The P2P Draft report is out

[Sasha]

Maybe this paper?

Yes, that's the one - that was an excellent find.

 

[Ember]

The ICC contains a statement on prevalence.

Prevalence:
~ 0.4 – 1% 2, 3
• affects all age groups, including children, all racial/ethnic groups, and all socioeconomic strata
• onset most commonly occurs between the ages of 30 and 50
• higher prevalence in females

These two studies are cited:

2. Jason LA, Richman JA, et al. A community-based study of Chronic Fatigue Syndr ome. Arch Int Med 1999; 159:2129-2137. [PMID: 10527290]
3. Lorusso L, Mikhaylova SV, et al. Immunological aspects of chronic fatigue syndrome. Autoimmun Rev2009; 8: 287-91. [PMID: 18801465]

The prevalence statement is found under the Epidemiology heading in the Introduction:

MYALGIC ENCEPHALOMYELITIS - Adult & Paediatric:
International Consensus Primer for Medical Practitioners

An International Consensus Panel was formed to develop International Consensus Criteria (ICC)1 and a physicians’ primer that includes the ICC, pathophysiology, and diagnostic and treatment protocols for myalgic encephalomyelitis (ME) based on current knowledge and clinical experience.
Goal: to enhance the understanding of ME and promote clarity and consistency in optimal clinical identification and treatment internationally
Target groups: primary care physicians, internists, pain and other health care practitioners, medical students

Myalgic Encephalomyelitis (ME): complex, acquired multi-systemic disease
Pathophysiology: Profound dysfunction/dysregulation of the neurological control system results in faulty communication and interaction between the CNS and major body systems, notably the immune and endocrine systems, dysfunction of cellular energy metabolism and ion transport, and cardiac impairments.
Cardinal symptom: a pathological low threshold of fatigability that is characterized by an inability to produce sufficient energy on demand. There are measurable, objective, adverse responses to normal exertion, resulting in exhaustion, extreme weakness, exacerbation of symptoms, and a prolonged recovery period.
Note: Myalgic encephalomyelitis (ME) is the name recommended for those meeting the ICC.

Classification: Myalgic encephalomyelitis has been classified as a neurological disease by the WHO since 1969. WHO stipulates that the same condition cannot be classified to more than one rubric because, by definition, individual categories and subcategories must remain mutually exclusive. Thus, it is essential that patients meeting the ICC for ME are removed from overly inclusive groups.

Myalgic encephalomyelitis:
neurological disease
WHO ICD G93.3

Epidemiology
Prevalence:
~ 0.4 – 1% 2, 3
• affects all age groups, including children, all racial/ethnic groups, and all socioeconomic strata
• onset most commonly occurs between the ages of 30 and 50
• higher prevalence in females

ME:
• generally sporadic
• endemic
• widely dispersed epidemics

Prognosis
• Currently there is no known cure.
• Early intervention and appropriate treatment strategies may lessen severity of symptoms.
• Restoration to full pre-morbid health and function is rare.4
• Prognosis for an individual cannot be predicted with certainty.
Paediatric: Children can be very severely afflicted.
• Children with less severe symptoms are more likely to go into remission than adults.

Etiology
Predisposing Factors: multifactorial and fairly individual
1. Genetic predisposition: increased susceptibility associated with

• Gene expression modifications: neurological, hematological, metabolic, sensory, immunological disease, function/response, infection, inflammation, cardiovascular, cancer, cell death and endocrine5-12
• Clusters of combined gene data suggest distinct genomic subtypes and disease associations.12,13
• Familial and twin studies indicate there is a higher degree of ME in relatives, to third generation.14

Environmental factors may outweigh genetic predisposition.15 Several epidemics support an infectious cause.16

2. Pre-onset environmental events that may compromise the neurological and immune systems, and increase susceptibility to infection: • minor infections
• immunization • exposure to new infectious agents, especially when traveling or following recent infections • contaminated water • recycled air in flights • blood transfusions • anaesthetics • toxic chemicals • heavy metals • severe physical trauma: whiplash/spinal injury/surgery • undue psychological stress17-23

Precipitating Events and Causal Factors: Most patients enjoyed healthy, active lifestyles prior to the onset of ME. Widely dispersed epidemics support an infectious cause. Symptoms at onset are usually consistent with an infectious process.

