Yes there are many names and it can get confusing for the reader, but repeating the same stuff over and over again is NOT the right strategy to get over that.

I’m a very avid reader and interested in this topic and I’m struggling not to give up at this point. You have probably lost most readers by piece #2.

Nice work with the charts!

Map 1:
http://www.flickr.com/photos/39874373@N03/3684680219/sizes/o/

Map 2:
http://www.flickr.com/photos/39874373@N03/3684680227/sizes/o/

http://seekingalpha.com/article/138920-stanford-financial-s-cfo-laura-pendergest-holt-a-victim-of-overzealous-regulators?source=yahoo

“show” vs “establish” vs. “is there”

Apparently nobody seemed to notice that we have not two but three phrases in the Provenge Panel question controversy: “show” vs “establish” vs. “is there”

(It all depends on the meaning of “is”

Many point out that a regulatory form question should have been:
“Does Provenge show substantial evidence of efficacy?”

But it was never asked in that form!

At first the question was posed as:
” Does the submitted data establish the efficacy of…”

And after the aborted vote which seemed to go toward “No” answer, it was changed to :
” is there substantial evidence that the product is efficacious.”

One can argue that it was changed from a too strong one to a too weak one.

“establish the efficacy” is more demanding than ” to show substantial evidence”
“is there substantial evidence”: is a weaker standard than “show substantial evidence”

Some people will perceive these phrases as three different ones, some as two different ones, some as all the same.

In mathematics “to show” is used interchangeably with “to prove”. So some people with scientific background may feel that “to show” and “establish” are equally strong. And many may feel that “is there” is a weaker then regulatory(?) “to show”.

It is clear, that the Provenge panelists perceived “is there” as weaker requirement than “establish”.
But the supposed proper question “to show” was never asked.

In my opinion (I knew you would ask:-) the question posed to the Panel was at first more demanding than regulatory one, and then it was changed to a weaker one than regulatory.

With all this in mind, I believe that analysts questioning CEO about this phrase changed in the middle of a vote, and asking if FDA will be happy with the change, was very much appropriate. In fact it should have been cleared up by the CEO perhaps in consultation with FDA. But both FDA and Dendreon’s CEO apparently don’t like transparency.

Chapter-7 had plenty of space to quote verbatim all the meaningless congratulatory statements but found no space to even note that the controversial question and it’s change. Pretending that it never happened and analyst were asking questions in vacuum.

As Ocyan suggested in his post http://investorvillage.com/smbd.asp?mb=971&mn=287784&pt=msg&mid=7535019 one can search FDA web site.

I found that the phrase “establish efficacy” is in fact quite common. See the examples referred below.

So?

Well, perhaps a conspiracy? Or perhaps this word-use politics go much deeper than Provenge. Perhaps different people use different wording to influence others?

I don’t know about conspiracy, it is the Mitchell’s domain.
But I do see how people often replace words with a seemingly similar ones, and yet inappropriate.

I already gave an example of word-politics from this very chapter-7, where Mitchell used inappropriate “panel-approved drug” to make his case stronger, knowing that Panels don’t do “approvals”.

So was the Panel’s 2nd question a result of a conspiracy or FDA politics or an innocent screw-up. I don’t think we will ever know. FDA likes to compete with CIA in keeping their internal processes secret from the public they serve.

Those that want to improve FDA should push for changes in regulations, for greater transparency, for minimizing conflicts of interest, etc… This anti-conspiracy crusade is just a distraction.

The links between FDA politics and Wall Street shenanigans if any, are most likely not a conspiracy but elements of COI.

= = =
Note_1, for those not familiar with Dendreon-Provenge story.
The 2007 Panel’s question-2 is now subject of the “conspiracy” theory, or an example of FDA politicking of the worst kind. It is not material any more to Provenge approval, which stands mostly on the strength of its newly completed in 2009 Impact trial.

Note_2. This perhaps should be posted on the IV Dendreon board. But IV board owner arbitrary censors posts. DeepCapture is so far remarkably patient with critics, as well as with some of it’s supporter’s gutter language and “subtle” idiotic threats to me.

