TMG minutes 2011 to 2021

11 January 2012, 11:00 – 12:00 ** Phone conference **

4. Proposal to extend the trial at older ages
 
A proposal has been submitted to the Health Technology Assessment (HTA) programme to extend the trial by inviting the women randomised in aged 71-73 for a further two extra screens (at ages 74-76 and 77-79 years). This is important because it would provide a bigger signal as to the effect of continuation of screening and provide a clear result by 2020, with no chance of a false negative result. It would also mean that the effect of screening for each separate age group could be seen.

In response to the queries raised by the HTA regarding how extending the trial to older ages would increase the power of the study, Richard Peto read the reply he provided to the HTA (see below).

Thanks for your thoughtful letter. I'd like to talk over my concerns, but meanwhile please read the attached revision of the age extension study protocol, and in particular the "Statistical power" section on page 6. We could well get a false negative for the effects of adding an early screen at ages 47-49, in which case the effects at ages 70+ need to be overwhelmingly reliable. At these older ages, however, if women were randomly allocated 0, 1 or 2 extra screens after 70 (in the ratio 2:1:1) then a trend test would have about the same power as randomisation of 0 vs 1 extra screens (in the ratio 2:2), but a trial of 0 vs 2 extra screens (in the ratio 2:2) would have a lot more power, especially for breast cancer deaths at ages 75-84. The appropriate criterion isn't just "power to detect at p=0.01", however; what we need is a narrow CI on the effects, and a p=0.01 result has a lower confidence limit of a negligibly small effect. A study of at least 2 extra screens vs none would offer this, and one of screening to age 79 would do so even better. If we get massively statistically reliable evidence about size of the effects of 2 extra screens, then we could infer reasonably reliably what just one would have offered, achieving what your HTA call was for in a more unambiguous way than a 3-way randomisation would.

Extending the trial for these two extra screening rounds would not affect the trial costs (for follow-up, record linkage etc). However there would be extra costs to breast screening units in providing more mammograms to the older women (1/6 of the women in the trial). This cost would increase gradually over time, and would not reach the full amount for a few years. The cost of these extra screens is estimated at £12m for 2 extra screening rounds.

It was agreed that it would be of great benefit to extend the trial for two extra screens in the upper age group. Subject to ethical approval, this could be tested in the 5 pilot sites by inviting the women randomised in aged 71-73 for a further screen 3 years later; this would indicate what issues might arise, as well as the uptake rates and costs. There may be some reduction in treatment costs due to cancers being detected earlier.

5. Any other business
 
The group were told about a separate trial that is being undertaken to look at treatment versus no treatment in low risk DCIS. This trial should shed light on the debate over under diagnosis and over–treatment.

6. Date of next meeting
 
It was agreed that the next meeting of the Trial Management Group should be January 2013 and should be coordinated with the meeting of the Data Monitoring and Ethics Committee.

Action: Kath Moser to circulate an email to fix a date for the next meeting of the Trial Management Group.

11:00 – 13:00 Cancer Epidemiology Unit, University of Oxford

Present

Professor Julietta Patnick (Chair)

Professor Dame Valerie Beral

Dr Lucy Carpenter Kath Moser

Professor Sir Richard Peto

Professor Amanda Ramirez

Professor Malcolm Reed

Professor Sir Mike Richards Sarah Sellars

Margot Wheaton Richard Winder

In attendance

Professor Janet Darbyshire Jenny Rusby

Hayley Abbiss (notes)

Apologies

Dr Robin Wilson

Documents circulated in advance:

• Agenda
• Draft revised trial protocol (Dec 2012)
• Draft patient information leaflet (Dec 2012)
• Minutes of TMG meeting 11 January 2012

Documents circulated at meeting:

• Trial progress at end of 2012; graphs of trial cumulative numbers by date
• Article: Extending the age range for breast screening in England: pilot study to assess the feasibility and acceptability of randomization (JMedScr)
• Article: The benefits and harms of breast cancer screening: an independent review (The Lancet)

1. Welcome and introductions (Julietta Patnick (JP))

Janet Darbyshire (JD) and Jenny Rusby from the trial Data Monitoring and Ethics Committee (DMEC) were welcomed to observe the meeting.

It has been one year since the last TMG meeting (by telephone conference). Progress on revising the protocol and information leaflet was delayed while we awaited the outcome of the Marmot Review. The Review (reporting at the end of Oct 2012) supported the continuation of the screening programme and, importantly for this trial, said “The impact of breast screening outside the ages 50-69 years is very uncertain. The Panel supports the principle of the ongoing trial in the UK for randomising women under age 50 and above age 70 to be invited for breast screening.”

2. Minutes of the last meeting (11 January 2012) and matters arising 

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

Matters arising:

Sarah Sellars (SS) gave an update on digital mammography: out of the 80 breast screening units, 66 were now fully digital and 4 had no digital machines (due to drop to 3 by the end of Jan 2013).

Kath Moser (KM) confirmed that the complaint received from a patient randomised in aged 72 had been referred to Janet Darbyshire (JD), Chair of the DMEC.

JP reported that the National Research Ethics Service recently received a Freedom of Information Request about the trial; they are going to supply the information requested with names redacted.

3. Trial update

a) revised protocol and patient information leaflet

Following the outcome of the Marmot Review the protocol and the trial patient information leaflet have been revised.

The group discussed the protocol and some further minor revisions were suggested. It is not intended to revise the protocol again and therefore it needs to be phrased in such a way to avoid necessitating further revision. KM confirmed that all members of the TMG will be co-authors of the protocol, and linked publication, as agreed at the TMG Jan 2012. JD requested that her DMEC membership details be amended to remove ‘statistician’ and replace with ‘epidemiologist’.

Action: KM to amend JD’s details.

Any further comments to be sent to KM by 18 January. KM to action the changes already agreed and any further suggested changes.

Action: All to send any further comments regarding the protocol to KM by 18 January 2013.

