The P2P Draft report is out

[biophile]

Evans M, Jason LA.
Effects of Time Frame on the Recall Reliability of CFS Symptoms.
Eval Health Prof. 2013 Sep 23. [Epub ahead of print]

This study serves as an investigation of the reliability of symptom data as reported by individuals with chronic fatigue syndrome (CFS), across three recall time frames (the past week, the past month, and the past 6 months), and at two assessment points (with 1 week in between each assessment). Multilevel model analyses were used to determine the optimal recall time frame, in terms of test -retest reliability, for each of the Fukuda et al. (1994) case defining symptoms. Results suggested that the optimal time frame for reliably reporting CFS symptoms was six months for sore throat, lymph node pain, muscle pain, post-exertional malaise, headaches, memory/concentration difficulties, and unrefreshing sleep. For joint pain, the optimal time frame was one month. Researchers who are interested in the assessment of CFS symptoms need to take recall time frame into account, especially when the intended goal is to standardize and improve the methods used to reliably and accurately diagnose this complex illness.

http://www.ncbi.nlm.nih.gov/pubmed/24064428

 

[WillowJ]

In fact if they assessed AFTER entry, it's a post-hoc analysis, which we know PACE already is in other areas, and that makes the situation even less scientifically good than a planned study. It makes you think they only picked people based on Oxford and then realized later, "Oh @!*^%, most people in the US and internationally use Fukuda, not Oxford!."

That's a good point, that this would be certainly bad study design and possibly bad planning. White et al. did not dispute that they had done this, when David Tuller complained about it in the New York Times. They merely said it was A-OK because all definitions had been used, without specifying the order or whether they were used independently.
http://www.nytimes.com/2011/03/15/health/15letters-STUDYINGAFAT_LETTERS.html?_r=0

The other problem with using Oxford prior to other definitions, is that it might exclude patients who might otherwise have been included, if using the inclusions independently. For example, White et al. interpreted Oxford as "fatigue is the main symptom", and many people might not say this is their "main symptom".

 

[biophile]

Here is why I don't think there is any good reason to assume that PACE diagnosed the CDC criteria using the 6 month symptom requirement at any point in the trial:

The short published version of the protocol only tells us so much.
The same information is in the longer unpublished version with additional information.

Both cite Reeves et al. (2003) recommendations for the CDC criteria.
http://www.biomedcentral.com/1472-6963/3/25

Both also mention using "An operationalised Likert scale of the nine CDC symptoms of CFS." as a secondary measure.

Looking at the baseline assessments ...

The short version states "The CDC criteria for CFS" citing Reeves et al. (2003).
The long version states "The CDC criteria for CFS (9 symptoms of CFS)", again citing Reeves et al. (2003).

Looking at the Screening/Baseline Procedures on pages 36-39 of the long version ...

Visit 1 mentions nothing about CDC criteria, the CFS diagnosis refers to the Oxford criteria. However, participants were given a bunch of baseline assessment questionnaires to fill out and return on Visit 2, including "The CDC criteria for CFS (9 symptoms of CFS)", so it is worth investigating what they mean by that.

Section 10 on pages 51-56 covers the measures/questionnaires used. Page 53 of the full protocol has a table of research assessments by time point: "CDC criteria for CFS" was assessed at baseline and 52 weeks. Also on page 53 is the end of the list of secondary measures, including "An operationalised Likert scale of the nine CDC symptoms of CFS." The closest to that is a CDC questionnare on page 156 is a Likert scale of eight symptoms of CFS.

However, "In table 6, the maximal CDC associated symptom count is eight, the 'ninth' symptom being fatigue. A symptom was counted as present if scored as 'more often than not', or more frequently than that."

http://www.meassociation.org.uk/wp-content/uploads/2011/06/FOI+from+Queen+Mary.pdf

I can't find mention of assessing fatigue on a similar Likert scale of frequency, but the Oxford criteria requires fatigue to be present more often than not, so they probably just used that.