= = = = = =
FDA examples:

http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020038s032lbl.pdf
Data submitted to the FDA was insufficient to establish efficacy in any childhood malignancy.

http://www.fda.gov/ohrms/dockets/ac/96/questions/3198q1.pdf
Do the results of the open-label, historically controlled studies conducted in France establish the efficacy of this regimen for use in the United States?

http://www.fda.gov/BiologicsBloodVaccines/Vaccines/QuestionsaboutVaccines/ucm070430.htm
“For phase 3 studies, the sample size is often determined by the number required to establish efficacy of the new vaccine, which may be in the thousands or tens of thousands of subjects. ”

http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/ucm072130.htm
Guidance for Industry: Safety, Efficacy, and
“Phase 3 clinical trials conducted to establish efficacy and safety. ”

http://www.fda.gov/NewsEvents/Testimony/ucm114741.htm
Potential Merits of Cannabinoids for Medical Uses
“These studies establish efficacy for a particular indication, examine additional uses, may provide further safety data …”

http://www.madcowprod.com/06202005.html

When Advisory Committees are called, they get to see the drug presented by the sponsor and then by FDA staff. Then the panel discusses the treatment.

After all that is done, the panel gets to vote on two, pre-specified, voting questions. They are regulatory questions. The FDA is simply trying to check the drug on two counts, Is it safe? and Does it show evidence of efficacy? The first voting question is simple and to the point, Is Provenge safe? All 17 panelists voted yes.

The second question was a problem. When the Chairman of the Advisory Committee, in this case Dr. James Mulé, read the question to the panel, here is what he read:

Does Provenge establish efficacy?

The panel struggled with that question. As one doctor said, it is not a question you can answer yes or no, which the panel required in order to tally votes.

Soon it was discovered that that question was not the regulatory question. Right there, right at that hearing, some FDA folks looked up the regulatory question and found out “Does Provenge establish efficacy?” is not a regulatory question.

That is when a lot of us said, “Hey, wait a minute here. Somebody has tampered with the regulatory question! Who gave that question to the Advisory Committee Chairman to read to the panel?”

So then, Chairman Mulé was given the regulatory question. Here it is:

Does Provenge show substantial evidence of efficacy?

So these are the two questions the Lazard boys were challenging Mitch Gold about.

Bastardized question –> Does Provenge establish efficacy?

Regulatory question –> Does Provenge show substantial evidence of efficacy?

These are the two questions. The first one was a bastardized question. Who did that? No treatment has ever had to answer that because it is asking the panelists if they are sure Provenge is 100% efficacious. No treatment before an FDA panel has had to measure up to that. Why did Provenge have to be measured that way? It just has to show substantial evidence, not a 100% sure thing.

Well, as we know, when the panel voted on the regulatory question, it was a convincing, 13-4. That didn’t work out for the Lazard boys, so Favus and Sendek tried to paint a picture that the FDA somehow lowered its standards and made it easier for Provenge by “changing the question”. The truth of the matter is, somebody played with the question (was it Pazdur & CDER?) and gave it to Dr. Mulé and when the panel struggled, the CBER folks looked up the regulatory question during the Advisory Committee hearing.

Since it was posted on an investment message board that Lazard Capital was a megashort, and the poster said he knew Elliot Favus, he knew they needed help. So they jumped on the question change acting like FDA made it easier for Provenge. No, FDA didn’t make it easier for Provenge, some of the folks at FDA looked up the question and discovered the regulatory question is: Does Provenge show SUBSTANTIAL EVIDENCE of efficacy? The panel voted yes 13-4. The Lazard Capital boys didn’t like that and too bad. They were wrong.

Here is the actual testimony – The FDA always wants to know if a treatment is safe and efficacious. You can read this public record here:

http://www.fda.gov/ohrms/dockets/ac/07/transcripts/2007-4291T1.pdf

The safety question was just voted on and the secretary announces it:

MS. DAPOLITO: Okay, for the record the vote was 17 yes, zero no, zero abstain for Question 1.

So then the Chairman, Dr. Mulé, moves to the second question, the efficacy question:

DR. MULÉ: Okay, we’ll move on to Question 2. Again I’ll read it. Does the submitted data establish the efficacy of sipuleucel-T in the intended population?

The panel struggled answering yes or no. Here are some panelists’ reactions:

“The question that I grapple with is, is the evidence that’s here so far, does it establish the therapy. Is the therapy established that, with full confidence,”

“Well, so I guess at this point I’m not entirely sure how to answer this question. It’s not a yes or no question in my opinion the way it’s phrased. I mean, it’s really very absolutely phrased,”

The panelists were having trouble with the question. So Dr. Mulé consulted with the folks from CBER who had been assigned the Provenge BLA:

DR. MULÉ: Dr. Witten, with respect to this question–

(Laughter)

DR. MULÉ: Is it — from your standpoint and the FDA’s standpoint, are you looking for definitive answers to this question? Is it necessary to rephrase this question?

