NHS Digital Data Release Register - reformatted

Cancer Research Uk projects

12 data files in total were disseminated unsafely (information about files used safely is missing for TRE/"system access" projects).

COVID RT - Assessing the impact of COVID-19 on radiotherapy in the UK. — DARS-NIC-625841-T2V6N

Opt outs honoured: Anonymised - ICO Code Compliant (Does not include the flow of confidential data)

Legal basis: Health and Social Care Act 2012 - s261 - 'Other dissemination of information'

Purposes: No (Charity)

Sensitive: Non-Sensitive

When:DSA runs 2022-06-29 — 2025-06-28

Access method: One-Off

Data-controller type: CANCER RESEARCH UK, UNIVERSITY OF LEEDS

Sublicensing allowed: No

Datasets:

  1. NDRS Covid Radiotherapy (CTRad)

Objectives:

The World Health Organisation (WHO) declared a COVID-19 pandemic on 11th March 2020. Healthcare systems, including the NHS, had to adapt rapidly, focusing resources to support COVID-19 infected patients whilst continuing, where possible, to provide ongoing care for other illnesses, including cancer.

As the COVID-19 pandemic has evolved, there has been increasing awareness of its “untold toll”, [3] arising as an indirect result of the pandemic on patients with cancer and other conditions. Modelling studies have projected the excess number of cancer deaths at 1 year in England and Northern Ireland due to delayed diagnosis and restricted access to surgery and systemic treatments, predicting 6,270 additional deaths in newly diagnosed patients, and 17, 915 additional deaths if all patients living with cancer are considered [4]

Radiotherapy contributes to the cure of approximately 40% of all cancers [6], with over 130,000 patients receiving radiotherapy each year in the UK yet has not been included in the modelling studies conducted to date. The studies’ usefulness to inform both radiotherapy practice and public health policy for cancer treatment is therefore restricted, highlighting the need to collect and analyse robust radiotherapy data from patients treated during the pandemic. Whilst cancer surgical services were often significantly disrupted during the COVID peak, radiotherapy services across the UK continued to treat cancer patients in often challenging circumstances. Adjustments to treatment protocols were required and implemented, in order to mitigate risk to patients of contracting COVID-19 (e.g. by reducing the duration of treatment schedules), to provide cancer treatment that would otherwise not be available (e.g. by using radiotherapy instead of surgery when surgery was unavailable) and to reduce the burden on radiotherapy departments affected by a reduced workforce due to staff sickness and isolation. The scale of these changes in radiotherapy practice, the clinical decision making underpinning them and their impact on cancer patient outcomes is unknown.

The National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (NCRI CTRad) identified the urgent and unmet need to understand the impact of COVID 19 on both radiotherapy patients and the radiotherapy service at a national scale. This led to this study –the COVID RT initiative, which has been developed in partnership with the Royal College of Radiologists (RCR), Society and College of Radiographers (SCoR) and The Institute of Physics and Engineering in Medicine (IPEM).

The aims of COVID RT are to understand why changes in radiotherapy treatment schedules were implemented during the pandemic and to then explore the impact of these changes on patient outcomes and the UK radiotherapy services. This first request is purely to understand the changes in patients radiotherapy treatment from COVID-19.

This study will give a national picture of the decision making by patients and clinical staff and the impact on patient's treatment. It also provides knowledge of how radiotherapy was used as a bridge to surgery when surgical services weren't viable due to the pandemic and therefore what are the further requirements for cohorts of patients.

The data subjects will be all individuals aged 18 years or over who received radiotherapy in participating UK Cancer centres between March 2020 and August 2021. The study was originally intended to be a rapid study of how the organisational changes for healthcare in the NHS in response to COVID-19 were to impact on radiotherapy services and cancer outcome. The vast majority of cancers occur in adults and so this was where efforts were focused as this was likely where the biggest changes in care would be observed and the biggest population impacted. The study team fully acknowledge that children and young people were also seriously affected by the pandemic but that was not the focus of this study. Rather the focus was intended to try and generate evidence to inform the health service on how best to deploy their radiotherapy resource during the pandemic using the evidence derived from the biggest population affected.

