28 January 2015

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