Archive for June, 2013

Drug and FDA News, June 2013

June 28th, 2013 1 comment

We’ve had a good discussion in the comments on the advocacy action to request another meeting with FDA. I asked FDA if they would be pursuing Guidance to Industry on ME/CFS drug development, and was told it is already underway. I updated the original post with the email response from Dr. Theresa Michele.

There are a few other FDA news items to share with you:


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Precision Is Required

June 25th, 2013 20 comments

Post updated June 28, 2013. See end of post for additional information from FDA.

Five ME/CFS advocates recently sent a letter to DHHS, FDA and select members of Congress requesting that FDA convene a second meeting with ME/CFS patients “to develop a clear regulatory pathway” for drugs to help us. This letter has been followed by a call for patients to email FDA in support of such a meeting. However, both the letter and the email template contain multiple statements that are inaccurate or imprecise. I am concerned that these errors are significant enough to potentially undermine the effectiveness of the letter with the very people it is meant to influence.

Part of my role as an FDA Patient Representative is to bring the ME/CFS perspective to FDA discussions. But another part of my role is to bring accurate information about FDA to the ME/CFS community. It is in that spirit that I point out a few of the errors in this letter and email campaign. I am not trying to micro-edit or nitpick. Rather, I believe that precision and careful crafting of requests can make us all more effective advocates.

The rules should not apply

The email template includes this statement:

FDA has the power and the authority to waive traditional regulations when healthcare demands, particularly when the disease is serious/life-threatening, as ME/CFS clearly is.

No, FDA cannot do this. FDA is one of the most highly regulated agencies in order to make it very clear what FDA can and cannot do. The products that FDA monitors and regulates account for a huge part of our economy. FDA has an extraordinary amount of power, but the regulations exist to constrain that power. FDA cannot look at a situation, wave a wand and say the traditional regulations do not apply. There are alternatives to “traditional regulations,” but those alternatives are themselves defined by more regulations.

No regulatory pathway

The letter sent to FDA and select Congressmen states, “The FDA must create such a regulatory pathway for ME/CFS.” I’m seeing this phrase – regulatory pathway – pop up in multiple places now. While the letter does not say so, I frequently see the phrase used in comparison to AIDS, tuberculosis and Alzheimer’s. To paraphrase the argument: those diseases have special regulatory pathways so we need one too.

But this is not correct. TB and Alzheimer’s do not have their own regulatory pathways. To my knowledge, there are no disease-specific or individualized pathways. There are special programs to accelerate review, and these were discussed at the FDA meeting by Melissa Robb beginning at page 74 of the meeting transcript. These programs include Accelerated Approval, Fast Track, Priority Review, and Breakthrough Therapy. These programs are all defined by regulations, but they do not lower the standard for safety and effectiveness nor are they specific to a single disease.

Where FDA does get disease-specific is in issuing Guidance to Industry. Guidance documents are intended to give FDA’s perspective on a specific issue or disease. For example, the draft guidance to industry on developing drugs for early-stage Alzheimer’s provides FDA’s thinking on the design of clinical trials for this purpose, including selection of patients, selection of endpoints, and ways to demonstrate disease modification. Guidance documents go through substantial processes of development, including a period of public comment. The documents also do not establish legal or regulatory requirements; the guidance is a non-binding recommendation from FDA to industry.

Guidance to industry on ME/CFS was proposed at the April meeting by several people, including Ms. Jody Roth from Eli Lilly. Dr. Theresa Michele, Clinical Team Leader in FDA’s Division of Pulmonary, Allergy and Rheumatology Products – where all ME/CFS drug applications are reviewed – said:

[G]uidance for industry is definitely, I think, an important next step. It’s something that we here at FDA are already thinking about. . . and we hope to be working on that definitely over the next months to a year or so. It takes a long time for a guidance from FDA, just the logistics of getting it through the system. FDA Drug Development for Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: Public Workshop Day 2, April 26, 2013, pp. 339-340.

The advocates’ letter was dismissive of the prospect of a report, saying: “A report of any kind, but particularly one that has no specific deadline, is a very poor outcome for the amount of work that was put forth by the FDA, the experts and, most importantly, this debilitated population of patients.” But there is a significant difference between a summary report of the meeting and a Guidance to Industry document. FDA can’t force drug developers to come into the area of ME/CFS. But FDA can encourage it, and can provide industry with the guidance it needs to design good clinical trials. From what I heard on and off the record at the meeting, FDA is ready and willing to do exactly that. A Guidance report would be an outstanding and much needed outcome from the meeting.

