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

I'm just looking at this now. It's all over the place. The lengths of the bars in Fig 2 do not even correspond to the values in Table 3. Happy to work with you on this to get this crap corrected or withdrawn.

 

Note that the confidence interval is sometimes given as +/- twice the standard error, not =/- twice the standard deviation. They may have plotted this, but this would still need correcting to say as much, and it doesn't explain why the error bars at T1 are different lengths despite the same standard error for both groups.

More importantly, this would probably mess up the stats downstream of these calculations.

 

What clearly matters most is the null hypothesis testing i.e. this:

"Patients who received CBT were significantly less severely fatigued across follow-up assessments than patients receiving CAU (-8.8, (95% confidence interval (CI)) -11.9 to -5.8); P<0.001), representing a medium Cohen’s d effect size (0.69). The between-group difference in fatigue severity was present at T1 -9.3 (95% CI -13.3 to -5.3) and T2 -8.4 (95% CI -13.1 to -3.7)."

We need to understand how they came to these figures, particularly the confidence intervals on these group differences. I suspect they are wrong!

 

Someone mentioned that at the second measurement moment T2 the CBT group shows a deterioration compared to T1, while the control group continues to improve. Why does the CBT group deteriorate when treatment stops and the control group continues to improve?

 

They say a difference of 6 is considered a clinically relevant effect for the CIS-20, and they cite this paper for that statement. I don't see that substantiated in that paper

For that chart showing standard errors for those figures, what's more important is the 95% confidence interval for the effect size, which is listed elsewhere in the paper. Confidence intervals aren't twice the standard deviation, they're roughly twice the standard error, assuming a normal distribution.

 

That's true, and they haven't mentioned that (as far as I can tell), but the change is also very small and not significant.

 

There are various possible explanations if this reflects reality:

• The experimental group were irrationally optimistic about what they were able to do as a result of the false information provided via the CBT mistakenly believed to be curative so long term attempting to undertake more than feasible given their persistent health issues making their health objectively worse
• The experimental group initially scored themselves better than they actually were as a result of researcher induced bias and then scored themselves more accurately after sufficient time had elapsed, so what appears to be a deterioration is rather more accurate reporting
• The experimental group and the people around them adjusted their behaviour to allow them to focus on the active intervention and reduce other activity giving a misleading sense of improvement, but subsequent to treatment the pressures of everyday life again intrude resulting in subjective deterioration
• Etc

These issues indicate the impossibility of ever drawing meaningful conclusions from an open label trial with only subjective outcomes, also that it is essential to look at total activity levels before, during and after the intervention if the aim of intervention is to enable participants to increase their activity levels. Also they hint at the difficulties of ever achieving adequate control over all factors in real life settings suggesting the foolishness of focusing on just one experimental design, rather than seeking convergent evidence from multiple sources/approaches.

 

Twitter thread from Lucibee about this study

where she highlights that protocol shows that the CBT used targets a "gradual increase in their physical activity".

 

True, but still interesting and you wonder what that means on the long run for those who actually worsened by this CBT trial.

 

Is it not really weird that the standard errors were exactly the same for both groups for different outcome measures, often at T0, T1, and T2?!

 

OK. The error bars in this figure (Fig. 2) actually show the 95% confidence interval (mean ± 1.96 x SE). That's not what's stated in the caption for this figure. So that's an error, but a presentational one.

What I don't understand is how you calculate an *overall* between-group difference from the values at T1 and T2. Calculation of the between-group difference at T1 or T2 alone is trivial.

 

While it's difficult to follow for me (especially today), I'm reading with interest. Please keep on analysing content, but I wanted to add some context/docs that might be helpful.

There was a S4ME thread on the announcement of this trial, which can be found here.

Particularly note the doc added by @Grigor , access here, where Knoop is discussing the trial.

• No trial ? treatment protocol made public, because of "intellectual property" and because "the treatment must first be tested in research"; ZonMw later reports that a trial protocol is accepted for publication by BMC, but so far no publication (possibly agreed with BMC to publish after trial publication). --> My bad! There is a trial protocol published after this interview. See: A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol - PubMed (nih.gov), published December 2021. On November 18th 2021 Knoop was not planning to make a treatment protocol published - I'm too hazy atm to discern if that's the same or different. (The BMC publication contains detailed info on the treatment, so I'd say it's the same?)
• (Nastily) conflates subjective questionnaire outcomes after research participants are trained to reframe cognitions (methodology flaw) with "listening to patients" (patient collaboration and agency)
• "Why are patient organizations so obsessed with objective measures? Objective measures are also subjective. They depend on how you interpret them."
• "medical research is increasingly moving away from objective outcomes and looking at what is relevant to the patient and how he feels." (again conflating bad research practise with patient representation & -participation)

Also note that participants were recruited via a website that repeatedly stated to candidate participants that CBT was a proven effective treatment for chronic fatigue (if it's removed, contact me for screenshots).