Data have been collected by cancer centres across England specifically for this study as part of patient's routine care. This study has not affected the care any patient received.

Each participating Cancer centre has captured data on the study audit form (with their own Caldicott Guardian approval) about their patients. These data sheets have then been submitted to the National Cancer Registration and Analysis Service (NCRAS). Here these data have been combined into a national dataset and pseudonymised (with a linkage file retained by NCRAS should further analyses be undertaken). This agreement is to seek permission/approval to transfer this pesudoymised file into a secure data environment for analysis by Cancer Research UK analysts. The analytical output they produce will then be shared with the wider research study team which include clinicians and academics from the National cancer Research Institute, the Universities of Oxford, Leeds, Cardiff, Swansea and Cancer Centres across the UK. Any such analytical outputs will be subject to statistical disclosure control as agreed by the National Cancer Registration and Analysis Service.

Data will be evaluated as a whole, providing a descriptive analysis of the changes in radiotherapy delivery across all centres as a result of the pandemic.

Additionally, data will be analysed by individual tumour site and other patient characteristics, to characterise the changes made to treatment schedules according to the primary tumour being treated and to understand any increased impact to any particular segment of the population.
Questions to be addressed using these datasets will include:

• Was radiotherapy treatment deferred due to COVID-19?
• Was radiotherapy treatment omitted due to COVID-19?
• Were alternative treatment schedules utilised to mitigate the risk of COVID-19 for cancer patients?
• Was concurrent chemotherapy reduced or omitted during the pandemic?
• What specific changes to radiotherapy treatment schedules were made across individual tumour sites?
• Did the indication for radiotherapy treatment change as a result of COVID-19?
• Did treatment intent change in light of the risks of COVID-19?
• Was the planned dose of radiotherapy delivered in its entirety?
• Were treatments interrupted or prolonged due to patients contracting COVID-19?
• Were changes to radiotherapy treatment decisions informed by clinician decision or patient choice?
• Were any changes to radiotherapy treatments implemented due to non-clinical reasons?
• What radiotherapy service changes have remained/should remain in place in the pandemic recovery phase?
• What lessons can be learned from the changes in practice to ensure an optimal
response for future pandemics

A pseudonymised extract of these data will be created and transferred to Cancer Research UK's Secure Data Environment (SDE).
These data will then be analysed within the SDE by named analytical staff at Cancer Research UK alongside identical data captured from Cancer Centres in Scotland, Wales and Northern Ireland. These data have been captured using the same audit form and are being sent to the relevant countries cancer registry where they are compiled into an equivalent pseudonymised dataset. Pooling these will enable a UK wide analysis .

Summary results will be calculated and used in this first research project to understand the affect COVID had on radiotherapy treatment as described in the study protocol. The original intention was to seek to link these data to other datasets available within the relevant cancer registry environment so changes in practice could be related to outcome. Obtaining the relevant permissions/approvals to simply access the data captured by the Cancer centres has proven challenging, however, so if we progress to undertake the linkages required to look at outcomes this will be the subject of a subsequent application. The data requested to be released in this application will be pseudonymised and will not be linked to other datasets.

The joint data controllers for this project are the University of Leeds, and Cancer Research UK. The University of Leeds is the listed sponsor for the study. Jointly, the two organisations make the decisions about how the data will be processed for this part of the study. University of Oxford do not undertake any data processing activities for this study nor are they a data controller for this study.

The University of Leeds' lawful bases for processing personal data and health data (defined as special category data) for the purposes of this project are:

Article 6:1(e): Specific task in the ‘public interest’ or task that has a clear basis in law, and
Article 9:2(j): Special category data used for “Archiving in the public interest, scientific or historical research or statistical purposes”, with a basis in law .

