The largest clinical trial in Great Britain on breast cancer screening was halted

https://www.bmj.com/content/370/bmj.m3337.full

Summary by C. Bour, MD

27 August 2020

A major UK breast cancer screening trial called AgeX [1], was halted, more exactly inclusion and randomization of new participants will not resume.
Age X is the acronym of the trial founded by British Gouvernment: it is a controlled randomized trial set up to expand the age bracket determined by NHS (National Health Service) for the breast cancer screening in UK.

The trial investigates the incidence and mortality from breast cancer in different groups and aims to evaluate the risks and benefits of expanding mammography screening for breast cancer beyond the current age range of 50 to 70 years by providing an additional mammogram to women aged 47 to 49 and up to 73 years of age. Announced as "probably the largest randomized controlled randomized trial ever performed in the world," AgeX has randomized 4.4 million women to date in the expanded age groups.
Normally, the goal was to recruit a total of 6 million women in the trial in order to ensure statistical significance and draw conclusions.

This trial had generated a strong scientific controversy on both methodological and ethical arguments when it was set up in 2009, as the women included in the trial were unaware that they were part of it.

The contesting was brilliantly led by the HealthWatch UK site under the chairmanship of Professor Susan Bewley, but also by medical author Mitzi Blennerhassett and independent scientific editor Mandy Payne.[2] [3]

Here we have summarized the entire issue [4], the authors pointing first and foremost to the omission of the informed consent of participating women.

They also denounced the fact that screening does not demonstrate sufficient evidence of effectiveness, but instead, it can be harmful for women who are not fully aware of all these risks, and that the number of mastectomies could increase with the inclusion of more women, which were also uninformed.

Finally, to make sure of the informed consent of women in the AgeX trial as well as in all screening programs, Susan Bewley, Mandy Payne and Mitzi Blennerhassett requested the National Screening Committee to use high-quality text boxes and charts with visual pictograms.
They asked investigators and auditors of all data resulted from AgeX trial, to use the rate of death for “all-cause” as main result. Then finally, they called for an independent investigation of the scientific quality, governance mechanisms and ethical issues arising from this trial in order to identify future high quality standards for the design and execution of future government-sponsored trials.

Discontinuation of the trial

The trial was halted alongside other screening services to allow the NHS to cope with covid-19 [5].
The researchers have announced that randomization will not resume.
However, they said that follow-up by electronic linkage to routine government records will continue “throughout the 2020s and beyond.”
The AgeX website [1] now says, “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 restarts, the AgeX investigators decided in May 2020 that further randomisation into AgeX should cease permanently.”
The trial’s team said : “Although the intent had been to continue until about 6 million had been recruited, 4.4 million will, with sufficiently long-term follow-up, suffice”

The contesting continues, an inquiry is requested

Commenting on the trial, M.Blennerhassett said, “Having sat on a local research ethics committee, I was shocked that this trial had been approved. When I raised concerns my questions were not answered. I was simply referred to the NHS Breast Screening Programme website which, at that time, had no information regarding the trial.”
Susan Bewley told The BMJ, “Although covid will be credited with ending AgeX, this trial would not have stopped prematurely with no fanfare were it actually answering a necessary research question that had been through proper channels of peer review and funding.
“This largest randomised controlled trial in history has been criticised for having no statistical plan or oversight at onset, and repeatedly changing protocol, numbers, and endpoints. Four million women have already taken part in this unethical human experiment, without having had their understanding checked and giving their explicit informed consent.”
Susan Bewley has called for an independent inquiry “to learn the lessons of this government funded research, sponsored by the University of Oxford, and approved by the Human Research Authority that rode roughshod over women’s rights for a decade … We need to ask the question: who approved this, and how much did it cost?”

Références

[1] http://www.agex.uk/
[2] https://www.healthwatch-uk.org/projects/breast-cancer-screening-age-extension/122-age-extension-trial-of-mammography-screening-part-5-april-2019.html
[3] Bewley S, Blennerhassett M, Payne M. Cost of extending the NHS breast screening age range in England. BMJ 2019;365:l1293. doi: 10.1136/bmj.l1293 pmid: 30971394
[4] https://cancer-rose.fr/2019/04/10/3924-2/
[5] National Health Service