A phase III, double blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non metastatic solid tumours ( ODR1718_261 )

Univeristy College London (UCL) requires access to NHS England data for the purpose of the following research project:

A phase III, double blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non metastatic solid tumours.

The following is a summary of the aims of the research project provided by UCL:

A clinical trial to find out whether taking aspirin daily for 5 years after treatment for an early-stage cancer, stops or delays the cancer coming back, which is testing if routine data sources can replace traditional approaches to patient follow up.

The primary outcomes of this study are:

- Overall survival for all participants

- Invasive disease-free survival for breast cancer

- Disease-free survival for colorectal cancer

- Disease-free survival for gastro-oesophageal cancer

- Biochemical recurrence-free survival for prostate cancer

Secondary outcomes are: In all participants these will include adherence, toxicity including serious haemorrhage, and cardiovascular events, as well as some tumour site-specific secondary outcome measures.

The following NHS England Data will be accessed:

• NDRS Linked Hospital Episode Statistics

o Admitted Patient Care

o Accident & Emergency

o Outpatients

• NDRS Linked Cancer Registration

• NDRS Linked Diagnostic Imaging Dataset (DID)

• NDRS Systemic Anti-Cancer Therapy Dataset (SACT)

• NDRS Radiotherapy Dataset (RTDS)

• NDRS Linked Cancer Waiting Times (Treatment Data) (CWT)

The level of the data will be pseudonymised.

The Data will be minimised as follows:

• Limited to a consented study cohort identified by UCL – UCL will provide the NHS Numbers and cancer site/morphology codes for the data required.

• Limited to data starting from trial initiation in 2015.

• For each individual patient, data will only be provided from date of enrolment into the trial and until 10 years after their completion in the trial.

• Limited to the following geographic areas: England.

UCL is the research sponsor and the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

Although Tata Memorial Centre (TMC) is the study sponsor, Tata Memorial Centre (TMC) will not carry out any controllership activities nor have the ability to limit or supress outputs

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.

The funding is provided by Cancer Research UK and NIHR HTA (Health Technology Assessment Programme). The funding is specifically for the stud described. Funding is in place until 31 August 2028.

The funder(s) will have no ability to suppress or otherwise limit the publication of findings.

Amazon Web Services provides backup services to UCL and will store the Data as contracted by UCL.

VIRTUS provides IT support to UCL.

No one else other than UCL listed above will be accessing the data.

Data will be accessed by a PhD student affiliated with UCL. The individual has completed mandatory data protection and confidentiality training and is subject to UCL’s policies on data protection and confidentiality. The individual accessing the data will do so under the supervision of a substantive employee of UCL. UCL would be responsible and liable for any work carried out by the individual. The PhD student would only work on the data for the purposes described in this Data Sharing Agreement (DSA).

There are 8 Public and Patient Involvement representatives with the Add-Aspirin trial who all support this research.

The national data opt-out does not apply where explicit consent has been obtained from the patient for the specific purpose.

Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out

No more data will flow under this agreement. Historically UCL transferred data to NDRS (at Public Health England now NHS England). The data consisted of identifying details (specifically NHS Number and Date of Birth) for the consented cohort to be linked with NDRS data.

NDRS provided the relevant records from the NDRS (HESAPC), NDRS (HESAE), NDRS (HESOP), NDRS Cancer Registration, NDRS (DID), NDRS (SACT), NDRS (RTDS), NDRS (CWT) datasets to UCL.

The Data contained no direct identifying data items but contained a unique person ID which can be used to link the Data with other record level data already held by the recipient.

The Data will not be transferred to any other location. The Data will not leave England.

The Data will be stored on servers at Amazon Web Services (AWS).

AWS’s role is limited to secure back-up of data stored in UCL’s Data Safe Haven. UCL uses offsite data centre services provided by VIRTUS data centre. VIRTUS does not have access to the data.

UCL uses offsite back-up services provided by AWS.

The Data will be accessed by authorised personnel on site and via remote access.

The Controller(s) must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract.

For remote access:

- Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA;

- Access controls granting users the minimum level of access required are in place;

- Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data;

- Multifactor authentication (MFA) is required for remote access;

- Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access;

- All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy.

The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose).

Remote processing will be from secure locations within England/Wales. The data will not leave England/Wales at any time.

Data will be accessed by individuals with an honorary contract with UCL. The individuals will act as an agent of UCL at all times under supervision from employees of UCL. Aside from this/these individuals, access is restricted to employees or agents of UCL who have authorisation from whom e.g. the Principal Investigator.

AWS and VIRTUS are not permitted to access the Data.

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

The Data will not be linked with any other data outside of this agreement.

There will be no requirement and no attempt to reidentify individuals when using the Data.

Researchers from the UCL will use the relevant subset of data to undertake the socio-economic analysis described above.

The expected outputs of the processing will be a publication in a peer-reviewed cancer research journal reporting on the comparison between trial-specific follow-up and routinely-collected health data for ascertaining key outcomes within the Add-Aspirin trial (an ongoing large phase III RCT in multiple cancer types). Submission planned for November 2023 with expected publication date Q1 - 2 2024.

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.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Public reports

• MRC CTU website

The target dates for production and dissemination of the outputs is Q1-Q2 of 2024.

The above publication, along with the previous publication on this work (see below), have the potential for wide-reaching implications for future conduct of cancer clinical trials. There is currently much interest in use of routinely collected health data for improving the efficiency of cancer trials and reducing the burden on NHS teams and resources. These publications report on both the practicalities of obtaining and using such data within trials, as well as the extent to which it is fit-for-purpose for the assessment of key (cancer and non-cancer) outcomes.

The following are specific benefits to patients are expected as an outcome subject to the findings:

- Streamlining the data collection process through routine health data could reduce the overall cost of conducting trials. This may contribute to making innovative cancer treatments more accessible for patients.

- A comprehensive assessment and comparison of trial data and HSD may provide a more holistic understanding of the impact of treatments on patients' overall health and quality of life by tracking mortality, recurrence, new cancer diagnoses and major non cancer events.

It is also envisaged that these listed above will also lead to public benefits.

A previous publication has detailed the process and practical considerations for accessing routinely-collected healthcare data for use in clinical trials to support other research groups in undertaking such work (Macnair et al. Trials (2021) 22:340).

Update as per latest confirmation report submitted 09 Jan 2024:

Publication in a peer-reviewed cancer research journal reporting on the comparison between trial-specific follow-up and routinely-collected health data for ascertaining key outcomes within the Add-Aspirin trial (an ongoing large phase III RCT in multiple cancer types). Submission planned for November 2023 with expected publication date Q1 - 2 2024.

The above publication, along with the previous publication on this work (see below), have the potential for wide-reaching implications for future conduct of cancer clinical trials. There is currently much interest in use of routinely collected health data for improving the efficiency of cancer trials and reducing the burden on NHS teams and resources. These publications report on both the practicalities of obtaining and using such data within trials, as well as the extent to which it is fit-for-purpose for the assessment of key (cancer and non-cancer) outcomes.