By David Tuller, DrPH
So, okay…The big enchilada from the US National Institutes of Health’s seven-year, $8-million, under-recruited and over-hyped study—”Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome”–was published last week in Nature Communications. It would be fair to describe the ensuing public debate over this massive text-and-data dump as spirited.
(NIH press release here; articles in The New York Times and Scientific American here and here.)
The study fell short of the initial number of intended participants and was interrupted by the pandemic. The long-awaited publication of the results triggered widespread outrage and dismay among patients as well as many scientists and clinicians specializing in the field. I’m a journalist and a public health guy, not a biologist or physician or statistician, so I’ll leave the in-depth analyses of the granular data to others. For now, I have a few observations.
First thing: Wow, what an arduous endeavor for the 17 sick participants! Amazing that they were willing and able to spend so many days putting themselves and their bodies on the line. They deserve enormous thanks.
Second thing: “Effort preference”—what the fuck? If you focus-grouped it, you couldn’t come up with a more demeaning and ridiculous name for the construct presumed to be driving the disabling symptoms that plague this particular group of patients. It is astoundingly tone-deaf–almost as bad as naming a devastating illness something as demeaning and ridiculous as “chronic fatigue syndrome.”
(As discussed in the illuminating thread about this paper on the Science For ME forum, the original version of the test used in the study for measuring effort preference appears to have been developed to assess anhedonia among depressed students. It is unclear why the NIH team decided to adopt it for use in this context. And as has been widely discussed on the forum and elsewhere on social media, the paper includes other significant flaws as well.)
Third thing: Scientific publications play to multiple audiences. Major news outlets generally focused on the signs of immune dysfunctions and other biological abnormalities. Putting aside for the moment the actual details of the findings, many members of the public likely came away from this one-day media event with a slightly greater respect for the seriousness and complexity of the illness than before. On a population level, that’s not nothing.
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Michael VanElzakker is a neuroscientist at Massachusetts General Hospital with a long-standing interest in ME/CFS and its neurological manifestations. I spoke with him recently about the NIH study.
What a shame it is, that Mike VanElzakker didn’t lead the NIH study.
I think that his focus on T-Cell activation is absolutely on-point and highlights quite well, the rather unhelpful way that the study was summarised in the published paper
Thank you both for your careful and sober analysis.
You have poured some oil on these troubled waters.
Am I right in saying that the 20% was of those who were deemed to have ME/CFS according to the study criteria? If so, does this point to there being something wrong with the study criteria, perhaps the inclusion of patients under insufficiently strict criteria? Is this study telling us that much stricter criteria need to be employed in studies on ME/CFS? And if only 10% of recruits got through the review process, what does that tell us about misdiagnosis in the community? (I guess there would likely have been other reasons for exclusion apart from not having the disease but mightn’t this low figure sound a misdiagnosis alarm too?)
As I’ve commented previously, I’ve repeatedly had to bat a ME/CFS diagnosis away from me over the last 20+ years and it’s really tiresome. (I wonder – could the effort involved in having to do that be affecting my “psychophysiology”??)
I appreciate that patient confidentiality/research ethics might get in the way of disclosure, but I’d love to know what the alternate diagnoses were that came to light over time in the 4 patients who got through the participant selection process. I think the authors of the study are right to pick up on this issue (see the second paragraph of the discussion section of the article). To my mind, the misclassification of these patients raises serious questions about the body of ME/CFS research to date.
Okay, maybe an antigen. Our immune system is behaving ‘as if’ it’s fighting a persistent antigen.
But after all this time, and this exhaustive lab work, no one has FOUND this posited antigen.
Golly, if only there were some other physiological INTERSECTION between fatigue, post exertional malaise, and immunity.
Mitochondria, anyone?
We have long known their energy role; we are now learning of the specific role in innate immune signaling.
There is even an ME paper about mitochondria starved of oxygen by WASF3 protein.
