The P2P Draft Systematic Review Is Up

[Esther12]

Intervention studies, for Key Question 2, must have a minimum duration of 12 weeks of treatment to be included given the cyclical nature of the condition. There was no duration or timing restriction on studies included for Key Question 1.

p13 ES-5

?

I don't really get that. I thought that the inadequate duration would have been referring to follow up rather than the length of treatment. What am I missing?

 

[Esther12]

Quality was based on whether it evaluated a representative spectrum of patients, whether it enrolled a random or consecutive sample of patients meeting prespecified criteria, whether it used a credible reference standard, whether the same reference standard was applied to all patients, whether the reference standard was interpreted independently from the test
ES-5
under evaluation, and whether thresholds were prespecified.23,29,30 Descriptive papers that compared diagnostic criteria and reported harms were not quality rated.

 

[Nielk]

How long was the duration of the first Rituximab study?

 

[NK17]

How long was the duration of the first Rituximab study?

Patients were given 2 Rituximab infusions, 2 weeks apart and then followed up to 12 months. This is the phase II study, randomised, double-blind and placebo controlled study published in Nov 2011.

 

[A.B.]

Exclusion Codes are clearly an expression of pure bureaucracy. We are fighting a war against a big machine.

The Rituximab results are one of the most important developments of the last few years. They should not be omitted for any reason. They do cast doubt on psychogenic explanations.

 

[NK17]

The Rituximab results are one of the most important developments of the last few years. They should not be omitted for any reason. They do cast doubt on psychogenic explanations.

Oh yes absolutely, still the machine is trying hard to downplay, obfuscate and hide this extremely important developments.
I see an urgency from some governing agencies to hasten and finish this review of evidence based medicine on old "evidence", so when in 3 years we'll have the new Fluge and Mella results and the UK study from UCL (Jo Cambridge) what are they going to do? Apologize? Review again? Even Nancy Klimas said that what they are doing here in the US is a bit premature.
Am I the only one seeing this? Please tell me that I'm not.

 

[Nielk]

I'm still reading the first page.
P1 - 2nd paragraph

“This most recent international consensus report advocates moving away from the term CFS in favor of ME to better reflect an underlying pathophysiology involving widespread inflammation and neuropathology, and to embrace the two terms as synonymous.”

7 T


The ICC embraces the terms CFS and ME as synonymous? I thought the ICC distinguishes between the two and says we need to remove ME from the broad CFS criteria.

 

[Dolphin]

I probably won't get around to looking at this systematic review in much detail before Oct 20, but I noticed a significant problem with the evidence about employment and CBT/GET, which they later concede is low strength evidence.



Mysteriously absent from the systematic review is the PACE Trial employment outcomes (McCrone et al 2012), the largest trial on the issue: http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040808

The employment and welfare etc outcomes were not significantly different between groups.

Why isn't that important information mentioned in the systematic review?

They mention the Work and Social Adjustment Scale (which is not the same as employment) results from the PACE Trial as "employment outcomes", but fail to include the actual employment outcomes?

I also can't find any mention of the actometer (null) results for CBT/GET trials, or walking test results for the PACE Trial.

Here's the questions on the WSAS so that people could quote it compared to the real employment measures reported in McCrone et al. (2012):

Please read each of the following questions and tick the appropriate box to indicate

No impairment Severe impairment
0 1 2 3 4 5 6 7 8

Because of my CFS/ME, my ability to work is
Impaired.

Because of my CFS/ME, my social leisure
activities (with other people, such as parties,
bars, clubs, outings. visits, dating, home
entertainment) are impaired.

Because of my CFS/ME, my home
management (cleaning, tidying, shopping,
cooking, looking after home or children,
paying bills) is impaired.

Because of my CFS/ME, my private leisure
activities (done alone, such as reading,
gardening. collecting, sewing, walking alone)
are impaired.

Because of my CFS/ME, my ability to form
and maintain close relationshipswith others,
including those I live with, is impaired.

 

[anciendaze]

But looking at the Lancet paper I count 53/641 formal withdrawals = 8.3% withdrawing?

(and an additional 32/641 or 5.0% lost to followup)

http://www.thelancet.com/journals/l...3611600962/images?imageId=gr1&sectionType=red

Errors in a review make me feel uneasy about other potential mistakes. Did I do something wrong?

This overlooks a fundamental problem in study design. With objective evidence of improvement reduced to a single objective test involving a 6-minute walk, the fact that about 1/3 of all groups declined to participate in two such tests, one before and one after, means objective evidence is virtually meaningless. (I'm working from memory here, somebody who has stayed with the subject should check on the actual percentages in different categories who declined the test.)

The problem has been addressed, if addressed at all, by talking about the differences in numbers or percentages who declined the test. What they completely ignored was the possibility something like GET increased stratification in the patient population, so the most severely affected were the ones most likely to decline the second test. N.B. you could be counted as a participant even if you provided no objective evidence of improvement at all.

I'll say this one more time: if you count the 30% or so who declined the only objective test as not having withdrawn from the study it becomes clear that the study authors were not interested in objective evidence.

So, what percentage of those listed as participants effectively withdrew from the objective measures of performance: 1.7%, 5%, 8.3% or 30%?

