The National Health Service (NHS) routinely offers breast screening every 3 years to all UK women aged 50-70. In 2012, an independent panel concluded that, while routine breast screening at ages 50-70 confers significant benefit to UK women, the advantages and disadvantages of starting breast screening at younger or older ages were uncertain (read report).
The AgeX trial will assess reliably the risks and benefits of offering an extra screen to women aged 47-49 (who will all be offered routine screening anyway three years later) and, separately, of offering additional screening to women after age 70 (who will already have been offered routine screening every 3 years at ages 50-70). Click here (PDF) for a copy of the AgeX Trial protocol.
The trial began in 2009, eventually involving about five-sixths of the 78 NHS breast screening centres in England (participating centres), and by the time randomisation ended in March 2020 it had randomised more than 4 million women to receive, or not receive, one additional breast screening invitation. The screening centres in England that did not participate were mainly those that used non-standard methods to invite women for screening. Screening records of trial participants are linked electronically with routinely collected government records to help assess the short-term and long-term effects of the additional screening.
In the participating screening centres groups of women (clusters) have been allocated at random, like tossing a coin, either for only the younger members of the whole group to be sent an additional screening invitation, or for only the older members of the whole group to be sent an additional screening invitation. A typical cluster might include a few dozen or a few hundred women who live near each other aged 47-49 or aged 71-73. All women in these age ranges in the cluster who are randomly allocated not to be invited, also join the trial as controls. For each separate age range the study will compare, over the next decade or so, what happens to women in the clusters invited for screening and in the clusters not invited.
This trial was embedded within the routines of the NHS breast screening programme in England, which currently uses two-view digital mammography. Other than randomisation, all aspects of screening was conducted exactly as normal in the breast screening programme, following its routine procedures.
The government’s Independent Breast Screening Review, published in December 2018, reviewed the governance and other aspects of AgeX. It recommended that “The AgeX Trial should continue until its planned end date, currently 2026, to enable the most extensive analysis possible of the impacts of extending the breast screening programme both in the younger and older age groups.” The Health Minister’s Parliamentary Statement, made at the same time as the Independent Breast Screening Review report was released, also recommended continuation of AgeX as planned.
Following the suspension of routine breast screening throughout the UK in March 2020 due to COVID, and the substantial and prolonged overload on breast screening services to be expected when screening re-starts, the AgeX investigators decided in May 2020 that further randomisation into AgeX should cease permanently. The trial itself will not cease, however, as follow-up by electronic linkage to routine government records continues throughout the 2020s and beyond. For breast cancer mortality the first report is scheduled to be on the follow-up to 2026, after which there will be subsequent reports on longer follow-up.
As in many trials, the interim mortality findings are kept under regular review by an independent Data and Safety Monitoring Committee, and are known only to this Committee (and those preparing the confidential reports to it). The decision that randomisation would cease permanently after March 2020 was taken by AgeX investigators who will remain unaware of the interim mortality findings until 2026.
FREQUENTLY ASKED QUESTIONS
Who is organising the trial and who is paying for it?
A team at the University of Oxford serves as the co-ordinating centre for the trial (further details). Funds from the Department of Health and Social Care were allocated to Public Health England for the additional screening invitations of women in the trial. Data analysis is funded by a quinquennial grant to Oxford from Public Health England and by the quinquennial core support for the Cancer Epidemiology Unit and the Population Health Research Unit (both in the University of Oxford’s Nuffield Department of Population Health) from the Medical Research Council and from Cancer Research UK.
How will information about trial participants be obtained and used?
The national breast screening database provides the investigators with information on trial entrants that includes patient identifiers needed for electronic record linkage to routinely collected NHS data held by NHS Digital and by Public Health England.
NHS Digital holds routinely collected NHS health records for England, including hospital admission data, cancer registrations, and death records, some of which are supplied by the Office for National Statistics (ONS), sourced from civil registration data. NHS Digital provides the study team with electronically linked information about these outcomes for individual women in all clusters whether or not they were invited for screening. To do this, identifiable data including name, NHS Number and date of birth is supplied by the study investigators to NHS Digital. Linkage to patient-identifiable data without consent and for access to medical records by those outside the healthcare team, has been approved under Section 251 of the NHS Act 2006. Public Health England provides investigators with information about screening history and further details about cancers.
The linked datasets provided to the study team are stored securely in accordance with the Data Protection Act and procedures and policies of the University of Oxford. Once provided, however, all these records are made anonymous so the researchers using them will not be able to identify any individual.
No direct contact with study participants will be made by the research team, and the statistical analyses and reports will all be of anonymised data. The data will be held only at the University of Oxford. No data has, or will be, released or shared in any form that would enable individual participants to be identified. Participants can request more information about how their data are being used by writing to the address given below.
Can participants opt out if they do not wish to be part of the trial?
Participants who wish to opt out of the trial should write, giving the single word “OPT-OUT” and their name, address and date of birth to: AgeX Trial Co-ordinating Centre, CEU, Richard Doll Building, Oxford OX3 7LF. This will in no way affect their screening or any treatment they receive.
What approvals have been obtained for the trial?
Ethical approval was obtained in 2010 and again in 2016 from Ealing & West London (now Harrow) Research Ethics Committee (ref: 10/H0710/9). Section 251 support for the trial was approved by the National Information Governance Board Ethics & Confidentiality Committee (ref: ECC 1-04 (b)/2010). The trial is registered under the Data Protection Act (Z575783X). The data security processes are approved under the NHS Information Governance Toolkit; and conform with Oxford University’s Information Governance and Information Security Policies (available here).
Where has the trial been registered?
Registrations are at ISRCTN33292440 (click here) and NCT01081288 (click here).