I would mention the 10kwizard was a pay site for a while,
not sure if they now are, but the SEC has a full text search
capability which can help with similar features now.

Many people seem to think the FDA is
nitpicking on stats. However, the issue with taxotere is sill fishing- post hoc cherry picking if you will. There is no "alpha" criterion if you can pick stuff you like. My optimisim earlier was that they could allocate the variance- noise or deviation- to specific causes in a robust and
credible way ( make a causal argument to supplement the statistics) and eliminate many of the stats-only concerns about post hoc analysis. Taxotere synergy could be a fluke, or maybe not, but beating the data to death, not trying to gloss over stuff, was the only way to convince anyone. Why do we need to guess about the survival benefit in provenge-only patients? Aren't they advertising it? Scatter plots, clustering, etc any way to separate drug effects in any specific patients, was the way to go. With the placebo group, they had a way to validate their model beyond some simple summary statistics.

AFAIK, the FDA is looking at the overall evidence, of course in a rather subjective way, and would and did consider evidence beyond statistical hardlines.

and the debate will center on
scientific or regulatory issues? There can't
possibly be enough new science to have stirred up
a debate and presumably you would invite Padzur to discuss
regulation, not science. Offhand, this looks like it has taken time from science which doesn't seem to be a good thing for future patients.
Any "trade group," including those involving scientists, needs to discuss
the larger environment from time to time but I wouldn't
view this discussion as a positive. I think my initial
reaction to the panel meeting, as an infommercial more
than anything, may parallel the perceptions of the larger community. Partisan science, the chemo versus the bio parties, could be a step in the wrong direction. Unfortunately, this
is shaping up like another branch of science similar to Creationism. While this group does have a lot of committee membership from commercial and academic institutions, it does seem intent upon promoting one specific theory or approach which could lead to separation from "science" at large.

I'd be much happier, for DNDN and patients, if they had
new empirical or theoretical results to debate as this would provide new information about provenge. Is anyone at DNDN doing science? If the others in this field had so much
faith in the product, you'd think they could manage to
get funding to look at provenge with the cooperation of DNDN and publich more provenge science.

Have you obtained a copy of any of the cd54 work and
compared the claims made there to the earlier
causality(drug/prognostic effects separation)
comments related to cd8 measurements? I haven't but
I'd be curious to know if you or anyone else have. A data and content centered debate would be more helpful than a regulatory debate.

It is exactly considerations like this
that make the DNDN disregard for
science more puzzling. Their IT infrastructure,
in vitro approach, and need to monitor contamination,
LPS is a good case in point, give them
the ideal platform from which to sort out these
inconsistent results. So, why the interest in
video and politics? A few IT guys playing with
their clinical monitoring data could probably
do quite a bit. Again, there is some hope their
new CFO is leading an array based science effort
but I won't make any assumptions until I
see some evidence ...

These are not in opposition.
After following DNDN now, I am quite convinced
that your last statement is misleading.
Practical considersations about what really motivates people and ethical considersations to insure maximum patient benefit demand we use the best possible tools and create the strongest possible incentives to get accurate and complete information on these products. I would make the same arguments about patent laws against those who want to give things
away ( " for ethical reasons"). DNDN is not doing any science and trying to use ignorance and opinion to get its product out the door. If they were even trying to back up the product with data I wouldn't be so critical but nothing they've done lately suggests they really care about accurate and complete characterisataion of the product and nothing will change if they can get it to market in this state.

If you want to use an emotional appeal and talk about ethics, then your next statement should be about getting rid of patent protection. Otherwise, look more carefully at maximizing product value. Unfortunately, practical considersations about human nature require something like an FDA to get people to do science and publish accurate information, not just promotional material.

this comes up on google,
not sure if anything has changed lately
( I don't usually keep up with licensing)
http://www.cortexpharm.com/html/news/04/01-07-04.html

The more important thing is the series of 10 or so papers
from Lilly ( IIRC, you can check pubmed ) showing a
progressively expanding role for AMPA in depression.
There was a startling problem with SSRI MOA and
time to clinical effect that everyone had to
gloss over. These kind of "subtle" problems are
opportunities for emerging technologies.

