NIH intramural research program update

[Kati]

Here is a very well thought comment from Janelle on ME Action request for comments. Thank you so much Janelle (I would tag you but forgot your screen name! )

Janelle added a comment in reply to USAWG submits questions to the NIH.


It's unclear why one would state: "Functional Movement Disorder was chosen to contrast post-infectious ME/CFS patients with a very well-studied group of patients with clear psychological illness with neurological presentation" and think that this would be helpful to the study somehow. It would seem this group is likely meant to control for the state of having symptoms yet be a negative control for biopathology. This would be based on assumptions based on negative findings (unless the FDA has approved a Medical Device to probe the psyche, of which I am unaware!) which are demonstrably unsound. For example, see "Psychogenic explanations of physical illness: Time to examine the evidence" [Wilshire C, Ward T, Victoria University of Wellington, Under Review].

*It is also unclear why it is thought that such an idea would play well with patients who in other years or other countries or with maleducated doctors and other HCPs and in society in general would themselves be classified as having "clear psychological illness with neurological presentation". This is an objectionable idea through and through. We don't appreciate it for ourselves, and we don't appreciate seeing other people be patronized in this manner, either.*

Please note that fatigue as an exclusion is not sufficient to rule out possible ME/CFS cases. Don't let the name fool you: Fatigue is not the sine qua non of ME/CFS. [Stein, 2005]

Also please note that there is such a thing as "fluctuating conditions". [Steadman, Shreeve, Bevan. 2015] Many conditions change from time to time and the circumstances in which they do are not necessarily understood. The fact that something changes (under whatever condition, even one that is not understood) is not proof that it is psychogenic.

It is easy for doctors or anyone to believe something is faked because they do not understand what is going on and their training has unfortunately led them to believe they should generally understand things. This misunderstanding has happened with a great many diseases in the past, such as multiple sclerosis, asthma, Parkinson's, and so many more it would make an awkwardly long list. Most likely it is past time to change the training so when doctors and researchers encounter something they do not immediately understand, that instead of falling into a maladaptive solution (like "functional disorder", or its historical equivalents like "hysteria") to solve their cognitive dissonance, they can instead seek a constructive solution that will actually support and help the patient, by asking good questions and furthering research, and learning to be comfortable with an unknown state (e.g., a diagnosis without a clear eitiology attached); meanwhile treating symptoms and comorbid conditions collaboratively with the patient, with the best science available.

Furthermore, it is my understanding that the NIMH considers that mental health may in some cases have non-biological risk factors, but if these gave rise to a disease, there would be biolocial sequalae, and it is the duty of the investigator to look for these biological sequalae. It may be inconsistent with the goal of the Institute that would be tasked with research about your FMD group's condition to class them as "clearly" not having any biological factors. [NIH, n.d.]

It may be more useful to consider that a study of ME/CFS may help develop the tools to know which technologies to use to study the patients you would today class as having FMD, and develop new ones.

As I mentioned, not so long ago patients with multiple sclerosis might have been used as people having "clear psychological illness with neurological presentation", but today MS and ME are compared and contrasted immunologically [e.g. Brenu 2016, Huth 2016, Dobryakova E 2015, White AT 2012], and MS may be used as a control group for ME/CFS or vice versa [Elfaitouri A 2013].

In summary, care should be taken that care should be taken that control patients truly belong in the expected group. Care should be taken that tests are not tared with a pathological result rather than with a healthy result.

Control groups should consist of both healthy patients, and patients whose biomedical characteristics are well-characterized. Patients whose biomedical characteristics are not well-characterized could be included in order to study their disease concurrently. However all the groups will need to be larger.

Postscript:
NIH got additional funding this year so funding cannot be an excuse for not being able to carry out good research. Besides which, ME/CFS has not gotten increases to keep up with inflation--which other diseases (that already have more than tenfold more funding per patient per annum, and diagnostic tests, and FDA-approved medications) have--and is overdue a simple inflationary increase even without "extra funding".

References:

Brenu EW and colleagues. 2016. J Immunol Res. A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis. https://www.ncbi.nlm.nih.gov/pubmed/26881265

Elfaitouri A and colleages. 2013. PLoS One. Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis. https://www.ncbi.nlm.nih.gov/pubmed/24312270

Huth TK and colleagues. 2016. Scand J Ummunol. Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis. https://www.ncbi.nlm.nih.gov/pubmed/26381393

Dobryakova E and colleagues. 2015. Front Neurol. The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders. https://www.ncbi.nlm.nih.gov/pubmed/25814977 (Not my favorite hypothesis, though I didn't read the full article.)

