Case Definition Bingo

bingoOur disease is plagued by too many case definitions, with the Institute of Medicine’s Systemic Exertion Intolerance Disease (SEID) being the most recent. Our federal agencies are thus far continuing the agnostic position of accepting whatever case definitions are proposed by researchers or drug sponsors. Communication from the IOM panel members has seemed contradictory at times regarding whether SEID replaces ME, or what to do with patients who do not meet SEID criteria. And advocates are arguing with each other over which definition is “right” and whether to support SEID. This includes some advocates claiming ME is not SEID, and that these two diseases should be kept separate.

This controversy gets to the heart of the IOM report, and the heart of its use and dissemination. It’s not possible to cover all aspects of this controversy in one blog post. Instead, I would like to come at it a different way. Rather than talk about the differences among these criteria, let’s consider the flip side problem of patients who meet more than one case definition. I’ll use myself as an example, and apply the major definitions. Then I’ll talk about a way to think about the muddle we’re in. For a nice overview of the definitions, see chapter 3 of the IOM report. Dr. Cindy Bateman also gave a great talk about SEID that explains some of the IOM Panel’s thinking behind the definition.


Ha! Just kidding! You know what I think of the Oxford definition. Let’s move on.

Fukuda CFS

  • Prolonged or chronic fatigue that persists or relapses for ≥ 6 months
  • Four or more of the following concurrently present for ≥ 6 months: impaired memory or concentration; sore throat; tender cervical or axillary lymph nodes; muscle pain; multi-joint pain; new headaches; unrefreshing sleep; post-exertion malaise

When I was diagnosed in 1995, I met these criteria including having all eight of the ancillary symptoms (plus a number of others like dizziness, fevers, etc). Today, I have the fatigue plus impaired concentration, muscle pain, joint pain, unrefreshing sleep and PEM every day. I still occasionally get sore throats, headaches and tender lymph nodes (and dizziness, orthostatic intolerance, etc). So I meet the Fukuda definition.

One thing to keep in mind is that Fukuda draws a really big circle. At the P2P Workshop in December 2014, Dr. Luis Nacul presented data that show 163 different symptom combinations are possible under Fukuda. When PEM is required, that number drops to 35 combinations (still very high). There is no question that there are people who will meet Fukuda but will not meet IOM SEID or the ME definitions. Therefore, I am not arguing that Fukuda CFS is equivalent to CCC or ICC or SEID.

Canadian Consensus Criteria ME/CFS

  • Fatigue
  • Post-exertional malaise and/or fatigue
  • Sleep dysfunction
  • Pain
  • Two or more neurological/cognitive manifestations
  • At least one symptom from two of the following categories: Autonomic; Neuroendocrine; Immune
  • Illness lasting ≥ 6 months

Yes to fatigue, PEM, sleep dysfunction, pain, neurocognitive (such as confusion, concentration/memory, disorientation, info processing, word retrieval, overload phenomena), autonomic (such as POTS, lightheadedness nausea, IBS), neuroendocrine (such as feverishness, temperature intolerance, loss of adaptability), immune (such as sore throat, flu like symptoms, tender lymph nodes), and obviously I meet the 6 month requirement (with an extra 20 years to boot). So I easily meet the Canadian Criteria.

International Consensus Criteria ME

  • Post-exertional neuroimmune exhaustion (PENE)
  • At least one symptom from three of the following four neurological impairment categories: Neurocognitive impairments; Pain; Sleep disturbance; Neurosensory, perceptual and motor disturbances
  • Immune, gastro-intestinal and genitourinary impairments. At least one symptom from three of the following five categories: Flu-like symptoms; Susceptibility to viral infections with prolonged recovery periods; Gastro-intestinal tract; Genitourinary; Sensitivities to food, medications, odors or chemicals
  • At least one symptom from energy production/transportation impairments: Cardiovascular; Respiratory; Loss of thermostatic stability; Intolerance of extremes of

I clearly have PENE according to the definition in the ICC paper, at the moderate (mostly housebound) level with occasional severe (bedbound) episodes. For the neurological impairments, I have difficulty processing information and short-term memory loss, headaches and significant widespread pain, unrefreshing sleep and disturbed sleep patterns, and I have the sensory and motor disturbances.

For the immune impairments category, I have flu-like symptoms, nausea/IBS, and sensitivity to medications and odors. In energy production, I have orthostatic intolerance, dizziness, air hunger, recurring feverishness, and temperature intolerance. So I easily meet the ICC definition.


  • A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest,
  • Post-exertional malaise, and
  • Unrefreshing sleep
  • At least one of the two following manifestations is also required: Cognitive impairment or Orthostatic intolerance

Importantly, these symptoms must be present at least half the time, and with at least moderate intensity. This is not a bad night’s sleep or minor forgetfulness. Not surprisingly, my doctor confirmed at my last office visit that I clearly meet the IOM SEID criteria, too.

So, Do I Get Bingo?

Where does that leave me? I meet criteria for Fukuda CFS, CCC ME/CFS, ICC ME and IOM SEID. You tell me: do I have one disease or four diseases?

