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

[Arvo]

Wait, so per their own website NKCV is an independent institution and treatment centre but it also outsources all treatment to Amsterdam UMC?

I really must be missing something.

 

[rvallee]

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.

This issue of bias and equipoise has been thoroughly destroyed, IMO. It only matters if people with influence within the system object, since it's political. There have been hints in the past, but none more blatant than when Richard Horton went on an international promotional tour framing the PACE researchers as independent and having taken a step back to objectively assess... the very thing they had made up and had been selling for years already. Even in politics it's rarely as nakedly corrupt as this.

PACE was the equivalent of a study by Theranos, using Theranos resources and employees being presented as an independent evaluation. With Theranos on the cover. And the manual for the study written by Elizabeth Holmes. This is banana republic level of not caring about the truth and just making stuff up. You can't have more blatant bias and conflict of interest than this.

Look at this horseshit. The lies. The lies!

 

[dave30th]

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.

That makes it a bit more complicated, I think. The conflict of interest would be more apparent if it were an independent business than if it's part of their responsibilities as university employees. Hm.

 

[Mark Vink]

Unfortunate that nobody touched on the strange numbers in table 3.

They report for example a standard error of 0.5 in the CBT-group at baseline. Because the sample size was 57, the standard deviation would be: 0.5 * sqrt(57) = 3.77.

This is extremely small. The mean was 47! In other papers, for example on ME/CFS patients, the standard deviation is around 12-15 points.

In Prins 2001, Table 1: Baseline characteristics of study participants, it is 3.9 so very similar

 

[Mark Vink]

That makes it a bit more complicated, I think. The conflict of interest would be more apparent if it were an independent business than if it's part of their responsibilities as university employees. Hm.

The director of NCKV is Prof. dr. Hans Knoop who outsources it to mental health or medical psychology at the UMC led by:
Prof. dr. Hans Knoop aka himself…

 

[ME/CFS Skeptic]

In Prins 2001, Table 1: Baseline characteristics of study participants, it is 3.9 so very similar

Thanks for pointing that out. I've made an error by only looking at some papers with results after treatment where the SD is often larger than at baseline. In this Long Covid trial it also increases from 3.7 to 12 (the figure they used for the power calculation). This increase in SD might point to ceiling effects, but that is a different matter.

Apologies for the confusion, will adjust my initial post.

 

[Jaybee00]

Gaffney




Dogma and doctrine!

 

[Mark Vink]

Thanks for pointing that out. I've made an error by only looking at some papers with results after treatment where the SD is often larger than at baseline. In this Long Covid trial it also increases from 3.7 to 12 (the figure they used for the power calculation). This increase in SD might point to ceiling effects, but that is a different matter.

Apologies for the confusion, will adjust my initial post.

Thank you, but there’s no need to apologise.

The people who should apologise are the authors who should have used standard deviation and not standard error. By using the latter, they give the impression that they do not want people to see the spread of their participants.

 

[Charles B.]

Gaffney




Dogma and doctrine!

Your years long crusade will harm patients even though this study I know nothing about doesn’t show that rehabilitative approaches will help patients.

I’m a serious scientist and definitely not opportunistically inserting myself in this debate for clout.

 

[Jaybee00]

What does this even mean? Like I seriously don’t understand what he is talking about.

 

[Charles B.]

What does this even mean? Like I seriously don’t understand what he is talking about.

He’s either shamefully ignorant or plain dishonest. BPS is the natural outgrowth of a desire to cut costs and increase pressure on those receiving state benefits. That an ostensible progressive would defend this is nonsensical. This is what happens when you’ve convinced yourself that you’re a genius without really knowing anything.

 

[Charles B.]

What does this even mean? Like I seriously don’t understand what he is talking about.

Is he still blocking replies to various tweets relevant to ME/CFS patients? I know he did so previously, but I am no longer on Twitter and can’t determine whether it continues.

 

[Hoopoe]

It's just the way he tries to distract from the fact that he's confidently expressing uninformed opinions on ME/CFS/LC and gets criticized for this by folks who know more about the topic.

 

[Trish]

For those without access to Tweets, here's some of the converation with Adam Gaffney:

davidtuller
@davidtuller1
·
17h
Hey @awgaffney, are you aware that the authors did not report their one objective finding--a null result for actigraphy at the end of therapy. So you're ok with the fact that they chose not to report objective data that sheds doubt on the subjective reports? Interesting! twitter.com/awgaffney/sta
Adam Gaffney:
I don't know anything about this study apart from reading it two months ago, but I will say that your years-long scorched-earth crusade against rehabilitative approaches to Long COVID and related illnesses will cause serious harm for patients whatever your motives

I'll only add that the crusade is far broader at this stage, and indeed is effectively now dogma and doctrine

Never thought I'd see the biopsychosocial model of medicine come under sustained attack, but here we are — what's fascinating is how this reaction comes across as progressively-coded while being profoundly regressive at its core.

