Posts Tagged 'cfs'

P2P: The Question They Will Not Ask — reposted with permission from OccupyCFS

Mary Dimmock and Jennie Spotila have written a very important post about a big problem with P2P. With their permission it is being reposted here in its entirety. (Thank you Mary and Jennie.)

 

P2P: The Question They Will Not Ask

July 21st, 2014 Jennie Spotila Leave a comment Go to comments

by Mary Dimmock and Jennie Spotila

cornerstone-contentThe most important question about ME/CFS – the question that is the cornerstone for every aspect of ME/CFS science – is the question that the P2P Workshop will not ask:

How do ME and CFS differ? Do these illnesses lie along the same continuum of severity or are they entirely separate with common symptoms? What makes them different, what makes them the same? What is lacking in each case definition – do the non-overlapping elements of each case definition identify a subset of the illness or do they encompass the entirety of the population?

Boiled down to its essence, this set of questions is asking whether all the “ME/CFS” definitions represent the same disease or set of related diseases. The failure to ask this question puts the entire effort at risk.

This fundamental question was posed in the 2012 application for the Office of Disease Prevention to hold the P2P meeting (which I obtained through FOIA). It was posed in the 2013 contract between AHRQ and the Oregon Health & Science University for the systematic evidence review (which I obtained through FOIA). It was posed to the P2P Working Group at its January 2014 meeting to refine the questions for the evidence review and Workshop (according to Dr. Susan Maier at the January 2014 Institute of Medicine meeting).

And then the question disappeared.

The systematic evidence review protocol does not include it. Dr. Beth Collins-Sharp said at the June 2014 CFSAC meeting that the Evidence Practice Center is not considering the question because there is “not enough evidence” in the literature to answer the question. However, she said that the P2P Workshop could still consider the question.

But the draft agenda for the Workshop does not include it. Furthermore, every aspect of the P2P Workshop treats “ME/CFS” as a single disease:

  • The P2P description of ME/CFS refers to it as a single disorder or illness throughout the meeting webpage.

  • The P2P website characterizes the names myalgic encephalomyelitis and chronic fatigue syndrome as synonymous.

  • Every section of the Workshop agenda lumps all the populations described by the multiple case definitions together, discussing prevalence, tools, subsets, outcomes, presentation, and diagnosis of this single entity.

A 20 minute presentation on “Case Definition Perspective” is the only lip service paid to this critical issue. This is completely inadequate, if for no other reason than because the presentation is isolated from discussions on the Workshop Key Questions and dependent topics like prevalence and natural history. As a result, it is unlikely to be thoroughly discussed unless one of the Panelists has a particular interest in it.

Why is this problematic? Because both the P2P Workshop and the evidence review are based on the assumption that the full set of “ME/CFS” case definitions describe the same disease. This assumption has been made without proof that it is correct and in the face of data that indicate otherwise, and therein lies the danger of failing to ask the question.

What if the case definitions do not actually describe a single disease? If there are disparate conditions like depression, deconditioning, non-specific chronic fatigue and a neuroimmune disease characterized by PEM encompassed by the full set of “ME/CFS” definitions, then lumping those together as one entity would be unscientific.

The most important part of designing scientific studies is to properly define the study subjects. One would not combine liver cancer and breast cancer patients into a single cohort to investigate cancer pathogenesis. The combination of those two groups would confound the results; such a study would be meaningful only if the two groups were separately defined and then compared to one another to identify similarities or differences. The same is true of the P2P evidence review of diagnostics and treatments: assuming that all “ME/CFS” definitions capture the same disease (or even a set of biologically related diseases) and attempting to compare studies on the combined patients will yield meaningless and confounded results if those definitions actually encompass disparate diseases.

There is a growing body of evidence that underscores the need to ask the fundamental question of whether “ME/CFS” definitions represent the same disease:

  • The P2P Workshop is focused on “extreme fatigue” as the defining characteristic of “ME/CFS,” but fatigue is a common but ill-defined symptom across many diseases. Further, not all “ME/CFS” definitions require fatigue or define it in the same way. For instance, Oxford requires subjective fatigue, and specifically excludes patients with a physiological explanation for their fatigue. But the ME-ICC does not require fatigue; instead it requires PENE, which is defined to have a physiological basis.