NIH PR on AMPA for depression:

http://www.nih.gov/news/pr/jul2007/nimh-24.htm

if it makes you feel any better,

http://www.investorvillage.com/smbd.asp?mb=58&mn=425&pt=msg&mid=2598590

I think this is litigation fallout, no?

http://www.sec.gov/Archives/edgar/data/1072379/000089102007000163/v30743e8vk.htm#102

Cost Recovery
The Company has submitted an application to the U.S. Food and Drug Administration (“FDA”) for cost recovery for its Phase II pivotal trial in brain cancer. If this application is granted, the Company will be permitted to charge patients or their insurers for the direct manufacturing costs of DCVax®-Brain during this clinical trial. Cost recovery is an extraordinary measure, and is only allowed in rare cases involving certain kinds of special circumstances. The Company considers its cost recovery application to FDA extremely important and central to the timing and overall implementation of its product development programs. The Company expects to receive a decision from the FDA on its cost recovery application in the near future.

this one is funny if nothing else:

I guess you could hide this under holiday schedule problems but it still is funny:

http://www.sec.gov/Archives/edgar/data/1127393/000119312506256297/d8k.htm
Item 8.01. Other Events

On November 29, 2006, the United States Food and Drug Administration, or the FDA, issued a Warning Letter to the Company. The Company received the Warning Letter on December 1, 2006 but because the Warning Letter was not sent to the regulatory contact on file with the FDA, and the actual addressee was out of the office for several days at the time, the package was consequently misplaced unopened. The Warning Letter was opened and read on December 13, 2006. The Warning Letter will be posted to the FDA’s website at www.fda.gov

rather than google, try SEC filings.
I did a quick search for 8K's with some
related terms. Need a little work on keywords
but this may be interesting for background :
( you'll have to remove returns to use links, sorry)

06/04/2007 http://www.sec.gov/Archives/edgar/data/1072379/000089102007000163/v30
743e8vk.htm#102 NORTHWEST_BIOTHERAPEUTICS_INC_ 8-K_ 1072379 dup_info_deleted h
ttp://www.sec.gov/Archives/edgar/data/1072379/000089102007000163/v30743exv10w1.h
tm http://www.sec.gov/Archives/edgar/data/1072379/000089102007000163/v30743exv99
w1.htm /SIC - ]2834)] Cost Recovery The Company has submitted an application to
the U.S. Food and Drug Administration ("FDA") for cost recovery for its Phase II
pivotal trial in brain cancer. The application process involves an inspection a
nd review meeting by BAG. Exhibits List-> | ]1 | ]2

you may want to mention this
to SEC webmaster and help establish my claim that
there is significant, unmet financial need for fulltext document search and structured documents along with custom search criteria implemented at home by nerd's using the SEC's API ( which they claim is a low priority).

Seriosuly, if you start a lettter writing campaign to decision makers, be sure to indicate that the small investor who happens to have any computer skills can mine SEC data and stock charts to look for statistical anomalies ( grant dates coinciding with price minima, sales coinciding with maxima, etc). Be sure to mention that correlation between various sources- patents, medical literature, etc- is essential to getting context and this requires providing an API for the use, not a fancy web interface that forces you to use a computer for manual operations.

Yes, but they aren't even trying.
If they are going to sell a reproducible product,
they ought to have some idea of what the important
parts of that product are. I'm not claiming it need be
perfect but certainly to support questionable stats it would help.

Consider this:
"it has become apparent from preclinical studies that the more important antigen-specific T-cell subsets to monitor may not be those directed to the antigen in the vaccine"

How can preclinical studies establish the [ clinical ] importance of somethings and if this is true, it is all DNDN has to show so far for biochemical results anyway. Add to that the possible antigen-independent mechanisms, blonde antigen response etc, and you have a lot of work to do and a lot of ways it would work even if they don't know the MOA. I don't see DNDN making any effor to find out.

No one ignores the validity of empirical clinical data, but then you have to have some decent criteria for discerning noise from reproducible results. If you don't know how it works then, even if a given trial result was due to a functioning vaccine and not statistical noise, there is no gurantee the next process will work the same way.