Cancer Research UK (CRUK)’s lawful bases for the processing of this data are as follows:

Article 6:1(f): Processing is necessary for the purposes of the legitimate interests pursued by the controller or by a third party, except where such interests are overridden by the interests or fundamental rights and freedoms of the data subject which require protection of personal data, in particular where the data subject is a child.

CRUK is a registered charity dedicated to saving lives through research, influence and information. CRUK commission, support and undertake research in order to generate evidence which is used to support improvements to the prevention, diagnosis, and treatment of cancer. This study is to improve the understanding of the impact which Covid-19 has had on radiotherapy activity at the height of the COVID-19 pandemic and, thereby, to better inform the NHS, clinicians and decision makers in local and central government, as to what both the impact of the decisions during the pandemic had on patients and how to mitigate this in the event of any future impact to the delivery of radiotherapy through a further pandemic or otherwise. The aim is to understand any decisions that negatively affected patients and to try and prevent these in future. We consider that these aims fall within the legitimate interests of CRUK and that the risks to the rights and freedoms of the data subject posed by this processing are both slight and are outweighed by the aims of the charity to improve cancer outcomes in line with our stated mission to see 3 in 4 people surviving cancer for 10 or more years, by 2034.

Article 9:2(j): Special category data used for “Archiving in the public interest, scientific or historical research or statistical purposes”, with a basis in law. As a medical research charity, we consider that the proposed processing of data for the purposes of this study, given the aims to asses the true impact of COVID-19 on patients and to inform the response to future waves of COVID-19 and/or future pandemics, fall within the definition of scientific research as laid out in the GDPR/ DPA2018.

The proposed work has been classed as audit/service evaluation (although research ethics approval has been sought and approved as in such applied research the boundaries between audit/service evaluation/research are not always clear). Therefore this audit/service evaluation work also has a research aspect.

There is already evidence of significant changes in cancer treatment pathways as a result of the COVID-19 pandemic and these will undoubtedly have had a major impact on outcomes from the disease. Evidence is urgently need to quantify and address these impacts.



REFERENCES:
3. Rosenbaum L. The Untold Toll — The Pandemic’s Effects on Patients without Covid-19. NEJM 2020; https://doi.org/10.1056/NEJMms2009984
4. Lai AG, Pasea L, Banerjee A, Denaxas S, Katsoulis M, Chang WH et al. Estimating excess mortality in people with cancer and multimorbidity in the COVID-19 emergency. Pre-print 2020; https://doi.org/10.1101/2020.05.27.20083287
6. Baskar R, Lee KA, Yeo R & Yeoh KW. Cancer and radiation therapy: current advances and future directions. Int J Med Sci. 2012;9(3):193-199. https://doi:10.7150/ijms.3635

Expected Benefits:

This project aims to understand why changes were made to RT treatment schedules across the UK, whether there were different impacts in different countries, to understand the impact on radiotherapy services and the potential impact to come for services and patients as a result of these changes. It will also lay the ground work for a follow up study to understand the impact of these changes on outcomes

NHS cancer services have been put under considerable strain throughout the ongoing COVID-19 pandemic. Evidence is urgently needed to help inform the recovery of services and how to prepare for future pandemics. This study aims to provide that evidence.

These data were captured at the height of the pandemic by NHS clinicians who were extremely busy and under extreme pressure. They did this because they recognised the data were vital in understanding how cancer care was being impacted and how best services could adapt to maintain optimal outcomes for patients. Sharing these data is in the public interest as if they are not analysed then we will not understand the impact of COVID on radiotherapy of which over 130,000 patients receive this treatment in the UK each year. This study has the potential to improve patient outcomes immediately and in future.

The proposed analyses will directly quantify the changes in care that the COVID-19 pandemic induced as well as the reasons why. These data are not available from any other source. As such, they are the only data available to achieve our stated aim of understand why changes in radiotherapy treatment schedules were implemented during the pandemic.

