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

[Dolphin]

Hm. They might insist they are including them in another study or something. Maybe they'll do three CBT long covid trials, call them all a success, then publish all three sets of null actigraphy findings together a few years later while explaining how they're not a good measure because they contradict the subjective ones.

The phrasing implies that both groups improved on that measure. But it's hard to tell. Obviously those findings were disappointing to them. I wonder why they even included them? And why, if they decided to, only for the T1 results, not T2 and T3.

Definitely worth writing to the journal and indicating that hiding salient data that might undermine your conclusions is research misconduct. The actual numbers won't change that. But it would be interesting if the non-intervention group actually did better, even if it wasn't statistically significant.

As you know, the 6-minute walking distances in the PACE Trial in the four trial arms all “increased” but still remained low.

 

[Arvo]

"We think,however, that the positive effects of cognitive behavior therapy (CBT) cannot be explained by outcome expectations of patients"

Interesting, as Knoop repeatedly emphasised the efficacy of CBT on the recruitment page, and I gathered that was because he is very aware that creating an expectation of efficacy from the start influences questionnaire outcome.

As he says in 2007: "Significant improvement following CBT is probable and a full recovery is possible. Sharing this information with patients can raise the expectations of the treatment, which may enhance outcomes without raising false hopes."
And
"The first clinical implication of the present study is that a therapist delivering CBT can tell the patient that substantial improvement is likely to occur and that full recovery is possible. By communicating this, the therapist can counterbalance factors that lower the expectations of the patient. Examples of such factors are a negative attitude of certain patient advocacy groups towards behavioural interventions or an oversolicitous attitude of significant others in response to CFS. There is empirical evidence that lower expectations of patients have a negative influence on therapy outcome."

Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? - PubMed (nih.gov)


He even promoted on the view that raising outcome expectations influences outcome. The summary of his 2008 dissertation says:
"It was concluded that significant improvement following CBT is probable and that full recovery is possible. Sharing this information with patients can raise the expectations of the treatment, which may enhance outcomes."


Edited to add: Ha! The reference he gives for his clam in the letter, Cho et al (the Wessely review), predates his assertions above. (2005) He actually uses Cho et al in the study above.

 

[Arvo]

Also:

Too many patients have felt misunderstood when others conclude there is nothing wrong with them in absence of an objective test result. By solely focusing on objective outcomes and stating that subjective experiences of patients are not valid outcomes the same line of reasoning is followed.

This is now the second time Knoop tries to equate shitty research methodology with patient advocacy and allyship. He also did it in the interview with Lou Corsius about the ReCOVer trial, where he conflated subjective questionnaire outcomes after research participants are trained to reframe cognitions (methodology flaw) with "listening to patients" (patient collaboration and agency). Which is of course a turd of an argument.

 

[Arvo]

Every outcome measure has shortcomings. Objective somatic markers are perhaps not sensitive to treatment expectations but often their association with relevant patient reported outcomes is weak.

Hoo boy. He's literally saying that his preferred outcomes are often not associated with objective somatic outcomes. So what exactly is the point of this whole operation then?

That wasn't exactly part of his project proposal and grant request as well: apart from of course the logical expectation of grant givers and other readers that preventing "fatigue" to become chronic means preventing disability (as that's what anyone would normally expect from something saying to prevent a disabling symptom), he says such things as:

Spoiler: Quotes from the ReCOVer project proposal and grant request

(all bolding his)

"We hypothesize that timely offering iCBT for fatigue, that is 3 to 6 months after COVID-19 diagnosis
or hospital discharge, will lead to significantly and clinically relevant lower fatigue severity (primary outcome), will reduce the proportion of patients who progress to chronic long-term fatigue and foster patients’ work ability, physical and social functioning and will give relief of other persistent physical symptoms (secondary outcomes) at follow-up as compared to care as usual."

and

"A novel approach will be applied in which an evidence-based intervention for chronic fatigue will be delivered in order to test its efficacy to reduce fatigue severity and prevent the fatigue from becoming chronic. This has never been studied before and if this approach proves to be effective, it could be beneficial for patients with fatigue after other infections as well……As chronic fatigue is known to be an interfering symptom which impairs functioning and work ability, preventing its development will also have a positive impact on the wider society."

and

"This unique opportunity to address fatigue in an early phase following an infection may prevent the development of chronic fatigue and has the potential to lead to substantial gains in terms of patient health and functioning."

and

"Quickly gathering evidence on the efficacy of iCBT for this patient group and the possible consecutive implementation of iCBT is a unique opportunity to help alleviate the pandemic's negative impact on patient's health and functioning."

