NIH post-infectious CFS study

[dancingstarheart]

Looks like 40 patients + controls
http://www.meaction.net/2016/02/09/...al-questions-re-nih-clinical-center-protocol/

Ron Davis is starting with only 20 patients & yet I have not heard people complaining that his sample is too small.

Ron Davis does not have NIH's budget.

 

[dancingstarheart]

If only it was a competition and if only the CDC and NIH were both interested in winning it, we wouldn't be in this mess.

Competition and collaboration. I think Ron Davis explained that well. I agree, we wouldn't be in this mess if the CDC and NIH had prioritized this disease properly.

There have been very few if any studies of this nature and scope performed to date. This study may or may not confirm a lot of previous studies, we don't know because we don't know the specifics yet.

Agreed, no specifics provided.

Because its not his study. He is looking at one particular aspect. This is a much broader study. There is no process of his to replicate. Who knows what his 5 year prediction was based on, but studies like this one can only help. I am sure if he advised on this study then he has included as many tests as he believes relevant.

NIH/NINDS still has to prove that they can put a decent study together. Final protocl with methods must be communicate to patient community and feedback obtained before study is initiated.

I must apologized... I was not familiar with how people split up a quote to address different parts. Just now figured out how to use the /QUOTE. So initial post looked like I added verbiage to the quote.

 

[valentinelynx]

This is not a study of a distinct disease - ME. It is a study of a symptom - fatigue ,that presents itself after an infection.

I remember Collins explaining to an interviewer that this study will also help us explain the fatigue that many cancer patients experience.

Forgive me, I can't look deeply (or much at all) into this right now, but I'm wondering how they determine whether the subject had an infection? I'm pretty certain my onset was due to infection, but don't know what the infectious agent was. Could have been Lyme, or a virus, or bartonella or brucella, etc. Are they only taking patients with a laboratory proven infection at onset of symptoms?

 

[Forbin]

I have decided that having a healthy post-lyme, and a functional movement disorders group is a luxury that we cannot afford.

My guess is that it is not a luxury, but more of an economic necessity. They may be bringing in Post Lyme and FMD not just because of their so-called "overlap," but also because those diseases each have some kind of budget (which may be as miniscule as that of ME/CFS). By combining the "fishing expeditions" of three diseases into one study, they may be able to bring more resources to bear than if ME was studied alone.

If they did drop Lyme and FMD from the study, I wouldn't be surprised to see that it still consisted of just 40 ME patients - only the testing of those 40 would be more limited

Including Lyme and FMD may principally be a decision based on an "economy of scale."

 

[Forbin]

Forgive me, I can't look deeply (or much at all) into this right now, but I'm wondering how they determine whether the subject had an infection? I'm pretty certain my onset was due to infection, but don't know what the infectious agent was. Could have been Lyme, or a virus, or bartonella or brucella, etc. Are they only taking patients with a laboratory proven infection at onset of symptoms?

I think the protocol, which has been removed, said something about having a doctor's verification that you had an infection around the time of onset. This might just mean that you told your doctor that you had an infection prior to, or concurrently with the onset of ME. I told my doctor that I'd had a prior infection earlier in the month, so he ordered a blood test that, surprisingly to me, indicated that my immune system was still fighting an infection, presumably the flu.

 

[duncan]

If they keep Lyme and FMD in the mix, I will be very interested to see the response of our patients to any tests that involve interpretative values, e.g. neuropsych evaluations, MRI's, etc.

What if FMD's aren't FMD's, and what if post-Lyme isn't post? Why include patients from two contested areas as controls in the first place when they've a slew to pick from? Why not pick a post-viral disease like mono? Why not steer as clear of controversy as you can - after all, the CFS focus alone is likely to generate bias?

Of course, if my concerns play out, at that point results will stick.

 

[Valentijn]

Ron Davis is starting with only 20 patients & yet I have not heard people complaining that his sample is too small.

The sample size needed partially depends on the number of comparisons made. With three control groups, that results in a lot more comparisons being made - three times as many for each measurement, in a study where there are a lot of measurements being made.

The FMD and Lyme groups weaken this study.

 

[Bob]

I can't remember if this is exactly the same as I've read elsewhere. Posting it here for reference.

A couple days later, Dr. Nath and NINDS Director Dr. Walter Koroshetz provided important clarifying information to Bob Miller and me, especially noting that enrollees will need to meet the Canadian Consensus Criteria and have Post Exertional Malaise. They said additional information will be posted on a website for patients and the community in the coming week. We wanted to reiterate them here for patients who are able to watch the webcast.

