But it's 'just' Chronic Fatigue Syndrome, so who cares

Not going to apologize in advance for the length of this. Not this time. If this is tl;dr, go to the bottom, and I’ll post direct links to only the most important items.

During the winter of 2011, the Lancet, arguably the most prestigious medical journal on the planet, published a paper that investigated “treatments” for Chronic Fatigue Syndrome. Dubbed with its acronym, the PACE trial was almost immediately controversial. It was published during a time when there was still active scientific debate over the involvement of the XMRV retrovirus (later confirmed to be a lab contaminant, prompting the retraction of the study published in Science in October 2009 that suggested a link, following a then-growing body of evidence linking it to prostate cancer), leading some to wonder how the therapies considered to show the most efficacy—Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET)—could be effective in a condition like CFS.

CFS is a term that was coined to describe what many believe was an outbreak of Myalgic Encephalomyelitis, most specifically in the mid-1980s in Incline Village, Nevada, but with similar contemporaneous outbreaks in Lyndonville, New York, among other places. There were other recorded outbreaks of this illness, including in 1934 in a hospital in Los Angeles, in the 1940s in Iceland, and, most notably, in 1955 at London’s Royal Free Hospital, following which the term ME was actually coined. There have been several criteria penned to describe the illness, with some considered overly broad, and others narrow. The criteria used to define the patient cohort in PACE was perhaps the loosest criteria yet seen, the Oxford Criteria. (New York Times writer David Tuller writes about issues with criteria here)

The initial paper can be found here. It was accompanied by an editorial, and a shit-ton of publicity. The authors spoke of ‘recovery’ and the return of these patients to normal function. There was worldwide coverage, from Reuters and CNN, to NPR and the Guardian, among many, many others. Included in this were more specifically medically-oriented websites such as Medscape and MedPage Today. The New York Times published David Tuller’s piece on the study, as well.

There was some initial criticism, mostly from ME (and/or “CFS”) patients, and their advocates. However, most of the coverage was fairly standard, perhaps a cut above a simple rewriting of press releases, which unfortunately is said to be fairly common these days when it comes to science reporting. It’s fair to say David Tuller’s piece was the one that asked the most questions about what it was exactly the paper said. The study authors responded here, and Tuller offered a response in kind.

PACE was a trial years in the making, which cost the equivalent of $8 million. A protocol for the trial had been published some years prior. Aside from the selection criteria, it was soon noticed that there wasn’t a heck of a lot in the way of objective outcome measures in the actual paper, though the protocol had stated there would be. But there were other changes, the most obvious having to do with a questionnaire that forms the basis for an outcome considered quite important in a great deal of medical research, the SF-36, which, it should be noted, is patient-reported. Well, the protocol set entry criteria as needing to be at or below 60, on a scale of 100, on the SF-36, though this was at some point revised upwards to 65-or-below. The original point set to serve as an outcome for ‘recovery’ was 85…but in the actual paper, this had been revised downward to…60.

This meant that, hypothetically, one could enter the trial with an SF-36 score of 65, and actually deteriorate, leaving with a score of 60, yet be deemed ‘recovered.’ And not only did this not seem to be a problem for peer reviewers at the Lancet (or anyone except for David Tuller who covered the publication in the media), the editor, Richard Horton, doubled down, claiming that criticisms were less than credible. Although there have been a few letters published in journals since, that is more or less how most of the criticisms have been characterized. UK Freedom of Information requests have almost all, if not all, turned down, in some cases being labeled as ‘vexatious’ by the study authors. There have been several patients and patient advocates who have detailed problems with PACE for a very long time now, but for the most part they have been roundly ignored.

Some months after the initial PACE paper, reports surfaced in the UK media that CFS researchers had been the target of death threats from sufferers. One headline read “Head Case,” while another groused about how such people had enough energy for death threats.