Another reason to not give them the benefit of the doubt is that they even admitted to not using the 6 month symptom requirement for the CDC criteria at 52 weeks follow up. While it is possible that they diagnosed CDC criteria using a 6 month symptom requirement at baseline and then also asked for symptoms over the last week, there is no indication that this is the case, especially when all the other assessment questionnaires used are also in the same table and appendix section. It is highly likely that PACE used the CDC symptom questionnaire on page 156 to assess caseness at baseline as well.

Considering the above and the multiple other blunders they have made in relation to assessing the recovery of their participants, I think it is fairly safe to conclude that the CDC criteria issue is just another blunder. The PACE Trial is an Oxford criteria study, they simply did not use the CDC criteria or London ME criteria as these are supposed to be used. Even if they did, the results still could have been unreliable because they all had to be screen through the Oxford criteria first, which is generally broader but may still exclude some patients which would otherwise meet CDC criteria or London ME criteria. As David Tuller pointed out, PACE should have recruited 3 independent groups.

 

[Sing]

I sent in my comments to cfsac, nih (P2P panel) and jspotila who will archive our critiques.

 

[biophile]

If PACE really did use the wrong symptom timescale for the Lancet paper as well, it means they failed to mention an obvious flaw in the interpretation of the results, which they then also triumphantly generalized to as many patients as possible including those who meet alternative CDC criteria and London ME criteria, or in their words "however they are defined".

Once again patients had to spend hours sifting through papers to find out what happened rather than getting a straight forward answer up front, or end up with evidence pointing towards something questionable but without a definite answer. Someone could always email the authors, but judging from other threads I have read, any questions get treated as formal freedom of information requests which are often refused, then White goes around complaining about being harassed.

 

[Ember]

They then also triumphantly generalized to as many patients as possible including those who meet alternative CDC criteria and London ME criteria, or in their words "however they are defined".

The Evidence Report states repeatedly that GET treatment findings may not be generalizable to ME patients:

GET improved measures of fatigue, function, and clinical global impression of change compared with controls. Treatment effectiveness may not be generalizable to all patients because no study used a case definition that selected for more disabled patients (i.e., case definition for ME).

GET improved measures of fatigue (low strength of evidence),function (moderate strength of evidence), and clinical global impression of change (moderate strength of evidence); treatment effectiveness may not be generalizable to all patients and may overestimate the benefit as no study used a case definition selecting for more disabled patients.

GET was superior to control groups in measures of fatigue, clinical impression of change, and function. These findings however cannot be generalized to all patients with ME/CFS as no study enrolled patients whereby PEM was a diagnostic requirement (ME case definitions) and only one study performed a subgroup analysis to determine if similar results were found in patients meeting the diagnosis of ME.

In summary, compared with control groups, there is moderate strength of evidence that GET improved function (weighted mean difference on SF-36 physical function (10.29; 95% CI, 6.71 57 to 13.86), and global change scores (RR 1.54; 95% CI, 1.26 to 1.89), and low strength of evidence that GET improved fatigue in ME/CFS patients fulfilling the Oxford (Sharpe, 1991) and/or CDC (Fukuda, 1994) criteria. However, subgroup analysis was inadequate to determine whether these benefits extend to patients with more disability meeting the criteria for ME.

 

[Bob]

@Ember, thanks for that. I don't remember seeing any sort of clarification/qualification in the draft executive report that there's no evidence that GET benefits patients with more disability. Perhaps that's another issue to be raised with them in a submission. Also, I think their comment about ME criteria perhaps strengthens our case (i.e. what we've been discussing) re the Oxford criteria. (Although, as part of my submissions, I'm arguing that their evidence base for GET, in general, isn't satisfactory.)

 

[Ember]

The Draft Report is a lumper's manifesto. It calls for protest!

In November 2011, Dr. Unger wrote, "Opinions of advocates, clinicians and researchers remain divided about whether CFS and ME are the same or different entities. However, we are following the discussions with interest and would consider any consensus that is reached by patient groups and the scientific community going forward."

Will they ever hear us?

 

[Ember]

If You Mean M.E., Just Say M.E.!
Posted by Mary A. Kindel on January 05, 2015

 

[Wally]

The Draft Report is a lumper's manifesto. It calls for protest!