  • When FDA asked CFS and ME patients to describe their disease, we did not say “fatigue.” Patients told FDA that post-exertional malaise was the most significant symptom: “complete exhaustion, inability to get out of bed to eat, intense physical pain (including muscle soreness), incoherency, blacking out and memory loss, and flu-like symptoms.”

  • Multiple studies by Jason, Brenu, Johnston and others have demonstrated significant differences in disease severity, functional impairment, levels of immunological markers and patient-reported symptoms among the different case definitions.

  • Multiple studies have demonstrated that patients with PEM have impairment in energy metabolism and lowered anaerobic threshold, and have shown that patients with depression, deconditioning and a number of other chronic illnesses do not have this kind of impairment.

  • Multiple studies have demonstrated differences in exercise-induced gene expression between Fukuda/CCC patients and both healthy and disease control groups.

  • The wide variance in prevalence estimates shines a light on the case definition problem. Prevalence estimates for Oxford and Empirical populations are roughly six times higher than the most commonly accepted estimate for Fukuda. Even Fukuda prevalence estimates vary widely, from 0.07% to 2.6%, underscoring the non-specificity of the criteria. Nacul, et al., found that the prevalence using CCC was only 58% of the Fukuda prevalence. Vincent, et al., reported that 36% of Fukuda patients had PEM, representing a smaller population that would be eligible for diagnosis under CCC.

  • The work of Dr. Jason highlights the danger of definitions that include patients with primary psychiatric illnesses, especially because such patients may respond very differently to treatments like CBT and GET.

By contrast, there have not been any published studies that demonstrate that the set of “ME/CFS” definitions being examined in P2P encompass a single entity or biologically related set of entities. From Oxford to Fukuda to ME-ICC, there are significant differences in the inclusion and exclusion criteria, including differences in the exclusion of primary psychiatric illness. The magnitude of these differences makes the lack of such proof problematic.

Given that treating all “ME/CFS” definitions as a single entity is based on an unproven assumption of the clinical equivalence of these definitions, and given that there is ample proof that these definitions do not represent the same disease or patient population, it is essential that the P2P “ME/CFS” study start by asking this question:

Does the set of “ME/CFS” definitions encompass the same disease, a spectrum of diseases, or separate, discrete conditions and diseases?

The failure to tackle this cornerstone question up-front in both the agenda and the evidence review puts the scientific validity of the entire P2P Workshop at risk. If this question is not explicitly posed, then the non-ME/CFS expert P2P Panel will swallow the assumption of a single disorder without question, if for no other reason than that they do not know the literature well enough to recognize that it is an assumption and not established fact.

http://www.occupycfs.com/2014/07/21/p2p-the-question-they-will-not-ask/

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Serious concerns!

Ms. Jennie Spotila has given permission to repost her assessment of the P2P study protocol here in its entirety. (Thank you Ms. Spotila.)

Please post comments on her blog http://www.occupycfs.com/2014/05/02/protocol-for-disaster/

As concerned as we are about IOM, P2P looks far, far worse!

Protocol for Disaster?

May 2nd, 2014 Jennie Spotila Leave a comment Go to comments

disasterThe study protocol for the systematic review of ME/CFS was posted by the Agency for Healthcare and Research Quality yesterday. It’s a recipe for disaster on its own, and within the broader context of the NIH P2P Workshop it’s even worse. Let me show you some of the reasons why.

Remind Me What This Is

The systematic evidence review is the cornerstone of the P2P process. The P2P meeting on ME/CFS will feature a panel of non-ME/CFS experts who will produce a set of recommendations on diagnosis, treatment, and research.

Because the P2P Panel members are not ME/CFS experts, they need background information to do their job. This systematic evidence review done by the Oregon Health & Science University under contract to AHRQ will be that background information. The systematic evidence report will be presented to the Panel in advance of the public P2P meeting, and will be used to establish the structure of the meeting as well.

The systematic review is the foundation. If done correctly, it would be a strong basis for a meaningful workshop. If done poorly, then everything that follows – the workshop and the resulting recommendations – will crumble. Based on the protocol published yesterday, I think “crumble” is putting it mildly.

