Archive for October, 2012

Puzzle Pieces

October 30th, 2012 13 comments

Let’s play a game. Imagine you have a large puzzle that makes an Impressionist picture of a colorful cottage-style garden. You can put it together as long as you have the picture on the box. First you assemble the lower left corner, all lavender and yellow flowers. Another section of red roses sits somewhere in the middle. Near the upper right corner is a section of white and gray paving stones, and you also put together an area of green herbs although you are not sure where it goes yet. This puzzle will take a lot of time to solve, but with the finished image on the box you know that you’ll put it together eventually.

Now imagine the box is gone. All you have is a white/gray blob, and lavender/yellow section, the red rose section and another green blob. The rest of the pieces are all mixed up together, and while you can separate out some edge pieces and consolidate others by color, without the box you cannot even be certain what the final picture should look like. It’s frustrating, isn’t it, to have all those pieces on the table and not see how it fits together or even know for certain that you have all the pieces. That’s the feeling I got reading the American Family Physician’s article on Chronic Fatigue Syndrome: Diagnosis and Treatment. I dissected the AAFP patient information sheet on CFS in a recent post, but now I think it’s important to examine this review article by the same authors. The article attempts to present a finished picture of CFS for family practitioners, but so many pieces are missing that the paper bears little resemblance to the CFS I live with.

Generally Speaking

“Chronic Fatigue Syndrome: Diagnosis and Treatment” by Dr. Joseph Yancey and Dr. Sarah Thomas gives an overview of CFS for family physicians. They review the Oxford and Fukuda criteria, the basic lab workup recommended by CDC, and a list of exclusionary conditions. In a section on etiology of CFS, the authors quickly cover the immune system, genetics, psychosocial, adrenal system, and sleep/nutrition. Finally, the treatment section focuses on cognitive behavioral therapy (they say it works), graded exercise therapy (this works too), nonpharmacological (nothing really helps) and pharmacological treatments (these don’t work either).

In the authors’ defense, there are significant space limitations in the American Family Practitioner journal: 1,500 to 1,800 words in the case of clinical review articles like this one. There is no way to include all the information about CFS that family doctors need in such a limited space. It also appears that neither Yancey nor Thomas are CFS experts, based on the very limited information I could find online. I emailed Dr. Yancey, the corresponding author for the paper, on October 24th with a few questions but to date I have not received a response.

Method Madness

Drs. Yancey and Thomas describe their research methods as follows:

A PubMed search was completed using the MeSH term chronic fatigue syndrome. The search included randomized controlled trials and clinical trials in English from the past 10 years. We also searched the Cochrane database, Essential Evidence Plus, the National Institutes for Health and Clinical Excellence guidelines, and the Centers for Disease Control and Prevention Web site. Search date: August 26, 2011.

This methodology accounts for some of the missing pieces. First, anything published after August 26, 2011 was not captured in the search. That includes the IACFS/ME Primer, NCI’s paper on the risk of cancer among elderly CFS patients, the ME-ICC criteria, and the Rituximab trial. But before we forgive the authors’ oversight of these papers based on the date of their literature search, consider a curiosity I found in the paper references. The authors cite one paper published after August 26, 2011: The FITNET trial of internet based CBT for adolescents with CFS is included as reference Number 27. Does that strike you as odd? If the authors truly limited themselves to the references found on August 26, 2011 then this paper should not be included. Furthermore, of all the papers published after August 2011 to include in a review of CFS treatment and diagnosis, why was a CBT paper the one cherry-picked by the authors?

Even within the boundaries of the search methodology, the authors missed some papers that would have been helpful in their overview sketch of CFS. I attempted to recreate the authors’ search in PubMed, and found more than 1,300 clinical study papers alone. These include all of the letters critical of the PACE study and Tom Kindlon’s many letters and papers on the potential harms and inaccuracies in CBT/GET studies. Other important papers such as the spinal fluid proteome by Schutzer, et al., the differential gene expression post-exercise paper from Light, et al., and the cytokine network modeling by Broderick, et al. were captured in the PubMed search but did not make it into this review paper.

Finally, there are several seminal papers that are not returned in the PubMed search. The Journal of Chronic Fatigue Syndrome published the Canadian Consensus Criteria by Caruthers, et al., in 2003. This case definition is gaining broad acceptance among policy makers and researchers, but it does not show up in a PubMed search because the journal was never indexed in Medline. Another example is the Van Ness, et al. study showing the significance of two-day exercise testing in differentiating CFS patients from controls. This is a critical paper, suggesting a possible diagnostic test (albeit an extremely unpleasant one) for CFS. But because the journal was never indexed, these papers do not show up in a PubMed search and so non-experts like Yancey and Thomas never see them.

Cognitive Bias

I do not know what Dr. Yancey and Dr. Thomas believe about CFS, including whether they believe the illness is primarily psychological in origin. After reading this paper, however, I fear this may be the case. I can best illustrate this through examples.

In the opening paragraph of the article, the authors say “CFS is often mentally and emotionally debilitating, and persons with this diagnosis are twice as likely to be unemployed as persons with fatigue who do not meet formal criteria for CFS.” What about physically debilitating? If the authors recognized the physical disability experienced by many CFS patients, and the physical suffering of all of us, wouldn’t they mention it in this paragraph? This simple omission is a very subtle way to communicate that people with CFS are not physically ill.

There is a brief discussion of the case definition in the paper. According to the authors, the 1988 CDC definition focused on physical symptoms, and the 1991 Oxford definition “emphasize mental fatigue over physical symptoms.” But the criteria, printed as Table 1 in the article, require fatigue to be “severe, disabling, and affects physical and mental functioning.” I’m no fan of the Oxford definition, but even I can see the requirement of physical disability. Again, Yancey and Thomas gloss right over the fact that CFS has serious, physical symptoms.