Precision is so important, especially in communicating with FDA. Claiming that other diseases have individual regulatory pathways is inaccurate. I think I know what the advocates mean here: that FDA should clearly state what endpoints and outcome measures should be used in clinical trials, and then shepherd review of products through the various pathways for accelerated approval. But that is not what the letter says, and therefore there is a risk that FDA will not understand that this is what they mean.

May I Have Another?

The fundamental request of the call to action is for FDA to hold a “true” stakeholders’ meeting by the end of the year to define a regulatory pathway for ME/CFS treatments. But why would FDA agree to hold another meeting when we’re only sixty days out from the first, especially when the meeting comment docket has not closed yet? While the letter cites numerous criticisms of the April meeting, it seems to ignore that requesting a second meeting so soon after the first and in this fiscal climate is extraordinary, and therefore a compelling case must be made in support of that request. I fear that the errors and imprecision in this letter and email campaign undermine the attempt to make a sufficiently compelling case.

Effective communication requires understanding the context and language of the audience. If we are imprecise or inaccurate, the audience will get distracted by our mistakes and lose sight of what we are actually trying to say. In turn, this can lead to the failure of the overall communication through misunderstanding or even outright dismissal. FDA’s language is based on statute, regulation and science. The errors I discussed are potential signals to FDA that we do not actually understand what the agency can do or the best ways FDA can help us.

ME/CFS advocates require the same of others. How do we react when someone says “chronic fatigue” instead of “chronic fatigue syndrome”? Or “CSF” instead of “CFS”? We expect clinicians, researchers and agency representatives to know our issues and our language. We all know the difference between the Oxford definition and the Canadian Consensus Criteria, and we justifiably react negatively if someone tries to tell us those definitions are basically the same thing. To communicate effectively with us, an agency representative would do well to be precise and accurate. Otherwise, we end up reacting to the mistakes in the message and the actual message gets lost.

To be effective advocates, we must also be precise and accurate and we undercut our own position if we fail to do so – even if the failure is accidental. I know the advocates who have called for this action, and have worked with them in the past on other efforts. Each of them is deeply committed to advancing the cause of ME/CFS patients. But as advocates, we have a responsibility to communicate as clearly and effectively as possible. It is worth the time and energy invested to craft a specific, accurate and strategic request that speaks to the context of the audience. Such a carefully crafted request focuses discussion on the substantive issue, rather than accidentally diverting attention with misstatements.

We owe it to each other and the ME/CFS patient community to get things right. We must speak with precision and clarity about complex topics, while also presenting a strong case for what ME/CFS patients need. It is not an easy thing to do, but it is essential to our collective and ultimate success.

Update June 28, 2013: After some discussion in the comments, I asked FDA whether the April meeting was sufficient to begin the Guidance to Industry process, and whether FDA would be pursuing it. Dr. Theresa Michele replied via email to me, in part:

With regards to the guidance for CFS—yes, we are working on it. The April meeting was an excellent starting point. Please be aware that the guidance process takes many months of internal writing and editing before anything is posted, since multiple groups at FDA have input into all guidances.   During this process, we will continue to take into account any new information that becomes available, such as the CDC study and the NIH Evidence Based Methodology Workshop. Once the guidance posts, it will be considered a “Draft Guidance” and FDA will take into account any comments we receive from the public before publishing a Final Guidance, usually several years later.

In the meantime, industry is not without recourse—the Division of Pulmonary, Allergy, and Rheumatology has made it very clear that we are extremely open to granting development meetings to any sponsor interested in developing products for ME/CFS. (emphasis added)

Meeting METS

June 21st, 2013 5 comments

It has been more than a year since I had a two-day exercise test. My exercise test report was full of all kinds of jargon, and over the last year I have been trying to decode and apply it to my pacing. One of these concepts is “METS,” a measurement of the effort needed to do an activity, and correlating my results to the real world has been nothing short of shocking.

METS is the Metabolic Equivalent of Task, and is a measure that expresses the relative energy cost of activities, with a MET of 1 equal to sitting quietly. Walking at a slow pace has a MET of 2, meaning that walking slowly costs twice as much energy as sitting quietly. In exercise testing, METS is calculated from the maximum amount of oxygen consumed (VO2max), although it is not intended to perfectly correlate to an individual’s metabolism. But for purposes of understanding the relative costs of different activities, and estimating parameters of an individual’s functional capacity, METS is used as a standard measure.

In my exercise testing, my VO2max (which is the maximum amount of oxygen I consumed) correlated to 5.9 METS. This means I can’t do any activity that requires more work than 5.9 METS because my body can’t perform that level of work. My anaerobic threshold (as I’ve previously explained) was very low. A healthy person with a maximum METS of 5.9 should cross the anaerobic threshold between 3.0 and 4.425 METS. In the first test, I switched to anaerobic energy at 1.9 METS. In the second test, my anaerobic threshold occurred at 0.92 METS. Needless to say, this is abnormally low!

