"Patients' power and PACE" (Lancet editorial accompanying PACE Trial correspondence)

[Dolphin]

"Patients' power and PACE" (Lancet editorial accompanying PACE Trial correspondence)

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60696-X/fulltext

The Lancet, Early Online Publication, 17 May 2011

doi:10.1016/S0140-6736(11)60696-XCite or Link Using DOI

Patients' power and PACE

Original Text

The Lancet

Once every few years, we publish a paper that elicits an outpouring of consternation and condemnation from individuals or groups outside our usual reach. The latest topic to have caused such a reaction is chronic fatigue syndrome (CFS), andmore specificallyPeter White and colleagues' randomised PACE trial published on March 5, this year.

In the PACE trial, White and colleagues set out to answer a question that has long troubled the CFS community: are the treatments recommended by clinical guidelinesie, cognitive behaviour therapy and graded exercise therapyreally the best option for patients with CFS? The trial's findings showed that, compared with specialist medical care alone, both treatments were associated with significant improvements in self-rated fatigue and physical function (the primary outcomes) after 52 weeks.

The response to the trial's publication was swift and damning. When is the Lancet going to retract this fraudulent study? demanded a Facebook group. A 43-page complaint (now available via Wikipedia) branded the trial unethical and unscientific. There were 44 formal letter submissions, eight of which we publish today, together with a response from White and colleagues.

Many of the letters critique the definitions of secondary outcomes, question protocol changes, and express concern over generalisability. But one cannot help but wonder whether the sheer anger and coordination of the response to this trial has been born not only from the frustration many feel about a disabling condition, but also from an active campaign to discredit the research. White and colleagues have been accused of having formed their opinion about the intended outcome before the trial began. This view is unjustified and unfair. The researchers should be praised for their willingness to test competing ideas and interventions in a randomised trial. The evidence might even suggest that it is the critics of the PACE trial who have formed their opinions first, ignoring the findings of this rigorously conducted work.

 

[Dolphin]

Submitted correspondence

The published letters can be seen in this thread:

http://forums.phoenixrising.me/show...published-and-authors-response-(and-editorial)

-----

Nearly all of the unpublished letters can be seen in this thread:

http://forums.phoenixrising.me/show...-letters-that-were-not-accepted-by-the-Lancet

 

[Valentijn]

"But one cannot help but wonder whether the sheer anger and coordination of the response to this trial has been born not only from the frustration many feel about a disabling condition, but also from an active campaign to discredit the research."

The Lancet is speculating about the sincerity of the response, but not entertaining the possibility of the validity of that response.

"White and colleagues have been accused of having formed their opinion about the intended outcome before the trial began. This view is unjustified and unfair."

I disagree that it would unjustified, given the extensive observable physical signs that have been published in many studies, versus the authors' previously documented belief that we only suffer from an incorrect fear of exercise and the incorrect belief that we are physically ill. Furthermore, most of the responses questioned the methods and definitions used in the study, rather than the intentions of White and colleagues.

"The researchers should be praised for their willingness to test competing ideas and interventions in a randomised trial."

The primary criticism is not that they tested these theories, but the manner in which they conducted and reported that testing.

"The evidence might even suggest that it is the critics of the PACE trial who have formed their opinions first, ignoring the findings of this rigorously conducted work."

I find it ironic (and disturbing) that the staff of the Lancet is actually doing what they're damning us for erroneously being accused of doing - dismissing opinions based on assumptions of the intent of people expressing those opinions, instead of examining those opinions objectively.

 

[Esther12]

Patients' power and PACE

Original Text

The Lancet

Once every few years, we publish a paper that elicits an outpouring of consternation and condemnation from individuals or groups outside our usual reach. The latest topic to have caused such a reaction is chronic fatigue syndrome (CFS), andmore specificallyPeter White and colleagues' randomised PACE trial published on March 5, this year.

In the PACE trial, White and colleagues set out to answer a question that has long troubled the CFS community: are the treatments recommended by clinical guidelinesie, cognitive behaviour therapy and graded exercise therapyreally the best option for patients with CFS? The trial's findings showed that, compared with specialist medical care alone, both treatments were associated with significant improvements in self-rated fatigue and physical function (the primary outcomes) after 52 weeks.

