to MRIS

iv) WCTU asked MRIS to return the spreadsheet with date and cause of death appended. This pseudonymised data was then joined to the clinical database in Stata during analysis.

If a patient was lost to follow-up the WCTU first requested the centre contact the patient‘s GP to obtain information on the patient‘s status. If needed and the patient had given the necessary consent, they were then traced via the National Health Service Information Service (NHS IC) or the NHS Central Register (now NHS Digital).

Expected output

Not stated in the previous version; added here.

No new outputs are expected as this DSA solely permits archiving and secure retention of data previously disseminated.

The NHS Digital data previously disseminated has been used to support the publication of the below journal articles.

Published papers:

Crosby T, Hurt CN, Falk S, Gollins S, Staffurth J, Ray R, Bridgewater JA, Geh JI, Cunningham D, Blazeby J, Roy R, Maughan T, Griffiths G, Mukherjee S. Long-term results and recurrence patterns from SCOPE-1: a phase II/III randomised trial of definitive chemoradiotherapy +/- cetuximab in oesophageal cancer. British journal of cancer. 2017;116(6):709-16.

Cox S, Hurt C, Grenader T, Mukherjee S, Bridgewater J, Crosby T. The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy. Radiotherapy and Oncology. 2017;125(1):154-9.

Cox S, Powell C, Carter B, Hurt C, Mukherjee S, Crosby TD. Role of nutritional status and intervention in esophageal cancer treated with definitive chemoradiotherapy: outcomes from SCOPE1. British journal of cancer. 2016;115(2):172-7.

Mukherjee S, Hurt C, Falk S, Gollins S, Staffurth J, Ray R, Bridgewater JA, Cunningham D, Blazeby JM, Roy R, Maughan T, Griffiths G, Crosby TDL. Long term results and patterns of recurrence from SCOPE 1: A phase II/III randomised trial of definitive chemoradiotherapy (dCRT) plus or minus cetuximab (dCRT plus C) in esophageal cancer. J Clin Oncol. 2016;34(4).

Crosby T, Hurt CN, Falk S, Gollins S, Mukherjee S, Staffurth J, Ray R, Bashir N, Bridgewater JA, Geh JI, Cunningham D, Blazeby J, Roy R, Maughan T, Griffiths G. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial. The Lancet Oncology. 2013;14(7):627-37.

Expected measurable benefits

Not stated in the previous version; added here.

No new benefits are expected. This DSA permits the secure retention of data for the purpose of recreating trial analysis and auditing.

Benefits reported

Yielded Benefits is not a requirement for new applications. 1) Benefits to the NHS The research outlined within this Agreement indicated that it was unlikely that cetuximab had an effect on patient outcomes. As a result of this the study ceased recruiting participants in 2012 and funds were re-allocated to areas where there may be a greater impact on patient outcomes. 2) Benefits to the Patients The SCOPE1 trial showed that these patients should not get cetuximab saving them from being given less effective treatment. The research also highlighted the possible need for nutritional support for these patients whilst being treated but further research is needed before practice can be changed. It also identified potential biomarkers that can identify patients who do particularly badly and who may benefit from additional treatment but again more research is required before practice can be changed.