Hello? Can we follow up on that? As a patient for almost 20 years, that would be my ‘effort preference’…
This study had a small number of ME/CFS participants in the end but I think it gives us at least some idea of what the misdiagnosis rate of ME/CFS might be. The management of ME/CFS has served as a basis/exemplar for a MUS project that has informed doctors that MUS misdiagnosis rates are at the low end and nothing for doctors to be overly concerned about. Doctors have also been told that to continue to investigate MUS patients past basic tests can cause them iatrogenic harm. But I’d say that this study strongly suggests the opposite. Conducted by US experts who appear to have gone to some considerable lengths to try to ensure that the participants do have ME/CFS, it surely points to misdiagnosis rates being unacceptably high (20% – 4 patients – in this study AFTER a confident ME/CFS designation had been given). I imagine that misdiagnosis is likely to be even higher in the community, perhaps in the region of 20 – 40% (similar to the initial MUS misdiagnosis rates in different specialty outpatient clinics in two London hospitals from a study conducted back in the ’90s). If ME/CFS is such a good exemplar for MUS, I think this study should surely serve as additional evidence for why patients need much more extensive investigation of their unexplained symptoms, not less, to prevent them from suffering iatrogenic harm through missed/delayed diagnosis.
Medicine needs to wake up now to the problem of misdiagnosis when patients have unexplained symptoms (of pain or fatigue, for example). For too long such patients have been under-investigated and cast into a MUS waste bin, ending up perhaps with a ME/CFS or FND label that imparted on them some credibility or a sense of belonging and that maybe gave their doctors comfort that the diagnosis box had been ticked. There’s obviously no problem if it’s the correct diagnosis, but it’s far from great if it isn’t. We can’t go on with patients being shown the door or being directed to cheap-option clinics or therapies that make blanket assumptions, miss true biomedical conditions and cause them to deteriorate through biopsychosocial neglect or positive iatrogenic harm. To my mind, this study with its 20% misattribution rate shows just how harmful the MUS construct can be. The evidence was there if only doctors had bothered to look – misdiagnosis of unexplained symptoms appears to be a very serious problem and much better diagnostic workups are therefore needed with these patients. If the lowish misdiagnosis rates that have been disseminated for FND/conversion disorder ever applied to FND/conversion disorder, (and I would take issue with them), they clearly do not apply to ME/CFS or to other medically unexplained problems. Patients with more difficult to diagnose symptoms must not continue to be used as a means of cutting investigations, appointments and healthcare budgets.
Thank you both for an insightful interview. it would be nice for each patients to be treated as if they matter, and their disease was taken seriously. The health care system doesn’t work like that here in Canada. You have a family physician and more often than not they have no one more knowledgeable to refer you to. They cannot name the different requirements to obtain a diagnosis. Because we have no medical specialty, no data is kept, we are not counted, we do not even currently have a diagnostic code, so we cannot be tracked in the system. These are huge impediments to people with a lifelong disabling disease, and the minute you are labelled as ME/CFS you are simply getting the minimum of the minimum care.
I am now 15 years into this disease and have known several who chose to end their lives through MAID or the DIY version. to be honest the NIH paper will not bring a breeze of hope in our community. From my point of view, they failed to understand the history of ME, it is telling from their concept of exertion preference. It is so damning, and as many said it, we have warned about having researchers who may well be on the BPS side of NIH. We were not heard and here we are 7years later.
I am so tired of how slow science moves, and how much BS we need to face days in, day out. sorry pardon my rant.
I hope it’s ok to post this here. A very sensible blog about the issues which many of us with ME find problematical wrt to the NIH ‘study’.
https://colleensteckelmeiccinfo.substack.com/p/nih-intramural-mecfs-study-finally?r=1qgwel&utm_campaign=post&utm_medium=email&fbclid=IwAR1BI94pWDaFH_MYh_m7NKpUMwj0N9MNUJBemg_SQbypL9oUknuLwMteKyY&triedRedirect=true