Finalising the protocol will be delegated to the co-investigators. Once finalised, the revised protocol will be submitted to the ethics committee as part of a notice of substantial amendment.

Action: KM to make further revisions to protocol and patient information leaflet and send to Ethics for approval, by end February 2013.

It was agreed that the final protocol should be submitted to a journal for peer- reviewed publication. Lancet Oncology was suggested.

Action: KM to submit protocol to journal for publication.

JD suggested that the co-investigators develop a statistical analysis plan although the full plan could be finalised at a later date before conducting the final analysis.

Action: Co-investigators to consider developing a statistical analysis plan.

The TMG agreed the appointment of Dr Gillian Reeves (GR) as the independent statistician on the DMEC. It was noted that GR, being located within the Cancer Epidemiology Unit, will have access to data that will not be available to the TMG, and as such the proprieties of the role must be observed in order not to compromise the integrity of the trial.

The revised patient information leaflet, which will form part of the published protocol, was discussed. Many comments were made and amendments suggested. It was agreed that some further extensive revisions were required following which it would be circulated again.

Action: KM to further revise the patient information leaflet and circulate by 18 January 2013 for approval.

The possibility that a woman may wish to attend for screening but opt out of the trial was discussed. However the TMG agreed it was not necessary to mention this within the leaflet as, should a woman object to being in the trial, then she could be removed from the trial analysis at that time.

b)   progress to date

KM described trial progress as outlined in the 2 circulated handouts. An estimated 800,000 women have now been randomised. As there was not time to describe other aspects of progress it was agreed that KM would circulate the committee with this information.

Action: KM to email the TMG with an update on progress.

4. Any other business

Proposal to extend the trial at older ages

Richard Peto (RP) highlighted the benefits of extending the trial by inviting the older women who had been randomised in aged 71-73 to a further two extra screens (at ages 74-76 and 77-79 years). Life expectancy in women is increasing and women in their mid 70’s are generally still in good health. Stopping sending invitations could send the message that there is a lowering of risk, which is erroneous. Offering this additional screening will add to the power of the trial.

The 5 pilot sites started randomising women in June 2009. As this is over 3 years ago, there would be older women who had been randomised in aged 71-73 and who would now be eligible, once the approvals are in place, to be invited in the next screening round. By June 2013, five other centres will be in this position. VB said it was important to start offering additional screening to the older women as soon as possible so as not to miss too many women. JP commented that the units need time to prepare for the changes, but if ethical approval was obtained in March they should be able to start in autumn 2013.

The trial, as currently formulated, is mandatory. Discussions should be had regarding the compulsory/voluntary nature of offering additional screening beyond the age of 73. If this is not mandatory, some screening units will opt out due to workload issues and this could result in the participating units being unrepresentative of the whole.

Margot Wheaton (MW) commented that offering additional screening will require changes to the NBSS software.

Action: MW to start discussing computing implications and software developments required.

The costs of offering additional screening were discussed. Overall around 0.5M women could be offered additional screening after age 73. Costs incurred will include this additional screening, although uptake is not expected to be high, and also the computing development. It was agreed that Public Health England (PHE) should be approached now and with a view to seeking approval for 18 months funding (until March 2015), estimated at £1.5-2M, on the recommendation of the TMG. Mike Richards (MR) suggested that the group could use 2014/15 to make a case for requesting further funding in the following years, looking at the long run and potential for reduced costs. He suggested that once recruitment stops then the money saved could be used to continue screening the existing older women within the study as they age; the advantage being that a cohort getting older will give a more reliable answer.

Action: Submit funding request for additional 18 months to PHE.

VB suggested the possibility of going to a research funding body if PHE won’t provide funding.

MR suggested that the different options are costed at this stage so that it is clear what the funding profile will be. This was agreed.

Action: KM to prepare costings.

5. Date of next meeting

January 2014, date to be confirmed.

Action: KM/HA to email TMG with proposed date.

11:00 – 13:00 Cancer Epidemiology Unit, University of Oxford

Present

Professor Julietta Patnick (Chair)

Professor Dame Valerie Beral Kath Moser

Professor Sir Richard Peto

Professor Malcolm Reed Sarah Sellars

Margot Wheaton

Dr Robin Wilson Richard Winder

In attendance

Keith Shaw

Hayley Abbiss (notes)

Apologies

Dr Lucy Carpenter

Dr Kevin Fenton

Professor Amanda Ramirez Professor

Sir Mike Richards

Documents circulated in advance:

• Agenda
• Minutes of TMG meeting 9 January 2013
• Trial progress as at January 2014
• Data progress as at January 2014
• Report on study population data for the first 4 years of the trial
• Report on screening data for the first 3 years of the trial
• Report of the parliamentary inquiry into older age and breast cancer

1. Welcome and introductions

Keith Shaw (KS) was welcomed to the meeting. KS is Data Manager for the trial (Cancer Epidemiology Unit).

Kevin Fenton (KF), Director of Health and Wellbeing for Public Health England (PHE), has agreed to join the Trial Management Group. He sent apologies due to a prior commitment.

Apologies were received from Lucy Carpenter (LC) and Mike Richards.

Amanda Ramirez (AR) has resigned following a change in her job which means she is now focussing on clinical work.

2. Minutes of the last meeting (9 January 2013) and matters arising

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

Matters arising:

Julietta Patnick (JP) reported a positive meeting recently with Cancer Research-UK who were very supportive of the NHS Breast Screening Programme.

JP reported that she had received a complaint from Susan Bewley in November 2013 expressing concerns about the ethical and scientific underpinning of the trial.

3. Trial update (KM)

a)    Randomisation, numbers, data

There has been much progress in obtaining trial data over the last year and KS has been central in managing this process. Reports were circulated in advance of the meeting. KS confirmed there have been no issues with accessing the data from the Quality Assurance Reference Centres (QARCs) since their transfer from the NHS to PHE.

