I have been out of the loop for a while so I have not read (and am not currently able to) the two long threads on the forums about the NIH study and the use of the EEFRT questionnaire. Have there been posts in those threads that have attempted to summarize the criticisms made so far, or perhaps an external blog post? An overview would help tremendously with catching up. Thank you to everyone who has been working on debunking this study. Moderators - I apologize if I should be replying to the existing threads instead of creating a new one, but I thought it would help people in the same situation as me find what they need more easily.
As a note, I have skimmed through Jeannette Burmeister’s blog post but it does not seem to be addressing in depth the methodological concerns as they are being discussed here and which are the ones I’d like to know about.
The most egregious fact seems to be that the claim that PWME show a different 'effort preference' is at best a weak statistical thing and would not be there if the authors had not excluded one of the normal control results as being 'aberrant'. In other words, a disinterested sensible interpretation of the findings is that they were most likely entirely negative and certainly not positive enough to make the interpretation plausible. Another serious problem is that subjects were made very aware of their status as patients and that the 'effort' tests were designed to find a difference in behaviour in relation to exertion. That means that any result could have occurred because patients were 'fulfilling a role' - which most people find it very hard not to do. Their mental processes would have been totally different from those of controls simply because they knew they were the test cases. So the fMRI data showing brain activity are completely uninterpretable.
After about 7 pages of discussion of the EEfRT task, I tried to summarise what we as a group had figured out so far by pulling out key observations. Hope this will help. Use of EEfRT in the NIH study: Deep phenotyping of PI-ME/CFS, 2024, Walitt et al Edit: The authors of the NIH study have proposed that the fact that pwME chose a lower proportion of hard tasks in the EEfRT task demonstrates that we have altered "effort preference". People on here think that it doesn't show that at all.
Study claimed that there was ongoing/chronic antigenic stimulation that was causing problems but they identified NO antigen. Had they identified said antigen, study would have been a game changer…. But they did not.
Laughing - back to that @Brian Hughes cartoon ---- apart from the subjective outcome criteria ++++ not that bad a study! Whatever you do don't mention the $8 million & 8 years --- it took to produce this!
I am actually working on a blog post for this purpose, but it's taking quite some time. I'm glad to have found this forum as the folks here are discussing the same issues I noted during my detailed read-through. I am also going through most of their citations to determine whether the information they present is supported by the references, and how many of the ME papers they cite take a BPS approach. Hopefully in the next few weeks I will be able to write everything up. Also, hello, this is my first post!
One of the other biggest concerns @cassava7 was the small size of the cohorts. For most of the studies, the size is considerably smaller than the headline sizes of 27 controls and 17 people with ME/CFS. Often more like 8 or 10 people in each group. Not many people actually made it to the second session of testing. Making it even worse was the lack of proper matching between the controls and ME/CFS group. Controls skewed substantially older; the ME/CFS group had substantially more people with a BMI >30. The result is that basically all of the studies are too small to produce any findings that can be relied on. Which is a shame. So, although there is an enormous amount of investigations and data in that study, there's a big chance that important findings were buried under statistical noise, and that statistical noise has been elevated to supposed findings. It's pretty much worse than not having done a study at all. Also, oddly, there was no mention of the WASF3 finding from this cohort, which was reported elsewhere.
