Saturday, December 22, 2012

The Oxford Definition
It's Baaack


I was at FDA this week to testify for approval of Ampligen for ME.  I was surprised when several people, including a representative of Hemispherxthe company that makes Ampligen felt assured that Dr. Beth Unger, head of CFS research at CDC, would vote for approval.

In my view, Beth Ungerwho should know the suffering that millions experience with ME better than most FDA committee memberswould vote for Ampligen approval when pigs fly.

Like most of the committee (9 to 4), Unger voted no, when it came to evidence of Ampligen's efficacy. She also voted with the majority (9 to 4) that the company did not supply adequacy of safety data. She voted with the majority (8 to 5) that the company did not provide sufficient efficacy and safety data to bring the drug to market.  However, she also voted with the majority of members (8 to 5) who said that the drug's safety profile overall was acceptable.

Vodka and Beets
Granted there were issues with the studiesbut there are issues with all studies, and side effects with all drugs, and on and on.  Of course you can make a strong argument for not approving a drug with problematic trials when there are other drugs on the market, but when there aren't any?  For a disease that afflicts 1 million Americans and 20 million worldwide?  When there are no drugs in the pipeline?  When the majority of the committee says it's safe?  Ampligen has a near 30-year history of helping patients, and there haven't been any fatalities from the drug.  How many FDA-approved drugs have that track record?

At FDA, Unger also said in her decision that more needs to be known about this "subset" of ME patients who responds to Ampligen.  If Unger, the late William Reeves and the rest of the sham scientists at CDC had bothered to investigate the disease seriously for the past 30 years, those "subsets" would have been defined by now and drugs would have been approved.  Now, CDC is finally running the study.  What are the odds CDC will discover anything useful?  Pleassssssssse.

Muddle, Muddle
Of course, when you muddle the definition of ME or CFS or whatever you want to call it for 30 years, when CDC lumps its CFS studies in with "idiopathic fatigue" and "unwellness," when CDC is looking for personality disorders in patients instead of viruses and retroviruses, when CDC cold calls depressed women in Georgia and Kansas and tells them they have CFS when they didn't know they had anything wrong with thembelieve me, if you have this disease, you know absolutely, the way you know if you like liver or chocolate or vodka or beets, that something is terribly wrong with youis it any wonder that the patient population gets muddled?  

Of course not, since that's the idea:  Muddle everything, so that there's no data to hang your hat on, so that ME remains a mystery forever and ever, so that you have job security until retirement.  Muddle, muddle, toil and trouble.

FDA:  More Studies
FDA also said it believes the data is interesting and the panel wants to see another Ampligen study.  From what I've learned, the company doesn't have money for another study now.  So how is that going to happen?

Alaine Perry
One other point, before I bring you the main pointI buried the leadof my post.

The FDA committee seems to think that the fantastic, and I mean fan-frigging-tastic presentations by patientsincluding several beyond-articulate patients who are also physiciansare outliers, in other words, in the committee's eyes, they're far sicker than the average patient.  

Thank God for Alaine Perry, a brave scientist on the Ampligen committee who has ME and voted for approval.  Perry, 52, senior adviser for Disability and Special Need Population, CMS Center for Strategic Planning, said that the average patient is very sick.  And when committee members were grousing about the problematic side effects of Ampligenthe flu-like symptoms, the headachesPerry also made clear, in her determined, resonant voice, that those are everyday symptoms of ME.  She explained that she works at FDA, but that's all she can do.  She went caroling one day—she said she loves to sing—but knew she couldn't sing in a choir every week.  She doesn't have the energy after work.  Perry broke down, and so did many people in the audience

Why does the committee think most ME patients aren't that sick?  Could it be the name CFS that CDC coined?  Could it be the useless research perpetuated by same?  Laurence Fishburne, where are you?  Where the hell is the CDC of the movie Contagion?  Not doing ME research, that's for sure.