There are 9 breast screening units that have not yet started randomising. 6 of these plan to start by the end of March 2014. There is no start date for the remaining three. Sarah Sellars (SS) reported that from April 2015 all women are likely to be screened using digital machines.

Valerie Beral (VB) requested that all future reports be marked as confidential and that all such material should be treated confidentially and not discussed outside the TMG.

b)   Ethical approval, protocol

A substantial amendment (to cover linkage to HES and other NHS datasets; offer screening throughout their 70s to women randomised in aged 71-73; revise patient leaflet) was submitted to the Research Ethics Committee (REC) February 2013 but was not approved.

Julietta Patnick (JP), the principal investigator, has since had discussions with the Chair of the REC to clarify their concerns. The main issues are around the leaflet and informing the control group.

It had been decided that rather than put in an appeal, it was better to submit a new substantial amendment that only covered linkage to NHS datasets, and a revised patient leaflet.

JP and KM have been redrafting the leaflet, and Public Health England is now assisting in reformatting the leaflet. As soon as the leaflet is finalised we will go back to the REC with a new substantial amendment. References in the protocol to continuing to send invitations to women over 73 will be removed.

SS stressed the importance of the new leaflet not looking similar to the NHSBSP information leaflet that is sent to all women as this could cause confusion. MW was concerned that if the new leaflet was bigger than.at present it would impact on postage costs.

It was agreed that it was urgent to finalise the new leaflet and go back to the REC as soon as possible.

Malcolm Reed (MR) requested that the new leaflet is sent to the TMG before it is submitted to Ethics with the new substantial amendment.

Action: KM to send patient information leaflet to TMG before submitting it to the REC with the substantial amendment.

4. Discussion of future plans

Funding is needed to continue to offer screening to women (who were randomised in aged 71-73) throughout their 70s. JP estimated that offering screening to 74-76 year olds would cost an extra £4 million per annum. Due to cuts within the NHS and PHE they will not be able to provide additional funding. JP confirmed PHE are supportive of the TMG reorganising current funds in order to generate funding for offering screening to 74-76 year olds.

The Health Technology Assessment Programme will not fund the continuation of an existing trial. Richard Winder asked whether approaching public/private partnerships for funding was an option. The NIHR was suggested as a potential funder. RP warned it would be unwise to seek any commercial sponsorship and VB agreed funding would need to be at ‘arms-length’. It was agreed that the TMG should get approval from the Ethics Committee, calculate what funding is required, and then talk to Professor Dame Sally Davies.

JP highlighted the main problems would be obtaining funding and recruiting services. It was discussed whether offering one more screening round was deliverable. Margot Wheaton (MW) stressed that staffing levels across the service are currently at a critical level.

MR suggested a 3 prong strategy – (i) getting the protocol right (ii) obtaining ethics approval (iii) obtaining funding. The costs would need to be worked out in parallel with this.

JP is expecting to be called to give evidence to the Commons Select Committee on Science and Technology inquiry into National Health Screening. VB advised that she will be providing written evidence to the Committee. The deadline is 26 February 2014.

PHE supports the continuation of randomisation beyond the two screening rounds currently agreed. They will require good evidence before deciding to extend, or not, routine screening to women under age 50 and over age 70, and support randomising until such a point is reached. Evidence for the younger women should be available in the early 2020s, for the older women in the late 2020s. The primary endpoints are breast cancer mortality up to age 60 for the younger, and up to age 80 for the older, women. The Data Monitoring and Ethics Committee will advise the TMG when, in their opinion, there is proof beyond any reasonable doubt that an additional screening invitation at ages 47-49 years or at ages 71-73 years will reduce breast cancer mortality by age 60 or by age 80 respectively. It will then be up to the TMG to decide what to do.

5. Any other business

TMG membership.

SS, MW and Richard Winder are due to retire by Jan 2015. They were asked if they would be interested in staying on the TMG to contribute their expertise – all said they would be. Mike Richards has stepped back from the TMG but agreed to remain a semi-sleeping partner. Amanda Ramirez has resigned her membership of the TMG. Robin Wilson plans to retire in 2016 and so we will need to find a radiologist to replace him.

It was agreed to invite someone currently working in the screening programme. Suggestions included Kim Stoddard, Programme Manager for North London Breast Screening Service; Monica Dale, Breast Screening Superintendent Radiographer. RP proposed inviting Dr Hongchao Pan, from CTSU, who is involved in the Early Breast Cancer Trialists’ Collaborative Group.

Publications.

It was agreed that we cannot write substantive papers at this stage. We plan to publish the protocol once it has been finalised, possibly in Lancet Oncology or Health Informatics; some process data could be included.

Next years meeting.

MR requested a longer meeting next year in order to allow for academic discussions and to look at detailed numbers, costs and times. It was proposed to include some presentations including one from RP on screening women through their 70’s. JP requested that a time line be drawn up. The DMEC will be invited to observe the TMG meeting and attend the presentations. It was agreed that the DMEC meeting should follow on after the TMG meeting.

Action: KM to submit the new substantial amendment including the revised patient information leaflet to the Ethics Committee, as soon as possible.

Action: VB to submit written evidence to Commons Select Committee

Action: JP/KM to invite new members to the TMG

6.Date of next meeting

TBA

11:00 – 13:30 Cancer Epidemiology Unit, University of Oxford

Present

TMG Members

Professor Julietta Patnick (Chair)

Professor Dame Valerie Beral Kath Moser

Professor Sir Richard Peto

Professor Malcolm Reed

Dr Lucy Carpenter

Dr Hongchao Pan

Margot Wheaton

DMEC Members

Professor Janet Darbyshire

Professor Gillian Reeves

Dr Jenny Rusby

Dr Rosalind Given-Wilson (from 13.00hours)

In attendance

Keith Shaw

Krys Baker (notes)

Apologies

Dr Kevin Fenton

Professor Sir Mike Richards Dr Robin Wilson

Professor Tom Meade (DMEC)

Documents circulated in advance:

• Agenda
• Minutes of TMG meeting 23 January 2014
• Trial progress as at January 2015
• Data progress as at January 2015
• Report on study population data for the first 5 years of the trial
• Report on screening data for the first 4 years of the trial 

1. Welcome and Introductions

New Member of TMG Honchao Pan (HP) was welcomed to the meeting. Keith Shaw (KS) Data Manager and Krys Baker (KB) Trial Administrator were also welcomed.

