[CFS-L] Serious concerns about the FDA meeting

[Samuel Wales]

I am grateful that the FDA has published its draft agenda.
I am grateful that the people who matter -- the sufferers --
are being included.

However, the focus on symptoms is problematic.

Here is the accompanying blurb:

The discussion on April 25 is dedicated to engaging
patients, as part of a participatory process, in dialogue on
the most significant symptoms and negative impacts
experienced in their daily lives as a result of their
condition.

I do not believe that this is the best way to include
sufferers.

To me it is a problem that the draft is focused on symptoms.


This is not a side point
==========

The best way to show respect to sufferers is to get the
fundamental nature of the disease correct in the first
place.

It is better to ask them what is needed instead of guiding
their answers with lifestyle-based questions.

Those questions steer away from progress on the disease.

===

This is not a side point. It affects the types of drugs
being developed.

We do not need the development of more stimulant drugs. We
do not need antidepressants.

Instead we need sincere research into drugs (and
non-patentable substances) that seek to address the
fundamental underlying PATHOPHYSIOLOGY of the disease.

===

There are some that exist (immune modulators and methylation
supplements, for example), but they are under-studied and we
need far better ones.

We also need clinical trials on antiretrovirals, for example.


This concern is not theoretical
==========

As we speak, an amphetamine is being "developed", meaning,
as far as I can tell, that somebody wants to label the
existing molecule for sale for the disease.

Given the history of this disease, it is possible that this
meeting was, in fact, specifically designed to push such
drugs, or other evasions from the pathophysiology.

That is how such meetings sometimes run: the outcome is
determined before the meeting even begins.


===

Including sufferers is good.

However, the FDA's choice of questions about lifestyle and
symptoms instead of root causes and pathophysiology suggests
a possible attempt to get them to answer the way they want.

This is because making the questions be about symptoms makes
the meeting be about symptoms. This in turn promotes
symptom-based drugs.


Example
==========

Panel 1 Questions:

1. What are the most significant symptoms that you experience
resulting from your condition? (Examples may include prolonged
exhaustion, confusion, muscle pain, heat or cold intolerance, etc.)

2. What are the most negative impacts on your daily life that result
from your condition and its symptoms? (Examples may
include difficulty
with specific activities, sleeping through the night, etc.)

a. How does the condition affect your daily life on the
best days and worst days?

b. What changes have you had to make in your life
because of your condition?

-- Draft agenda

Questions about symptoms and lifestyle constitute an
invitation to promote purely symptom-based drugs.


Selection bias
==========

I have pointed out before the selection bias inherent in the
meeting: only people who are relatively well will attend.[1]

Not a single hospitalized, tube-fed, bedridden, or
housebound sufferer will physically attend the meeting.

To my knowledge, the bereaved of sufferers who died will not
attend the meeting.

===

This will bias the answers regarding lifestyle and symptoms.

===

If the FDA is insincere, it will help pharmaceutical
companies push more lifestyle drugs and palliative symptom
drugs on sufferers.

Stimulants, antidepressants, and Lyrica can be harmful.
Existing ones are already usable off-label should there be a
need for them. This is the wrong direction to go in.


Salad endpoint
==========

In a previous FDA meeting, there was an endpoint called the
"salad endpoint": if you can make a salad, then you are
better.

This was completely well-intentioned in the context of NK
cell counts (as it was first stated). But it is a problem
if it is misunderstood.

It fits perfectly with the widespread, misopathic myths
about the disease being a "condition" involving effort (as
opposed to attacking almost every system in the body with 50
symptoms not being unusual).

===

The FDA liaison praised the salad endpoint. Perhaps that
was with good intentions, but we have no evidence of that
from the FDA as a whole so far.

One can imagine the advertisement:

If you can't make a salad, try Uppita stimulant! Ask your
doctor now! [May cause serious worsening of the disease it
is ostensibly targeted at. May cause death.]


Endpoints the FDA needs to consider
==========

If symptom-based endpoints are necessary, I propose more
like these:

1) the "did not die and can leave the hospital" endpoint
2) the "is not in extreme pain" endpoint
3) the "does not need a feeding tube" endpoint
4) the "is no longer bedridden" endpoint
5) the "is no longer housebound" endpoint
6) the "can enter a moldy room" endpoint


Is the FDA serious?
==========

I expect a serious agency to acknowledge the most
fundamental fact about the disease: the fact that it is a
serious disease.

While I am grateful for the outward appearance of taking the
disease seriously, there is no evidence that the FDA is
sufficiently serious about the disease.


===

While we will always welcome sincere efforts at progress,
given the history and the above, it is not unreasonable for
sufferers to conclude that this is more evasion.

The only way to convince us otherwise is to make tangible
progress immediately.


Conclusion
==========

I believe that this meeting is at least in part designed to
pacify advocates and help out a few drug companies who want
to sell palliatives like stimulants.

I will be happy to be corrected, but I do not welcome
apologia from those who profit (or believe that they do)
from the status quo.

I implore all people considering attending the meeting to:

1) Please attend the meeting

2) Please make it plain that we are talking about a
DISEASE

3) Please include the [ENTIRE range of severity] in
everything related to the disease

Samuel


[ENTIRE range of severity]

http://thekafkapandemic.blogspot.com/2013/03/three-damaging-myths-about-severity.html


Footnotes
==========

[1] I submitted testimony about the selection bias
inherent to the the official meeting. Mary Gross at the FDA
graciously promised to include it. Her email to me was
dated Wed, Mar 20, 2013. Randi at the FDA later confirmed
and Mary Gross again confirmed on Apr 1, 2013.

I want to sincerely thank both of them. It is greatly
appreciated, especially as I was having difficulty using the
web software due to accessibility reasons. Their
assistance, to me, demonstrates good intentions.

Physical mail is a hardship for severe sufferers, which is a
point that I believe the FDA was unaware of.

It is critical that the FDA allow email (NOT only website)
submissions in the future to avoid accessibility issues with
websites.

Selection bias due to channels of communication is a
problem.


--
The Kafka Pandemic: http://thekafkapandemic.blogspot.com

The disease DOES progress. MANY people have died from it. ANYBODY
can get it. There is NO hope without action. This means YOU.