Oxford Definition
But there's more. A couple of weeks ago I asked CDC's Unger via email why is CDC using the antiquated Oxford* definition in its partnership with HRSA (Health Resources and Services Administration), along with Fukuda** and Canadian Consensus Criteria*** in its continuing education courses? The Oxford definition requires only fatigue, unlike the other definitions of ME, which require immune, neurologic and autonomic symptoms.
I also asked Unger:
  • For most CFS-literate physicians and patients, using all three definitions is a problem. That’s because the Oxford definition requires only fatigue as a symptom. In contrast, Fukuda requires fatigue and four other symptoms.* According to most CFS-literate physicians, the Canadian Consensus Criteria (CCC) is the most accurate and thorough of these three definitions, and requires the following: fatigue, post-exertional malaise and/or fatigue, sleep dysfunction, and pain; two or more neurological/cognitive manifestations and one or more symptoms from two of the categories of autonomic, neuroendocrine and immune manifestations.**
Given the significant differences in definitions, does CDC believe using all three definitions is problematic?  Why or why not?
  • By focusing on fatigue, the Oxford definition neglects other important symptoms embraced by CCC, as well as other symptoms in the original Fukuda definition. Fatigue is characteristic of many illnesses, from cancer and heart disease to depression.  Thus, with the Oxford definition, CFS morphs into a vague disease—it’s only vague by the Oxford definition, not by CCC.  Using the Oxford definition makes it more difficult for doctors to distinguish pathological fatigue of CFS from ordinary fatigue and from illnesses that have fatigue as a symptom—and that’s most illnesses. For all these reasons, Oxford is, in the view of most patients and CFS-literate physicians, a woefully inadequate and inaccurate definition.  Does CDC understand the problems with the Oxford definition?
  • Does CDC want there to be confusion about the disease?  
  • If CDC doesn’t want there to be confusion, why does it use all three vastly different definitions in the HRSA CME courses?
  • Over and over again, CDC states in meetings and in its medical articles that CFS is a poorly understood disease. Other researchers and clinicians look to CDC for guidance. Does CDC understand that by using all three of these vastly different definitions, CDC is causing the disease to be poorly understood?
  • The CCC definition describes the illness that most patients and CFS-literate physicians understand to be CFS. Given that using multiple definitions results in confusion and heterogeneous populations, why not make this critical change and use only CCC? Please explain why CDC won’t do this.

CDC’s Response

Through its press office, CDC—I assume it was Unger, since I directed my questions to her—replied:
CDC has developed several CFS CME courses, including Diagnosis and Management of Chronic Fatigue Syndrome (see http://www.cdc.gov/cfs/education/diagnosis/index.html) which was prepared in collaboration with other CFS subject matter experts, including non-CDC clinicians in private practice and academic settings. Among other things, this CDC CME course provides information about multiple CFS case definitions, such as those mentioned in your query. CDC uses the 1994 case definition, but recognizes there are additional case definitions that can be useful. CDC is committed to providing accurate, evidence-based CFS information that is relevant to various audiences, including CFS patients, clinicians who treat CFS patients, researchers, and others.
 
I believe this information addresses the questions you asked.  You may wish to contact HRSA directly about questions regarding CME courses produced by that agency.
 
Thank you for your interest in CDC’s CFS research program.


This article is copyright CFS Central 2012. All Rights Reserved. You may quote up to 150 words from this article as long as you indicate in the body of your post (as opposed to a footnote or an endnote) that the excerpt is by Mindy Kitei for CFS Central. You may not reprint more than 150 words from this article on blogs, forums, websites or any other online or print venue. Instead, refer readers to this blog to read the article. 
 
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*Oxford definition
fatigue as the main symptom; definite onset and not lifelong; fatigue is severe, disabling and affects physical and mental function; fatigue should persist for 6 months or more and be present 50% of the time; other symptoms, especially myalgia, sleep and mood disturbance may be present.
**Fukuda definition:
Patients must have four of the following:

Self-reported impairment in short term memory or concentration severe enough to cause substantial reduction in previous levels of occupational, educational, social, or personal activities; sore throat; tender cervical or axillary lymph nodes; muscle pain; multi-joint pain without swelling or redness; headaches of a new type, pattern or severity; unrefreshing sleep; post-exertional malaise (PEM) lasting more than 24 hours.



***
Canadian Consensus Criteria:
Neurological/Cognitive Manifestations: Two or more of the following: confusion, impairment of concentration and short-term memory consolidation, disorientation, difficulty within formation processing, categorizing and word retrieval, and perceptual and sensory disturbances—e.g., spatial instability and disorientation and inability to focus vision. Ataxia, muscle weakness and fasciculations are common. There may be overload phenomena: cognitive, sensory—e.g., photophobia and hypersensitivity to noise—and/or emotional overload, which may lead to crash periods and/or anxiety.


One or more symptoms from two of the categories of autonomic, neuroendocrine and immune manifestations:


Autonomic Manifestations: orthostatic intolerance neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS), delayed postural hypotension; light-headedness; extreme pallor; nausea and irritable bowel syndrome; urinary frequency and bladder dysfunction; palpitations with or without cardiac arrhythmias; exertional dyspnea.


Neuroendocrine Manifestations:  loss of thermostatic stability—subnormal body temperature and marked diurnal fluctuation, sweating episodes, recurrent feelings of feverishness and cold extremities; intolerance of extremes of heat and cold; marked weight change—anorexia or abnormal appetite; loss of adaptability and worsening of symptoms with stress.