Certainly the gene expression or other array approaches would give them some idea what to look at but they aren't even doing this, AFAIK but maybe their CFO ( from AFFX) could be leading their science now. LOL.

did you see SEC terror list?
I have to believe that was a PR stunt but it
makes the point I've been trying
to make for months now- the fulltext filing
search is helpful. But, you must always remember
that context is important: after sending
e-mail to Iraq regarding cyanide( it turns
out the expert on a certain drug reaction is in
Iran and two drugs differ by a group that is
"CN" in one case) , I can probably now
add the CIA to my enemies list along with JHU neurology,
most biotech longs, democrats, republicans, the district court webmaster, and DewDiligence.

LOL.

you are ignoring what oncologists say <sarcasm>

This is probably clutter but after your attempt at humour
I thought this looked insightful by comparison:

http://www1.investorvillage.com/smbd.asp?mb=971&mn=138924&pt=msg&mid=2456256

Re: Cancer Doctor blog: Provenge (sipuleucel-T) made by Dendreon is a Prostate Cancer Breakthrough
"The treatment results in significant increases in T-cell responses to PA2024. After activation, the cells are re-infused into the patient. [...] It was found that the T-cell responses thus obtained are specific. "

If you don't appreciate how funny this is, go back and read the briefing documents. This is actually a disguised concern, not proof that it works.

We agree on many of these points,
but please see some of my other posts
specifically those supporting the FDA decision.

DNDN needed management that understands the importance
of details- maybe their CEO doesn't need to
know what TOF-MALDI-MS stands for but someone who
can appreciated that small things could matter
could be a big plus ( the lack of an in vivo target
is a big deal- either they aren't looking properly
and it really does generate PAP responses [ not
out of the questions ] or it uses a different mechanism
[ including attack on conformational epitope- note
that blonde highlights change shape ] or it
doesn't work [ which they may even be able to prove in vitro]).
I think in one recent CC someone even asked about antigen lifetime and Gold or Urdal quoted a "shelf life" as if
it were somekind of known number like the speeed of
light. Since they don't know how it works and there is
some literature suggesting that immunological properties
change during storage, you would think they would have someone actually looking at this.

Simply relegating their only science- cd54- to a legal role when the efficacy was so questionable was a big blunder. The way Urdal was talking it was "clinically meaningful" or words to the effect that it meant something to patients.

Does anyone know if Gold is showing that cartoon at investor presentations? You would think he would be highlighting the
problems ( opportunities ) and explaining how they are attacking them to create real value ( patents that lead to optimized products and spark the interest of potential collaborators that don't want to make a career out of cartoon MOA's).

let me apologize for recent string of
rather vacuous posts but isn't it normal,
when discussing lawsuits, to include a phrase
such as " we believe these are without merit "
when saying " we will vigourously defend..."?

Sorry, but after cd54 stuff and biotech filings
more generally, it is important to remember exactly
what they said, and not be impressed with an implication.
Literally, they say they are defending the actions,
not defending the company against them- hope that is
just an oversight, not a freudian from the guilty :)

to make a larger point in biotech,
adjectives are the best way to hide facts
or numbers you don't like. "Positive" or
"encouraging" results as opposed to specifics in
clinical results are quite common. "Relatively
minor" is too vague to be legally wrong- it could
mean between 18 and 21 years old- old enough
to kill under orders but not old enough to
follow recent evidence suggesting health benefits
for alcohol so you can sue a drug
company when you have a heart attack
( sorry, but everything I've
read lately on provenge is about politics, thought
it helped make the point).

actually this is a trite plot now,
the real excitement comes from
discovering new stuff- either good as is self-evident
("we figured out how to cure cancer") or
even seemlingly or truely bad- even in the worst
case that provenge doesn't work we liquidate and
move on.

have you seen any evidence they are?
All I know about is the cd54 stuff and some
briefing documents that suggest they can't pinpoint
the in-vivo target. Maybe they have a secret effort
but I'd consider that to be material information :)
Instead of the regulatory actions, I'd be more
worried about disclosure of things like this, "
we conclusively proved it can't work the way
it was designed to work." Don't you think that
would be just as important as an inspector
finding an ungrounded coffee maker?
( I just made that up, it isn't a refernce to
anything to indicate range of regulatory concerns).
LOL.

