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Sense about science / PACE: The research that sparked a patient rebellion and challenged medicine

Cheshire

Senior Member
Messages
1,129
PACE: The research that sparked a patient rebellion and challenged medicine
by Rebecca Goldi

In 2011, researchers announced that PACE, the largest treatment trial in the history of chronic fatigue syndrome, had been a great success. That seemed like good news since there is no known cure for this devastating disease that affects over a million people in the United States alone, including Laura Hillenbrand, the best-selling author of Seabiscuit, and jazz pianist Keith Jarrett. Exercise and psychotherapy, the researchers said, can significantly improve and sometimes cure chronic fatigue syndrome (CFS), which is also sometimes called myalgic encephalomyelitis (ME). Headlines announced the study finding around the world; it was simple, as The Independent wrote, “Got ME? Just get out and exercise, say scientists.”

The finding struck many ME/CFS sufferers as preposterous—and their concerns about the way the trial was designed and conducted, after long being dismissed, were suddenly supported in a recent investigative tour de force by David Tuller, academic coordinator of UC Berkeley’s joint masters program in public health and journalism. In response to his investigation, six scientists from Stanford, Columbia, and elsewhere sent an open letter to the editor of The Lancet demanding a fully independent investigation into the trial. After three months with no response from The Lancet, the letter was republished with 42 signatures. After that, The Lancet editor, Richard Horton, emerged from witness protection and invited the group to submit a letter about the concerns for publication. The study is under increasing scrutiny by scientists and science writers about whether its conclusions are valid.

The question of how all this happened and how the criticism is being handled have sent shockwaves through medicine. The results from PACE (including these) have been published in prestigious journals and influenced public health recommendations around the world; and yet, unraveling this design and the characterization of the outcomes of the trial has left many people, including me, unsure this study has any scientific merit. How did the study go unchallenged for five years? And how could journalists have recognized the problems before reporting unqualified, but unjustified, good news?

http://www.stats.org/pace-research-sparked-patient-rebellion-challenged-medicine/
 

Cheshire

Senior Member
Messages
1,129
There's also an editorial:

On PACE
by Trevor Butterworth

So what happens when the largest trial of its kind produces a result that overturns patient expectations and understandings? The institution of medicine trusts the trial; that’s the power of science, after all: the capacity of an appropriately designed study to disentangle perception from probability, cause from correlation, personal bias from objectivity. The PACE trial was “rigorously designed,” according to CNN, and it was published in one of the most prestigious medical journals, The Lancet, so its conclusions not only had the power to affect the way the condition was treated, they had the power to set the agenda for further research, potentially foreclosing other approaches.

As a result of PACE, the UK’s National Health Service, the Centers for Disease Control, the Mayo Clinic, and Kaiser all ended up recommending cognitive behavioral therapy and exercise for ME/CFS. There is now a PACE-like trial in children—MAGENTA. PACE has become the paradigm for understanding a condition affecting millions of people.

http://www.stats.org/editorial-on-pace/
 

sarah darwins

Senior Member
Messages
2,508
Location
Cornwall, UK
This is a good article, and quite detailed too, and I think we should thank the author for her work.

Absolutely. She seems to have done the legwork. For example:

Under the 2013 Criterion iv, “passing” either the fatigue or the physical functioning threshold automatically results in their recovery on the ME/CFS criteria for each of the three types of criteria for ME/CFS used. In other words, the fourth criterion is effectively erased in the 2013 revision. The result is that the single objective measurement of the recovery criteria—that the patient no longer meet an originally specified definition of CFS—is no longer in place. This was such a shocking revelation, considering that the authors claim not to have changed the fourth criterion, that we asked the authors to confirm, which they did.

Worth noting that this Sense about Science is nothing to do with the UK organisation of the same name, which is a very different beast.
 

Comet

I'm Not Imaginary
Messages
693
http://www.stats.org/editorial-on-pace/

The reaction to patient criticism and Tuller’s story by the PACE researchers and the Lancet has been to deflect rather than to dissect; and the story has become one of questionable demands for patient level data and social media provocations and threats.

While these are not trivial issues, they are something of a distraction from the fundamental one, which is that the way PACE was designed and redesigned means it cannot provide reliable answers to the questions it asked. There is really not a lot that can be said to mitigate that; it’s a terminal prognosis.

I have been wondering lately if the PACE data release is really that important. We know the flaws of the study. Do we really need the data to discredit the study? Doesn't it do that all by itself? But how do we educate media/docs/researchers/family/etc?

But there is one more important thing to say. Sometimes, justice is blind to those who serve its cause. Perhaps the service is not so easily rendered in the kind of heroic narrative that tempts Hollywood—the easy clarity of right triumphing over wrong. It takes digging in the weeds to understand who did what and why that was important—and we prize effortlessness, especially the effortless kind. David Tuller may not get a Pulitzer Prize for investigating PACE trial on a blog; but his service to—and we do not exaggerate—millions of sufferers around the world make it hard for us to think of another work of journalism so deserving of commendation.
My bold.
 

jimells

Senior Member
Messages
2,009
Location
northern Maine
I have been wondering lately if the PACE data release is really that important. We know the flaws of the study. Do we really need the data to discredit the study? Doesn't it do that all by itself? But how do we educate media/docs/researchers/family/etc?

No, we don't need the data to discredit the study. Their own words in the abstract of the long-term followup study thoroughly discredits the study:

http://www.ncbi.nlm.nih.gov/pubmed/26521770
Sharpe et al said:
There was little evidence of differences in outcomes between the randomised treatment groups at long-term follow-up.

