25 March 2019

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.