Apologies were received from Kevin Fenton (KF), Mike Richards (MR), Robin Wilson (RW) and Tom Meade (TM). 

2. Minutes of the last meeting (23^rd Jan 2014) and matters arising

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

Matters arising:

TMG membership – Sarah Sellars and Richard Winder have now retired from their posts. They will continue to be named as authors of the protocol but a footnote will state that they have retired. HP is a new member. New membership of the TMG will be discussed later in the meeting.

The recent criticisms of the trial were discussed, and it was decided that this would not be the focus of the meeting.

Malcolm Reed (MR) asked for there to be more communication with the TMG between meetings; it was agreed that KB would circulate periodic updates. 

3. Trial Update – Kath Moser (KM)

a)    Randomisation, numbers, data

As at the end of December 2014, 64 out of the 69 breast screening units due to take part in the trial had started randomising. Of the 5 remaining units, 1 is due to start soon. There was some discussion as to whether it would be better to exclude these 5 units from the trial. The TMG felt that a final date should be set for them to commence the trial. However the DMEC meeting later that day decided that these 5 units should not be excluded from the trial. There are a further 9 units which will not be participating in the trial – one is private, and 8 use a non-standard method of creating screening batches. An estimated 1,846,000 women have been randomised to date, with the number randomised increasing by 44,700 per month.

Keith Shaw (KS) is receiving data downloads; there is currently a delay due to changes in PHE data release procedures; the application to PHE for data release is in hand. 1.5 million women have so far been flagged at the NHS Central Register for deaths and cancers.

Members of the TMG were not concerned with the variation in batch sizes across units, and agreed that it would not compromise the statistical power of the trial.

b)   Ethical approval, protocol

The updated protocol (version 3.0) had been circulated together with the new Patient Information Sheet; also a poster, which will be circulated to GP surgeries for them to display. Ethical Approval for Substantial Amendment 3, which included these documents, was granted on 4 November 2014.

The TMG agreed that the leaflet is more detailed, and that the Protocol is more comprehensive.

4. Discussion of future plans and 5. Discussion of scientific matters

LC suggested collecting data on characteristics of women who had not attended breast screening; Richard Peto (RP) agreed that this would be a good idea, but it would need to be a separate project.

KS and KB will be setting up a trial website. TMG suggestions for content included Protocol, minutes of meetings, links to trial registers, and to breast cancer charities for patients. Also include up to date numbers of women in the trial.

The intention is to publish the protocol very soon.

JP informed the meeting that PHE were keen for a response to published criticisms. MR felt that publishing a response would distract from the main scientific points. This was discussed and it was agreed not to respond in print to the criticisms. Trial documents would be made available on the trial website.

The changed context of the trial was outlined: whereas initially the trial was opportunistic, now PHE have stated that future decisions about extending routine NHS breast cancer screening outside the age range 50-70 years should await the emergence of reliable evidence as to its effects. The trial can provide this information.

The TMG discussed recommendation 3 from the parliamentary inquiry into older age and breast cancer “to gather evidence for the benefits and risks of breast screening for women above the current screening age”. It was decided that a sub-group of the TMG would be set up to explore this recommendation. This would include Kevin Fenton (KF) amongst others.

Valerie Beral (VB) described the 5 datasets that will be linked to the trial records thereby providing a wealth of data – screening history and screening going forward, death registration, cancer registration, cancer outcomes, and Hospital Episode Statistics.

6. Any other business

Janet Darbyshire (JD) raised discussion of the name of the DMEC and their role. She said the DMEC can provide advice on data monitoring and safety. In terms of ethics their role is advisory, they do not make decisions in relation to ethics – that is for the REC to do.

There was some discussion on the various models of trial management and oversight. It was agreed that although members had not experienced this model before, they were happy with the model adopted for the Age Extension Trial.

TMG members would be informed once the website was up and running.

7. Date of next meeting

TBA

11:00 – 13:00 PHE Wellington House, London

Present

TMG Members

Professor Julietta Patnick (Chair)

Professor Dame Valerie Beral

Mrs Claire Borrelli

Mrs Jacquie Jenkins

Professor Iain Lyburn

Ms Kath Moser

Dr Hongchao Pan

Professor Sir Richard Peto

Professor Malcolm Reed (by phone conference)

DMEC Members

Professor Janet Darbyshire

Professor Gillian Reeves

Ms Jenny Rusby

Visitors

Professor David Heymann (PHE)

Ms Anne Stevenson (PHE)

In attendance

Mr Keith Shaw

Ms Krys Baker

Apologies

Professor Kevin Fenton

Professor Sir Mike Richards

Dr Lucy Carpenter

Mrs Margot Wheaton

Dr Rosalind Given-Wilson (DMEC)

Professor Tom Meade (DMEC)

1. Welcome and Introductions

New members, Professor Iain Lyburn (Consultant Radiologist), Claire Borrelli (Radiographer and Education & Training Manager) and Jacquie Jenkins (National Breast Screening Programme Manager), were welcomed to the meeting. Visitors Professor David Heymann (Chair of Public Health England) and Anne Stevenson (National Programmes Lead for the Young Person and Adult Screening Programmes - representing Prof Kevin Fenton) were also welcomed. Introductions were made from all committee members.

Apologies were received from Prof Kevin Fenton (KF), Prof Sir Mike Richards (MR), Dr Lucy Carpenter (LC), Margot Wheaton (MW), Dr Rosalind Given-Wilson (RGW) and Prof Tom Meade (TM).

DH needed to leave the meeting early and so it was agreed to bring agenda item 4 forward.

