Header graphic for print
Dangerous Drugs & Medical Devices News & Commentary on Prescription Drug & Medical Device Lawsuits

Testimony of Suzanne Parisian Concerning the Ortho-Evra Patch

Posted in Misc. Drugs

Expert Witness Suzanne Parisian gave this testimony in an Ortho-Evra lawsuit entitled Arbino v. Johnson & Johnson.

Q. Where does it say it's similar? It just says it contains an estrogen and a progestin.
A. Called a combination hormonal contraceptive. As you know, those have been on the market since 1960. So, the information that you're asking me in one sentence may be lost on them, because they have been using and prescribing combination hormonal contraceptives, and this is being represented to them as a combination hormonal contraceptive.
So, you are asking what would every physician, board certified OB-GYN see when they see that, and I think that you cannot take it out of context. This is being provided to them as a product that is approved by the FDA and is a combination hormonal contraceptive.
So, it may be lost on when you take that sentence out of context and try to say that all OB-GYNs would know there's no information about this product as a transdermal because, obviously, it is now being provided to them as approved.
Also, it's been provided to the FDA as comparable to an oral contraceptive in terms of allowing bridging of data
So, it's not a clear-cut sentence taken out of context and what would be interpreted by all OB-GYNs.
Q. How about the sentence that starts the next paragraph The use of combination hormonal contraceptives is associated with increased risks of several serious conditions, including myocardial infarction, thromboembolism, stroke, hepatic neoplasia and gallbladder disease. And then it continues.
Any reason to doubt that a board certified OB-GYN, in 2001 or 2002, didn't know that combination contraceptives, for at least thirty-five or forty years, were associated with an increased risk of myocardial infarction?
MS. PARFITT: Objection Again, she can't get behind the minds of every board certified OB-GYN. I object to the form of the question
Doctor, if you can respond to the question, okay.
A. Again, the terms are not clear-cut, because you are talking about to an OB-GYN who has used combination hormonal oral contraceptives since 1960, and then you are taking it out of context, because if you look at the paragraph above, you just said that there is no epidemiological data, and then you are coming back here talking about birth control pills. We are switching between transdermal and birth control pills.
So, that second paragraph is providing information that a board certified OB-GYN and a family practitioner, they are not the only ones who prescribe — OB-GYNs are not the only ones who prescribe birth control pills.
Okay. So, you're talking about family practitioners. You're talking about general practitioners. You're talking about nurse practitioners. You're telling them that this product is of the same risk as an oral contraceptive.
Now, if you know from the data, that's not necessarily true, because up in the paragraph above it, they say there's no data to tell you if this actually performs like an oral contraceptive.
So, in some ways, the second paragraph is speaking specifically about the history of oral contraceptives.
Q. Is there any reason to doubt that anyone, board certified OB-GYN, family practitioner, didn't know in 2000 that there's an increased risk of thromboembolic events associated with hormonal contraception?
MS. PARFITT: Objection The question was just asked, and she gave a very detailed response to the question.
I think in light of the fact we got a late start today, we need to start to move forward and not ask the questions twice.
Q. (By Mr. Winter) You can answer the question, Doctor. That was not the question I asked before.
A. You're talking apples and oranges. Yes, there has been a history, and this is the class labeling. There has been a history of increased risks of oral contraceptives.
Having gone through all the documents and seen even corporate documents, we know, sitting here today, that the company knew that this product did not perform as a birth control pill. But they're actually using class labeling for a birth control pill and telling physicians and all the people who prescribe it from state to state, that this has an increased risk which is associated with birth control pills.
There's never been a transdermal contraceptive product, and that's not what's stated there. It states that they are talking about class labeling, that birth control pills have an increased risk of several serious conditions.
So, if I was a physician who was prescribing a birth control pill, I would see that, and I would read that as being consistent with oral contraceptives, which, as we know, is what the FDA was told, that this product was consistent with an oral contraceptive.

EXAMINATION

BY MR WINTER:
Q. Good morning.
A. Good morning.
Q. Sorry for the late start, Doctor, but I'd like to begin by asking you about some documents already marked
You've just been handed a document marked as Exhibit 1, which is an FDA memo. I take it although though I didn't go through every document that you brought with you, you did review documents that the FDA produced in response to subpoenas served in this case; correct?
A. Yes, sir.
Q. And you know how Bates numbers work. We can agree that that Bates number on the bottom means this was produced by the FDA?
A. Yes, sir.
Q. Now, you worked at the FDA for approximately four years?
A. Yes, sir.
Q. '91 to '95?
A. Yes, sir.
Q. Okay. Now, did you work in the Center for Drug Evaluation and Research?
A. No, sir.
Q. Okay. You know who Doctor Houn is; correct?
A. Yes, sir.
Q. Now, she was, at the time of this memo, which is November of 2001, the office director, correct?
A. Yes, sir.
Q. Now, you were on what's call the device side of FDA?
A. Yes, sir, Center for Devices.
Q. And was your most senior position on the device side equivalent to an office director in the Center for Drug Evaluation and Research?
A. No, sir. I was the chief medical officer.
Q. Which would be higher or lower than the office director?
A. I'm not sure where it would fall. There were six office directors, and there were only two chief medical officers. I wasn't with the director of office of Device Evaluation So, I'm not sure exactly where it would fall.
Q. Now, you understand that on or about November 20th, 2001, FDA approved Ortho Evra for marketing in the United States; correct?
A. Yes, sir.
Q. Now, when FDA makes this determination, they usually document that determination; correct?
A. Yes. You mean approve it?
Q. Yes.
A. There's an approval package, and I believe this memo may have actually been on the FDA's website.
Q. As part of the approval packet —
A. Correct.
Q. –for Ortho Evra?
A. Correct.
Q. By the way, when you worked at FDA, were you involved in the approval of any transdermal product?
A. I don't believe so. We had ionophoretic devices, but I don't know that we had transdermal. Sometimes those are lumped into the transdermal.
Q. Sitting here, you do not recall being involved in the approval of a transdermal product while you were at FDA?
A. Only the iontophoretic, which was a drug release type of a product but it's a device.
Q. And Ortho Evra was approved as a medicine as opposed to a device; correct?
A. Correct, under the drug regs, correct.
Q. Looking at Exhibit 1, did you ever sign off on any medicine for approval purposes while you were at FDA?
MS. PARFITT: Objection.
A. No, sir.
Q. (By Mr. Winter) Now, I've looked at your report, and there is discussion in your report about two reports of pulmonary embolism during the phase three studies of Ortho Evra
Are you familiar with those two reports?
A. Yes, sir.
Q. Now, if we look at Exhibit 1, what it does, it documents Doctor Houn's concurrence with the Division of Reproductive and Urological Drug Products to grant market approval for Ortho Evra
So, it's the office director concurring with a division recommendation to approve; correct?
MS. PARFITT: Objection.
A. Yes, yes, sir.
Q. (By Mr. Winter) Now, if you look on in the memo, it says: Overall PEARL index for this product is similar to oral contraceptives.
You understand what the PEARL index is?
A. Yes, sir. And that is what their primary indication was in terms of showing efficacy, was the similar PEARL index to oral contraceptives.
Q. No reason to doubt that Doctor Houn meant what she wrote in Exhibit 1?
MS. PARFITT: Objection.
A. No, sir. Nor have I ever suggested that there would be a reason to doubt what she wrote based on the information that she was provided.
Q. (By Mr. Winter) Now, the next sentence says: Safety was comprehensively reviewed by the Division.
Any reason to doubt what Doctor Houn wrote there?
MS. PARFITT: Objection.
A. Well, her words speak for themselves. She states that the FDA has approved this product based on meeting the minimum standard of safety and effectiveness.
Q. Actually, what she says: Safety was comprehensively reviewed by the Division
Any reason to doubt the veracity of that statement?
MS. PARFITT: Objection
A. No, sir, in that she's talking about the data that was provided to the FDA.
Q. (By Mr. Winter) And then the next sentence says: Careful consideration was given to the two cases of venous thromboembolic events.
We can agree that that refers to those two reports of pulmonary embolism in the research studies?
