The P2P Draft report is out

[Marco]

This is a point I keep coming back to. A cluster is the best way to get a homogeneous patient cohort for research. There is one caveat though. You should not mix clusters, except perhaps in close temporal and geographic proximity, such as Incline Village and Londonville. There is no guarantee the the Incline Village cluster and the Royal Free Hospital cluster are the same, at least not until we have biomarkers.

By using a cluster you might be able to more easily find diagnostic biomarkers. Once you have those then most of this debate becomes moot.

Assuming of course that these outbreaks are related in any way to the vastly greater number diagnosed with ME/CFS or even that the various outbreaks are related to each other. Diagnostic and research criteria/efforts may have been unproductively skewed by trying to accomodate these 'outbreaks of ME' when we don't have any evidence to suggest that these were anything other than unrelated cases of encephalitis like illnesses.

 

[Sing]

I appreciate the need for clinical criteria and also for criteria as a base for disability payments as someone mentioned. We also need criteria for research studies. But what we have learnt in other diseases that we have got to grips with is that none of these are the same criteria as the others. Criteria for making a clinical diagnosis are quite different from criteria for research. And criteria for disability payments should be different again because issues about certainty and severity skew things out of all proportion.

As far as I can see this report is asking for criteria for research purposes - that is the justification they give for their stakeholder group - to improve research. Yet they do not say this clearly and to be honest I doubt they understand these issues (I will post again more fully now that I have actually read the draft summary).

In other words there is no reason to think what they are proposing to do will be of any relevance to patients' problems with getting decent healthcare. This is not what this proposal is about at all, sadly. No way should the research criteria for RA be used for advising GPs how to refer patients. And I still come back to the fact that for research we do not want one set of criteria.

Would you give an example or two of what "research criteria" for us might be? I honestly want to understand what you mean. Would it be something simple like a spinal fluid finding or PET scan finding or NK cell finding--one such or a combination? If you don't want to be that specific, could you outline what such a criterion or set of criteria would look like or do--for research purposes?

 

[Ember]

From what I have seen of available epidemiology a study that recruited on an non-selective basis from chronic fatigue sufferers in a defined population then you might have double or even five times as many cases but these can easily be stratified for features that are relevant to the specific study.

Are you perhaps underestimating the problem? With reference to the Reeves criteria, Jason (2009) finds, “Using these new criteria, the estimated rate of CFS has increased to 2.54% (Reeves et al., 2007), a rate that is about 10 times higher than prior CDC estimates (Reyes et al., 2003) and prevalence estimates of other investigators (Jason, Richman, et al., 1999).”

The International Consensus Panel cites this finding in its Primer introduction:

Remove patients who satisfy the ICC from the broader category of CFS.
The purpose of diagnosis is to provide clarity. The criterial symptoms, such as the distinctive abnormal responses to exertion can differentiate ME patients from those who are depressed or have other fatiguing conditions. Not only is it common sense to extricate ME patients from the assortment of conditions assembled under the CFS umbrella, it is compliant with the WHO classification rule that a disease cannot be classified under more than one rubric. The panel is not dismissing the broad components of fatiguing illnesses, but rather the ICC are a refinement of patient stratification. As other identifiable patient sets are identified and supported by research, they would then be removed from the broad CFS/CF category.

Research on ME:
The logical way to advance science is to select a relatively homogeneous patient set that can be studied to identify biopathological mechanisms, biomarkers and disease process specific to that patient set, as well as comparing it to other patient sets. It is counterproductive to use inconsistent and overly inclusive criteria to glean insight into the pathophysiology of ME if up to 90% of the research patient sets may not meet its criteria (Jason 2009). Research on other fatiguing illnesses, such as cancer and multiple sclerosis (MS), is done on patients who have those diseases. There is a current, urgent need for ME research using patients who actually have ME.

Research confirmation:
When research is applied to patients satisfying the ICC, previous findings based on broader criteria will be confirmed or refuted. Validation of ME being a differential diagnosis, as is multiple sclerosis (MS), or a subgroup of chronic fatigue syndrome, will then be verified.

The ICC provides “a refinement of patient stratification.”