In discussing the biopsychosocial model of CFS etiology, the authors say: “CFS is often associated with depression, which has led many physicians to believe that CFS is a purely psychosomatic illness. Evidence supporting this conclusion is lacking.” Fair enough. But then they say, “Strong evidence suggests that childhood trauma increases the risk of CFS by as much as sixfold.” Sigh. I covered this in my dissection of the patient information sheet. Childhood trauma may have physical systemic affects, but I am not aware of any evidence showing that CFS patients have higher rates of trauma compared to patients with other illnesses like MS or lupus or diabetes or cancer. In my opinion, it is misleading to single out childhood trauma as a risk factor for CFS in the absence of such evidence.

The authors devote space and attention to CBT and GET studies, and this is understandable given the fact that CBT and GET treatments have received the most study in CFS. CBT “can help persons with CFS recognize how their fears of activity lead to behaviors that ultimately cause them to feel more fatigued and disabled.” It is true that CBT can help patients correct activity avoidance behavior, but in my experience this is a very small minority of patients. Even the CDC, target of so much criticism, does not describe CBT this way. The CDC says: “CBT can be useful by helping them pace themselves and avoid the push-crash cycle in which a person does too much, crashes, rests, starts to feel a little better, and then does too much once again.” This is a more appropriate description of CBT that acknowledges the importance of self-management and the prevalence of the push-crash cycle, as opposed to the activity avoidance highlighted by Yancey and Thomas.

Graded exercise therapy is very controversial for CFS patients, mainly because traditional GET uses a scheduled increase process as opposed to a patient-driven increase process based on symptoms. Not surprisingly, this issue is not discussed in the paper. The authors do mention that a heart rate monitor can be used to avoid overexertion during exercise, but there is no mention of the body of evidence on CFS exercise testing and pacing methods. They even cite a study that suggests improvements in GET do not correlate with increases in exercise capacity, suggesting that GET may actually work by “decreasing symptom-focusing behavior in persons with CFS.” Pacing, the only behavioral technique that truly helps CFS patients, is not mentioned by name, although the authors do say:

Patients should be encouraged to take rest periods as necessary, and to practice relaxation techniques. Although there is no evidence these modalities are effective, they are unlikely to be harmful and may be helpful.

Neither CBT nor GET is curative because it does not target the underlying mechanism of illness. CBT is not curative for cancer or heart disease either, for the same reason. Drawing the conclusion that these therapies are not curative because of the patient is a fallacy, but this is the conclusion that Yancey and Thomas suggest:

Despite the positive results of CBT and graded exercise therapy, the effects are usually moderate and rarely lead to resolution of CFS. Patients with poor social adjustment, a strong belief in an organic cause for fatigue, or some sort of sickness benefit (i.e. financial incentive) tend to have worse responses to therapy. Unlike with many other illnesses, membership in a CFS support group was associated with worse outcomes.

The study cited by the authors in support of these statements is this one from 2002. That study points out its own limitations: it uses the Oxford definition, lost 17% of the patients to follow-up, and did not actually measure the exercise capacity of the patients. But this is the kind of evidence that is sufficient for Yancey and Thomas.

The overall tone, selective quotation, and reference choices give me the impression that the authors believe CFS to be a psychological condition, at least in part. I do not know this for a fact, but if I read only this article about CFS and nothing else, I would believe that it is an emotional problem. It’s not just the amount of space devoted to the psychosocial research. The authors focus on the psychological elements to the exclusion of discussion of physical disability, post-exertional malaise, and the well-documented physiological findings in this illness.

Missing Pieces

There are huge gaps in this paper. Orthostatic intolerance, an issue for most CFS patients, is not mentioned at all. Post-exertional malaise is not explained, and no CFS exercise studies are referenced. The importance of medications and other treatments in managing sleep and pain issues is ignored, and pain is barely discussed at all.

This article illustrates a few pieces of the puzzle, mainly CBT, GET and the psychosocial model of CFS. A family physician reading only this article would not be able to separate chronic fatigue from CFS patients, and would understand almost nothing about the complexity of CFS. I found the tone to be generally hopeless: try therapy and exercise but it probably won’t help you much. Maybe a motivated physician would visit the CDC website (and this illustrates the importance of fixing problems in those materials).

No one will be able to assemble the CFS puzzle using the pieces in this article. Too much evidence is ignored, too much emphasis is placed on the psychosocial pieces, and there is very little information about how to manage the other symptoms of the illness. I know the full picture exists and I can identify the gaps. But a family physician who does not have the picture of the box will not recognize all that is missing and will never be able to assemble the pieces in a way that will help CFS patients.

I fear that doctors will rely on this article to provide the same kind of advice I received from doctors in 1994: keep going to the gym, staying in bed is the worst thing you can do, get some counseling, there is nothing else we can do to help you. This bad advice and hopelessness did not help me, and may have even hurt me by keeping me much more active than my body could tolerate. It was years before I found and received adequate care for pain, sleep, and orthostatic intolerance, and even more years before I found expert help for pacing and activity management. This article will do nothing to change the way doctors treat CFS, and will reinforce the destructive pattern already in place.

Patient Focused Drug Development

October 25th, 2012 7 comments

The FDA hosted a public meeting this morning to discuss the Patient Focused Drug Development (PFDD) initiative. The meeting was available via webcast, and a transcript will be published on the FDA website. CFS is on the list of candidate diseases to be included in this process, so the meeting was of great relevance to us as patients and advocates.

