“CFS and ME is a serious disease or set of diseases for which there are currently no FDA approved therapies” ‘Voice of the Patient’ Document
The FDA’s Patient Focused Drug Development Initiative marks the first time the FDA is implicitly
The Chronic Fatigue Syndrome community spoke and the FDA really listened…
including patients narratives and needs into their drug development process. Designed to more “systematically gather patients perspectives on their conditions and available therapies,” the Initiative was one response to Congress’s concern that chronic illnesses were being left out.
How the Initiative will ultimately affect drug development remains to be seen, but, in as misunderstood a disorder as ME/CFS, simply having the FDA listen to ME/CFS patients and then accurately report on what they said is a big step forward.
The good news is that the FDA really listened. The ‘Voice of the Patient’ document they produced emphasizes the costs (severity) of this illness, and cites the same two major symptoms (post-exertional malaise, cognitive problems) as the Canadian Consensus Criteria (CCC). If the IOM contract goes forward, this ‘Voice of the Patient’ document provides validation by an important branch of the government of key aspects of the CCC.
The FDA’s frequent statements, both in this document and elsewhere, acknowledging that they consider chronic fatigue syndrome to be a serious disorder on the order of heart disease and kidney failure, make it more and more difficult to continue to push the severity of this tragically misnamed disorder under the rug any more.
No one who sits through patient testimonies at CFSAC can help but be staggered by the problems many people with ME/CFS face, or the emotional and financial costs this illness produces. At CFSAC patients are, for the most part, preaching to the converted. The FDA Stakeholder’s meeting gave the chronic fatigue syndrome community a chance to talk to an entirely new audience – an audience desperately in need of hearing the real facts. This document suggests that audience heard them.
Key Themes
“The patient input … strengthens our understanding of the burden of CFS and ME on patients …”‘Voice of the Patient’ Document
That the key themes the FDA laid out are in fact the key themes of this illness suggests the FDA listened well.
The FDA highlighted the knock-out punch that felled so many people with ME/CFS so quickly
Acute Onset – The first theme the FDA mentioned is one of the most striking aspects of this illness – the fact that many people can remember the day they got ill. This sudden onset is just not just interesting, but scientifically relevant as well. The fact that the FDA put this theme first – a theme that can only be intellectually intriguing to the medically community – was encouraging.
Huge Loss of Functionality – The FDA noted that many people with ME/CFS “were formerly highly successful and productive professionals or students … who now struggle with even the simplest aspects of day to day living.”
Key Symptoms Outlined – “Of over 50 symptoms identified, the most frequently mentioned included severe fatigue or exhaustion, impairments in cognitive functioning (e.g., concentrating or processing information), chronic pain, sleep difficulties, blood pressure drops and dizziness, sensitivity to light, sound and temperature, and susceptibility to infection.”
The Key Symptom in Chronic Fatigue Syndrome Highlighted – The FDA highlighting of PEM, again suggests that they heard and picked up on a key aspect of ME/CFS: ”Post-exertional malaise refers to crashes that exacerbate symptoms that are often caused by even minimal exertion. They can last for days, weeks or even months.”
Treatments Desperately Needed – People with ME/CFS have tried many treatments, often without success. “Patients are desperate for research and development of treatments that can: (a) better relieve their most significant symptoms and (b) address the underlying cause(s) of their disease.”
Devastating Effects on All Aspects of Life – “CFS and ME takes a devastating toll on the lives of many patients and their families, including loss of careers, decreased quality of family life, social isolation, and feelings of hopelessness.”
Panel Discussion
In the overview of the panel discussion, the FDA emphasized that patients reported ME/CFS being much more than about fatigue, again highlighted the cognitive and post-exertional problems, reported that crashes can be triggered by even minimal exertion, and that abrupt onset often occurred after some sort of systemic infection.
Symptoms
The FDA highlighted three categories of symptoms: cognitive symptoms, physical symptoms, and post-exertional malaise/crashes.
The FDA suggested that cognitive and neurological symptoms were the most distressing found in ME/CFS
Cognitive – The FDA gave first place to cognitive and neurological symptoms which they suggested, based on a show of hands, were the most debilitating. (Personally, I would disagree with that . Fatigue/PEM is much more debilitating for me, but then again I’m a lot healthier than most.)