 

[Stuart]

Assuming of course that these outbreaks are related in any way to the vastly greater number diagnosed with ME/CFS or even that the various outbreaks are related to each other. Diagnostic and research criteria/efforts may have been unproductively skewed by trying to accomodate these 'outbreaks of ME' when we don't have any evidence to suggest that these were anything other than unrelated cases of encephalitis like illnesses.

"The vastly greater number" are due to the creation of new definitions with watered down criteria that end up not being the M.E. that was defined by the outbreak clusters that created the disease in the first place!

The cohort mess is created by this "vastly greater number." This "vastly greater number" is full of idiopathic fatigue and misdiagnosed patients. This is the portion that is confounding the research! If you can't 'accommodate' outbreaks that look like each other and create chronically ill patients with the same conditions, why then do you want to lump in "the vastly greater number" created by much less common characteristics?

The ignored biological data IS consistent in these outbreaks. It is a starting point that makes sense. There could be differences and you will discover that by researching them, that is if there are patients and samples to be had. Time is running out to have them.

 

[Jonathan Edwards]

Would you give an example or two of what "research criteria" for us might be? I honestly want to understand what you mean. Would it be something simple like a spinal fluid finding or PET scan finding or NK cell finding--one such or a combination? If you don't want to be that specific, could you outline what such a criterion or set of criteria would look like or do--for research purposes?

It would not need to be based on lab findings. It could be the CCC for instance. It would be used for standardising the recruitment to research studies of a certain type or purpose. The CCC would I think be inappropriate for making decisions in the clinic or about disability. They might be used for that in practice but I doubt it would be a sensible thing to do.

 

[Jonathan Edwards]

Are you perhaps underestimating the problem? With reference to the Reeves criteria, Jason (2009) finds, “Using these new criteria, the estimated rate of CFS has increased to 2.54% (Reeves et al., 2007), a rate that is about 10 times higher than prior CDC estimates (Reyes et al., 2003) and prevalence estimates of other investigators (Jason, Richman, et al., 1999).”

I don't think so. I am basing my figures roughly on a relatively recent population based study using different criteria sets. I prefer not to indicate which study for reasons relating to the complex political implications of the P2P draft - which I hope to post about tomorrow when I can work out what to say. Now that I have read it I am pretty clear what has been going on. The question is how to describe that in a useful way. Sorry not to be more specific.

 

[Kati]

By using a cluster you might be able to more easily find diagnostic biomarkers. Once you have those then most of this debate becomes moot.

Unless the biomarker is a virus or a pathogen, I have a hard time imagining that all cluster patients get the same immune response, an the exact biomarkers. it seems to me that immune responses to an infection can vary from one subject to the other.

Does it make sense?

 

[alex3619]

Unless the biomarker is a virus or a pathogen, I have a hard time imagining that all cluster patients get the same immune response, an the exact biomarkers. it seems to me that immune responses to an infection can vary from one subject to the other.

Does it make sense?

I don't think it does make sense. Sure there would be individual variation. Sure, there are probably those infected who do not get ME. But of those with ME, with remarkably consistent symptoms, there is almost certainly common pathophysiology driving those symptoms. That will lead to biomarkers.

However a pure pathogen causation hypothesis might almost fit what you describe. This is a pathogen doing it all, but only going nasty in people for reasons due to its nature and not the host. Such as enteroviruses that lose regions of nucleic acid and enter an alternate lifecycle. Or a completey novel pathogen we have yet to discover. Even then I would expect to see pathophysiology biomarkers.

 

[alex3619]

Assuming of course that these outbreaks are related in any way to the vastly greater number diagnosed with ME/CFS or even that the various outbreaks are related to each other. Diagnostic and research criteria/efforts may have been unproductively skewed by trying to accomodate these 'outbreaks of ME' when we don't have any evidence to suggest that these were anything other than unrelated cases of encephalitis like illnesses.

If you found markers in one outbreak, and then tested a wider cohort, you would be testing that marker. Using an outbreak cohort would give you a clean population, and help find biomarkers more easily. They would still have to be tested on the general patient population.

Possible unrelated clusters are why you do not mix patients from different cluster outbreaks.

 

[Ember]

The CCC would I think be inappropriate for making decisions in the clinic or about disability. They might be used for that in practice but I doubt it would be a sensible thing to do.