Non-identifiable data are being processed to understand the impact COVID had on an expected cohort size in excess of 50,000 patients who received Radiotherapy during 2020 and early 2021. The results of the study are to inform the service of how this impacted patients and ultimately, how this impact affected patient outcomes so that the learning can be shared back with the health services to prevent any further negative impact for patients across the UK and indeed for any other country worldwide. The aim of the study is to understand the impact COVID had for patients receiving radiotherapy and therefore to provide evidence for current and future decision making. There is no current evidence of the impact covid had on radiotherapy. There is anecdotal evidence that patients planned treatment of radiotherapy had been changed, that patients who would normally get radiotherapy didn’t and that patients who wouldn’t normally receive radiotherapy received it due to the impact to other treatment. It is imperative we understand the impact on patients in order for the health service to make the right decisions for patients now and in the future.

Data have specifically been collected for this study and are therefore the essential component of the study.

The outputs of this study have the potential to inform health services decisions as COVID continues to affect people’s lives and to plan and respond to future pandemics. It has the potential to benefit hundreds of thousands of patients in the event of another coronavirus pandemic in the UK and far more worldwide.

Benefits of the study could start to be achieved immediately and therefore further delays to undertaking the study could lead to patients not being able to benefit from the results of this study .

Outputs:

As a result of data processing, the following outputs (but not limited to) are likely to be produced:

reports – grey literature reports published by CRUK or the NCRI, written by the project team. Grey literature is not peer-reviewed but can include reports, pre-prints, blogs etc., all of which CRUK may use as part of publishing results from this study. https://library.leeds.ac.uk/info/1110/resource_guides/7/grey_literature
submissions to peer reviewed journals will be made as a result of this study to ensure peer review process and confidence in the results of the study
presentations –results showing analyses that are publishable will be used in presentations wherever opportunities exist that could improve our knowledge of the impact of COVID and therefore be beneficial for patients
conferences – as with presentations, results are likely to be presented at relevant conferences.

The level of data contained in the outputs will be aggregated data with small number suppression applied. Any aggregated data contained in any output will meet Cancer research UK’s statistical disclosure policy.

The results of this study and the communication plan for results will be determined in order to provide vital information of the impact of covid to radiotherapy providers and health services across the UK and will be of use to countries worldwide. The results in peer reviewed journals will provide the scientific community with further understanding of the impact of COVID on cancer and contribute to improvements for patients from the current COVID pandemic and any similar future pandemics .

All outputs and communication regarding this study will be undertaken only with agreement from the study team.

The project was initiated, shaped and developed by NCRI’s CTRad executive group, which includes patient and public representatives. These patient representatives were able to provide feedback on the study design. Three webinars were also held in the planning stages at which patient representatives were also present.
The study will continue involving patient and public representatives throughout its course. The study team will continue to use existing PPI collaborations to ensure they are able to contribute to both the analyses and the dissemination of findings. This will include individuals in the NCRI patient and public forum, those who collaborate with CTRAD and the panels already established in the collaborating academic centres

The study team is 12 months post planned target dates. Due to the ongoing impact of COVID the study team intends to analyse these data and publish them as soon as possible so that the results can inform health services and benefit patients

Processing:

There will be no flow of identifiable information into NHS Digital.

There will be no flow of identifiable information from NHS Digital. The data that will flow to CRUK will be pseudonymised, record level, special category health data.

There will be no subsequent flow of data once the transfer of data from NHS Digital to CRUK has occured. Only outputs of analyses that meet CRUK’s statistical disclosure policy will be released from the SDE in accordance with CRUK policies.

The following steps summarise the data journey for this study:

Identifiable data captured directly by cancer centres with each Caldicott Guardian’s approval has already been collected by NHS Digital.