This is the problem confronting all the advocates who are claiming that SEID is not ME. Many patients, like me, will meet the criteria for both. And when this point is raised in discussion, some people have suggested that there are two separate diseases. But if you follow that idea to its logical conclusion, two diseases means two different revenue streams for NIH funding. It also means a drug approved for one disease will need to be approved for the second disease.

If we are talking purely about case definitions, as opposed to real people, then yes ME is absolutely not SEID because the ICC and IOM SEID are different criteria. ICC requires more symptom categories, and specifies the symptom manifestations in each category. And neither ICC ME nor IOM SEID are Fukuda CFS. Dr. Lenny Jason’s most recent paper is just one illustration of that. So if we are purely talking about the definitions – the separate descriptions of requirements for diagnosis – then I think it is logical and clear that ME is not SEID is not CFS.

But that’s not the only context for discussion. Case definitions are hypothetical until they are applied to real people. And when you apply those four definitions to me, I meet them all. This does not mean I have four diseases. It means that these four definitions each describe the disease that I have. Do you see the distinction?

That is the crux of the matter. This thing, this disease that we have, the disease we described to FDA, the disease we can recognize in each other in about five minutes – this thing has been described (with varying degrees of success) by all four criteria. Fukuda CFS is clearly the broadest and least useful definition. Fukuda allows too many combinations of symptoms, and only a fraction of those include PEM. Therefore, it is possible to meet Fukuda and not meet IOM SEID, and what to do with those patients is a quandary for another discussion.

But to claim that IOM SEID is not ICC ME is not CCC ME/CFS is true only in the literal sense that these criteria do not use the same words to describe the disease state that I have, and that many of my readers have. It may be possible to meet one of these descriptions and not another, but that does not automatically mean we all have different diseases, especially when the overlaps among those descriptions seem so large.

I have one disease. That disease has been described in different ways by different groups. The intersection of those descriptions and our experiences as patients must be studied. We need data to understand the characteristics of the patient populations identified by each definition. There will likely be substantial overlap – but is there a biomarker that unites us? Are there subtypes that distinguish us? Is one description demonstrably more sensitive and specific than the others? Did IOM SEID successfully pare down to the most essential elements of the disease, or did they strip out too much?

I have one disease. That disease has been described in different ways. I want my disease to be researched so that the less accurate and less useful descriptions can be retired.


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Did P2P Receive Your Comments?

missingpagesThe P2P report is scheduled to be published on April 14, 2015, but new information may call the legitimacy of the report into question. Based on NIH’s response to my FOIA request, I believe it is possible that the Office of Disease Prevention (ODP) never properly logged some of the public comments on the draft report – including the comments from the CFS Advisory Committee.

First, a brief review of the public comment issue. In early January, ODP told advocates that public comments on the P2P draft report would not be retained. Several advocates, including myself, filed FOIA requests for those comments. In the meantime, I offered to publish the comments of any advocate or organization who wished. The P2P Library is quite impressive, and a terrific example of the quality work of many advocates.

On February 27, 2015, NIH responded to my FOIA request with 308 pages of public comments. I knew there would be comments in the packet that I had not seen before, but I did not expect comments to be missing.

But that is exactly what I discovered. Dozens of comments that I know were submitted to the ODP were not included in the FOIA release. Here are three examples (although there are many more):

Why were these comments omitted from the FOIA release? I can think of two explanations. One possibility is that the FOIA office’s document search was grossly inadequate, and they missed dozens of comments collected by ODP. The second possibility is that ODP did not properly retain some of the comments submitted by the public, and therefore those documents were not available for the FOIA search and release.

If this second possibility is true, then the P2P panel never saw CFSAC’s comments, or the many other comments that we know were submitted on time. And if that is the case, then ODP breached its own policies, and the panel did not have the benefit of all those comments in revising the P2P report.

Throughout the P2P process, NIH has touted the public’s role of participating in the meeting and commenting on the report. Stakeholder participation improves the quality of the reports and helps the non-expert panel balance all sides in the final product. Now we must confront the possibility that reams of public comment on the draft report were lost, discarded, or otherwise went missing. How can we say that the April 14th report is, in fact, the best product of this process?

I have appealed the FOIA release, challenging the adequacy of the document search. If ODP has these comments, then a second search should capture them. I’ve also reached out to the P2P panel in an attempt to verify whether they received these missing comments. As always, I’ll let you know what I find out.

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Expired Opportunities

expiredNIH funding of ME/CFS research has bumped up against a deadline that could have dire consequences for 2015 and beyond. The primary mechanism for grant applications has expired.

Grant applications to NIH must be submitted in response to calls for proposals. Sometimes that takes the form of an RFA, in which money is set aside for a specific purpose. ME/CFS advocates have been begging for an RFA for years without success.

The usual way to submit a grant application is in response to a Program Announcement, and this has been the norm in ME/CFS for many years. However, the current Program Announcement EXPIRED on February 25, 2015. In the past, these announcements have been extended by a year or more, as an apparent matter of routine. But not this year. The only way to submit an ME/CFS grant proposal now is for collaborative research at the NIH Clinical Care Center, and that program announcement expires on March 20, 2015.