The Key Questions

You can’t get the right answer if you don’t ask the right questions. (Dr. Beth Collins-Sharp, CFSAC Minutes, May 23, 2013, p. 12)

As I wrote in January, the original draft questions for the evidence review included whether CFS and ME were separate diseases. That question is GONE, my friends. Now the review is only looking at two things:

  • What methods are available to clinicians to diagnose ME/CFS and how do the use of these methods vary by patient subgroups?

  • What are the benefits and harms of therapeutic interventions for patients with ME/CFS and how do they vary by patient subgroups?

These questions are based upon a single and critical assumption: ME and CFS are the same disease. Differences among patient groups represent subtypes, not separate diseases. The first and most important question is whether the ME and CFS case definitions all describe one disease. But they’re not asking that question; they have already decided the answer is yes.

The study protocol and other communications from HHS (including today’s CFSAC listserv message) state that the P2P Working Group refined these study questions. The implication is that since ME/CFS experts and one patient served on the Working Group, we should be satisfied that these questions were appropriately refined. But what I’m piecing together from various sources indicates that the Working Group did not sign off on these questions as stated in the protocol.

Regardless of who drafted these questions, they cannot lead to the right answers because they are not the right questions. And when you examine the protocol of how the evidence review will be conducted, these questions get even worse.

Protocol Problems

The real danger signals come from the description of how this evidence review will be done. The issue is what research will be included and assessed in the review. For example, when asking about diagnostic methods, what definitions will be considered?

This evidence review will include studies using “Fukada [sic], Canadian, International, and others“, and the Oxford definition is listed in the table of definitions on page 2 of the protocol. That’s right, the Oxford definition. Oxford requires only one thing for a CFS diagnosis: six months of fatigue. So studies done on people with long-lasting fatigue are potentially eligible for inclusion in this review.

The description of the population to be covered in the review makes that abundantly clear. For the key question on diagnostic methods, the study population will be: “Symptomatic adults (aged 18 years or older) with fatigue.” There’s not even a time limit there. Three months fatigue? Four? Six? Presence of other symptoms? Nope, fatigue is enough.

There is a specific exclusion: “Patients with other underlying diagnosis,” but which conditions are exclusionary is not specified. So will they exclude studies of patients with depression? Because the Oxford definition does not exclude people with depression and anxiety. We’ve seen this language about excluding people with other underlying diagnosis before – and it results in lumping everyone with medically “unexplained” fatigue into one group. This protocol is set up to result in exactly that. It erases the lines between people with idiopathic chronic fatigue and people with ME, and it puts us all in the same bucket for analysis.

And what about the key question on treatment? What studies will be included there? All of them. CBT, GET, complementary/alternative medicine, and symptom-based medication management. It’s not even restricted to placebo trials; trials with no treatment, usual care, and head-to-head trials are all included.

Let’s do the math. Anyone with unexplained fatigue, diagnosed using Oxford or any other definition, and any form of treatment. This adds up to the PACE trial, and studies like that.

But it’s even worse. The review will look at studies published since January 1988 because that was the year “the first set of clinical criteria defining CFS were published.” (page 6) Again, let’s do the math: everything published on ME prior to 1988 will be excluded.

Finally, notice the stated focus of the review: “This report focuses on the clinical outcomes surrounding the attributes of fatigue, especially post-exertional malaise and persistent fatigue, and its impact on overall function and quality of life because these are unifying features of ME/CFS that impact patients.” (page 2) In other words, PEM = fatigue. And fatigue is a unifying concept in ME/CFS. Did anyone involved in drafting this protocol actually listen to anything we said at last year’s FDA meeting?

Bad Science

Credit: ElodieUnderGlass

Maybe you’re thinking it’s better for this review to cast a broad net. Capture as much science as possible and then examine it to answer the key questions. But that’s not going to help us in this case.

This review will include Oxford studies. It will take studies that only require patients to have fatigue and consider them as equivalent to studies that require PEM (or even just fatigue plus other symptoms). In other words, the review will include studies like PACE, and compare them to studies like the rituximab and antiviral trials, as if both patient cohorts were the same.

That assumption – that patients with fatigue are the same as patients with PEM and cognitive dysfunction – is where this whole thing falls apart. That assumption contaminates the entire evidence base of the study.