Maybe one way to understand this is as the further neoliberal transformation (i.e. degradation) of our social fabric. To rework/distort/contort a quote from Margaret Thatcher: there is no societal context, are only individual patients & pharmaceuticals.
_______________

I've had a go at replying, along with many others:

Here's what I said:
Hi
@awgaffney
. I think you have seriously misunderstood what this is about. Have you ever met a person with ME/CFS who was prescribed CBT/GET treatments and as a result became much much sicker for years? There are thousands of us. How about listening instead of pontificating. 1/

I have no problem with the BPS model where relevant. As a #pwME my concern is fraudulent research that claims efficacy using questionnaires patients have been persuaded by therapy to fill in differently, while hiding the lack of objective data that shows no improvement. 2/

@awgaffney
you have been hoodwinked by psychiatrists funded by insurance industry who have built lucrative careers on the false premise that ME/CFS is psychosomatic. The core symptom is post exertional malaise - severe relapse from normal level activity. Exercise harms #pwME.
__________

Edit: I'm not blocked yet, but I expect I will be.

 

[Charles B.]

For those without access to Tweets, here's some of the converation with Adam Gaffney:

davidtuller
@davidtuller1
·
17h
Hey @awgaffney, are you aware that the authors did not report their one objective finding--a null result for actigraphy at the end of therapy. So you're ok with the fact that they chose not to report objective data that sheds doubt on the subjective reports? Interesting! twitter.com/awgaffney/sta
Adam Gaffney:
I don't know anything about this study apart from reading it two months ago, but I will say that your years-long scorched-earth crusade against rehabilitative approaches to Long COVID and related illnesses will cause serious harm for patients whatever your motives

I'll only add that the crusade is far broader at this stage, and indeed is effectively now dogma and doctrine

Never thought I'd see the biopsychosocial model of medicine come under sustained attack, but here we are — what's fascinating is how this reaction comes across as progressively-coded while being profoundly regressive at its core.

Maybe one way to understand this is as the further neoliberal transformation (i.e. degradation) of our social fabric. To rework/distort/contort a quote from Margaret Thatcher: there is no societal context, are only individual patients & pharmaceuticals.
_______________

I've had a go at replying, along with many others:


Here's what I said:
Hi
@awgaffney
. I think you have seriously misunderstood what this is about. Have you ever met a person with ME/CFS who was prescribed CBT/GET treatments and as a result became much much sicker for years? There are thousands of us. How about listening instead of pontificating. 1/

I have no problem with the BPS model where relevant. As a #pwME my concern is fraudulent research that claims efficacy using questionnaires patients have been persuaded by therapy to fill in differently, while hiding the lack of objective data that shows no improvement. 2/

@awgaffney
you have been hoodwinked by psychiatrists funded by insurance industry who have built lucrative careers on the false premise that ME/CFS is psychosomatic. The core symptom is post exertional malaise - severe relapse from normal level activity. Exercise harms #pwME.
__________

Edit: I'm not blocked yet, but I expect I will be.

Ive never seen him respond to a patient. We can’t enhance his profile.

 

[bobbler]

Sidenote that sort of is more of a discussion about how (perhaps not with a legal case but we need to begin to show what they must either have seen or chosen to ignore) even with things like CBT it should be obvious that the coercive techniques + the particular condition they have chosen have made for a really significant 'recipe' in 'bias' (I'm not sure that is just what it is)

By which I mean we should be able to take people of different severities and pretty visibly show how their cognitive and physical fatigue shows itself, pretty visibly, in making said individuals obviously vulnerable in the space of a video.

Whether you are severe and that is after a few heavy duty questions or someone - a la 'CBT' - barracking you barrister-wise with questions and questioning your perspective or asking you to describe detailed things, or moderate and you get to do GET first and are just put into either needing desperate to not just sit down but get your head down and are therefore in an either wet rag tired or still obviously tired but almost seem hyper from trying to keep eyes open state.

THAT is when said people are told to fill in said questionnaires, which it might be worth, aren't well written to make sense re the condition, and aren't short or easy to use.

And you could show how easily pushed around to have words put in their mouth just to get out of the room these people are - even the most assertive of everyone, but when you have been made so ill that survival instinct and desperation will lead to it.

Further it would be worth noting the vulnerable situation people would/might perceive themselves to be at risk of should the person read their answers and not be happy with them - it seems more than feasible given the automatic accusation of 'didn't try hard enough' for those who didn't get better from harmful therapies that 'not giving the correct answer' to someone who could write to your GP and influence significantly care and other support mighn't be a risk you can take etc.

It is so worrying that such individuals are going anywhere near severe people. It really is such huge cognitive damage and psychological brainwashing harm that these individuals will be at what I would say are significantly at risk from significant harm from - given how exhausted their brains will be and these being 'pushed further' I find it ethically shocking and terrifying/disturbing.