But there is another troubling signal. The last meeting of the CFS SEP to review ME/CFS grant applications was September 2014, and there is no meeting currently scheduled. In 2012-2014, the SEP met three times per year, usually once in January/February, once in April/May/June, and once in September. Why is there no early 2015 meeting? This means that applications submitted in the last six months are just sitting at NIH, waiting for the SEP to be convened.

What does all this mean for NIH funding of ME/CFS research in 2015? Worst case scenario – there is none, unless a researcher can shoehorn an ME/CFS project into another program announcement. Best case scenario – NIH is preparing to issue a new program announcement or RFA to take advantage of the P2P and IOM findings. I’ve sent an inquiry to Dr. Mariela Shirley, chair of the Trans-NIH ME/CFS Research Working Group, and will report what I hear from her.

UPDATED MARCH 13, 2015: I emailed Dr. Shirley asking if NIH will issue a new Program Announcement/RFA, and when the CFS SEP will meet again. On March 12, 2015, she replied:

Dear Ms. Spotila,

Information about funding opportunities is published in the NIH Guide to Grants and Contracts.  Anyone can join the weekly listserv for the Guide TOC to review all newly published content . Please note that the “Guide” is the official notice vehicle for NIH funding opportunities.  A spring meeting date for the ME/CFS SEP has not yet been set.

UPDATED MARCH 20, 2015: As noted by Anonymous in the comments, the SEP will meet on April 14, 2015.

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2014 NIH Spending on ME/CFS Studies

KEEP-YOUR-EYES-ON-THE-PRIZE-LEFT-449x372There is no denying or avoiding the importance of the IOM report and its associated controversies, but ME/CFS advocates must keep eyes on the prize: NIH funding for ME/CFS research. The 2014 spending numbers are out and NIH did not make headway on ME/CFS.

ME/CFS research spending totaled $5,384,373, or 231st out of 244 categories. In 2013, we were 226th out of 237. Fibromyalgia research received twice as much; TMJ received 3.6 times as much; Lyme disease received 4.6 times as much; and MS received more than 20 times as much research funding. Ironically, “burden of illness” research on many different diseases received 14.6 times as much research funding as ME/CFS, a disease with a documented economic burden of $20 billion a year.

Every year, I dig into the numbers reported by NIH. You can read my analyses of 2011, 2012 and 2013 spending. In 2014, NIH increased its ME/CFS research spending by $265,652 over 2013, or 5.2%.  We are one of only 17 categories (7% of the total) to have funding stay essentially flat compared to 2013. Significantly, 62% of the disease categories had funding increases in 2014, putting the lie to the “funding is scarce” excuse.

Category Breakdown

For the first time since 2011, there are no grants included in NIH’s list that are unrelated to ME/CFS. The projects broke down this way:

  • Only one study investigated psychological treatments. Dr. Michael Antoni received $557,747 for his study of telephone based patient-partner cognitive behavioral stress management.
  • Two grants will study orthostatic intolerance in some way. First, Dr. Dikoma Shungu received 499,000 to use imaging, plasma, urine, and spinal fluid to try to distinguish ME/CFS patients from patients with Major Depressive Disorder by examining oxidative stress. Second, Dr. Leonard Jason received $389,326 for his grant to study ME/CFS prevalence among young people, and examine whether orthostatic intolerance is related to neurocognitive function.
  • Dr. Ben Katz received $701,137 for a very important new grant to conduct a prospective study of CFS in college students who develop mononucleosis. These kinds of epidemiological studies are critical to understanding the natural history of ME/CFS.
  • Neuroendocrine immune and biomarker studies are the biggest category of spending, by far. Dr. Fabien Campagne is studying gene expression profiles as possible diagnostic biomarkers. Dr. Roland Staud and Dr. Leorey Saligan both continued their work on markers and mechanisms for fatigue. Dr. Jim Baraniuk continued his grant on exertional exhaustion.
  • Five additional new grants were awarded to look at immune signaling and biomarkers. Dr. Jarred Younger received $493,846 to conduct daily immune monitoring in ME/CFS, healthy, and sick subjects. Dr. Roxana Moslehi received $273,447 to investigate patients from Dr. Dan Peterson’s practice, looking for genetic and immune links to CFS, autoimmune disease and Non-Hodgkin’s lymphoma. Dr. Jim Baraniuk received $272,125 for his study of miRNAs in cerebrospinal fluid, looking for biomarkers and subsets. Dr. David Patrick of the University of British Columbia received $196,179 to look at immune gene expression after an exercise challenge. Finally, Dr. Mary Ann Fletcher received $487,064 for a very important study of gender differences in ME/CFS patients, extending important work on immune signaling and pathways.

Trend Spotting

The main reason to do this analysis is to track the year to year trends in research spending. And the research category trends are still pretty good.