In fact, this review protocol makes an assumption about how the Institute of Medicine study will answer the same question. It is possible (though not assured) that IOM will design diagnostic criteria for the disease characterized by PEM and cognitive dysfunction. But this evidence review is based on an entirely different patient population that includes people with just fatigue. The conclusions of this evidence review may or may not apply to the population defined by the IOM. It’s ridiculous!

But it’s the end use that really scares me. Remember that this systematic evidence review report will be provided to that P2P Panel of non-ME/CFS experts. The Panel will not be familiar with the ME/CFS literature before they get this review. And the review will conflate all these definitions and patient populations together as if they are equivalent. I think it’s obvious what conclusion the P2P Panel is likely to draw from this report.

I would love to be wrong about this. I would love for someone to show me how this protocol will result in GOOD science, and how it will give the P2P Panel the right background and foundation for the recommendations they will draft. Please, scientists and policy makers who read this blog – can you show me how this protocol will produce good science? Because I am just not seeing it.

What Do We Do?

This protocol is bad news but it is by no means the last word. Plans are already in motion for how the advocacy community can respond. I will keep you posted as those plans are finalized.

Make no mistake, this evidence review and P2P process are worse than the IOM study. We must respond. We must insist on good science. We must insist that our disease be appropriately defined and studied.

http://www.occupycfs.com/2014/05/02/protocol-for-disaster/

FDA Webinar, chance for Q&A and comments April 23, 2014

FDA is hosting a webinar about the draft guidance document “Guidance for Industry Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis: Developing Drug Products for Treatment”.

Note: the webinar will be close-captioned and there questions/comments can be submitted in real-time using a chat window. (It is safe to assume that personal information should not be submitted as this would then be available for all to see onscreen.)

Public comment on the draft guidance should also be submitted to the docket DOCKET NUMBER: FDA–2014–D–0264 http://www.regulations.gov/#!docketDetail;D=FDA-2014-D-0264 – as it then becomes part of the public record.

FDA’s Guidance Webinar series aims to foster collaboration and transparency in the development of guidance documents through direct outreach to affected stakeholders.” (http://www.fda.gov/Training/GuidanceWebinars/default.htm)

FDA Webinar: Guidance for Industry Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis: Developing Drug Products for Treatment – April 23, 2014

The Office of Medical Policy (OMP) in CDER presents another in a series of webinars on 60-day guidances for industry on Wednesday, April 23, 2014 from 1PM – 2PM EDT. The topic is “CHRONIC FATIGUE SYNDROME”.

Guidance for Industry Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis: Developing Drug Products for Treatment

FR NOTICE

PUBLICATION DATE:  03/11/2014

COMMENTS [DUE] DATE:  05/12/2014

DOCKET NUMBER: FDA–2014–D–0264 http://www.regulations.gov/#!docketDetail;D=FDA-2014-D-0264

SPEAKERS:

Janet Maynard, MD and others

Medical Officer

Division of Pulmonary, Allergy, and Rheumatology Products

Office of New Drugs

CDER/FDA

SUMMARY: This guidance is intended to assist sponsors in the development of drug products for the treatment of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). This guidance focuses on specific drug development and trial design issues that are unique to the study of CFS/ME and on the FDA’s current thinking on how effective treatments can be developed for CFS/ME. The points discussed in this guidance may not be applicable to all drug products. The FDA encourages sponsors to design clinical programs that fit their particular needs and to discuss their planned approach with the Division of Pulmonary, Allergy, and Rheumatology Products (DPARP).

For questions concerning the webinar, please contact Marsha Holloman (301-796-0731)

Webinar information on FDA’s Web site: http://www.fda.gov/Training/GuidanceWebinars/default.htm

______________________________________________________________

Guidance Webinar Online-Access Instructions:

To access this webinar, follow the link provided below. Audio will broadcast from your computer speakers.

After following the link, enter as a guest and provide your FULL NAME and organization (i.e. “John Smith – FDA/CBER”). The host will then allow you to enter. If you experience technical difficulties email Jeffery.Rexrode@fda.hhs.gov for assistance. Closed captioning will be provided. Questions/Comments can be submitted live via a Q/A chat window.