We asked questions about the criteria for enrollment, reference to Reeves criteria in the draft protocol, role of ME/CFS experts and the choice of control groups. According to the principal investigator of the study, Dr. Nath:

• Enrollees will meet all definitions for ME/CFS, including Canadian Consensus Criteria, IOM, Fukuda and Reeves, in addition to post-infectious onset.
• Post-exertional malaise (PEM) is a criteria, and will be specifically studied with extensive testing before and after exercise challenge.
• Dr. Ian Lipkin of Columbia University’s Center for Infection and Immunity has been advising the investigators on the study design and protocol.
• Expert clinicians will be used in patient selection, including those participating in recent multi-site studies of ME/CFS. This information was also learned separately by MEAction.
• Control groups: Asymptomatic Lyme was chosen to contrast post-infectious ME/CFS patients to patients who recovered from an infection. 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.
• They seek to have 40 PI-ME/CFS patients, and they will study them longitudinally, hoping to learn how and whether the disease changes over time.
• Testing will be extensive.

See more at: http://simmaronresearch.com/2016/02/hear-more-on-tuesday-about-nih-study-during-cdcs-grand-rounds/

 

[duncan]

Having a logic behind control group selection is not necessarily the same as having good logic.

 

[jimells]

Ron Davis is starting with only 20 patients & yet I have not heard people complaining that his sample is too small.

I predict that Dr Davis will expand his study if he can raise enough money.

NIH and CDC have both shown they are incompetent to organize a proper research program. It should be obvious that any multi-million-dollar, multi-year project needs a plan and a leader, whether the project is ME research or building a bridge. So what do we get from NIH - one very limited, poorly conceived study organized by people who don't seem to know much about my illness.

Here is a six page document from Dr Davis explaining his study.

And here is a blank web page describing the NIH study.

NIH is dead from the neck up. It is time for the current leaders to retire.

 

[jimells]

Are they only taking patients with a laboratory proven infection at onset of symptoms?

They are being selected by expert clinicians, apparently. Not many details of the criteria have been published, and the ones that were published on the participant recruiting notice are now invisible.

 

[Bob]

I agree with @viggster, that its difficult to please this group! Here's the NIH doing exactly what we've been asking the government agencies to do for decades (i.e. to take the illness seriously and to carry out credible biomedical research, using competent biomedical researchers). They decide to do a serious and incredibly complex in-house study (which is in addition to what we've asked for - there was no pressure for them to do an in-house study - so it's entirely voluntary), with a top researcher taking the healm (if they weren't taking it seriously they wouldn't waste the time of a top biomedical researcher, or design such a complex study). They're even getting advice from Prof Lipkin who is a very highly respected scientist (he's so passionate about the subject that he's put us in his bucket list) who is undoubtedly telling them to take it seriously and to get it right. They wouldn't waste his time if they weren't serious about it.

They're profiling the patients correctly and carefully, as far as we know (i.e. CCC and post-infectious with post-exertional malaise) in precisely the way we would want them to. They're doing longitudinal investigations before and after exercise tests (which is precisely what we would demand, and is clearly well-informed and carefully thought through). They're including a two day exercise test, as far as we know, which is precisely what some of you would demand, although I'm not happy about it being obligatory. They're asking participants to do an in-house one-week stay so they can monitor and take tests. The battery of tests is huge, complex and comprehensive, unlike anything we've ever seen before, and will use the NIH's top-of-the-range state-of-the-art equipment to observe longitudinal changes in cells, DNA, DNA expression, RNA, proteins, the immune system, etc, etc, etc.

The testing is so wide that it's being called a fishing expedition. A fishing expedition is exactly what is needed, IMO, unless you think you know the cause of ME already. (Ron Davis is doing an almost identical highly sophisticated fishing expedition.) (And in my opinion, to complain about this study in terms of it being a fishing expedition is like shooting yourself in both feet - anyone who makes such a complaint doesn't represent me - and is potentially harming the community, IMO.)

And to top it all, the leaders of the NIH and this project have been reaching out and communicating with the patient community and listening to concerns.

My guess is that this study will cost many millions - perhaps between 5 and 10 million dollars.

So, what's not to like? What have they got wrong? They put out a provisional protocol that wasn't ready for public consumption, and/or they didn't consult/communicate with the community enough from the beginning. And some of the project leaders are learning about ME from scratch (they probably knew nothing about it before embarking on the study - but Vicky Whitemore probably knew nothing a few months ago, and has made an excellent impression on many in the community). And the NIH leader (who isn't involved in the detailed study design) doesn't properly understand the illness and talks about 'fatigue' more than we'd like.