Weaselling out of that now by saying that the association of objective outcomes like an actometer with patient reported outcomes is weak is....something. He could have reported that before getting a pile of money for supposedly preventing the negative impact of the pandemic on patient's health and physical functioning.


Edited: weird english

 

[chillier]

Proposed alternative outcomes, like physical activity assessed with actigraphy or physical fitness are no reliable markers of fatigue, and are also influenced by the perception of patients and subjectively experienced symptoms. Research showed that a substantial number of patients with severe fatigue do not have deviant physical activity levels.(7) This was also found in our sample, i.e. 81% of participants had a fluctuating active activity pattern, and only 19% had a low active activity pattern. A reduction of fatigue will not necessarily lead to increased levels of objective physical activity or vice versa.(8, 9) Also, reduced fatigue levels do not necessarily concur with improved aerobic capacity.(8) In our study there was no significant difference between the conditions in the increase in physical activity assessed with actigraphy.

From the authors response re actimetry, it sounds like they might have actually collected really valuable natural activity histories for n=114 patients for possibly 6 months (inferring from the methods in the abstract). They even give us a tantalizing snippet of differences they claim to observe of different types of patients (fluctuating versus stable). Imagine collecting a bunch of useful data and electing to publish something useless like this instead.

The most interesting piece of data they present they decide to present in an argument for why this data isn't of interest.

 

[Sean]

By solely focusing on objective outcomes and stating that subjective experiences of patients are not valid outcomes

Nobody is rejecting subjective outcomes. Just unblinded subjective outcomes used on their own. That has always been the position. Stop misrepresenting it. That is not a winning strategy.

 

[Arvo]

they might have actually collected really valuable natural activity histories for n=114 patients for possibly 6 months (inferring from the methods in the abstract)

The ReCOVer study proposal says "12 days of actigraphy" for baseline assessment. (edited to add @chillier : However this is no guarantee of what they did in practise. After all they also changed study aim and recruitment requirements.)

They even give us a tantalizing snippet of differences they purport to observe of different types of patients (fluctuating versus stable)

I don't think it's very significant in observing "types of patients"; to me it seems the logical difference between patients in their first year who could still do stuff and therefore do stuff whenever they can, and those who were from an early stage already too sick to do much (or who rest more due to pacing advise).

They also don't aim for gathering interesting data, they do this because of a dutch CBT element that divides patients in two groups: those who are low active, and those who are still doing activities (but rest/crash in between), for their own specific type of patronising. They make a whole Thing of this, but it's fluff to catch criticism that not all patients are activity-avoidant, and to still justify CBT for this group, like they still need to be "taught" how to behave in order to recover. Bleijenberg, Knoops mentor, explains it here in this 2005 newspaper article.

In ReCOVer low-actives immediately started graded activity, fluctuating active will "first have to learn to spread their activities more evenly across the day and week before they start with graded activity."

 

[dave30th]

Nobody is rejecting subjective outcomes. Just unblinded subjective outcomes used on their own.

of course. they keep repeating the same bullshit

 

[chillier]

The ReCOVer study proposal says "12 days of actigraphy" for baseline assessment. (edited to add @chillier : However this is no guarantee of what they did in practise. After all they also changed study aim and recruitment requirements.)

I don't think it's very significant in observing "types of patients"; to me it seems the logical difference between patients in their first year who could still do stuff and therefore do stuff whenever they can, and those who were from an early stage already too sick to do much (or who rest more due to pacing advise).

Thanks @Arvo that's interesting. As you say as they haven't published it they could have done anything, and 12 days wouldn't be long enough anyway. Asides from this paper I do think it's possible there are different types of patient that you could describe in terms of stability or frequency of fluctuation. The decodeME questionnaire had a question about this and the vast majority of patients have described themselves as 'fluctuating' or 'relapsing remitting' but not all. To really tease that apart you'd need the natural histories.

 

[Trish]

Todd Davenport responding to David Tuller's tweets about the study

Copy of Todd Davenport's tweets:

Wow, this study is super-messy. Of course if you involve an intervention of telling people they're not fatigued or that their fatigue isn't relevant (reframing), then you will have at least some of them say they feel better without objective evidence of functional improvement.

This study's interpretation depends on (1) end points that aren't validated in the study population, (2) you accept their cheerleading of 'statistical and clinical significance' without looking at the data, and (3) you won't look at the dichotomous secondary outcome measures.