Access link: https://collaboration.fda.gov/gfiwebinar

http://www.fda.gov/Training/GuidanceWebinars/ucm392577.htm

Connections, study contact info

One of the highlights of (most) meetings is the opportunity for connecting with people. Such was the case with the IACFS/ME conference held last week in San Francisco.

(There have been some excellent summaries of the IACFS/ME conference — among them: http://phoenixrising.me/archives/24323 , http://phoenixrising.me/archives/24390 , http://phoenixrising.me/archives/24452 , http://phoenixrising.me/archives/24522 , http://phoenixrising.me/archives/24553 , and http://quixoticmeblog.blogspot.com/2014/03/detailed-notes-from-all-4-days-of.html .)

Over and over people talked about how they had exchanged emails with this person or that person for years but had never met in person until this meeting.
ME is such a horribly isolating illness. Even caregivers are often isolated.

Therefore being able to meet other advocates in person, being able to exchange ideas with clinicians/researchers, etc. is exciting and invigorating (and exhausting).

Among the people I spoke with was Dr. Jim Baraniuk who has a study that will start soon (he did not say when). He provided the following contact info for it:

Exercise and Brain Scan Study
Purpose: to understand Chronic Fatigue Syndrome (CFS)
Who: Adults (over 18 years old) with and without CFS are invited to participate.

What: Subjects will have magnetic resonance imaging (MRI) brain scans then bicycle exercise tests.
They will stay overnight, then have a 2nd exercise test and MRI the next day.

Where: Clinical Research Unit, Georgetown University, Washington D.C.
Compensation for time and travel will be paid.

Contacts: Telephone 202-687-8231, FAX 202-687-9886

E-mail:cfsresearch@georgetown.edu or baraniuklab@gmail.com
Georgetown University Medical Center (edit *)

When you contact the lab you might ask (among other things) for clarification about the extent of the bicycle exercise testing, the criteria for patient selection, whether or not any cognitive testing will be done as well (if so, at which points during the study). Please share the responses you get and help us make them widely available.

Many of us came away from the IACFS/ME conference with information on numerous studies and avenues of exploration, getting lots of ideas, hearing hints about soon-to-be-published studies and great connections (some new ones, some long-standing ones but first time in-person meetings)…..

This was a real treat and I am deeply grateful to everyone who helped facilitate attendance at the meeting.

 

(*edited  – disclaimer – I have no connection to and accept no responsibility for the study or participation in it. Thanks for the reminder TK.)

READING THIS Exit Stage Right

(http://www.occupycfs.com/2014/03/13/exit-stage-right/) MAKES Ms. LOPEZ-MAJANO’s PUBLIC COMMENT on 11 March 2014 seem even more significant:

“Even before arriving at their first meeting, CFSAC members need to be well versed in the history, politics, science, breadth of illness, and issues of concern to the community, as well as what has transpired since the committee’s current inception in 2003.

They also need to be ready to work. Right away!

During the December 2013 meeting Dr. Kaplan said “The Center of Excellence idea I think is extremely important and one that I think we should be recommending…”

It is disconcerting that Dr. Kaplan seemed quite unaware that Centers of Excellence have been mentioned more than 130 times in 10 years of CFSAC meetings. It seems to me that he is not familiar with the past work of the CFSAC.

If committee members haven’t made the effort to find out what CFSAC has discussed, then I wonder if you are sufficiently involved with and knowledgeable about this illness and the issues surrounding it.

Committee members also need to be actively involved in the committee’s work. This includes during meetings, in working groups etc.

I understand that not everyone will have input on every point of discussion. However, when committee members are not active participants, it seems those members are chair-warmers – or worse yet, just there to pad their resumes.

Most of you don’t have this illness. WE however are seriously impacted by it at all times and very few advocates are healthy enough to work on all that needs to be done to improve our situation. So we need an effective CFSAC to help us.

Since this committee is charged with making recommendations to and advising the Secretary of Health and Human Services, you need to do everything you can to ensure that this committee works efficiently and expeditiously.

Additionally, despite assurances from HHS that CFSAC terms would be staggered, five six [updated 13 March 2014 to include resignation of Jordan Dimitrakoff] committee vacancies will occur between May and July (2014). Any committee comprised of only 11 voting members, will be unable to work expeditiously if new members need time to learn about the committee, the illness, etc.