To be fair…NO, OF COURSE THREATENING SCIENTISTS IS NOT ONLY A CRIME BUT WRONG ON EVERY LEVEL. Did it happen? Quite possibly, although the idea that it justified the headlines seems highly questionable, especially in light of this discussion. Well, whatever. I bring this all up mostly because it would be poor form to leave it out, but once again there was reason for coverage that, wittingly or not, doesn’t do much to emphasize either the reality of ME nor the paltry and unsuitable research that’s dogged us for decades, resulting in zero treatments, beyond recommendations that we engage in CBT and GET. (Earlier this year, the Institute of Medicine issued a report that recommended the name of the condition be changed to reflect that exertion is actually NOT something we should be prodded towards.)

More research followed: most notably a 2013 paper discussing recovery, though we have also seen researchers determined to look elsewhere. Yes, Rituximab is a chemotherapeutic agent used in some cancers, as well as Rheumatoid Arthritis. A 2011 paper from Norway, as well as a 2015 followup, seemed to indicate some very positive outcomes, though it wasn’t exactly accompanied with much media coverage (although New Scientist did weigh in earlier this year). Other coverage wasn’t quite so glowing; this blog eviscerates one doctor, not without cause, for utilizing this drug in clinical practice prior to a sufficient body of evidence being established; however, this speaks to desperation having penetrated past patients, directly to physicians that try to treat CFS patients, as well. That said, they weren’t too impressed with the research, either, asking of the Norwegian oncologists, “What were they thinking?” And it’s also fair to point out that they weren’t alone in their criticism, though that comment is signed by a gaggle of what for ME/CFS patients are a ‘usual suspects’ of psychiatric theory in this disease. (In the thread following that comment, however, a researcher who’d pioneered research into Rituxan disagreed with their criticism, and is now working to help launch clinical trials in the UK)

Fast-forward to last week. The aforementioned David Tuller had previously published a fairly long work on CFS, relative to the horrible mismanagement of investigation into the condition by the Centers for Disease Control and Prevention. Prevention? Yikes. Well, Tuller has apparently been working on criticisms of PACE for awhile, and last week filed a four-part deconstruction, in three installments:

TRIAL BY ERROR: The Troubling Case of the PACE Chronic Fatigue Syndrome Study

TRIAL BY ERROR: The Troubling Case of the PACE Chronic Fatigue Syndrome Study (second installment)

TRIAL BY ERROR: The Troubling Case of the PACE Chronic Fatigue Syndrome Study (final installment)

After years of as much avoidance as they could muster, the authors of PACE—and the Lancet—now were faced with something that wasn’t coming from a mere patient, something that would be far more difficult to simply ignore. Ah, but timing is everything. What wasn’t publicly known was that there was another PACE paper in the pipeline, which was published on Tuesday in the Lancet Psychiatry.

It was accompanied again by an editorial, and another PR effort, though nowhere on the scale of the initial paper, or much else to do with CFS, like XMRV, for instance. Still, this was unlike any other I’ve ever seen. The Daily Mail’s article was bad enough, and fairly typical of how this sort of thing has gone for a very long time. The Daily Telegraph, though, took the cake. Their Science Editor Sarah Knapton went just a little further, with a sub-headline that blared “Oxford University has found ME is not actually a chronic illness.”

I’ve seen nasty, ignorant crap before, but never in a place like this. The Science editor at the Daily Telegraph? Well, I do at least realize that one mustn’t get too upset at eyeball-grabbing headlines, because they’re usually not written by the writers themselves…usually it’s the editors? Wait…um…

Well, this has set off a bit of a controversy, with pieces devoted to the absolute stupidity of the coverage, in the Guardian, in Science, and in a patient’s own article that followed in the Telegraph the next day. (There was also a similar piece in the Irish Independent, along with another companion piece written by a patient, in this case the Irish gentleman who has, along with others, done a great deal of work in criticizing PACE.)

The headline in the Telegraph was so strong that the authors actually had to walk it back.

Enter James Coyne. Coyne has been openly critical of “Biopsychosocial school” of psychiatry, advocates of CBT and such, for some time, based on skepticism of claims versus actual data, and has cast a wary eye of sorts towards those who have made great claims of efficacy of CBT in CFS for awhile, but never really engaged directly.

He has now.