2. Minutes of the last meeting (28^th Jan 2015) and matters arising

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

Matters arising:

TMG members found the mid-year newsletter useful. A similar communication will be sent to TMG and DMEC members in 2016. There was a discussion about how many participants were required to produce a reliable result from the trial. It was agreed that randomisation needed to continue until the mid 2020s to inform policy.

The trial website is up and running with web address www.agex.uk

Action: Send mid-year newsletter to TMG and DMEC members later in 2016

4. Screening women throughout their 70s

• The TMG agreed that scientifically it makes sense for the older women to be invited for additional screenings beyond 71-73.
• It would take time for screening units to implement adding the older age group into their batches and there will also be implications on staffing and resources within BSU’s.
• PHE said that the trial budget was fixed
• The priority for PHE is to make sure that the BSUs prioritise the clinical work and do not miss their targets.
• The PHE budget is currently being prepared for the 2016/17 financial year.It was agreed that the TMG need to see a breakdown of the funds being allocated to all units. PHE agreed to provide these figures.
• Software would need to be written to implement any change.
• Ethics approval would need to be sought for any changes.

Actions: A timeline was agreed as follows:

1. In the next month the budget will be reviewed by PHE. They will provide the budget to the TMG well before April 2016.
2.  In the next month Cancer Epidemiology Unit (CEU) will provide estimates of numbers of women in their 70s by BSU.
3. IL, CB and JJ will assess the workload and clinical implications at the local BSU level.
4. The application for ethics approval for additional invitations to women in their 70s will be prepared over the next month.
5. 3-5 units to be selected to pilot extending screening to women in this age group. The pilot will begin when ethics approval has been granted and funding for the pilot is available.
6.  A further pilot will be conducted in one of the units currently inviting all women aged 47-49 (paid for out of trial funds but not contributing to the trial) to assess the feasibility and acceptability of being requested to no longer invite this age group and withdrawal of the associated funds.
7.  By March 2017 it was hoped that all participating units should be inviting for screening the trial women aged 74+
8.  PHE to assess the possibility of providing screening on request for women aged 47-49 in BSUs not participating in the trial who are being requested to stop inviting all women in this age group for screening.

3. Trial Update

• As at the end of December 2015, 65 out of the 69 breast screening units due to take part in the trial had started randomising. Of the 4 remaining units which had not yet started, 3 plan to commence randomisation in 2016.
• 2.4 million women had been randomised as at Dec 2015
• The study population data for the first 6 years of the trial was described. 10,229 screening batches had been randomised during this period, which included 1,974,712 trial participants. Currently around 500,000 women are being randomised per year.
• The screening data for the first 5 years of the trial was described; date of first offered appointment, screening date, recall, biopsy, etc - for the women randomised in.
• The surgical procedures data were discussed and further detail requested.

Action: Further information on surgical procedures (from HES if possible) will be prepared for the next meeting

It was confirmed that all screening is now digital.

Action: Self-referrals derived from screening history data to be prepared for next meeting.

Action: Uptake by breast screening units using routine screening data, to compare with trial data, to be prepared for next meeting.

Action: Use screening history data to investigate whether women invited aged 47-49 in the trial come back when routinely invited for screening aged 50-52.

6. Any other business

Future Publications

Interim analyses and publication of protocol requested by JP and KM. RP suggested that the protocol should be published in a major journal such as Lancet Oncology once the revision of adding the 74-79 age group has been approved. It was also agreed to add the protocol to the website once published, and in the meanwhile a summary may be added to the website once ethical approval has been obtained.

Meeting for participating BSUs

It was agreed that a meeting would be arranged during 2016 for all participating BSUs, to feedback information about the trial including some interim numbers.

Action: Arrange meeting during 2016 in Oxford for participating BSUs

HSCIC

The study is currently awaiting approval from HSCIC for release of HES data, the application is being reviewed in the next couple of weeks.

Leaflet (PIS)

When putting together the next ethics application, to include changed wording of the PIS to ask those invited for screening to cancel appointment if they do not wish to attend screening.

7. Date of next meeting

Feb 2017 KB will send doodle poll

11:00 – 13:30 Cancer Epidemiology Unit, NDPH, Oxford

Present

TMG Members

Professor Julietta Patnick (Chair)

Ms Krys Baker

Professor Dame Valerie Beral

Dr Lucy Carpenter

Mrs Jacquie Jenkins (via conference phone)

Ms Kath Moser

Dr Hongchao Pan

Professor Sir Richard Peto

Professor Malcolm Reed Mr Keith Shaw

DMEC Members

Professor Janet Darbyshire (chair of DMEC)

Dr Ros Given-Wilson

Professor Gillian Reeves

Ms Jenny Rusby

Apologies

Professor Kevin Fenton

Professor Sir Mike Richards

Mrs Claire Borrelli

Professor Iain Lyburn

Professor Tom Meade

1. Welcome and Introductions

Apologies were received from Prof Kevin Fenton (KF), Prof Sir Mike Richards (MR), Mrs Claire Borrelli (CB), Professor Iain Lyburn (IL) and Tom Meade. It was noted that Margot Wheaton had retired.

2. Minutes of the last meeting (11^th Jan 2016) and matters arising

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

Matters arising:

Action points:

JJ explained that the new budget showed an overall reduction as 9 BSUs who were not part of the trial but were inviting all women 47-49 had been asked to stop inviting these women from Dec 2016. This released money which in due course could be put towards inviting some trial women 74+. For screening JJ said it was unlikely to be possible to start inviting women 74+ until 2018, possibly slightly earlier i f IT issues could be sorted. VB explained that the trial has ethical and CAG approval to add two follow up screening invites at 74-76yrs and 77-79yrs in the women randomised in aged 71-73. We are waiting for an IT program to be written and for a review of capacity in Breast Screening Units (BSUs). This would be piloted first in one or two centres in the next 12 months or so.