The response to the trial's publication was swift and damning. When is the Lancet going to retract this fraudulent study? demanded a Facebook group. A 43-page complaint (now available via Wikipedia) branded the trial unethical and unscientific. There were 44 formal letter submissions, eight of which we publish today, together with a response from White and colleagues.

Many of the letters critique the definitions of secondary outcomes, question protocol changes, and express concern over generalisability. But one cannot help but wonder whether the sheer anger and coordination of the response to this trial has been born not only from the frustration many feel about a disabling condition, but also from an active campaign to discredit the research. White and colleagues have been accused of having formed their opinion about the intended outcome before the trial began. This view is unjustified and unfair. The researchers should be praised for their willingness to test competing ideas and interventions in a randomised trial. The evidence might even suggest that it is the critics of the PACE trial who have formed their opinions first, ignoring the findings of this rigorously conducted work.

Fantastic.

"When reading these letters my own prejudices about CFS patients, and occasional perusal of the angry writings of random internet postings, led me to believe they were really about something quite other than what they explicitly expressed. This is unjustified and unfair, but because they are weak and powerless I can get away with it and present them as being unreasonable when they get upset by it. It clearly shows that they don't understand how science works."

Imagine if a letter to the Lancet had cited some anonymous internet posting from a doctor attacking CFS patients, and talked as if that was representative of the mentality which underpinned the Pace trial. I wonder if that would have been seen as fit for publication?

I have to admit that re this: formed their opinion about the intended outcome ... I didn't even see it as an accusation. I thought White and Chalder were quite open about it in there own work. That doesn't mean that they couldn't have run a fair trial and presented the results as clearly and honestly as possible, but to act as if they started Pace without presumptions about the treatments; or that had pacing been shown to be as effective as CBT or GET, this would not have undermined much of their own work and careers, is just silly.

 

[Dolphin]

Fantastic.

"When reading these letters my own prejudices about CFS patients, and occasional perusal of the angry writings of random internet postings, led me to believe they were really about something quite other than what they explicitly expressed. This is unjustified and unfair, but because they are weak and powerless I can get away with it and present them as being unreasonable when they get upset by it. It clearly shows that they don't understand how science works."

Imagine if a letter to the Lancet had cited some anonymous internet posting from a doctor attacking CFS patients, and talked as if that was representative of the mentality which underpinned the Pace trial. I wonder if that would have been seen as fit for publication?

Good analogy.

Regarding White and co being praised for testing out the therapies: they ran away from objectively measuring activity by dropping actometers and also generally didn't use biomedical outcome measures.

They had an idea from previous trials what outcome measures they thought might work in CBT and GET (and still made plenty of changes between the published protocol and what was finally published).

 

[Esther12]

Good analogy.

Thanks. And thank you for posting this and all the letters up... even if it's not restored my faith the way CFS is treated by the UK medical establishment.

 

[Enid]

I guess they would respond like this - it's their own credibility (with Sharpe and Co - whom they clearly support) in the obvious failure to understand or accept the nature of ME in the first place. Perhaps they should be less biased and reflect the growing specialist findings/understanding of the severities and pathologies too.

 

[TinyT]

Thanks for linking the published & unpublished letters. They made me feel a little better after reading the crap that the Lancet published re 'CFS' patients response.

The trial's findings showed that, compared with specialist medical care alone, both treatments were associated with significant improvements in self-rated fatigue and physical function (the primary outcomes) after 52 weeks.

Gee umm.... No, no they didn't. The improvements were not clinically significant, they were only marginally statistically significant and that was only because the results and outcome measures were skewed/altered.

The Lancet's response and that of White and colleagues feels like we are trying to have an argument with a petulant child. "I'm right, I'm right, not listening anymore, nah nah nah naaah na!" (That was the Lancet/white etc just incase I've confused you).

Their response is disheartening but I shouldn't have expected better.

Where to from here?

 

[oceanblue]

Love it, Esther12, thanks.

I think it's worth pointing out that the reason there was so much attention to the secondary outcome of 'normality' is that these figures produced the headlines around the world about decent recovery rates - and that's exactly what the authors intended. Note that while they are now happy to clarify they didn't report recovery in the original paper, they didn't clarify this with any of the media at the time - in fact they set out to mislead with phrases like 'back to normal'. (I think that would be libellous if it wasn't true).