Dr. Snell explains in his P2P presentation that the two-day exercise test is used successfully for making disability decisions. Dr. Dan Peterson, a CCC author, uses it to measure treatment outcomes, and in its Laboratory/Investigative Protocol, the International Consensus Panel uses it as a test for PENE, the cardinal feature of ME.

 

[Nielk]

Someone else asked if my statement that CCC is not best that can be done on today's evidence means I disagree with the 50 experts.

First, one of them, at least, has already changed her mind. In fact, she admitted she mostly signed because she felt this was "her people" and she wanted to support her people. But when she read the goals of IOM contract and how it was going to be done, she said this is exactly what's needed, and the science is strong enough that it's time.
Second, some of the ones who signed are also authors on the ME-ICC, which the authors said should be used.
Thirdly, some who signed, which said IOM contract should be cancelled, are now sitting on the IOM committee to either endorse the CCC, ME-ICC, another one or create a new one. Did they change their mind?
Fourthly, not all ME/CFS experts signed.

I will be glad with any progress from Fukuda or Oxford. And CCC would be progress. However, since some of the ME/CFS experts authored the ME-ICC, that one might actually be better. Just picking one and then advocating for it, whether you are patients or scientists, is not scientific. It hasn't been validated through a trial on actual patients, especially to see how well it distinguishes from patients with other diseases. In this day and time (as opposed to when Fukuda was created), something more than doctors writing "this is our opinion" is needed to get the endorsement of medical societies and be credible, even if it is backed by decades of clinical experience.

It is true that 1 pulled her signature when the IOM contract information came out but, about 15 more added their signature. So, I'm afraid this argument does not have much weight.
Some experts authored the ME-ICC but, as they have stated in their letter to the secretary, they felt that the CCC was the place to start with because it has been tested over ten years now unlike the ICC.

It is also true that less than a handful who signed are now serving on the IOM. I don't know what their incentive was to do so. Maybe they thought that since the IOM is going forth, it would be better if they served on it then others. It is still not an argument over the 46 other experts who have taken the very bold move of signing this historical letter.

In addition, many were contacted after the release of the IOM contract, asking them to reconsider and only 1 choose to do so.

It is not the place of the government to define disease. It is the medical experts who define criteria for diseases. Certainly, the IOM has NO experience in defining disease. They have never done so. Yet, HHS is comfortable accepting whatever clinical diagnostic criteria they come up with. They are so confident in that panel with half of the members who are ignorant of the disease, that they are already getting ready to "roll out" their findings and devising ways of how to disseminate these new criteria nationwide. I guess they find this panel credible without many years of testing. I guess this is called authentically scientific?

 

[RustyJ]

I agree fatigue has many different mechanisms. So it might be good to do a study of idiopathic fatigue with ME or CFS groups for comparison. But it's also good to include MS, fibromyalgia, depression, lupus groups to compare to find the distinguishable mechanism. My understanding is that the Lights are doing this in an NIH-funded study right now. They already did MS and fibromyalgia comparison. I understand they were funded to compare gene expression of other illnesses to ME/CFS. I think this is what this report recommends. But, they already know there is a disease entity that has neurocognitive and pain and PEM that distinguishes it by symptoms from people with unexplained idiopathic fatigue.

I believe a problem for Dr. Edwards and possibly others is the vague term of "post-exertional malaise." The experience is so different from people who get tired easily or are tired most of the time and have nothing else. It is so different that it must have a different mechanism as just being prone to fatigue.

Let me explain PEM, or "activity or stressor-induced neuroimmune symptoms" as I like to call it. It starts off with activity or a stressor. The stressor could be emotional, psychological, viral or physical trauma. Basically, it's anything that challenges the autonomic/neuro-endocrine-immune system and its ability to maintain homeostasis under that challenge. The one we deal with on a day to day basis, that is more often, is activity.

So, I have a "good day." I get dressed, looking stylish and healthy. I feel normal. So I go to run a few errands. Symptoms start after about three hours of running errands.(I can't do long ones, like 45 minutes of grocery shopping. I'm talking 15 minutes in a store at a time, then back to driving/sitting.) The first symptom is hoarse voice. It's mild. Adrenaline kicks end.