 

[Mark Vink]

I don't know whether this has been posted elsewhere on this forum, but here's the questionnaire used for the primary outcome - Checklist Individual Strength.

It's not clear from the study whether they administer the whole questionnaire and then extract the 8 items of the fatigue subscale, or just use those items.
(ref: https://oml.eular.org/sysModules/obxOml/docs/ID_369/v057p00353.pdf)

Items on the fatigue subscale (True >>> Untrue) are as follows:
I feel tired.
Physically I feel exhausted.
I feel fit.
I feel weak.
I feel rested.
Physically I feel I am in a bad condition.
I get tired very quickly.
Physically I feel in a good shape.

Scale range is from 8 to 52 (each item scores from 1 to 7, where higher score = more fatigued) - so a score of 32 is midway. In the validation study, the average score in a white-collar population sample was about 20 on the fatigue subscale. Those with a "mental reason for fatigue" (whatever that might be) scored an average of 39.

If an intervention is targeting "unhelpful thoughts" around fatigue, then I would have thought it's fairly easy to move a point or two on each item in a more favourable direction just simply by reframing.

Ty;

Kuut: “Scores on the fatigue severity subscale of the Checklist Individual Strength (CIS), range 8 to 56, with higher scores indicating more severe fatigue; a score of ≥ 35 indicates severe fatigue“

Your PNG: “Subsequently the four subscales are calculated by summing the respective items subscale 1: Subjective feeling of fatigue items 1, 4, 6, 9, 12, 14, 16, 20.”

 

[Mark Vink]

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.

Spoiler: Something weird has happened with the criteria for study participants as well.

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? )

Spoiler: Some details from the trial protocol

The 2021 trial protocol states:


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:


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.

Have a look at how ZonMW spells her last name, that pretty much sums up that study…

 

[Arvo]

Have a look at how ZonMW spells her last name, that pretty much sums up that study…

Knowing what it is before you check the file...

How embarrasing, it has been corrected though.

 

[Arvo]

That makes it a bit more complicated, I think. The conflict of interest would be more apparent if it were an independent business than if it's part of their responsibilities as university employees. Hm.

I'm still confused by it. A november 2021 PDF on ancillary activities of employees at AmsterdamUMC lists Knoop as chairman of the NKCV.

The organisation "AmsterdamUMC" was created in 2018 from the administrative merger of the two academic hospitals in Amsterdam: the AMC (connected to the University of Amsterdam) and the VUmc (connected to the Vrije Universiteit, Free University).

I found a quality charter of AMC psychiatry, which is a joint statute from the AMC department of psychiatry AND the NKCV, so while they are together and share the statute it is also presented as two entities. But it also says: "...the Dutch Knowledge Center for Chronic Fatigue (NKCV) is part of the care offered by the psychiatry department. The NKCV focuses on the treatment of chronic fatigue (somatic symptom disorder) within specialized mental health care."
(But then why name NKCV as a separate entity in the first paragraph, other subdepartments aren't mentioned there? Also of course note that treating "chronic fatigue" is treating "somatic symptom disorder".)

It has some info on NKCV.

So far it looks to me like Hans Knoop is a researcher at the department of medical psychology of the AMC (not an active HCW, and e.g Kuut is listed as researcher at the medical psychology dept of the VUmc, so the other hospital, but they are both part of the NKCV team), and the NKCV is an independent institute and treatment centre, chaired by a researcher at the AMC medical psychology department, that gets hired by (or outsources to?) the AMC department of psychiatry for treatment.

So far it doesn't look like a simple construction to me. The psychiatry department & NKCV quality charter states that NKCV is located at the AMC location, but the NKCV site itself states that its visiting address is the outpatient clinic of the VUmc.

I also found a newsletter of the UMC Medical Psychology of december 2021 that Kuut wrote an article for. She mentions ReCOVer and the research agenda Knoop wrote with Wessely and Moss-Morris. About the NKCV she says:

"It is still relatively unknown that a psychologist, in particular a cognitive behavioral therapist, can also be used for physical complaints such as long COVID, persistent fatigue and cognitive problems. A specialized treatment center for long-term fatigue, the NKCV, also sees relatively few patients with long-term fatigue complaints after COVID. This is remarkable given the large numbers of patients with COVID, and the expectation that a significant proportion of these patients will have persistent complaints. Factors that may contribute to this is the reluctance of doctors to refer to a psychologist for long COVID. In addition, patients may worry that the persistent complaints mean that unknown damage has occurred to the body." (bolding mine, "lung covid" corrected to long covid)


I'm doing too poorly to pursue it further, and cognitive issues make it difficult atm. Maybe another time.



(Attached:
- Quality Charter AMC psychiatry department and the NKCV, auto-english translation,
- QC AMC psych. dept. and the NKCV original,
- UMC Medical psychology newsletter december 2021, auto-english translation.)