I would say this study is an excellent example vindicating my practice of reading a scientific paper inside-out: read the method and look at the tables/figures before reading results and discussion, skipping the introduction. Avoid the hype. This study is much ado about nothing.

 

[rvallee]

Interestingly, they now claim in their response that there was no difference in the actigraphy results. Has anyone ever seen a response in correspondence that cites data deliberately left out of the actual study? ADD: And isn't it research misconduct to fail to report results that do not support your conclusions. I mean, they're acknowledging they had null results for this outcome. It's a disgrace not to include them in the report of the trial.

This really puts into question the work that journals and reviewers are doing here, if they can't even clue in on obvious stuff like this. Or even pretend to react once pointed out. We had to chase most of this stuff from PACE, and here they have no shame admitting it because it has been formalized. Fraudulent research is now an acceptable model in healthcare, even when the disastrous outcomes are documented.

It's really been a sort of slow creep where excuses that used to be unthinkable to admit are just now routine and acceptable. And this is a pattern, it's clearly been made acceptable to just not bother much with validity when it comes to chronic health issues. It's probably the most disturbing shift in all of academia. What used to end careers when found out is now just plainly admitted in defiance, a very clear: "and what are YOU going to do about it, uh?"

This week the US Supreme Court rendered a judgment on a case that turned out to be entirely fictional, and the Justices siding with the fabricated case don't even care and react defiantly to being found out. The corruption here is comparable, this is staggering. The institutions seem to have just stopped pretending to work as intended, post-truth and all. They're corrupt and proud of it because it goes very well for them.

 

[rvallee]

"Significant improvement following CBT is probable and a full recovery is possible. Sharing this information with patients can raise the expectations of the treatment, which may enhance outcomes without raising false hopes."

That's basically like someone saying "if I put my finger on the scale, I can get any number I want". The shamelessness is almost as breathtaking as the fact that almost no one seems to care about blatant, overt admissions of fraudulent behavior and reporting on a massive scale. This is not science, this is the exact opposite of science. It's just plain fraud.

 

[Sean]

This is not science, this is the exact opposite of science.

It is anti-science. Not pseudo-science, not non-science. Anti-science.

They are deliberately doing the opposite of robust scientific methodology. Because whenever they use robust methodology it fails to deliver any support for their pet hypothesis/model. All they are left with is sophistry and increasingly brazen lies.

So here we are. Medicine, at least in this area, is indisputably and profoundly broken, and the rest of the profession seems incapable of stopping the carnage and turning it around, or even interested in trying (with the usual honourable exceptions).

The real question now is how are they able to keep getting away with it? Why are they such a protected species? Who benefits from all this?

 

[Shadrach Loom]

The real question now is how are they able to keep getting away with it? Why are they such a protected species? Who benefits from all this?

It’s the profession of psychology itself, in all its forms, which benefits. Clinical psychology, psychology in industry, secondary and tertiary education in psychology, psychological medicine: collectively, these are vast industries.

And wherever psychology operates, it is pretty useless, and poorly evidenced. Occupational and forensic psychology are mere voodoo*. Clinically, talking cures may possibly help people who are mildly neurotic or depressed, but their main value seems to be as part of triage before people with moderate to serious mental illnesses can access crude - but often effective - pharmaceutical remedies.

So this profession, dedicated to training further acolytes and finding supposedly useful work for them to do, marks its own value-assessing homework, and does so as self-servingly today as in the days of the original fraud Freud.

Occasionally, there is a coincidence of interests with insurance companies and benefits bureaucrats, as in the PACE scandal, or indeed with other public services or with biomedical clinicians, but the rot in psychology is endemic and structural.


*I could go into lots of detail on this, but hopefully everyone here has at some point had absurd personality assessments foisted on them by HR or training types, and again hopefully no-one here regards them as any better than astrology, so we can be spared that discussion.

 

[Arvo]

The shamelessness is almost as breathtaking as the fact that almost no one seems to care about blatant, overt admissions of fraudulent behavior and reporting on a massive scale.

In that same vein I was baffled at the openness in the project proposal/grant application on what I personally see as major, multiple COI issues, and that the grant giver (ZonMw) didn't flag that as problematic.

Knoop, senior author and the grant applicant for this study, is director of NKCV, whose business is supplying CBT (they just got reprimanded for how they advertise it). At least three other authors are his employers at NKCV. (Lead author Kluut, Csorba and Pauëlsen).
Just that fact alone should IMO be an issue as NKCV, and these auhors personally, directly benefit from a positive result in several ways.