Onset Survey
1,000+ patients
75.6%: infection alone or
infection + 1 or more factors:
environmental exposure, physical
trauma, vaccinations, other stressors
Vernon SD. CFIDS of America

1. Infectious agents associated with ME
Viruses: • Enterovirus24-26 • Epstein Barr virus (EBV)27 • Human herpes virus (HHV 6 and 7)28, 29 • Cytomegalovirus30 • Parvovirus B1931
Bacteria: Chlamydophila pneumonia32 • Mycoplasma33 • Coxiella burnettii27
It is unclear whether these infectious agents initiated ME or are opportunistic and developed due to an impaired immune system. No one virus has been universally implicated for all patients. A prospective study reported that six months following acute infections of Epstein-Barr virus, Coxiella Burnetii, or Ross River virus, 11% of the patients had CFS.34 This supports the presence of ME subtypes. Antibody testing for a number of viruses revealed subtype-specific relationships for Epstein Barr virus and enterovirus, two of the most common infectious triggers for ME.27

2. Possible etiological process: A growing body of evidence suggests that a primary cause of ME is neuropathic viruses that may infect neurological and immune cells and damage the capillaries and micro-arteries in the CNS bed causing diffuse brain injury. The initial infection may cause profound dysregulation of immune system pathways that may become chronic or cause autoimmunity even when the level of the infectious agent is reduced.35

ME Phases
1. Infectious Onset/Acute Phase < 6 months: Most patients have a distinct acute onset where flu-like or upper respiratory symptoms or other signs of an infectious process are evident. The incubation period usually runs a few days to a week. Instead of recovering, the patient’s condition worsens, and the symptoms that identify the distinctive character of ME begin to appear as a cluster. Approximately 20% of patients have a gradual onset that may follow events that compromise the immune system, making them vulnerable to new or reactivation of persistent latent infections that can further overwhelm the immune system.26
2. Chronic Phase > 6 months: Generally, symptoms tend to be more stable in the chronic phase. Some patients have some improvement in the chronic phase while others have a progressive decline in health.

 

[Sasha]

I read a comment on Jennie Spotila's blog that ME/CFS is 236th on NIH’s grant list out of 247 ailments, in terms of funds allocated.

Does anyone know the source of this?

 

[Denise]

I read a comment on Jennie Spotila's blog that ME/CFS is 236th on NIH’s grant list out of 247 ailments, in terms of funds allocated.

Does anyone know the source of this?

It probably comes from here:
http://report.nih.gov/categorical_spending.aspx
By clicking on the year (top row), the funding sorts by decreasing amounts.

 

[Sasha]

It probably comes from here:
http://report.nih.gov/categorical_spending.aspx
By clicking on the year (top row), the funding sorts by decreasing amounts.

Oh! So it does. It has a lot more rows in Excel than it looks like it does on that page! Thanks.

 

[Sasha]

Turns out we're actually 229th out of 237 this year.

 

[Bob]

The ICC contains a statement on prevalence.
...
These two studies are cited:

2. Jason LA, Richman JA, et al. A community-based study of Chronic Fatigue Syndr ome. Arch Int Med 1999; 159:2129-2137. [PMID: 10527290]
3. Lorusso L, Mikhaylova SV, et al. Immunological aspects of chronic fatigue syndrome. Autoimmun Rev2009; 8: 287-91. [PMID: 18801465]

Thanks Ember.

The info in the Jason paper is included in the Jason paper that we've been citing in this thread for the cost to society data.