The real value of METS is in understanding the energy cost of activities relative to each other. The Compendium of Physical Activities is a list of the METS of numerous activities, and provides a way to look at the intensity or work capacity needed for those activities. When I took the METS results from my test and applied it to the Compendium, I was shocked to see the kinds of activities that are outside my functional capacity.

As I said, my absolute maximum capacity is 5.9 METS. This means I should not attempt any activity over that limit. Examples of activities out of my reach include scrubbing a bathroom with vigorous effort (6.5 METS), moving household items upstairs (9.0 METS), carrying 16-24 pounds up stairs (6.0 METS), or shoveling snow (6.0 METS). Many of the activities are things that I have long since given up on ever doing again, such as hiking (7.8 METS) or swimming slow laps (6.0 METS).

It is more shocking (devastating?) to see the activities over my functional capacity at my anaerobic threshold. On the first test, my AT occurred at a METS of 1.9. This means that any activity over 1.9 METS requires me to rely on anaerobic metabolism. As a result, I can’t sustain those activities for very long and I experience severe and disproportional fatigue afterwards. So I have to be very cautious with those activities, even on non-crash days. What kinds of activities are over the 1.9 limit?

  • mild stretching (2.3 METS)
  • Hatha yoga (2.5 METS)
  • general kitchen activity (3.3 METS)
  • light cleaning (2.5 METS)
  • washing dishes (2.5 METS)
  • cooking, moderate effort (3.5 METS)
  • changing bed linens (3.3 METS)
  • container gardening (2.3 METS)
  • light weeding (3.5 METS)
  • playing piano (2.3 METS)
  • showering (2.0 METS)
  • walking at a slow pace (2.8 METS)

These are basic tasks of living. Some of these I don’t have to attempt (like changing bed linens) because I am fortunate to live with a helpful husband. But if I lived alone? I know so many patients who live alone and have to expend all their energy just doing the basic chores of daily living, and then spend time recovering from them. The METS limit also helps explain why walking at a slow pace has been so difficult for me. I can do it for a short time, but with caution and the risk of crashing. Now I know that it is over my AT limit of 1.9 METS, so OF COURSE it is difficult for me.

Not surprisingly, the activities I spend the most time on are under the 1.9 METS limit. Sitting and watching tv (1.3 METS), reclining while reading (1.3 METS), and knitting (1.3 METS) are all in that safe zone. But as my exercise report noted, when I am crashed my AT occurred at < 1.o METS, which means lying down and doing nothing, or even sleeping, is at or above my limit. The other important thing to note is that METS and the Compendium are both focused on physical activities. I have found no way to measure cognitive load or capacity.

A healthy person spends most of her time under the anaerobic threshold, even while exercising. When she finally crosses her AT, she experiences the rapid onset of fatigue and will stop the activity and rest. And even if she reaches her maximum oxygen consumption and bonks, she will recover to normal within a day or two.

My exercise test shows that my entire energy system is broken all along these stages. I spend most of my time over my anaerobic threshold, except for when I am sitting and reading or knitting. Because I spend so much time over my AT, I have become accustomed, even immune, to increasing fatigue and the signals to stop and recover. And I bonk on a regular basis, without ever approaching my VO2max.

In the last year, I have had to examine all of my activities and modify where I could to try and accommodate these limits. But I don’t live in a world where I can stop washing dishes and cooking and showering. I don’t want to give up slow walking or baking or light gardening just because it is over my AT. Over many months, I have used the heart rate monitor, METS Compendium and a perceived exertion rating of “somewhat hard” to control my physical activity levels. I know it is not practical (or desirable) for me to live below the AT/1.9 METS limit. But I have really struggled to find the right balance between the two extremes of never getting off the couch and cooking/gardening/walking until I bonk. It seems like there should be a big slushy middle ground, but I have struggled to find it.


Requesting an Investigation

June 18th, 2013 8 comments

You may recall that at the May 23, 2013 CFS Advisory Committee, voting members Eileen Holderman and Dr. Mary Ann Fletcher stated on the record that they had been intimidated for expressing their views. With assistance from two fellow advocates, I have a transcript of this portion of the meeting. Neither Chairman Dr. Gailen Marshall nor Designated Federal Officer Dr. Nancy Lee made any public comment about these allegations at the meeting or afterwards. No concern was expressed, and no investigation was promised.