NIH, NIMH. n.d. Strategic Research Priorities, Objective 2. https://www.nimh.nih.gov/about/stra...search-priorities/srp-objective-2/index.shtml

Steadman K, Shreeve V, Bevan S. 2015 Jan. Fluctuating Conditions, Fluctuating Support: Improving organizational resiliance to fluctuating conditions in the workforce. http://www.theworkfoundation.com/DownloadPublication/Report/378_FCFS_Final.pdf

Stein E. 2005. Assessment and Treatment of Patients with ME/CFS: Clinical Guidelines for Psychiatrists. http://www.mecfswa.org.au/UserDir/Documents/psychiatry_overview_me_cfs.pdf

White AT and colleagues. 2012. Psysosom Med. Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls. https://www.ncbi.nlm.nih.gov/pubmed/22210239

Wilshire C, Ward T. 2015 Nov. Psychogenic Explanations of Psysical illness: Time to examine the evidence. Victoria University of Wellington. Under Review. https://www.researchgate.net/public...physical_illness_Time_to_examine_the_evidence

 

[Aurator]

Somebody had to recruit Walitt, or suggest him, or approve him. I don't imagine he just hijacked the position of lead investigator.

This is most likely a top down problem; regardless, I don't think for a second it is limited to Walitt.

My guess is either he was singled out as the right man for the job by a committee strongly biased towards the idea that ME/CFS is psychosomatic, or no-one was actually too keen on having the job in the first place considering all the scrutiny from "hysterical" patients that was likely to go with it. Maybe Walitt was felt to be the least vulnerable to being swayed from his task by such scrutiny.

I now suspect we're only kidding ourselves if we believe that when they were setting this up the people at NIH whose task it was suddenly felt all warm and fuzzy towards PwME, were suddenly and unanimously of the view that ME/CFS was highly unlikely to be a psychological condition, and were united by a new philanthropic urge to redress the terrible disservice they all freely acknowledged to one another had been done to patients of this disease over the years.

I'm not saying that a scattering of individuals at NIH aren't prepared to give ME/CFS the benefit of the doubt as a genuine disease, but contempt for ME/CFS and its patients has long been part of the medical profession's esprit de corps, and to be a big softie and go against that just because there might be a grain of truth in an insignificant group of patients' version of events is risking a big loss for potentially very little gain.

 

[BurnA]

Somebody had to recruit Walitt, or suggest him, or approve him. I don't imagine he just hijacked the position of lead investigator.

This is most likely a top down problem; regardless, I don't think for a second it is limited to Walitt.

I think this is a bit speculative.
Yes, he had to be appointed no doubt, but we dont know that he didn't actually apply for the top position (Naths) and was declined and offered this instead.
The fact he is working in the nih means someone values his work. But we don't know who and we don't know their involvment in this study.
I think we should reign in the conspiracy theories until we know a bit more and indeed get some responses.

 

[duncan]

I agree @BurnA: There are a lot of unknowns.

However, to suggest Walitt might not be the only investigator from this study who subscribes to this brand of voodoo science is not a conspiracy theory; it's a possibility we might be foolish to ignore given the nature and gravity of the proposed study.

Think Lyme, and think back to around 2000. A seminal NIH effort was undertaken to determine the efficacy of currently recommended therapies. A Lyme Patient Group reportedly was assigned to monitor the effort to make sure everything was on the up and up. The NIH made it look proper and above board. The result was a bifurcated effort that defined Lyme treatment to this day, and left many Lyme patients feeling betrayed.

And we all know the old platitude about history repeating itself.

I also would like to point out that Walitt didn't magically "poof" into the role of lead investigator. If it was by committee decree, then fine, we need to confirm that, too.

I think we should discuss intelligently the possible ramifications for what we have uncovered so far.

We have potentially serious problems here - not of our own doing - and to downplay them by reducing some to conspiracy theories may not be the best approach.

 

[BurnA]

I agree @BurnA: There are a lot of unknowns.

However, to suggest Walitt isn't likely the only investigator from this study who subscribes to voodoo science is not a conspiracy theory.

I also would like to point out that he didn't magically "poof" into the role of lead investigator.

I think we should discuss intelligently the possible ramifications for what we have uncovered so far.

We have potentially serious problems here - not of our own doing - and to downplay them by reducing some to conspiracy theories may not be the best approach.

I'm not downplaying the consequences of having this person in the position he is in, in fact I made no reference to any consequence of his appointment.

However I will now, I dont want him there, the ramifications could be very serious indeed.

But our enemy is Walitt and whoever subscribes to his theories. Do more people on the team subscribe to these theories ?
Is it possible - Quite likely. But even then we have no knowledge if the other ( non psych) members of the team give Walitt and co. the time of day.

I can easily rebutt your argument and say that Nath had to be appointed to his role, therefore the NIH must believe this is a disease brought on by central nervous system infection.

We can't take one individuals appointment and extrapolate it to mean that the NIH believes one particular thing.