These data will be pseudonymised by NHS Digital and transferred securely on to the CRUK Trusted Research Environment hosted by AIMES. CRUK and Leeds will be joint data controllers, with AIMES a data processor.

Aggregated data will then be released from the Trusted Research Environment for outputs of the study. Before these data can be released from the TRE they will be subject to assessments to ensure they are anonymised in line with NHS Digital and CRUK policy.

Data will be analysed using statistical software packages to create summary statistical outputs, with calculated confidence intervals. Data will not be linked in this study. However, datasets from England, Wales, Scotland and Northern Ireland will be pooled to create a UK wide dataset.

As linkage is not being undertaken and the data received will be pseudonymised, no steps are being undertaken to mitigate the risk of re-identification via linkage. However, steps will be taken to remove all identifying variables and pseudonymise the dataset prior to it being released from NHS Digital to the research team.

No date are being matched to publically available data and so no steps are being taken to mitigate the risk of re-identification.

There will be no requirement/attempt to re-identify individuals in the dataset.

Data processing of the data disseminated by NHS Digital is only carried out by substantive employees of the listed data processors (CRUK) who have been appropriately trained in data protection and confidentiality. Data will only be processed for the purposes as set out in this data sharing agreement.

All data will be stored on the CRUK Secure data environment, detailed below, and accessed securely via remote login, secured using two factor authentication. Data cannot be removed from the SDE. Only aggregated outputs can be requested to be released from the SDE which are checked to meet CRUK’s statistical disclosure policy before being released from the environment

The data will be stored on a Trusted Research Environment, namely CRUK’s Secure Data Environment. This environment, provided and managed by Aimes, is ISO27001, 27017, and 27018 accredited and works to the NHS DSPT standards. All data will be held on encrypted servers belonging to and located at Aimes’ offices:

The role of AIMES is purely to provide the secure infrastructure for these data to be securely stored and accessed by the named individuals who will be analysing these data. AIMES are not part of the project team, will not analyse these data and are not involved in any decision making of the study.

MR503 - Adjuvant Tamoxifen Treatment - Offer -More? - ATTOM — DARS-NIC-148286-3RWRG

Opt outs honoured: Yes - patient objections upheld, Identifiable, Anonymised - ICO Code Compliant, Yes (Section 251, Section 251 NHS Act 2006)

Legal basis: Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007 , Section 251 approval is in place for the flow of identifiable data, National Health Service Act 2006 - s251 - 'Control of patient information'. , Health and Social Care Act 2012 – s261(7), Health and Social Care Act 2012 – s261(7), Health and Social Care Act 2012 – s261(7); Other-Section 251, National Health Service Act 2006 - s251 - 'Control of patient information'., National Health Service Act 2006 - s251 - 'Control of patient information'.; Other-Section 251

Purposes: Yes (Academic)

Sensitive: Sensitive, and Non Sensitive, and Non-Sensitive

When:DSA runs 2019-03-18 — 2022-03-17 2018.03 — 2021.12.

Access method: Ongoing, One-Off

Data-controller type: UNIVERSITY OF BIRMINGHAM

Sublicensing allowed: No

Datasets:

  1. MRIS - Cause of Death Report
  2. MRIS - Cohort Event Notification Report
  3. MRIS - Scottish NHS / Registration
  4. Civil Registration - Deaths
  5. Demographics
  6. Cancer Registration Data
  7. MRIS - Flagging Current Status Report
  8. Civil Registrations of Death

Objectives:

Background Information
Breast cancer is the most common female cancer. In the 1990’s 5-years of tamoxifen treatment was the standard but there was uncertainty as to whether tamoxifen should be given for longer. The aTTom (Adjuvant Tamoxifen Treatment - Offer -More?) trial, which commenced in 1991, was designed to determine if giving tamoxifen for longer than 5 years was beneficial. aTTom is a clinical trial of an investigational medicinal product and falls under the clinical trials regulations for medicinal products.