In November 2011, Dr. Unger wrote, "Opinions of advocates, clinicians and researchers remain divided about whether CFS and ME are the same or different entities. However, we are following the discussions with interest and would consider any consensus that is reached by patient groups and the scientific community going forward."

Will they ever hear us?

@Ember,
They can hear, but they are choosing whom and to what they want to listen to. One of the things that we need to do as a community is to make sure that the majority of the ME community is heard, so it becomes quite clear when the HHS/NIH/CDC is cherry picking whose voice to listen to.

MEAdvocacy.org is working on some ways to overcome this problem, so hopefully in 2015 we will have a clearer, stronger voice in D.C.

 

[Research 1st]

Once again patients had to spend hours sifting through papers to find out what happened rather than getting a straight forward answer up front, or end up with evidence pointing towards something questionable but without a definite answer. Someone could always email the authors, but judging from other threads I have read, any questions get treated as formal freedom of information requests which are often refused, then White goes around complaining about being harassed.

Yes. It's largely pointless for UK patients to complain about what looks like state directed disinformation that is in place and protected, for a reason. (UK citizens requiring FOIA requests for a public funded 'scientific' study that won't release the study data in full is outrageous, but shows the nature of the need to desperately protect evidence from prying eyes of apparent scientific fraud).

In 2015 there are still people, females especially stolen from their family (abducted) and placed in psychiatric wards for the crime of having an acquired neurological condition, ME CFS. This is only possible because of the hyped up claims of the effectiveness of GE CBT. Stealing young female adult patients from their homes reminds me that 'single' women were locked in American psychiatric wards for alleged promiscuity in the 1970's. In Ireland, single mothers (women out of wedlock) were also placed in work houses. Many abuses (physical/sexual/mental) took place against these women who did nothing wrong.

Asking people for access to their public bodied funded data who think ME CFS patients 'do ME' for 'secondary gains' (financial, family or doctor sympathy) for full transparency is a non starter. At all times, they perceive themselves as victims, not the patients they cause other people to subsequently abuse in the name of 'medicine'.

P2P, IOM, PACE, UK Nice Guidelines scored an own goal, by publishing non science, as science and claiming there never was any 'proof' for them to follow up on. If only that was true, they would gotten away with it legally, but masses of research on 'CFS' has taken place since the 1990's, and the pieces of the puzzle are in place, you just need the pathogen to associate past research to and re-test the patient population to get the figures.

I think you all deserve a medal for staying calm and rational by going over the P2P/IOM/PACE so expertly when it's easy to be driven insane by such blatant disease denial that de-legitmises your very real suffering of a biological disease.

 

[Sing]

@Research 1st Yes, some of us are on the far side of insanity, past it, breathing the free air, and unwilling to be governed by such forces. You have come to the right place. I appreciate your passionate voice and many contributions!

 

[mango]

I’ve tried my very best to write comments now (with plenty of help and copying from these threads, infinite thanks!).

I’m afraid that maybe I haven’t been able to express myself well enough, perhaps left things open to misinterpretations, made glaring mistakes, forgotten something super important etc.

Would anyone be willing to read through them and check them for me? I’m not looking for perfection, just a “sanity check” Fair warning though: it’s very wordy… ME ate my ability to write succinctly, sorry.

 

[Esther12]

I will. pm me if you want. I might be rubbish too though!

Would anyone be willing to read through them and check them for me? I’m not looking for perfection, just a “sanity check” Fair warning though: it’s very wordy… ME ate my ability to write succinctly, sorry.

 

[Bob]

If anyone is submitting anything about the six minute walking test results from the PACE trial, please note that there were no improvements in the CBT group when compared to the "usual care" (aka "specialist medical care")* control group.

It's important to distinguish this comparative outcome from the absolute improvement, because that's what the P2P panel should be focusing on, and it's what the evidence report rightly focuses on for the other PACE outcomes.

So it's correct to say that CBT demonstrated no improvements in the six minute walking test when compared to the usual care control group.

