Generations Study (ODR_2014_317B)

The Institute of Cancer Research requires access to NHS England data for the purpose of the following research project:

Generations Study (ODR_2014_317B)

The following is a summary of the aims of the research project provided by the Institute of Cancer Research:

The purpose of this study is to investigate genetic and environmental risk factors for cancer and mortality, with a focus on breast cancer aetiology, by establishing and gaining long-term follow up of a cohort of more than 100,000 women in the UK aged 16 years and older at entry. The study would especially:

1. investigate gene-environment interactions and risk of breast cancer;

2. examine the separate contributions of shared environment and shared genetics to familial breast cancer risks;

3. examine the aetiological roles for breast cancer of changing hormone levels, exercise and anthropometric variables through adult life, as well the roles of other behavioural, environmental and serological factors;

4. search for common low penetrance genes and polymorphisms affecting risk of breast cancer;

5. evaluate outcomes after breast cancer (including mortality, breast cancer recurrence and other diseases) in relation to lifestyle, treatment, genetics and tumour characteristics.

Although the main focus of the study is breast cancer, the study would also enable analyses similar to 1–5 to be undertaken for other cancers and major diseases.

The following NHS England Data will be accessed:

• NDRS Cancer Pathway

• NDRS Cancer Registrations

• NDRS National Radiotherapy Dataset

• NDRS Systemic Anti-Cancer Therapy Dataset

Access to these datasets is necessary to evaluate outcomes after breast cancer (including mortality, breast cancer recurrence and other diseases) in relation to lifestyle, treatment, genetics and tumour characteristics.

Additionally, the following NDRS linked Hospital Episode Statistics datasets will be accessed:

• NDRS Linked HES Admitted Patient Care

• NDRS Linked HES Outpatients

Access to these datasets is necessary for the study team to apply algorithms developed to ascertain breast cancer recurrence and non-cancer outcomes in the breast cancer patients.

The level of the Data will be pseudonymised.

The Data will be minimised as follows:

Limited to a study cohort identified by the Institute of Cancer Research. The cohort consists of more than 100,000 women in the UK aged 16 years and older, who have consented to participate in the study.

The Institute of Cancer Research 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.

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 comes from multiple sources. The funders include:

• Breast Cancer Now

• Institute of Cancer Research

Funding to continue the work described will be sought on an ongoing basis. The funders will have no ability to suppress or otherwise limit the publication of findings.

The Institute of Cancer Research is the sole controller and will also process the Data. There are no other organisations involved as a Controller or Processor.

There is an Oversight Committee made up of senior members of Breast Cancer Now (the funders) and The Institute of Cancer Research (the sponsor), to provide oversight. The Oversight Committee will not have access to the Data.

Data will be accessed by substantive employees of ICR and:

• PhD students enrolled with the Institute of Cancer Research (part of University of London). The individuals have completed mandatory data protection and confidentiality training (as recommended and required by NHS) and are subject to ICR’s policies on data protection and confidentiality. The individual accessing the data will do so under the supervision of a substantive employee of ICR. ICR would be responsible and liable for any work carried out by the individual. The PhD students would only work on the data for the purposes described in this Data Sharing Agreement (DSA).

• Individuals holding an honorary contract under the supervision of a substantive employee of ICR (a named controller or processor) for the purposes described in this DSA only. ICR must maintain records in a single location that cover the following details of each individual given access under an honorary contract:

- Their substantive employer;

- Their role in respect of the purpose for the processing specified in the DSA;

- The start date and end date of the duration in which the Data will be accessed by the individual under an honorary contract;

- The necessity for the Data to be accessed by the person(s) holding an honorary contract, instead of a substantive employee of an organisation named as controller or a processor in this DSA;

- Confirmation that an appropriate contract is in place which follows the relevant guidance and is countersigned by the substantive employer of the honorary contract holder.

- The individuals have completed mandatory data protection and confidentiality training (as recommended and required by NHS) and are subject to ICR’s policies on data protection and confidentiality.

A Public and Patient Involvement and Engagement group helped refine the purpose of the research. The group strongly supported the collection of the data for the purposes of the general research. A Participant Panel has been recently set up to involve participants in an ongoing proposed use of the data.

This Agreement was novated from Public Health England (PHE) to NHS England in 2022. The Institute of Cancer Research had previously transferred data to PHE. The data consisted of identifying details (specifically NHS Number and Date of Birth) for the cohort to be linked with NHS England data.

For the purposes of this Agreement, the Institute of Cancer Research will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number and Date of Birth) for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the NDRS Cancer Pathway, NDRS Cancer Registrations, NDRS Linked HES OP, NDRS Linked HES APC, NDRS Systemic Anti-Cancer, and NDRS National Radiotherapy (RTDS) datasets to the Institute of Cancer Research. 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 controlled by The Institute of Cancer Research only.

The data will not be backed up in another location.

The Data will be accessed onsite at the premises of ICR and by authorised personnel via remote access using ICR devices.

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).

The Data will not leave the UK at any time .

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

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

The Data will be linked at person record level with data obtained from participant questionnaires, blood testing laboratories; urine testing laboratories; physical activity monitors; ultrasound; and MRI breast examinations.

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

Researchers from the Institute of Cancer will process the Data for the purposes described above.

The expected outputs of the processing will be:

• A report of findings to study participants via regular newsletters

• Submissions to peer reviewed journals: The study team expect to produce several papers per year. The data will be part of a resource rather than a specific project.

• Presentations at appropriate conferences, seminars, and webinars

• Publication of dashboards on the Institute of Cancer website

• Publication through press releases and blogs

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

• Webinars open to the scientific community.