Immune Manifestations: tender lymph nodes, recurrent sore throat, recurrent flu-like symptoms, general malaise, new sensitivities to food, medications and/or chemicals.

19 comments:

  1. Unfortunately, I agree with what Mindy has to say about Dr. Unger and the CDC; I wish it were otherwise. I have talked with Dr. Unger several times by telephone, and my impression is the same as Mindy's: "In my view, Beth Unger—who should know the suffering that millions experience with ME better than most FDA committee members—would vote for Ampligen approval when pigs fly."

    Perhaps I have become cynical--30 years of suffering from a devastating illness might cause that--but I am wondering if the building up of patients' hopes only to dash them in that FDA meeting was not purposeful. Everything I know of Dr. Unger tells me that she is a very serious woman and her first concern is doing what she considers to be her job, which appears to be, firstly, protecting her agency, the CDC. My impression is that she would see all of us in early graves before she admits the CDC's past misdeeds, and so far includes preventing recognition of M.E. as a serious and life-threatening illness. After all, there are a great many M.E. sufferers, and if this motley group ever decided to take serious action together, we might get serious attention from media and government. It seems to me that the government agencies are doing their best to "control" us by carrots and sticks, and using our "patient" organizations to do so.

    Patricia Carter

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  2. this is all so Kafkaesque and I don't use that cliche lightly in this case. Trying to get the CDC and the NIH to do their job properly is like fighting with jello.

    Very well put, Mindy. I'm still trying to get my damaged brain around the argument that the CDC is doing right by its mandate by posting ALL the published case definitions of CFS even if some of them are not backed by data and ridiculous. Perhaps they should also post the research of alchemists so everyone is completely well informed.

    michael

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  3. Unger's vote should have been expected. But WTF was Komaroff thinking?

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  4. I AM SO SICK OF BEING SICK!! 20 Horribly sick years! The reality is no dx tests, no treatments, no support from any government agencies!
    Thanks for the excellent recap Mindy; heart breaking but accurate.
    I agree with above posts. How can we show a strong front when we barely leave our homes. I am lying next to an undecorated Xmas tree and haven't shopped for my son yet and tomorrow is Christmas Eve!!!

    We need a professional lobbyist with Robert Millers access to the President.

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  5. Sorry I linked this article without reading the copyright Mindy. I will try to delete.
    I just loved the article but have to stop sharing.
    Sorry,
    Gina

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  6. Hemispherx HAD the money to run the new study that the FDA asked for back in 2009, after it lied about FDA approval being imminent in June of that year, causing the stock price to increase by more than 1400 percent.

    They had the money, they just didn't use it. If anyone is mad, they should be mad at William Carter and Hemispherx, for not running the larger study that was requested THREE YEARS ago.

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  7. Was it Unger who opened her first presentation to us "the patients" with the slides of the glorious new CDC offices, when we were all waiting to here about our non-existent access to care or treatments! This when we were terrified that we had an HGRV that we were at risk of passing on to our family and friends.

    Unger did some stuff on alcoholism and if i remem rightly it was psyche based stuff.

    More government crowd control, at the expense of real lives.

    Same old, same old......

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  8. Only about 15% of patients respond to Ampligen - better subgrouping would strengthen Hemipherx studies as Dr. Unger among others pointed out. This isn't news to anyone including Hemispherx. @Beth is correct, the anger needs to be directed at a company which a 30-year history focused on profits not patients. Anyone who thinks Bill Carter is focused on patients is not paying attention to their business model.

    One of the reasons the Oxford criteria and the ICC are so very different is because the authors of the Oxford criteria believe that patients mistake symptoms such as undifferentiated fatigue, which about 25% of people in primary care present with, for symptoms of a serious disease. The focus is ideological rather than clinical. It will be difficult to merge two completely different criteria - the CDC already tried in 1994. The result is a wishy washy criteria that allows two patients to have no symptoms in common other than fatigue that has lasted six months.

    However, listing the definitions on the site is not the same as using them.

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    Replies
    1. CDC should not list Oxford definition for the reasons Mindy articulated. It's not an accident that it is a BS definition; it's part of the Wessely School's program since day one to purposefully conflate ME with Idiopathic CF in order to make ME disappear in a sea of fatigue- then insurers won't have to pay to treat us. Since CDCs goals are the same, they love Oxford and their own BS Reeves Criteria since they both hide ME under a pile of garbage. There is no excuse for CDCs crimes.

      Delete
  9. The number of patients who responded to Ampligen wasn't higher because some of the people on it didn't have ME. Of course, every drug has nonresponders, but the the situation with Ampligen was more problematic, since some of those on the drug didn't have ME.

    The Oxford definition does not describe ME. It describes people who are tired. That's not ME. The Canadian Consensus Criteria describes ME; Oxford describes virtually every disease on the planet, because every disease has fatigue as a symptom. Therefore it is a useless and inaccurate definition, and it should be retired.

