OPINION
PACE is valueless for one reason: the combination of lack of blinding of treatments and choice of subjective primary endpoint. Neither of these alone need be a fatal design flaw but the combination is.
The only possible mitigation of this flaw would be if:
1. There were no acceptable alternatives to a subjective primary outcome measure, and
2. The authors fully understood the nature of the flaw and the reasons why it is so serious, and
3. The authors were meticulous in trying to avoid all forms of bias that are likely to arise from the flaw.
It has been apparent from the outset that alternative objective endpoints were available. These might not be ideal in a blinded study (the blinded Norwegian rituximab study chose a subjective end point for preference) but an objective primary endpoint would have been practical. The objective endpoints in PACE used as secondary measures tended to show no difference in outcome.
The authors (and colleagues) have repeatedly indicated in public that they do not understand the flaw in the PACE trial design, as made clear by claims that the study is ‘robust’ and of high design quality. Moreover, the authors have not been meticulous in trying to avoid bias that might arise. On the contrary they appear to have acted in ways more or less guaranteed to maximise bias. (The details are well documented but are secondary to the main problem.)
The recent follow up study may be of some use in confirming the sensible conclusion to draw from the objective measures used in PACE – that it provides no evidence for any benefit from CBT or GET. It strengthens the case by suggesting that at longer term follow up even the subjective measure differences disappear. It also highlights again the authors’ lack of understanding of trial design problems. Moreover, as outlined by Dr James Coyne, it provides further evidence for the authors’ tendency to continually introduce bias in their analysis, apparently through a lack of understanding of basic data interpretation and statistics. One might expect errors of this sort from a clinical trainee, but not from a professional research team.
I am surprised and troubled that clinical and research colleagues in the ME/CFS field have said so little about the problems with this study. It has been left to David Tuller and James Coyne to raise the issue again. Regardless of other issues relating to the illness (that have been grossly misrepresented in the popular media recently) it needs to be recognised and agreed that the PACE study is not a suitable evidence base for clinical practice guidelines.
Jo Edwards
Professor Emeritus, Dept Medicine, UCL
16 thoughts on “Prof. Jonathan Edwards: PACE trial is "valueless"”
thank you, Professor Edwards. your advocacy, and research, are saving lives.
you’re helping bring this disease out of the dark ages of victim-blaming, into
a modern world with modern effective treatments. you bring hope.
*tears of gratitude*
I also just want to say thank you, Professor Edwards. It seems patients can be easily dismissed, but someone of your stature will be taken more seriously.
We need more people of your calibre and integrity to speak out on our behalf. Again, thank you.
Thank you Jonathan for talking sense. I too want to know why our ME Drs aren’t speaking out more. The reason I suspect is that they are all too scared of loosing their jobs or grant money like others before them. We should be challenging them all to make statements like yours and be asking for retraction of the paper. Dr Vallings , NZ step up ???
Thank you Professor Edwards. Your time and insight are greatly appreciated.
A valuable intervention, thanks Jo. But why am I not surprised that British ME researchers and clinicians have said so little about PACE? The Charter of the UK CFS/ME Research Collaborative states:
“3.2.3 Members will be required to sign a declaration that they will not take part in the harassment or abuse of researchers. Neither will they take part in orchestrated campaigns against those conducting peer-reviewed research.”
If you were a member your scientific disagreement could easily be regarded as harassment. Posting it on #MEAction would show you support an orchestrated campaign. No surprise the psychiatrists insisted on this bizarre declaration. It’s had the intended chilling effect.
Thank you for your support. Has anyone considered the negative effect this type of fony research has on patients mental health. For one it upsets, frustrates and yes leaves me with a feeling of hopelessness. Is this just a way of not providing research money to help people with ME?
Thank you Professor Edwards, and also ME Action for posting your opinion here. I speak on behalf of the team running and supporting the Let’s Do It for ME campaign when I say that we are grateful for your sincere concern for people with this disease and for your role on the Invest in ME Research Advisory Board, and to the charity for engaging your interest in ME/CFS, as you described in your statement of July 2013 -http://www.ukrituximabtrial.org/Rituximab%20news-July13%2001.htm
I was diagnosed in 1992 and left UK before the NICE guideline and fatigue (ostensibly ME) clinics were set up, and was shocked to discover, by joining the online community in 2010, how badly care in the NHS has deteriorated over that time, which wouldn’t seem possible, and is the reverse of how science and technology enables progress in testing for and treating other organic diseases. Thanks again.