2012 2013 2014
Total spending $4,518,182 $5,118,721 $5,384,373
Not CFS Related 1.77% 1.5% 0
XMRV 16.43% 0 0
Psychological 20.14% 10.4% 10.36%
Orthostatic intolerance 7.01% 11.7% 16.5%
Neuroendocrine Immune 54.65% 76.4% 73.14%

(To see the analysis going back to 2009, click here.)

As you can see, the trend is pretty steady. The spending on psychological studies remained even from 2013, and there is only a slight variance in the orthostatic and neuroendocrine immune categories.

Every single funded grant was reviewed by the CFS Special Emphasis Panel, although that does not mean that every single ME/CFS application received by NIH was sent to that Panel. I think it is pretty likely though, unless an applicant requested and justified sending the application to a different study section.

Another important stat is that there were six new grants in 2014 (Katz, Younger, Moslehi, Baraniuk, Patrick, Fletcher) for a total of $2,423,798. That’s 45% of the total amount. It’s great to see new projects starting, but it reveals a vulnerability too. Just keeping our research funding steady at this low level requires many successful new applications each year. It will take conscious effort from NIH and from researchers to push our funding level higher.

The overall funding trend is not terrible, but it’s not great either:

Adjusted Spending $ Increased (Decreased) % Increased (Decreased)
2008 $3,175,262
2009 $3,810,851 $635,589 20%
2010 $4,248,535 $437,684 11.5%
2011 $5,009,672 $761,137 18%
2012 $3,696,068 ($1,313,604) (26.2%)
2013 $5,041,521 $1,345,453 36.4%
2014 $5,384,373 $265,652 5.2%

As I said, our funding level basically stayed flat from 2013 to 2014, with both years rounding down to $5 million. Sure, a 5% increase is better than nothing, but only 17 of 244 research categories stayed flat in their funding. A whopping 151 (or 62%) of those categories saw an INCREASE in funding. So there is obviously money to go around.

The outlier in that table is 2013, which showed a 36% increase over 2012. But that was only because 2012 was such a lousy year with a drop of 26%. If you take 2012 out, the increase from 2011 to 2013 was only $32,000 – basically flat.

And that’s the real metric here. Our research funding has been between $4 and $5 million per year for the last seven years. And what does NIH project for 2015? Another $5 million. So despite the P2P report, and all the CFSAC recommendations, and the IOM report, we are at the same level and projected to remain there.

This is unacceptable. I don’t know what has to happen to force a change, but force it we must. No matter what you think of SEID or the IOM criteria or the news coverage or your fellow advocates, we must find a way to force NIH to dramatically increase its investment in ME/CFS research.

Because while I am not a fortune teller, I can easily predict that if we do not secure this increased investment then we will be sitting here in 10 years and having the same damn conversations about SEID and IOM and news coverage and our fellow advocates. Nothing will change if the research funding does not change. Nothing. I guarantee it.

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PEM Differential

diagnosisstampOne of the post-IOM controversies consuming advocates at the moment is the concern that SEID criteria are non-specific and will include people who do not have our disease. The failure to list exclusionary conditions, including psychological disorders, has drawn criticism from some advocates and at least one expert clinician. This is a legitimate concern because if the SEID criteria capture people who do not actually have it, then we are simply perpetuating the problems with the Oxford and Fukuda definitions, both of which have been demonstrated to include people who have fatigue that is not caused by our distinct disease. But will the SEID criteria open the floodgates to people who have only depression or anxiety or other fatiguing illnesses? The answer is no, if the SEID criteria are correctly applied.

Correct diagnosis is critical for clinical care and research. Overly broad groups of subjects can produce misleading research results, and incorrect diagnoses harm patients. For years, advocates and experts alike have pointed to post-exertional malaise as the symptom that distinguishes our disease from other fatiguing illnesses. PEM was a focus of the Voice of the Patient report from FDA, and is also one of the core symptoms identified by Dr. Leonard Jason’s research as essential for diagnosis. The IOM agreed, and made PEM mandatory for diagnosis with SEID.

The IOM report described PEM as:

worsening of a patient’s symptoms and function after exposure to physical or cognitive stressors that were normally tolerated before disease onset. Subjective reports of PEM and prolonged recovery are supported by objective evidence, including failure to normally reproduce exercise test results (2-day CPET) and impaired cognitive function. These objective indices track strongly with the presence, severity, and duration of PEM. (p. 86)

The IOM also found PEM to be a characteristic symptom of ME/CFS:

The existence of PEM can help physicians confirm a diagnosis of ME/CFS earlier rather than only after extensive exclusion of other conditions. Several studies have found that PEM best distinguishes ME/CFS from idiopathic chronic fatigue and may help distinguish it from other fatiguing conditions with a lower frequency of PEM. (p. 85-86)

The IOM report cites several papers finding PEM in major depressive disorder and multiple sclerosis, but interpreted them with caution because the prevalence of PEM depends on how it is defined and assessed. If these papers did not define PEM as the exacerbation of multiple symptoms after physical or cognitive exertion, then the findings would not be applicable given how IOM defined PEM.