I also have a question on study aims. There are at least three sources (the grant application, the ZonMw project site, and the recruiting website) that state that the aim of this trial is to study if CBT prevents Long Covid/chronic fatigue after Covid19. (So not if it treats it when it's already established for a while.) Does this match the paper?

I've also made a doc with a selection of some pages from a FOI request made by the dutch Steungroep ME en Arbeidsongeschiktheid regarding ReCoVer. The whole document can be accessed here:
Beslissing ZonME op WOB-verzoek ReCOver-onderzoek.pdf (steungroep.nl)
and the selection PDF below.

I haven't read the whole document (it's 100 pages), but my eye fell on a couple of things that matter (see PDF attachment below). @dave30th , tagging you as I think you'll find this interesting, and part of the PDF I added below is in english.

Note:

• that the thing tested here is, as per this grant application, to prevent rather than treat chronic fatigue after Covid-19
• that Knoop, as usual, has his eyes on "fatigue after other infections" - dude is after making Long Covid part of one big ball of treatment consumers with ME, Q-fever, mono and tick borne disease & more.
• that this document appears written in May 2020: deadline the 14th, latest reference the 2nd. It states that "a substantial subgroup is expected to develop persistent post-Covid-19 chronic fatigue". Knoop expected this. ZonMw accepted this. They knew. That will be received well with the thousands of LC patients who got sick in the last years while The Netherlands followed a immunity-by-infection policy and did little to prevent infections as long as hospitals seemed to cope./s

Instead of warning for it, Knoop stayed quiet and tries to build business, career and income on it.
​

• that again Knoop claims CBT is effective for chronic fatigue
• the fabricated but claimed involvement of the patient community; Longfonds and Qsupport might be "active in support for COVID patients" but they do not represent the Long Covid patient community. This is not a patient-driven or -supported study by far. (See also point 1.8 in the PDF)

The second part of the PDF is in dutch, but I added it because it contains imortant information regarding the assessment by ZonMw of his project on relevance and quality.

Section 1.13 states strong points:

"CBT is, like the researchers indicated, a proven effective intervention for chronic fatigue in people with different chronic illnesses (including infectious diseases).
According to the researchers this is the first study in which CBT is used to prevent chronic fatigue.
....
Research group with much experience in this area
Patient organisations are involved in the research"

Weak points (1.14 and 2.2) are that it's only looking at short term outcomes and the setup of the study. ZonMw suggests looking at "quality of life" instead of employment, as there are a lot of old people in the COVID-19 population. They also find it unclear what "care as usual"means for the control group.

They remark: "The researchers are clearly enthusiastic about iCBT." Though she wonders if it's ethical to withold this easy-accesible treatment to participants while it could prevent developing chronic fatigue.


Edited to change some poorly translated english
Edited to correct a mistake: there is a published study protocol

 

I've not looked at the whole FOI document, but the deadline for the grant application form was the 14th of May 2020
The final (I think elaborated) grant request was received by ZonMw in June 2020. The decision to fund him was taken and communicated in July 2020. (FOI doc)
In early August 2020 the grant approval was made public. (See thread on S4ME & article David Tuller)
In oktober 2020 the trial started (ZonMw page screenshot personal collection)
I swear I have a screenshot, though I can't find it, that the trial was closed for participation in February 2022


I'm getting too poorly to add all the links, I will do that later.

 

Aside from the pseudoscientific BS about CBT, someone on twitter asked a question that needs to be asked and almost never is: what the hell does CBT have to do with sleeping habits and the other themes they chose?

This is exactly as substantial as using CBT to teach cooking. Why? Literally no reason for it, unless someone's job is to sell CBT. The specific format is useless, adds nothing to the outcome and only serves to employ cheap CBT therapists.

There is not a single actual reason to use some psychotherapeutic model to deliver generic information. This is all nothing but a giant scam that uses a pseudoscientific construct in order to appear scientific, which is basically insane.