NIH asks for public input into ME/CFS literature search by July 17th

[Vicariousdancing]

The NIH is doing a literature search on ME/CFS in preparation for P2P. (See more about P2P here http://forums.phoenixrising.me/inde...-cfs-dec-9th-and-10th-2014.30990/#post-474590)

If we can't get P2P cancelled, it would be good if they had good information. So I figure Phoenix Rising is the place to find smart people with the good literature.

The NIH is going to find thousands of articles in the database search and we know a lot of them are pretty bad.
I'm wondering if we could "stack the deck" with the good stuff: credible studies that show the biological underpinnings of ME.

Also, anyone who has a Dr. appt. with or in contact with someone who might have unpublished research, it would be great if you could mention this.

Erica Verrillo advocates sending the "good stuff" even if it doesn't quite meet the stated requirements. which are circuitous.
http://www.cfstreatmentguide.com/blog/p2p-invites-input-from-the-public

Stated requirements:
http://effectivehealthcare.ahrq.gov...pageaction=displayproduct&productID=1906#8766

DATES: Submission Deadline on or before July 17, 2014.

ADDRESSES: Online submissions:

http://effectivehealthcare.AHRQ.gov/index.cfm/submit-scientific-information-packets/

Please select the study for which you are submitting information from the list to upload your documents.

Email submissions: src.org">SIPS@epc-src.org.

Print Submissions

Mailing Address:

Portland VA Research Foundation
Scientific Resource Center
ATTN: Scientific Information Packet Coordinator
PO Box 69539, Portland, OR 97239
Shipping Address (FedEx, UPS, etc.)

Portland VA Research Foundation
Scientific Resource Center
ATTN: Scientific Information Packet Coordinator
3710 SW U.S. Veterans Hospital Road
Mail Code: R&D 71
Portland, OR 97239.

FOR FURTHER INFORMATION CONTACT: Ryan McKenna, Telephone: 503-220-8262 ext. 58653 or Email: src.org">SIPS@epcsrc.org
http://effectivehealthcare.ahrq.gov/submit-scientific-information-packets/?pageaction=view&TID=256

 

[Sasha]

I'm having trouble reading this morning (not well) but I couldn't tell, on a quick scan, whether they would include stuff that's unpublished. There's some important stuff that's in the pipeline and/or has only been reported at conferences - I'm thinking the latest Fluge & Mella Rituximab research in particular and, @Jonathan Edwards, I don't know if your pre-trial study has unpublished results that could go forward.

My brain has pretty much fallen out of my head this morning but there was loads of exciting stuff reported at the IACFS/ME and IiME conferences this year (and I don't know whether all the stuff at last year's IiME has been published yet). I heard last year about a study that Nancy Klimas did showing that if you push PWME past their anaerobic threshold, their ANS tanks and takes the immune system with it but I've not seen that published yet.

Should we be contacting our researchers to get them to submit their unpublished stuff to this P2P review? It's only in the last very few years that we've had this explosion in research and I don't think we've seen a lot of it published yet.

All depends, though, on whether they want unpublished stuff and, like I said, I don't have the brains today to think straight.

@Tom Kindlon, @alex3619 ... trying to think who else would be interested in this.

 

[biophile]

One thing which should be made clear to the P2P is that despite the hype, CBT/GET (and perhaps other treatments) have not yielded clinically significant improvements to objective measures...

CBT/GET have no or only minimal effect on poor walking test distances:
http://www.ncbi.nlm.nih.gov/pubmed/21334061

CBT/GET have no effect on poor physical activity levels:
http://www.ncbi.nlm.nih.gov/pubmed/20047707

CBT/GET have no effect on poor employment outcomes, total service use, welfare dependency, insurance payouts, etc:
http://www.ncbi.nlm.nih.gov/pubmed/22870204

 

[alex3619]

@Sasha, under EBM nearly everything you referred to is inadmissible. Is it a high grade study? No, then according to the rules it will either be ignored or put so far down a list as it will never be seen to. This is the MAJOR problem with EBM in a field of research that is still in the exploratory phase. Stuff can get seen to based on technical requirements, but quality exploratory research will get ignored. Only by sidestepping the evidence based rules can science actually be addressed. This is a huge part of why so much EBM is Zombie Science, or otherwise very poor science, if its science at all. I still argue that much of psychiatric research also cannot be considered under EBM, as many of the diagnoses are not proven, unstable, and change every few years.

That doesn't mean we couldn't make submissions. It also doesn't mean that we couldn't make submissions particularly on the basis of upgrading for quality, or downgrading for lack of quality. P values, replication, size of study, effect sizes, all these matter. So does objective or subjective evidence.

The PACE trial has many counts against it, so that it CANNOT be considered highest grade evidence, for example, under any EBM review, as it would have to have its evidence grade downgraded by one or even two steps. Any failure to do this is a failure of the EBM process.

I have forgotten a lot of the technical stuff related to P2P now, my memory does not stretch back that far. Maybe someone else could comment further.

 

[Sasha]

@Sasha, under EBM nearly everything you referred to is inadmissible. Is it a high grade study? No, then according to the rules it will either be ignored or put so far down a list as it will never be seen to.

Depends whether the principles of EBM are to be intelligently applied or not. According to the P2P criteria (my cut and paste has messed up the numbering):

Key Questions​

1. 1. 1. What methods are available to clinicians to diagnose ME/CFS and how do the use of these methods vary by patient subgroups?
         1. What are widely accepted diagnostic methods and what conditions are required to be ruled out or excluded before assigning a diagnosis of ME/CFS?
         2. What is the accuracy and concordance of diagnostic methods?
            1. 1. What harms are associated with diagnosing ME/CFS?

