Thursday, January 10, 2013

FDA'S DOUBLE STANDARD



A mad-as-hell Sid Wolfe of the watchdog group Public Citizen sued FDA about the agency's refusal to ban the highest dose of the Pfizer Alzheimer's drug Aricept--and lost. Studies don't show increased efficacy of the 23-milligram pill compared with the lower doses of 5 and 10 milligrams.  However, the higher dose does show increased toxicity, including, Wolfe said, increased mortality.


According to a comprehensive article by reporter Ed Silverman, the director of the FDA’s Division of Neurology Products, Rusty Katz, explained his reasoning for keeping the higher dose by posing a question and then answering it:  “Does the absence of a demonstration of any superiority of the 23 milligram dose to the 10 milligram dose on measures of overall functioning, coupled with the increased incidence of potentially significant adverse events, argue against the approval of this product?” The 23 milligram dose is “clearly superior to the 10 milligram dose” on a cognitive measure.* “In my view, this strongly argues for a conclusion that the 23 milligram dose is very likely to also have an effect on overall functioning, despite this not having been demonstrated directly in this study” [emphasis added].

Reporter Ed Silverman also wrote that given the few Alzheimer's treatments available, FDA believes that physicians may decide the added side effects justify the benefits. 


Following that logic, FDA, Ampligen's side effects are in most cases, minor or manageable, and given that there are no FDA-approved ME treatments, shouldn't Ampligen be approved?  Instead the FDA committee, while endorsing Ampligen's safety, voted that the drug didn't meet FDA's standards for efficacy--though it was "probably effective."  Probably effective sounds an awful lot like the "very likely" of two paragraphs up.

Why the double standard, FDA?  Could it be FDA is throwing the pharmaceutical giant a big bone because the patents on the lower doses are expiring?  Could it be that FDA believes Alzheimer's to be more important than ME?  Could it be, as Sid Wolfe suspects, that FDA doesn't want to admit it was wrong in approving the 23 milligram dose in the first place?


Sid Wolfe also testified at the FDA Ampligen hearing on December 20 that Ampligen shouldn't be approved either.  (And a patient I talked to at the meeting said she overheard him say that cognitive therapy works.) 

Here's Ed Silverman's story, if you want more info.

*In three of the four tests, there was no increase in cognitive function at the higher dose.

Wednesday, December 26, 2012

Medical Sadism


For me, the most appalling thing about the FDA Ampligen committee meeting wasn't Ampligen's nonapproval.  It was a very sick ME patient leaning on a cane who showed me the prescription a sadistic, condescending neurologist had given herafter admonishing her for using a cane.  Gazing at the script for several seconds, I first felt confusion and then the patient's humiliation.  The prescription read:

Tai Chi  

I told this story to a friend who's had ME for more than 20 years, and he said in all seriousness:  At this point, I'd take that cane and bash the doctor's head with it.   

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.

Saturday, October 27, 2012

CDC Toolkit:
Despite Its Inaccuracies, CDC Won't Remove It

Last spring, members of the Chronic Fatigue Syndrome Advisory Committee (CFSAC) ruled that they wanted the CDC Toolkit about "CFS" removed from the CDC website because it’s inaccurate and because it’s giving false information to millions of doctors about ME.  For instance, the Toolkit endorses Cognitive Behavioral Therapy and Graduated Exercise Therapy (GET), which have been shown not only to be unhelpful with people with bona fide CFS but GET can actually be harmful.  That's because the hallmark of ME is post-exertional crashing.  The more you do, the worse that crashing generally is, and sometimes patients don't recover from those crashes.

Furthermore, the Toolkit states that there are no labs and diagnostic tests other than routine labwork to rule out other diseases that mimic ME, when in fact this is untrue. Many tests show abnormalities with ME patients.  For example, bona fide ME patients usually exhibit low natural killer function and abnormal tilt-table testing for autonomic dysfunction, and several published studies attest to these abnormalities.

At the CFSAC meeting this month, head of CFS research Dr. Beth Unger was asked by CFSAC member Steven Krafchick if the Toolkit was going to be taken down.  And Dr. Unger replied, “No.”

I emailed CDC a list of questions about the Toolkit, and below was the response.  Most problematic, CDC stated in its reply:  "The information in the Toolkit is not inaccurate, and we have verified this repeatedly in discussions with clinicians who care for CFS patients."

Given that the Chronic Fatigue Syndrome Advisory Committee has made a strong recommendation to remove the Toolkit, and given that the Toolkit is inaccurate, why hasn’t it been removed? 

"CDC continually reviews and assesses the best way to present information. CDC has determined that the agency’s website is an appropriate channel for providing the CFS Toolkit information to patients, clinicians, other stakeholders, and the public. This information is also available in hard copy in the form of booklets. The information in the Toolkit is not inaccurate, and we have verified this repeatedly in discussions with clinicians who care for CFS patients.  We have plans to revise the presentation and clarify issues that have been identified by CFSAC member Eileen Holderman and Dr. Lily Chu. There still remains a need for basic introductory information about this illness for primary care physicians, including those serving Spanish-speaking populations. The Toolkit, in both its English and Spanish versions, serves this need."


Who at CDC is responsible for making the decision to keep the Toolkit?
 
"For most CDC websites, content decisions are reached through a collective understanding among various CDC professionals with expertise in scientific subject matter and the presentation of complex public health information. CDC also consults with clinicians and other interested individuals about the ongoing need for information about CFS and has been advised that the Toolkit helps meet this need. CDC will continue to work with others to review the Toolkit and update and expand this information as appropriate."


Why isn’t CDC listening to the Chronic Fatigue Syndrome Advisory Committee?
 
"CDC does listen to the Chronic Fatigue Syndrome Advisory Committee places great value in recommendations made by the Chronic Fatigue Syndrome Advisory Committee. We consider all recommendations made by this committee. For example, the recent revision of the CFS website  was initiated in response to CFSAC recommendations.  CDC solicited specific comments from CFSAC members on the CFS web page and used these comments to make improvements to the site.  We are taking the same approach with the Toolkit."