A general thread on the PACE trial!

Sometimes humour is the best way to get people to gain insights. If scientists were to appreciate the funny side of these (and many other such) absurdities, then they would inevitably have to realise the rubbish science involved.

 

Reading this from Horton and my hypocrisy detector is going WOO WOO WOO.

https://twitter.com/user/status/1272226559655587841


Horton helped the abyss gaze back. He helped enable pseudoscience and the politicization of medical science. He can be mad all he wants, this is the house he helped build.

 

Is there really no way to prove that ME/CFS is not deconditioning? It's not about us knowing, but about convincing others who still seem to believe it, or at least turn a scientific blind eye to it. Interventions trialled for one illness, being prescribed for a different illness, without any trials of it for the second illness. Surely even NICE would have to see something a bit risky there?!

So my thoughts are:

1. Need to avoid the confounding factor, that some more severe pwME will inevitably also be deconditioned, given their enforced inactivity.
2. Best way to do that might be to only look initially at those more mildly affected, who are sufficiently active to not be deconditioned. This avoids the confounding factor.
3. Do whatever is necessary to prove these pwME are not deconditioned.
4. Once you have proof that these pwME are not deconditioned, you then have proof that the primary physical impairment of ME/CFS is not deconditioning! Major step.
5. Once you have proved '4', you then have good evidence that even for more severe cases of ME/CFS, the primary physical impairment is still not deconditioning, even though secondary deconditioning may be present.
6. Once you have demonstrated the above, you have then proved even to the dumbest scientist or politician, that GET and CBT-a-la-GET were trialled for an illness that pwME do not suffer from, and have never been trialled for the illness they do suffer from.
7. You then have proof that untrialled treatments are being being prescribed to pwME.

If we could argue '7' conclusively to NICE, then they might want to consult their lawyers.

Any thoughts @Jonathan Edwards, @PhysiosforME?, @dave30th ?

 

Well yes, maybe it would not need a standalone trial, but an authoritative assessment of existing evidence. To me it seems that the key thing is to prove, to a high degree of certainty, that pwME suffer from a different illness to that which GET etc were trialled for, because that must surely kill off any last hope the BPS die hards might cling to.

At the moment we do not have (I don't think anyway) a definitive trial, study, whatever, whose core objective is to show that the primary physical impairment of pwME is not deconditioning. All there is I believe are lots of assorted bits of secondary evidence from assorted sources, which does not carry the targeted clout needed I don't think.

And if that evidence is already out there, then why are we not applying that as per my above post?

 

I think the best way forward is through the COVID cohort. I literally just read a thread asking about whether anyone else was super fit and now can barely walk without getting winded and increasing symptoms. It's mixed of course, and basically shows why the impression of active ambitious people exists, because lazy people don't mention being lazy, only super active people will mention it, as only ambitious people would. Such a cheap exposure bias. BPSers absolutely suck at identifying their own biases.

This cohort is early into this and already facing the PEM wall. Since it will be a rolling cohort this can be done pretty much at any point. It presents itself within a few days and in mild cases too. I see the exact same language, about crashes, relapses, malaise after exertion, running into a wall, sometimes delayed and leading to days of serious deterioration.

Since it's basically impossible to study ME early on, given the 6 months standard, this is pretty much the only way to study a cohort where deconditioning absolutely cannot explain why they are showing the same symptom pattern as a decades-long moderate ME patient.

I have no idea who would be convinced about trying this, though. Since we can't get anything funded I guess we can only wait for someone to do it. But I think this is the key. It's too sudden and identical to perpetuate the deconditioning trope.

 

Sadly, Barry, we have already proved that ME is not deconditioning. The PACE trial showed it was not deconditioning because there was no improvement on the objective measures.

Right at the beginning when they first suggested deconditioning was the problem all they had to do was look at patients and they would have seen it was not true - things are more complicated now because people with chronic fatigue are considered to have the same disease and they are more likely to be deconditioned rather than the typical ME presentation where there are flare ups and remissions. They never looked because they knew they were wrong right from the first day.