    Yes, the company that manufactures Ampligen has had its issues, and I wrote about them back in 1994, but in my view Unger is in no position to suggest anything. Dr. Beth Unger is a disgrace, as is CDC, doing mumbo-jumbo psychiatric research into personality disorders in CFS while patients die of rare cancers and heart failure.

    How Unger can live with herself is beyond my understanding.

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  10. If only 15% of patients with Oxford criteria CFS responded to Ampligen, then that is about the same % that responded to CBT and GET in the mighty PACE Trial, yet that result was paraded as a success.

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  11. I have been angry and fed up with Carter and HEB . . . but he is what he is and owns the damn company. I'd hoped he'd eventually partner with or sell out to a larger pharma but he hasn't.

    Sadly, he is a businessman and probably a good one as he manages to milk money out of the ups and downs of the stock price . . . the people at the CDC, though, are doctors and researchers who are supposed to act in the public interest.

    michael

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  12. This headline would really shake up things.

    Malicious manipulating hedgies bought officials and made millions on the back of suffering (dieing) cfs patients...

    Unger and Komaroff - corrupt or easy to blackmail ?

    Carter is so incompetent,his lousy presentation of data was so absurd,i hope a big pharma will make a hostile takeover of HEB and soon Ampligen will be available for every sufferer of CFS !

    Merry Christmas and never give up your hopes here!

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  13. Unger and Komaroff - corrupt or blackmailed ?

    Something to think about here.

    Merry Christmas

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  14. Why would a government that MINDFULLY belittles and neglects CFS & ME, while broadcasting to the world that we are a bunch of psycho-lazya$ses (who just need therapy and more exercise) want to help treat us?

    I mean, do people really believe that Ampligen's FDA approval is even a possibility?

    I doubt it --> EVER.

    CFS progress will never occur until we are marching/rolling in the streets (i.e., ACT-UP style). Resistance, revolt, and revolution are history's only proven solutions.

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  15. In Short Order -- Dr. Judy Mikovits (Radio Interview, 11/04/12):


    “You should consider...Myalgic Encephalopathy (ME) as a “NON-HIV AIDS” ...

    “This is not about being tired. It is a crippling disease”...

    “...I see this as an Acquired Immune Deficiency...

    ...If so, it’s (ME is) still an Acquired Immune Deficiency."

    Notes re: 2-hour interview:

    www.mecfsforums.com/index.php/topic,14019.0.html

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  16. Same as with the Mikovits "HGRV"-fraud, people should heed any criticism coming from "our side" – it was a big mistake vilifying all the Mikovits-critics.

    If Komaroff voted against Ampligen in that meeting, I would guess he had his reasons – when Komaroff does or says something, he usually has put some considerable thought into it, and I will expect the same with his vote. Have you considered asking him what his reasons were? Any criticism of Ampligen by Komaroff should be well heeded. Ask him about his reasons like you would ask a friend, when he has a different opinion. You might learn something, if only how to better convince him.

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  17. Tony Mach,

    It's not Komaroff's decision to vote against Ampligen that's the major problem here. It's CDC muddling the definition of the illness that has led to problematic markers for companies to use in determining drug efficacy.

    Yes, the studies were problematic, and that, I believe, is why Komaroff voted against the drug's approval.

    But, if CDC hadn't purposefully come up with the idiotic name CFS, followed by muddling the definition and mocking those with the disease, there would be agreed-upon markers and drugs by now and patients would be treated with respect and would have hope.

    I've interviewed many HIV and ME patients on Ampligen, and the drug's side effects are mostly mild--certainly less problematic that the effects of the disease--and the drug hasn't killed anybody. And it has helped many people. AZT, the first drug approved to treat HIV/AIDS, was a much more problematic drug. It was approved because HIV/AIDS was taken seriously, and ME is not. FDA saw the disease as an epidemic and wanted to do its part to help. THAT'S the point, Tony Mach.

    And as far as Dr. Judy Mikovits is concerned, she did her best to help patients. Yes, XMRV has been shown to be contamination, but what's your point? Scientists make mistakes all the time. Mikovits was the first scientist in a very long time to try to help patients, and that's especially why patients defended her findings to the end. She championed patients, so patients championed her.

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  18. Everybody seems to understand that the CDC is the problem, and always has been, yet patients keep allowing them to usurp our energy with "meetings" and "phone calls" and "public comments" that go unheeded. Unger has made her position abundantly clear; she has published that we are suffering from childhood abuse and various other psychobabble ailments. Listen to her! Don't believe that she wants to learn from us; she wants us to learn from her. She is in business to muddle our disease. OPPOSE HER! Pigs don't fly.

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