Efficacy of cognitive behavioral therapy targeting severe fatigue following COVID-19: results of a randomized controlled trial 2023, Kuut, Knoop et al

Yes, he did put a positive spin on it, and quoted results as if they mean somehting significant. He dismissed the suggestion that CBT just gets people to stop complaining, (ie to fill in questionnaires differently, I assume he means).

Summary of the program on YouTube:
In his weekly clinical update, Dr. Griffin discusses variant specific clinical performance of a SARS-CoV-2 rapid antigen test with focus on omicron VOC, ventilation in buildings, COVID-19 mortality among selective serotonin reuptake inhibitor users, risk of post-acute sequelae of SARS-CoV-2 infection associated with pre-coronavirus disease obstructive sleep apnea diagnoses, trajectories of the evolution of post COVID-19 condition, and efficacy of cognitive behavioral therapy targeting severe fatigue following COVID-19.
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He did talk about the importance of physical therapy needs being different for those with PEM who need pacing.
 
Trish said:
He did talk about the importance of physical therapy needs being different for those with PEM who need pacing.
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where did he talk about this?

Does anyone have handy the Dutch study that included the long-delayed actigraphy results from three papers that showed they did not reflect the positive subjective reports published years earlier from the same studies? Was Knoop involved in one or more of those?
 
ME/CFS Skeptic said:
Think it was this one: https://pubmed.ncbi.nlm.nih.gov/20047707/
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It is stunning isn't when you read this and realise these people believe that their 'effect' is actually real rather than just responses to their questionnaire, rather than another measure that should be being triangulated with other things.

I'm continually astounded how these people hug to their own questionnaires with leading questions done under certain influencing conditions, with high drop-outs normally filtering out what I guess would be the most ill patients, are somehow 'the effect' and 'certain' vs the feedback of sometimes the very same patients who were on said trial saying 'when you don't strait-jacket me with certain questions and conditions but ask whether my fatigue is better and certainly the illness then this has not helped'.

Imagine if someone who didn't have this bigotry targeted at making sure their voice wasn't heard did something like a work course, and were saying 'this didn't work' in a general warning, perhaps reporting harm longer-term and had objective evidence that logically meant that what they were saying was correct being told that 'our very specific leading survey is the whole truth and fact and says the opposite'. It's nonsense.
 
Arvo said:
Damn, I can't go on with the doc, but the reviewers for ZonMw noticed problematic stuff (like when you're recruiting beyond 6 months then it's no longer about preventing chronic fatigue, there's no patient participation, CIS target not very concrete etc.) Answers from the research team/Knoop look at quick skim interesting.
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Could you please point me to where this question was mentioned and also the preventing bit? It was also mentioned on the website but this looks more interesting.
 
Grigor said:
Could you please point me to where this question was mentioned and also the preventing bit? It was also mentioned on the website but this looks more interesting.
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Regarding prevention, I made some notes earlier on all the times prevention was named as the aim, and am now making a doc out of it with page number reference. I'll post it here when done. It's clear the intention of the study was to prevent chronic fatigue after the acute phase of covid-19.

You can check page 60 and 70 for the reviewer remark and Knoop's response. It's in dutch, they'll be GTranslated in my doc.

Apart from the changed study aim, something else doesn't add up, I think.

Summarized: Knoop says he never saw a study fill up so fast, but also extended the criteria time frame due to feasability, negating his study aim in the process.

Due to the prevention aim, the study group would be recruited between 3-6 months after positive covid test or hospital admission. When feasability is questioned due to a lack of post-acute covid patients with "fatigue" in this timeframe (we're talking just after the first wave), Knoop repeats the 3-6 month timeframe [it's about prevention after all], but says that this can be extended to 9 months if not enough patients are available, or "in the unlikey case that this would not suffice" up to 12 months.

This is what the reviewer responds to when they say that in that case it would no longer be about prevention.
(Knoop made clear that less than 3 months fatigue is the acute stage, after 6 months fatigue is chronic.)
And Knoop answers that there is enough inflow for recruitment and expects that ample measures are taken to recruit the aimed-at 114. They do foresee the possibility that there's a time window on having enough patients available that got sick with COVID 3-6 months earlier, that these patients might arrive in a short time frame and the group will be too big for them to include and treat on time, but they are taking steps to prevent that situation (training planning, personnel selection etc.), and in the eventuality that it does happen then they will use as small as possible steps of extension to increase inflow, 7/8 months (as six months is rather arbitrary and "At 7 or 8 months there is also an extremely short duration of complaints compared to previous intervention studies in which there was a duration of complaints until intervention of years." When you talk about prevention this is a bs comparison, as those studies were not about that, but ok, 7 or 8 months extension in case it gets tricky for feasability despite measures to prevent that. (This is June 2020)


In his ZonMw ReCOVER study promo interview Knoop was bragging about how many people "spontaneously registered themselves" to participate. He says: "I have many years of research experience, but I have never seen a study fill up so quickly."