After listing the many different types of cognitive symptoms found, the FDA noted that some formerly very successful people reported an inability to conduct basic activities such as reading or writing, that concentration periods could be very short, decision-making was ‘very stressful’, and communicating could be very difficult.
Physical – Severe fatigue and exhaustion and weakness lead a long list of physical symptoms, with “many participants” reporting they were unable to stand for long or walk “even a few blocks” or sustain activities for long. The FDA categorized symptoms according to how frequently they were perceived to have occurred.
- “Many participants” reported problem with sleep (insomnia, unrefreshing sleep, etc.), chronic pain (headaches, migraines, nerve pain, stomach pain), sore throats, hypersensitivity to light, sound, and other stimuli.
- Some people reported orthostatic intolerance and similar symptoms (dizziness, spatial disorientation, and gastrointestinal symptoms.
- A few reported problems with depression, fear and anxiety – “not as a symptom, but as a consequence of the devastating impact of the disease.” (Note that depression, fear and anxiety – all common outcomes of chronic illnesses – were at the bottom of the list.)
Post-Exertional Malaise
Some patients expressed the expectation and “legitimate fear of what happens when we overexert ourselves” knowing that “you will pay for it.”’Voice of the Patient’ document
The FDA – listening closely – gave the most attention to post-exertional malaise and the problem of ‘crashes’. Recognizing that PEM, more than anything else, defines the chronic fatigue syndrome experience, they dug more deeply into this symptom than any other.
It was the ‘collective experience’, the FDA said, of ‘acute, debilitating PEM’ that the audience gave the most attention to.
The FDA considered post-exertional malaise to be the key symptom in ME/CFS…
It was gratifying to hear this for two reasons: One, the CCC, ICC and Pediatric Definition of ME/CFS agree. Two, the degree of post-exertional malaise found in ME/CFS is different from other disorders.
The fact that this term, which was coined by the ME/CFS community, has entered the lexicon of the medical community attests to that fact. (The first record of it in Pubmed is a 1994 paper by Dr. Komaroff.) Fibromyalgia has fibro-fog, cancer fatigue has ‘chemo-fog’, ME/CFS has ‘brain-fog’ – three similar terms to describe the similar cognitive issues found, but only ME/CFS has PEM or post-exertional malaise, and only in ME/CFS do ‘crashes’ make up such a major part of the illness.
Eskimos have different words for the many different types of snow; people with fibromyalgia have wonderfully descriptive terms for pain, and the chronic fatigue syndrome community’s ‘snow’ is ‘crashing’ – a wonderfully descriptive term in itself. ME/CFS patients described complete exhaustion, collapse, intense physical pain, incoherency, blacking out, memory loss, flu-like symptoms, being like a ‘brick’, feeling like their heads were ‘going to explode’, and the need for total darkness.
The fear caused by the unpredictability of crashes, the surprisingly mild exertion needed to provoke a crash, how the ‘postness’ of PEM can vary from minutes to days, were all noted by the FDA. It is interesting that the section on triggering crashes did not mention exercise, but poor sleep, stress, infection, and weather changes were mentioned. While crashes are a core part of ME/CFS, the FDA acknowledged that their duration and degree of severity ranges widely.
Impact
Impact is an important topic, as disorders with greater impact (and more unmet needs) are given some breaks in the FDA drug review process. A drug to treat lupus, for instance, which did not meet its endpoints at years end was nevertheless approved because of the dearth of treatment options available for that disorder.
FDA clearly understood the impact ME/CFS causes: they cited the ‘severe limitations’, the loss of careers, the need to take less fulfilling and less responsible jobs, the disability, the physical and social isolation, the inability to make plans given the illness’s variability, the ‘harsh financial’ losses, and, finally and fittingly, the feelings of ‘hopelessness, emptiness and despair’ that that these impacts can produce.
Treatment
The FDA began by noting how ‘striking’ the many different treatments people with ME/CFS used were, and the widely varying degrees of efficacy achieved.
Despite the harsh treatment Hemispherx and Ampligen received from the FDA, the ‘Voice of the Patient’ document reported dramatic reports of improvement, including one person for whom Ampligen was a ‘miracle drug’. Stating that many patients went through a ‘complex process of trial and error’, the FDA acknowledged that patients were working hard to find relief.