The purpose of an advisory committee is to collect the advice of a diverse group of experts. The Federal Advisory Committee Act is designed to maintain a balance of points of view, and ensure that a committee hears public input and discusses issues before the public. If any voting member has been intimidated or threatened with removal from the committee for expressing an opinion then the entire advisory committee process has been undermined. If the intimidation was perpetrated by a federal employee, then there is a very serious problem.

Let me be clear: I do not know if these allegations are true. I do not know who threatened Dr. Fletcher with removal from the committee for expressing her views. I do not know what was said that made Eileen Holderman feel intimidated. But I don’t have to know the details. Two voting members have alleged that they and an unknown third member have been intimidated or threatened. Those allegations are very serious, were made on the record, and must be investigated.

Accordingly, I have joined with twelve organizations and twenty-three advocates to request that the General Counsel of DHHS investigate these allegations. The allegations are too serious to be swept under the rug and never mentioned, like it’s a dirty little secret. The public has a right to know if the allegations are true, and we have a right to see corrective action taken if that is required. The letter takes no position on whether the allegations are true. All we ask is that a proper investigation be conducted by the General Counsel’s office. You can see the letter here, and the text follows below:

Dear Mr. Schultz,
On behalf of the undersigned organizations and individuals, I am writing to request your immediate investigation into alleged intimidation of three voting members of the Chronic Fatigue Syndrome Advisory Committee (CFSAC), a Department of Health and Human Services advisory committee housed within the Offrce on Women’s Health. As organizations and advocates serving patients with Chronic Fatigue Syndrome (CFS), we have a longstanding interest in federal policy regarding CFS.

At its most recent public meeting on May 23,2013, voting member Eileen Holderman stated that Dr. Nancy Lee, the Committee’s Designated Federal Officer (DFO), had intimidated her and two others. Voting member Dr. Mary Ann Fletcher stated that she had been threatened with eviction from the Committee for expressing her views. The third member subjected to the alleged intimidation was not identified. We have enclosed a transcript of portion of the meeting during which these allegations were made, and highlighted the allegations on pages 3 and 4.

The independence of the CFSAC and the balance of views among the membership are essential to its advisory role. Threats or intimidation of voting members for expressing their views, particularly by the DFO, would materially impair the CFSAC’s ability to formulate recommendations to the Secretary. Despite the seriousness of these allegations, neither Dr. Lee nor Chairman Dr. Gailen Marshall made any public comment, nor did they promise to look into the allegations or take corrective action.

Therefore, we must ask you to investigate these allegations immediately, and establish whether any voting member of the CFSAC has been intimidated or threatened for expressing their opinions.

Thank you for your prompt attention to this matter.


Mary Dimmock, for the undersigned organizations and individuals


Sometimes It’s One of Those Times

June 11th, 2013 13 comments

Sometimes, life just vomits in your lap. One thing after another goes wrong, and you feel like you’re juggling roaring chainsaws while pedaling a unicycle.

Or maybe that’s just me.

2013 has been challenging, to say the least. I’m fully aware that things could be much much worse, but it has been a struggle to keep my spirits (and those chainsaws) up. ME/CFS advocacy has been a whirlwind this year, from Public Citizen to the FDA meeting to becoming an FDA patient representative to monitoring the CFS Advisory Committee to researching what’s happening at NIH. All of those efforts have required time, focus and energy. And then there’s writing this blog. My goal has always been to post twice a week. I have a loooong list of posts I want to write, and I even mapped out a schedule through the end of July. On top of all that, two people in my family have faced potentially life-threatening health problems this year.

I’m not sure how much longer I can keep my balance on the unicycle with the chainsaws.

I guess everyone faces times like this, where life has gotten so crazy that you have to come up with a new approach. The threshold is lower with ME/CFS though, because stress is so toxic to our bodies and because our limitations are so severe. I simply cannot write as much as I would like, or take care of my family the way I would like. I have to keep reminding myself that I am, in fact, disabled and I can’t keep imposing full-strength expectations on myself. The best way to lower your stress is to lower your expectations.

I need to give myself a break, and catch my breath. I need to reorient. I need to rest. This blog is a high priority, but I may not manage two posts a week. I have many more requests for my time and energy than I can fulfill, so that means saying no to someone. And I have to design a sustainable way to move forward. I still haven’t learned to be patient with my limitations, and I hate confronting that part of my reality.

I guess this is just a long-winded way of saying that this is one of those times. Everybody has them. It’s tough. We get through it.


No Facts for YOU!

June 6th, 2013 14 comments

The NIH funding argument is a broken record: Advocates and researchers say, “We want more funding!” NIH replies, “We need more applications!” And advocates and researchers reply, “Your review panel is made up of dentists!”