Best wishes,
Jo Best
Team Let’s Do It for ME!
Thank you, Mike Dean, for quoting 3.2.3 of the UK CFS/ME Research Collaborative.
The careful and scientific analysis of the flaws in the PACE trial cannot surely be construed as ‘harassment’ or ‘abuse’.
I suppose posting on MEAction could be construed as support for an ‘orchestrated campaign’.
I guess this is the point at which some British ME researchers and clinicians might stand for scientific truth, even at the risk of some personal cost. They will anyway be on the right side of history.
I hope you’re right, Christine, that Jo Edward’s ‘valueless’ would not be misconstrued but taken as criticism of design flaws in PACE. That doesn’t excuse the unprecedented Declaration. The CMRC is for M.E. charities, researchers and clinicians, not the public. If they retain 3.2.3, there should be balancing requirements, such as: members will not orchestrate or take part in media campaigns to harass or abuse patients.
Professor Edwards, thank you so much for pin-pointing this once and for all. As vice-chairman of the Danish ME Association it means a great deal that professionals like you speak up – especially as the psyhiatric approach to ME is still a strong issue here in Denmark. On behalft of the Danish ME patients – thanks again and keep up your good work
Cathrine Engsig
ME Foreningen, Denmark
Hi Catherine,
We are looking for help finding someone who can translate http://my.meaction.net/petitions/pace-trial-needs-review-now into Danish. We already have versions posted in French, Japanese, Norwegian, German and Swedish. If you know of anyone who can help, please email [email protected]
Thanks!
If you need this translated into Dutch, contact me. I have ME too, so it may take me a while to do it.
I just want to remind everybody, that Prof. emeritus Malcolm Hooper in 2010 a made a complaint against the Medical Research Council followed by a 442 pages report, detailing the failings of the Medical Research Council and specifically the PACE trials:
“Magical Medicine. How to make a disease disappear. Background to, consideration of, and quotations from the manuals for the Medical Research Council’s PACE Trial of behavioural interventions for Chronic Fatigue Symdrome / Myalgic Encephalomyelitis together with evidence that such interventions are unlikely to be effective and may even be contraindicated.”
http://www.investinme.org/Article400%20Magical%20Medicine.htm
Well worth a read!
Heartfelt Thanks, Jonathon. You are an inspiration and I really hope others will find a way to join you, in whatever way they can…
I feel so dismayed to learn from Mike Dean’s post that The Charter of the UK CFS/ME Research Collaborative states that members are required to sign a declaration that they will not take part in orchestrated campaigns against those conducting peer-reviewed research.” Harassment and abuse should never be condoned but what is wrong with freedom of expression? Or campaigning or helping others to be heard? The right to freedom of expression is recognized as a human right under article 19 of the Universal Declaration of Human Rights and recognised in international human rights law in the International Covenant on Civil and Political Rights (ICCPR): “The free communication of ideas and opinions is one of the most precious of the rights of man. Every citizen may, accordingly, speak, write, and print with freedom, but shall be responsible for such abuses of this freedom as shall be defined by law.” (Wikipedia: Freedom of Speech).
I believe also that scholarly criticism is essential and the way that science progresses in the search for truth…
Supporters of PACE have for years appeared to ignore the biomedical evidence that shows ME to be a biological illness and they have relentlessly publicly criticised and dismissed the views and concerns of people with ME who choose to have regard to the biomedical research and to exercise their inalienable right (as recognised in the NICE Guidelines) to choose what happens to their bodies.
I bow to every clinician, researcher, academic and advocate who has spoken up for people with ME.
Regarding the UK CFS/ME Research Collaborative. Behind the Scenes, published by The Young ME Sufferers Trust – https://www.dropbox.com/s/92m09l9tq55pihh/Behind%20the%20Scenes%20-%20Research%20Collaborative.pdf
Just noticed this discussion on PR
http://forums.phoenixrising.me/index.php?threads/time-for-me-assoc-to-quit-the-uk-research-collaborative.41010/
Seems to me the ME Assoc should not leave the CMRC. They opposed squandering $8m public money on PACE and FINE from the outset. Meanwhile, the continuing presence and contribution of the UK Science Media Centre at the CMRC should be critically evaluated.
If the new US Science Media Center decides to report on ME research, it will be interesting to see if they take orders from the UK SMC. I doubt it somehow.
http://www.sciencemediacenter.org/usa/
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