Physical therapies such as stretching worked for some, but not for others. Patients reported clever ways they’d adapted to their reduced energy levels, as well as a large variety of diagnostic tools and biomarkers (yes, the FDA said biomakers) clinicians used to monitor their progress.
Confusion and frustration marked ME/CFS patients search for good treatments
The FDA noted – much to the patients credit – that they felt that even small increments in improvement, could yield substantial improvements in quality of life. That’s the mark of a ‘mature’ group of people who, while not happy with their situation, have adjusted well to it.
One of the most interesting aspects raised was the reduction in the effectiveness of treatments over time. For some reason, drugs that work tend to lose effectiveness in some people (many people?) – and then need to modulated or switched out – with something that does work, which then loses its effectiveness, which then needs to be switched out, etc.. This is an example of a system that Dr. Cheney said tended to pull back patients after he’d pushed in a healthier direction.
Frustration at the difficulty in finding knowledgeable practitioners was voiced, and then finally, and importantly, the FDA reported the willingness of some patients to undergo significant risks in the search for effective treatments.
Conclusion
It was a good first step for the FDA, but it was only a first step. A guidance document remains to be produced, but more importantly the issues that have left a large community without the benefit of drugs or even drug company interest need
The FDA has a lot of work to do before drugs start flowing to ME/CFS patients
It was a good first step for the FDA, but it was only a first step. A guidance document remains to be produced, but more importantly the issues that have left a large community without the benefit of drugs or even drug company interest need to be addressed – and it’s not clear that the FDA, at this point, is interested in taking that on.
Tomorrow the FDA will be the subject of a congressional hearing that will address how well it is implementing the FDASIA bill that authorized the patient initiative, and directed the FDA to get more drugs more quickly to people with chronic illnesses. The four key parts of FDASIA include
- Giving the authority to collect user fees from industry to fund reviews of innovator drugs, medical devices, generic drugs and biosimilar biological products;
- Promoting innovation to speed patient access to safe and effective products;
- Increasing stakeholder involvement in FDA processes; and
- Enhancing the safety of the drug supply chain.
With regards to ME/CFS we expect questions to be asked about the FDA’s outreach (or lack of it) to drug companies for the Stakeholder Meeting.
Thank you Cort for this excellent summary on the FDA’s “Voice of the Patient” document and all the links you provided. There is absolutely no one who does a better job of keeping the patient community informed than you do, and I continue to remain amazed and truly grateful. I would suggest that patients print the 23 page FDA document and provide a copy of it to their physicians who know very little about ME CFS. It will be interesting to see what (if anything!) transpires at tomorrow’s (Nov. 15th) congressional hearing. Maybe we will actually have viable treatment options available to us during our lifetimes after all.
Thanks Pat – good idea about printing out the document…it really is a great summary of ME/CFS….
Cort, good article and for once positive direction. I might only comment that fibromyalgia is more than pain. Many patients with fibromyalgia also suffer autonomic effects such as loss of heart rate variability and endocrine and immune dysfunction. We all suffer, and while FM is more notorious, some of the reasons are not positive. Dr. Frederick Wolfe would have us all labeled as people who complain of too many symptoms. Having been diagnosed with both FM and CFS, I can say that each has its own distinctive basket of tricks. We desperately need sound diagnostic criteria that search for biological effects.
Thanks Celeste. FM is getting its own FDA stakeholders meeting I believe. Either disease is too rich in symptoms to be characterized by either fatigue or pain, and the ANS problems occur in both. Now that the FM researchers are beginning to look at the immune system, it’ll be fascinating to see what they uncover.
That is all great news except that I suffer from post exertional malaise as well and I have FM. It is hopeful that they might stumble on something that helps me as well but more important than any of that is that they listened and heard. That is breathtaking.
I have no doubt Gillian that some breakthroughs in ME/CFS will translate to FM and vice versa. It behooves people with either disorder to keep an eye on what’s happening in the other one. I have no doubt that PEM is a real WU(&$#( in FM as well.
Being in the midst of an ongoing and worryingly deepening ‘crash’ since July 2012 and consequently feeling despair is overtaking hope, this post has lifted my spirits considerably.
I had actually watched the live streaming of this meeting and am now delighted that it has been reported so accurately with well hi-lighted symptoms and important aspects of living with this disease.