And of course, the they should have never relied soley on self-reports for primary measures.

 

[Dolphin]

Love it, Esther12, thanks.

I think it's worth pointing out that the reason there was so much attention to the secondary outcome of 'normality' is that these figures produced the headlines around the world about decent recovery rates - and that's exactly what the authors intended. Note that while they are now happy to clarify they didn't report recovery in the original paper, they didn't clarify this with any of the media at the time - in fact they set out to mislead with phrases like 'back to normal'. (I think that would be libellous if it wasn't true).

And of course, the they should have never relied soley on self-reports for primary measures.

Also, one person was told by the Lancet that the authors had a chance to comment on the accompanying editorial (which said a strict definition for recovery was used i.e. quoting the within the normal range as figures for recovery) but the PACE Trial authors didn't comment on it.

 

[In Vitro Infidelium]

Where to from here?

Well we could learn from the experience but I doubt that will happen. There was never any doubt that The Lancet would defend its publication of the PACE article and the integrity of article authors. To advance the wholly legitimate criticisms of the PACE trial required limited and reserved responses which acknowledged the academic and professional standing of The Lancet, the PACE study and the articles authors. Had this been achieved, any published letters would have been accessible by The Lancets readership without the presence of a (in anyway justifiable) derogatory accompanying editorial. Instead we have M.E/CFS patients cast as pathological in our resistance to what is presented as unquestionably a valid treatment, to an audience that may soon have unprecedented control over the commissioning of treatments in England, and a consequent increase in influence over treatment content throughout the UK. Patients, and patient advocate organisations need credibility with their doctors, previously achieved credibility on the part of M.E/CFS patients and organisations in the UK has undoubtedly been lost, to absolutely no purpose and in circumstances where the loss was predictable and avoidable.

PACE proved one thing beyond doubt, that CBT/GET treatments while they 'may' be safe, are not cost effective treatments for M.E/CFS. It is that one single 'negative' that could persuade health commission authorities in the UK that CBT/GET is not worth including in future health plans, the problem now is that everyone who is involved in health service commissioning in the UK has been given a picture of those who are 'anti' CBT/GET as being 'not credible' and the argument of cost effectiveness may be lost before it can even be made merely because of who the argument is coming from.

We will never 'out science' the scientists, and it doesn't matter how 'right' we are, when it comes to influencing bureaucracies, be they medical or otherwise the only rules of the arena that we can be effective under are those classified as PR (public relations), where appearance matters. The response to Lancet article was a lesson in how not to succeed.

IVI

 

[Firestormm]

Well we could learn from the experience but I doubt that will happen. There was never any doubt that The Lancet would defend its publication of the PACE article and the integrity of article authors. To advance the wholly legitimate criticisms of the PACE trial required limited and reserved responses which acknowledged the academic and professional standing of The Lancet, the PACE study and the articles authors. Had this been achieved, any published letters would have been accessible by The Lancets readership without the presence of a (in anyway justifiable) derogatory accompanying editorial. Instead we have M.E/CFS patients cast as pathological in our resistance to what is presented as unquestionably a valid treatment, to an audience that may soon have unprecedented control over the commissioning of treatments in England, and a consequent increase in influence over treatment content throughout the UK. Patients, and patient advocate organisations need credibility with their doctors, previously achieved credibility on the part of M.E/CFS patients and organisations in the UK has undoubtedly been lost, to absolutely no purpose and in circumstances where the loss was predictable and avoidable.

PACE proved one thing beyond doubt, that CBT/GET treatments while they 'may' be safe, are not cost effective treatments for M.E/CFS. It is that one single 'negative' that could persuade health commission authorities in the UK that CBT/GET is not worth including in future health plans, the problem now is that everyone who is involved in health service commissioning in the UK has been given a picture of those who are 'anti' CBT/GET as being 'not credible' and the argument of cost effectiveness may be lost before it can even be made merely because of who the argument is coming from.

We will never 'out science' the scientists, and it doesn't matter how 'right' we are, when it comes to influencing bureaucracies, be they medical or otherwise the only rules of the arena that we can be effective under are those classified as PR (public relations), where appearance matters. The response to Lancet article was a lesson in how not to succeed.