VB reported on self-referrals. The self-referral rate among women aged 47-49 randomised not to be screened is 0.9%, whereas among women aged 71-73 it is about 10%. As there were so many women not invited at 71-73 who self-referred, the degree of contamination could be greater than anticipated following the pilot and greater numbers of women to be randomised could consequently be required. RGW reported that previous trials had encouraged women over 70 to self-refer for breast screening. JJ also reported that PHE does encourage women to return for breast screening in their 70s despite there being little evidence in support of this.

There was some discussion on how this number could be minimised. RP said that it gave a greater case for recruiting as many over 70 women as possible to increase numbers.

Action: Discuss with PHE the inconsistency in their approach to women over 70.

Action: Start inviting those aged 74-76 ASAP. Look at BSUs that have a high self-referral rate.

It was noted that the meeting held in the Richard Doll Building in Oxford in September 2016 for representatives from Breast Screening Units (BSUs) had been well received and had a good attendance from BSUs.

3. Mid-year update

TMG members found the mid-year newsletter useful. A similar communication will be sent to TMG and DMEC members in 2017.

Action: JP/KB Send mid-year newsletter to TMG and DMEC members later in 2017

4. Updated Protocol with recent Amendment

Amendment 4.0 approved Sept 2016 included an:

Updated protocol to include option for two extra breast screening invitations in 74-79 age group, reference to the trial as “AgeX” in the protocol’s title, text, and descriptive material, revision of the Introduction and Background to bring them up to date.

Updated patient Information sheet which include changes to reflect possibly inviting women for screening throughout their 70s, ask women to let their screening office know if they are unable to attend their appointment, mention that record linkage to routinely collected NHS data will use data from NHS Digital (previously HSCIC),following a request from NHS Digital that this be mentioned. There was some discussion to clarify the intended exclusion from analyses of women who had had previous breast disease or breast surgery. It was agreed that the types of previous breast disease and of previous breast surgery would be looked at when relevant hospital data were available.

It was also agreed that the implementation of the extra screens should be carried out paying attention to a shortage of workforce within the BSUs.

Action: Discuss types of previous breast disease at next TMG meeting when relevant data are available.

5. External review

A document was circulated containing all data sources. The study has recently had approval from NHS Digital for the provision of hospital admissions data (HES) data earlier this year. HES records for 2.5 million women will be provided this spring/summer. Other data sources include PHE for screening data, cancer outcomes data and cancer screening history. ONS provide mortality and incident cancer data via NHS Digital.

Public Health England (PHE) have recently asked for an independent external review of the AgeX trial to be carried out, and a letter describing the results of the review was circulated to members. The anonymous reviewers wrote a strongly favourable report in support of the trial with an average score of 9.3 out of 10. The reviewers asked for a clarification of a couple of points. The TMG discussed response to the reviewers proposed by RP. It was agreed to clarify some of the responses and give more succinct replies to the questions and send our response to PHE.

Action: RP to edit our response to PHE and send it to them.

6. Plans for inviting women 74-79

2016 Summary of European Commission Recommendations on Breast Cancer Screening was circulated. They conditionally recommend screening for women 70- 74. The fact that there is no evidence for recommending this gives good grounds for supporting the trial.

RP stated that the EBCTCG was currently undertaking a review of individual data from all previous trials of breast screening; results should be available by 2018.

7. Trial update

As at the end of December 2016:

• 65 breast screening units are randomising
• 2,933,000 women are estimated to have been randomised to date
• 1,873,000 aged 47-49
• 1,060,000 aged 71-73
• the number of women randomised is increasing by an estimated 45,300 per month
• 29,000 aged 47-49
• 16,400 aged 71-73
• Almost all mammography now digital
• Inner city BSUs tend to have lower uptake 

8. Any other business

RGW reported a concern regarding a shortage of Radiographers and Radiologists which may have an impact on the trial that was expressed at the British Society of Breast Radiology meeting in Nov 2016. VB was attending a meeting of Breast Screening Radiologists on the 23^rd February 2017. It was suggested that the investigators describe the trial at scientific meetings.

Action: Trial needs to be actively communicating with BSUs in order to explain its rationale and importance, as was done in the early years of the trial. In particular present information about AgeX at scientific meetings.

Action: Need to start pilots for adding screening invitations 74+

10:30 – 12:30 Cancer Epidemiology Unit, NDPH, Oxford Minutes

Present

Professor Julietta Patnick (Chair) (JP)

Ms Krys Baker (KB)

Dr Isobel Barnes (IB)

Professor Dame Valerie Beral (VB)

Dr Lucy Carpenter (LC)

Professor David Hunter (DH)

Dr Hongchao Pan (HCP)

Professor Malcolm Reed (MR)

Professor Sir Mike Richards (MAR)

Mr Keith Shaw (KS)

Apologies

Mrs Claire Borrelli (CB)

Professor Kevin Fenton (KF)

Mrs Jacquie Jenkins (JJ)

Professor Iain Lyburn (IL)

Professor Sir Richard Peto (RP)

1. Welcome and Introductions

Apologies were received from Prof Kevin Fenton (KF), Mrs Claire Borrelli (CB), Professor Iain Lyburn (IL) and Mrs Jacquie Jenkins (JJ). JP welcomed Professor David Hunter and Dr Isobel Barnes to the TMG. Isobel has succeeded Kath Moser who retired in April 2017. The committee also thanked Kath for her work in setting up the trial.

2. Minutes of the last meeting (20^th Feb 2017) and matters arising

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

Matters arising:

It was noted that some DMEC Members were present at the 2017 TMG meeting. However this year the DMEC met earlier, on the 22^nd February 2018, and a note from the DMEC to the TMG was circulated in the papers for this meeting.

Action points:

The “Be Clear about Cancer” campaign run by PHE inviting over 70s to attend for breast screening is not evidence based and has had some unwanted effects on the trial, by increasing screening among the controls. PHE has agreed to consider the AgeX TMG views on suspending these campaigns. 