But the grant application alone lists 3 things that I think are each big conflicts of interest. (See screenshots attached)

• The researchers boast that "If shown to be effective, fast implementation of CBT will be possible due to the expertise and experience present in the project group.". They lists that this is because the project group contains cognitive-behavioural therapists, "researchers with experience in nationwide implementation of behavioural interventions, and clinicians and institutes with experience in the training and supervision of therapists in new internet interventions."

So the NKCV team are raring to go with this, and will themselves supply the "tested" therapy and set up its implementation elsewhere. This is extra bad as Knoop & co, in their project proposal to ZonMW, made clear in May 2020 that they expected Long COVID to become an issue (so lots op potential clients for them), saying that the COVID-19 pandemic "will likely result in debilitating long-term symptoms in a large group of patients." (bolding theirs) (Instead of warning people that they foresaw this, they cheer over the "unique opportunity" this was.)
​

• A 12 month follow-up to this study is planned, which is likely to be funded by NKCV. So found effectiveness leads to another study/publication, funding for another study & publication (which could also be from ZonMw again), and the opportunity to fund another publication by the industry. (These are three different ways of having benefit from a positive result.) Also: NKCV, a CBT treatment center directed by the senior author and grant applicant, that plans to comprehensively apply CBT and gain income based on this study, funding a follow-up on this trial - nothing to see here folks.

• The project group "will train and supervise therapists who want to deliver the intervention. For this we will develop a training programme." For NKCV (home of the leading author and senior author and grant applicant) training is one of their three activities. I doubt that the project group will provide such training and supervising for free.

So I see three ways in which NKCV announces to immediately benefit from a positive result. Still, the study protocol states under COI statement: "The authors declare that they have no competing interests."
​

In 2020, Ostengard et al. stated that: "Funding by a commercial source (eg, a pharmaceutical or medical device company) and authors’ financial conflicts of interest have been shown to be associated with statistically significant results and favourable trial conclusions being reported more frequently." (link)

To me it seems an obvious and huge problem that disqualifies this study as independent/free of bias & conflict of interest, but they are so open and blatant about it that I'm even starting to doubt myself.

 

[Arvo]

Ah @dave30th, this might interest you, following your discussion with one of the authors on Twitter.

More defenses of the observation that the authors left out the only objective data, that was relevant for their conclusion. And that this is research misconduct.

• actimeter outcomes were not primary or secondary but an "other study outcome"
• the data didn't fit in the paper (they will be published separately, which is customary)
• Anyway, we said it in our letter when asked about it didn't we?
• DARVO - it's "shameless" and an "extreme accusation" to say they have covered up data.
• The criticiser (Fen) is "angry or disappointed" about the setup of the trial and the results (and that's why she "accuses" them of leaving out data).
• Stop accusing us of covering up data
• Let's just stop discussing this

(Also Rovers rather would have published a study showing the cause of Long COVID and related effective and targeted treatment. Or gotten funds for that, which they didn't.)​

If the translate button doesn't work and a precise transcript is necessary, I could try to make one.

 

[dave30th]

Is NKCV a private entity or part of the university?

 

[Arvo]

Is NKCV a private entity or part of the university?

I don't know.

It's a foundation, so they seem separate, but they are closely affiliated with the university's psychiatry department, and Kuut's bio in the study protocol says: "Amsterdam University Medical Centers, Expert Center for Chronic Fatigue, Department of Medical Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands." like it's part of it.

But their own page says:

"mental health institution
Stichting Nederlands Kenniscentrum Chronic Fatigue is an independent mental health institution. We work closely with medical specialists from Amsterdam UMC to expand knowledge about chronic fatigue."

 

[Arvo]

At some point NKCV was part of the dutch business register Kamer van Koophandel (KvK), but they are "written out as corporation".

link

Edited to add: they were registered as foundation.

 

[Arvo]

NKCV says:

"mental health institution
Stichting Nederlands Kenniscentrum Chronic Fatigue is an independent GGZ [=mental health] institution. We work closely with medical specialists from Amsterdam UMC to expand knowledge about chronic fatigue."

and

All diagnostics and treatment is outsourced by the NKCV to Amsterdam UMC, location VUmc.

AmsterdamUMC says:

The NKCV is part of the GGZ care of the AmsterdamUMC and is part of basic care. The AmsterdamUMC has a contract with all health insurers for the provision of this care. The personal contribution applies.

So this looks like the NKCV is an independent institution that outsources diagnosis and treatment to AmsterdamUMC, and as such (an independant institution) is part of the mental health care of AmsterdamUMC.

Looks very enmeshed to me.

(Edited to change detail on treatment)