This is the link for Jason's prevalence paper:
http://archinte.jamanetwork.com/article.aspx?articleid=415556

This is the relevant info (a 0.42% prevalence rate):

Findings indicated that CFS occurs in about 0.42% (95% confidence interval, 0.29%-0.56%) of this random community-based sample.

And this is the link to the second paper (Lorusso et al. 2009):
http://www.sciencedirect.com/science/article/pii/S1568997208001808

The paper is behind a paywall, and the relevant text from the abstract is as follows (0.4-1% prevalence):

The estimated worldwide prevalence of CFS is 0.4–1% and it affects over 800,000 people in the United States and approximately 240,000 patients in the UK.

I've looked at the full paper, and it does not include further details re prevalence. It simply says the same as the abstract:

The estimated worldwide prevalence of CFS is 0.4–1% and it affects over 800,000 people in the United States and approximately 240,000 patients in the UK [4,10].

These are the two references that it refers to. I haven't looked at them:

[4] Devanur LD, Kerr JR. Chronic fatigue syndrome. J ClinVirol 2006;37:139–50.
[10] King C, Jason LA. Improving the diagnostic criteria and procedures for chronic fatigue syndrome. Biol Psychol 2005;68:87–106.

 

[Denise]

Is it worth looking at the references in this article re prevalence?
http://www.biomedcentral.com/1741-7015/9/91

 

[Bob]

Is it worth looking at the references in this article re prevalence?
http://www.biomedcentral.com/1741-7015/9/91

Thanks Denise,
That's a UK study, and it estimates prevalence rates to be at 0.2% (compared to Jason's estimate of 0.42%) for "any of the study case definitions."
Depending on the criteria used, its estimates range from 0.11% to 0.2%, and even as low as 0.03% using the authors' own epidemiological case definition (ECD):
"The estimated minimum prevalence rate of ME/CFS was 0.2% for cases meeting any of the study case definitions, 0.19% for the CDC-1994 definition, 0.11% for the Canadian definition and 0.03% for the ECD."

So it's a UK-based study, and its estimates are much lower than Jason's. I'm not sure how helpful it is for our case, esp with an estimate as low as 0.03% using their own criteria.

 

[Denise]

Thanks Denise,
That's a UK study, and it estimates prevalence rates to be at 0.2% (compared to Jason's estimate of 0.42%) for "any of the study case definitions."
Depending on the criteria used, its estimates range from 0.11% to 0.2%, and even as low as 0.03% using the authors' own epidemiological case definition (ECD):
"The estimated minimum prevalence rate of ME/CFS was 0.2% for cases meeting any of the study case definitions, 0.19% for the CDC-1994 definition, 0.11% for the Canadian definition and 0.03% for the ECD."

So it's a UK-based study, and its estimates are much lower than Jason's. I'm not sure how helpful it is for our case, esp with an estimate as low as 0.03% using their own criteria.

Sorry - I was not clear - are there any references that are useful?

 

[Bob]

@Sasha

I can't remember if anyone has compared disability in ME with disability in other illnesses such as MS.
I thought Beth Unger has said something about it at a CFSAC meeting, but I can't remember any details.
I'd be surprised if there wasn't any such research, but my memory is useless.

But I have got a list of some (mean) SF-36 physical function scale scores for other illnesses and for healthy adults, if it's any help for anyone. Strangely, I haven't got any scores for ME patients, so this list isn't any use unless we can find details for ME to make a comparison. (Is anyone aware of any research showing mean SF-36 physical function scores for ME patients?)

The SF-36 physical function scale is from 0-100 where 100 is the most-healthy score. It's a self-report measure for physical disability/incapacity.

SF-36 physical function scores.