2. What are the (a) benefits and (b) harms of therapeutic interventions for patients with ME/CFS and how do they vary by patient subgroups?​

1. 1. 1. 1. What are the characteristics of responders and non-responders to interventions?

[...]

Study Designs: For all KQs we will include randomized controlled trials (RCTs). For KQ 1a we will also include derivation, validation, and cohort studies. For KQ 1c and 2b [2b is missing from their list above] we will also include cohort studies with comparators. For all KQs we will exclude uncontrolled observational studies, case control studies, case series, and case reports.​

The 2-day CPET stuff should qualify, for example. I'd hope they'd also accept critique papers on PACE. I'd like to see them receiving a formal and very public submission of material criticising PACE.

 

[alex3619]

The key material is what is NOT in those questions. The EBM approach ranks papers. The bureaucratic assembly of such papers for P2P is going on behind the scenes, and almost certainly use rules that are not designed for the task.

I think its very important if we want to submit papers to address issues like replication, effect size, p values, and the questions ... how relevant are the papers? One of the good things is that there pretty well are no RCTs addressing the key question. The very phrasing of that demonstrates a failure to grasp the issues:

For all KQs we will include randomized controlled trials (RCTs).

For KQ 1a we will also include derivation, validation, and cohort studies.

The 2 day CPET really has to be included or we can demonstrate the P2P is a farce. These are controlled cohort studies, not blinded, so far as I can see.

RCTs really only make sense in terms of treatment trials. Ideally they need to be double blinded too. So they apply on the therapeutic side. I would downgrade most CBT/GET studies, and upgrade Lerner's findings due to effect size. How they go about that is critical, and it takes time and careful examination. I doubt they can do that for many papers.

The main evidence of harms comes from patients. The fundamental science supports us, but nobody has actually done a study to demonstrate that GET is bad for us. Indeed, what evidence we have in controlled trials is secondary and not the point of the trials. For the most part what was examined has not been the things that go wrong in patient's experience.

So far as I am aware, few diagnostic studies of high value have been replicated, though with some of the p values etc. they can be considered to be probably robust. Only the 2 day CPET has had good independent replication in a controlled study, though I think in the next year or two we are going to see quite a few immunological findings get independently replicated to a high standard. At least I hope so. It really helps when you finally know what to test for, instead of stumbling in the dark. It also helps when you have high homogeneity in the study cohorts using CCC for example.

Ideally one of the things coming out of the P2P would be recognition of the 2 day CPET, and probably recommendation for urgent replication and validation of many of the new immune findings. On drug therapies, they need to look at Ampligen again I think, but given the FDA finding I think it wont get much prominence.

 

[Seven7]

I hav eno idea what to do so we don't end up duplicating efforts. If anybody needs assistance let me know what I can do. Maybe look for reaserch or somebody looks and I load????? Please advice.

 

[Nielk]

@alex3619 said

The main evidence of harms comes from patients. The fundamental science supports us, but nobody has actually done a study to demonstrate that GET is bad for us. Indeed, what evidence we have in controlled trials is secondary and not the point of the trials. For the most part what was examined has not been the things that go wrong in patient's experience.

Doesn't it work equally for the benefits of GET? Didn't the trials rely on patients' measures? Why only rely on patients when they support benefits of GET but ignore them when they demonstrate negative outcomes?

 

[alex3619]

@alex3619 said

Doesn't it work equally for the benefits of GET? Didn't the trials rely on patients' measures? Why only rely on patients when they support benefits of GET but ignore them when they demonstrate negative outcomes?

They would argue that in the case of benefits its about controlled trials, in which standard subjective instruments were used.

Personally I think that subjective information is only useful as an adjunct to objective evidence. Its no substitute.

 

[jspotila]

I just want to throw out a couple of points. I agree with @alex3619 that the rules of EBM are not in our favor, and that the evidence grading happening right now is all behind the scenes (until the review is published in the fall).

The request for information is written to focus on unpublished clinical trial data. However, Dr. Beth Collins Sharp said at last week's CFSAC meeting that people could submit other materials as well.

This evidence review is looking at published literature, but it is also looking at "gray" literature - poster sessions, conference abstracts, etc.

If you are in contact with a researcher who has unpublished clinical trial data, PLEASE share this info request with them and encourage them to submit. The deadline is July 17, so they have to move fast.

In terms of assembling material for submission, I know @Tom Kindlon has submitted his harms paper, so that is fantastic. Lori Kroger (PANDORA) is also coordinating an effort to pull materials together.

A really big concern is the key questions, and the parameters of the protocol. For example, they are looking at clinical trials of 12 weeks or longer. They are only looking at studies with subjects 18 and over, which means some of the orthostatic intolerance work in adolescents will be ignored. And the Solve ME/CFS Initiative has gone on the record to say that the study protocol is flawed because the search strategy is skewed towards CBT/GET.

I strongly agree with Erica Verillo! They are inviting input, so let's do it. I don't care if they get the same study from five different people. I would love for them to get thousands of pages of material. If we can get even a SINGLE researcher to submit unpublished data, that's a big win.

I suggest that people not try to assemble a comprehensive citation list. What are the most essential papers/data that address the key questions OR address the gaping holes between the key questions. Focus on that stuff.

One final note - be prepared to provide public comment on the draft report in the fall. We'll have four weeks to do it, and I'm confident that we will have a lot to say.

 

[biophile]

Material about patient symptoms and experiences...

FDA Drug Development Meeting for (CFS) and (ME) transcripts + meeting summary
https://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind1306A&L=CO-CURE&P=R3731

ME/CFS survey presented at US Food and Drug Administration Drug Development Workshop
http://www.iacfsme.org/LinkClick.aspx?fileticket=YkMRCzqkxnQ=&tabid=36

There may also be some equivalent unpublished results from the CDC multi site study but I am rusty on that.

What about the Action for ME surveys?