Ok, so, following that there was no need to expand to 9 months, or the "unlikely" 12 months, right?

So why were the extensions used for feasability and is the study group used "3-12 months post-COVID-19"?

(The paper also doesn't mention prevention, when it was their setup. Can you do that, change your study aim after getting a grant for a different, more ambitious goal? Was it dropped in the peer review process, as they couldn't claim it as "prevention" per the study aim? )

The 2021 trial protocol states:

Changes in trial design following approval
At the beginning of the study, the upper limit for including patients was extended from initially 6 months to 12 months after diagnosis or hospital discharge (inclusion criterion b). This enhanced the feasibility of the project as patients from the first COVID-19 wave in the Netherlands were then eligible when initiating recruitment in October 2020
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So...they stretched entry criteria so they could still include first-wave patients when starting too late to include them (the problem the ZonMw project review pointed out, but they said they could avoid), negating the whole setup and aim of their project doing so. Which they try to justify with:

"In the ReCOVer study the upper limit for including patients was extended from initially 6 months to 12 months after COVID-19 diagnosis or hospital discharge. Despite this extension, we are still able to test whether we can prevent the development of chronic fatigue. Although a duration of 6 months is generally used to define chronic fatigue, this cut-off is somewhat arbitrary. Also in cases where fatigue is present since 12 months after COVID-19 it can be considered as a relatively short duration compared to previous intervention studies where patients have been included with an average fatigue duration up to 5 years)
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Of course this is utter bs reasoning, as those studies were not about prevention, but later stage treatment. This is also the same bs reasoning Knoop used in June 2020 to justify possibly extending the recruitment criteria of his "prevention" study from 6 to 7/8 months, now stretched to justify the actual extension from 6 to 12 months.
Also, when someone's incapacitated by "fatigue" for 10 months already you are too late for "prevention".
To call the the six month mark "arbitrary" when discussing the possible extension to 7 or 8 months (with claimed measures in place to avoid that eventuality), was already weak, but here they demonstrate that they truly just declared it "arbitrary" on a whim because they needed it stretched to get to their participant number. Of course acute < 3 months & chronic > six months was simplistic to begin with, but you need to draw a line somewhere, and it was their own assertion this was how it would work, until it didn't suit them.


In line with this, the recruitment web page clearly said the study was about prevention, but then mentions participants will be 3-9 months since diagnosed with c-19 (so the extended timeframe, no "small steps"), and the questionaire used to see if you might be eligible for participation uses 3-12 months (the "unlikely" scenario). So they recruited for participation assessment in the extended timeframes.

Still, Knoop was sure he would be able to make 114 when he submitted his project plan, so with the stream of self-registers, quickly filling up the study, I reckon it should not have been difficult to get to 114 3-6month patients out of 721 assessments, no? Why was extension necessary for feasability when he says he was swimming in possible participants, "I have never seen a study fill up so quickly."?

This project went from being about prevention (what they got the grant for, it was a special study making use of an "unique opportunity"), to being about prevention while participants were already well into the phase where their "fatigue" was deemed chronic by the researchers themselves (Schrödingers cat has a rival, Knoop's chronic fatigue- It's both preventable and already chronic), to not being about prevention at all but about up-to-12-month fatigued patients being "less severely fatigued" after CBT.
 
Good examples of ideologues who simply ignore reality and construct whatever they need for their conclusion to work out. Conclusions that they had for decades, in mindless indifference to the millions suffering from their incompetence.

If they paid the slightest attention to data, they'd know that the 6-week mark is already a good predictor of chronicity, that past this point recoveries become more rare, and rarer still over time. But they just choose whatever they want, mostly sticking to the historical arbitrary mark of 6 months. There is a case to make that early rest can prevent. But it has to be early, basically immediate. We already have data on this, and they just don't bother adhering to reality.

It's truly fantasy medicine. They don't observe anything, don't hypothesize, certainly don't test anything. They simply make assumptions, most of them false and easy to falsify, and run with it. But because this is an area that gatekeepers don't care about, they just rubberstamp anything that aligns with manufacturing the fiction that there is nothing to do here.

None of this is legitimate. This whole system needs to be rebuilt from scratch, it clearly cannot perform, doesn't deliver anything and even makes a mockery of the idea that medicine is scientific, when really it's a mix of science, with loads and loads and myths and traditional politically-driven beliefs.
 
Peter Trewhitt said:
As always @dave30th, a useful and clear account.

These are issues that were research methodology 101 when I was an undergraduate some forty five years ago, how do the BPS advocates just not get the problems with subjective outcomes used in unblinded trials, when I suspect they would never accept it in a drug trial?
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especially when they withhold the objective data--what little there is.
 
@Grigor and those interested, here is a collection I made on the original aim of this study (prevention of chronic fatigue after COVID-19) and the timeframe used for the participant criteria (which relates to the study aim). I copied the relevant info and collected it in one file.