The goal of the Patient Focused Drug Development Initiative is to create a more systematic way for FDA to collect and use patient perspectives on the burden of disease and the risk/benefit ratio of treatments. While patient input is used in a variety of ways in the drug approval process, it is not as systematic and comprehensive as is needed. Dr. Janet Woodcock, the director of FDA’s Center for Drug Evaluation and Research, explained that FDA wants to understand patients’ perspectives on the burden of illness, how it affects daily life, how treatments affect those symptoms and outcomes, and what degree of risk is acceptable for the benefits. Every patient has a different experience of disease burden and tolerance for risk, so collecting single patient input on these questions may not capture the full spectrum of patient experience. The selection of twenty conditions (from the proposed list of thirty-nine) is intended to be a pilot program to help the FDA figure out how best to collect this input more generally.

Dr. Teresa Mullin, Director of the Office of Planning and Informatics, explained that making a determination of the balance between treatment risk and benefit requires an analysis of the condition and the current treatment options. Patients can speak to the clinical manifestations of the condition that have the most significant impact on them, as well as other aspects of the condition that affect daily life. Patients can also speak to how those impacts change with disease progression, and share their own experiences of the current standard of care and all treatments being used (including non-pharmacological treatments). While many of these issues have been considered and discussed from the clinicians’ point of view, it is very common for patients to have a very different view of the symptoms they feel most affect daily life or how well treatments work (or not) over time. Dr. Mullin said that the objective of this PFDD process is to create a systematic way to collect broad patient input and capture it in a usable and useful format to be used by review panels when considering products for approval.

In discussing why the FDA selected the thirty-nine candidate diseases, Dr. John Jenkins, Director of the Office of New Drugs, said that collective patient community input was essential throughout the approval process from the oversight of trials through post-approval safety issues. He pointed out that the patient perspective is very different from that of consumer safety advocates. For example, patients with asthma have a very different risk tolerance with inhaler medications compared to safety advocates who do not have asthma. Several division directors explained why their divisions had proposed specific diseases, including Dr. Theresa Michele from the Division of Pulmonary, Allergy and Rheumatology Products. Dr. Michelle is also FDA’s ex officio representative to the CFS Advisory Committee, and she spoke about the severity of CFS and why her division recommended its inclusion in the PFDD process.

Most of the remaining time of the meeting was devoted to hearing public comment. In an attempt to give everyone time to speak, comments were limited to two minutes but this was not enforced by the meeting moderator. Patients and advocates representing diverse conditions spoke about why their disease should be part of this process, including Alpha-1 antitrypsin deficiency, alopecia, ALS, Alzheimer’s, amyloidosis, arthritis, angioedema, Batten disease, blood cancers, brain tumors, dystonia, gastroparesis, hereditary cancers, inflammatory bowel disorders, interstitial cystitis, kidney diseases, lung diseases, melanoma, migraine,  muscular dystrophy (including Duchenne), and narcolepsy. Four members of our CFS community spoke: Mary Dimmock, Joe Landson, Amy Squires, and Mary Schweitzer.

Several things struck me during all the public testimony. First, I found it heart-breaking to listen to so much suffering. Dealing with CFS, we sometimes have blinders on and I think we forget how many other millions of people are suffering from poorly understood diseases with no treatment and no help. One man with ALS said he would celebrate if he had some of the other diagnoses on the proposed disease list, and did not understand why ALS was missing from the list. A woman with gastroparesis described her suffering in brutal detail, and drew a parallel between her experience and having the stomach flu every day. How many times have we CFS patients described our illness as having the worst influenza every day? It quickly became clear that for all the advances in medical care, there are too many diseases and too many patients and too many families suffering.

Second, a number of advocates pointed out that by selecting individual diseases, FDA had caused a “disease war,” in which groups were competing to get on the list. As an alternative, they proposed hosting PFDD meetings on body systems (lungs, nervous system, immune system, etc) or other factors (such as severity or availability of treatments). They reasoned that the combination approach would allow more diseases to be represented and capture more diverse patient input.

My personal opinion is that this would be a mistake. This is intended to be a pilot process to collect input that will be useful to drug review panels. I do not believe that a systems approach will collect the level of detail on CFS or other illnesses that is necessary for reviewers. How can a meeting on gastointestinal disorders capture a sufficient level of detail on patients with Crohn’s disease and gastropareisis that can be used in the drug approval process for a treatment for only one condition? And what about diseases like CFS and amyloidosis that do not have a single body system “home”? I believe FDA needs to drill down to a fine level of detail in collecting and understanding patient perspectives, so I hope they will not start combining conditions in an effort to cram more disease groups into these meetings.

Your input is necessary now! The public docket to submit comments on the disease list closes on November 1st. If you can, please write to FDA and give your perspective on how CFS meets the following criteria:

  • Disease areas that are chronic, symptomatic, or affect functioning and activities of daily living;
  • Disease areas that reflect a range of severity;
  • Disease areas for which aspects of the disease are not formally captured in clinical trials;
  • Disease areas that have a severe impact on identifiable subpopulations (such as children or the elderly);
  • Disease areas that represent a broad range in terms of size of the affected population
  • Disease areas for which there are currently no therapies or very few therapies, or the available therapies do not directly affect how a patient feels, functions, or survives.

FDA will take several months to review the collected input and decide upon the first twelve diseases for PFDD meetings in 2013 through 2015.

Mary Dimmock’s Comments to the FDA

October 25th, 2012 3 comments

Mary Dimmock presented a shortened version of these comments at the FDA meeting today on the Patient Focused Drug Development initiative. She has kindly given me permission to post her comments in full here.

My name is Mary Dimmock and I am a member of a national alliance of patient organizations and patient advocates representing patients with Chronic Fatigue Syndrome, also known as myalgic encephalomyelitis or ME/CFS.

The popular misconception is that ME/CFS is chronic tiredness due to deconditioning, depression or poor diet. That is what I thought until my energetic, smart, adventurous 23 year old son was struck down by ME/CFS after contracting Giardia while backpacking across Asia. Overnight, he went from academic excellence and scaling mountains to being unable to work, seldom able to leave the house and too often unable to do more than lay on his side in a dark room, in constant pain.