And, some of you are not comfortable with two out of three of the control groups. But I think the asymptomatic Lyme control group is a very sensible choice. I'm not comfortable with the FMD group because there might be some significant or substantial overlap with ME. But demonstrating similarities or differences between ME and FMD isn't necessarily a problem. As long as the FMD patients don't experience PEM and/or constant exhaustion, it could be a useful control. I acknowledge a problem here, but I think it's too much for us to have expected the NIH to foresee a problem here. Community consultation was lacking.

I'm not saying everything is perfect with this study, but I question whether our community's perspective can be a little skewed at times, because of our very justified suspicion and scepticism.

 

[duncan]

@Bob, for one thing, we cannot unread what was posted eight days ago.

So, to help qualify an unqualified and polemically perceived disease, they select two other contentious and disputed diseases?

Isn't this illogical on an intuitive level alone? On an intellectual level, well, it stumps me.

Then there are the other questions, which may or may not be adequately resolved. We will need to see.

When you factor in the possible consequences, for some of us the possibility of harm or misguided intent is a very real concern.

 

[Sean]

Haven't read all the thread. But having trouble seeing what the big problem is with this study.

Prizes don't go to people who keep fighting yesterday's battles.

 

[duncan]

Fair enough.

Was there a battle? I've heard of some second-hand communications, and some vague acknowledgements and equally vague commitments to listen to our patient community better.

I must have missed the battle.

Wasn't looking for a prize either, unless you consider precise and meaningful research a prize.

 

[Bob]

When you factor in the possible consequences, for some of us the possibility of harm or misguided intent is a very real concern.

I don't deny that there are very real concerns. I share some. But it seems to me that the issues can be ironed out. The NIH are listening, interacting and taking it seriously!

This has the potential to be the biggest study that has ever been carried out for ME. And these are new people at the NIH. These aren't the people who have harmed us in the past.

I understand the cynicism but when people start campaigning against the biggest study ever carried out in the history of ME, on the basis that it's a "fishing expedition", then I don't think it's helpful, but it actually goes against my personal interests! Give me more multi-million dollar fishing expeditions please! As many as possible! Keep them coming.

 

[BurnA]

I predict that Dr Davis will expand his study if he can raise enough money.

NIH and CDC have both shown they are incompetent to organize a proper research program. It should be obvious that any multi-million-dollar, multi-year project needs a plan and a leader, whether the project is ME research or building a bridge. So what do we get from NIH - one very limited, poorly conceived study organized by people who don't seem to know much about my illness.

Here is a six page document from Dr Davis explaining his study.

And here is a blank web page describing the NIH study.

NIH is dead from the neck up. It is time for the current leaders to retire.

I realise there is a lot of anger here but i would say be careful what you wish for. If the current leaders retired now where would that leave us ? With a new set of leaders we have to educate about ME? Great, all the advocacy work of the past few years gone up in smoke, how many years would that set us back ?
I have seen a lot of calls for recognition and studies for ME to be performed by the NIH, then just when we get it within our grasp do you really want the leaders to retire ?

To suggest that the NIH is incompetent and doesn't have a plan or a leader for this project is disingenuous. If I were Avindra Nath reading this forum I would be very insulted and probably wondering if this project is worth it, if that is the response.

We know they made a mistake with the Reeves criteria, but they are reacting to the patient response. Its not fair to point to a blank page as if that provides evidence of incompetence when actually its a sign they are willing to listen and engage.
I just don't see what further criticism of the NIH at this point, is achieving. Its time to catch our breath, wait for the official protocol and hopefully start this study. Its never going to be perfect for everybody but once the selection criteria are correct, this study has the potential to be better than any study ever performed on ME/CFS patients.

 

[Denise]

This thread mentions concerns submitted to NIH by the USAWG re the clinical study.

 

[duncan]

@Bob and @BurnA : I hear you.

Maybe this is a foundational effort. Maybe we forget the mistaken post - or we don't and we treat this as a fixer-upper.

That is preferable, I think. I believe most if not all of us WANT to believe in this NIH effort. We want this to be the first step in can be.

So excuse the cynicism, but I think we all share that earned distrust to an extent. We've learned it the hard way. And when we see something wrong, we know to keep silent might not help, and could hurt.

Maybe we can discern more tomorrow with the Grand Rounds.

 

[Woolie]

"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"

What a joke, @mfairma. Not at all well studied, very heterogeneous, and no evidence of "clear psychological illness" at all. Psychologically, these folks look pretty much how you would expect someone to look if they had debilitating neurological illness. See:
https://www.researchgate.net/public...physical_illness_Time_to_examine_the_evidence