I urge the Secretary to ensure that every voting member of the CFSAC is well aware of the committee’s work, of issues regarding this illness and of the issues of importance to this community.

I also urge the Secretary to require that the DFO provide appropriate orientation to committee members.

These actions will help ensure that the committee can always work at full-speed to help those affected by this illness that plagues my grandchildren and so many other people.”

 

 

Summary of April 26, 2013 FDA meeting (day 2)

Recently FDA released a summary (http://www.fda.gov/Drugs/NewsEvents/ucm386705.htm) of the April 26, 2013 FDA Workshop on Drug Development for Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME). You may recall that this was the second day of a 1.5 day meeting and on this day, there were discussions about identifying quantitative outcome measures and determining which treatments produce improvements.

Remember that FDA is currently producing a guidance document for CFS and ME drugs that will provide advice for pharmaceutical companies and industry to expedite research for treatments. Our input will be needed on this. Note – typically when a draft guidance is released there is a 60 day comment period.

Additional information about the meeting and links to transcripts etc. can be found here: http://www.fda.gov/Drugs/NewsEvents/ucm369563.htm

Mary Dimmock has questions —–

(Mary has given permission for this to be shared widely and reposted)

Mary Dimmock asked IOM and HHS some questions about the IOM study. Find out if she got answers…

HHS recently issued an FAQ about the IOM contract. As Jennie Spotila, Erica Verillo, Lois Ventura and Jeannette Burmeister pointed out, the FAQ falls far short of providing useful answers, is misleading and leaves critical questions unanswered.

Like the fundamental question: “What disease is HHS developing definitions for – ME or the diverse conditions that meet the overly broad “CFS” criteria?

I recently asked that question of both IOM’s Kate Meck and HHS’ Dr. Nancy Lee. From their answers, which I summarized below, the only possible conclusion is that the IOM study is intended to establish diagnostic criteria for the diverse conditions that meet the overly broad “CFS” criteria and that ME will be treated as a subgroup.

All of us, patients, advocates and experts alike, must reject this as completely unacceptable. We must call on HHS to acknowledge that ME is not part of the overly broad CFS. We must continue to call on HHS to adopt the Canadian Consensus Criteria.

We all know the problem. ME, the neurological disease characterized by post-exertional malaise, cognitive issues and immunological dysfunction has been buried inside of “CFS”, a diverse collection of medically unexplained fatiguing conditions. Numerous authors, especially Dr. Jason of DePaul, have reported extensively on the serious research and clinical problems caused by these overly broad CFS definitions, definitions that lump biologically unrelated conditions together. Dr. Bruce Carruthers summed it up simply, “There is a poignant need to untangle the web of confusion caused by mixing diverse and often overly inclusive patient populations in one heterogeneous, multi-rubric pot called ‘chronic fatigue syndrome.”

Having rejected the Canadian Consensus Criteria as unacceptable, HHS is conducting three separate initiatives to develop its own criteria. But what does HHS intend to do about the “web of confusion” that ha been created by “CFS”? What disease will these new criteria describe?

The ME/CFS IOM Statement of Work is ambiguous on this point as it uses the same jumbled, non-specific disease labels that have gotten us into this mess to begin with. The SOW states:

the Committee will consider the various existing definitions and recommend consensus clinical diagnostic criteria for this disorder [ME/CFS]. . .
The Committee will also distinguish between disease subgroups . . .
For the purposes of this document, ME/CFS shall be used to refer to Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS), Neuroendocrine Immune Disorder, and other terminologies in use for this illness.

I asked both Kate Meck at the IOM and Dr. Lee, the designated federal official for the CFS Advisory Committee (CFSAC) to clarify what “scope of disease” had been specified in the IOM contract. Has the IOM been contracted to develop clinical criteria specifically for ME? Or has IOM been contracted to develop clinical criteria for the range of unrelated fatiguing conditions that meet the “CFS” criteria? I asked Dr. Maier of NIH and Dr. Beth Collins-Sharp of AHRQ a similar question on the NIH Evidence Based Methodology Workshop process and am waiting on a promised response.

Here’s a summary of the responses I received from Dr. Lee of HHS and Kate Meck of the IOM:

Both Dr. Lee and Ms. Meck said that the scope of disease to be covered by the new clinical criteria has not been specifically defined at this point and that this will need to be defined as the process goes forward.