Healthy Adults (mean) 96.6 [1]
Hepatitus C patients (mean) 79.3 [1]
Class I heart failure patients (mean) 79.2 [1]
Major Depression patients (mean) 71.6 [1]
Osteoarthritis of the hip patients (mean) 62.4 [2]
Rheumatoid arthritis patients (mean) 62.3 [2]
MS patients (mean) 53.5 [3]

Normative Data:
Normative Data: All adults ages 16+ (median) 95 [4]


References:

1. Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables
J Juenger et al. Heart 2002;87:235–241
http://heart.bmj.com/content/87/3/235.full.pdf

2. Health related quality of life in multiple musculoskeletal diseases: SF-36 and EQ-5D in the DMC3 study
H S J Picavet, N Hoeymans 26 July 2003
Ann Rheum Dis 2004;63:723–729. doi: 10.1136/ard.2003.010769
http://ard.bmj.com/content/63/6/723.full.pdf

3. Quality of life in multiple sclerosis: development and validation of the 'RAYS' Scale and comparison with the SF-36
Zeev Rotstein et al.
International Journal for Quality in Health Care 2000; Volume 12, Number 6: pp. 511-517
http://intqhc.oxfordjournals.org/content/12/6/511.full.pdf

4. Normative Data:
Health Survey for England (HSE) 1996 (All adults, ages 16+)

 

[Bob]

Sorry - I was not clear - are there any references that are useful?

If you mean references that are useful for prevalence rates, then I don't think there are. It uses data from English primary care clinics rather than data from other research papers.

 

[Denise]

If you mean references that are useful for prevalence rates, then I don't think there are. It uses data from English primary care clinics rather than data from other research papers.

Thanks Bob.
I didn't want to leave a possible stone unturned.

 

[Ren]

From the other P2P thread, Bob wrote:

Hi Sasha, I can delete this post after you've considered it. Oxford are a broad/inclusive set of criteria that simply diagnoses "chronic fatigue" (no other symptoms required.) Would you also be able to include a comment about removing research evidence that was based on a general 'chronic fatigue' recruitment criteria (i.e. equivalent to Oxford) whether Oxford was used or not? I think a lot of CBT/GET research might be based on recruitment criteria that simply required chronic fatigue for a period of time. They don't all use Oxford.

Does anyone remember which study/researcher (Price? Prince??) claimed to use patients diagnosed according to Fukuda, but in reality, they did something like accept patients with chronic fatigue minus the other Fukuda requirements? I thought this might be in line with Bob's comment above and that the phrase "equivalent to Oxford" was really important.



Edit: I believe this is the paper I had in mind...
J.B. Prins, G. Bleijenberg, E. Bazelmans m.fl., Cognitive behaviour therapy for chronic fatigue
syndrome: a multicentre randomised control trial (2001). Lancet, vol. 357, sid. 841–847.

This link has comments by Kindlon and Goudsmit: http://www.ncbi.nlm.nih.gov/pubmed/11265953

This link is the paper, free full text: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)04198-2/fulltext

Patients were eligible for the study if they met the US Centers for Disease Control and Prevention criteria for CFS,1 with the exception of the criterion requiring four of eight additional symptoms to be present. Severe fatigue and severe functional impairment were defined by cut-off scores—a score of 40 or more on the subscale fatigue severity of the checklist individual strength and a score of 800 or more on the sickness impact profile. Additional inclusion criteria for this study were age between 18 and 60 years and residence within 1·5 h travelling time of one of the study centres. Additional exclusion criteria were previous or current participation in CFS research, pregnancy, and current treatment to achieve pregnancy.

.

 

[jspotila]

I have not been able to keep up with this thread, but @Sasha encouraged me to pop in and share a few thoughts. For a 19 page draft report, there are a lot of issues that require comment and many of them could be bolstered with knowledge of the scientific literature. But this makes it very intimidating to many of us. With the holidays, I have been too overwhelmed to even begin to work on my own comments. I assume some of you may feel the same way.

But I don't think knowledge of the literature is required to put together good comments. There are some obvious scientific issues they missed, but I'm actually just as concerned about the policy issues. For example, they did not prioritize among their recommendations. Does that mean research on homeopathy is just as needed and important as research on biomarkers? That having another meeting on case definition is more important than funding Centers of Excellence? I'm not comfortable leaving that to NIH to decide as they will. Knowledge of the literature is not necessary to comment on that kind of thing.