A. Yes, sir.
Q. So, can we agree, there's no question that FDA, prior to approving Ortho Evra, gave careful consideration to those two reports?
MS. PARFITT: Objection
A. That's what it states, yes.
Q. (By Mr. Winter) Now, the next sentence says: This product increases the risk of venous thromboembolic events, as do other combined hormonal forms of contraception, and this fact is included in the labeling.
You agree with that statement; right?
A. Well, the FDA, this is the FDA's interpretation of it yes. We've never questioned that they approved the product.
Q. And, well, well say okay to that one. But then, what about the fact that the increase risk of venous thromboembolic events is included in the initial labeling. Do you see that sentence?
A. Correct There was a description of the two events in the labeling. Now, we're aware this is a negotiated labeling in terms of between the company and the FDA.
Q. But whatever the negotiations were, those two reports of PE and those phase three studies were described in the first package insert for Ortho Evra; correct?
A. Yes. And we haven't stated otherwise.
Q. Okay. And while it's in negotiation, who has final authority when labeling is going to be approved for a product that hasn't yet come on the market?
A. Well, when you are talking about final authority, it is a negotiated process, and I think the GAO and OIG have all stated that most labelings negotiated at the very end of the package, and there's a time constraint in terms of user fees.
So, it is actually a negotiated process, and FDA is trying to get the best labeling that they can that reflects the clinical trials.
So, it is not that the FDA wrote that labeling, but Doctor Houn is obviously signing off on the final label.
Q. Well, didn't the medical officer who reviewed the NDA for Ortho Evra suggest language as to those two reports of PE?
A. He suggested language that would inform the physician that there was an increased risk and that the risk for VCE for this product was not known, since it is not a birth control pill, and he wanted that information reflected in the final labeling
Q. And that information was, in fact, reflected in the final labeling; correct?
A. There is labeling that describe the two PEs, correct So, FDA did sign off on its final labeling.
Q. And the initial labeling also said that the relationship of Ortho Evra to these events was unknown because it was not an oral conceptive, but a transdermal product; correct?
A. I believe it did. Do you want me to look specifically at the very first labeling?
Q. We will.
A. Okay.
Q. But your recollection is that it does have some discussion?
A. I know that the two PEs are discussed.
We can specifically look at what you want to look at, if you want, at this point in time.
Q. Well, let&
#039;s go on a little bit fur

ther with Exhibit 1 for a second.
The last paragraph, see that? I've reviewed the action package.
Now, the action package is the totality of information that FDA pulled together at the conclusion of its review of the NDA; correct?
MS. PARFITT: Objection.
A. That's what an action package is.
Q. (By Mr. Winter) And then it says: I presented, meaning Doctor Houn, my labeling comments to the Division about three weeks before the date of this memo. Correct?
A. Correct, that's what she stated.
Q. And she wanted inclusion of racial breakdown of the efficacy database?
A. That's what it states.
Q. And moving statement about efficacy failure in obese women forward to highlight this observation Right?
A. Correct.
Q. And then the Division transmitted these comments to the sponsor, and the final labeling was agreed to; correct?
A. Correct And it was based on the clinical information that was provided for the product to the FDA.
Q. And the clinical information provided to FDA for this product did include those two reports of PE; correct?
MS. PARFITT: Objection
A. Correct. But we also know that those reports of the PE came from the clinical lots. This was not the manufactured lots. So, from what the FDA's approval was, this was a well controlled product with the estrogen levels within the twenty micrograms in terms of delivery.
So, the FDA did approve a product described it very carefully in the first labeling, and that was the product that they approved.
Q. And the labeling talked about an increase, potential increased risk of thromboembolic events; correct?
A. It specifically talked about two patients that had occurred in the clinical trials that had BTE.
MR. WINTER: Why don't we mark this one.
(WHEREUPON, a certain document was marked Defendant's Deposition Exhibit No. 2, for identification as of March 11, 2008, and is attached hereto.)
MS. PARFITT: Thank you.
Q. (By Mr. Winter) Doctor, if you could take a look at Exhibit 2.
A. Yes, sir.
Q. You can quickly leap through it I'm going to ask you some specific questions, but this is the initial prescribing information for Ortho Evra, approved by FDA in November of 2001; correct?
A. Correct And it's the 20 micrograms of PE, correct.
Q. Now, you're not a board certified OB-GYN; correct?
A. That's correct.
Q. Okay. Now, let's look at a couple of these sections. First, if you could go to Page 849, do you see the last on the Bates range?
A. Yes, sir.
Q. It's up front?
A. Oh yes. They're all the same number, otherwise. 849.
Q. In the Indications and Usage section — I'm sorry. How about trying 407779?
A. That's the document ID.
Q. All right. Find Indications and Usage.
A. Okay. That might work better.
Q. Yeah, yeah that will work easier. I believe it would be Page 10.
A. Okay.
Q. The paragraph that Doctor Houn wanted about the question of efficacy in women greater than 198 pounds is in the approved labeling?
A. Let's see, specifically. Right.
MS. PARFITT: Objection.
A. I didn't think she said 198 pounds, specifically. She just said obese women…just to be precise.
Q. (By Mr Winter) And, then, it also has the reference for the patient labeling to discuss with patients above 198 pounds the need for choosing the appropriate contraception.
MS. PARFITT: Are you referencing Exhibit 2, or are you referencing Exhibit ?
Q. (By Mr. Winter) Exhibit 2, the paragraph right after, "with respect to weight", the next paragraph says: Healthcare professionals who consider Ortho Evra should discuss the patient's individual needs in choosing the most appropriate conception option. Correct?
A. Correct. That is what's confusing me. It doesn't come from Doctor Houn
Q. Doesn't she say that highlight this observation in the patient, in the professional labeling and patient labeling; correct?
MS. PARFITT: Objection.
A. No. She said that you have to say about efficacy failure in obese women They're saying here about using a second form of birth control. That's a different statement from what she's saying.
Efficacy failure could mean that you would say that it should not be used in women over 198 pounds.
Q. (By Mr. Winter) Isn't that highlighting to the healthcare professional in the Indications that they need to discuss with patients more than 198 pounds what their needs are in choosing the most appropriate contraception?
MS. PARFITT: And the objection is, if you are asking if that's what Exhibit 2 says, that's one question If you're asking whether or not Exhibit 2 reflects what's said in Exhibit 1, that's a different question It's not clear which question you're asking.
Q. (By Mr. Winter) Let's take the first question Isn't that what the Indications and Usage say?
A. It does say that about healthcare professionals, but it doesn't come directly from Doctor Houn's letter.
She's saying that they want to say that it's the efficacy failure in obese women, meaning it doesn't work in obese women, which is a little different than discussing that you need to have other considerations.
Q. Didn't she say in Exhibit 1: Efficacy failure, highlight this observation, professional labeling and patient labeling. Correct?
MS. PARFIT: Objection The document speaks for itself.
A. Well, the document speaks for itself.
When I read the words, efficacy failure, means it doesn't work in obese women, and they need to highlight that observation in professional labeling and patient labeling.
It was chosen to put in here that women over 198 pounds should discuss — So, that's how they chose to say that. That is not necessarily coming exactly from her letter.
Q. (By Mr. Winter) The paragraph before it we just talked about that. It says: Ortho Evra may be less effective in these women after discussing the efficacy failures. Correct?
MS. PARFITT: Objection
A. When they say may be less effective, which is actually a softer statement than what she's saying, which is efficacy failures.
So, that, obviously, was negotiated as to what they were going to put in there.
When you say something is an efficacy failure, that's saying it doesn't work and you need to tell physicians that it's not going to work in women over 198 pounds, which in the American population is significant, because there are many women over 198 pounds.
Q. (By Mr. Winter) And that's what's reflected in the Indications and Usage section; correct?
MS. PARFITT: Objection
A. It's not clearly stated that it does not work. We're talking about in terms of the wording of the labeling. It's suggesting that a physician needs to know that it may not work for 198 pounds and over, that there has to be a discussion.
She's clearly saying that there's an efficacy failure in women over 198 pounds. This is a little bit softer language, in that a physician can read this and think that a woman over 198 pounds, that this would be a suitable product and that you need to discuss it but it's good for her.