Back and forth. Back and forth. Dr. Nancy Klimas said at the April FDA meeting that only 1 in 8 of her applications to NIH for ME/CFS research are approved – a 12.5% success rate. In contrast, Dr. Susan Maier (NIH) reported to the CFS Advisory Committee that the 2012 acceptance rate was 18%. To my knowledge, she has not presented data on the historical acceptance rates, but she said at the May 2013 CFSAC meeting that she does have those numbers. Dr. Maier literally begged the CFSAC audience to increase the numbers of applications. Dr. Mary Ann Fletcher repeated the complaint that grants are reviewed by the wrong people. Back and forth. Back and forth.

What truly bugs the crap out of me about this argument is that these are factual questions with factual answers. The historical acceptance rate for ME/CFS grants is something that can be measured, as can the number of applications. Why aren’t we having the discussion based on data? Multiple researchers have said on multiple occasions that there is no point in submitting an application for ME/CFS research to NIH because the CFS Special Emphasis Panel that reviews these applications is not staffed by ME/CFS experts. But again, this is a factual question! Who serves on the CFS Special Emphasis Panels? How many of them are ME/CFS experts? Instead of repeating perceptions, let’s examine the FACTS. I have attempted to do just that, but have been thwarted by NIH policy. It’s time to tell you that story.

Last year, I exchanged multiple emails with Dr. Susan Maier and Don Luckett at NIH in an attempt to get the CFS SEP rosters. Some of those rosters were posted on the Center for Scientific Review website, but most were not. On October 19, 2012, Mr. Luckett emailed me:

We no longer post this roster online due to threats some previous panel reviewers have received. Anyone who wishes to view the roster is advised to submit a Freedom of Information Act (FOIA) request to the NIH FOIA office.

Based on that advice, I filed a FOIA request on November 1, 2012 requesting 1) the complete membership rosters for each meeting or other activity of the CFS SEP for the last ten years and 2) documentation in NIH’s possession relating to threats or alleged threats made against one or more member of the CFS SEP in the last 10 years. My intent was to evaluate the rosters to see how many experts participate, and to understand the nature of these alleged threats. Many readers are no doubt familiar with allegations of threats against certain researchers in the UK, so I think it is important to establish the facts behind the allegations – especially since these allegations are the stated reason for requiring a FOIA request for the SEP rosters.

On February 11, 2013, the NIH responded to my request. They found 94 pages of records responsive to the two requests, but they only sent me four redacted pages. The remaining 90 pages were withheld in their entirety under the FOIA exception for “clearly unwarranted invasion of personal privacy.” Needless to say, I appealed this decision on March 7, 2013. The basis of my appeal is:

The only way for the public to know whether the CFS SEP is staffed with scientists with the appropriate expertise is for those rosters to be public, just as they are for the panels in other areas of research. It is no invasion of privacy to disclose the names of the individuals appointed to this advisory committee. I am not requesting anything that is not available to the public in the case of hundreds of other panels.

Furthermore, there is a significant public interest in documents related to the alleged threats made against previous panel members. Specifically, I was told that these alleged threats were the reason that the panel rosters were no longer available. NIH cannot refuse to release the rosters and then also refuse to release documents that may or may not support that policy decision. It is entirely possible that these alleged threats are merely rumor and hearsay, but there is no way for the public to know if no information is released. Given that the alleged threats are being used as the justification for withholding information that would otherwise be available, and that up until a few months ago was available, the public benefit of accountability and openness clearly outweighs the small potential harm of disclosing these documents.

I am not requesting anything unusual. Review committee rosters at NIH are public. You can go on the CSR website and see the names and office addresses for hundreds of advisory committee members across many disease areas. I’m not requesting special treatment – I am asking for information that is available to other interested members of the public. Instead, not only am I prevented from reviewing the rosters, I am prevented from seeing the evidence that is being used as the basis for denying me the rosters.

As a result, we cannot have a fact-based conversation about the CFS SEP. Is it populated with dentists and non-experts? Or has the composition of the SEP improved over the years? Knowing these facts are critical to a productive dialogue about whether it’s worth the effort for ME/CFS researchers to apply for funding. And because we are denied access to these facts, we are stuck in the back and forth argument of whether more applications will lead to more money. In trying to protect the privacy of reviewers, NIH is perpetuating the perception that ME/CFS grants are reviewed by unqualified scientists.

I am still awaiting the NIH’s response to my appeal.

Updated June 7, 2013: Several people have pointed out that the May 2013 SEP roster is available on the CSR website. This makes the denial of my FOIA request even more ludicrous, and I will be updating my appeal accordingly.


