The PACE trial – Part 1 Moving the Goalposts
Slide 1 –
Half the research spending for ME in a 10 year period went on the widely discredited £5M PACE trial.
Gordon Brown 2008 – Ask the Prime Minister
The Medical Research Council has made it clear that research into M.E. is something that we are taking very seriously indeed. It’s a very big part of the research plan for the future, and I hope we will be able to report results in due course.
Slide 2 –
The PACE trial is taught in Universities and text books as an example of how not to conduct a clinical trial.
Slide 3 –
Over 100 experts and 80 charities want an independent review and 40 MPs want a public enquiry.
Carol Monaghan MP Glasgow North West SNP House of Commons debate 2019
When the full details of the trial become known this will be put down as one of the biggest medical scandals of the 21st Century.
Slide 4 -
The authors had a strict plan which had been approved and published.
But they decided to change that plan after the trial had started.
Dr Bruce Levin Professor of Biostatics
If you say you are going to do something, and you get funded to do it,
and approved by all kinds of review committees, then you ought to do it.
You are not allowed to wiggle out of it, it’s not good science, not good statistics.
Slide 5 –
The changes resulted in the publication of a study that was fundamentally flawed and uninterpretable.
Professor Brian Hughes National University of Ireland (Northern Ireland presentation)
Even if you know nothing more about the PACE trial except than it’s a non-blinded trial based on self report, you know enough to know that you cannot rely on that trial. That trial is not a good study. By definition, no matter what the researchers say, no matter what journals publish it, no matter how people defend it, it’s fundamentally flawed.
Slide 6 – “If you are reading a study that is un-blinded with subjective outcome measures then you may as well stop reading it” –
Students for Best Evidence, supported by Cochrane UK
Professor Brian Hughes National University of Ireland (Northern Ireland presentation)
Blinding is when in a therapy study for example you don’t tell the participant what the therapy is supposed to do. You don’t tell the participant that they are in the ‘good’ therapy group instead of the ‘bad’ therapy group. You come up with a way of hiding that information from the participant so that their self reports don’t become biased by expectation. Because if you’re told over and over again ‘you’re getting a fantastic therapy, this is wonderful’ when you fill out the questionnaire you’re going to say ‘the therapy was wonderful, I’m feeling a lot better now’.
Slide 7 –
Subjective measures, like questionnaires, are not reliable, especially when the treatment encourages patients to think positively.
Faulkner 2016, Centre of Welfare Reform
Carol Monaghan MP Glasgow North West SNP House of Commons debate 2019, reading participant in PACE trial testimony
"I started to feel like I had to put a positive spin on my answers.
I could not be honest about just how bad it was, as that would tell them I wasn’t trying and I wasn’t being positive enough. When I was completing the questionnaires, I remember second guessing myself, thinking after every answer ‘ is it really that bad? Am I just not looking at things positively enough?’"
Slide 8 –
“In cases where blinding is not possible or feasible the outcome measures must be objective!”
Students for Best Evidence, supported by Cochrane UK
Dr Fred Friedberg PhD Research Associate Professor
We need more than just a self-report that is telling us they don’t feel limited. So if we have an actigraph to confirm what they’re doing we’ll have a sense of what changes there are objectively, more objectively than just a self-report where people are trying to put together what their functioning has been.
Slide 9 –
Actimeters which objectively measure activity were dropped at the end of the trial because a Dutch study reported negative results.
(PACE trial steering committee minutes. Info obtained by FOI request 2018)
John Peters ME patient and FOI requester
We looked at the minutes of the management committees and we saw that they dismissed the actimeters at the end of the trial because the readings didn’t confirm the subjective improvement. And I think that is a massive giveaway, because it reveals, straight off, that they’d become so convinced that they were right, that if any evidence didn’t fit, it was the evidence that was wrong.
Slide 10 –
They also lowered their definition of improvement and recovery.
Recovery was lowered to a level similar to patients with congestive heart failure.
(Agardy 2017 Journal of Health Psychology)
Carol Monaghan MP Glasgow North West SNP House of Commons debate 2019
It was discovered that the authors had altered the way in which they measured improvement and recovery to increase the apparent benefit of the therapies. Reanalysis shows that the improvement rate fell from 60% to just 21% and the recovery rate from 22 to just 7%.
Slide 11 –
“The claim that patients can recover is not justified by the data and is highly misleading to clinicians and patients”
(Wiltshire et al 2017 – Fatigue: Biomedicine, Health and Behavior)
Dr Bruce Levin Professor of Biostatics
This redefinition allowed the investigators to massively exaggerate the success of the trial results. The characterisation of the results and the spin that these investigators have applied to the results are not really justified.
Slide 12 –
Changes meant 13% of participants were already classed as recovered on a key measure before the trial had even started.
(Geraghty 2017 - Journal of Health Psychology)
Dr Bruce Levin Professor of Biostatics
So as a result of these changes, 13% of patients were already recovered at the start of the study. In other words ‘congratulations you are eligible, with your consent you are involved in the trial…oh, congratulations you’re now recovered’.
Slide 13 –
“I’m shocked that the Lancet published it…I don’t understand how it got through any kind of peer review”.
(Dr Ron Davis, Professor of Biochemistry and Genetics, Director of the Stanford Genome Technology Center)
David Tuller DrPh, Senior Fellow in Public Health
PACE is a major case of scientific misconduct and really needs to be investigated at the highest levels of the MRC and UK medical establishment. It is impossible to have a study in which participants meet outcome thresholds at baseline. If 13% of participants have met an outcome threshold at baseline and you do not reveal that in your study, that is research misconduct. It is very clear, it is not hard to figure out.