I didn't want to post this
but do you think they wanted the efficacy
to appear to be the problem so they
could hide some embarassing problems with mfg?
The scenario would be, "sure they mentioned some
mfg problems that we can fix but did you see how
bad our efficacy case was? No one would approve
this so selling my shares was based on public info..."

This isn't trivial and a few problems would have been
expected but when you see things like the cd54 results
and hear things like "governance issues" you have to wonder about these guys.

<sarcasm>these are just more
governanace, or maybe governement issues.
LOL
What more do you need to know? Aren't you satisfied
with the cartoon telling you how provenge works?

Btw, Gold is an MD. And your credentials are?

<sarcasm>

that sounds more credible
anyway than the last suit. I have to confess to
ignoring some details here on what mgmt said and
the specific trading rules but clearly anything
that gets more disclosure is good for everyone
as long as legitimate competitive interests and IP
rights are maintained.

These are the kind of not-so-publicized things that, if
they exist regardin the clinical dat and are brough out, would extend the class period well prior to the AC meeting.

Whatever happened to the mono data once the tax+pro data came out? Did anyone
ever come up with a model they felt good about or see credible numbers? Instead of the fixation on a stupid accounting judgment, most investors would be concerned about the known attributes of the only near-term product...

<sarcasm>wow,
I would have thought Gold would be soliciting criticism,
second guessing himself, thinking he could be doing
more to find out how provenge cured Mr. Garcia,
planning a more dedicated effort to understand
provenge so that there wouldn't be any issues as they
translate it to neuvenge etc.

I'm surprised...
</sarcasm>
I hate to beat this to death but this is an important
point- the data is arguable and the only thing that would
help it win the acceptance of responsible critics is
supporting science. This was true before, and is true
today and is still not understood or appreciated by many at DNDN. It isn't
just a political affront to try to advertize an testiminialize and politicize provenge, it is
a disservice to patients who would benefit more from
accurate science than trying to spin questionable and confusing data.

I'm not advocating "Science for science's sake" or
"managment is the only one responsible" characature positions. Rather, if you look at the simple business issues related to "what would a potential customer think" in terms of "honest" considerations ( what does the product do as opposed to how many free trips can you give to the Medicare admin folks), supporting science was a feasible way to demonstrate and qualify the product value.

what about those "2" people a week ago,
I think there was a whole page of one
guy talking to himself with 2 aliases that
never got deleted but I think wall did delete
a post that was insulting to me ( although I
thought the other clutter was important
and the insults were reasonable).

Personally the thing that I find alarming on IV
is that you can appparently delete any of your
old posts so it is hard to document someone's track
record("I was never pumping that POS").
Yahoo is bad too as they claim not
to be moderated but introduce biases by
deleting things they don't like...

I thought this was funny though.
There are plenty of things they said
that could have been designed to be confusing
but none of those mentioned seems to apply.

Everything that he probably knows came out in the
briefing documents so during the class period
claimed there isn't much basis for any of this.
I don't think DNDN has to provide a link to
these documents but they certainly weren't concealed.

as with biotech pr,
it is probably better to rely on primary documents
as opposed to news item ( in this case that would be
the complaint) but this is too stupid to believe.
As you know, I've been critical of DNDN for many
things and consider their earlier PR to be ( in my opinion intentionally ) misleading or confusing. But the points made here are simply not right and probably areas where
DNDN was "honest to a fault" to avoid this kind of action:

"(1) that the FDA's determination of the Company's BLA could come earlier than the highly touted May 15, 2007 date"

DNDN is now responsible for telling share holders how the FDA works? LOL.

"(2) that study D9902A was not a complete clinical trial due to the limited number of enrolled patients, and therefore it lacked complete statistical significance;"

I guess they never quoted a p value or mentioned how many people were in the study. They were quite clear that the
basis as primarily the one study. I think the author thinks that "Complete" has some meaning and probably that "significance" mean something like "grandiose" or "awe inspriing" as opposed to "p<.05" ROFLMAO.