The original 10-year follow-up period for the aTTom trial patients was in reached October 2015. However long term toxicity remains a concern and continued follow-up of these patients is vital to determine the impact of extended tamoxifen on breast cancer specific and overall survival. To this end (and following the recommendations of the Medicines and Healthcare products Regulatory Agency) ethical approval (research ethics and CAG approval) has been sought for a follow-on study called aTTom-Extended (Extended follow-up of patients enrolled in the aTTom trial). aTTom-Extended falls outside of the remit of clinical trials governing medicinal products. aTTom-Extended will continue to follow-up the aTTom patients for an additional 10 years (REC specified end date December 2027).

Data Controller
The University of Birmingham requires mortality data and data on any new cancer registrations relating to the cohort for use in the aTTom/aTTom-Extended studies for the purpose described below.

Organisations Involved
aTTom and aTTom-Extended are sponsored (in accordance with the Research Governance Framework for Health and Social Care) by the University of Birmingham which is the Data Controller. The Chief Investigator is based at the University of Birmingham. The CRCTU is one of two trials units within the University of Birmingham the other being the Birmingham Clinical Trials Unit (BCTU) which is responsible for the analysis of aTTom (performed by the Trial Statistician). The statistical lead moved from the University of Birmingham to the University of Oxford in September 2010. Under this Data Sharing Agreement this individual is not permitted to access the data. The University of Birmingham expects to enter into formal contractual arrangements with the University of Oxford which would enable the latter to become a data processor on behalf of the former. Once that is signed, the University of Birmingham will provide a copy of the signed contract and apply for an amendment to this Data Sharing Agreement to authorise access to the data by the statistical lead and his team.

Information about patients with breast cancer who took part in the aTTom trial was collected from NHS organisations (oncology hospitals and General Practitioners) in compliance with the clinical trials regulations, this included patient identifiers and medical information about the patients breast cancer diagnosis and treatment in addition to date and cause of death (where known). This data was collected on a Case Report Form (CRF) and supplied to the aTTom Study Office, University of Birmingham where it was entered onto the trial database. Data from NHS Digital is also supplied to the aTTom Study Office, University of Birmingham and date and cause of death entered into the same trial database.

The data supplied by NHS Digital will only be accessed by individuals with Approved Researcher accreditation who hold substantive contracts with the University of Birmingham. Ethics and ONS approval was granted in January 2015 to send the date and cause of death received from ONS to the NHS organisation treating the patient to clarify discrepancies in the data supplied by the NHS organisation and to request additional information about site and date of recurrence of the patients breast cancer. This practice will come to an end when the aTTom trial is closed with participating NHS organisations which is planned for the end of 2017. Other than this exception, access to data supplied by NHS Digital will be restricted to individuals, working under appropriate supervision on behalf of the University of Birmingham, who are subject to the same policies, procedures and sanctions as substantive employees of this organisation.

Why is This Work Being Undertaken?
The University of Birmingham is undertaking this work to improve the care of patients with breast cancer not only in the UK but worldwide. Breast cancer is the most common female cancer, with over 45,000 new patients diagnosed in the UK per annum and 1.1 million worldwide. Five years of tamoxifen treatment remains the standard of care for many women worldwide with oestrogen receptor positive breast cancer but there remains uncertainty as to whether tamoxifen should be given for longer. Ultimately this work could save the lives of thousands of women per annum. The continued provision of date and cause of death is vital to this goal.

Aims of the Work
The objective of the aTTom trial is to determine if treating women with oestrogen receptor positive breast cancer with adjuvant tamoxifen treatment for an additional 5 years above the current standard of care is better in terms of disease-free survival, overall survival and late toxicity. The original intent was to follow aTTom patients annually for at least 10 years after recruitment. This time point has now been met and preliminary analyses performed. However late toxicity remains a real concern. This will be addressed by continued collection of ONS survival and cause of death data as part of aTTom-Extended.