He is not alone. One million Americans of all ages, races and socioeconomic groups and 17 million people worldwide have been struck down overnight by this complex, multi-system disease that causes significant immune and neuroendocrine abnormalities; brain dysfunction and neurocognitive defects; cardiovascular and autonomic disturbances and abnormalities in energy production including mitochondrial dysfunction. As a result, patients suffer devastating functional impairment that results from the profound exhaustion, unrefreshing sleep, joint and muscle pain and cognitive problems that include difficulty thinking, slower processing speed and impairment of memory. These symptoms are exacerbated after even minimal mental or physical activity and can result in a relapse called post-exertional neuroimmune exhaustion that can last hours, days, or weeks. For some, even minimal activities like talking to a friend on the phone for a few minutes, taking a bath or making a meal for themselves can cause post-exertional neuroimmune exhaustion.

The CDC has said that ME/CFS can be as disabling as multiple sclerosis, lupus, rheumatoid arthritis, heart disease, end-stage renal disease… and similar chronic conditions.”  Patients can be sick for decades and many have been sick since outbreaks in the mid-1980s. Twenty-five percent of patients are bed-bound, house-bound or wheel-chair bound. Ten percent of patients are pediatric, some as young as 5. The inability to attend school, play with friends or even participate in family activities during their developmental years has a particularly harsh and lifelong effect on children. Overall recovery is rare and one study found that patients are more likely to die prematurely from cancer, heart disease or suicide.

And yet, today, there are no treatments for ME/CFS that are capable of even minimally improving patient functionality of changing the long-term outcome of the disease. There is only one ‘disease modifying’ drug being progressed through the FDA review process. The lack of agreement on definition, endpoints and how to measure treatment outcomes has impeded drug development. The drugs that are used provide only very limited relief for specific symptoms like pain but have little impact on the overall level of functioning. There are a small handful of experts nationwide who will prescribe antivirals or immune modulators to try to change the course of the disease but most doctors are unwilling to prescribe such drugs. Some of this reluctance is because they do not recognize that for patients, the disease severity warrants the risk.

The resultant reality for many patients is that they will spend every one of the rest of their days in pain, disability and isolation, functionally so limited that they are unable to work, care for their families or even sometimes take care of themselves.

It is time that we peeled back the misunderstanding and looked closely at the severity of this disease, the dramatic loss of functionality that these patients experience and the total lack of approved treatments. It is time we looked at how these patients would view the benefit-risk of a drug that would give them back even a small portion of their lives.

Please include ME/CFS for the one million Americans who suffer from this terrible disease. Please do this for all those sons and daughters who are not yet sick so that they never have to experience the nightmare that my son lives every single day.

FDA Input Sought

October 20th, 2012 7 comments

As part of its commitment under the recently approved Prescription Drug User Fee Act (PDUFA V), the FDA will be conducting an initiative, called the patient-focused drug development initiative, to provide for a more systematic approach to obtain the patient’s perspective on the disease severity and the currently available treatments. The intent is to ensure a thorough understanding of the severity of the treated condition and the adequacy of the existing treatment options.

This initiative will be conducted for each of 20 different disease areas over a period of 5 years. The FDA has nominated an initial list of 39 diseases, including ME/CFS, using the following criteria:

  • Disease areas that are chronic, symptomatic, or affect functioning and activities of daily living;
  • Disease areas that reflect a range of severity;
  • Disease areas for which aspects of the disease are not formally captured in clinical trials;
  • Disease areas that have a severe impact on identifiable subpopulations (such as children or the elderly);
  • Disease areas that represent a broad range in terms of size of the affected population
  • Disease areas for which there are currently no therapies or very few therapies, or the available therapies do not directly affect how a patient feels, functions, or survives.

The next step in the process is for the FDA to gather public input between now and November 1st on which of disease areas should be selected for inclusion in this initiative. Additional disease areas may also be nominated during this time.

Note that initiative is in addition to the ME/CFS FDA stakeholder meeting that Dr. Woodcock, Director of the Center for Drug Evaluation and Research at the FDA, has already committed to.

How can you help:  For ME/CFS, this is an excellent opportunity to help the FDA better understand how ME/CFS affects the patients. Your support is essential to ensure that ME/CFS is one of the 20 selected diseases.

Please send your comments in by November 1 to ensure that the FDA understands why ME/CFS should be selected as one of the 20 diseases.  

Comments can be submitted electronically, or by regular mail to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Make sure you include the docket number (FDA-2012-N-0967).

Further information on the patient focused drug development initiative and the list of 39 diseases initially nominated can be found here.


This. Is. Why.

October 17th, 2012 27 comments

I’m on the verge of tearing my hair out, and I suspect I’m not the only one. The American Academy of Family Physicians published a review article about CFS (paywall) on Monday, accompanied by a patient information sheet. From the very first sentence, this information sheet is a disaster. It packages harmful misinformation for family doctors to share with patients. Let’s take a look:

Chronic fatigue syndrome (CFS) is a disorder that causes you to be very tired.

NO! No it does not! A person with sleep apnea is tired. A nursing mother is tired. A perfectly healthy person studying for the bar exam is tired (ask me how I know). CFS does not make me tired. CFS causes prostration, a medical term that means a collapse from complete physical or mental exhaustion. Using the word “tired” is not only medically inaccurate, it falsely minimizes the severity of my disease and my experience.

People with CFS may have other symptoms, such as poor sleep, trouble with remembering things, pain, sore throat, tender lymph nodes, or headaches.