MS.PARFITT: And this refers to Exhibit 2?
MR WINTER: Referring to Exhibit 2.
A. Exhibit Number 2. And Exhibit Number 1, she's just outright saying it is an failure, which is a little bit more of an extreme, that you don't use it for women over 198 pounds. This is actually not a good product for them
Q. She approved what'sin Exhibit 2?
MS. PARFITT: Objection.
A. Again, it's a negotiated labeling. So, she — Obviously, the product has been approved by the FDA, and I ne
ver suggested that it hasn't The FDA was using the info

rmation that they were being provided.
So, if you're asking me specifically about what Doctor Houn said in her letter, yes, she did approve it but she said efficacy failure and that physicians need to have that information
It is a little different in terms of what's written there.
Q. Didn't she approve specifically what's written there in Exhibit 2?
MS. PARFITT: Objection The question has been asked and answered. Actually, multiple times.
A. She reviewed the packet Let's see the date that it was approved on
Q. (By Mr. Winter) Look at the first page, Doctor.
A. Okay. First page. It should have a date on it. November 20th which is exactly the same day that she's writing the letter. November 20, 2001 is the date that this was approved, and this is the date of her letter.
Q. Now, if we go back up to Page 9 of Exhibit 2, the Indications and Usage section, the same section
A. Yes, sir.
Q. There is the breakdown by race of the efficacy database. Do you see that?
A. Yes, sir.
Q. Which is a comment that Doctor Houn wanted incorporated in the labeling?
A. Yes, sir.
Q. Okay.
A. And I think it had been discussed in the medical officer's review, too.
Q. Now, let's move forward to the Warnings section of Exhibit 2.
A. Page 13?
Q. Page 13. Now, the first warning, that box, you see that on cigarette smoking?
A. Yes, sir.
Q. Is that class labeling language?
A. Yes, sir.
Q. For —
A. For birth control pills.
Q. Yeah For combination oral contraceptives, that cigarette smoking, black box is class labeling?
A. Yes.
Q. In fact there are several places in the Ortho Evra package insert that incorporates class labeling for combination oral contraceptives; correct?
MS. PARFITT: Objection
A. The company chose, in their discussion about the design of their labeling, to use class labeling.
Q. (By Mr. Winter) And FDA approved that judgment; correct?
A. Based on the representation the company had made that it was comparable to an oral contraceptive.
Q. And FDA's review of whatever data it had available to it to make whatever independent judgment it wanted to make about the comparability of Ortho Evra to an oral contraceptive; correct?
MS. PARFITT: Objection
A. I don't understand the question. Could you please restate that?
Q. (By Mr. Winter) Sure.
MS. PARFITT: Actually, I'm not sure that was a question
Q. (By Mr. Winter) Well, FDA does look at data regarding oral contraceptives; correct?
MS. PARFITT: Objection
A. There are approved oral contraceptive products, correct.
Q. (By Mr. Winter) And that data regarding those approved products is available to FDA; correct?
MS. PARFITT: Objection
A. In that they are approved products that are approved by the FDA, yes.
Q. (By Mr. Winter) And during the review of the Ortho Evra NDA, FDA did look at data it had regarding approved oral contraceptives; correct?
MS. PARFITT: Objection.
A. In terms of this NDA, it was based on bridging data for this company's oral contraceptives.
So, actually, the company had represented to the FDA that this product behaved exactly like it's oral contraceptives. So, therefore, the FDA had looked at their oral contraceptives before.
The class labeling was labeling that is generally available to help manufacturers design labeling. It is not mandatory labeling.
So, if, indeed, a company knows that its product is not an oral contraceptive or does not behave like an oral contraceptive, then it is not appropriate for them to have chosen to just rely on the oral contraceptive label.
From what FDA was told by this company, then it would make perfect sense for them to have allowed them to rely on oral contraceptive labeling.
Q. (By Mr. Winter) If you could look in the first paragraph after that box, you see the second sentence? There's no epidemiologic data available to determine —
A. Yes, sir.
MS. PARFITT: Why don't you let him complete the sentence.
A. Is there a question?
Q. (By Mr. Winter) Well, you read the whole sentence?
A. Yes. There's the second sentence there that I read.
Q. Right Is that class labeling, that sentence?
A. No, because that's talking about transdermal route compared to an oral route.
Q. Any reason to doubt that a board certified OB-GYN in 2002 wouldn't understand that sentence?
MS. PARFITT: Objection.
A. Well, I think you're asking me something that — I mean, you may want to rephrase that because I don't know exactly what you want on that.
In terms of aboard certified, would a board certified? I believe there are board certified OB-GYNs in this case, and I think to talk about what they would know or would not know, but as a person who has written labeling, to assume that all OB-GYNs have never used a transdermal product would know what that means is a large assumption, particularly in 2001, because there had been no transdermal oral contraceptives — I mean, transdermal contraceptives.
So, you are asking how would they know. There had not been any epidemiological studies. There had been no information So, there would not be a large database for even a board certified OB-GYN to understand what that means.
Q. (By Mr. Winter) Well, isn't that sentence saying there is no data available to determine whether transdermal would be different than oral?
MS. PARFITT Objection
A. Well, you're asking me two questions.
You're asking me what an OB-GYN would have known in 2001.
Q. (By Mr. Winter) No. Actually, that was not the question.
The question was, is there any reason to doubt that a board certified OB-GYN would not understand that sentence?
MS. PARFITT: Objection. This witness is not in the position to read the minds of every board certified physician when they read that label.
Answer the question, if you can.
MR. WINTER: You can answer the question
A. I think I did. I think I did. In terms of labeling, it really does not convey any information Of course, there hadn't been any epidemiological studies, because this product hasn't been on the market.
In terms of a transdermal route, this is in the context of a product that is being marketed and provided to them as a contraceptive product, which would be the sentence before it.
So, this type of a statement is really unclear what it means to aboard certified OB-GYN. When you take the statement before it that this is similar to combination hormonal contraceptives, which most OB-GYNs have had use of since 1960.
Q. Where does it say it's similar? It just says it contains an estrogen and a progestin.
A. Called a combination hormonal contraceptive. As you know, those have been on the market since 1960. So, the information that you're asking me in one sentence may be lost on them, because they have been using and prescribing combination hormonal contraceptives, and this is being represented to them as a combination hormonal contraceptive.
So, you are asking what would every physician, board certified OB-GYN see when they see that, and I think that you cannot take it out of context. This is being provided to them as a product that is approved by the FDA and is a combination hormonal contraceptive.
So, it may be lost on when you take that sentence out of context and try to say that all OB-GYNs would know there's no information about this product as a transdermal because, obviously, it is now being provided to them as approved.
Also, it's been provided to the FDA as comparable to an oral contraceptive in terms of allowing bridging of data
So, it's not a clear-cut sentence taken out of context and
what would be interpreted by a

ll OB-GYNs.
Q. How about the sentence that starts the next paragraph The use of combination hormonal contraceptives is associated with increased risks of several serious conditions, including myocardial infarction, thromboembolism, stroke, hepatic neoplasia and gallbladder disease. And then it continues.
Any reason to doubt that a board certified OB-GYN, in 2001 or 2002, didn't know that combination contraceptives, for at least thirty-five or forty years, were associated with an increased risk of myocardial infarction?
MS. PARFITT: Objection Again, she can't get behind the minds of every board certified OB-GYN. I object to the form of the question
Doctor, if you can respond to the question, okay.
A. Again, the terms are not clear-cut, because you are talking about to an OB-GYN who has used combination hormonal oral contraceptives since 1960, and then you are taking it out of context, because if you look at the paragraph above, you just said that there is no epidemiological data, and then you are coming back here talking about birth control pills. We are switching between transdermal and birth control pills.
So, that second paragraph is providing information that a board certified OB-GYN and a family practitioner, they are not the only ones who prescribe — OB-GYNs are not the only ones who prescribe birth control pills.
Okay. So, you're talking about family practitioners. You're talking about general practitioners. You're talking about nurse practitioners. You're telling them that this product is of the same risk as an oral contraceptive.
