Transcript of FDA February 23 News Conference on prasugrel advisory panel

The FDA provided CardioBrief with a transcript of a news conference that took place on February 23 with Janet Woodcock, director of the Center of Drug Evaluation and Research, and John Jenkins, Office of New Drugs. They spoke with reporters from Bloomberg, Reuters, and Dow Jones.
Although the transcript does not contain any significant information not already published, it might provide CardioBrief readers with a deeper insight into the thought process of the FDA.

     Editorial comment on the transcript:

A close reading of the transcript creates the impression that Dr. Woodcock is trying to protect an unspecified number of employees in the Cardio-Renal Division, the Office of Drug Evaluation, and the Advisory Committee staff. I don’t think there needs to be a witch hunt here, but I do think there needs to be more transparency: who spoke with whom, and who ultimately made the decision? How many people were involved? Did anyone object or suggest an alternate course of action?

However, an FDA spokesperson, Crystal Rice, has informed CardioBrief that “we will not be providing any further information or details at this time.” I guess the FDA’s view is that they are willing to admit that they made a “mistake,” but that once having admitted the mistake they have no further public obligation about the issue.

Here is the transcript:



Moderator: Karen Riley

February 23, 2009

3:30 pm CT




Coordinator:      Excuse me, this is the operator. I would like to announce that today’s conference is recorded. You may begin.


Judy Leon:      Okay thank you operator. This is Judy Leon from FDA’s Office of Public Affairs. And I just want to do a roll call where – we just want to make sure that we have reporters on the line who we had talked to earlier. So could we ask you all to identify yourselves and your media outlet please?


Jared Favole:      Jared Favole, Dow Jones Newswires.


Judy Leon:      Thanks Jared.


Susan Heavey:      Susan Heavey, Reuters.


Judy Leon:      Thank you Susan.


Tom Randall:      Tom Randall, Bloomberg.


Judy Leon:      Okay, thank you Tom. Anybody else on the line? Okay. For the three of you, we have Doctor Janet Woodcock, FDA’s Director for the Center of Drug Evaluation and Research and Doctor John Jenkins, Office of New Drugs.


                              And they were very eager to take the questions that you are interested in asking on today’s topic. So without wasting any time, I want to turn the call over to Doctor Woodcock and I will ask any of you to go first, let us start with Tom.


Tom Randall:      All right. Well I guess we could – maybe if we could just start with a little bit of (ethic) chronology of what happened when Lilly contacted you and how the decision was made to remove Doctor Sanjay Kaul from the panel.


Janet Woodcock:      Thank you. Yes, this is Janet Woodcock and thank you all for joining us. The chronology is the following and (unintelligible). This – what happened was a series of small errors, and as often is the case when those small errors line up, they led to a mistake.


                              The first thing that happened was when the paperwork was screened, that Doctor Kaul submitted, it was noted by a conflict of interest screener that he had these abstracts and they screened them for financial conflict of interest, but they did not focus on the fact that there might have been a question of intellectual bias.


                              So that was the first mistake. So that was not brought to anyone’s attention and that was at the time of the screening. So Doctor Kaul was added to the roster of the Advisory Committee. And that was posted along with the rest of our reviews and the company presentations and so forth on Friday.


                              When Lilly saw this, of course the companies always follow their – what people say about their investigational drugs and so forth, they contacted the Cardio-Renal Division Friday late, very late, after the posting and so forth and pointed out his work, his abstract and what he had published on the drug.


                              This was after business hours that the Cardio-Renal Division then conferred amongst the Office of Drug Evaluation (one) and they decided there was a question of whether this had constituted intellectual bias.


                              Now we have a procedure and policy in our Advisory Committee Handbook. And we can fax that to you all, oh it was emailed or faxed to all of you. So you can see what is laid out there as far as the standards for intellectual bias and also the procedures that are to be followed if some determination would be made.