Can you spot what’s missing? Post-exertional malaise! The generally accepted hallmark symptom of this disease is not on the list. It is the first symptom on the Fukuda criteria list of accompanying symptoms. But it’s not listed here and not explained to the patient.

Not everyone with CFS has all of these symptoms.

I know hundreds of CFS patients. Every single one of us has experienced these symptoms for extended periods of time, if not daily, over the course of years. While it is technically correct that the Fukuda criteria do not require all of those symptoms, it is an oversimplification to simply say we don’t have all the symptoms. And of course all the other symptoms and overlapping conditions are not mentioned at all.

Childhood trauma (for example, physical or sexual abuse) may raise the risk of getting it.

I am aware of two studies that showed a higher prevalence of childhood trauma among CFS cases compared to healthy controls (this one and this one). Here’s the problem: childhood trauma may raise the risk of many disorders later in life. Without comparing the prevalence rate of trauma among other illness groups, there is no way to know if the association with CFS is unique. Are there studies comparing the incidence of childhood trauma among people who develop multiple sclerosis, rheumatoid arthritis, cancer, hepatitis, heart disease or  . . . oh, that’s right. Doing that kind of study in those illnesses might be offensive because those illnesses are real. But we can do those studies in CFS with no problem.

Two treatments can help with CFS: cognitive behavior therapy (CBT) and graded exercise therapy. With CBT, a therapist teaches you about how your thinking affects how you feel and act. With graded exercise therapy, you slowly increase your physical activity, which hopefully increases your function.

You know where this is going, right? Setting aside the arguments about whether CBT and GET studies actually show a benefit, and setting aside how this sort of statement plays right into the mental illness meme, let’s talk about GET. Will GET increase CFS patients’ functional ability? Maybe some patients, but it should be pursued with extreme caution and prejudice. As the work of the Pacific Fatigue Lab and my own exercise testing results show, the energy metabolism systems of CFS patients are severely impaired. We do not make or use energy, or recover from activity, the way other people (including other illness groups) do. Graded exercise must be undertaken very carefully because it takes very little activity to push a patient into a severe crash.

I shudder to think about how family doctors will use this information sheet, and what it will do to the patients who receive it. What is truly remarkable about it is that it bears only a passing resemblance to the full review article and the AAFP’s patient education page on CFS. But this watered down, oversimplified summary of misinformation about CFS will undoubtedly be used, and it is likely to make things worse for patients, not better.

So does anyone – journalists, doctors, policymakers, or other observers – wonder why the CFS Advisory Committee and patient advocates have been begging CDC to fully revise its website and remove the harmful content that filtered into this information sheet?

This is why.

Does anyone wonder why the CFSAC  recommended that the CDC remove its Toolkit from the CDC website?

This is why.

Does anyone wonder why an alliance of organizations and patients wrote a lengthy and heavily referenced position paper in support of that recommendation?

This is why.

Does anyone wonder why there was such vigorous disagreement at the CFSAC meeting about whether professional societies like the AAFP should be invited to participate in revising the CFS case definition?




Update November 2, 2012: Author Toni Bernhard published a great article about the AAFP patient information sheet.

Update October 31, 2012: I’ve also published a detailed analysis of the AAFP review article on CFS.

Blaze of Glory

October 16th, 2012 13 comments

Pacing is . . . actually, my descriptions of pacing generally involve expletives that are not appropriate for this blog, so we’ll stick with “Pacing is challenging.” One positive side effect of my pacing efforts, though, is that I am still celebrating my birthday one month after the fact.

Last week, I went out for a birthday lunch with Friend K. We’ve been friends for 22 years now, and K knew me for four years before I got sick. We went to law school and took the bar exam together, and undertook a mammoth road trip together. When I started dating my husband, K was the first friend I asked to check him out. Hanging out with K is great because she really gets the illness, and so I don’t have to talk about it but I can if I want to. She told me the latest stories about her sons, and generally made me laugh my ass off. For a few hours, I felt like a normal person having lunch with her best friend, and it was glorious.

I also went out for a birthday dinner last week with Friend M. I met M soon after I got sick, and she is another rare gem: a friend who gets it. M and her husband read a prayer at our wedding, and she is one of the most loyal and giving people I know. For my birthday, M took me to one of my favorite local restaurants for dinner and we closed that place down. The meal was sublime, but having M’s undivided attention for four hours was even better. She told me some great stories about her eight year old daughter, including the “court proceedings” in which M has been accused of posing as the tooth fairy. I felt just like the women at the table next to ours, enjoying a girls’ night out with one of my closest friends. These moments of normalcy, of interacting with the world the way I used to, are so rare and precious.

And then there was the payback. The day after that dinner, I was crashed but I didn’t care. It was totally worth the pain and post-exertional relapse. I was still high on the joy of being with my friends. But then I was crashed for two more days, and I started to question the price of normalcy.

My attempts to implement stricter pacing techniques have challenged me far more deeply than I expected. I’m questioning everything now. Before the exercise testing, I was absolutely convinced that having occasional episodes of normalcy was worth the crash days. Outings like these feed my spirit and make me so happy. But now I wonder if it’s the right thing to do. Do I have to give up the last few remnants of my healthy life in order to cope with my sick life? How do I strike the right balance between accommodating my physical limitations and hanging on to who I am? What else do I have to give up in order to live crash free?

I feel like these are deep, existential questions. For 18 years, I have sacrificed my body in order to enjoy occasional outings with my friends, to participate in CFS advocacy, and to take care of my family. If pain and crashing was the price of continuing to participate in my life, I paid it gladly. But is this the right way to balance the equation? Is having dinner with a friend worth three days in bed? Facing that consequence is not fair, and I don’t want my life to be this way. But this is my reality. I need some kind of owner’s manual to tell me how to figure this out. Do I punish my body by exceeding my physical limits? Or do I punish my soul by living within those limits? It’s a no-win situation, and I don’t know how to answer these questions any more.