A disease which can come on literally overnight with a viral infection cannot be caused by deconditioning. It makes no sense that an athlete would be too afraid to exercise back to full fitness because of bodily sensations, they are used to working through the pain. But then none of it makes sense, they just talk so fast and so loud it is easy to miss the actual content. The neat story is all thta you remember.

There are a number of papers which say their results show that deconditioning is not a factor and it makes logical sense. The BPS theory is that we become more and more deconditioned and they use the severely affected as a kind of proof, but being severely affected is not universal or linear which it would be if they were right in their ideas.

People can be really bad then better for years. They can find an answer for everything but you can make up a story for anything.

Years ago, I wished we had the science to prove to them that ME was physical but I came to realise that there was not proof enough in the world. They accuse the science trials of all the faults they have in theirs (which proves they know how to run a trial but just don't!)

 

But this is my whole point @Mithriel. Yes, of course I know it is well proven enough for sensible people to understand that deconditioning is not the issue for pwME. Of course I know that. But the fact is, like it or not, there are still people, influential people, who cannot, will not, see that. And we are doing ourselves no favours if we just say "well, it's because they are stupid, etc, etc".

The reason we do not get anywhere with such sectors within science, is because we do not present a solid, single point of confirmation, that the primary physical impairment with ME/CFS is not deconditioning; we may not yet know what it is, but we most certainly do know what it is not. We instead rely on examples such as you cite, an assorted collection of secondary indications from assorted sources, that give far too much wriggle room to those who choose to wriggle off of hooks.

In my career as an engineer, there are many times I have needed to argue a case for something or other, towards very intelligent people who I nonetheless think to be wrong about something. Firing scattered fragments of arguments from scattered sources of data just does not cut it. People are supremely good at seeing the lack of a coordinated argument as a lack of evidence for your cause, and for good reason in truth ... if an argument is uncoordinated then flaws may very well lie within the gaps, even if not obvious. But people exploit that.

So you have to pull it together, in a concise and logically progressed argument. If you can present each simple step in the argument as irrefutable, and people have no choice but to agree with at each step, then by the time you get to the end they have to buy into the whole argument. And if they don't then maybe some lawyers will.

It's not about convincing us. We are the easiest people to convince, because we already are convinced, because we know the truth. It's a hell of a lot harder to convince those we need to convince most.

Your post makes perfectly good sense, except for the assumption that all the current evidence, and how we present it, is enough. If it were enough then we would not still be trying to convince these people of the truth, so it's clearly not enough. The reason is because of what I say above.

 

I think I see what you mean. We will never persuade the likes of Wessely but persuasive, conclusive evidence may let us go round them.

It might be worthwhile doing a well publicised large scale trial as what we have is things like the CPET trials where the results do not match deconditioning.

As it stands, most of our researchers are trying to find the actual cause of the disease to disprove BPS theories but there are lots of accepted diseases where the cause is not known so that could take years especially with the amount of money we get for research.

 

YES! In terms of pwME's health per se, finding a cure and cause is vital. But sadly a more immediate impact on the health of pwME is due to the crass assertions and zealous beliefs of deconditioning. The latter might be easier and quicker to finally overthrow at this point, especially with NICE guideline update on the way.

And from what others and yourself have maybe pointed out, it perhaps would not need to be fresh medical trials? Maybe simply a pulling together of the known evidence, and collating it into something more cohesive.

But if it were simply an article, then it would need a good, logically progressed argument, step by step I think, as per my earlier post, or better. First clearly show deconditioning to not be the issue. Then argue that treatments being prescribed have not been trialled for the illness the ME/CFS is, but only for the illness it definitely is not.

Is there possible mileage here for an article @dave30th?

 

Collating all the evidence against the deconditioning idea into a single coherent argument makes sense, maybe a review article on all the available evidence?