                              What happened next, and bear with me in this, so it was an error for the folks that were dealing with this at the time. They did not really talk to the Center policy makers about this. What they did was they consulted with the Advisory Committee staff in the Center and that was okay, but then those folks did not talk to their Center (carriers), they consulted with Advisory Committee staff in the Office of the Commissioner.


                              Those folks did not consult with their supervisors. Instead all these people got together and decided that it was too late to make a formal determination of whether there was a conflict of interest or not, I mean of intellectual bias or not, all right. And so basically Doctor Kaul was simply disinvited because had he shown up and then it had been determined that he had intellectual bias, then he would have been here and been not been able to serve. So he was disinvited.


                              That is not the correct procedure. And at every step of the way, some error was made by multiple parties, not invoking or following the correct way of doing this that led to the fact that he was disinvited from the Advisory Committee meeting. So that is what happened.


Judy Leon:      Tom, did you have a follow up? And we will allow each of you to ask a question and a follow up. So Tom, did you have a follow up?


Tom Randall:      So, just one follow up? Is that?


Judy Leon:      Well we will see how much time we have.


Tom Randall:      All right. I guess what are you doing right now to both address some of the concerns that have been raised about the panel itself for prasugrel and, you know, that panel specifically? And also how – what are you doing to address these things happening in the future, to prevent it from happening in the future?


Janet Woodcock:      Well as soon as we realized what had happened, and this was not until after this Advisory meeting was held, we put in place procedures along every step of the way that all the individuals at all these different checkpoints are aware now. And I think it would have to break down at every single step again for this to happen again. So I can pretty confidently say that this is not going to happen again.


Judy Leon:      Okay, Jared, would you like to ask a question now?


Jared Favole:      Yes thank you. Thank you Doctor Woodcock. My question is, so was it not a mistake that he wasn’t on the panel, i.e. was it correct that he had an intellectual bias, is that the correct decision?


Janet Woodcock:      The – that issue was never formally evaluated by the FDA. Now Doctor Jenkins, who is on the phone, has an opinion on that. I have not looked at all his writings myself so I will defer that to John.


Judy Leon:      Doctor Jenkins, would you like to take that question?


John Jenkins:      Yes, as Janet said, there never was a formal agency determination about whether it rose to the level of intellectual conflict or bias. I looked at the five abstracts that were published at the American Heart Association meeting and I looked at some citations that we found on the Web of interviews that Doctor Kaul gave to the media after those presentations.


                              And in my own personal opinion, I did not see anything in those writings or in those statements that would preclude him from serving as a member of the committee. That is my personal opinion. It is not based on the full vetting of everything he may have ever written or said about prasugrel. But I think he would have been a very valuable member of the committee. He was asking many of the questions that we ourselves ask about applications and studies.


Judy Leon:      Okay Jared, would you like to ask a follow up?


Jared Favole:      Yes. So I mean does this lead from the sense of (unintelligible) call and to question the panel itself? I mean understand the panel voted unanimously to approve – to recommend, excuse me, recommend approval for the drug. But when you have one instance, and I understand it is only one, but one instance where somebody was, I guess, disinvited is the word, (unintelligible) the panel because intellectual bias does not also review singularly, it appears that it taints the rest of the panel?


John Jenkins:      Not the people on the panel, but the panel on that day if that makes sense.


Janet Woodcock:      Well as John said, we presented these issues in our presentations to the Advisory Committee. And they are the type of issues that we struggle with on a daily basis, and we at FDA are very familiar with.


                              So we believe we got reasonable advice from the Committee. Obviously many people are recused all the time from every Advisory Committee for a variety of reasons. Many people on any given day cannot come to an Advisory Committee because they have schedule conflicts, not conflicts of interest. And they may have varying views about a matter.


                              So we feel we have nine extremely competent individuals who were able to give us advice. We believe that it was a very – it was a mistake that Doctor Kaul was not included amongst the advisors at this meeting, but we do not believe that invalidates the results of the panel.