It has not yet been possible to commence sending the invitations to the 74-76 years olds. Some funds for this will come from the money released from the Breast Screening Units that were screening 47-49 year olds, without randomisation.

3. Mid-year update

TMG members found the mid-year newsletter useful.

4. Trial Update

VB presented a report prepared by the AgeX investigators for the meeting of the PHE Breast Screening Programme Research Advisory Committee (RAC) in January 2018 (which she had attended). VB explained that, at the meeting, PHE representatives unexpectedly suggested that some women who were randomised into AgeX when they were aged 70 should have been offered routine screening instead. The trial investigators found, however, that there were discrepancies between the definition of age used by PHE and that used for routine breast screening invitation procedures (which also applied to AgeX). PHE asked that this apparent discrepancy be reported to the DMEC and regulatory authorities. The AgeX DMEC met on 22 February 2018 and agreed that no change to the AgeX trial materials or procedures was necessary at present, and this information was conveyed to members of the TMG.

The TMG discussed if there were any steps that the trial might have taken to avoid this issue, pointing out that the method that the screening programme procedures currently use to define age was based on year of birth and that women aged 70 who were due to turn 71 by the end of the year were not eligible for routine screening. VB reported that the trial investigators continued to be in discussion with PHE about this.

VB presented the report based on other work to date:

4.1   Recruitment: 3.1 million women have been randomised up to 31/03/17; 67% of those aged <50 and 69% of those aged 71+ allocated to be invited for screening have accepted.

4.2  Numbers randomised: The study is now randomizing just over 500k women per year. The annual number of women randomised is likely to be stable from now on, as no more screening services are joining the trial. Recently the proportion of older women has increased slightly, largely because women born in the post-war baby boom are now reaching their 70s.

4.3  Randomised batches: There has been some increase in the average batch size over the last few years. The number of batches randomising women to be invited or not are similar.

4.4  Excluded records: The number of women who could not be flagged has increased in the last two years. This is due to the care.data episode which led to about 3% of people requesting that their health data not be passed on to others.

4.5  Data sources: Data on those randomised and follow-up data come from 7 different sources. The numbers randomised, screening outcomes and death data were available up to 31/3/2017, but information on tumour characteristics (COSD data) was last available in 2013 and on past cancer screening history in 2015. It is hoped that planned improvements in PHE data systems will reduce these delays and simplify data transfer. There are still relatively small numbers of women with 5 years follow-up. SMR reported asked to be kept updated about the timeliness of provision of cancer data (including COSD).

5. Report by DMEC

The report issued by the DMEC who met in 22^nd Feb 2018 had been circulated.

6. Presentations about AgeX at Scientific Meetings

JP will be presenting information about the Trial at the Symposium Mammographicum conference in July 2018. The audience is people working in breast screening, mostly radiographers. The TMG agreed that since the trial started new radiologists and radiographers have been appointed and stressed the importance of keeping them informed about the trial.

HCP and RP have been working on a meta-analysis of breast screening around the world to present at the Early Breast Cancer Trialists’ Collaborative Group meeting in April 2018.

The TMG agreed that more conference presentations and liaison with PHE were important.

7. Membership of TMG

It was agreed that all TMG members who had not attended 2 consecutive meetings would receive a letter to ask if they wished to continue as members of the TMG. If a meeting was missed for the third time, the member would generally be replaced on the committee. The TMG members agreed that it is essential to have Radiologist and Radiographer representation on the TMG. MR suggested that a second lay representative such as a patient representative was appointed and offered suggestions on where to find lay representation

It was suggested that Suzanne Wright (Head of Implementation & Training for PHE Screening) replace Margot Wheaton as a member of the TMG.

Action: KB contact MR to find and appoint a 2nd lay representative Action: JP to invite Suzanne Wright to become a member of TMG

Action: JP/KB write to TMG members who have not attended for 2 consecutive meetings to ask if they wish to continue as members of the committee.

11.30-13.30 Cancer Epidemiology Unit, NDPH, Oxford

Present

Professor Julietta Patnick (Chair) (JP)

Ms Krys Baker (KB)

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)

Dr 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)

1. Welcome and Introductions

JP welcomed new TMG members SW, LW, GR and AH.

It was also noted that Kevin Fenton and Iain Lyburn had resigned from the TMG.

2. Minutes of the last meeting (12/03/2018) and matters arising

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

3. Breast screening incident at PHE and report of Independent Review

VB and RP described the breast screening incident in 2018. In summary the Review concluded that the AgeX Trial was not the cause of the incident. Since September 2018 PHE has updated the method of calculating age for sending breast cancer screening invitations and the AgeX protocol was amended to incorporate these changes for the eligibility of trial participants. 

This was not expected to make any material difference to the AgeX trial.

4. Revised protocol September 2018 

The new protocol was described by RP. Follow-up up of the trial participants will be indefinite. JJ noted that PHE policy now stated that routine screening was up to a woman’s 71st birthday.

5. Progress Report

5.1   Data sources: Updated randomisation data was received in the last few days. There are delays in the reporting for some of the associated datasets. Cancer outcomes data (COSD) have not been received from PHE since March 2017. HES data will be updated once the new randomisations have been flagged at NHS Digital. Deaths have been notified until July 2018. Screening history of participants has not been received since Sept 2015. Plans are to update all datasets as soon as possible

5.2   Recruitment: 3.6 million women have been randomised; 2.3 million in the younger age group and 1.3 million in the older age group.

5.3   Excluded records: National Opt-Outs are being applied to women who had been randomised to exclude them from follow-up.

5.4   Age distribution: It was noted that the number of 71-73 randomisations were rising due to the baby boom effect of the 1940’s and 1950’s. It was also noted that the number of randomisations in the 47-49 age group were decreasing due to the reduction in births in the early 1970’s. The total thus remains fairly constant.

It was confirmed that the intention to treat analysis will be of women who were previously screened. Breast and cervical screening correlated well with attendance rates in AgeX. Women who have had previous breast disease diagnosed would be excluded from the principal analyses, but all randomised women will be accounted for in the analyses.