I don’t know how to embed Tweets (yet) and will collapse when I’m done with this, so please forgive me. Best I can do at the moment.

“Shameful.”

And on and on.

They got this guy angry. It took years, a lot of work, a lot of clueless dismissal of people that shouldn’t have been dismissed, because their criticisms were actually valid, and a NY Times journalist, but they did it. Now, there are a lot of things that could be said about some of these psychiatrists and how much money they’ve managed to save the NHS from investigating CFS from anything but a psychiatric perspective, not to mention the insurance industry, but we need to keep all fact-based for now. The implications are probably pretty significant, though—all the more because the casting of CFS as being something best mediated through CBT & GET strongly suggests it is of psychiatric origin, no matter how many times the authors claim that’s not what they’re doing. The result of that is physicians almost never taking it seriously leading to a volume of suffering I’ll go out on a limb and suggest constitutes the greatest scandal in the history of modern medicine. I can speculate wildly, though—I’m not bound by any considerations. These people were. And are.

Yesterday, Coyne published this blog. Most of us have gotten used to the idea that things are never really going to change for us. If they do, the past 10 days may well be seen as a big moment, as we once viewed the publication of the XMRV paper in Science. Someone who is actually scientifically credible is telling Simon freakin’ Wessely, winner of Sense About Science’s John Maddox prize, the President of the UK’s Royal College of Psychiatry, who was Knighted by the UK Government, is telling THAT guy, “Evidence, please.”

Perfectly reasonable request, but all too often directed at us, and it’s a difficult question for us to address, because of a lack of research into CFS, beyond pilot studies, anyway. No funding. Oh…TONS and TONS of psychiatric research, though. They never seem to have a problem with funding. ($8 million for ONE STUDY?) But that’s a whole other matter.

I just never thought I’d see someone with any credibility be able to direct a barb like that at someone like Wessely.

Tuller was unsuccessful in soliciting comment from any PACE researchers, or the Lancet, for that matter. Of course, they requested the blog owner allow them a platform to respond, which he did.

PACE trial investigators respond to David Tuller

Tuller’s response here…maybe they should have quit while they were ahead? The long, detailed deconstruction of their study was one thing. This is an absolute evisceration, and well-deserved.

David Tuller responds to the PACE investigators

***

Will anything change? It’s hard to say. The UK’s NICE Guidelines remain what they are and have been, not that anyone should expect anything to change overnight, particularly in the absence of a retraction (and we all know how long it took the Lancet to retract that other paper, don’t we. The NHS is still recommending CBT & GET. King’s College, home to Simon Wessely, is still in favor of CBT & GET.

In the USA? Well, the CDC has archived their “Toolkit,”, which contained a direct link to the UK’s St. Bartholomew’s, where PACE principal Peter White oversees a CBT and GET for CFS, but they are still actively recommending CBT and GET for CFS, even though the Institute of Medicine’s report

recommending a name change to specify the problems with exertion was published 9 months ago.

On a level not as pegged to policy, someone plugging a book about psychosomatic theory is still getting plenty of ink in the Guardian. And sub-Perez Hilton geniuses will probably be pulling crap like this until, well, until they can’t anymore. But among those one would assume are able to think for themselves, well, maybe one day the brilliant minds at outfits like RationalWiki will realize that there’s something actually going on with this illness beyond pointing fingers at a small number of alleged assholes, which is all they seem to care about (not that they are alone in this, amongst the ‘skeptic’ community).

***

In the 1980s it was said, following controversy surrounding papers suggesting that the cause of “CFS” was the Epstein-Barr virus, that the New England Journal of Medicine vowed never again to publish anything involving the condition. To date, they have made good on that. Although Science retracted the also-controversial XMRV paper two years after publication, they have recently published research from Columbia University. But other journals have steered clear. If this paper is retracted, do more journals adopt the NEJM’s approach? Beyond that, I also wonder what happens to research since 2011 that cites PACE, and that includes four reviews.

Whatever happens next, it shouldn’t be boring, that’s for sure.

thelancet.com

virology.ws

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telegraph.co.uk

Youtube Video

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blogs.plos.org

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