Summarized: the study aim was to research if CBT would prevent COVID-19 fatigue to become chronic by applying it before the chronic phase (>6 months) arrived. This goal was repeatedly stated: the researchers made clear that this was a unique opportunity for this study, and in the project proposal said that the CBT would be “delivered timely in order to test its efficacy to prevent, rather than treat, chronic fatigue. This has never been studied before…”

There was mention of the possibility to extend the timeframe of the participant criteria a bit beyond six months (7/8/9 months in steps) if there weren't enough participants, to increase inflow (which already alarmed a ZonMw reviewer as that would mean studying the prevention of chronic fatigue after it had already entered the chronic phase - not possible), but the researchers were repeatedly confident that they would have ample candidates. An extension up to 12 months was mentioned as an option but deemed an unlikely scenario. After the trial Knoop again confirmed that there were more than enough participants. So on paper there was no need to stretch the entry criteria and with it torpedo the study aim.

Still, after getting the grant approval (where criteria extension was no condition, as the researchers assured the ZonMw committee feasibility would be fine), the researchers used the "unlikely" greatly extended timeframe of up to 12 months for the research criteria, effectively pulverising their study goal, as (also by their own standards) participants would be well into the chronic fatigue phase, so no possibility to study its prevention. In the 2021 trial protocol it is stated this was done for feasibility, and the researchers try to make the claim that "prevention" can still be studied, as the participants' chronic fatigue is still of shorter duration than that of participants in other CBT studies. This is not only nonsense and goalpost-moving (these studies were not about prevention), but it (ironically also) stretches the same argument (which was used earlier to justify extension to 7/8 months) well beyond reason.

Reading the abstract and using term search, the final publication makes no mention of the goal to prevent chronic fatigue after acute COVID-19 by using CBT, or using it in a “timely” way. Instead it is a run-of-the-mill CBT-for-fatigue trial, with the usual problematic issues, that speaks of “reducing severe fatigue” with CBT in patients who have had COVID-19 up to 12 months before, and whose fatigue was already chronic.

The sources are:

The FOI request documents
  • Project proposal forms from 13th of May 2020
  • ZonMw reviewer response to the project proposal
  • The letter to Knoop with a positive recommendation for his project with a list of issues he needed to address from 4th/5th of June
  • Grant application forms from June 16th 2020
  • A reply from Knoop to the issues he needed to address (these are mentioned in full here)
  • ZonMw reviewer response to the grant application
  • A letter from Knoop to the ZonMw committee commenting on the reviewers' remarks
  • The grant approval letter to Knoop from 13th of July 2020
And
  • The ReCOVer recruitment website moenacovid.nl (tired after covid)
  • the 2021 trial protocol
  • the 2023 ZonMw post-study promo interview

If you are interested in this study, I recommend looking at the FOI files as they contain a ton of information, also in english. It gives a lot of trial content, but e.g. also discusses an awaited upcoming Australian sibling of this trial, and shows signs of problematic COI's and claims.

The files can be found here (click "WOB verzoek ReCOVer-onderzoek" at the bottom of the page)

A PDF with the english grant application forms (an exerpt from the original FOI request documents) can be found at the bottom of this post.
 

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Peter Trewhitt said:
As always @dave30th, a useful and clear account.

These are issues that were research methodology 101 when I was an undergraduate some forty five years ago, how do the BPS advocates just not get the problems with subjective outcomes used in unblinded trials, when I suspect they would never accept it in a drug trial?
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It's not them who's the problem. They're just taking advantage of a system that wants their stuff and doesn't care how they do it.

It's the regulators, the gatekeepers, the funders and the institutions that allow this that are to blame. None of this BS should ever be considered, it only keeps going because people want it, approve it and fund it.

Obviously they see the issues with their research. And they don't care. They get funded anyway, awarded, promoted, the lot. They are like a group of students who were somehow allowed to make their own curriculum, without any oversight, and self-grade the entire program. Without surprise, everyone graduates with full honors, 100% mark. The teachers are to blame here. The administration is to blame. Everyone involved can see this is all BS, they just don't care because no one stops them.
 
rvallee said:
Everyone involved can see this is all BS, they just don't care because no one stops them.
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I think people can't recognize problematic practices like relying on self-reported outcomes in CBT studies that set out of modify how participants view these outcomes.

They believe they're doing good science and are met with refusal not because there are serious problems with the science but because of the stigma of mental health or something like that.
 
dave30th said:
It looks odd, but I don't know statistics well enough to really have an opinion about what it could mean. I'm also not clear on when/why one would use a standard error rather than a standard deviation.
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Standard deviation shows spread, but standard error is used to compare means between groups, usually via significance testing using confidence intervals. But in this case, as the numbers in the two arms are essentially the same, we can just use standard error as a proxy for standard deviation.
 
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