The P2P Draft Systematic Review Is Up

[Nielk]

http://www.occupycfs.com/2014/09/22/draft-systematic-review-is-up/

Jennie just posted this"

The draft systematic evidence review on the Diagnosis and Treatment of ME/CFS has been published.

This review is extraordinarily important because it is being presented to the P2P Panel in a closed door session any day now. This review will be the only evidence presented to the P2P Panel in advance of the Workshop on December 9-10, 2014. Expert presentations at the Workshop may support, refute or expand upon the review, but it is likely that the Panel will ascribe very heavy weight to this report.

I have not read the report yet, and will hold off on commenting until I do. A group of advocates is working together to review the material and prepare highlighted issues that others can use in their comments.

Public comment on the review will be accepted through October 20th. Regardless of whether you plan to submit comment, please read at least the executive summary of this report if you are able to do so. It will be one of the most important documents on ME/CFS published by the government this year.

I hope many of you will take the time to read this carefully. We have till October 20th to comment on this.

 

[alex3619]

CBT good, GET good, PACE trial strong evidence. What else did anyone expect?

 

[biophile]

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.

Searches were conducted of electronic databases including MEDLINE (1988 to November 2013), PsycINFO (1988 to January 2014), the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through November 2013), and the Database of Abstracts of Reviews of Effects and the National Health Sciences Economic Evaluation Database (through the 4th quarter 2013). The searches were supplemented by reviewing reference lists and requesting scientific information from drug and device manufacturers.

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 CBT, GET, SMC 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.

 

[biophile]

The PACE trial described previously was a large 12-month good-quality trial (n=641) comparing four interventions: CBT; GET; an adaptive pacing therapy; and a usual care control group.[98] Attrition was low with only 1.7 percent withdrawing overall and adherence was not reported.

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?

 

[Sean]

This one is scaring me. It will have the superficial appearance of independence and objectivity.

 

[Hope123]

My suggestion is if you read something you disagree with or that deserves a qualifier, write in your comments.

In addition, if there is something you DO like, comment on that as well.

Also, if posters don't mind, I would say feel free to send in comments posted by other PR members that you agree with. That way, they can see which areas ME/CFS patients care about the most and also this gives the impression we are paying attention to things.

Also, note that the public comment period on the draft report by the NIH P2P Committee members, which incorporates not only this draft technical report but also presentations to the Committee in December (you can register to watch it live online here: https://prevention.nih.gov/programs...ention/upcoming-workshops/me-cfs/registration) has been extended to 30 days (near Jan 12, 2015) from 14 days.

That extension is partly because of Rep. Zoe Lofgren's letter to NIH's Dr. Frances Collins. Several advocates asked for an extension of the public comment period so Rep. Lofgren's office responded to that. If you live in the San Jose, CA area or even if you don't, drop them a line thanking them for their work on advocating for ME/CFS and for this extension. It is rare for members of Congress to receive thank-yous so we can make our issue stand out by being different and polite.

Her e-mail form only takes responses from people who live in her district but the bottom of her homepage allows snail mail or calls to be made to her office from anywhere:
http://lofgren.house.gov/contact/

http://lofgren.house.gov/

 

[Hate ME/CFS]

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

 

[A.B.]

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.

The review claims CBT results in better employment outcomes, on page 5. Evidence to the contrary is ignored as you said.

Another weakness of the review is lumping different definitions together. We already know that the Oxford definition applies to a different group of patients than the ICCC. I see no justification for assuming that conclusions based on one definition apply to another. Speaking of ME/CFS as single illness is hopeless.

My sympathies to patients who will be affected by this review.

 

[Sean]

From pages 27-31

"There is low strength evidence, based on 14 trials, that CBT, either group or individual; self- instruction booklets; pragmatic rehabilitation; peer-to-peer counseling; and symptom consultation provide improvement in fatigue, function, quality of life, and employment in adult patients with ME/CFS.

When combining all studies comparing any type of counseling to no treatment, support, relaxation, or adaptive pacing there is low strength of evidence that counseling improves fatigue (8/12 trials showed positive effect), functioning measures (5/12 trials showed positive effect; 2/12 showed mixed results on measures), quality of life (2/5 trials showed positive effect; 1/5 showed mixed results on measures), and global improvement (3/3 trials showed positive effect).

Harms of counseling and behavioral therapies were poorly reported but there is low strength of evidence that CBT is not associated with harms based on one moderate-sized trial."

Five trials (n=1,065) of counseling compared with no treatment, support, relaxation, or adaptive pacing reported employment outcomes including proportion working full- or part-time, hours worked per week or per 24-hour period, and level of work impairment measured by the Work and Social Adjustment Scale.

Results were primarily positive.

Both trials measuring work impairment with the Work and Social Adjustment Scale reported significantly better scores for the CBT group compared with controls (mean scores of 3.3 vs. 5.4 at 6 months; p<0.001 on scale scored with range 0-8; mean scores of 21.0 vs. 24.5 at 1 year; p=0.0001 on scale scored with range 0-45).