                              And I would like to defer to Doctor Jenkins if he has anything more to say about that.


John Jenkins:      Yes, I actually attended the panel discussion. And the FDA presentation that Doctor Unger gave raised many of the same questions and issues that Doctor Kaul has raised.


                              And I think the Committee discussed a lot of those same questions about the validity of the study end point, the results, the benefits that were primarily for non-fatal heart attacks versus the risk of bleeding.


                              So I think the discussion at the Committee was very robust. I think there is too much of an emphasis placed in the media on the actual vote. We pay much less attention to the actual vote than we do to the discussion and the explanations that people give of why they voted a certain way. So I think we got very good discussion of this application at that panel.


Judy Leon:      Okay. Thank you Doctor Jenkins. Susan Heavey?


Susan Heavey:      Hi. Thank you both for taking the time here. Could you specify what role Eli really played if any? There is some speculation out there that they actually called the FDA and pointed out the studies that the panelists had done?


Janet Woodcock:      Yes. I mean as we said, after the roster was posted on Friday, that would be the first time Eli Lilly or anyone outside would become aware who the Committee members were going to be.


                              And of course every firm with an investigational drug tracks all – they are almost required by FDA to track all scientific presentations or other studies that are done on that drug or even an approved drug.


                              So they knew what contributions in the literature were from any individual, and they called the FDA. Yes, they called our Division of Cardio-Renal Drugs and talked about these abstracts and so forth that have been presented and pointed out that a point of view had been professed in these – in some of these abstracts.


                              And as we have sent you, there is a part of our vetting procedure that that potential Advisory Committee member, for potential intellectual bias. And that is not very well defined in the materials. We will send you the materials.


                              But it also says very clearly in there that the Commissioner’s designate and the Center Director will make that a decision about that.


Judy Leon:      Okay, let us go another round. Tom…


Susan Heavey:      (Excuse me).


Judy Leon:      …did you have another question for…


Tom Randall:      Yes I do. Why wasn’t the Drug Safety and Risk Management Subcommittee involved in the panel?


Janet Woodcock:      Yes. All right. I will have Doctor Jenkins answer that question.


John Jenkins:      Yes, this was a preapproval meeting. And we do not routinely include the Drug Safety and Risk Management Committee in preapproval Advisory Committee decisions.


                              We looked at the data for 2007 and 2008 and there were 39 preapproval Advisory Committee meetings and only four of those were joint meetings between the Therapeutic Area Committee and the Drug Safety and Risk Management Advisory Committee.


                              And those were all for drugs that already had existing risk management plans or clear indication that FDA was planning a risk management plan.


                              Now in this case, the safety issues that were in main question were the bleeding risk, which is a well known risk of this type of drug, all the anti-platelet therapies including Aspirin have a risk of serious bleeding adverse events. So that is something that the cardiology community is very well versed in.


                              And the other main risk that was identified was the signal of increased cancers reported in the Prasugrel (orm). But going into the Committee, we had already had our Division of Oncology Products review those data. And their position was that it was not a worrisome signal.


                              So we were not proposing any sort of a risk management plan for the cancer observation. So going into the meeting, I think the Division as they were setting up the meeting did not see a particular need to include the drug safety and risk management experts.


Judy Leon:      Okay. Susan, would you like to ask another question?


Susan Heavey:      Yes, I just wanted to follow up on this intellectual bias because I have been to a number of panels and (unintelligible) the financial conflict of interest be an issue, but I have not come across the intellectual bias before. Have there been other cases that you could site? And why not just have the panelists be non-voting if you get a chance to make an agency decision on whether or not he should be there.


Janet Woodcock:      So, yes, there have been other cases. For example, sometimes a Committee member will actually be the person representing the position in front of the Committee. All right? For example, Doctor Sid Wolfe petitioned the Agency to remove propoxyphene or Darvon, Darvocet from the market. And we recently had an Advisory Committee on that.