It will never convince the hardcore believers but may prevent the next generation going down that same blind alley. Ironically the original proponents aren't all that wedded to their deconditioning theory anyway, they seem to move between "explanations" as and when it suits them. Faulty cognitions, central sensitisation, whatever. The only thing that matters to them is that the treatment must be GET/CBT.

 

1&2 Day CPET studies have shown substantial overlap (on the 1st day) between patients and controls, with some patients having above average cardiovascular fitness (VO2Peak - so the heart/lungs are not deconditioned) for their age/sex, which suggests that for many patients, deconditioning cannot be considered a perpetuating factor.

Unfortunately, it is impossible to prove this for all patients.

 

re deconditioning, there's this old thread: https://forums.phoenixrising.me/thr...itioning-alone-causes-pain-and-fatigue.15944/

 

But surely it is not about proving it for all patients! Some pwME will inevitably be deconditioned due to activity limitations enforced by their illness. All you have to prove is that a statistically significant number of people, who are properly diagnosed to be still suffering from ME/CFS, definitely are not deconditioned. You have then clearly shown that deconditioning is not the primary disabling physical impairment that pwME suffer from. Surely that is the crux of what needs proving. At which point you have then shown that pwME are being prescribed treatments, GET etc., for a condition they do not suffer from.

Even for those pwME who do have consequential deconditioning, it would still not be safe to prescribe GET, given it has not been trialled for the primary condition they are suffering from.

I appreciate some of my terminology may be technically incorrect, but I'm sure my meaning is clear.

 

I can't read the article because it's behind a paywall but I will assume this quote is legit:

https://twitter.com/user/status/1274395475387600899


Horton has no issue playing both police and judge on bad science, especially in allowing it. I have no idea what he's saying here, that scientific publishing is not his problem? That he's not responsible for the substance of the papers published in his journal? That it's not scientific journals' job to actually vet the substance of scientific research? That retraction is the only way to actually police? Except PACE can't be allowed to be criticized because it has been vetted and is thus unquestionable.

Frankly that explains a lot and especially his politicization of PACE. But it is a damning admission that explains so much about why medical science publishing is very much part of the crisis of validity in scientific publishing.

Don't ask him, he just works there as editor-in-chief and doesn't know what's going on unless it's framed positively at which point obviously PACE underwent endless rounds of review and it's such high science it should be illegal to even question it.

What an utter ass.

 

I put this here, even though PACE is not mentioned in this New Yorker article from two days ago. But other bumps in the road for The Lancet editor in chief are mentioned and he gives this interesting quote regarding the newly retracted hydroxochloroquine study:

“Science is not immune to having bad people. There are bad people in society, and there are bad people in science. Science is very vulnerable to deceit. . . . When somebody submits a paper to The Lancet, the first thing I think is not, Do I need to consider research misconduct?” He acknowledged the political appeal of the hydroxychloroquine study, in light of Trump’s remarks. “It certainly excited our editors and peer reviewers about the possibility of answering that question,” Horton said. “And we all made a collective error, and that collective mistake was to believe what we were being told.”

The journalist is London based Sam Knight.

The Lancet Editor's Wild Ride Through The Coronavirus Pandemic

Moderator note: This post has been copied to Richard Horton on Covid-19

 

Well no, it wouldn't. If secondary condition B is caused by primary condition A, then attempts to directly fix condition B, without first fixing condition A, are doomed to failure.

It's akin to replacing a fuse that blew because of an electrical fault. You can replace all the fuses you like but they will not fix the problem, until you fix the electrical fault that is the primary cause of the problem. Elementary. You'd think highly educated scientists could get their heads round that.

 

Not really sure where else to put this... Retweeted by James Coyne.

https://twitter.com/user/status/1282021043469787137

 

I wasn't sure where to post this:


https://twitter.com/user/status/1281848757626306561