Another CFSAC Done Gone

October 6th, 2012 16 comments

The CFS Advisory Committee held its second meeting of the year on October 3-4, 2012. Last time, I organized my summary around the good, the bad, and the WTF moments. This time, I am organizing around the discussion themes. Overall, I felt this meeting was more substantive than in the past. There were even hints of introspection and data driven discussion.

Agency Updates

Assistant Secretary Dr. Howard Koh attended the opening of the meeting, and provided an update on the Department’s efforts since the last meeting. I was watching the meeting via webcast, and my feed froze during Dr. Koh’s comments. However, the portion I did see contained nothing new. Dr. Koh did not provide any details on the Ad Hoc Working Group beyond what we already know. Unlike previous meetings, he did not take questions from the members. Although he said “the committee has gotten stronger,” he did not announce the appointment of a new member to replace Dr. Rose. The committee bylaws require vacancies to be filled within 90 days, so the failure to appoint a replacement is a violation of the bylaws.

Both the FDA and Social Security Administration gave substantive presentations to the Committee. In my opinion, this was the high point of the meeting. Both Dr. Sandra Kweder (FDA) and Arthur Spencer (SSA) provided detailed information about their agencies and CFS related data. Dr. Kweder reported on the status of nine investigative new drug applications for CFS. Mr. Spencer provided disability data that the committee has been requesting for years. The overall approval rate for Social Security disability among cases where CFS is the primary diagnosis is 21%, in contrast to a national overall rate of 30%. I’m looking forward to seeing the slides from both these presentations because there was a lot of good information in them.

NIH and CDC also gave detailed updates. Dr. Susan Maier (NIH) reported that several new members were added to the Trans-NIH ME/CFS Working Group, including Dr. Harvey Alter. It’s very good news that Dr. Alter is staying involved in CFS despite the end of XMRV. Dr. Maier also provided (for the first time) data on the acceptance rates for CFS-related grant applications. The overall success rate is 25%, and in FY2012 the success rate is 18%. These rates are higher than the overall rate across NIH. Most of CDC’s report was focused on various education initiatives including CMEs offered through Medscape and CDC, as well as video of patient vignettes for the MedEd Portal that will be finished next year.

That ToolKit

CDC announced that after extensive debate, they have decided not to remove the ToolKit from the CDC’s website. Dr. Beth Unger said that they believe it should be available until it can be updated to reflect the other website revisions. Surprisingly there was little fanfare or reaction to this announcement. At its June meeting, the CFSAC had recommended that the ToolKit be removed. Dozens of patients testified in June and at this meeting that the ToolKit is harmful misinformation, and a coalition of groups and individuals submitted a detailed position paper to CDC in support of that June recommendation. Despite all that, the CDC has decided to keep the ToolKit. There was no pressure or reaction on the record from CFSAC members. No one asked why this decision was made, and no one besides Mr. Steve Krafchick pointed out that CDC is ignoring the CFSAC recommendation. CDC got off very lightly on this score, and I still can’t believe that no one raised a stink about it.

Chicken, Meet Egg

As I said above, Dr. Maier presented data on the approval rates for CFS applications to NIH. In light of that data, Dr. Gailen Marshall asked the committee why they thought NIH funding was so low. The high approval rate suggests that the problem is not NIH’s willingness to spend money but that there are few applications coming in. Dr. Mary Ann Fletcher spoke frankly about the perception in the research community that it is extremely difficult to get funding. She cited an unnamed researcher who left the field because of it, and pointed out that Dr. Nancy Klimas is quite successful in her applications for HIV and Gulf War Illness funding but not CFS. Eileen Holderman pointed out that the illness name, and particularly CDC’s definition and use of the name, dilutes our disease into simple chronic fatigue. This discussion tied in nicely with public comment by Matthew Lazell-Fairman and others that the decades of neglect and active denigration of the disease by CDC and other federal policy makers has created the climate where researchers believe they will not get funding. This circular discussion recurs at every single CFSAC meeting, but this time it led to the recommendation of creating a CFS study section at NIH.


Biomarkers in CFS was a recurring theme on both days of the meeting. Dr. Jordan Dimitrikoff gave a presentation on the challenges faced by those studying Chronic Pelvic Pain Syndrome to identify biomarkers, not just for diagnosis but also to generate hypotheses about potential treatments. This is very similar to the approach of several CFIDS Association grants, in which a symptom or biomarker is queried to identify a possible drug to address that symptom or marker. Dr. Dimitrikoff acknowledged that the “true experts are the patients,” and he advocated setting aside cognitive bias to evaluate data and create learning networks. Dr. Fletcher then presented data from her research with Dr. Klimas and Dr. Gordon Broderick which identified different gene expression profile networks in CFS and Gulf War Illness patients, especially in immune pathways. This presentation complemented Dr. Dimitrikoff’s nicely, giving very specific examples of how biomarkers could lead to identifying potential drug treatments.

Discussion covered several very important points. First, that the case definitions are producing too much variability among patients. Without animal models, it is very difficult to study patients in a meaningful way without narrowing down the clinical presentation. Second, biomarkers must be distinctive in order to be useful. It is not enough to distinguish healthy controls from CFS patients. Biomarkers must distinguish between CFS and other chronic inflammatory conditions. In other words, if a biomarker cannot distinguish CFS from rheumatoid arthritis or lupus then it is of less utility than one that can. This has implications for both diagnosis and treatment trials.