Other Relevant Background
The aTTom trial randomised 8863 women from 178 UK hospitals between July 1991 and March 2005. Data has been received from ONS since its conception in the mid-1990s. The overall objectives for aTTom (and latterly aTTom-Extended) have remained the same.
The aTTom trial has been funded by a number of organisations over the years including the Medical Research Council and more recently Cancer Research UK.


Date and cause of death are required from ONS via NHS Digital in order to perform Kaplan-Meier disease-free and overall survival analyses for the aTTom/aTTom-Extended trials and to determine other potential causes of death (e.g. endometrial cancer). For aTTom this data was collected to provide missing data for patients taking part in the trial who were no longer seen by a medical practitioner or were lost to follow-up for the purposes of the trial. For aTTom-Extended data provided by ONS will be the only source of data for these analyses.

Yielded Benefits:

Tamoxifen is still in widespread use and is saving thousands of lives world-wide. The aTTom trial has shown that taking tamoxifen for 10 years is more effective than taking tamoxifen for 5 years. Many women are now being advised to take tamoxifen for 10 years. Tamoxifen can often lead to side effects such as hot flushes. Putting up with these for 10 years can be quite a burden for some patients. Rare but serious side effects from tamoxifen include an increased risk of endometrial cancer (cancer of the womb lining). The aTTom-Extended study was recommended by the Medicines and Healthcare products Regulatory Agency to continue the long term follow up of patients enrolled into this study. No benefits have yet been yielded as a result of the aTTom-Extended study.

Expected Benefits:

The intention is to analyse the data at sequential time points and to publish this information in peer reviewed journals.

The benefit in analysing and publishing the aTTom data are that they will allow clinicians to make evidence based decisions for women with early breast cancer taking endocrine therapy. Acting on this data on a world wide scale will potentially save many relapses and deaths from breast cancer in the future but clinicians need to see long term data on breast cancer events and overall survival

The magnitude of any effect in aTTom is incompletely captured at present which is why long term follow up is essential to capture late events.

Tamoxifen is an inexpensive drug so drug costs are a minor component to any cost benefit analysis. The data from aTTom will allow clinicians to provide individualised advice on the risks and benefits of extended adjuvant therapy based on the individual risk of late recurrence. The higher the risk the greater the impact of treatment in reducing risk will be.

Because individualised decisions will be made making detailed calculations of the health economic benefits is a complex project which can only be accurately conducted with complete data. Extrapolating from the data there is the potential to reduce cancer mortality by 2-3% if the whole population is treated but if a risk stratified approach is used then the absolute reduction will be somewhat smaller in the whole population but can be much larger in the treated group is restricted to high risk cases such as node positive disease only. Different approaches will be used in different parts of the world.

aTTom is one of only two adequately powered studies designed to determine the clinical utility of extended adjuvant tamoxifen after 5 years of prior tamoxifen. The ATLAS study has already published the first analysis of the data from the hormone receptor positive subset (hormone receptor unknown cases have been excluded from this analysis). This study shows a significant reduction in breast cancer relapse and breast cancer death. aTTom has reported preliminary findings in abstract form only showing very similar results but has not yet submitted to a peer reviewed journal as further follow up for overall and breast cancer specific survival was needed.

The preliminary results of the aTTom trial in the context of ATLAS are already impacting on International guidelines such ASCO, National Comprehensive Cancer Network (NCCN) and St Gallen International Breast Cancer Guidelines. These guidelines are provisional based on the abstract reports and are subject to review pending the full manuscript publication of aTTom and updated analysis from ATLAS. The National Institute for Health and Care Excellence (NICE) are currently updating guidelines for the management of early breast cancer and will only cite peer reviewed journal articles thus the publication of aTTom is of critical importance to the completeness of an ongoing NICE work stream. Ahead of NICE the association of Breast Surgeons (ABS) and the UK breast cancer group UK Breast Cancer Group (UKBCG) are currently formulating adjuvant endocrine therapy guidelines.