• Social media – ICR may share published research on ICR’s social media

• Co-hosted events such as scientific seminars

• Posters displayed at scientific conferences

• Press/media engagement

• Participant newsletters

Production and dissemination of outputs is ongoing. It is expected the study team will produce several papers per year. The data will be part of a resource rather than a specific project. Examples of publications where the Generations Study outputs are cited include:

International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts: https://ascopubs.org/doi/full/10.1200/JCO.23.01101

The Times: https://www.thetimes.co.uk/article/walking-for-just-30-minutes-a-day-cuts-womens-risk-of-breast-cancer-s5cb78fhrww

The Independent: https://www.independent.co.uk/news/uk/breast-cancer-now-london-nhs-england-b2462311.html

The Telegraph: https://www.telegraph.co.uk/news/2023/12/11/exercise-cuts-breast-cancer-risk-young-women-study-finds/

Other examples of publication references are listed below:

Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women: https://pubmed.ncbi.nlm.nih.gov/32012248/

Night shift work and risk of breast cancer in women: the Generations Study cohort: https://pubmed.ncbi.nlm.nih.gov/31138896/

Breast Cancer Risk After Recent Childbirth: A Pooled Analysis of 15 Prospective Studies: https://pubmed.ncbi.nlm.nih.gov/30534999/

Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women: https://pubmed.ncbi.nlm.nih.gov/29931120/

Smoking and risk of breast cancer in the Generations Study cohort: https://pubmed.ncbi.nlm.nih.gov/29162146/

The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, 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 use of the data could

• help the system to better understand the health and care needs of populations.

• lead to the identification or improvement of treatments or interventions, or health and care system design to improve health and care outcomes or experience.

• advance understanding of the need for, or effectiveness of, preventative health and care measures for particular populations or conditions such as obesity and diabetes.

• inform planning health services and programmes, for example to improve equity of access, experience and outcomes.

• provide a mechanism for checking the quality of care. This could include identifying areas of good practice to learn from, or areas of poorer practice which need to be addressed.

• support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

A specific expected benefit to patients is improved care through advanced understanding of the need for, or effectiveness of, preventative health and care measures in a population of cancer survivors. For example, better understanding of the importance of lifestyle factors, contributing to the body of evidence that can shape guidance for this population.

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 or developing clinical and public health guidelines for or within the NHS or Department of Health, or treatment decisions in relation to specific patients.

Clients and decision makers will need to take action based on the information provided to them in order to realise the potential improvement opportunities. For example by reviewing and evaluating the whole body of evidence and making a decision through relevant scientific advisory committee.

The findings will be disseminated as described above, which will ensure promoting the results within the scientific community and the public which will increase the impact. In addition, BCN, the funder, often creates patient and public facing information material. BCN and ICR may translate the scientific findings to the public. As researchers, we will also stay informed about current work of relevant advisory bodies and will share our findings in call for evidence when and where considered suitable.

The methods and participant characteristics of the Generations Study have been described in:

The Breakthrough Generations Study: design of a long-term UK cohort study to investigate breast cancer aetiology: https://pubmed.ncbi.nlm.nih.gov/21897394/

Scientific publications from this study have provided information on a wide variety of exposures, the results have contributed to the body of scientific knowledge on the causes of cancer (as evidenced by the number of times each paper has been cited). Also, a recent publication, a research collaboration co-led by the Generations researchers, has attracted considerable media attention. This initiative produced the largest study of its kind on physical activity and pre-menopausal breast cancer risk, incorporating data from Generations Study. It looked at levels of physical activity and cancer diagnoses amongst 547,000 women who had not gone through menopause. The women were followed up for an average of 11.5 years, during which time 10,231 were diagnosed with breast cancer before menopause. Researchers at The Institute of Cancer Research, London, ranked the data by the amount of physical activity women reported they did during their leisure time, such as sports, cycling and recreational walking. The results showed that the most physically active women, those in the top 10% of physical activity levels, were 10% less likely to develop breast cancer before menopause, compared to the least physically active women, defined as those in the bottom 10% of physical activity levels. The analysis took into account other breast cancer risk factors and lifestyle behaviours, such as BMI, family history of breast cancer, smoking and alcohol consumption. This research has been featured in media such as The Times, The Independent, The Telegraph as well as BBC Radio. For details, see the reference and links to the articles below:

International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts: https://ascopubs.org/doi/full/10.1200/JCO.23.01101

The Times: https://www.thetimes.co.uk/article/walking-for-just-30-minutes-a-day-cuts-womens-risk-of-breast-cancer-s5cb78fhrww

The Independent: https://www.independent.co.uk/news/uk/breast-cancer-now-london-nhs-england-b2462311.html

The Telegraph: https://www.telegraph.co.uk/news/2023/12/11/exercise-cuts-breast-cancer-risk-young-women-study-finds/

Other examples of publication references are listed below [number of citations in Google Scholar]:

Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women: https://pubmed.ncbi.nlm.nih.gov/32012248/ [20]

Night shift work and risk of breast cancer in women: the Generations Study cohort: https://pubmed.ncbi.nlm.nih.gov/31138896/ [65]

Breast Cancer Risk After Recent Childbirth: A Pooled Analysis of 15 Prospective Studies: https://pubmed.ncbi.nlm.nih.gov/30534999/ [166]

Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women: https://pubmed.ncbi.nlm.nih.gov/29931120/ [285]

Smoking and risk of breast cancer in the Generations Study cohort: https://pubmed.ncbi.nlm.nih.gov/29162146/ [249]