So that is when the folks from CBER looked up the regulatory question. Dr. Celia Witten, the Spokesperson for FDA for this hearing, sets the record straight:

DR. WITTEN: Yes. The regulatory definition is “provide substantial evidence.” So that’s our standard. Is there substantial evidence that it works. Is there substantial evidence of efficacy, if that helps. So is there substantial evidence.

DR. MULÉ: Okay. So just to clarify what you’re asking, is there substantial evidence that the product is efficacious.

DR. WITTEN: Yes.

After they voted on the regulatory question, the secretary announces the vote:

MS. DAPOLITO: Okay, for the public record, the question was, is there substantial evidence the product is efficacious. The vote was 13 yes, 4 no, zero abstain.

So the panel voted overwhelmingly positive on the regulatory question much to the disdain of the Lazard boys. That is why Favus and Sendek acted like jerks on the conference call. They had nothing going in their favor so they tried to confuse things. They were wrong.

IF THIS SCUMBAG WAS STILL IN JAIL ,WHERE HE BELONG OR DEAD PROVENGE WOULD ALREADY BE ON THE MARKET….AND FATHERS AND GRANDFATHERS WOULD BE SPENDING TIME WITH LOVED ONES U SOB…

You are one sad, sad individual. Don’t you have anything better to do than poke holes in the hard work that those are doing to reveal these crooks for who they are?

Stop wasting your time fighting against people doing good and join them. You go after the wrong people.

Jeff

DCN > criticism that aspects have been overlooked, when eight more chapters remain to be published, is disingenuous.

Not “overlooked” . _Intentionally_ omitted to make false points.

When you use cheap tricks of omission and twisting facts, your credibility is diminished. Errors are OK, but one should be able to admit it and correct them.

I point out only a small subset of tricks used by Mitchell. See for example his expression “panel-approved drug”. Mitchell (presumably) knows that Panels don’t “approve” any drugs. He is twisting the words just like presumably whoever it was that twisted the 2nd question posed to the panel.

Sure, in his case it is a small thing, comparing to a formal Panel question, but it is still distasteful to me.

Here we go again…

I’m shocked.
Well, not really, but I should be
You took many weeks to study Dendreon’s Provenge story and wrote a 15 part expose. But you appear to be ignorant on one of the most controversial aspects of Provenge approval process?

Didn’t you bother to read the minutes of the Provenge Panel meeting? Are you not aware of a controversy over the efficacy question?

You wrote: “The FDA panel asked two questions. Is Provenge safe? And, is there “substantial evidence” of efficacy?” But this is an implicit lie, a lie by omission, and you know it!

In short:
The second question posed to the Panel was: (page 370) Does the submitted data establish the efficacy of sipuleucel-T in the intended population?
After several No votes and the panel members questioning the use of the word “establish” which suggests unequivocally that Provenge works, the question was rephrased. And the voting redone with:

(page 378) is there substantial evidence that the product is efficacious.

Well, I believe that you did read the minutes, and are very well aware of the controversy surrounding the change of the question.

So why are you pretending to be surprised that some of the financial ANALysts actually did they work and tried to question CEO about this issue. And to tried to find out if FDA is happy with the final, modified question.

Perhaps you should instead criticize other ANALysts and journalists for limiting themselves to just congratulations, and not asking hard questions. It is their job and duty after all to try to find out as much as possible. It is not their job to be smiling flower delivery boys.

I’ve heard from people that the proper wording of the second question should in fact be like that in the final, corrected vote. That this is the normal FDA phrase. I think somebody pointed to actual FDA statement or regulation which clarifies this(?) You should include this if you can.

If the original question was inappropriate, the FDA owes an explanation. It could have been an innocent screw-up, or very much not an innocent one.

Instead you switch to your favorite and gossipy theme of who knew whom. This could eventually be helpful to show a conspiracy, but a wrongdoing has to be established first. Asking pointed or tough questions of CEOs is most appropriate and not a wrongdoing!

So far you have added very little, and in this case even tried to gloss over and mislead about an major controversy surrounding Provenge in 2007.

Mitchell : “I’m not one for conspiracy theories, but…”

Very funny!
= = = =
(*) minutes of the Provenge Panel meeting: http://www.fda.gov/ohrms/dockets/AC/07/transcripts/2007-4291T1.pdf )