After about four hours, the fatigue starts. But the adrenaline can override it. Next symptom, if I don't stop, is hot and cold flashes. If I don't stop, next symptom is severe headache. Next is mental fog. In my case, I also have fibromyalgia. So the pain in my upper back shoulder comes in.

Basically, it's like my body is forcing me to stop and rest. It's like I am coming down with the flu but without the respiratory parts.

Now, if I had stopped at hoarse voice or fatigue, I could have avoided the other symptoms right then. But, even three hours of running errands will result in fatigue, mental fog or even headache coming in within 48 hours. Actually, it seems mine comes 36 hours after activity.

I really think these symptoms connected to a simple stressor, even as little as running errands for a couple of hours, distinguishes us from someone who gets tired easily. It's the other symptoms that give clues to the mechanism in our disease, our type of fatigue.

PEM has been very clearly defined as an amplification of ME fatigue. Both terms refer to the same mechanism. PEM is not a vague term:

Mark Van Ness et al has clearly defined PEM in terms of immune and endocrinal abnormalities and exercise testing with a 95% probability. His work is being used clinically and in legal representation. The work supports the Light findings, so it is independent verification.

It is the only clinical test to validate ME fatigue and PEM.

Once you accept this point, many arguments against ICC, or even CCC fail.

The thing about this is that they have gone far beyond the dithering and are actually doing it.

The science has moved on, beyond this debate, beyond the NIH reports; they are simply out of date.

 

[Nielk]

But are we not agreed that there are no 'correct' patients here. Anyone who has disabling fatigue deserves investigation just as much. We cannot presuppose that there is 'an illness' we want to carefully define unless we have some theory to test about what that illness might be. We certainly might have a theory that there is a type of fatigue that is independent of classical depressive mood changes at onset. So it makes sense to stratify patients according to presence of depression and look at results in each group separately. The same might well be true for PEM. One might have a theory that fatigue with PEM is fundamentally different in mechanism. The range of existing criteria may cover the range of options as well as one can with sets of criteria but I come back to the fact that real, successful research, in my experience, does not depend on defining one set of criteria for a presumed illness category. For RA there have always been four basic sets of criteria and different sorts of studies have used one or more of these for different purposes.

The disease that we are talking about is a distinct disease with it's own history here in the U.S. The disease coined "CFS" by the CDC in 1984 was due to an outbreak in Lake Tahoe. This disease had specific manifestations and findings. Drs. Peterson and Cheney were the local doctors there and were so disturbed by what they were seeing that they called in the CDC in order to see their findings. What they were seeing was eerily similar to the 1955 Royal Free outbreak in England of ME.

The CDC had sent two rookies out who were way over their head and ignored many of the real facts present. It is the CDC who decided to make this a "fatiguing" illness and o rename it "chronic fatigue syndrome". The CDC was not interested in recognizing another major infectious disease when they were busy battling AIDS. It is with this in mind that they created the CDC's Fukuda Criteria which was so murky as to include many who suffered from all types of "fatiguing and mood illnesses".

By devising the Fukuda Criteria, HHS has done a grave injustice to all patients who suffer from the disease ME. It has been 30 years now and HHS has not agreed in recognizing ME as a separate entity. We are not any closer in solving the mystery nor have we found a treatment.

The world experts have done their part. They have created the CCC and ICC only to be rejected by the DHHS. Experts from all over the world have researched this disease but the problems are two-fold. 1- There is a pitiful amount of public funds for research. 2- Until recently, the cohorts were so watered down that the results of research efforts cannot be conclusive.

@Jonathan Edwards - You have stated that in all your years being a clinician and in research, the criteria never mattered. I can't argue with you because I respect you as an excellent clinician and researcher in your field. I just have a question for you. When you were researching the treatment of Rituximab for RA, What if 1/4 of your patients actually suffered from Fibromyalgia and another 1/4 from Osteoarthritis (both have similarities with RA) How successful would your findings have been?

What I would like you to consider is that many of us have been severely sick, living a disabled, painful life for decades. We have felt rejected, neglected and abused by our government health agencies. You are pretty new to the scene of this disease. We have been fighting this for too long. Most of us do not have many years left. We need to see ME be tackled as the serious, distinct disease it is. It is only then that there could be some hope for a better future.