Unlike the Canadian and International Consensus Criteria, the IOM lists no exclusionary conditions. Many people seem to have interpreted this to automatically mean the criteria are too broad. But the IOM explained that people can have SEID and other diseases, whether it is obesity, hypothyroidism, or cancer. Under Fukuda, any of those diseases would preclude diagnosis with CFS, but comorbidities are a fact of life.

For example, I have obstructive sleep apnea that arose after my diagnosis under Fukuda. Technically, this should disqualify me from diagnosis under those criteria. However, my sleep apnea is perfectly controlled by use of a CPAP machine. The data from the machine show that I do not have sleep apnea when I am using the machine (which I do, every single night). Yet I am still sick. So why should having sleep apnea, especially if it is well-controlled, exclude me from diagnosis? Certainly, the sleep apnea should be taken into account if I participate in a research study, and could possibly disqualify me from some studies. But it should not exclude me from diagnosis with the disease.

The same is true of other comorbidities. Why should someone with hypothyroidism which is being adequately treated be denied diagnosis with SEID if they have PEM, sleep problems and cognitive dysfunction? If someone has PEM, severe fatigue that prevents them from working, unrefreshing sleep and orthostatic intolerance, what difference does it make if they also have depression? Doesn’t that person deserve treatment for depression as well as management of SEID?

In my opinion, comorbidities are not the concern. The legitimate concern is whether SEID would, like Oxford and Fukuda, be applied to patients who have only depression or only anxiety (or only other fatiguing illnesses). Research has shown that Oxford and Fukuda both erroneously include people with “just” depression (and I do not mean to minimize the suffering of depression) and not the distinct disease described by ME or SEID criteria. This would be a fatal flaw of SEID criteria, because we know that studies like PACE have included high numbers of people with fatigue but not our disease, and this could account for the small signal of CBT and GET effectiveness reported in PACE (notwithstanding all the other legitimate criticisms of how PACE was conducted and analyzed).

But unlike Oxford and Fukuda, SEID requires the hallmark characteristic of PEM. If post-exertional malaise is unique to our illness, then correctly applied SEID criteria should not misdiagnosis people with other fatiguing illnesses as having SEID. Why? Because if a patient does not have PEM, they would not be diagnosed with SEID. And if a person has PEM and the other core SEID symptoms, then they have our disease regardless of what other conditions they may have. Therefore, if a person has only clinical depression or only hypothyroidism or only multiple sclerosis, that person does not qualify for SEID because he/she would not have PEM and the other core symptoms.

The IOM committee is staking the position that PEM is so distinct that no differential diagnosis is required, because differential diagnoses are needed only when multiple diseases present with similar symptoms. Once a clinician has established that a patient not only has severe debilitating fatigue, but also has PEM, unrefreshing sleep, and cognitive dysfunction and/or orthostatic intolerance, there is no need to exclude other conditions. This is a distinct symptom presentation, and will not – if correctly applied – result in people who do not have the disease being included in the patient population. Remember that Dr. Jason’s research identified PEM, unrefreshing sleep and cognitive dysfunction as the core symptoms of the disease, especially when frequency and severity cutoffs are applied (as IOM also recommended).

The real issue, in my mind, is whether these criteria will be correctly applied. Chapter 7 of the IOM report and the materials for clinicians both include questions and tests to determine if a person has PEM. However, given the misinformation already extant about our disease, and the outright prejudice among some in the medical profession, we cannot take it as a given that healthcare professionals will suddenly be able to recognize PEM correctly. That is why the educational recommendations of the IOM report are so critical, and why I believe we should be vigilant about whatever materials HHS ends up creating as part of an education campaign. It is unquestionable that many healthcare professionals need remedial education, and CDC’s current education materials are grossly inadequate. But this is a different problem from the fear that the SEID criteria themselves are not sufficiently specific to exclude those who do not have the disease.

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Your Move, HHS

chessSince the IOM report came out, the patient/advocate online community has been on fire. Everyone is staking out a position. You like the name, or you don’t; you think the definition will work, or it won’t. And I have plenty to say about these issues, too. But what I don’t hear people asking is: what is HHS going to do with this IOM report?

HHS itself has made a single, bland statement. Dr. Nancy Lee said on the CFSAC listserv that, “We are committed to working with our Federal partners, stakeholders, and experts in the field, as well as with the HHS Chronic Fatigue Syndrome Advisory Committee, to review the report’s recommendations and appropriate next steps.”

That’s inside-the-beltway-speak for “we’ll get back to you.”

Remember that HHS received the report at least a week before it’s public release. Remember that the sponsoring agencies received a briefing from the IOM committee about the report, and Dr. Clayton said they were “breathtakingly clear” about their recommendations. I realize that government moves slowly, and there will probably be meetings and actions proposed and approvals sought and so on. But the patient population is reading and discussing the report in public (as well as in private), and I think we all know that HHS monitors the blogs and forums. So we are telegraphing our analyses, controversies, and plans to HHS while they remain silent.