Living in the Uk, where my health authority spends ZERO on any form of treatment/support for patients with M.E./CFS, I am hopeful that strides made within the FDA may eventually find their way across the pond.
Thanks once again for such an informative piece. I look forward to reading the outcome of the congressional meeting.
Hi
Thank you for the information and your great job. The document sounds good at first sight, but I think some points are tricky. Mainly this one: the FDA says cognitive and neurological issues are the most debilitating: it is not true. The most important is the incredible exhaustion – which can even make you bedridden and not eat or to dress yourself in severe cases. The exhaustion comes from mitochondria issues which make the muscles weak as they are unable to produce sufficient ATP (energy) – the heart also is a muscle and thus much effected by this. It is not able to produce enought energy to pump the blood in the whole body if you stand or walk. If the FDA puts congnitive and neurological issues in first place: this does not discribe our illness and its debilitating state and on top of this it is opening again the doors for psychiatric treatment. This is just wrong and not helpful at all. I think it is important to stay cautious, I would not be surprised if they are just trying to pave the way for making this illness a psychological issue again.
Kind Regards
Nina
If memory serves right the FDA actually reported accurately on what the patient said. I remember thinking when so many people raised their hands to that question that that was not so good and that it did not reflect my experience. The FDA did, however, several times focus on post=exertional malaise and noted that even minor activity can cause relapses or crashes.
If the conclusion about cognitive issues being paramount was drawn from a show of hands of patients present, it stands to reason that patients for whom fatigue is paramount would be underrepresented in such a group. More of them would be too fatigued to attend, whereas cognitive dysfunction wouldn’t keep people away, just confused.
Good point Sandra – I never thought of that 🙂
Thank you Sandra & Cort. That’s the point. The people beeing able to attend meetings like that of cause mainly have issues with the cognitive side of ME/CFS, if not they would’t be able to go there. But they do not represent the severly ill and disabled of us. We do have severe cognitive problems as well, but they are not the key symptom. And it is partly because of the similiarities of mild ME/CFS cognitive symptoms with psychological issues that this is so often mixed up. This is not of help. We need the severe illness to be recognized in order to show the difference to other illnesses and to be able to diagnose ME/CFS correctly. This is so import!
This was really good news. I hope it spreads to the governmental agencies that will have the authority ( and avoid politics and personal ambitions ) to really get the ball rolling. I see what this devastating disease can do to a person who is terribly hampered by this affliction. Loss of a considerable quality of life. I am going to watch the hearing now. I called that phone number that was given on the website’s hearing notification document: 202-225-2927 because I was wondering if it would be postponed due to the sub-committee hearings on the Affordable Care Act. Was told it is ongoing. Website: energycommerce.house.gov. Click on “hearings & vote” and then “Reviewing FDA’s Implementation of FDASIA” Get back to you later. Thanks so much, Cort. You are invaluable and I hope you have the strength to continue your valuable course of action.
Thanks Carol. It’ll be interesting to hear how it goes 🙂
Hey Cort, have you heard anything new about biovista and the combo therapy CNS/IMMUNOLOGY?
Nada…..the CAA is keeping a tight lid on the news for some reason which I cannot figure out….I think we’re supposed to hear more around the beginning of the year..
I remember the precise day of onset. It was when I ate unwashed figs from my Fig tree, then noticed they were coated with an oily substance. Inasmuch CFS is an energy disease, it should be considered a Mitochondrial disease. 27 years later I was finally tested for, and found to have, auto antibodies to Mitochondria. Doctor said I’ve had them a long time.
Regarding studies of correlation of insecticide spraying and onset of CFS, the silence is deafening. State departments of Agriculture may be withholding information. Perhaps a non government agency would be best to collect data.
I think there all sorts of ways to get ME/CFS. I remember sitting in Dr. Reas office in Dallas and hearing him say that most of MCS cases resulted from exposures from farm chemicals and some of them surely had ME/CFS as well.
In order for the Department of Agriculture to withhold information on the correlation of insecticide spraying, however, they would have to collect it first and I would be totally amazed and gobsmacked if the D of A or any federal agency collected information on risks factors in ME/CFS. (I would be surprised if the Dept of Ag knows what ME/CFS is actually.) I imagine there are, though, academic studies that look at insecticide spraying and disease…
When I read that “post-exertional malaise” is an expression coined by the ME/CFS community, it made me wonder: who is the very first person to have resorted to the “crash” metaphor? My, that was clever! And what a legacy! Any idea Cort?