I want to make it clear, I am not saying that the NIH don't all think Walitt is great and he knows it all, I am saying we have no evidence of that.
If we dont have evidence, we are speculating.
Speculation weakens an argument, we have good evidence that this guy is our enemy, let's focus our attention on getting him removed.

 

[viggster]

Collins wrote to me on Feb. 17 after I sent him a note with some concerns and suggestions for improving communications between NIH and the patient community. His letter is posted here:

http://www.meaction.net/2016/02/22/bad-timing-collins-says-of-nih-response-to-cfsac/

Note that our exchange predates the announcing of the NIH intramural team & Wilitt as clinical investigator.

 

[viggster]

Just catching up. The amount of rampant speculation in this thread could fill 15 or so pages of a web forum.

 

[viggster]

What's the protocol for data disclosure with this type of study? Does the high number of tests relative to the small number of subjects suggest they may not be able to share enough data without concern of identification?

Perhaps this is common knowledge, but it hasn't reached me. I'd like to know when and how we, and other researchers, will have access to data, data, data.

As PACE has taught us, never assume.

NIH requires data to be shared, but there is an exception for small human studies so we need them to clarify whether they will make all data from this trial available to other scientists. NIH data sharing policy is here:
https://t.co/wGT6fVQ8Ep

 

[Ecoclimber]

Just catching up. The amount of rampant speculation in this thread could fill 15 or so pages of a web forum.

Having been a science journalist yourself, I would not use the terms "rampant speculation" but rather what any journalist would do, investigate. ME/CFS patient community has 35+ historical record not to be so naive again unless we check the facts. The onus is on the NIH to prove us wrong.

Claims concerning Lead Clinical Investigator, the Ron Walitt, are deeply disturbing. Evidence includes authorized NIH symposiums concerning his research into chronic pain, fibromyalgia, chronic fatigue. He has concluded that there were no biomedical abnormalities and therefore, a psychopathophysiology explanation.

Given a key role concerning this study, I would not want him in this position that would refute his research, interpretation of that research and his dogmatic conclusions. I believe he has competing interests. Otherwise, he would be required to retract a great deal of his published research papers and articles concerning chronic illnesses.

This is best I can gather on their org chart and Ron Wallit position as lead investigator on the NIH Study

NIND
Office of the Director (OD)
Walter J. Koroshetz, M.D. Director, NINDS

Division of Intramural Research (DIR)
Alan Koretsky, Ph.D. Scientific Director
Avindra Nath, M.D. Clinical Director


NINR National Insitute of Nursing
Institute Director, Dr. Patricia A. Grady
is organized into four main areas that report to the Office of the Director: the Division of Management Services (DMS), the Division of Intramural Research (DIR), the Division of Extramural Science Programs (DESP), and the Division of Science Policy and Public Liaison (DSPPL).

Division of Intramural Research
Scientific Director, Dr. Ann Cashion

Symptom Management Branch
NINR’s Medical Officer, Dr. Walitt collaborates with the scientists in the Division of Intramural Research

 

[viggster]

Having been a science journalist yourself, I would not use the terms "rampant specualtion" but rather what any journalist would do, investigate.

I'm not talking about Walitt's positions or what he has said publicly - I'm talking about the speculation as to why he was named lead clinical investigator, and even more speculative, WHAT IT MEANS. For those of you who have decided that Walitt's involvement means that "NIH" as an entity is trying to prove ME is psychosomatic, I'll remind you that Dr. Nath's first slide last week included clinical trials with immunotherapy drugs as part of NIH's plan. That is not what you do with psychosomatic illnesses.

And in the letter Collins wrote to me that I posted at ME Action, he reiterates that the 40-patient intramural NIH study is just the beginning of the NIH research program.

NIH moves slowly, far more slowly than any of us want it to. But there is movement, and I view it as positive movement. As for Walitt, as I said on twitter he causes me concern and I want more information on his role and how he was chosen.

 

[Scarecrow]

Just catching up. The amount of rampant speculation in this thread could fill 15 or so pages of a web forum.

You exaggerate, of course.

But the speculation is understandable given all the blunders and that involving patients seems to be something of an afterthought.

Onwards and upwards.

 

[viggster]

involving patients seems to be something of an afterthought.

I would not characterize patient involvement as an afterthought, but it is happening slower than any of us want it to. NIH put together a protocol and a team and now they're getting feedback on it. Nath said the protocol is fluid and he is open to changing it. I wish there were a more formal way of communicating in place - for our sake and for theirs.

 

[Ecoclimber]

For those of you who have decided that Walitt's involvement means that "NIH" as an entity is trying to prove ME is psychosomatic, I'll remind you that Dr. Nath's first slide last week included clinical trials with immunotherapy drugs as part of NIH's plan. That is not what you do with psychosomatic illnesses.

