Paper on final P2P Report

[jimells]

Thanks @halcyon, I guess I am incredulous that this tiny paper is a report. Big talk, big effort, big money, tiny report.

... from tiny minds.

p.s. maybe I should clarify: the report doesn't really come from the authors. They are just doing a job. The report actually comes from incompetent NIH managers.

 

[Dolphin]

I've edited the title to show this is a paper on the report, not the report itself.

 

[Bob]

I've just done a second reading, and my interpretation was more positive this time. I don't know why. I picked out positive extracts as I went, and I've quoted them below. I think there's some really positive stuff here:

Both society and the medical profession have contributed to the disrespect and rejection experienced by patients with ME/CFS. They are often treated with skepticism, uncertainty, and apprehension and labeled as deconditioned or having a primary psychological disorder.

Strong evidence indicates that immunologic and inflammatory pathologic conditions, neurotransmitter signaling disruption, microbiome perturbation, and metabolic or mitochondrial abnormalities are potentially important for the definition and treatment of ME/CFS.

The public, provider, and research communities are frustrated with the minimal progress to improve the state of science for ME/CFS over the past 20 years. Patients want their concerns to be heard, a meaningful recovery (not just incremental improvement), and a cure.

Although psychological repercussions (such as depression) may accompany ME/CFS, it is not a primary psychological disease. Several symptoms associated with ME/CFS substantially overlap with other pathologic diseases (such as fibromyalgia, major depressive disorder, and several chronic pain or inflammatory conditions).

Current research has neglected many of the biological factors underlying disease onset and progression. Research priorities should shift to include basic science and mechanistic work that will contribute to development of tools and measures, such as biomarker or therapeutics discovery. The following questions need to be answered: What is the pathogenesis of ME/CFS? What are the roles of virologic mechanisms, especially herpesviruses? Does mononucleosis lead to ME/CFS in adolescents? What are the roles of other pathogenic agents? Is this a genetic disease? Is there a gene–environment interaction? Is it a spectrum disease? Are different pathways responsible for different symptoms?

Innovative biomedical research is urgently needed to identify risk and therapeutic targets.

Investing in bench-to-bedside research for ME/CFS is recommended. Developing biomarkers and diagnostic tests should be a priority.

Valid prognostic tests that can guide treatment strategies using genomic, epigenomic, proteomic, and metabolomic strategies to identify critical biomarkers that will be clinically applicable should be developed. Gene expression, protein, or metabolite signatures that can correctly diagnose ME/CFS and distinguish it from other chronic conditions while predicting disease severity and clinical outcomes are needed. Determining the most important physiologic measures and pathophysiology, as well as genome-wide association studies and phenotyping, are essential for stratifying patients. Functional magnetic resonance imaging and imaging technologies should be further studied as diagnostic tools and methods to better understand the neurologic dysfunction of ME/CFS.

Previously collected research data should be analyzed to advance knowledge and inform trial development and design and facilitate necessary clinical studies. In particular, drug therapies used for fibromyalgia or other pain-related syndromes and disorders should be examined for effectiveness in ME/CFS.

There is a need for "omics"-based drug repurposing and neurobiology studies. With the use of bioinformatics techniques, large data sets should be developed and stored in a central, publicly accessible database for future investigations. New knowledge might include an understanding of molecular mechanisms underlying ME/CFS, new ways to perform pathway analyses, or new pharmacogenomic drug discovery or repurposing.

An integrated, systems-level approach should be followed to understand how immunologic, neurologic, and metagenomic factors may contribute to ME/CFS. Immunologic mechanisms of ME/CFS and pathways associated with disease progression must be defined and characterized (such as defining cytokine profiles involved in pathogenesis, studying inflammation, and comprehending the basis for the natural killer cell dysfunction seen in many patients). Longitudinal studies to explore the possibility of a progressive immune exhaustion or dysfunction in ME/CFS remain important.

Studies of identical twins to identify gene expression biomarkers are needed. Both male and female models must be used to explore the role of sex, X-chromosome genes, and hormones in developing ME/CFS.

 

[halcyon]

I've edited the title to show this is a paper on the report, not the report itself.

Is there actually a difference between the two documents? All I see different is the published paper has a short abstract that's not in the report from the NIH site.