"(4) that the Company's studies failed to show that Provenge slowed the spread of prostate cancer;"

If he can get Small to testify I could even believe there is substance here but I also believe that people really can see UFO's. If he can actually bring evidence into the open that shows this to be true then I will stop laughing but I'm
pretty sure based on other statements he is talking
about the lack of significance. Further, the class period
for this cause is wrong- this would go back for years.
He has to mean for purchasers who didn't read the briefing documents for this class period, no?

"(6) that this change in accounting allowed the Company to manipulate its financial statements, and make the Company appear financially stronger and more attractive to investors.
"

A develpomental stage biotech company makes an accounting change and their whole financial situation needs to be reassessed? Is this a joke? This guy should have written the
Xinlay NDA- it is just a funny.


Essentially, if you appreciate how funny and annoying this complaint is, you can probably appreciate how Small feels about presentation of the cd54 results as they both has the same concern for accurate context.

I think my earlier suggestions on
triple-blind analysis is still worthy
of consideration at DNDN and the FDA. Even if
FDA doesn't by it right away, they could publish
papers and get people interested in working with them.
<sarcasm>
While I'm not sure this will work as good as
threats against opposing oncologists,
</sarcasm>
if you had a blinded party that could analyse the data with
prognostic factors and predict which were drug
and placebo patients based on excess survival,
that would eliminate all the questions about
after-the-fact ad hoc rationalization. My wavelet
technique would be one way to separate them once
you have predictive model ( based on casuality as
much as possible rather than fitting).

To reiterate another point, if they had an MOA and all the gene chip results from prior patients and had calibrated the results from pure cultures of things like DC's or NK's they wouldn't have to guess on endpoints. They would probably
be able to tell confidence in PSA dynamics versus someother
endpoint and impress everyone when they got stat sig on
the chosen endpoint.

if it makes you feel better,
they deleted my whole board and denied
it ever existed, even when I sent them
a google cache hit from part of it...

you really need to look at pix here:

Imagine if they could get data like this
as a function of time and correlate
with survival ( raw and improved):
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17341312

They would have the only in house immunomodel with
any predictive value after just a few patients
died. Insted, they have a cartoon and a hard
to read graph and confusing PR on the cd54
FACS and an MOA that doesn't make sense.

They probably wouldn't even need to separate
the cells as the principal component analysis would
probably tell them what they have. Rather than try
to guess what is important with FACS, you
can get just about everything here ( Again,
as a function of time).

Sure, this doesn't work for small molecules and is
not accurate due to protein translation rate differences, but
measuring the bleach or a selected cytokine based on
gene results is not difficult once you have
some idea what is important.

I thought he had cancer relatives?
As far as money goes, I think the issue is
"hunger" - the dose response curve for a lot of
people isn't of constant slope ( effort/$ fluctuates
with absolute $ level and the "payoff matrix" for
a scam can be attractive). That is, if you don't
really care then unlimited money will only get so
much effort.

It is possible he simply doesn't understand the problem
and, in fact, he may understand "fight" but not "product development" ( science essentially). There wouldn't
be anything to fight over if he had a convincing
case that the product does something. Even as an MD
he must have read the prescribing information
once in his lifetime- where does he think that
stuff comes from, just some CRO somewhere?

Care to comment on the business side of some science
scenarios? That is, if they bought enough affx expression
array chips to look at 2-3 times during provenge maturation,
what would it cost and what would they get during a clinical
trial or on commercial patients?

Personally I think one hacker with one computer in a
basement could have siftef through the clinical data by
now. I wouldn't trivialize the gene expression array
logisitics but given the IT infrastructure they
surely have and the AFFX CFO you'd think they could
do better than trying to present confusing cd54 results.
The nice thing about the arrays, as opposed to
something like FACS, is you need to have less of
an idea of what you are looking for and the software
for system ID is getting better.