Costs to services were rising. JJ will put together a case to ask DHSC for more money, this would be reviewed by the trial team in Oxford (costs for 74-76 year olds should be included the proposal).

Action: JJ to put together a case to ask for increase in screening cost per patient for AgeX.

6. Extending invitations to women aged 74-76

Screening 74-76 year olds is an important step in the trial as two invitations will increase the statistical power by approximately fourfold.

It was agreed that sending a second breast screening invitation to women aged 74- 76 would be feasible and is supported by PHE. It was noted that there continued to be a shortage of Radiographers, although assistant practitioners have been trained up is some regions and this system seems to be working well.

It was also agreed that a meeting would take place between PHE representatives and investigators in Oxford to identify the willing and capable breast screening units in which to begin this.

SW will need to build a program to select women in this age group for a second screen. The timeframe will depend on other PHE commitments.

Action: JJ, SW and Oxford investigators to meet to identify potential willing and capable sites in which to invite 74-76 year olds for a second breast screen following randomisation.

Action: SW to estimate the additional IT work required.

7. Communications and Correspondence

JP has presented the trial at two meetings since the last TMG meeting, at Symposium Mammographicum and the British Society of Breast Radiologists.

A newsletter was not sent in 2018 due to the incident at PHE, it is hoped that a newsletter would be sent to breast screening units within the next three months.

It was agreed that a summary of the TMG minutes would be included on the AgeX website.

It was agreed that investigators will aim to publish the AgeX Protocol in a peer reviewed Journal such as the Lancet Oncology. 

It was suggested that the trial investigators may like to formulate a communication strategy to share what has been happening with the AgeX Trial.

It was noted that communication directly from participants was small and comprised mainly of women wishing to opt-out of the trial and asking to be included in the trial after age 71 and in the 47-49 year age groups. Other queries included questions based on personal experiences and asking for advice.

8. National Opt-Outs

SW described how national opt-outs were applied for the AgeX trial.

9. Any Other Business

The TMG agreed for SW to work on the AgeX selection algorithm to make it compatible with the Next Test Due Date (NTDD) selection method for breast screening. This method was now becoming more popular in breast screening units and the trial may lose participants if this selection option is not made available when a batch is being created.

Action: trial investigators to meet with SW to discuss randomisation for breast screening batches created using NTDD.

10. Date of next meeting

It was agreed that the next AgeX TMG would take place in the spring of 2020, about a month after the AgeX DMEC meeting.

11.30-12.30 Teleconference

Present

Professor Julietta Patnick (Chair) (JP)

Ms Krys Baker (KB)

Dr Isobel Barnes (IB)

Professor Dame Valerie Beral (VB)

Mrs Claire Borrelli (CB)

Dr Lucy Carpenter (LC)

Mrs Jacquie Jenkins (JJ)

Dr 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)

Apologies 

Professor David Hunter (DH)

Mrs Annie Hogg (AH)

1. Welcome and Introductions

JP welcomed TMG members

2. Minutes of the last meeting (25/03/2019) and matters arising

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

COVID-19

JJ explained that all Breast Screening Units in England have closed according to local NHS Trust policies on social distancing. Every screening unit will re-open for breast screening activities independently when local social distancing measures are achieved. It is not clear whether mobile screening units will be able to offer screening due to the lack of space for distancing and handwashing facilities. JJ will keep the AgeX co-ordinating centre informed of the re-opening of each Breast Screening Unit.

The TMG members recognised that while it is important for TMG members to champion the trial, the trial would need to wait to start randomising again until the Breast Screening Centres had caught up with all of their outstanding NHS commitments, which would take longer than usual due to new social distancing measures that would need to be put in place. The trial investigators recognised that randomisations into AgeX may need to be halted for some time, but that it was important to continue follow up of existing trial participants. It was agreed that the Investigators would use this time to catch up on all data provisions from external sources.

Action: JJ inform AgeX Trial co-ordinating centre when a BSU re-opens for screening.

3. Numbers randomised

About 4.0 million women were randomised up to end March 2019, 2.5 million aged

<50 years and 1.5 million aged 71+ years. The numbers randomised up to end March 2020 were not yet available. SW explained that from April to June 2019 a mailing company contracted by some screening centres to send out screening invitations had failed to enclose the AgeX Participant Information Sheet with the invitations. PHE is working to identify these women and remove them from any information sent to the trial investigators. No more than 5000 women from 8 NHS Trusts appear to be involved.

Some women randomised to be invited for screening in early 2020 who had not been screened or invited before COVID-19 lockdown March 2020 may not have been screened because of the suspension of breast screening services by individual NHS Trusts. It was important that they be invited when the screening centres start working again.

4. Progress report

4.1   Following the 2018 breast screening incident the final report of the Parliamentary enquiry in December 2018 and recommended that AgeX should continue “until its planned end in 2026”. Formal Government statements in both Houses accepted this recommendation.

4.2   The Parliamentary enquiry delayed data collection and record linkage, but not randomisation. In late 2018 PHE changed its definition of the age when women were eligible for routine screening, the AgeX protocol was revised accordingly. There have been substantial improvements in data linkage since 2019.

4.3   In December 2018, Cancer Research UK funded fully the application for continued financial support during 2019-2024 for some members of the AgeX Trial Co-ordinating Committee, based in the Nuffield Department of Population Health in Oxford.

5. DMEC report to TMG March 2020

The DMEC report was presented to the TMG congratulating the breast screening units and trial team on randomisations and improved data linkages. There were no concerns raised from the DMEC.

6. Communications and Correspondence 

It was noted that, as reported in previous meetings that communication directly from participants comprised mainly small numbers of women wishing to opt-out of the trial and asking to be included in the trial after age 71 and in the 47-49 year age groups. Other queries included questions based on personal experiences and asking for advice.

7. Any Other Business

No other business was raised.

8. Date of next meeting 

Spring 2021.

10.00-12.00 Via videoconference

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.