 

[Esther12]

I've not read it closely yet, and might put off doing so for a while, but it seems to me they've avoided making the sort of direct criticisms that are needed to really move things forward (other than of Oxford, and that's not so important to me personally).

eg this looks like the most critical thing of the past:

Both society and the medical profession have contributed to the disrespect and rejection experienced by patients with ME/CFS. They are often treated with skepticism, uncertainty, and apprehension and labeled as deconditioned or having a primary psychological disorder.

Wessely wouldn't phrase things like that, but I don't think that there's anything there he'd directly disagree with.

The talk of 'meaningful recovery' will be (probably rightly) viewed as a criticism of PACE's recovery criteria by people who have been following this issue, but not to most doctors/researchers.

I agree with this statement. It is inconsistent and is seemingly trying to please everyone. It does not throw out the PACE results and puts too much emphasis on patient self-help. It is all a matter of how one interprets this report/article.
See this link http://www.eurekalert.org/pub_releases/2015-06/acop-pst060915.php
Scroll down to #2
The featured headings are: "No diagnostic methods proven effective for diagnosing ME/CFS" & "Counseling therapies and graded exercise may improve fatigue and function in some patients."
This is what many will hear/understand from this. By not negating/throwing out PACE results or at least point out the dangers and harms, they have left the door totally open of perpetual promotion of CBT/GET.

I do not understand how patients can approve/accept this.

In isolation, I don't think that report is bad. In the context of how CFS has been treated over the last few decades I think that any report which is not really active in condemning the how CBT and GET have been sold to patients in that time is harmful.

 

[Dolphin]

Is there actually a difference between the two documents? All I see different is the published paper has a short abstract that's not in the report from the NIH site.

Interesting point. Haven't looked at either yet. Would prefer not to have to read both if they're both the same.

 

[Sean]

Some more quotes:

Clinicians have a poor understanding of the condition, and patients are typically underserved. Studies of ME/CFS are fraught with methodological problems,...

Some instruments used to evaluate ME/CFS are not validated, are inappropriate, and may be misleading. All of these issues contribute to inconclusive research results and a lack of definitive knowledge about incidence and prevalence and potential causes and treatments.

Some instruments used to evaluate ME/CFS are not validated, are inappropriate, and may be misleading. All of these issues contribute to inconclusive research results and a lack of definitive knowledge about incidence and prevalence and potential causes and treatments.

There are few disease-specific clinical trials; a disconnect on ways patients, clinicians, and researchers define meaningful outcomes; a lack of well-controlled, multifaceted studies using large, diverse samples; and limited public and private research dollars directed at ME/CFS.

Patients want their concerns to be heard, a meaningful recovery (not just incremental improvement), and a cure. Educational efforts are needed to assist patients and clinicians to better understand ME/CFS. The scientific community also has a responsibility to address issues that are meaningful to ME/CFS patients.

Although focusing on fatigue alone may identify many ME/CFS cases, it does not capture the essence of this complex condition. Prior studies may have inadequately excluded individuals with these distinct diseases, leading to delayed or conflicting diagnoses, contradictory treatments, suboptimal care, and inappropriate health care utilization.

It is critical that research studies include patients with limited access to clinical services (e.g., non-ambulatory patients).

However, existing cross- sectional studies and small clinical trials with limited applicability have provided few insights into ME/CFS treatment.

Thus, these interventions [counselling & behavioural therapies, & GET) are not a primary treatment strategy and should be used only as a component of multimodal therapy.

Most studies have significant methodological limitations and primarily take place in specialty clinics in relatively homogeneous populations. These trials often use subjective, unclear, and poorly defined end points (that may not be meaningful to patients) and fail to provide information on why there were high dropout rates. Thus, variability in inclusion and exclusion criteria such as the case definition, co-morbidities, patient population, and disease severity has significantly hampered progress in the clinical and research domains focused on assessing and treating ME/CFS.

The failure to give adequate attention to the severity of the physical, social, and emotional impact of ME/CFS has caused harm and diminished hope.

End points need to be clarified: what is statistically significant, what is clinically significant, and what is significant to the patient.

That is a big one for me. The failure to properly distinguish between these is a major stumbling block.

The symptoms patients consider clinically meaningful are not in the scientific literature; this discordance must be rectified.

Agree, though I would phrase it as 'the symptoms patients consider clinically meaningful are not adequately described and accounted for in the scientific literature'.

This covers the first 7 pages, up to the Future Directions and Recommendations section (pp 8-16). I will look at that section later today, or maybe tomorrow...