 

[medfeb]

The Rituximab results are one of the most important developments of the last few years. They should not be omitted for any reason. They do cast doubt on psychogenic explanations.

I agree with this comment and with Esther's comment. The length of the trial should refer to the length of followup not the length of the actual treatment. If I remember correctly, Rituxan's usual dosage is less than 12 weeks on some indications like B Cell Lymphoma so a conservative approach to the initial trial would have been appropriate.

Good comment to add for anyone sending in comments.

 

[A.B.]

@anciendaze I was under the impression the definition of recovered wasn't based on the six minute walking test to begin with. But I could be wrong, I find it hard to understand the PACE trial.

 

[alex3619]

The NIH P2P is a death sentence for CFS/ME patients.

It will probably turn out to be, but we are not there yet.

 

[alex3619]

Exclusion Codes are clearly an expression of pure bureaucracy. We are fighting a war against a big machine.

I see it more as a war of science against management, psychiatric and political ideology.

 

[medfeb]

The ICC embraces the terms CFS and ME as synonymous? I thought the ICC distinguishes between the two and says we need to remove ME from the broad CFS criteria.

That's how I read it also, Neilk. Looks like another error. That section seeks to leave the impression that the consensus is that ME is either a subtype of CFS or the two are the same.

 

[anciendaze]

@anciendaze I was under the impression the definition of recovered wasn't based on the six minute walking test to begin with. But I could be wrong, I find it hard to understand the PACE trial.

The original study protocol had two objective measures: monitoring total patient activity with actimeters; the six-minute walk test. These were listed as secondary measures, which pretty well defines the attitude of the authors. Dropping the actimeters, after they had been bought, out of concern for the trouble they were causing patients, was one gambit in dispensing with objective measures entirely. Allowing patients who declined before or after walk tests to be counted as participants without contributing any objective evidence of effectiveness was the second act. This has not changed the rhetoric of the study authors.

The whole thing was a classic bait-and-switch. Only the authors know if they ever intended to go through with objective measures of effectiveness.

 

[Kati]

I do not think that the P2P people are aware of the large pitfall of the PACE trial,
1) they don't know that the end measure value was change halfway into the study to include more patients as 'recovered'
2) they don't know that the PACE trial people refuse to release their raw data for the publis to scrutinize
3) they don't know about the covert conflicts of interest that surrounds the PACE trial
4) they are assuming that PACE included only patients with CFS however due to the broad and useless Oxford definition PACE included depressed patients and patients with idiopathic 'I've got 4 kids' patients.

We are once more getting screwed.

 

[catly]

Information about who was involved in this seems to be largely just marked as:



It would be helpful to know who was involved in the draft.

Probably because they really don't want anyone to know who was involved in the review and conclusions.

 

[Nielk]

I do not think that the P2P people are aware of the large pitfall of the PACE trial,
1) they don't know that the end measure value was change halfway into the study to include more patients as 'recovered'
2) they don't know that the PACE trial people refuse to release their raw data for the publis to scrutinize
3) they don't know about the covert conflicts of interest that surrounds the PACE trial
4) they are assuming that PACE included only patients with CFS however due to the broad and useless Oxford definition PACE included depressed patients and patients with idiopathic 'I've got 4 kids' patients.

We are once more getting screwed.

That is exactly the problem with this type of evidence based paper review they are doing. They are using every criteria out there with such a broad definition, that it is the result is skewed from the get go. In addition, the review was done by people who have no experience with ME/CFS.

 

[NK17]

I do not think that the P2P people are aware of the large pitfall of the PACE trial,
1) they don't know that the end measure value was change halfway into the study to include more patients as 'recovered'
2) they don't know that the PACE trial people refuse to release their raw data for the publis to scrutinize
3) they don't know about the covert conflicts of interest that surrounds the PACE trial
4) they are assuming that PACE included only patients with CFS however due to the broad and useless Oxford definition PACE included depressed patients and patients with idiopathic 'I've got 4 kids' patients.

We are once more getting screwed.

Then we PWME should let them know. It's the same old same situation. How do we get this message out there loud and clear?
I think we need to draft a letter and get it signed by our ME doctors.
This time we need @Jonathan Edwards signature too.
We need to put this black on white. The P2P is jaded if it uses as foundation heavily biased studies, above them all the PACE!
This whole situation is so absurd, the name path 2 prevention is absurd to start with, is as if you're trying to prevent malnutrition using as evidence flawed studies done by some crazy psychiatric lobby who believes in force feeding the malnourished!! You know what happens when you give a normal meal to a malnourished and malfunctioning body?

 

[NK17]

That is exactly the problem with this type of evidence based paper review they are doing. They are using every criteria out there with such a broad definition, that it is the result is skewed from the get go. In addition, the review was done by people who have no experience with ME/CFS.

People with absolutely no knowledge about ME/CFS doing an evidence based review based on flawed criteria (Oxford and Fukuda) are either delusional or clearly working for the system. And the system, the status quo or whatever you'd like to call it, is not coming to our rescue, is not working on behalf of PWME, is not moving science forward and out of the tainted and mired waters it has condemned millions of very sick people to live.