But we need to know what HHS thinks and what HHS is going to do. Fellow advocates, we really need to know this because we must shape our own advocacy to push the right levers and get the results we want. Here are some of the questions I’m thinking about:

  • Will CDC accept the SEID definition, especially the requirement of post-exertional malaise? CDC has refused to make PEM a requirement for years.
  • Will CDC use the name SEID, but simply lay it on the Empirical or Fukuda definition? This would be disastrous for us.
  • Will CDC take down its Toolkit, and put a properly revised one in its place? Advocates have been battling with CDC to remove the recommendation for GET for years.
  • Will HHS appoint an SEID czar, as IOM recommended, to oversee the dissemination of the new name and criteria?
  • Will the National Center for Health Statistics create a new diagnostic code for SEID? Who will be charged with writing that proposal and seeing it through?
  • Will FDA adopt SEID as required criteria? Thus far, FDA has been agnostic on the case definition and said it will accept definitions specified by sponsors. But if FDA were to focus on SEID, that might require sponsors to reanalyze their data to examine participants who meet SEID criteria.
  • Is NIH giving the P2P Panel a chance to revise their recommendations in light of the IOM report? For example, the draft P2P report recommended, “that the ME/CFS community agree on a single case definition (even if it is not perfect).” Does the P2P Panel think that SEID meets that need?
  • And the $100 million question: Will NIH finally step up and provide the funding we need to effectively research this disease?

The answers to these (and other questions) should shape our advocacy. To that end, I faxed a letter to my Congressmen today asking them to find out what HHS intends to do about the IOM recommendations. You can see the text of my letter here, and I urge you to send a similar letter to your own Congressmen as soon as possible.

The advocacy debates will continue to rage for many weeks. In the meantime, it’s your move, HHS. You commissioned this report for $1 million. How will you put its recommendations into practice?

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NPR Interview

Miriam Tucker has been covering ME/CFS for some time now, and published a great piece for NPR about the IOM report today. I was interviewed for the piece, and I can say that Miriam understands this disease, much like David Tuller and some of the other journalists who have covered the topic.

The reality of journalism – even online journalism – is that word count matters. Miriam’s piece came in at about 800 words, not much room to cover the complex issues arising from the IOM report. And I tend to be a wordy person, so I’ve posted my complete email interview with Miriam from yesterday.


Miriam, I haven’t had a chance to review the report yet, so my reaction is based on the briefing documents and the event today. I also posted a quick blog post.

What do I think of the criteria?
I think the IOM Panel got a lot of things right with the new criteria. They focused on the central feature of the disease, post-exertional malaise, and limited the required symptoms to a short list. They also make recommendations on frequency and severity, which Dr. Jason’s work has shown is essential. Finally, it appears that this diagnosis is no longer a process of exclusion, as CDC and other entities have insisted for decades. When I was diagnosed, my doctors focused on ruling things out, and CFS was the diagnosis of last resort after everything else was eliminated. Now if you meet these criteria, you have this disease. That is a huge shift, and I’m not sure if people have really keyed in on that yet.

What do I think of the name?
SEID will be controversial, especially for the advocates like myself who argued for use of the term myalgic encephalomyelitis. The name does two things right – it focuses on the key symptom of PEM, and it uses the word “disease” which is very important. However, I think this is a risky change. It could take a long time to secure a diagnostic code, and it’s not clear who will be responsible for making that proposal. Another concern is that the name change will be made, but not the definition change. In other words, if CDC simply renames the disease to SEID but does not actually shift to the new criteria, then we are no further ahead. The name and criteria should be used together to make a clean break from the diagnostic waste basket of CFS.

What do I like/what done better?
I would like to see data that support SEID as a better name than ME.

Will it help patients?
That all depends on how widely and how accurately the criteria are implemented. Again, the name and criteria should be used as a clean break and not simply replacing CFS with SEID.

What do I want to have happen next?
I want to hear from HHS. So far, the only statement I have seen is the one from Dr. Nancy Lee that I’ve copied below [NB: the statement went out on the CFSAC listserv on February 10]. That is a non-statement as far as I’m concerned. I want to know if CDC will adopt these criteria, and accept PEM as mandatory for diagnosis. I want to know if CDC and HRSA will roll out the material for clinicians. And the most important issue of all: will NIH actually invest the research dollars necessary to understand and treat this disease? Without a substantial and meaningful increase in research funding, all these other issues will be meaningless.

Statement from Nancy C. Lee, MD, Deputy Assistant Secretary for Health – Women’s Health and Director of the HHS Office on Women’s Health:

The HHS Office on Women’s Health and the other sponsoring agencies* want to thank the Institute of Medicine (IOM) Committee on Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) for its thoughtful analysis in developing this important report. We are pleased with the committee’s recognition of the impact that ME/CFS has on the lives of many Americans. With their recommendation of a streamlined, yet evidence-based set of diagnostic criteria, the IOM committee has taken a critical step toward assisting medical providers in making a diagnosis for those with this serious and debilitating illness.

We are committed to working with our Federal partners, stakeholders, and experts in the field, as well as with the HHS Chronic Fatigue Syndrome Advisory Committee, to review the report’s recommendations and appropriate next steps.