Now, if you know from the data, that's not necessarily true, because up in the paragraph above it, they say there's no data to tell you if this actually performs like an oral contraceptive.
So, in some ways, the second paragraph is speaking specifically about the history of oral contraceptives.
Q. Is there any reason to doubt that anyone, board certified OB-GYN, family practitioner, didn't know in 2000 that there's an increased risk of thromboembolic events associated with hormonal contraception?
MS. PARFITT: Objection The question was just asked, and she gave a very detailed response to the question.
I think in light of the fact we got a late start today, we need to start to move forward and not ask the questions twice.
Q. (By Mr. Winter) You can answer the question, Doctor. That was not the question I asked before.
A. You're talking apples and oranges. Yes, there has been a history, and this is the class labeling. There has been a history of increased risks of oral contraceptives.
Having gone through all the documents and seen even corporate documents, we know, sitting here today, that the company knew that this product did not perform as a birth control pill. But they're actually using class labeling for a birth control pill and telling physicians and all the people who prescribe it from state to state, that this has an increased risk which is associated with birth control pills.
There's never been a transdermal contraceptive product, and that's not what's stated there. It states that they are talking about class labeling, that birth control pills have an increased risk of several serious conditions.
So, if I was a physician who was prescribing a birth control pill, I would see that, and I would read that as being consistent with oral contraceptives, which, as we know, is what the FDA was told, that this product was consistent with an oral contraceptive.
Q. If you go down to the next paragraph, it says: The information contained in this package insert is principally based on studies carried out in women who used combination oral contraceptives with higher formulations of estrogens and progestins than those in common use today.
Do you see that sentence?
A. Correct. And this is talking about birth control pills, the higher estrogen levels.
Q. And by "higher estrogen levels", what do you understand that to mean?
A. Higher than 50 micrograms.
Q. So, the class labeling, that's more class labeling, right, that sentence?
A. That is class labeling, correct
Q. The class labeling for oral contraceptives, in terms of describing risks, was based on studies done involving pills with more than 50 micrograms of estrogen?
A. It's been done on various formulations of estrogens and progestins, but they are saying some of this information contained in the packet is from studies carried out before. But again, this is oral contraceptive labeling.
Q. And carried out studies before and the higher formulations of estrogen, they're specifically referring to studies involving oral contraceptives with more than 50 micrograms of estrogen?
MS. PARFITT: Objection.
A. Well, they don't state that.
Q. (By Mr. Winter) I know they don't state that, but it's your understanding; correct?
A. It would be that the FDA was saying that there are higher formulations of estrogen and progestin than had been in the past but the FDA does not specifically state a number in their class labeling.
Q. But your understanding is that the class labeling, in terms of warnings, in part, is based on data involving higher formulations of estrogen, meaning more than 50 micrograms, and higher formulations of progestin And on the progestin side, what's the highest?
MS. PARFITT: Objection, compound question
A. I mean, well, the FDA is basically saying the common use today. That's all they're saying. They're not being specific. They're not even talking about which progestin, because some of that, you know, which progestins are we talking about. FDA isn't very specific on that statement, either, because we can get into dosing, but progestins vary.
Q. (By Mr. Winter) With respect to the estrogens, the higher formulation relates to products with more than 50 micrograms?
MS. PARFITT: Objection, misstates her testimony.
A. Actually, there is not a level of estrogen that has been stated as a safe level, and the FDA has very specifically not given an estrogen level, but the trend, since 1988, has been to reduce the amount of estrogen
So, what the FDA is saying, in a nonspecific way, is that commonly-used estrogen levels are lower than when the FDA originally developed this statement, but it does not have a statement as a magic level of acceptable estrogen
As you and I know, most estrogen is around 35 micrograms, 30. So, there's been a trend since '88 to reduce the level of estrogen and progestin
Q. (By Mr. Winter) Doctor, the question is as follows. The sentence says: The information contained in this package insert is principally based on studies carried out in women who use combination oral contraceptives with higher formulations of estrogens and progestins.
So, I'm just going to ask you about —
MS. PARFITT: Let's finish the sentence.
Q. (By Mr. Winter) Than those commonly — than those in common use today.
All right So, you've already told me progestin has a lot of variability to it. This is the question: Studies carried out in women who used combination oral contraceptives with higher formulations of estrogen doesn't the class labeling in that regard refer to studies in women using oral contraceptives with more than 50 micrograms of estrogen?
MS. PARFITT: Objection The question has been asked and answered.
A. The FDA doesn't state that.
Q. (By Mr. Winter) Whether or not they state that, don't you know that that's what those studies involved?
MS. PARFITT: Objection
Q. (By Mr. Winter) If you don't know the amount involved in those studies referenced in this label, then you tell me, Mr. Winter, I don't know how much. I don't know what FDA is talking abo
ut.
A. I do know what FDA is talk

ing about. They're talking about common use today. Common use today would be primarily 35 and 30 micrograms of ethinyl estradiol, EE.
But there's been other estrogens that have been used at those times and other progestins, but they're talking about what's commonly being prescribed when this class labeling was written
Q. Do you know what amount of estrogen is used in the studies that the information contained in this package insert is principally based on?
MS. PARFITT: Objection, asked and answered
A. I can't state that because the FDA hasn't stated it. We just know that in terms of prescribing trends and the products that have been approved, and we don't even have a date on when this class labeling was originally approved, but in terms of the trend in the United States, that's what they're talking about. They're not saying that there is one magic level.
Because there's variability, even in the studies. What that statement is saying is that there's a trend towards reducing estrogen and progestin
Q. Whatever the trend is, Doctor, the question is, do you know, when it says the information contained in this package insert — do you see that start of the sentence?
A. Yes, sir.
Q. — is based principally on studies. Do you see that?
A. Yes, sir.
Q. Okay. Those studies upon which the information is principally based, do you know how much estrogen the women involved in those studies were receiving?
MS. PARFITT: Let me object. Mr. Winter, I do believe you have attempted to ask that question three, four, maybe even five times. She's given you her response. I don't think her response now differs because you have stated the question one more time.
I'm going to object and, frankly, ask that we start to move on here, so we can get through the day's testimony.
MR. WINTER: Well will get though today's testimony.
Can you answer the question?
A. I believe I've answered it over and over again, because we're talking about studies that have gone from 1970 on- 1960 on.
Q. (By Mr. Winter) If you could turn to the next page.
A. You don't want to do the next sentence?
MS. PARFITT: We're on Page 14?
Q. (By Mr. Winter) Actually, go back a page. There's a description of the epidemiological studies described in the package insert. Do you see that?
A. Yes, sir.
Q. And then there's –It ends with a sentence: For further information, the reader is referred to a text on epidemiological methods.
A. Yes.
Q. Is that class labeling?
MS. PARFITT: Objection.
A. It may be, and I think it feeds into that last sentence of the paragraph above, which we didn't address, which is the rate and the effect of lower doses still has not been determined.
Q. (By Mr. Winter) Is that class labeling in that sentence?
A. That is, yes, the effect of long-term use of combination hormonal contraceptives with lower doses of both estrogen and progestin, by any route, remains to be determined
Q. And we don't know if the next paragraph is class labeling?
A. I don't recall if it is or not.
MS.PARFITT: I'll just object I believe we were focusing on the very last sentence of the last paragraph I believe the question was the entire last paragraph.
Q. (By Mr. Winter) Either way, do you know if the last sentence in that paragraph on Page 13, or the whole paragraph, the last paragraph is class labeling or not?
MS. PARFITT: Objection
A. I don't want to say it is. It would be consistent with class labeling.
Q. (By Mr. Winter) If we go to Page 14, Thromboembolic Disorders and Other Vascular Problems. Do you see that heading?
A. Yes, sir.
Q. You have A, Thromboembolism Do you see that?
A. Yes, sir.
Q. That paragraph that starts "an increased risk", going down to the words, elect not to breast feed, do you see that paragraph?
A. Yes, sir.
Q. Class labeling or not?
A. There may be components of it that are class labeling, particularly the breast feeding information
Q. Well, that — For example, the first sentence: An increased risk of thromboembolic and thrombotic disease associated with the use of hormonal contraceptives is well established.
