5 May 2021

Present

Professor Julietta Patnick (Chair) (JP)

Dr Isobel Barnes (IB)

Professor Dame Valerie Beral (VB)

Mrs Claire Borrelli (CB)

Dr Lucy Carpenter (LC)

Mrs Annie Hogg (AH)

Professor David Hunter (DH)

Mrs Jacquie Jenkins (JJ)

Associate Professor Hongchao Pan (HCP)

Professor Sir Richard Peto (RP)

Professor Malcolm Reed (MR)

Professor Gillian Reeves (GR)

Professor Sir Mike Richards (MAR)

Mr Keith Shaw (KS)

Dr Louise Wilkinson (LW)

Dr Suzanne Wright (SW)

Ms Krys Baker (KB) - minutes

1. Welcome and introductions

JP welcomed TMG members and investigators. It was noted that Annie Hogg wished to resign as a lay member of the TMG.

2. Minutes of the last meeting (30/04/2020) and matters arising

The minutes of the last meeting were accepted as an accurate record.

3. Numbers randomised 

In March 2020, at the start of the national coronavirus lockdown, NHS Breast Screening Centres suddenly stopped their work, so they also ceased randomising women into AgeX. It was expected that when the Centres resumed offering screening, priority would be given to inviting the backlog of women aged 50-70 who had missed their routine appointments because of the lockdown, so any attempt to restart AgeX would be given low priority. Hence, in May 2020 the AgeX investigators decided to cease randomisation into the trial, with the last randomisations having been done just before the end of March 2020. (Those randomised to be invited but not yet screened by the end of March 2020 would be screened some months later, and remained in the trial.)

From 2009-2020, AgeX cluster-randomised some 2.8 million younger women (age about 47- 49, in 21,000 clusters) and 1.8 million older women (age about 71-73, also in 21,000 clusters) to receive, or not, one additional breast screening invitation.

4. Progress report 

4.1  As specified in the protocol, the main analyses will be of all randomised women without prior cancer or breast disease who would have been likely, if invited, to undergo mammographic screening and be electronically followed up. These unbiased exclusions (which improve mean compliance among those in the main analyses) reduce the main analyses to only about 2 million younger and 1 million older women. Linkage to further national datasets that will arrive during 2021 will determine the numbers that will be in the main analyses of outcomes by random allocation.

4.2   Randomisation ended in March 2020, but electronic follow-up continues indefinitely. Follow-up involves linkage to several different national databases to determine cause-specific mortality; hospital admissions; breast cancer incidence; and information about the characteristics and treatment of any breast cancers. The relevant datasets all get provided to AgeX but arrive intermittently (typically about once a year) and are sometimes delayed, but these problems are settling down.

4.3  All AgeX screening clinics are in England. Public Health England (PHE) was set up in 2013 and became responsible for all screening. PHE is now being abolished. Later in 2021 AgeX is expected to revert to NHS control, and PHE-controlled databases that AgeX uses are expected to come under the control of NHS Digital. It is expected that this transition will not disrupt AgeX governance or follow-up.

4.4  The investigators hope to publish the protocol and some results (but not on mortality) as soon as electronic linkage to all the relevant datasets is available for all participants. Unblinded mortality results are not expected to be reported until there has been follow-up to 2026. This timescale was endorsed by the 2018 Parliamentary enquiry into breast screening, and accepted by the Government in both Houses of Parliament in 2018.

5. DMEC report to TMG April 2021

The DMEC report was presented to the TMG congratulating the breast screening units and trial team on the continued successful progress of the trial. Of particular note were the continued high quality and timely data linkages. There were no concerns raised from the DMEC.

6. Other communications and correspondence

Communication directly from participants comprised a small number of women wishing to opt- out of the trial. A favourable opinion to continue the trial was received from CAG, following submission of the annual report. Both the ethics committee and R&D departments at Hospital Trusts have been informed that randomisation into AgeX has ceased.

7. Any other business

There was a discussion regarding women who had been invited for screening for AgeX before the pandemic, who had not been screened due to screening centres suspending screening.

The trial investigators were assured that these women would have been prioritised once breast screening had resumed and that they all should have been offered a screen. 

8. Date of next meeting

It was agreed that the next AgeX TMG would take place in mid-2022.