June 3rd, 2013 23 comments

The good news, I guess, is that we survived another CFS Advisory Committee meeting. The bad news is that much of what happened made no sense to me. Some excellent summaries of the meeting are available, including this very detailed recap from Phoenix Rising. I would like to tackle a few of the topics that had me shaking my head, or asking myself if my experience of reality is so at odds with the Committee’s. This post is long, and I apologize for that. Here’s my report card on these head-scratcher issues:

Meeting Mechanics

I know how difficult it is to prepare for and moderate two full days of contentious meetings, and I imagine it is more difficult to do so when the meeting will be held in public. However, I was struck by how poorly some of the administrative aspects of this meeting were conducted. For example, the procedure for meeting and comment registration is unnecessarily complicated for a patient population that struggles with multiple forms of cognitive dysfunction. I hope this can be simplified.

On the first day of the meeting, Dr. Gailen Marshall said that members would be limited to three minutes for comments during discussion. He did not enforce this limit evenly, including on himself. More than one observer noted how long his own comments were, and how he sometimes monopolized discussion. I happen to think that a Chairman needs leeway to cover certain topics, but sometimes this seemed excessive. Participation by other Committee members is very uneven: Eileen Holderman, Dr. Mary Ann Fletcher and Steve Krafchick speak most frequently; Dr. Jordan Dimitrikoff and Dr. Susan Levine fall somewhere in the middle; Dr. Adrian Casillas, Dr. Lisa Corbin, Dr. Dane Cook, and Rebecca Collier rarely if ever spoke. It did seem like the non-voting liaisons were integrated into the discussion, and had opportunities to ask questions and offer feedback.

I was very frustrated by the evident lack of preparation for even simple agenda items. For example, when approving the list of ME/CFS organizations for linking on the Office of Women’s Health website, the Committee did not have a list in front of them and they approved the criteria on Day 2, after approving the list on Day 1. One of the criteria was that organizations would consent to being linked, but on Day 1 Dr. Lee said that was not checked, so the criteria list on Day 2 had to be amended. It was a mess, and hard to follow. A similar lack of preparation was evident in the discussion of the High Priority List, as we’ll see. There is simply no good reason for the lack of preparation. Why didn’t a staff member type up the list of criteria and list of organizations, provide it to the Committee and post as a slide, so everyone knew what they were voting on? The disorganization and confusion wastes time, at the expense of other issues.

One mechanic that worked fairly well, in my opinion, was the audience Question & Answer. The audience questions led to some very significant discussion, especially regarding CDC. Some people feel that Dr. Marshall should not curate these questions, and I thought that the “answer” discussion tended towards domination by the Committee instead of actual answers to the questions. However, I think the value of this kind of interaction was very clear and I hope this will continue.

High Priority Recommendations

From a procedural perspective, we scored a small victory here. Dr. Marshall acknowledged that the list was not handled correctly last year. I pressed the Committee to devote an appropriate amount of time to discussion of the list, and I was shocked when they agreed. I don’t know what happened at lunch, or who said what, but apparently there was enough concern expressed that Dr. Marshall said they would move the discussion to Day 2. They discussed the list and how to use it going forward, and voted on it in public as required by FACA. Procedurally, they handled the issue correctly.

But the substance of their decision is perplexing, at best. No list was posted, and it did not seem like the committee members had a single piece of paper in front of them with the full list. Items were added – but without reading some of the additions into the record – and a process for removing items was discussed but not used. Dr. Marshall downplayed the fact that several recommendations had been altered from the original form, saying that “the spirit is there.” Dr. Lee said that the old recommendations chart would now be a historical document, and the High Priority list would be the working list. Dr. Marshall said that of the eight recommendations the Committee made last year, three were complete and the other five would be added to the list. But he did not specify which recommendations he considered complete, and no one asked him to be specific. I can make a pretty good guess, but we won’t know for certain until the final list is posted.

And amid all this back and forth, Dr. Marshall said that the list was never intended to prioritize one recommendation over another within the list. Everything on the list is of equal importance. No one questioned or objected to this. This may not seem like a big deal, but it is. By acquiescing to this equal priority description, the Committee created a situation where holding a disability workshop is of the same priority and importance as holding a case definition workshop. I don’t think most members would agree with that statement, but now they’re stuck with it.

So what did they select as the high priority recommendations? The Committee combined the original seven recommendations on the January 2012 list, five of the eight recommendations made in 2012, and two recommendations added by Eileen Holderman. These items are listed in chronological order. New recommendations will be added to the list automatically, and the Committee will have to vote to remove an item once they are satisfied with the response from the Assistant Secretary. I’ve drafted my best guess at the specific recommendations they approved (given the lack of precision on the 2012 recommendations), and I’ll post the official version when it becomes available. Is this list ever going to matter? Technically, I think it matters a great deal but I’m not sure the Committee shares that view.