*The Agency for Health Care Research; the Centers for Disease Control and Prevention; the Food and Drug Administration; the National Institutes of Health; and the Social Security Administration.

The report can be found at the following link:

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IOM: Report Card

It’s here. A new case definition and a new name. It will take some time for me to get through the 300 page report and prepare a more detailed analysis. But based on the press conference and summary, how did the report stack up to my criteria for success?

Post-exertional malaise: This was my drop dead deal-breaker, and the new definition makes PEM the central feature of the disease. Dr. Clayton said that PEM was “the essence of this disorder,” and it is required for diagnosis.

Core features: As I had hoped, the new definition requires only four symptoms for diagnosis: a substantial decrease in function (work, school, social); PEM; unrefreshing sleep; and cognitive dysfunction and/or orthostatic intolerance. These core symptoms also match what Dr. Lenny Jason’s work has shown. At the press conference, Drs. Clayton, Bateman and Rowe all emphasized that this is an evidence-based definition.

Frequency/Severity: Another requirement I was hoping to see. The new definition requires symptoms “persist for at least 6 months and be present at least half the time with moderate, substantial, or severe intensity.”

Name: CFS is out, but so is ME. Citing a need to focus on the key feature of the disease, the committee proposes Systemic Exertion Intolerance Disease. Um, what? Dr. Lenny Jason told David Tuller that the patient community will not like or accept this name. I think he’s probably right about that.

Making the diagnosis: As I hoped, the report provides guidance on how to make the diagnosis, with an algorithm, short list of tests, and clinician materials to be published soon.The committee insists that any healthcare provider can make this diagnosis and start treating patients. I want to read more in the report about how they think this is possible, given the radical under diagnosis we currently face.

No psych: Dr. Clayton was emphatic at the press conference that this disease is not somatization. I’ll be reading the report carefully to see how they address the psychosocial theory.

Where To Next: This is the BIG question. Will HHS accept this name and definition? Who will submit the proposal to create a new code in ICD-10, and what category should it lodge in? Will the name CFS simply be replaced with SEID, without refining the research cohort selection?

Dr. Clayton said that this report gives advocates the “fodder” to “act up.” Will we? Can we find a way to pull together and use the good parts of this report to advance the cause? That is the question that will keep me up tonight.

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IOM: The Big Day

IOMOn February 10th, the Institute of Medicine committee will release its report Beyond ME/CFS: Redefining an Illness. The release event will be webcast at 11am Eastern. The report contents are under embargo until the release, although rumors are flying about its possible contents. HHS has already been briefed on the report, and I believe members of Congress have also been briefed (although I don’t know how many).

Good or bad, this report is likely to have a huge impact on ME/CFS advocacy. But how do we define a good or bad report? Some advocates have said that anything other than an adoption of the 2003 Canadian Consensus Criteria will be a failure. This outcome seems unlikely to me, only because it would be hard for anyone to justify spending $1 million and more than a year to simply adopt something that already exists. I think everyone would agree that a report that goes in the direction of broad Oxford-like criteria or psychogenic language will also be a complete failure. Again, this seems unlikely to me given that the committee includes a number of experts who would never agree to such a move. In fact, Dr. Klimas made comments at the P2P meeting that suggested she thinks narrow criteria would identify clean cohorts for biomarker and treatment discovery.

Until we have the report, we won’t know where it falls on the good-bad continuum. But I find it helpful to think about critical elements for success in advance, in order to more fairly judge the report on its merits (or lack thereof). So here are my personal must haves for a successful report:

Post-exertional malaise: This is nonnegotiable to me. The new definition must require PEM. The report should also explicitly define PEM, distinguish it from the single symptom of fatigue, and make suggestions on how it can be measured in clinic.

Core features: Dr. Lenny Jason has shown in multiple papers that criteria focusing on the core features of the disease are more precise, without incorporating patients with primary psychiatric disorders. Dr. Jason’s work shows that PEM, cognitive dysfunction and sleep disturbance are the three core features. Pain and autonomic dysfunction are frequently experienced by some patients but may be more useful in subsetting. So I think a successful definition should not present a laundry list of required symptoms like the 1988 Holmes or even the ME-ICC.

Frequency/Severity: Another theme of Dr. Jason’s work is setting minimum thresholds for frequency and severity in order to weed out people who do not actually have this disease. I hope the new definition will address issues like how long someone has to be sick to qualify for diagnosis, how frequently symptoms are experienced, etc.

Name: CFS or anything like it has to go. I argued in one of my memos to the IOM committee that ME was a better name, both because of evidence of inflammation in patients and because a diagnostic code already exists. I heard a rumor that ME will not be the new name, but the person who made that statement did not cite a specific source for the information. A new name will be problematic, as we may languish code-less for years, and still face the problem of the code being listed under “symptoms” instead of “neurological diseases.”

Making the diagnosis: The report should provide guidance to clinicians on how to make the diagnosis. What tests should be run? What diseases should be eliminated? Should we be referred to specialists, and which ones? Previous studies have shown that 80% of people with this disease may be undiagnosed. The report should provide recommendations on how to change that.