For example, see things like this.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...



http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...

then for our community edification,
please explain the basis for your comfort level?
And, fwiw, I'm surprised Wall didn't delete
that exchange from yesterday between one person and
himself :)

ignorance is bliss I guess :)
You epitomize my characterization of
managment's attitude- I'm sure Gold is comfortable
too and I would speculate that Small is annoyed or
even disgruntled. You should never be complacent,
especially given the data and theory "we" have right
now. Maybe Gold has a secret source of insight into
this matter and feel's that the company's core
proprietary cassette is as good as it gets but
even in this case he hasn't done a good job convincing
anyone else of the product's value.

Since you seemed to pick out a few cancer related
problems you apparently have at least skimmed the lit.
Take a look at history and current status of
immunotherapy and tell me why you are comfortable.

by now, you'd think they would
have an in vitro assay and scatter plots
of predicted versus observed survival
for all possible classes of patients so
they know how best to flatter their product
( select the right patients). Obviously, if they
aren't sick ( incorrect diagnosis is sometimes
a big source of effect dilution ) then you probably
won't see much benefit within 3 years. If they are too
sick, presumably ( and I emphasize we don't have any data)
they won't generate an effective response in time.

By digging up dirt for the last few years and attacking problems they would now be getting flattering results rather than having to just guess. Real explanations for things
that dilute the clinical results remove doubt that the sucesses, rather than failures, wwere the flukes and
earlier ignorance now lets them use the product more
effectively ( if only has to be safe and effective when used as directed by DNDN...).


btw, someone on IV claims Gold was blaming human nature, not
the questionable data for their failure to get approval? Is this for real?
While CEO's don't often criticize their own products, you would think that finding a few problems would be expected when developing a semi-empirical immunotherapy. What have they found out about provenge lately? If Gold really thinks
this is a problem with human nature at the FDA I don't see
them investing a lot in science of even understanding the problem ( at least not the way I perceive it).

It might be entertaining to get Gold on an FDA improvement
panel and see what he suggests to fix the problem or just
ask him on a CC.

this is just a debate over words,
if they got a few encouraging results
to add to the clinical data and managed
to convince a journal to publish it,
then it would sell itself to anyone who was
skimming through pubmed. But they need to
generate the "advertisement" ( the paper)
to get the science to "sell itself."

So, yes, they don't need to push or politically
"sell" it but they do need to market it and make
the interesting feaures known. If it was understood
they wouldn't need science but if they could isolate/publish
a few unknowns they could probably attract collaborations.
I get the feeling this may be embarassing to some
non-science managers( "What, admit that our product
and understanding are imperfect?").

The gene expression results from DC's or NK's as a function
of time correlated with improved survival you would think
would be interesting. I've never priced large quantities
of AFFX arrays but compared to making cartoons it
may be worth some time.

see my posts on iv,
they need a competent adversary who
can contrast provenge to the competing
products. A motivated competent person with
biases different from the sponsor in an "honest"
debate is the essence of the process. Do you want
to find people who don't know what a vitamin is?

If you want an example from other industries,
look at things like the RMBS litigation re JEDEC
and see what the issues were there. The idea is
to get disclosure of motives and debate facts
and merits so motives aren't as important.
Sure, people can conceal motives but that doesn't
seem to apply in this case.
I made seveal sarcastic remarks on IV - worth
reading for humour value.

the times they are a changing,
the reason I keep advocating biotech investing is
that the theory is STARTING to have predictive
value and you can,in some cases, turn this from
gambling on managment knowing which trees
to harvest to looking at all the supporting evidence
to predict product success ( the company of
course can not react in real time to each
new scientific advance, esp if one of them disproves
their whole platform ).

If you don't have a theory side, this comes down to
gambling on management knowing enough to tell
people, "pick the bark from the PAcific Yew tree,
and if you get some hemlock bark don't tell
Small about it ."
( sorry, just need to keep making fun of the cd54 thing...)