                              Dr. Wolfe was actually also a member of the panel. But he stood on the other side of the aisle so to speak and he made the case for removal. And he, you know, had his (taun). So people who have a very strong advocacy position, and that is what is described in this Policy and Guidance Handbook of which we sent you a section, all right, those who have a strong advocacy position get to come to the committee meeting; either speak on behalf of a position, either that a drug should be taken on or off or this or that should be done, or they get to speak in the public session of the meeting and say their piece, okay.


                              So, it is – we are seeking unbiased advice from a group of experts. We certainly have ample opportunity here from advocates for various positions, both pro and con. We hear from them every day.


                              So when we have an Advisory Committee to be in an atmosphere where the individuals are considered not so biased by prior commitments to a point of view, that they are not able to consider the evidence before them in an impartial manner.


Tom Randall:      And is it common for a company to try and influence the makeup of the panel?


Judy Leon:      Could you – was that Tom?


Tom Randall:      Yes. Sorry.


Judy Leon:      Could you identify?


Tom Randall:      Sorry for speaking out of turn.


Judy Leon:      You need to identify yourself if you are going to ask a question please.




Tom Randall:      Sure. Yes.


Janet Woodcock:      It is – yes. The question was is it common for companies try influence the makeup of the panel? Since we have adopted this practice of posting at a certain time, you know, the roster and everything, we hear both from companies, not uncommonly, who bring up different findings, as well as other advocates’ members of various sides of the advocacy community.


                              Not long ago, I heard, and there was a very strong push from an advocacy group to remove a very senior member of an Advisory Committee from participating in a panel. And they put on a full court press about that. Okay, and I will not say of course where – what – in what setting that was in, but it was a very, very strong push.


                              So this is not at all uncommon from all sides of the points of view shall we say.


Judy Leon:      Okay. Jared did you want to ask another question?


Jared Favole:      Yes. There were I think three members I guess, permanent members of the Cardiovascular and Renal Committee – Advisory Committee, excuse me, who were not at this meeting. Were they recused for financial conflict of interest, for intellectual bias or I guess scheduling conflicts?


Janet Woodcock:      I do not know. I know I talked to the individuals who has worked on this. And some people were recused for financial conflicts which is – happens almost every Committee meeting we have.


                              I do not – no one was recused for intellectual bias and I do not know about scheduling. John do you know anything else?


Judy Leon:      Doctor Jenkins?


John Jenkins:      I do not know about scheduling issues. I do know that there were quite a number of individuals that were screened for the Committee and were recused for financial conflicts. So, I don’t – as Janet you said no one was excluded for intellectual bias.


                              I think it is relatively rare actually that we exclude for intellectual bias because as Janet said, Doctor Wolfe was excluded for that reason from the Propoxyphene meeting recently.


Janet Woodcock:      Although he appeared at the meeting, and for, you know, and presented at the meeting. Yes.


Judy Leon:      We have time for just one more question.


Jared Favole:      I guess – if I can take it – this is Jared from Dow Jones again.


Judy Leon:      Okay.


Jared Favole:      How many people were considered for this meeting who were recused, not just the people on the permanent members, but outside members like, you know, maybe Doctor (Nisty), (Mistay) and I know there are a few other names who were potentially considered. I do not know if he actually was but…


Janet Woodcock:      I don’t know how many. I was told that a number of people were screened and had to – and could not qualify because of conflicts of interest. Often because their institution had taken money from one or more parties say, had done a study for a competitor, not necessarily that person, but yes, it is difficult to find people who are knowledgeable in this area who have not participated in clinical trials.


Judy Leon:      Okay. I would like to thank you all for joining us this afternoon, and as always, you can follow up with the FDA’s Office of Public Affairs, either me, Judy Leon, Karen Riley or Sandy Walsh. Thank you everyone.




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