Dr. Kweder’s presentation on the FDA and CFS treatment trials focused on the importance of outcome measures in order to quantify whether a treatment is having an effect. Outcome measures are not necessarily biomarkers; for example, there is no biomarker for migraines. But the more objective and quantifiable an outcome measure is, the more useful it is in clinical trials. Dr. Kweder pointed out that CFS has no single accepted case definition, no quantifiable way to measure symptoms and no biomarker for disease presence or activity. These are barriers to clinical trials, and partially to blame for the lack of trials in CFS. Dr. Kweder cited fibromyalgia, irritable bowel syndrome and depression as examples of conditions that received more clinical trials when those barriers were addressed. The FDA stakeholders’ meeting in spring 2013 will focus on identifying valid reliable outcome measures for CFS clinical trials.

There is a significant difference of opinion about whether we already have biomarkers and outcome measures for CFS. Dr. Fletcher and others cited a variety of measures already in use by researchers and clinicians. Dr. Fletcher was adamant that biomarkers did not need to be exclusive to CFS in order to be useful. Dr. Kweder said that a quantifiable biomarker or outcome measure must correlate to how the patient feels or fares. She also noted that heterogeneous conditions need larger clinical trials, so identifying subgroups can help target a treatment to those it is most like to help.

Case Definition

This is such a controversial topic, perhaps I should not expect a discussion of it to go smoothly, but the committee struggled once again to chart a way forward. Dr. Nancy Lee said that the case definition issue was discussed in at least one meeting with Secretary Sebelius, and that the Secretary was clear that the case definition must come from the medical community. Dr. Lee said that a recommendation from the committee that the Secretary endorse or adopt a specific definition will go nowhere. Dr. Marshall tried to focus discussion on designing a process that would produce a definition, but the committee quickly got snarled in the complexity of the problem.

One of the most contentious issues was whether the medical community has already endorsed a definition. Mr. Krafchick pointed out that the IACFS/ME used the 2003 Canadian Consensus Criteria in writing the Primer, and that it was the body of experts in this condition. Dr. Lee argued that the entirety of the medical community needed to endorse a definition, and Dr. Fletcher countered that this was not only unrealistic but was not a standard applied to any other illness. The root of this disagreement is the status of the IACFS/ME versus other medical societies. When the American College of Rheumatology endorsed a definition of fibromyalgia, the rest of the medical community accepted it because the ACR is a defined sub-specialty of medicine. Dr. Marshall drew a sharp distinction with the IACFS/ME, which is not a sub-specialty that offers board certification, and insisted that the American Colleges must have input into the definition in order for it to be widely accepted. This led to another vigorous argument over whether ME/CFS experts should address the definition or if non-experts should be invited to provide input and endorsement. The committee split over this, and in the end voted 5-4 (with one abstention) in favor of limiting input to the ME/CFS experts at this stage.

The other thorny question was whether to start with one of the existing definitions (Fukuda v. Canadian Consensus 2003 v. International Consensus 2011 – and different members referred to these papers by different names which made it even more confusing) or start from scratch. Dr. Dimitrikoff and Dr. Dane Cook recommended learning from definition processes in other illnesses such as lupus or IBS. Dr. Ermias Belay and Dr. Unger from CDC both advocated for a data driven process, relying on their multisite study that should be completed next year (although they did not promise a finished paper next year). This led to frustration among Dr. Fletcher, Mr. Krafchick and others about delay and the need for immediate action and leadership. After much wrangling, the committee settled on the 2003 Canadian Consensus Criteria as the starting point for a process to produce a clinical definition (see text of recommendation below).

One thing that got lost in this discussion was the role of patients. My impression from the preliminary discussion on October 3rd was that Dr. Marshall and others recognized patients as important stakeholders in this process. But the role of patients was not discussed on October 4th,  and the final text of the recommendation did not specifically include or exclude us. I don’t think it is an exaggeration to say that there will be hell to pay if patients are excluded from the process of creating a new case definition.

Committee Effectiveness

At the end of the first day, Dr. Marshall invited committee discussion on recommendations or other issues for the next day’s session. This led to a discussion of how effective the Committee is in its work. Dr. Lisa Corbin and Mr. Krafchick expressed concern about the committee’s recommendations not receiving feedback or action. Dr. Lee stated that a response to the June recommendations is still in preparation, to which Mr. Krafchick noted that 111 days had passed since that meeting. It was also clear, once again, that members are not receiving materials related to the meetings. Dr. Krafchick had not seen Assistant Secretary Koh’s letter in response to the November 2011 meeting, and was told that “it’s on the website.” Does this mean that such key documents are not sent to members, or that they are not even notified when such information is posted to the website? Members were asked to read several articles in preparation for the case definition discussion the next day (again suggesting that they were not sent in advance), but the existing CFS case definitions were not among them. To be frank, I think it is appalling that more preparation is not done for these meetings and it clearly hampers the effectiveness of discussion. I also wish that members would give more thought to the phrasing of their recommendations in advance. The editing-by-committee process at the end of each meeting is frustrating to watch, and a little more care in proposing motions might help with that.

Final Recommendations

These are the recommendations to the extent I was able to capture the language. The final version may vary slightly:

  1. CFSAC recommends that the Secretary promptly (before 12/31/12 or as soon thereafter as possible) and in consultation with CFSAC members convene at least one stakeholders (ME/CFS experts) meeting to examine the Canadian Consensus case definition (Carruthers, 2003) and its utility for diagnosis and treatment of ME/CFS.
  2. CFSAC recommends that there be a standing committee for review of ME/CFS proposals at NIH.
  3. CFSAC recommends that NIH issue an RFA of $7 to 10 million to establish outcome measures, including but not limited to biomarker discovery and validation, in ME/CFS patients. (Note: This replaced a recommendation limited to just biomarker discovery and validation passed by the committee during the same discussion.)
  4. CFSAC recommends to the Secretary that she endorse the Coalition 4 ME/CFS option 1 proposal for the ICD10-CM that was recommended at the 9/19/12 NCHS public meeting. (Note: The committee passed this recommendation despite advice from Dr. Nancy Lee (DFO) that the Secretary would not intervene in the ICD10-CM process.)
  5. CFSAC recommends that the Secretary allocate specific funds to study cluster outbreaks of ME/CFS.
  6. CFSAC recommends that the Secretary allocate funds to study the epidemiology of patients with severe ME/CFS.
  7. The members also voted unanimously to send a thank you letter to President Obama.