The biologicals are a bit of a primitive thing
without theory - if you change the terms a little, you could
just as easily describe provenge or tumour lysate
approaches as something a witch might suggest
( taking parts of sex organs, incubating, and then
injecting into people isn't hard to put into those terms).

science doesn't sell itself,
one job of management is to make the produce
value and make it obvious. If you really
mean politics you mean fraud. There may be
some shrewdness in competitive tactics but
when push comes to shove the value is largely
in the science. This is true of any business,
except here it is what people are used to thinking
of as science.
Making product attributes known, selling and
honestly promoting it, isn't politics as much
as marketing. If the product is that
good, even in some niche, the CEO has to discover and push this
information, not political maneuering[sic]. This
works on the FDA, the prescribers, patient advocates,
and maybe even Mr. Garcia would be interested and
you don't have to worry about it exploding.
There is always risk that some information isn't too
flattering but you need to find more information and
context until you get the best answer, not try to spin it
and hope no one notices.

Given all the interest in immunotherapy and the questionable clinical data, it is a bit disconcerting the only outside collaborator they have found in these last few years couldn't even get his plane to DC. You;d think people would be beating down the doors for cost-share collaborations with this
first working immunotherapy. If they really had confidence in it, or could even use some shrewd tactics to get
sceptical researchers to "try it," everyone with applicable
research funding would be playing around with provenge
variants.

Talk to AFFX or any other array company,
you'd think they could find a cost effective way
to characterize provenge maturation just by brute force-
look at mRNA in the culture medium as a function of
time and look for obvious things that correlate with
improved survival etc.

they need to act serious toward cassette.

What do you think it would cost to have 2-3 full
time scientists and support stuff dedicated
to the cassette science and technology?
For that matter, what can Shiffmann do to
get some help from AFFX for serial gene expression
results from the provenge soup? Correlating
this with survival, raw and improved, would
help a lot. Not sure what the gene chips cost
but compared to waiting for clinical data
when you don't know exactly what your drug
is it could look cheap in retrospect. If you noted
increased genes for various cytokines it may
be easier than probing the broth
at random for things you expect.
With a serious science effort, the FDA may look
more favorably on a Phase IV ( not saying this
changes the efficacy data, but for related influences
it sure beats a cartoon and testimonials).


Right now, that effort could align well with regulatory
requirements. Presumably to maximize the alignment,
you would want to find an in vitro assay that
you have some hope of correlating with real
clinical outcomes ( improved survival, not raw
survival ala Urdal vs Small).

Besides a lab effort, if they want people to take the
modelling seriously, they should be trying to show
how consistent it is. There should be scatter plots
everywhere showing predicted survival and the
effects of things on observed survival.
Starting with a plot of the placebo
group with observed=predicted would help- even
if a bit noisy. If this can't explain 6 month
differences they need to keep working. It could
be very simple in terms of time of diagnosis compared
to disease course but they need to come up with
markers or "trajectories" that can measure these large
offsets.

in light of lawsuit, let me repost my critique


http://www1.investorvillage.com/smbd.asp?mb=58&mn=333&pt=msg&mid=2144684


There are a number of things DNDN is doing that I don't think are really great including the way their PR presents their
limited scientific results ( see comments earlier on my conjecture regarding Small's attitude related to this ).

However, I have to reserve judgement on the specific suit until I read a (free) copy of the complaint.

Concerns about the ability to find convincing efficacy data from the interim look relate to the whole TTP and dynamics/trajectory issue yet again. I'm not claiming DNDN should have invested in a heroic, high-risk effort to find the world's first surrogate
marker for PC regression. However, they could have reasonably
diverted money from their PR efforts into a core science effort
focused on, at minimum, an in vitro assay that captures
some of the in vivo dynamics, provenge gene expression or
even simple cytokine assays as a function of time to later
correlate with patient outcome, etc. What would this cost,
a few $M/year? Of the 200+ employees how would anyone
here break them down?
Knowing the problems with the data
and the ways for addressing them, you would think if they
really had confidence in their product this would be job 1.



The amount of tractable science that could be done with
the in vitro approach and the payoff in time scales
and logicistics, aside from any product optimization issues,
could be tremendous. The payoff from a promo video and
sales staff or regulatory positions when the FDA and doctors
just want data is questionable at best. Even more speculative science, that could show zero return, would have been well worth the risk ( it has some chance of working while a promo video and cartonn would not work against a rational FDA or doctor).