IVI

In essence IVI I agree with what you have written. I think PACE proved more than that 'one thing' you mentioned, but, yeah, I agree that is part of it.
As for never outing scientists - in this instance perhaps not - but 'we' did manage to discredit FINE and the more reasoned critiques of this trial have raised concerns.
But I also doubt it will have been enough to prevent the continued practice of CBT and GET - and why should it? It is some practitioners who should be accountable for their approach with patients and not these interventions themselves.
Critique the PACE methods and results as a scientic research trial by all means - I have in my reduced-capacity-state; but this oftentimes attack on individuals as well as the interventions themselves - has given the Lancet and the Authors room to breath.
And that is a shame.

 

[Esther12]

Well we could learn from the experience but I doubt that will happen. There was never any doubt that The Lancet would defend its publication of the PACE article and the integrity of article authors. To advance the wholly legitimate criticisms of the PACE trial required limited and reserved responses which acknowledged the academic and professional standing of The Lancet, the PACE study and the articles authors. Had this been achieved, any published letters would have been accessible by The Lancets readership without the presence of a (in anyway justifiable) derogatory accompanying editorial. Instead we have M.E/CFS patients cast as pathological in our resistance to what is presented as unquestionably a valid treatment, to an audience that may soon have unprecedented control over the commissioning of treatments in England, and a consequent increase in influence over treatment content throughout the UK. Patients, and patient advocate organisations need credibility with their doctors, previously achieved credibility on the part of M.E/CFS patients and organisations in the UK has undoubtedly been lost, to absolutely no purpose and in circumstances where the loss was predictable and avoidable.

I think that the lessons you want us to learn put an impossible responsibility upon CFS patients, and not nearly enough upon those at the Lancet. Maybe there were some terrible, ranting letters sent to the Lancet, but those published all seemed good, and written in a professional and respectful manner. That the Lancet chose to disparage the writers of these letters through some guilt by association fallacy that condemns all CFS patients for the failings of any, is just embarrassing. We've seen this sort of thing before, with other minority groups, and it should be a no more acceptable way of treating CFS patients than any other group. Whatever the failings of some, this does not justify a prejudicial approach to other members of these groups - we should all be treated as individuals and allowed to speak for ourselves.

How could we come up with a way of preventing poor letters being sent to journals when the publish and promote Pace in the way that they did? Many patients will be justifiably angered, and even if expressing that to the Lancet might not be helpful for us, I don't think that I have any right to stop them from doing so, or any mechanism for achieving such censorship - any more than black civil rights leaders were able to stop all black violent crime.

 

[Mark]

Well we could learn from the experience but I doubt that will happen. There was never any doubt that The Lancet would defend its publication of the PACE article and the integrity of article authors. To advance the wholly legitimate criticisms of the PACE trial required limited and reserved responses which acknowledged the academic and professional standing of The Lancet, the PACE study and the articles authors. Had this been achieved, any published letters would have been accessible by The Lancets readership without the presence of a (in anyway justifiable) derogatory accompanying editorial.

...

We will never 'out science' the scientists, and it doesn't matter how 'right' we are, when it comes to influencing bureaucracies, be they medical or otherwise the only rules of the arena that we can be effective under are those classified as PR (public relations), where appearance matters. The response to Lancet article was a lesson in how not to succeed.

IVI

Your point that, in order to be taken seriously, patients and patients' organisations need to express their criticisms in the right language and with the appropriate and respectful tone is well taken IVI, and as you know, Phoenix Rising is particularly committed to insisting on a measured tone and the avoidance of personal attacks.

At the same time, as Esther12 has pointed out, when the patient community numbers somewhere around a quarter of a million in the UK alone, it is clearly not possible for any individual or organisation to restrain some patients from expressing themselves publicly with great anger, and indeed it's a hard and frustrating battle for all of us to restrain that anger even without the challenges of the physiology of ME/CFS itself. That anger and bitterness is very deep, and very heartfelt, and editorials like this one in the Lancet only add to those feelings.