A. That would be class labeling.
Q. Then it goes on to describe case control studies and cohort studies.
Do you think that's class labeling?
A. Yes.
MS. PARFITT: You're taking it down to the cohort, John?
MR. WINTER: Correct, yes.
A. Yes, I believe it would be.
Q. (By Mr. Winter) What about the sentence: The risk of thromboembolic disease associated with hormonal contraceptives is not related to length of use and disappears after hormonal contraceptive use is stopped.
A. Yes. Because you can tell by the references, the references that they're citing in this paragraph are oral contraceptive references.
Q. And just so you and I are on the same page, for example, there's a parenthesis (2), closed parenthesis in that paragraph, and if one went to the end of the prescribing information and looked at Number 2, we'd find the support for that sentence; correct?
A. Correct.
Q. And if we looked at all of the references to this package insert, we'd find out the extent to which a particular study involved a patient receiving 80 micrograms or 50 micrograms of estrogen, to the extent the study discloses that; correct?
MS. PARFITT: Objection.
A. We'd find oral contraceptives. In fact, all the articles are oral contraceptives to 106. There is no reference for a transdermal patch
Q. (By Mr. Winter) This is all — These references are all class labeling references; correct?
A. Correct.
Q. Okay. Now, the paragraph, "in the large clinical trials", do you see that one?
A. Yes, sir.
Q. Is that class labeling?
A. No.
Q. Okay.
A. This comes directly out of the clinical trial that is provided to the FDA.
Q. All right Now, the sentence, the second sentence of that paragraph: It is unknown if the risk of venous thromboembolism with Ortho Evra use is different than with use of combination oral contraceptives.
That would be unique to the Ortho Evra labeling?
MS. PARFITT: Objection.
A. Yes, sir.
Q. (By Mr. Winter) And that would be something that was part of the negotiations between FDA and the people at Ortho McNeil prior to the approval of labeling; correct?
MS. PARFITT: Objection.
A. Well, yes. But interestingly, at that time, there was a known risk for the clinical trial, and it was not included in that description in terms of the 118 per 100,000 women years, patient years. So, that's not in there.
Q. (By Mr. Winter) But the two reports were?
A. There were two written reports, but there is no report for a physician that would say that the risk is actually from the clinical trials known to be increased over what would have occurred, say, for an oral contraceptive.
Q. The next paragraph is that class labeling?
MS.PARFITT: Again, just for the record, beginning with "as with any combination"?
MR. WINTER: Correct
A. That would be class, but then it has a statement specifically for Ortho Evra about it should be discontinued immediately.
Q. (By Mr. Winter) Was it your understanding that if you looked at the class labeling, there's sometimes little spaces to put in the name of the product?
A. Yes. That's what I'm saying. That is specific for Ortho Evra. It would not be class labeling, if you're going word by word.
Q. You don't think the sentence, "should any of these occur or be suspected, the product should be discontinued immediately", that's not class labeling, o
r that sentence is actually extra for Orth

o Evra?
MS. PARFITT: Objection
A. No. Well what I'm saying is the inclusion of the word, Ortho Evra, would be specific to this product. Obviously, that does not appear in class labeling… since we're being very specific as to what comes from where.
Q. (By Mr. Winter) Is the sentence without the specific name of the product in the class labeling?
MS. PARFITT: Objection. It misrepresents the document. It misrepresents testimony. She's already responded to that question
Frankly, this entire document is out of context. I object to that question
A. You may want to state it again Go ahead. The question?
Q. (By Mr. Winter) Is the sentence, "should any of these occur or be suspected, the product should be discontinued immediately", is that class labeling?
MS. PARFITT: Objection
A. It would be typical of class labeling.
Q. (By Mr. Winter) Now, moving on to Myocardial Infarction, is the first paragraph class labeling?
A. Would you read back the class labeling document. That would probably be faster. There is a document that the FDA has for this product. I believe it came out in '99 for the class labeling.
Q. I don't have it with me, Doctor.
MS. PARFITT: Do you want to look in your box?
A. Well, I could because otherwise we're just going to be talking about every sentence.
Could I go look in the box?
Q. (By Mr. Winter) Sure.
A. Now, specifically, what were you asking me?
Q. We were in the Myocardial Infarction section
A. This is the 2000 labeling. This is the 2004 guidance label. So, it may have been in draft form. I don't know when it was first issued. It fits the labeling better.
Okay. So, this was the — I want to just say what labeling.
Q. Sure.
A. So, this was the June, 2000 labeling. It was issued. Comment was received. So, it was a work in progress until the final draft came out in 2004, because some of the comments in the labeling that we're talking about actually appear later in the finalized 2004 and didn't appear in the 2000. So, it's a work in progress that ended up in the 2004, but it seems to be fitting this labeling better than the 2000 myocardial infarction Do you want these as exhibits?
Q. We'll mark them
A. Okay. There we go. What was the question?
Q. Well, the question was, before you went to look for that document, was the first paragraph, an increased risk of myocardial infarction, was that class labeling or not?
A. Yes, it is.
Q. What about the next paragraph, smoking in combination with?
A. Yes, it is.
Q. Could we go back, just to clear something up on the last paragraph of thromboembolism that we talked about?
A. Thromboembolism. Okay.
Q. "That should any of these occur or be suspected", that sentence, is that class labeling?
A. I'm looking. Actually, that very last sentence is not class labeling.
The other one said, "Symptoms of retinal vein thrombosis should be evaluated immediately."
So, this one actually has a statement that Ortho Evra should be discontinued immediately. That's new.
Q. So, that sentence, just so I am clear, is not class labeling?
A. It is not in the 2004 class labeling. Let me look at the 2002.
I do not find it in either of the drafts. So, it's not class labeling, that last statement with "Ortho Evra should be discontinued immediately". So, that was added.
Q. Now, just to make sure we were right on something, then, the paragraph above that in the labeling, "in the large clinical trials"?
A. Oh that's definitely Ortho Evra labeling. That's from their clinical trial.
Q. I understand it is from the clinical trial.
Is there something in that class labeling that says, describe X?
MS. PARFITT: Object to the question You can answer.
A. No.
Q. (By Mr. Winter) Okay. And that paragraph does talk about the two reports of pulmonary embolism, correct Exhibit 2?
MS. PARFITT: Objection, asked and answered
A. There are two pulmonary embolism cases described. No rate, no rate of embolism, but there are two descriptions.
Q. (By Mr. Winter) Now, if we could go back the third paragraph of the Myocardial Infarction, is that class labeling? Hormonal contraceptives may compound?
A. It actually is derived from the first paragraph of myocardial infarctions, I believe, in terms of the risk of hypertension Because there is a statement about the risks that's mainly in women with underlying risk factors of pulmonary artery disease, which is smoking, hypertension, hypercholesteremia, morbid obesity and diabetes. So, it fits in that.
Q. Okay. What about the next paragraph of the Myocardial Infarction section? Is that class labeling?
A. The next paragraph?
Q. Yes.
A. You mean where it talks specifically about norgestimate and norelgestromin?
Q. Correct.
A. No. That would be — The reference to the progestin is not in class labeling, that one sentence, See Clinical Pharmacology.
I'm looking at the rest Let's see what we've got here. That Number 97 statement actually comes from a study on third-generation oral contraceptives and risks of myocardial infarction
Q. All right. Is there a class labeling for third-generation contraceptives?
A. There is labeling for desogestril containing products, because that's the only officially approved progestin that's third generation
So, there's a statement that goes in specifically for any birth control pill that would have desogestril.
Q. And was that class labeling incorporated into the Ortho Evra labeling?
MS. PARFITT: Objection.
A. I don't believe the data from desogestril is a desogestril progestin
Q. (By Mr. Winter) Just to complete the thought the class labeling for the third generation, for the only approved third-generation product is not incorporated in the Ortho Evra labeling?
MS. PARFITT: Objection.
A. I do not believe that it is.
Q. (By Mr. Winter) All right. Now, could we go to Cerebrovascular Diseases, C, in Exhibit 2.
Is the first paragraph of that section class labeling?