No psych: Any credence given to psychogenic explanations for the disease will be a failure. Agnostic statements on whether this is a psychological disorder will also be a failure.

Where To Next: Ideally, the report should make recommendations on where we go from here. Should a new prevalence study be done? Should CDC retool its multisite study? How should research on subjects that did not require PEM be interpreted going forward? How should the definition be rolled out to healthcare providers?

This may not be a comprehensive list of essential elements for success. What do you think is essential in a successful IOM report? What deal breakers would make the report a failure?

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Guest Post: Slightly Snarky

Joe Landson authors this guest post on the chasm between patient experiences and the people who need to understand them.

We suffer through many devastating symptoms, but today I’m only thinking of one. It’s perhaps the most devastating effect of this illness, while not actually being a symptom at all.

It’s the sensation of being surrounded by idiots – the feeling that we have described our symptoms over and over, documented them, even proposed peer-reviewed literature-based explanations for them, only to hear the response: “So… you feel tired?” On orthostatic intolerance: “So, you feel dizzy?” On irritable bowel: “So, you have a tummyache?” It’s such fun I could go on, but I’ll stop there.

This non-symptom that probably all of us experience has led to the distinct impression that only other patients and caregivers get it, that we must cling to each other to keep from losing it completely. Indeed, our cliquishness has prompted many psychiatrists and social scientists to theorize that we suffer from mass hysteria. (Of course that’s impossible; we’re much too socially isolated to have mass anything.)

Of course, clinicians and government health officials must sympathize with our plight, because they have the mirror image of this condition. With a group of us in a room, they apparently experience the unshakable sensation of being surrounded by catastrophizing hypochondriacs. At least they act like they are, based on referral patterns, research funding levels, and non-adherence to the FACA. It’s the best explanation I can think of for how we’re treated – regardless of whatever sympathetic lip service we receive in meetings and conferences.

And so we float past each other, health workers and patients & advocates; trapped in our respective knowledge bubbles.

The problem, of course, is not limited to us. There has long been a chasm between how patients experience an illness on one hand, and how medical professionals define and treat it on the other. It’s a recognized problem that several efforts try to address. One of these efforts is patient-centered outcomes research, pursued by the Food & Drug Administration (FDA), amongst others.

Towards this goal, the FDA revised their guidelines for ME/CFS treatment research. The way I read the FDA’s instructions is this: Don’t have a validated outcome? Make one up. Make up anything, validate it statistically, and show that your proposed intervention moves the outcome score upwards on a graph. Show that the intervention is otherwise safe (to the patient and the graph), and we’ll strongly consider approving it. I hope I’m misreading it, but that’s how I see it, and it does not bode well for serious research. On the other hand, it may get a treatment approved in our lifetimes. Time will tell.

I have other doubts. Is patient-centered research really the best way to fill the chasm between the illness we have, and the one others (don’t) see? Probably some medical professionals equate patient-centered anything to putting the patients in charge of the asylum. (Given some of the doctors we’ve met, wouldn’t this be an improvement anyway?) For me, the phrase patient-centered research recalls Count Rugen (the six-fingered man) testing his suction-based torture device on Westley and asking, “And remember, this is for posterity so be honest. How do you feel?” (What could be more patient-centered than that?)

Speaking of doctors we’ve met, I will never forget the Veterans Affairs rheumatologist calmly explaining to me that while he treated fibromyalgia, which was real because it had a pressure point test, he could not treat chronic fatigue syndrome, which was just a form depression. Interestingly, he made this pronouncement shortly before his colleagues dropped the pressure point diagnostic test for fibromyalgia, and replaced it with a revised definition that sounds an awful lot like a functional disorder. Reality comes and goes, doesn’t it?

In Brain on Fire: My Month of Madness, Susannah Cahalan describes her experience with NMDA Receptor Autoimmune Encephalitis (AE). Its symptoms are utterly indistinguishable from psychosis or schizophrenia; brain scans show nothing. Moreover, doctors’ approach to the illness is a self-fulfilling prophecy. If treated as a psychiatric disorder, AE gets worse and becomes permanent or fatal. If treated as the autoimmune disease it is, AE may ameliorate and even remit to a full recovery, as it did for Cahalan. She acknowledges she was lucky, and that society really has no firm idea how many are unlucky, given a vague psychiatric label, and left to rot or die.

AE may or may not have specific medical answers for us. However the situation is absolutely the same. If health care providers continue to treat us as if we have belief issues, then their own belief will self-fulfill. Our condition will effectively become permanent, and more of us will succumb to paranoia and despair.

Of course, correcting doctors’ beliefs will not suddenly make us well. The best it might do, in the short term, is end the graded exercise and other “treatment” imposed by Count Rugen Peter White and others.

Our beliefs must change, too. Not about our illness per se: Rather, we have start believing that no matter how few or poorly funded, folks genuinely are trying to help us. There is no conspiracy; instead, there is a giant chasm in medical knowledge that has swallowed us up, along with other diseases, too.

And I have to stop being so snarky. Tomorrow.

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