But your response above seems to me to fail to recognise that the Lancet is being completely disingenuous in presenting the reaction of patients and patents' groups in the way that it has - selectively quoting the reaction of "a Facebook group" (unnamed), and criticising the complaint that the trial was "unethical and unscientific" - without mentioning who made that criticism (Professor Hooper) and without publishing 36 perfectly reasonable criticisms of the study.

Here are the actual letters which were sent to the Lancet and not accepted for publication:

http://forums.phoenixrising.me/show...-letters-that-were-not-accepted-by-the-Lancet

...and I would be interested to hear from you in what way those letters failed, and how they might have expressed themselves better in order to succeed - I hope you will tell us how those letters could have been more successful, IVI, because in the absence of such a constructive critique, I don't see what lessons we can learn from this intransigence except that letter-writing and reasoned argument is pointless when those arguments are not being heard, and that more direct approaches are now necessary.

Here is how the Lancet characterised the reaction to PACE:

Once every few years, we publish a paper that elicits an outpouring of consternation and condemnation from individuals or groups outside our usual reach...

The response to the trial's publication was swift and damning. When is the Lancet going to retract this fraudulent study? demanded a Facebook group. A 43-page complaint (now available via Wikipedia) branded the trial unethical and unscientific. There were 44 formal letter submissions, eight of which we publish today, together with a response from White and colleagues.

(As an aside: the "individuals or groups outside our usual reach" are, presumably, a quarter of a million chronically sick patients, so I would query why those patients are 'outside of the usual reach' of a medical journal?)

But the key question I must ask you, IVI, is this: Which of those 36 unpublished letters failed in the objective to be "limited and reserved responses which acknowledged the academic and professional standing of The Lancet, the PACE study and the articles authors"? It looks to me that none of the ME patients' charities' letters were published. Where, exactly, did they go wrong?

So: which of those unpublished letters, and which reactions from which patients and patient organisations, were presented in the wrong way to be taken seriously? Evidence, please. Do you really think it is fair for the Lancet to characterise the reaction to PACE in this way, and use this reaction as an excuse for refusing to address the substantive issues?

The reaction against the PACE trial has been presented as if it were an extremist and unscientiific one, based on prejudice - but is that really the case? Do the letters listed in the link above really fit that characterisation? If those letters do not fit that description, then who or what is the Lancet criticising, and why do they not stick to responding to the substantive issues raised, and ignore the expressions of anger on Facebook groups?

In my personal opinion, there is ample evidence - ample evidence - that the PACE trial was fraudulent, unscientific, and unethical. It is nice to know that a Professor and a Facebook group agree with me on those points. It is not nice to hear, after the flaws in PACE have been detailed in 36 sober and restrained scientific letters that the Lancet failed to publish, that the entire critique of PACE is a scientific conversation that is to be dealt with by ignoring those criticisms because some of the things said on the internet about the study were a bit rude.

Well, I'm sorry if it is rude to call an unscientific, unethical, and apparently fraudulent study "unscientific, unethical and fraudulent", but if even the most reasoned critiques are not listened to, I am at loss to know what I should call it, and what I may now call the Lancet. And if I am not allowed to call a fraudulent study a fraudulent study, and if that allegation prompts not an investigation but a condemnation of the people making that claim, without an examination of the reasons for that claim, then how may fraudulent studies ever be addressed?

The Lancet would do much better to actually listen to and engage with the substantive issues raised, rather than to stick its fingers in its ears and accuse those making the criticisms of unthinking rudeness - because the anger that is felt is very real, very widespread, and very much justified, and that anger is only going to grow and deepen with every brick wall that is encountered. And one way or another, that anger will inevitably be expressed.

 

[Enid]

Yep Mark - sticks it fingers in it's ears. And tries to turn the tables - not too subtley on the perceived "oppostion". This "opposition" is the ignored research/findings/pathology only.

 

[Graham]

Our problem here is that we are trying to criticise a professional standpoint, and history is littered with examples in science, medicine and just about everywhere else where the status quo is defended long after the case against it has been proved. It's human nature, and "experts" are just as prone to it as everyone else. It is incredibly rare to come across an expert who is truly relaxed and open-minded about their own beliefs. The problem is not "were our criticisms valid?" - they still are. The problem is how do we change things? I think part of the answer lies in a different technique running parallel to the existing one. We need a sort of Trojan Horse approach - a less confrontational style that tries to draw out the inherent contradictions that lie within their position, and pushes them towards realising it for themselves.