It would be interesting to find out…I wonder how you would do that….I know there are ways.
Ha! I’m sure a bunch of people could be held responsible. I think that it’s something many of us just come to because it’s such an accurate way of describing what it feels like. I know it’s been around for at least 10 years. I used to say it (still do unfortunately) and I remember the first CFS patient conference I went to here in Salt Lake, when someone used that term. I turned to my husband in sheer amazement that these people were speaking my language. I heard all kinds of things that were so familiar like “I just hit the wall.” It was surreal for both of us, and very validating for me, even though it was a bit of a downer as far as the outlook for the future went. PEM wasn’t being bandied about just yet then though, and it’s going to be a key term in my opinion.
people who are scared to admit cognitive problems have had there brains bashed out by ignorant in all things me/cfs mcs fms medical drs who have loaded them over the years with serotonin based anti depressants and even ect 27 off them for me
they are ignorant but in my opinion criminally so for the harm they have done to millions
WyoGal here…computer problem resolved, and just discovered your latest post Cort.
This is groundbreaking. Not perfect but strong progress. Validation for those of us elder
citizens who’ve had it so long. Its been 23+ years for me. So much wisdom in the
comments. Without being able to access others and share our stories, this “condition”
truly leaves us isolated, and more often than naught, without hope.
Shortly after my diagnosis, I read Osler’s Web, and it angered and frustrated me to the
point of rage. Holistic modalities have been my avocation since my 20’s. At 64 years,
having what I consider a “holistic illness”, those physicians and practitioners willing
to step out of the box and listen have kept me going. Holistic you say? Yes…for me,
the evolution in understanding this illness has led me to KNOW that it affects every part
of my body…every part. Any medical person who insists otherwise to me will not be
a part of my team.
Insisting on respect, and active listening is my right as a patient. When I have succumbed to the relentless onslaught this causes, I’ve stumbled and fallen toward being a victim.
Thankfully I’ve just tiptoed into that abyss. Its damn hard not venture deeper. Somehow
through the magic of technology, and networking with others like you Cort, we stand even
more united and proactive on having our voice heard. Its imperative.
To all who have responded, it means the world to me. Wyoming is my adopted state. Its people pride themselves on being independent. With only 500,000 in our entire state, we
truly are isolated by a rugged terrain. It amplifies the loneliness and isolation this illness
brings.
Blessings to those of us who travel this path journey. We are not alone, and that is priceless…as are you Cort.
More later, Linda WyoGal
PS Cognitive issues? I’ve made a 45% improvement in a year. A year ago I wouldn’t have responded…was in communications for years…couldn’t communicate without mistrusting what I wrote and said. I’ve stayed off the blogs, simply reading and deeply appreciating. This is only a part of my symptoms, but huge for me. More later…WyoGal
I am the secretary. Rik Carlson is the President. We live in Burlington, Vermont. You can e-mail either of us anytime. Thank you.
My daughter was struck down by ME/CFS and ended up virtually bed-bound, confused and unable to lead anything like the life a 15/16/17 yr old should. She is now getting very much better with the help of Dr John Eaton and reverse therapy. I urge anyone to look at this gentle, unbullying, considered and effective approach. http://www.reverse-therapy.com
Well done and thank you for the post, glad the FDA is listening… but one comment made I have to disagree with ..
“but only ME/CFS has PEM or post-exertional malaise, and only in ME/CFS do ‘crashes’ make up such a major part of the illness.” not true, PEM and the crash and burn is a major symptom and issue for Fibromyalgia, Lupus, and many other chronic ailments .. all of us can say if I do X today, I WILL pay for it … ME/CFS does not hold a monopoly on that ( I wish but then I would not wish the crash and burn.. on anyone )
BB
Esta
I agree Esta. I meant it in a ‘linguistic fashion’; only in ME/CFS has the term ‘post-exertional malaise’ become identified with the illness. I looked up PEM in Pubmed and it showed up with ME/CFS. I agree though that it must be present in many other disorders 🙂