Invisible Information

One of the things I said we should watch for at the meeting was any mention of the Ad Hoc Workgroup. Guess what? They never mentioned it once. This is one of the things that has me questioning if my reality is different from the Committee’s. Dr. Lee made such a point of talking about the Workgroup in 2012, and their report was published in March. But at this meeting? Total silence. It’s as if the Workgroup doesn’t exist. And not a single Committee member brought it up or asked a question. Why? What is the status of this group? What did the Committee think about the report? Did they even READ the report? Am I the only person who thinks this is strange?

The other thing that received almost no attention is the response from the Assistant Secretary to the Committee’s October 2012 recommendations. This was posted to the CSFAC website shortly before the meeting (pdf link). Again, I don’t understand why the Committee doesn’t simply review these at the outset. Instead, the only discussion was when Steve Krafchick objected that the response to the recommendation to hold a case definition workshop was not actually responsive (see the discussion on case definition below for more details).

The risk of ignoring or glossing over the official responses to CFSAC recommendations is that we miss opportunities to understand the basis for those responses. For example, buried on page 3 of the response is this statement: “To date, CDC has not been able to confirm the occurrence of outbreaks of CFS.” This leaves me wondering how in the world CDC characterizes the outbreaks at Incline Village and Lyndonville. But because the Committee does not discuss the responses, these questions don’t get raised. If I write to CDC or submit a question for the next PCOCA call, I will probably be ignored. But a CFSAC member could ask these questions and get answers on the record. Instead, this information – and the opportunity to learn even more – is effectively invisible, and it has no apparent effect on Committee members and discussion.

Oh CDC, You So Crazy

The CDC’s report of activities was ho-hum, dry, and devoid of much of interest. It was not until the Q&A sessions that we actually learned anything important.

The very first question was whether CDC would use the two-day cardiopulmonary exercise testing in phase 2 of its multisite study. Dr. Unger said that the clinicians in the multi-site study felt a two-day exercise test was “not advisable.” She elaborated that patients travel some distance to get to the physicians involved in the study and that a two-day test was not feasible. It was not clear to me whether the concern was the time required or the physical impact on the patients. I was very surprised that the clinicians (Natelson, Klimas, Peterson, Kogelnik, Bateman, Lapp, Podell) were the ones who advised against using the test because most (if not all of them) have used two day testing for some of their patients. Steve Krafchick pressed Dr. Unger, stating the importance of two day protocols for exercise and neuropsych testing in order to objectively capture the effects of post-exertional malaise. Dr. Unger said they would rely on questionnaires for functional outcomes and the clinicians’ observations of clinical course. Krafchick said it was a mistake to eliminate the testing, and asked if Dr. Unger had talked to Dr. Chris Snell. Dr. Unger said, “No.” My jaw hit the floor. How could it be that Unger has never talked to Snell about CPET? They’ve been at meetings together, including the recent FDA meeting where Snell gave a presentation on two-day CPET. I still can’t wrap my brain around this. Two day CPET provides objective evidence of metabolic dysfunction, post-exertional malaise and estimate of disability. CDC, how could you refuse to use this test?!

Another great question for CDC was whether the website would include a highlighted warning that exercise can be dangerous for ME/CFS patients. Dr. Belay answered that the website states exercise can exacerbate the illness, and Dr. Marshall asked about the equivalent of a black box warning. Dr. Belay said they could consider it. Dr. Fletcher followed up with a reminder that the Toolkit recommends exercise as a therapy, and Dr. Belay said CDC has revised the Toolkit and it is going through clearance. My jaw hit the floor again. Why didn’t Dr. Belay think to mention that in his routine report? It’s obviously of interest to the Committee since they recommended last year that the Toolkit be removed from the website. I guess Belay was planning to wait until the revision was complete, because when Steve Krafchick asked if Committee members could see it for review or comments Dr. Belay responded, “Why?” and “we don’t do that.” Seriously? Dr. Marshall pointed out comments could be useful, and Dr. Lee said they could send informational copies to interested members for feedback.