I also don't think anyone should feel pressured to respond to every single thing wrong with the report. I think it would be more valuable to have many people commenting on the issues they feel are most important, than to have fewer comments that are more detailed and comprehensive. I've seen draft comments from a few people, and I will be trying to be comprehensive myself. Personally, I think it would be powerful to have dozens (or more!) of people comment on how the report glosses over the need for NEW MONEY.

I will be publishing my comments on my blog, but I don't know how close I'll cut it to the deadline. I actually haven't started them yet, although I've been cogitating on it. I won't be inviting others to sign on, but people are free to adapt what I publish. I also think it's important to remind and encourage people to tune in to the CFSAC meeting on January 13th.

I have not been able to keep up with every post in the discussion thread, but from what I've seen people are identifying good issues. If every single person who has commented in that thread sent in a comment, even if it is not detailed and comprehensive, that would be fantastic!!

My suggestion is that you pick the most important issues in your mind, whether it is the ME v. CFS question or the need for new money or the recommendation for multimodal therapy or whatever. It might be more manageable to focus your efforts on those top priority issues, and write a really good comment on that.

 

[Sasha]

Thanks, @jspotila - I agree with everything you've said there!

The main thing is that we respond at all, and on the stuff that's most important to us.

 

[Nielk]

To insist that the Oxford Criteria should be eliminated, and not to insist that the Fukuda Criteria should too, is a missed opportunity in my opinion.

The reason behind the 2012 CFSAC recommendation to convene a workshop to work on the criteria starting with the CCC, was to move on from the Fukuda which is too broad of a "fatiguing" definition. CFSAC, experts, patients and advocates have been urging the CDC for many years to replace the Fukuda with the CCC on their website as the current accepted criteria.

In order to move ahead with the science for this disease, old criteria need to be retired. With other diseases, when new criteria are found based on current science, past criteria are retired. If the new criteria are not perfect, they will be modified as needed. Why is it that with this disease all old outdated criteria are still being used and even worse, they are considered with the same value? Is this logical?

I feel that this is an opportunity to voice our opposition. If we don't do it now, will we be stuck for another 30 years with this?

In addition, we were told at the start that the three efforts; IOM, P2P and CDC study will work in synergy. Does that mean that the resulting p2p report will have an effect on the IOM one?

The other thing to keep in mind is; in what way will this report advance the science for the disease?

The draft report, as it stands now, is unscientific by the fact that it just makes statements (of opinion?) without supporting documents/references. It lacks focus and the recommendations are just lists that have been picked up from a variety of places with no emphasis of importance or order. There are contradictions of opinions which probably reflect the different opinions of the panel members. It's as if they each called out information that they felt were important (or remembered?)


I cannot fault the panel members. They probably did the best they can under the circumstance. I do fault the parameters and the process. I fault HHS for picking this inappropriate process for this work. I fault them for making this disease as political as it is.



Do you really think that the NIH did not know what the result would be by throwing in the Oxford Critera in the mix? You think that this was not done exactly for the reason of making sure that the PACE trial would be a big part of the study?



Charging 5 people to learn everything about a disease that is controversial in 2 days and then have 24 hour to come up with a comprehensive sensible report That advises on meaningful recommendations is an impossibility.


There are so many conflicting statement in this draft, like stating the prevalence of 1 million and then stating that because of the lack of set criteria, we really don't know the prevalence. They state that ME/CFS exists yet, they admit that because of the lack of biomarkers and the various criteria, we really don't know what it is:



48 Studies of ME/CFS are fraught with methodological problems, preventing a clear understanding

49 of who is affected by ME/CFS: there are no agreed-upon parameters for defining ME/CFS, no

50 accurate ways of identifying and diagnosing ME/CFS, and 163 symptoms have been associated

51 with ME/CFS.