This needs to be shouted from the rooftops. Instead it has been largely buried and ignored.

We do need the data to investigate possible fraud by the researchers. If the data reveal evidence of harm that was buried by the researchers, they might need to revise their retirement plans. Think of what happens to pharmaceutical companies when they hide harms from their drugs.
 

SilverbladeTE

Senior Member
Messages
3,043
Location
Somewhere near Glasgow, Scotland
"P.A.C.E.?
A DEN OF STIIIIIINKIN' EVIL!
COVER YOUR NOSE BOO, WE WILL LEAVE NO CREVICE UNTOUCHED!"

~
"SQUEAKY WHEEL GETS THE GREASE!"
~
So Sayeth Minsc & Boo!

:D


tumblr_nqhvya2DtE1t4tltzo1_500.jpg


(the gamers will get it I hope, lol)
 

medfeb

Senior Member
Messages
491
Looks good...

Just a check on the following quote from the article
Patients could not be suffering from “primary” depression or anxiety—in other words, depression or anxiety that is considered to be the patient’s most significant diagnosis. However, secondary depression was acceptable, and in fact quite common among the patients

However, the PACE protocol said
The research nurse (RN) will use a standardised psychiatric interview (the Structured Clinical Interview for DSM-IV – SCID) [30], under supervision by a participating centre PI or nominated deputy, to exclude those who are at significant risk of self-harm and those with psychiatric exclusions listed in the Oxford diagnostic criteria for CFS.

Oxford defines these psychiatric exclusions:
Patients with a current diagnosis of schizophrenia, manic depressive illnes, substance
abuse, eating disorder or proven organic brain disease. Other psychiatric disorders (including depressive illness, anxiety disorders, and hyper-ventilation syndrome) are not necessarily reasons for exclusion.

And the 2011 PACE publication appears to reflect that. Was this reported differently in one of the other PACE publications or did they somewhere say that primary depression and anxiety were excluded?
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I have been wondering lately if the PACE data release is really that important. We know the flaws of the study. Do we really need the data to discredit the study? Doesn't it do that all by itself? But how do we educate media/docs/researchers/family/etc?
They are fighting a rhetorical defence which may go on for many years. If we had the data it would probably be game over, though it would take a fair while for experts to analyze it. The data is a shortcut, its clear history will show the PACE trial was seriously flawed, and nothing will save it.
 

A.B.

Senior Member
Messages
3,780
The data will also let people such as Coyne re-analyze it and show how much bias was introduced by the post-hoc changes to the protocol. I'm sure he would love it. PACE authors would find themselves exposed as manipulative liars with suspicious, no, alarming conflicts of interest.
 
Messages
2,087
They are fighting a rhetorical defence which may go on for many years. If we had the data it would probably be game over, though it would take a fair while for experts to analyze it. The data is a shortcut, its clear history will show the PACE trial was seriously flawed, and nothing will save it.

The thing about the data requests is it allows the authors to continue to say we can't release the data due to trial ethics blah blah blah.
Of course they continue to ignore the flaws in the trial and now the data release becomes the story instead of the trial flaws.

They wrote to the wall st journal explaining how they have released data to researchers but unfortunately can't release the data any other way blah blah blah.
The data is a side issue. One worth fighting but even if we get the data and even if it backs up the authors claims the trial is still useless.

My fear is it might back up the papers claims and the authors would spin such a story saying their paper stands up to scrutiny.
Even though of course the trial itself is fundamentally flawed.
 

Comet

I'm Not Imaginary
Messages
693
They are fighting a rhetorical defence which may go on for many years. If we had the data it would probably be game over, though it would take a fair while for experts to analyze it. The data is a shortcut, its clear history will show the PACE trial was seriously flawed, and nothing will save it.
Yes, agreed. :) I guess my point is that even if we don't get the data, the trial is still seriously flawed and seriously bad science.

We may never get the data, but we do know many significant flaws in the trial (conflicts of interest, changed objectives, patients worsening in the trial yet still possible to be declared cured, high drop out rate, proper CBT doesn't allow one to say he or she still feels sick even if he or she really does, improper patient inclusion criteria, etc).

Why aren't those things alone 'game over'? Seems to me that there is no need for a defense to go on for many years when we already know how poorly PACE was executed. Of course, that and a buck or so will get you on the bus. That is, if you can make it to the bus stop...
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Why aren't those things alone 'game over'?
Because science involves adversarial argument. We have to bring these things to the attention of enough doctors and researchers. If we have proof its rubbish science it does not matter if we cannot get that proof out to others. Science is about communication as well as hypothesis testing.

Its been very little time as science goes since we had traction on the problems we have been complaining about for up to thirteen years now. The Virology Blog articles are still having an ongoing impact, and more and more science articles are being produced. By increasing the controversy through denying data requests the PACE investigators are actually increasing scrutiny, and more and more of the methodological and other flaws will be seen in the wider scientific community.

Think of it this way. They know they are in trouble, but there is no central authority to put a stop to the shenanigans. Nor would we want one, because that would be another place that science could be abused. Instead its like the proverbial camel with the massive pile of straw on its back. In the end it will be one tiny straw that collapses the camel, but that piece of straw will be on top of many many other pieces of straw.

The more controversy there is, the more it will be talked about. The more its talked about the more scientists will see the flaws. Everything they have done lately accelerates the process. There is too much information out there now.

The only thing that might save them, however improbable, is release of the data. They NEED to show they are above board and did everything right, but that option looks close to absurd.