 

[heapsreal]

I think another person who has cfs/me can diagnose another with the illness after talking with them for say a half an hour. I have probably met 6 people face to face with cfs/me. The first thing i pick up on is the cognitive ability, difficulty trying to recall someones name for example and see the strain on their face trying to recall it, alot like someone who has just finished a night shift, probably have been up all night. I said talk for a half hour for a reason as by the end of the talk you can see the energy draining from them and the difficulty they now have in following ones conversation.

It doesnt take long for us to pick cfsme in someone else and we dont need to tick off the boxes of the CCC either, we just know after chatting with each other and sharing a few moments of our ME history. I think in an earlier post someone mentioned the doctors that have been in this field dont need to follow any criteria, ticking boxes, they just know. I think the criteria is needed for those who dont know much about cfs/me.

I guess what im saying is they need some cfs/me experts with lots of clinical hands on, being on these boards like the p2p. I would guess that they would add what biomarkers they thought were relevant the 2 day exercise test which picks PEM, nk function test, cytokine studies etc, to confirm the diagnosis. Not much has been mentioned to rule out other illnesses??

We all know and the experts in the field know, why are they trying to reinvent the wheel again. Its almost if they dont believe any of us. I can see it now, they are going to waste a crap load of money on telling us what we already know instead of using the money for research eg Lipkins, Montoya, Klimas. WOW the wheel IS round and the sky ISNT falling.

 

[Marco]

"The vastly greater number" are due to the creation of new definitions with watered down criteria that end up not being the M.E. that was defined by the outbreak clusters that created the disease in the first place!

The cohort mess is created by this "vastly greater number." This "vastly greater number" is full of idiopathic fatigue and misdiagnosed patients. This is the portion that is confounding the research! If you can't 'accommodate' outbreaks that look like each other and create chronically ill patients with the same conditions, why then do you want to lump in "the vastly greater number" created by much less common characteristics?

The ignored biological data IS consistent in these outbreaks. It is a starting point that makes sense. There could be differences and you will discover that by researching them, that is if there are patients and samples to be had. Time is running out to have them.

Leaving aside idiopathic fatigue and misdiagnosis there are many on this forum who meet the CCC and ICC criteria, with or without apparent viral onset, who nevertheless were not associated with an 'outbreak'. Are they then confounding the research?

As regards ME, a case could be made that only those directly affected in the Royal Free incident can legitimately claim a diagnosis of benign myalgic encephalomyeltis. Everything else is pure speculation.

 

[Tuha]

I have to say that I am completly lost from this P2P. I tried to read this thread, I saw some advocate´s/ patient´s statements but they are so contradictory. I have impression that we are not able to find any agreement in our community. What positive brought us this year regarding ME? Governements dont listen us, patient´s advocates are arguing, we dont have money for ME research. Patients are completly lost and dont understand what´s good anymore. The situation doesnt look optimistic at all but maybe in 100 years it will be different. Pity that we will not be here.

 

[heapsreal]

I have to say that I am completly lost from this P2P. I tried to read this thread, I saw some advocate´s/ patient´s statements but they are so contradictory. I have impression that we are not able to find any agreement in our community. What positive brought us this year regarding ME? Governements dont listen us, patient´s advocates are arguing, we dont have money for ME research. Patients are completly lost and dont understand what´s good anymore. The situation doesnt look optimistic at all but maybe in 100 years it will be different. Pity that we will not be here.

That's about right.

Needs more research but we won't give you money to do it, say those who know the pin number to the govt bank account.

Multitude of reasons as to why they don't seem eager to put funds into research????

 

[Esther12]

Better to have patients disagreeing over whether it's helpful/unhelpful than unified in thinking it's terrible imo. Progress!

 

[RustyJ]

Better to have patients disagreeing over whether it's helpful/unhelpful than unified in thinking it's terrible imo. Progress!

I guess we could discuss its merits for another 25 years. By then most of us would have forgotten this and they can then bring out another report saying exactly the same thing in the name of progress.

 

[Sasha]

I guess we could discuss its merits for another 25 years.

I hope that people will actually write in with their comments. I'll certainly be doing that.