The continued collection of data and the subsequent publication of future analysis is essential to ensure that the recommendation to continue tamoxifen treatment for up to 10-years do not have any foreseen long term negative health effects or that where these do exist such as the known increased risk of endometrial cancer and endometrial cancer death are as fully documented as possible. Target dates are as specified in response to the specific outputs question.

aTTom is a high profile study which has been presented in provisional format at an ASCO and ESMO plenary sessions. The current findings are very widely known and the peer reviewed manuscript will be submitted to the Lancet which has a very high impact factor thus information will be very well publicised and readily available to guideline groups and individual breast cancer clinicians making patient level recommendations.

In summary ongoing analysis of the aTTom trial will result is a series of future publications that will add to the totality of evidence of the benefits and possible harms of extended adjuvant tamoxifen. This data is essential to policy makers and clinicians to guide treatment decisions for patients in the future.

Outputs:

The outputs produced for aTTom to date include presentation of the preliminary results of the trial at the American Society for Clinical Oncology (ASCO) (Journal of Clinical Oncology 31, No.18 Suppl: 5-5) and at the European Society for Medical Oncology (ESMO) (European Journal of Cancer 49, Suppl 2, S1-S1028) in 2103. The results were presented as plenary presentations at these auspicious oncology meeting. The results demonstrated a relapse-free survival benefit for extended tamoxifen treatment. However an increase in endometrial cancer was also reported. This work has yet to be published as further follow up for overall and breast cancer specific survival was needed prior to publication and there have been subsequent delays caused by issues with ONS data access.

The intent is to publish this work in the Lancet Oncology (a high impact peer review journal) as soon as possible. A draft publication has been written but further analysis is on hold pending the approval of this application. Any resultant publication will be open access. It is anticipated that there would be a press release from Cancer Research UK and the University of Birmingham associated with the publication of this paper.

Further publications in peer reviewed journals are also planned on long term toxicity and survival.

A lay version of the findings will be made available on the Cancer Research UK aTTom website and on the CRCTU aTTom website.

All outputs will contain only data that is aggregated in line with the ONS and HES Analysis Guide.

Processing:

Data Flow
ONS data is received from NHS Digital. The data is provided to the Operational Director of the CRCTU within the University of Birmingham.

The downloaded files are saved in a restricted access folder on a clinical trials server within the University of Birmingham’s CRCTU. Patients within the downloaded files are identified by supplied member number and name. The patient’s date and cause of death and information on new cancers are manually entered into the relevant patient record within the aTTom trial database (i.e. the two datasets are combined). The files downloaded from the Data Exchange Service and the aTTom trial database are stored in separate areas of the same clinical trials server. Only approved researchers who are substantive employees of the University of Birmingham have access to this folder and the aTTom database.

Permissions to the database are granted by the CRCTU Database administrators. Permissions to the restricted access folder are granted by the CRCTU IT team.

Data containing no identifiers other than the patient’s unique trial number, date of birth, date and cause of death (obtained from the NHS or ONS) in addition to the medical data collected for the trial, is extracted for analysis from the trial database using remote access methods by the trial statistician who is based in BCTU. Data downloads are taken for statistical data cleaning, presentation, or publication. The first planned publication being after 10-years of follow has been completed as part of the aTTom trial. The statistical output is saved in a restricted access folder on the BCTU clinical trial server.

Patient record level data from ONS will not be made available to any third parties other than those specified except in the form of aggregated outputs in line with the HES Analysis Guide. For clarity, no data will be shared with the University of Oxford or individuals from the University of Oxford under this Data Sharing Agreement.

ONS terms and conditions relating to the data being shared under this agreement will be adhered to.

Record level data or data containing small numbers will not be shared with any other organisation.

All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract .i.e: employees, agents and contractors of the Data Recipient who may have access to that data).