A. The first sentence, yes.
Q. What about the second sentence?
A. The second sentence is really a derivative of the first sentence.
Q. Then, the next paragraph?
A. The next paragraph would come from the class labeling.
Q. Okay. All right. I'm sorry. Did you finish?
A. Yes, that's correct So, it actually comes from the numbers.
Q. The next heading, D, Dose-related Risk of Vascular Disease from Hormonal Contraceptives, is that paragraph class labeling?
A. Yes.
Q. Okay. Now, the next heading is Persistence of Risk of Vascular Disease. Is the first paragraph class labeling?
A. It's not in the 2004 label.
Q. 2004 guidance?
A. 2004 guidance, right, in terms of their class labeling.
If I remember, when they wrote the label, they also took information from the NuvaRing labeling, because it was actually getting approved about the same time. So, it's not just class labeling. It is also drawing from other manufacturers' labeling
Q. If we look at the last sentence of that paragraph on the Persistence of Risk of Vascular Disease, do you see the reference that it involves studies?
MS. PARFITT: And you're referring to "However, both studies are performed"?
Q. (By Mr. Winter) Studies with combination hormonal contraceptive formulations containing 50 micrograms or higher of estrogen
Do you see that?
A. Yes, sir. I see the statement. And the reference —
MS. PARFITT: I don't think there's a question.
Q. (By Mr. Winter) So, you would understand that to mean, goin
g back to that question from abo

ut twenty-five minutes ago, on higher formulations of estrogen, do you remember we talked about that in the warnings section?
MS. PARFITT: I'm going to object
Q. (By Mr. Winter) Do you understand the discussion about formulations containing 50 micrograms or higher of estrogen to be consistent with the warning statement information contained in this package insert is principally based on studies carried out in women who used combination oral contraceptives with higher formulations of estrogen.
MS. PARFITT: Objection
A. You're saying are these two things related?
Q. (By Mr. Winter) Yes.
A. And I say, no, they're not related. This is specifically talking about this paragraph and those two studies.
Q. Can we agree that those two studies involved women receiving combination hormonal contraceptive formulations containing 50 micrograms of estrogen or higher?
MS. PARFITT: Objection
A. That's what the FDA has stated there, and it's specifically talking about the two studies that precede it.
Q. (By Mr. Winter) The next sentence in the next paragraph: It is unknown whether Ortho Evra is distinct from other combination hormonal contraceptives with regard to the occurrence of venous and arterial thrombosis.
Class labeling?
A. Specific to Ortho Evra.
Q. Are you aware of any epidemiological evidence that says there's an increased risk of arterial thrombosis associated with Ortho Evra, as opposed to combination oral contraceptives?
MS. PARFITT: Objection.
A. Are you talking about the two epidemiological studies? There's the one from Jerric (phonetic) and the ones from Graham.
Q. (By Mr. Winter) I'm asking you any epidemiological evidence that says there's an increased risk of arterial thrombosis with Ortho Evra compared to a combination oral contraceptive?
MS. PARFITT: Object to form.
A. So far as the information is focused on venous thrombosis, there's data in terms of the FDA's adverse reporting and the company's adverse reporting from myocardial infarction that would be an arterial thrombosis, but the epidemiological studies have primarily captured patients that had a venous thrombosis.
Q. (By Mr. Winter) So, the answer is you're not aware of any epidemiological evidence that says there's an increased risk of arterial thrombosis associated with Ortho Evra when compared to a combination oral contraceptive?
MS. PARFITT: Objection, misstates her testimony.
A. Well, you're asking me two things. In terms of the epidemiological studies, the epidemiological studies have focused and captured patients with venous thrombosis.
If you are talking about epidemiological evidence, were something to suggest that there are safety issues, then you would talk about adverse event reports for myocardial infarction, that would be an arterial thrombosis.
Q. I asked epidemiological study. So, that was not my question.
A. No. You changed it You said, first, epidemiological studies, and then you said epidemiological evidence.
So, in terms of an epidemiological study, they haven't captured arterial thrombosis, but in terms of epidemiological type of evidence suggesting that there could be an issue with arterial, there is some evidence for that but the studies are focused on venous. They've captured venous data.
MR. WINTER: I want to close Exhibit 2 for a second. Before we get to my next exhibit, if you don't mind, why don't we mark — I think you looked at two guidance documents.
MS. PARFITT: Yes.
MR. WINTER: Why don't we make them 3 and 4. We're going to mark as Exhibit 3 the Guidance document dated June, 2000, and we will mark as Exhibit 4 a Guidance document dated March 2004, which already had, looks like Exhibit 23 on it or at least the sticker says 23.
(WHEREUPON, a certain document was marked Defendant's Deposition Exhibit No. 3 and 4, for identification as of March 11, 2008, and is attached hereto.)
Q. (By Mr. Winter) Doctor, before we move on to Exhibit 5, there is some highlighting at least on the front page of both of these documents, meaning Exhibits 3 and 4, and I believe there was some highlighting on one page of Exhibit 4.
I take it that's your highlighting?
A. Yes, sir.
(WHEREUPON, a certain document was marked Defendant's Deposition Exhibit No. 5, for identification as of March 11, 2008, and is attached hereto.)
Q. (By Mr. Winter) You've just been handed Exhibit 5, Doctor. You reviewed this FDA memo?
MS. PARFITT: Just give her a moment to read the memo.
MR. WINTER: No, no, no. I'm not going to ask any questions until I find out if Dr. Parisian, in fact, had reviewed Exhibit 5 prior to today.
MS. PARFITT: We've seen or taken a glimpse at it. So, she can respond accurately to that question
A. I have seen what the FDA had asked for the information, and I cited that on my report, 166. I don't believe I had seen the FDA's response memo.
Q. (By Mr. Winter) Just so I understand, I did study your report. Do you make a reference, and I think you said paragraph 166?
A. Page 166, paragraph 329.
Q. That would be one of your appendixes, on appendix–
A. Appendix 6, I believe.
Q. Just so that we're clear.
A. Uh-huh.
Q. If I'm looking at paragraph 329 —
A. Yes, sir.
Q. — that is the FDA request internally to perform an analysis?
A. Yes, and that's what this is in reference to.
Q. Exhibit 5 is the internal FDA analysis of post-marketing spontaneous reports?
A. I believe it would be, because the requested information was forwarded to the FDA by J & J on June 4th. So, this actually appears to have been what was forwarded to the FDA, and then the FDA's response, review of the information
Q. You understand that Exhibit 5 is an internal FDA review of adverse event information provided by the sponsor of Ortho Evra; correct?
A. Yes, sir. And I was just saying that I hadn't seen this particular document, but I was aware that there actually had been information provided to the FDA.
So, this would be the subsequent FDA. So, I was checking to see if, actually, I had recorded seeing this, and I hadn't recorded seeing this.
Q. Did you look at the 5,000 pages or so that FDA produced in response to the document request in this proceeding?
MS. PARFITT: Objection, vague.
A. I've looked at many documents that the FDA has provided. I don't know what the number would be. If I saw that, I would have put it in my request, but there have been many discussions of various reviews. So, this specific document, I don't know if I saw it or not.
Q. (By Mr. Winter) Well, take a few seconds to look at it because I'm going to ask you a couple of questions about it.
A. Okay.
Q. Exhibit 5 was prepared by the same individual who reviewed the NDA for FDA; correct?
A. Well–
MS. PARFITT: Objection.
A. The final sign-off was by Dr. Davis and Dr. Monroe, which had worked with the NDA.
Q. Dr. Davis was the medical officer who prepared the review of the Ortho Evra NDA; correct?
A. Yes, sir. But he probably had a consult with another area to get the number of the adverse events and information So, you asked me who prepared it. He was not alone in that he prepared this.
Q. Exhibit 5 reflects some collaborative effort within FDA?
A. Probably, more likely than not.
Q. Now, if we look at the first page of Exhibit 5 —
A. Actually, I don't want to say that, because he didn't say that he got a consult, and he's really not talking about the adverse event that they would have gotten from the data. He's talking about the information that the company has provided to him. So, he's d
oing his own review. So, I don't want to

say it was a joint effort.