In addition, I feel that the "sugar coating" that they use by stating that there is so much stigma for patients, they feel misunderstood, there is a heavy burden on the patients..etc, is really used as a reason why there is a need for :



344 7. Improve treatment. Patients should be active participants in care and decision-making.

345 Lessons can be learned from palliative care, such as compassion, communication, and

346 symptom management to improve the quality of care. Studies examining the role of self-

347 management techniques as part of a comprehensive treatment plan for patients with

348 ME/CFS during and after clinical interventions should be explored. The modest benefit

349 from CBT should be studied as adjunct to other modalities of treatment such as self-

350 management. Future treatment studies should evaluate multimodal therapies.



What we really need is specialists in the disease who understand the science. We need to adopt current criteria based on science like the CCC and/or ICC. We need research to find real biomarkers.



In their conclusion, the draft report states:



365 harm. Thus, for needed progress to occur we recommend (1) that the Oxford definition be

366 retired, (2) that the ME/CFS community agree on a single case definition (even if it is not

367 perfect), and (3) that patients, clinicians, and researchers agree on a definition for meaningful

368 recovery.



Isn't this what the CFSAC recommendation was all about? The ME/CFS community has already agreed on starting with the CCC and improving on it as needed.



In addition, they state:



105 ambulatory patients). A clear case definition with validated diagnostic tools is required before

106 studies can be conducted



So, we are back to square one - the CFSAC recommendation.

 

[Ember]

I feel that this is an opportunity to voice our opposition. If we don't do it now, will we be stuck for another 30 years with this?

In addition, we were told at the start that the three efforts; IOM, P2P and CDC study will work in synergy. Does that mean that the resulting p2p report will have an effect on the IOM one?

The other thing to keep in mind is; in what way will this report advance the science for the disease?

I don't plan to comment on the Draft Report. The US government's determination to ignore expert opinion is too galling for that. Dr. Unger has spent the past few years gathering data on ME/CFS patients through her multi-site study. She told the Panel that we need improved patient outcome measures specific to ME/CFS; but to develop questionnaires that will better capture patients' experience, we first need focus groups to identify the most important illness factors.

Dr. Unger has provided input to the IOM Committee over the past year. Now the NIH Draft Report recommends another team to mastermind a research definition: “Assemble a team of stakeholders (e.g., patients, clinicians, researchers, federal agencies) to reach a consensus on the definition and parameters of ME/CFS.” Won't that team also be charged to “coordinate with two ongoing HHS efforts concerning ME/CFS in order to minimize overlap and maximize synergy?”

The mandate of ongoing HHS efforts concerning ME/CFS is to waste time and money, or worse:

Since the expert ME/CFS scientific and medical community has developed and adopted a case definition for research and clinical purposes, this effort is unnecessary and would waste scarce taxpayer funds that would be much better directed toward funding research on this disease. Worse, this effort threatens to move ME/CFS science backward by engaging non-experts in the development of a case definition for a complex disease about which they are not knowledgeable.

The Draft Report calls for protest.

 

[OneWaySurvival]

I have decided, personally, not to formally comment on the P2P draft report. I am joining other patients and advocates in continuing to protest the whole process of P2P for ME/CFS.

I feel that this process should never have been chosen for this "controversial" topic. The parameters set upon it by the NIH were meant to assure an unsound, inferior result.

I second that!

The NIH is forcing a process on us that is more costly, more draining on patients (how many times are they going to ask us to publicly comment to painfully educate and re-educate panel members with no ME experience? And why is that our job anyway?), and with a much longer wait for valid research than if they simply put their full weight and effort into expediting the recommendations from our experts to use the CCC as a starting point.

They are playing games with us, and our suffering grows.

 

[Isamu]

The 17 million came from the Office of Research on Women Health.

"Roughly 17 million people worldwide (one to four million in the United States) are estimated to have ME/CFS. ME/CFS strikes people of all ages and racial, ethnic and socioeconomic groups, and is diagnosed two to four times more often in women"

http://orwh.od.nih.gov/research/me-cfs/aboutmecfs.asp