The NIH Intramural ME Study: “Lies, Damn Lies, and Statistics” (Part 1) Posted on June 10, 2024 by Jeannette Burmeister https://thoughtsaboutme.com/2024/06/10/1/
@cassava7 I think this piece is quite good at summarising the potential problems with the study, while staying neutral in tone, and staying away from “accusatory rhetoric” which might put off someone who initially had a good impression of the study. Errors, omissions, potential bias: Why some ME experts are calling for a retraction of the NIH intramural study - The Sick Times https://thesicktimes.org/2024/03/19...for-a-retraction-of-the-nih-intramural-study/
Very damning when presented all side-by-side. This really was mainly a biopsychosocial paper, having chosen to make the irrelevant effort preference the main piece of evidence, and it's not credible in the slightest that it wasn't the real intent and purpose all along, given Wallit's horrid history of being wrong about this and being so desperate to prove it at all costs. Given the way it's framed, this is basically setting it up to be all FND, having found that it's some reward circuit where nothing is impaired. I do mainly see in the wild opinions from MDs that it's depression or "undiagnosed mental illness" (which is kind of bizarre considering that it takes about 45 seconds for the average physician to tack at least one of those, zero tests required), but otherwise the framing of "they think they can't do, but they can" is the most common one after that, which by framing it as lack of motivation is basically all the same idea using different words. Some years ago, we learned that the Norwegian government allocated 28M Euros in funding to be reserved strictly for biomedical research, then most of it was hijacked by psychosomatisers to do this kind of BS, with some tokenistic lab work to cover up the main BPS angle. The NIH basically did the same here, they have some biomedical research in there, but choose to make prominent a completely fringe piece of misused evidence. But the researchers behind this test think it's fine, even though it wasn't even intended to be used this way, which is a whole other layer of disturbing. It's as if nothing matters here. Words have no meaning. It's really disturbing to see just how wasteful and broken medical research is. They're not following the evidence, they're walking in circles and picking up the pieces they drop behind them, with intent and purpose. But you point it out plainly and you're called mad. What a freaking world.
To me, it's not the "effort preference" that is the most objectionable. It could well be that ME/CFS patients can exert as much as similarly deconditioned subjects if pushed or encouraged to. The biggest problem is that the paper completely ignored PEM, other than for the purpose of screening the subjects, and subsequent decline if you continue to push. We all know the end point will be complete immobilization for a long time, if not forever., if you continue to push. Then, it blames pacing for the "effort preference", essentially saying that the subjects felt tired because they were afraid of becoming tired. Hopefully they'll focus on the catechol and other physiological abnormality that they found rather than dwelling on the "effort preference" going forward. But they could well use the catechol and rTPJ abnormality to equate ME/CFS to depression if they want to take it in the direction of BPS. Nath has been on the publicity circuit claiming that the paper found that ME/CFS to be purely physiological, so maybe he'll counter-balance Wallitt as they go forward with it.
Did they completely ignore PEM? From what I recall of the symposium - though I don't have the energy to seek out where in the video they said it - they used a 1-day CPET then tested biomarkers to see what abnormalities arose the next day.
PEM is mentioned 3 times in the study, as opposed to 26 times for “effort preference”. There no mention of PEM anywhere in their mechanism hypostheses. There is one mention of PEM in relation to recruitment, and two mentions as subjective patient reported symptoms in interviews. This study was supposed to basically perform every test on pwME and figure out what is wrong. I think you could say that given PEM is the hallmark characteristic of the disease, only having these three mentions amounts to ignoring it. I am not aware that much was measured specifically after the CPET except metabolics and cortisol. Additionally, only 8 people with ME/CFS did the CPET which creates very small sample size to reliably test anything post CPET anyways.
Yeah, looking at the actual study, I think this is the extent of testing performed one or more days post-CPET: And no meaningful differences from the above: Cortisol was only tested one hour later.
If I recall correctly, the 1-day CPET was used as a proof that the subjects were able to exert as well as the controls. PEM was mentioned only as the reason for not performing 2-day CPET. Basically, they looked for post-exercise anomaly while ignoring post-exercise worsening of symptoms. They already discounted the symptoms as effort preference, so they probably didn't see a need to remeasure it.
#noteverytest. Eg I didn't see any mention of vasopressin. The below poster abstract was published after the NIH paper, but vasopressin (aka antidiuretic hormone) is a pretty basic and well understood component of renal/vascular/fluid homeostasis. Low Vasopressin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome P4-4.006 (2024, Neurology) —