And in the letter Collins wrote to me that I posted at ME Action, he reiterates that the 40-patient intramural NIH study is just the beginning of the NIH research program.

NIH moves slowly, far more slowly than any of us want it to. But there is movement, and I view it as positive movement. As for Walitt, as I said on twitter he causes me concern and I want more information on his role and how he was chosen.

NIH has earned this legacy. To date, there is no established cause for this illness. The research could show that Dr. Nath was wrong. Otherwise, It would make Walitt's years of research null and void. If you watch the two hour video that I posted and determine that is not so, let me know. There are competing interests here which would normally disqualify a researcher.

 

[Snowdrop]

Speculation is indeed not fact. But it can be warranted. Many times in life we make decisions based on imperfect knowledge and partial data. We can't say things with certainty from that but I wouldn't go treating speculation as if it were merely people pulling things out of thin air.

People speculate often because the issue is of some import and when there is no easy access to complete data often speculation is based on a history of who did what in relation to the issue at hand. It's a guide and not one to be overlooked as irrelevant.

People and institutions do change but until such point that we 'see' it for real in their actions I think there is some relevance to anticipating things in a certain light (speculated) in order to try and keep things honest.

 

[viggster]

Speculation is indeed not fact. But it's can be warranted. Many times in life we make decisions based on imperfect knowledge and partial data. We can't say things with certainty from that but I wouldn't go treating speculation as if it were merely people pulling things out of thin air.

People speculate often because the issue is of some import and when there is no easy access to complete data often speculation is based on a history of who did what in relation to the issue at hand. It's a guide and not one to be overlooked as irrelevant.

People and institutions do change but until such point that we 'see' it for real in their actions I think there is some relevance to anticipating things in a certain light (speculated) in order to try and keep things honest.

Yes, these are good points. I have told my contacts at NIH that they need to be more open and transparent, because in the absence of good information patients are filling in the blanks with their worst fears.

 

[Aurator]

For those of you who have decided that Walitt's involvement means that "NIH" as an entity is trying to prove ME is psychosomatic, I'll remind you that Dr. Nath's first slide last week included clinical trials with immunotherapy drugs as part of NIH's plan. That is not what you do with psychosomatic illnesses.

It's good to hear these reassurances, and the more reassurances we receive direct from the horse's mouth the better.

Ultimately, it's perhaps better to speculate rampantly and elicit reassurances that the speculation is unfounded than to exercise tight-lipped self-control and find out too late that our unvoiced suspicions were only too well founded.

I suspect everyone, no matter what side of the fence they're on and what their particular persuasions are, wants the study to be as productive as possible; both sides being open and honest with one another from the outset about their intentions and concerns is perhaps the best way of achieving that. I don't think many people would dispute that of the small but still considerable amount of public money that has been spent on ME/CFS research to date very little of it has achieved anything substantial.

 

[duncan]

...because in the absence of good information about ME/CFS, some NIH investigators may be filling in the blanks with our worst fears.

Which is more worrisome, I wonder.

 

[Snowdrop]

@Aurator
Well said.
Would be good to have a diagram of the NIH players and where they all fit in with the study.

 

[Kati]

You are what you publish and you are what you say.

It is interesting (and telling) that the community gained respect for Dr Nath, who may not have great experience with ME community but knows how to do science, and how to study the immune system.

In contrast, Walit has shown us who he is from what words came from his own mouth, and from what he's published.

And while we do not know yet what role he will play in the NIH intramural study, we know he comes second on the list after Nath.

As I said before, he may well be the go-to person or group of people for ME/CFS within the walls of NIH. This is a scary thought but it would explain the decades long of ignoring and dismissing, underfunding and refusing grants from our me experts. It would also explain in part at least, the perpetuation of the stigma and neglect of an entire disease.

I also said before that people like him do not change their minds. Rarely scientists actually come forward and say 'I was wrong'. The influence of these psychologizers not only have to be stopped, they should be excluded for fear of 'polluting' the minds of real scientists.

There I said it. Weeding needed.

 

[Nielk]

I think this is a bit speculative.
Yes, he had to be appointed no doubt, but we dont know that he didn't actually apply for the top position (Naths) and was declined and offered this instead.
The fact he is working in the nih means someone values his work. But we don't know who and we don't know their involvement in this study.
I think we should reign in the conspiracy theories until we know a bit more and indeed get some responses.

What conspiracy theory? It is a fact that he is the lead clinical investigator on this study. It is clear that someone on a greater scale than him assigned him to this job. Walitt is not new at the NIH. His colleagues and those higher up know his beliefs on fibromyalgia and chronic fatigue. These are all facts.

Trying to find excuses for the NIH for appointing someone like him to be clinical head of our study is lunacy. This is just more of the same that has been going on for the past 30 years. Why did NIH not appoint someone like harvey Alter who has solid experience with this disease as lead?