The GET group did record a small improvement compared to the usual care control group, but I think it's safe to say that this was not a "clinically useful" improvement when compared to usual care. Or you could say it was a 'small' effect size (when compared to usual care), which can mean roughly the same thing.

And, whereas GET demonstrated an improvement from to 312 to 379m in the six minute walking text, this is misleading without the full context, because it doesn't take into account the improvements seen in the control group. If we make an adjustment for the "usual care" control group, then the improvement in the GET group is from 344 to 379m. (So that's an improvement of 35m when compared to the usual care control group.)

I'm not suggesting that any of this information should be included, or that it should be phrased in the way I've phrased it, but if you are including it, then please keep these issues in mind. And please ask questions if you need clarification.


* The PACE trial uses the term "specialist medical care" (SMC) for the main control group, and the P2P evidence report has interpreted this to mean "usual care". The P2P evidence report only refers to "usual care", so our submissions can/should also refer to the "usual care" control group instead of, or as well as, the SMC control group.

 

[Ember]

The Evidence Report also states that CBT treatment findings may not be generalizable to ME patients:

In summary , there is moderate strength of evidence that counseling techniques was associated with global improvement (41 to 70% vs. 25 to 31%), and low strength of evidence that counseling techniques improved overall functioning (SF-36 physical function weighted mean difference 7.73; 95% CI, 3.58 to 11.87), fatigue (27 to 76% vs. 7 to 65%), and employment outcomes in ME/CFS patients. The effects may not be generalizable to a more disabled population as no study used a case definition for ME and only one study analyzed patients fulfilling the London ME (Dowsett, 1994) case definition and may have been underpowered to detect a difference.121

But the Draft Report makes no reference to ME.

 

[Denise]

Even though NIH has said that public comment is welcome regarding the draft report by the P2P, NIH has also said that it will not retain submitted comments.

If you submit comments to the P2P panel, please send them to JSpotila for archiving.

Additional info:
http://www.occupycfs.com/p2p-library/

 

[Sean]

Estimate of NIH Funding for various conditions in 2014

http://i.imgur.com/92ttER5.png

Also has the source reference.

http://report.nih.gov/categorical_spending.aspx

 

[Anne]

People, can you help me with a list I need for a comment: examples of promising research leads which have not yet been followed up with large-scale studies due to the lack of funding?

I'm thinking:
- the findings of metabolic abnormalities in the 2-day maximum CPET tests (Stevens Protocol)
- NK cell dysfunction
- protein profiles in CSF differentiating ME/CFS from controls as well as Lyme patients (the Schutzer study)
- signs of inflammation such as cytokines (others?)
- abnormalities in the gut microbiome
- a possible autoimmune factor
- autonomic system dysfunction, orthostatic intolerance

All of the above measured in a 2-day exercise test, capturing the physiological implications of PEM/PEC (for those patients able to undergo such a test)

Help me specify others! Other immune system abnormalities? Specific brain abnormalities? What else?

 

[Bob]

People, can you help me with a list I need for a comment: examples of promising research leads which have not yet been followed up with large-scale studies due to the lack of funding?

I'm thinking:
- the findings of metabolic abnormalities in the 2-day maximum CPET tests (Stevens Protocol)
- NK cell dysfunction
- protein profiles in CSF differentiating ME/CFS from controls as well as Lyme patients (the Schutzer study)
- signs of inflammation such as cytokines (others?)
- abnormalities in the gut microbiome
- a possible autoimmune factor
- autonomic system dysfunction, orthostatic intolerance

All of the above measured in a 2-day exercise test, capturing the physiological implications of PEM/PEC (for those patients able to undergo such a test)

Help me specify others! Other immune system abnormalities? Specific brain abnormalities? What else?

Hi Anne,
I think you'll find some of this listed here, esp the CPET & NK cell research:
https://docs.google.com/document/d/1ZzUELQ0ki_hO00iGKfi4hpq9nR-hxPphBjmJPXhgY_E/edit?pli=1
(The list is a year old, so it won't include recently published research.)

If you still need some specific papers, then please ask again.