HealthWatch has from its outset campaigned for clinical trial integrity. For almost a decade we have been raising awareness of concerns over the questionable ethics of the largest randomised controlled trial in history. Known as "AgeX" it was launched in 2010 and at its height aimed to enrol six million women in England to measure effects of extending the age range for routine breast cancer screening from 50-70, to 47-79.
This page details our investigations and exposés.
Related external publications
- Critics say wider breast screening trial 'unethical' (Claire Wilson, New Scientist, 10 Nov 2014)
- Times letter sparks media frenzy: HealthWatch experts urge women to think twice before accepting catch-up screening invites (17 May 2018)
- "'Misleading' invitations left patients feeling manipulated" (Ben Rumsby and Deborah Cohen, The Sunday Telegraph, p 10, 27 May 2018)
- "Cost of extending the NHS breast screening age range in England" (Bewley, Blennerhassett and Payne, The BMJ, 10 April 2019; or read full-text version free here.
Seven years into the Age Extension trial of mammography screening, in September 2016, the target number of trial participants was quietly doubled, to "at least six million". The upper limit to the age range was extended from 73 to 79, inflicting extra mammograms on women already at increased risk from overdiagnosis and overtreatment. It has been re-named and re-branded; there have been changes to the protocol, the research hypothesis, and to the primary and secondary outcomes.
HealthWatch has been highlighting concerns over this mammoth trial almost since its inception, and our recent BMJ Analysis* describes the ethical flaws. In this HealthWatch Update we describe these and the procedural issues around the trial in more detail. We ask, will this research, with its constantly-shifting goalposts, ever be fit for publication in a serious peer-reviewed journal?
Information for prospective patients in the clinical trial of extending the age range for breast cancer screening has been updated at www.cancerresearchuk.org. After long term pressure from HealthWatch and others, it is good to see that the trial is now being described more openly. It is clearly stated that the policy on screening the extended age ranges will depend on the outcome of this trial, although that won't be known until 2022.
We were dissatisfied that the Research Ethics Committee (REC) did not appear to take our previous concerns seriously, so we sent an appeal letter on 29th December 2014. This letter is here. We itemised 20 issues that needed to be addressed by the REC. After regular prompting, we eventually received a reply dated 20th March 2015, Oversight of REC decisions is provided by the National Research Ethics Advisors’ Panel (NREAP). In summary, this body dismissed most of our concerns, and allowed the study to proceed unconditionally.
Our intensive lobbying has achieved substantial results, albeit still incomplete. Main points:
- The proposed new patient information sheet will now actually tell women that they are entering a clinical trial.
- The Harrow Research Ethics Committee approved* a substantial amendment to the protocol, on 14th October 2014 This amendment is incorporated in the new protocol, version 3.
- The protocol now runs to 11 pages, instead of eight originally. It still falls far short of Good Clinical Practice (GCP) compliance; for example there is nothing about quality assurance or publication policy, and in general it doesn’t come close to following the ICH format. There is now a little detail on data processing, and there is a statistical power calculation (although based on contentious assumptions). The sponsor has refused permission for HealthWatch to publish this version of the protocol. This is strange in view of the current moves towards transparency of commercially sponsored trials.
- At the REC meeting, the investigators stated that full roll-out of the age extension will be dependent on the results of this trial. However the trial website still states that “The age extension will proceed regardless of whether this study goes ahead or not, and therefore regardless of whether the phasing-in is randomised or not.”
* We are using the informal terms `approved’ and `approval’ for clarity and brevity. The official term is `favourable opinion’.
During August-October 2014 it emerged that two protocol amendments were submitted to the ethics committee, and rejected. The first rejection letter is dated 14th February 2013. The objections are uncannily similar to the ones raised by HealthWatch members who did not have the benefit of seeing the requested amendments. It reads as follows (our bold):
The members of the Committee taking part in the review decided that they could not give a favourable ethical opinion of the amendment, for the following reasons:
This amendment seeks to shift the emphasis from a pragmatic opportunity (while resources were being expanded) to compare women who were or were not invited for breast screening in the extended age range, almost a service evaluation, to a randomised trial. The name of the study has changed from evaluation to randomised to reflect this intention.
Currently women between 50 and 70 years are invited to present for mammography screening. The overall benefit of this is increasingly doubtful, as better research is published, but the information women are given does not reflect this. The present policy is based on quite old randomised controlled trials, more recent data being from observational studies which are less robust.
Successive governments have been committed to extending the age range for a long time. In 2010 the Department of Health committed to extending the age range at either end, so that women over 47 and up to 73 years would also be invited. The Cancer Epidemiology Unit in Oxford (headed by Sir Richard Peto) has for years argued for randomisation of the age extension roll-out in order to collect data on effectiveness. This converted the roll-out into a randomised controlled clinical trial, which is how it is described by the government.
The controversy over mammography screening centres on the possible harms. For any screening test that is not 100% specific or accurate, and if the disease concerned only affects a small percentage of people, there will usually be far more false positive results than real positives. That is very clearly the case for mammography screening. Hence more women have unnecessary surgery than have real cancers treated. The question is whether on balance this is worth the effort, cost, and harms of screening.