 

[Dolphin]

I agree with this statement. It is inconsistent and is seemingly trying to please everyone. It does not throw out the PACE results and puts too much emphasis on patient self-help. It is all a matter of how one interprets this report/article.
See this link http://www.eurekalert.org/pub_releases/2015-06/acop-pst060915.php
Scroll down to #2
The featured headings are: "No diagnostic methods proven effective for diagnosing ME/CFS" & "Counseling therapies and graded exercise may improve fatigue and function in some patients."
This is what many will hear/understand from this. By not negating/throwing out PACE results or at least point out the dangers and harms, they have left the door totally open of perpetual promotion of CBT/GET.

I do not understand how patients can approve/accept this.

The press release wasn't just a summary of the P2P report but also the two AHRQ review papers:

ETA: Actually, on a re-read, I notice the P2P paper isn't mentioned at the start. They're more on the AHRQ reviews.

Source: Eurekalert
Date: June 15, 2015
URL: http://www.eurekalert.org/pub_releases/2015-06/acop-pst060915.php

[Embargoed news from Annals of Internal Medicine]

Two systematic evidence reviews evaluate diagnostic methods and
treatments for myalgic encephalomyelitits/chronic fatigue syndrome
----------------------------------------------------------
Diagnosis: http://www.annals.org/article.aspx?doi=10.7326/M15-0443
Treatment: http://www.annals.org/article.aspx?doi=10.7326/M15-0114
Editorial: http://www.annals.org/article.aspx?doi=10.7326/M15-0647
URLs go live when embargo lifts

Up to 2.5 million Americans suffer from myalgic encephalomyelitis
(ME)/chronic fatigue syndrome (CFS), a debilitating multisystem
condition characterized by chronic, disabling fatigue and other
symptoms, including pain, sleep disturbance, neurologic and cognitive
changes, motor impairment, and altered immune and autonomic responses.
Because the condition is characterized exclusively by symptoms,
physicians have wondered if the illness is 'real.' Articles published
in this issue of Annals of Internal Medicine suggest that ME/CFS is
prevalent and real. The following reviews were conducted as part of a
larger report to inform a research agenda for the National Institutes
of Health (NIH) 2014 Pathways to Prevention Workshop, which was
established to identify research gaps in selected scientific areas.

No diagnostic methods proven effective for diagnosing ME/CFS

The diagnosis of ME/CFS is based on nine sets of clinical criteria
that attempt to distinguish it from other conditions that also present
with fatigue. Currently, there is no consensus about which, if any, of
these clinical criteria should be considered the reference standard.
Researchers reviewed 44 published studies to evaluate and compare
methods for diagnosing ME/CFS. They found that none of the current
diagnostic methods have been adequately tested to determine how well
they differentiate patients with ME/CFS from patients with other
conditions. The researchers recommend more definitive studies in
broader populations to address the research gaps.

Counseling therapies and graded exercise may improve fatigue and
function in some patients

Patients with ME/CFS experience a broad range of symptoms. Currently
there is no FDA-approved treatment for the condition, but many
medications have been used off-label. Researchers reviewed 35
published studies to determine the benefits and harms of treatments
for adults with ME/CFS. The researchers found limited evidence
indicating that rinatolimod improved measures of exercise performance
compared with placebo in patients with severe debilitation from
ME/CFS. Low to moderate strength evidence showed that counseling,
behavior therapies, and graded exercise therapy improved measures of
fatigue, function, global improvement, and work impairment. The
researchers caution that these treatments have not been adequately
tested in broader patient populations that may meet more specific case
definitions of ME/CFS. More research is needed to evaluate these and
other treatments.

Notes: For an embargoed PDF, please contact Angela Collom at
acollom@acponline.org. To speak with one of the review authors from
Oregon Health & Science University, please contact Tracy Brawley at
brawley@ohsu.edu or 503-494-7009. To reach the author of the
editorial, Dr. Anthony Komaroff, please contact Brigham and Women's
media relations team at bwhmediarelations@partners.org or 617-525-6370.

###

Media Contact

Angela Collom
acollom@acponline.org
215-351-2653
http://www.acponline.org

--------
(c) 2015 American Association for the Advancement of Science (AAAS)

 

[WillowJ]

I was going to ask if the Eureka Alert people had some kind of problem with the IOM report (which is more realistic in its assessment about CBT/GET), but the Annals of Internal Medicine have remove the link from the top (and I can't even find a clicky link at the end, although it remains listed in the citations and all other citations have clicky links).