POSNOC - POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy. A randomised controlled trial of axillary treatment in women with early stage breast cancer who have metastases in one or two sentinel nodes

University Hospitals of Derby and Burton NHS Foundation Trust requires access to NHS England data for the purpose of the following research project:

POSNOC - POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy. A randomised controlled trial of axillary treatment in women with early stage breast cancer who have metastases in one or two sentinel nodes

The following is a summary of the aims of the research project provide by University Hospitals of Derby and Burton NHS Foundation Trust.

The aim of the POSNOC Study is to for women with early stage breast cancer and one or two nodes with macrometastases, to assess whether adjuvant therapy alone is no worse than adjuvant therapy plus axillary treatment, in terms of axillary recurrence within 5 years.

Primary Objective

For women with early stage breast cancer and one or two nodes with macrometastases, to assess whether adjuvant therapy alone is no worse than adjuvant therapy plus axillary treatment (i.e. less than 2% absolute risk difference), in terms of axillary recurrence within 5 years.

Secondary Objectives

(i) To assess lymphoedema and other arm morbidity, quality of life, and anxiety at three years for women in the two allocated groups.

(ii) To assess the following outcomes at five years in the two allocated groups.

(iii) To assess axillary recurrence, loco-regional recurrence, distant metastasis, time to axillary

recurrence, survival (axillary recurrence free, disease free and overall), contra-lateral breast cancer and non-breast malignancy yearly after the 60 month timepoint until the end of the data collection period (2025) from routine medical records and data linkage (e.g. NHS England).

(iv) Economic Evaluation

Participants will be allocated to one of the two intervention groups, via a remote, secure internet based randomisation system developed and maintained by the Nottingham Clinical Trials Unit (NCTU).

The Data requested will help determine which, of two, current health strategies, is the better at achieving long term freedom from disease recurrence and survival. This will inform practice going forward.

Whilst the rate of recurrences and death will be higher in the first 5 years, there is still considerable cancer-related mortality beyond this point and therefore clinically important information can be obtained from the requested data. Therefore, this data request is for a 10 year follow-up period from 2014-2025.

The following NHS England Data will be accessed:

NDRS Cancer Consolidated Data Set:

Necessary to, for example, provide details which confirm diagnosis and site of diagnosis of interest, to identify any adjuvant therapies which patients may have had and which could affect the primary outcome, and to identify if patients had radiotherapy.

Civil Registration Deaths:

Necessary to identify patients who have deceased during follow-up.

The level of the Data will be identifiable necessary to enable linkage of the Data held.

The Data will be minimised as follows:

• Limited to a study cohort of approximately 1500 participants included in the POSNOC trial

• Women aged 18 years or older, fit for axillary treatment and adjuvant therapy

• Have been diagnosed with early-stage breast cancer and received primary breast surgery and sentinel node biopsy.

• Limited to data for patients diagnosed and randomised between August 2014 and July 2021

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 it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care.

The funding is provided by National Institute for Health Research Health Technology Assessment Programme (project number 12/35/17). The funding is specifically for the POSNOC - POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy described.

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

The University of Nottingham is a processor acting under the instructions of the University Hospitals of Derby and Burton NHS foundation Trust. The University of Nottingham’s role is limited to data analysis and contributing to the conclusions of the research.

A Public and Patient Involvement and Engagement group helped refine the purpose of the research. The group supported the collection of the data for the purposes described above. PPI members reviewed all versions of materials made available to participants are content that the Data requested under this Data Sharing Agreement would be compatible with the expectations of the participants enrolled in the POSNOC trial.

A PPI member sits on the Trial Steering Committee (TSC) and has contributed to discussions about the consent and PIS documents outlining the use of the NHS data.

Independent Cancer Patients' Voice (ICPV) is a patient advocate group independent of established UK cancer charities and aware of the value of medical research to both public health and to the national economy. They have been involved in reviewing the patient facing material for the POSNOC study.

The University Hospitals of Derby and Burton NHS Foundation Trust will transfer data to NHS England. The Data will consist of identifying details NHS Number, Date of Birth, and a unique person ID for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the NDRS Cancer Consolidated and mortality datasets to the University of Nottingham.

The Data will contain no direct identifying Data items but will contain 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 be stored on servers at the University of Nottingham.

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

The Controller 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 the UK. The data will not leave the UK at any time.

Access is restricted to employees the University of Nottingham.

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

The identifying details will be stored in a separate database to the linked dataset used for analysis. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

Statisticians from the University of Nottingham will analyse the Data for the purposes described above.

The expected outputs of the processing will include:

· Submissions to peer reviewed journals: results will be submitted to a peer-reviewed journal with a view to presenting to coincide with journal release of results, probably at a national conference. This is aimed to occur within 1 year of the final data release from NHS England.

· Reports: results will also be disseminated, in a simplified form and after the publication, to those participants who indicated that they wished to receive them. It is hoped that the results will influence public health policy.

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 research outlined provides the opportunity to produce worldwide benefits in respect of efficacy of this type of surgery, by either preventing unnecessary surgery, or providing assurance to those who have undergone surgery.

The findings of this research study are expected to contribute to evidence-based decision-making for policymakers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study.

The dissemination is anticipated to contribute to decisions on patient healthcare of direct benefit to its provision and, as such, is in the public interest. Whichever treatment is found to be superior can be expected to be included in guidelines for future health care.

The peer reviewed journal publication will become part of a body of information which will be used to formulate policy about the optimal treatment of women with breast cancer. This will have impacts on the individuals who have breast cancer themselves and may have economic implications; if the more intensive therapy is found not to be superior to the less intensive therapy, a considerable cost saving, and resource saving should be realisable. If the more intensive therapy is superior, then it may still be cost effective in terms of the life years saved.

It is hoped that through publication of findings in appropriate media, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients.

A number of charities and organisations have been involved in the development and promotion of the POSNOC trial, as outlined in the protocol.

This long-term data will provide robust evidence to inform clinical practice and NICE guidelines to improve patient outcome.

Yielded Benefits is not a requirement for new applications.