October 3rd, 2012 6 comments

I delivered the following testimony via telephone to the CFS Advisory Committee on October 3, 2012.

I would like to note something that Dr. Nancy Lee said today: “Nothing about me without me.” That’s what we’re asking for. FDA is moving in this way. We want HHS and its agencies to do so as well. Do nothing about me without me. Take our input. Leverage our expertise. We are highly motivated to assist you.

Even the newest members of this Committee have heard enough testimony from patients to recognize the despair that comes from living with a disabling, incurable disease that is barely recognized by most healthcare providers. My fellow advocates have spoken eloquently about the grinding isolation, pain and despair that they endure day after day.

But no one talks about the despair engendered by these meetings and the work of this Committee. I have heard many patients say that they don’t believe this Committee will ever help them. That there is no point in following your work because the government does not listen to your recommendations. There are patients who have abandoned the hope that this Committee will produce meaningful change. Their lives are the same, day after day, and they believe that all this Committee does is talk. After each meeting, and even today, I’ve observed a surge in frustration, disappointment and despair among my fellow advocates because another opportunity for progress has been lost.

Everyone at the table today has invested many hours in the work of this Committee. Regardless of your good intentions and engagement in these discussions, what matters to patients is meaningful change. If good intentions were all that was needed, we would have been cured long ago. Patients are looking for concrete progress, and they don’t see it here.

What do I mean by concrete progress? Performance measurement and metrics are buzzwords, but it all comes down to measuring change. Dr. Maier’s slide on the approval rates for ME/CFS proposals to NIH is an excellent example of this. Another hypothetical example is that NIH says that there are not enough ME/CFS research applications coming in to justify an RFA. But what if we could measure progress on that? First, we would need to know how many applications would be enough; that would be the goal. Then at each meeting, NIH could report on how many applications had been received in the previous six months. We could see whether the number of applications was increasing or decreasing over time, and we would know exactly how far we were from reaching the goal. This type of goal setting and progress measurement could be repeated across all the domains of this Committee. In my experience, knowing where you stand relative to a goal naturally leads to more targeted action.

But we don’t measure progress that way right now. The only goals we have are your recommendations, and the only measurements we see are the responses noted in the Recommendations Chart, which has not been updated since November of last year. And this is why we despair after each meeting – nothing is changing in our lives and we can’t identify what progress is being made, if any, through this Committee.

In the absence of metrics from your side of the table, I thought I would share with you my own metrics. I tracked a variety of things in my day-to-day life in order to share some concrete numbers with you.

  • 111 days have passed since your last meeting
  • I have been disabled for all of those days
  • I left the house a total of 21 times, typically for three hours or less
  • 5 of those outings were for healthcare visits
  • I had an additional 9 email and phone exchanges with my healthcare team
  • I paid to have groceries delivered 7 times
  • I paid to have my house cleaned 7 times
  • My doctors currently prescribe 9 different medications for me
  • I took a total of 1,554 pills since your last meeting
  • I had 4 episodes of tachycardia and near fainting
  • There were 14 days since your last meeting when I could not get out of bed
  • I could not drive a car at all
  • I could not take a walk at all
  • This Saturday is the 18th anniversary of the day I got sick. If I had given birth on October 6, 1994, that child would now be an adult.
  • ME/CFS ripped into my life 6,567 days ago. I could have spent those days building my legal career or writing books, or maybe both.
  • Instead, for 6,567 days I have endured every insult and change that ME/CFS has thrown at me.

These are my metrics and this is my charge to you: Show me progress. Show me measurable change. Make a difference so that I can stop counting how many days and how many ways ME/CFS is destroying my life.

Meeting This Week

October 1st, 2012 3 comments

UPDATE: You can watch the meeting via webcast OR you can call in to the meeting in listen-only mode at  1-866-761-7202. Passcode: 3117619.


The CFS Advisory Committee will meet on Wednesday and Thursday this week. The registration deadline for attendance and for public comment has passed, but I’ve collected some important links for you. I will be watching the meeting (and I hope you will too!) and will publish a summary on Friday.

  • The Federal Register notice for the meeting indicated:  “The meeting will be live-video streamed at  . . . Listening-only audio via telephone will be available on both days. Call-in information will be posted on the CFSAC Web site.” The video link is not working, Update: the link is now working but still no call-in information has been posted yet.
  • The agenda for the meeting was posted after the deadline for comment registration had passed.
  • Public comment is scheduled for both days of the meeting, and will include comments from Lori Chapo-Kroger, Mary Dimmock, Pat Fero, Sue Jackson, Matthew Lazell-Fairman, Alexander Lopez-Majano, Denise Lopez-Majano, Jadwiga Lopez-Majano, Matthew Lopez-Majano, Billie Moore, Faith Newton, Matina Nicholson, Donna Pearson, Amy Squires, Charlotte von Salis, and me.
  • For background on how the committee functions, check out my post CFSAC Basic Facts.
  • Hopefully we will hear an update on the Department of Health and Human Services Ad Hoc Working Group.
  • I am continuing to investigate the committee’s membership background, including who nominated them and profiles of new members Dr. Adrian Casillas and Dr. Lisa Corbin.
  • One member of the committee resigned shortly after the meeting in June 2012. The committee bylaws (not currently available on the website) require a replacement be appointed within 90 days but there is no indication on the agenda that a new member will be sworn in for this meeting.