NHS Digital Data Release Register - reformatted
Cancer Research Uk
Project 1 — DARS-NIC-148286-3RWRG
Opt outs honoured: Yes - patient objections upheld
When: 2016/04 (or before) — 2018/12.
Legal basis: Section 251 approval is in place for the flow of identifiable data, Approved researcher accreditation under section 39(4)(i) and 39(5) of the Statistical Registration Service Act 2007 , National Health Service Act 2006 - s251 - 'Control of patient information'.
- MRIS - Cause of Death Report
- MRIS - Cohort Event Notification Report
- MRIS - Scottish NHS / Registration
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.
The data supplied to the University of Birmingham will be used only for the approved medical research project.
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.
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.
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).