Q. Other than Dr. Davis and Dr. Monroe?
A. Correct. They're the only two names on it. So, it could have been just in-house in their one division
Q. According to Dr. Davis, the methods used by Ortho-McNeil with respect to the submission of data on the post marketing adverse events was acceptable; correct?
MS. PARFITT: Objection
A. This is dated June 7, 2004, before their meeting with the company, and from the information that he had been provided by the company, he found that it was acceptable.
Q. (By Mr. Winter) And their conclusion seemed balanced and fair?
MS. PARFITT: Objection
A. From the information he had, but this was prior to the discussion on of the Net 1 data and finding that the contraceptive was different than what he thought he had actually approved.
Q. (By Mr. Winter) You had a conversation with Dr. Davis about this?
MS. PARFITT: Objection
A. No. But in terms of the record, there actually — that's where I went to my time line, and there actually was a meeting coming up, and that's actually in June when they started discussing the Net 1 data
So, Dr. Davis and Dr. Monroe actually stated at that meeting, and from the documentation, they were concerned about the safety and they were concerned that the estrogen delivery was higher than what they had been led to assume.
Q. (By Mr. Winter) This exhibit refers to the adverse event reports, correct, received as of some date in 2004?
MS. PARFITT: Objection.
A. It's coming from the sponsor. So, you're relying on the sponsor to have provided them with the adverse event desk and thrombotic embolic events.
It's not saying that it is coming from FDA's database. So, this is information being provided to them by the company.
Q. And the information that Dr. Davis and Dr. Monroe are looking at is adverse event reports of deep vein thrombosis, pulmonary embolus and CVAs, which are cerebral vascular accidents; correct?
A. Coming from the company, they're not looking at the FDA's database.
Q. Okay. And when they looked at the data from the company, and we'll agree it is from the company, the conclusion was what?
MS. PARFITT: Objection It's too broad. Is there a specific question? There's a lot of information contained in that three-page document.
A. Well, their conclusion at the time speaks for themselves. We see the reviewer's recommendation
Q. (By Mr. Winter) And the recommendation was what?
MS.PARFITT: I will just object. Did you want her to read the document into the record? We have the document in front of us. Do you want her to just read it? Is there a question?
MR. WINTER: Yes, there is.
MS. PARFITT: What's the question?
MR WINTER: What was the conclusion?
A. Do you want me to read the conclusion?
Q. (By Mr. Winter) If all you can do is read it then read it.
A. As noted in the brief discussion above, although the initial impression was that the incidents of VTE events, DVTs plus PEs and CVAs was a potential safety concern Upon further analysis of the data, this concern is not substantiated. The Division will continue to watch the number of reported SAEs for the Ortho Evra contraceptive patch, but it does not seem necessary at this time to make any changes in the labeling or issue any warnings.
Q. And that's as of June 20th?
MS. PARFITT: Objection Is what as of June 20th?
MR. WINTER: That conclusion
MS. PARFITT: As written in that document? If you can answer that question Is that the conclusion written in the document as of this date?
A. Well, the document was originally generated June 7th, with final sign-off on the document June 21st by Doctor Davis, and June 23rd by Dr. Monroe, and that was right before meeting with the company, which was going to be held June 29th
So, that was how the FDA was walking into the June 29th meeting.
Q. (By Mr. Winter) Now, the FDA received a briefing package from the sponsor in March of 2004; correct?
A. It was May.
Q. And Net 1 was in that briefing package; correct?
A. Correct.
Q. So, any reason to doubt that Dr. Davis had read that before he signed off on Exhibit 5?
MS. PARFITT: Objection How would she possibly know what Dr. Davis did? Is there a reason for you to know what Dr. Davis was reading?
A. No. That would call for me to speculate when he actually read it.
In terms of meetings, there's no set time you would have to read it. You would just have to read it before you go in the door, if you read it
Q. (By Mr. Winter) I take it that you don't know, one way or the other, whether or not he read Net ?
A. Well, actually I do. If he had read Net l, he would have stated it in his memo, that he was concerned about an increased risk, because that would have been considered in his determination about the information…particularly, since Dr. Davis and Dr. Monroe both were quite excited about Net 1 at the subsequent meeting. So, it is not mentioned in that document.
Q. Meaning Exhibit 5?
A. Correct. In Exhibit 5, it is not mentioned.
Q. Did you — You've never worked in the office of Clinical Pharmacology and Bio Pharmaceutics at FDA; correct?
A. That is correct.
Q. And is it fair to say that you have never conducted a pharmacokinetic study?
A. That would be fair. Have I reviewed pharmacokinetic studies? Yes, as a medical officer, but I have never conducted them, correct.
Q. And is it fair to say that there's no paper listed in your C.V. that you either authored or co-authored involving a pharmacokinetic study?
A. That would be correct.
Q. Now —
A. And I don't believe I'm the expert to be talking about pharmacokinetic studies. I believe there are a multiple of those, other than the context that I would have reviewed them as a medical officer.
Q. If we were to go and look at sign off or clearance letters for 510K while you were at FDA, how many would bear your signature?
A. Since I was not a division director, I would not have signed off on them, but how many would I have been involved in, over seven hundred.
Q. Appreciate that, but the answer is, there would be none?
MS. PARFITT: Objection, misstates her testimony.
A. That's correct because the Division director would sign off on them But there would be documents that I have signed off on that would have gone and fed into the final sign-off as a medical officer.
Q. (By Mr. Winter) If we were to look for approval letters for PMAs during this same time that you worked at FDA, would we find any approval letters for a PMA that you signed?
A. No, because that would be at the division director or the center director level. (A break in the proceedings was taken at this time.)
Q. You know Dr. Judith Jones?
A. Yes, I do.
Q. Do you respect her?
A. Yes. She actually encouraged me to go into consulting.
Q. Do you trust her judgements?
A. It depends. Would I give her my son? I don't know. So, I don't know what you're talking about.
Q. You trust her judgments regarding matters involving medical devices or pharmaceuticals?
MS. PARFITT: Objection.
A. Not necessarily for medical devices.
Q. (By Mr. Winter) Pharmaceuticals?
MS. PARFITT: Objection.
A. Well, I don't know in what context you're talking about in terms of pharmaceuticals, because I know Dr. Jones is an epidemiologist and has a company that does reports, and she's the president of that company.
So, I don't know in what context you're talking about.
MS. PARFITT: I'm going to object. It's an extremely broad question I'm objecting with regard to pharmaceuticals and devices. That's an extremely broad question I'
m sure she has good judgments on some, and others, perhaps she's doesn't.
Q. (By Mr. Winter) Do you consider her to be a competent epidemiologist?
MS. PARFITT: Objection
A. I mean, you know, that's a hard question. She is an epidemiologist I have been involved in cases where we are on the same side, and oftentimes against each other.
So, I don't know in what context you are talking about She is an epidemiologist She has worked at FDA. She has a business in Washington, D.C.
(WHEREUPON, a certain document was marked Defendant's Deposition Exhibit No. 6 for identification as of March 11, 2008, and is attached hereto.)
Q. (By Mr. Winter) Doctor, you now have in front of you what's been marked as Exhibit 6. It is about a forty-some-odd-page document Before I start asking you any questions about it you've seen Exhibit 6 before?
A. Let me look.
MS. PARFITT: Take a moment and look through it.
A. Let me look at it, because it can be a different format from what I've seen
Q. (By Mr. Winter) Have you seen Exhibit 6 before?
A. I have seen Exhibit 6, but I downloaded mine from the FDA's website for the review package. I believe this is a FDA pharmacology, bio pharmaceuticals review package, and the Bates numbers are different, but it is exactly the same package that I'd seen before.
Q. Okay. You're familiar with the 014 Study?
A. Yes, sir, PHI-014.
Q. That study was part of the initial NDA submission; correct?
A. Yes, sir.
Q. Actually, it was in Volume 6; right?
A. Yes, sir. It is actually added. It had not been a planned study for the IND, and then it was added for the company as a bio availability study.