The Committee discussed a review of the CDC website, including the photos which portray people yawning at work, going for slow walks, etc. Several committee members (and many patients) feel the photos are misleading because they do not portray the seriousness of the illness. Dr. Unger responded that they want to portray a “positive” side. Seriously? To be frank, it is conversations like this one that make patients wonder what planet CDC lives on that they think there is a positive or lighthearted side to ME/CFS. The discussion moved into case definition because the CDC website and medical education material lists multiple criteria, including the maligned Oxford definition, even though CDC says it endorses and uses Fukuda. There was more discussion of the 2-day CPET, whether the Canadian Consensus Criteria is difficult to use, and whether there was enough information to endorse the Canadian Criteria immediately as many advocates insist. Unfortunately, and typically, there was no resolution on any of these issues and case definition raised its ugly head again and again.

A Rose By Any Other Name . . . .

So we come to case definition. In October 2012, the CFSAC recommended that the Secretary:

promptly convene (by 12/31/12 or as soon as possible thereafter) at least one stakeholders’ (Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)experts, patients, advocates) workshop  in consultation with CFSAC members to reach a consensus for a case definition useful for research, diagnosis and treatment of ME/CFS beginning with the 2003 Canadian Consensus  Definition for discussion purposes.

And the Assistant Secretary responded in writing on May 1, 2013:

The National Institutes of Health (NIH) is convening an Evidence-based Methodology Workshop process  . . . to address the issue of case definitions appropriate for ME/CFS research. However, it will not cover in detail a clinical case definition. The Office of the Assistant Secretary for Health, Department of Health and Human Services, is actively pursuing options for a separate effort that would work in coordination with the NIH process, but result in a case definition useful for clinicians who see patients with symptoms that may be ME/CFS. . . . .

The EbMW consists of a thorough, unbiased evidence review of the literature related to clinical research outcomes compared across case definitions and culminating in a workshop composed of experts and patients. The workshop participants and panel members will use the evidence review to evaluate the strength of evidence for case definitions with the goal of identifying the most consistent outcomes. . . . The first organizational meeting for the EbMW on ME/CFS was held on February 19,2013. A timeline for the process is being developed.

The wording of the response is very important: the EbMW will address the issue of case definitions appropriate for ME/CFS research. That does not say they will identify the correct or new research definition – just that the issue of appropriate research definitions will be addressed.

These two paragraphs from Assistant Secretary Koh’s response translate as follows: 1) No, we will not have a stakeholders’ workshop as you recommended in October 2012. 2) We will have an EbMW to address definition issues related to research. 3) We are “actively pursuing options for a separate effort” on a clinical case definition.

Understandably, several CFSAC members were upset that the answer was No-but-we’ll-do-something-else. This is what led to the fireworks at the end of Day 2. Several members reacted strongly to Dr. Susan Maier’s report that the unidentified people who attended the meeting on February 9th submitted a list of 35 to 40 potential candidates for the EbMW’s organizational committee to the Office of Disease Prevention for vetting and selection. Dr. Maier could not identify that list of candidates, although she did say that there were CFSAC members and advocates on the list. We have no timeline for publication of this list, either. Dr. Fletcher was particularly vocal about the secrecy and long timeline

I have to say that I am not surprised that the answer was “no, but . . . ” and I’m not knocking the EbMW. Dr. Beth Collins-Sharp from the Agency for Healthcare Research and Quality gave a detailed explanation of the methodology used for evidence reviews, and it is quite robust (and includes a patient viewpoint). I suspect that this is the same kind of evidence review that was requested by the CFSAC years ago in order to have a State of the Science Workshop, and which was never completed. The State of the Knowledge meeting in April 2011 was basically a State of the Science-Light kind of meeting. AHRQ’s last review on CFS was completed in 2002, so it is certainly time for an update.

The problem here is that we don’t have enough information to judge the EbMW process, since we don’t know who is on the organizing committee. We can’t judge the case definition process, since we have absolutely NO information about it whatsoever. And this leads to the real problem: THIS IS TOO SLOW.

As Dr. Wanda Jones reminded us in her welcoming remarks on Day 1, government moves slowly. It does indeed, and this creates extraordinary frustration for every patient and advocate involved. It seems unlikely (at this point, anyway) that the Canadian Consensus Criteria will be adopted as an interim measure, and none of the other case definition processes will bear fruit within the next six months. The government apparently expects us to wait patiently and calmly as this process unfolds at a bureaucratic pace. We don’t have a choice about the waiting part, but I don’t think the expectation that we will be patient and calm is realistic at all. This issue is too huge, too important, too divisive, and too slow. People are angry and will continue to be so, unless the government can demonstrate urgency.

If anyone from HHS is reading this post, may I suggest that you improve the way you communicate around this issue as a first step? The FDA communicated openly with us, and also produced a great meeting. Look to FDA for ways to productively and positively engage the patient advocate community. If you don’t, we are likely to see fireworks of one kind or another at every CFSAC meeting going forward.