Whatever you do, don't get the wrong idea about my feelings on this. I have had ME since 1999, my son since 1989. I am horrified by the shockingly bad quality of the studies that our present policies are based upon, and I fully understand, agree with and support the many people who are campaigning against it. But we do have to ask ourselves what do we want more, to continue to expose the truth but be ignored as raving extremists, or take a more careful role and plan to influence change?

I'm sounding too pompous and preachy, aren't I? Sorry about that.

 

[ukxmrv]

No worries Graham, we can always try it for 10 years and see how it turns out. Richard Horton sounds like a sensible chap and I'm sure he will listen to reason if we approach him like sane people.

No, seriously. I've been campaigning for nearly 30 years and have written countless polite and considered letters to medical journals, newspapers etc. Any new ideas gratefully accepted.

My own personal viewpoint is that we have nothing to lose by the confrontational approach. AIDS patients used it very well and so should we. They were vilified, had many hostile press and other attacks. Argued among themselves and with doctors. In the end they pushed and fought for change. Occupied buiding, chained themselves, had huge public protests. We don't have their physical strength, numbers of supporters and existing infrastructure though.

At the same time we can adopt any other strategies that work and experiment. We just need some that do work though.

If careful planning and strategy is needed we can do that. The problem is that some of us have run out of ideas.

Don't be sorry. Just think of ideas and let people know. We'll do anything that works. Thank you.

 

[Sean]

Also, one person was told by the Lancet that the authors had a chance to comment on the accompanying editorial (which said a strict definition for recovery was used i.e. quoting the within the normal range as figures for recovery) but the PACE Trial authors didn't comment on it.

The PACE authors are more than experienced, intelligent and informed enough to know exactly what the consequences of that uncorrected 'error' would be.

I will leave you all to draw your own conclusions.

 

[Graham]

Hi ukxmrv

I know! You are right, which is why I meant what I said about needing to work in parallel with the strong protests. We need them - very much so - and people have to be in no doubt of our frustrations. I have no illusions about persuading Richard Horton and the like to change their minds, but two things are happening: even the psychologists are beginning to say that we need to fund money for bio-medical research, and letter campaigns like John Greensmith's together with local clips about people with ME are beginning to change the public perception of ME at a local level (in the South-East the sad Lynn Gilderdale case has had extensive and repeat coverage). One of the reasons that the reactions to our criticisms is so strong is that the "experts" are feeling threatened by it all. I think that is due to the tireless campaigning by you and by others for so long, and by the mounting body of research evidence. I think you have been effective - it's just that it always takes so very very long to shake the establishment.

We need to see what will be attractive to the media and chase it. I was trying out ideas on how to get the message across with the blog that Bob and I did - I'm not claiming for one minute that it was earth-shattering, but it is our first attempt at trying to make a simple point in a way that is easily accessible. We need to find clear-cut messages, ways to communicate them simply and clearly to a wider audience, and how to get that message spread about.

OK, put me down as an optimist! But something has to keep me going. Like you, I'm not going to give up.

 

[Hope123]

But we do have to ask ourselves what do we want more, to continue to expose the truth but be ignored as raving extremists, or take a more careful role and plan to influence change?

I'm sounding too pompous and preachy, aren't I? Sorry about that.

Your views are your views and I can respect that but at least as it pertains to this thread, please read the link Dolphin cited. The submissions to Lancet WERE polite and non-extremist. Horton says they received 44 submissions, 8 + the 30 or so on that link means that 38/ 44 submission were polite/ non-extremist; that leaves only 6 formal submissions that we don't know about yet Horton makes generalized negative statements about ALL ME/CFS patients and advocacy groups. How fair is that? I suggest we keep writing/ responding to scientific articles in polite, rational manner (of course, other methods should be considered also) -- if the editors of journals/ newspaper/ etc. choose to discriminate against ME/CFS patients/ groups in print or other media, I can't help them but at least we'll know where they stand (and they'll have to eat their words in the future). Like I said, you can't make this stuff up. Let people indict themselves with their own words.