Dr. Lee indicated that the panel itself would need to resolve this issue and that possible outcomes could be ME as a subgroup of the broader CFS, ME as part of a spectrum that includes these other conditions, or ME as a separately defined disease. Ms. Meck indicated that HHS would be asked to clarify what scope of disease was intended at the first meeting. I raised the concern with Ms. Meck that the scope of disease directly affects panel selection and evidence base selection but she felt that the panel and process would be able to adjust as needed.

In a follow-up email, Dr. Lee confirmed the above statements but also reiterated an earlier point she had made that the IOM task list specifies that the “committee will also distinguish between disease subgroups”. She also said that in order for the target audience – defined as the primary care physicians – to effectively use the resultant guidance, “it is important to start a bit broad and then have criteria which distinguishes between subgroups.”

These answers are profoundly disturbing.

First, the statement that the scope of disease has not yet been defined is frankly hard to believe. This is a million dollar contract and panel selection is due to be announced soon. How can such a critical issue as the scope of disease to be covered by the new criteria be undecided at this point? If it really is undecided, who will decide and how? What criteria have been used to select the panel? And will that panel still be the appropriate one once a decision is reached on what disease or diseases the new criteria will cover?

But the statements about subgroups and spectrum of illnesses are much more disturbing.

Yes, ME is a complex disease that needs to be broken down into legitimate subgroups in order to better understand the disease and the treatment options. Perhaps those subgroups are based on whether onset is sudden or not, the level of severity of the disease or the nature of the immune profile and viral load. But let’s be realistic. What is the likelihood that the panel selected for the IOM study is going to be able to identify proper subgroups of ME itself when our experts are still working through that? Or when the evidence base lacks the ME specific studies – studies done with proper ME definitions – that would be needed to substantiate ME subgroups?

At the same time, we have an agency with a long-term commitment to studying medically unexplained chronic fatigue as the single clinical entity, “CFS”. We have an agency that has taken the position that Oxford, Fukuda and the Canadian criteria all describe the same set of patients for whom one set of clinical guidance is appropriate. We have an agency that questions the scientific evidence surrounding even post-exertional malaise and its measurement while simultaneously rejecting the Canadian Consensus Criteria because it does “not account for scientific evidence developed since 2003.” We have the CDC’s Dr. Unger, rhetorically asking at the May 2013 CFSAC “If a patient doesn’t have [PEM], wouldn’t you still manage them as a “CFS” patient?” And we have the IOM adopting the same overly broad view of CFS as HHS in recent IOM publications on Gulf War Illness.

Now we have Dr. Lee stating that the target audience of the new criteria is the primary care physicians and that they need criteria that start broader and then distinguish between subgroups. What about the patients who desperately need criteria that accurately reflect their disease?

What are we to conclude from all this? HHS has not committed to criteria specific to ME. HHS is not talking about the proper subgroups of ME that we all envision. HHS intends the IOM study to define criteria for the broader set of CFS conditions, with ME characterized as a subgroup. Or worse, ME becomes a subgroup of the even broader chronic multisymptom illness (CMI).

Either way, this will be a disaster that will degrade ME research and worsen the abysmal clinical care and stigma that ME patients receive today. This is the nightmare scenario that we all fear.

If HHS truly wants to reverse the chaos and the grievous harm to patients caused by years of sloppy definitions, it will first and foremost declare that ME, the disease described by the Canadian Consensus Criteria, is not the same disease as the overly broad “CFS” and should not be considered as either a subgroup of CFS or part of a spectrum of CFS diseases.

And if HHS cares not only about primary care physicians but also about the ME patients that they treat, it will acknowledge the harm done to patients by its clinical guidelines as reported at a recent Mount Sinai conference. CDC will immediately highlight PEM as a hallmark symptom of ME, will provide “black box warnings” about the adverse effects of exercise on ME patients and will point clinicians to the Canadian Consensus Criteria and the IACFS/ME primer.

Beyond that, HHS needs to immediately require that the Canadian Consensus Criteria be used in every study funded by NIH, even if it is used in parallel with Fukuda as an interim step.

Patients, advocates and experts alike must demand and accept no less, especially in the context of the IOM study and the NIH Evidence Based Methodology process.