Three trials reported the number of hours, either per week or per 24-hours, individuals were working, with one trial reporting significantly more hours worked per week for the CBT group compared with relaxation (mean hours of 35.57 vs. 24.00 at 5 years; p<0.04), however, one trial reported significantly more hours worked on 24-hour timetable in CBT group compared with support group but not the no treatment group (treatment effects for CBT vs. support: -9.6; 95% CI, -17.1 to -2.0; p=0.0132 and CBT vs. no treatment: -5.9; 95% CI, -13.2 to 1.4; p=0.1134), and one trial reported no differences between groups.

Two trials reported no differences in the proportion of individuals working full- or part-time at 1 year or 5 years.

Mysteriously absent from the systematic review is the PACE Trial employment outcomes (McCrone et al 2012),…

says biophile, and I can't spot it in the references listed in this section either. (Ref Numbers: 76, 78, 79, 84, 89, 98)

Also worth noting that 5 of the 6 refs are from the same basic crowd and ideology.

No bias here, folks. Move along...

In summary most trials of CBT or other counseling techniques suggested improvement in overall functioning and fatigue symptoms in ME/CFS patients though in a trial that followed individuals up 5 years after counseling, this affect was no longer seen.

In addition, studies used various measures to detect decreases in fatigue or improvements in overall functioning and results were often similar based on the measure being used, but difficult to compare across measures.

Also, few studies reported the clinical significance, if available, of the improvement in scores.

Harms were rarely reported.

 

[A.B.]

GET appears to be associated with harms in some patients whereas the negative effects of being given a diagnosis of ME/CFS appear to be more universal.

This sounds disturbingly Wesselyian (in the Conclusion).

It is not the diagnosis that causes harm - it's framing the illness as psychogenic that causes harm.

 

[beaker]

I shudder to think about the money spent on this, that could of been spent on research.
Shameful.

 

[medfeb]

Please send in comments as Hope123 suggested.

But even if you do not, please keep providing your comments here. Comments like those above that point out the deficiencies and oversights are incredibly useful for those who will be sending in comments.

Thank you to all who do!

 

[medfeb]

Biophile
This study -

McCrone P, Sharpe M, Chalder T, et al. Adaptive pacing, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome: a cost-effectiveness analysis. PLoS ONE. 2012;7(8):e40808. PMID: 22870204.​

was excluded from consideration in the review because they said it looked at the wrong outcomes.

The outcomes that they said they considered were

We considered outcomes of overall improvement, fatigue, function, quality of life, and employment which we considered clinically significant and conducive to the systematic review methodology. Given the breadth of symptoms in ME/CFS, we a priori elected to not review symptom related outcomes except for fatigue. (P.124)​

Hard to guess why they excluded that paper unless they excluded it based on the abstract alone.

Great catch

 

[Sidereal]

Biophile
This study -

McCrone P, Sharpe M, Chalder T, et al. Adaptive pacing, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome: a cost-effectiveness analysis. PLoS ONE. 2012;7(8):e40808. PMID: 22870204.​

was excluded from consideration in the review because they said it looked at the wrong outcomes.

The outcomes that they said they considered were

We considered outcomes of overall improvement, fatigue, function, quality of life, and employment which we considered clinically significant and conducive to the systematic review methodology. Given the breadth of symptoms in ME/CFS, we a priori elected to not review symptom related outcomes except for fatigue. (P.124)​

Hard to guess why they excluded that paper unless they excluded it based on the abstract alone.

Great catch

This little gem is buried in the Discussion:

However, with the exception of a difference between CBT and APT, there were no significant differences in either lost work time or benefits between the treatments during follow up. In fact, benefits increased across all four treatments.

 

[user9876]

Good-quality studies are considered likely to be valid. Good-quality studies clearly describe
the population, setting, interventions, and comparison groups; use a valid method for allocation
of patients to interventions; clearly report dropouts and have low dropout rates; use appropriate
methods for preventing bias; assess outcomes blinded to intervention status; and appropriately
measure outcomes and fully report results.

PACE gets reported as a good quality study but I thought (I've not checked) that at least some of the assessments were not blinded and its very hard to do. Also they have not fully reported results - in fact they have barely reported any of the values defined in the trial protocol.

Edits: Thinking a bit more about it since primary outcomes are based on patient reported questionnaires and patients are not blinded then the primary outcomes are not blinded. I think that will be true for all CBT interventions.

 

[user9876]

They also excluded the Rituximab study due to its duration

 

[Esther12]

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

To Be Added For Final Version

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

 

[NK17]

They also excluded the Rituximab study due to its duration

Are you talking about the new multi center Phase III study that just started in Norway?

 

[user9876]

Are you talking about the new multi center Phase III study that just started in Norway?

No the excluded the original study (See the appendix of excluded studies)

Fluge O, Bruland O, Risa K, et al. Benefit
from B-lymphocyte depletion using the anti
-
CD20 antibody rituximab in chronic fatigue
syndrome. A double-blind and placebo-
controlled study. PLoS ONE.
2011;6(10):e26358. PMID: 22039471.
Exclusion code: 12

With Exclusion code 12

12 Inadequate duration

 

[NK17]

No the excluded the original study (See the appendix of excluded studies)


With Exclusion code 12

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