Q. And included in the initial NDA submission?
MS. PARFITT: Objection
A. Yes. And it's discussed by the medical officers and the people who are doing the bio pharm review.
Q. (By Mr. Winter) Have you looked at the report for the 014 Study, as it was submitted in the NDA?
A. Primarily, the summaries that have been done by the reviewers, the bio-pharm people and the medical officers, because I think in terms of my role with the FDA, the germane is what did they comprehend in terms of the PHI-014 Study.
As you know, there was a correction factor used that Dr. Abrams put into calculating the release of estrogen, and in terms of the FDA reviewers, there's nothing that states in the documents that I've seen from the reviewers, that they were aware that there had been a calculation used to reduce the amount of estrogen and, also, in terms of the internal corporate documents until 2005, there really had not been a discussion among management that they were all suitably aware that Dr. Abrams had used that calculation
Q. Well, sitting here, do you know if the calculation done by Dr. Abrams is, in fact described in the report?
A. It may occur, but in terms of the medical officer, and the medical officer was not aware of it in terms of the final labeling of the product, in terms of the white paper that was produced about the issue for physicians, they weren't made aware of it. And in terms of the FDA's toxicology, pharmacology people, they were not aware of the correction factor to reduce the estrogen
I believe I saw Dr. Allen stated that there wasn't a place within the document where some correction factor, which he didn't elaborate on, was presented.
So, somewhere in the documentation, there may be a correction factor, but it was not appreciated by the FDA from the documents that they have.
Q. And your conclusion that it was not appreciated is based on a discussion with any of the reviewers?
MS. PARFITT: Objection.
A. No. It's based on the review of the medical officer's review, and I cite specifically in the review where — in the Appendix 6 where Dr. Davis describes the PHI-014 Study and his appreciation of that study and the use of the 20 micrograms, which is, as you and I know, the result of the calculation to reduce the estrogen that was actually measured in that study, and he has no statement that he was aware that that product number was reduced.
So, I'm relying on what did the FDA medical officers appreciate, what did they include in the labeling, what type of literature was released by the company.
Even the company did not appreciate that that correction factor was used until 2005, by their own internal document, other than Dr. Abrams, according to Dr. Houn's memo, problem memo 2005.
Q. (By Mr. Winter) These are inferences that you're drawing?
MS. PARFITT: Objection
A. No, they're not inferences. In terms of a medical officer, if there had been used a correction factor that had to significantly reduce the measure of estrogen, it would have been stated in his medical review. It was not stated in his medical review. It was also not stated in the medical review of the toxicology, pharmacology. It was not stated in the labeling.
Nowhere is there a discussion of the use of a correction factor to reduce the measured estrogen in terms of the human being and the delivery of estrogen So, there's nothing that supports that FDA was aware that there actually had been a correction factor used by Dr. Abrams.
Then, you go to the own company's information, and there's a discussion in the company that they were not aware that a correction factor had been used in PHi-014.
So, in terms of the facts and the written documentation, there's nothing to support that either the FDA, or until 2005, members of the company were aware that there had actually been a reduction factor used by Dr. Abrams.
So, I would say it is factual evidence. It is not my opinion. It is not a discussion. It is just in terms of reviewing the documents, there's nothing to support that FDA was aware of that correction factor.
Q. (By Mr. Winter) Do you have any reason to believe that anyone in FDA read the report as part of the NDA?
MS. PARFITT: Objection
A. In terms of the NDA, if you read the NDA, it's not clear cut that there was a correction factor used. That's why I say Dr. Allen actually talks about that it appears somewhere in the document, but if you look at the summary, if you look at the information that goes with the protocol, there's no discussion of a correction factor.
Actually, even in the literature that was published by the company, there is no discussion of a correction factor.
Q. (By Mr. Winter) I guess, and I apologize for maybe asking this question again, but I take it that you've actually not read the study report for 014?
A. Which one? Are you talking about Johnson and Johnson's study report?
Q. Yes.
A. And it is discussed, and I believe the POE numbers that I read in terms of 014 are discussed in my opinions and in my documentation So, I have read the company's report.
Q. And you're saying that the correction factor is not discussed in the report?
A. I'm saying that the use of the correction factor is not clearly described in the report, any information provided to the FDA or to physicians.
It is a significant change in terms of estrogen delivery.
Q. Is there any reason to believe that Dr. Davis or the author of Exhibit 6, Dr. Chatterjee, read the entire report for 014?
MS. PARFITT: Objection She's not here to testify with regard to every document that Dr. Davis and Dr. Chatterjee may or may not have read and reviewed and the context in which they read and reviewed information, if, in fact they read or reviewed information
Q. (By Mr. Winter) That's what I just thought the doctor said for fifteen minutes, but if she's not going to testify about that then let me ask another.
Could you look at Page 4 of Exhibit 6. You see first the recommendation from the Office
of Clinical Pharmacology and Biopharmac

eutics was, the application is acceptable. Do you see that?
A. Yes, sir.
Q. And there, apparently, were no outstanding issues at the time of this report, which was dated when?
MS. PARFITT: I object to the question
A. Are you asking me what date it is?
Q. (By Mr. Winter) Yes.
A. Okay. Let's see.
MS. PARFITT: Date of the document.
A. The date of the document is 12/21/2000. No…the date of the submission
Q. I will help you, Doctor. Look at the last page.
A. Last page. Okay. It was 11/16, would be 2001, and November 19th, 2001 for Parekh, P-a-r-e-k-h
Q. If you go back to Page 4, the Comments to the Sponsor.
A. Okay.
Q. You see that first line, actually the first sentence?
MS. PARFITT: The question is, do you see it?
A. Yes, I see it Comments to the Sponsor.
Q. (By Mr. Winter) What's your understanding of the request for data justifying a choice of the current dissolution medium?
A. The dissolution medium is the medium they use for doing the testing for in-vitro testing. Dissolution is used in terms of determining how much product is released when you put this in a fluid medium over a period of time.
Q. Is that the same as what happens when the patch is placed on someone's skin?
A. No. It is an in-vitro test. It has nothing to do with bioavailability.
Q. Your understanding was additional data was submitted regarding the dissolution medium?
MS. PARFITT: Objection
A. The dissolution medium? I'm not clear if it was or not but again, it's a medium that is used just for testing the in-vitro release of a path It's basically a fluid.
So, they're asking the type of medium. It's a standard test that is used for transdermal patches.
Q. (By Mr. Winter) Would you go to the next page?
Any reason to question the first conclusion that the sponsors submitted satisfactory data to accept the 150 UGs and 20 UGs as daily amounts of drugs that are delivered in vivo?
MS. PARFITT: I'm going to object to the question It is broad.
Try to tighten the questions up, Mr. Winter.
Q. (By Mr. Winter) You can answer it.
A. That would support that they were not aware that a correction factor was used, and that's where you get the 20 micrograms per EE.
So, that would go along with what I just stated about their appreciation that the PHI-014 had produced that type of bioavailability, and that is what I was saying is an incorrect number in terms of the correction factor and Dr. Abrams' testimony of using the correction factor to reduce the number to 20 micrograms. That was key in this approval and Dr. Davis' approval, that that was the number that was shown in PHI-014 as the estrogen that was delivered for approval of this product.
That's why the correction factor in that study is so crucial, because that is not the number that actually came about in bioavailability studies.
Q. If you go over to the next page, you see the second bullet point from the bottom, with the two whiteouts, or blackouts or grayouts. Do you see that?
A. Yes, sir.
Q. Now, FDA does that, from time to time, because it's got proprietary information and it's disclosing something publicly?
MS. PARFITT: And just for clarification, which blackouts or whiteouts are you suggesting to her?
MR. WINTER: Yes.
A. Those would represent redaction Sometimes it's the FDA, sometimes it's the manufacturer that is the source of redaction
Q (By Mr. Winter) If we look at the bottom here, it's an FDA document. Can we agree that the source of the redaction is FDA?
MS. PARFITT: Objection.
A. Not necessarily. Oftentimes, FDA will ask a company as to what needs to be redacted.
Q. Do you know what the alternative manufacturing site FDA said was not acceptable?
A. That would be the LTS site, the Lowman site. So, they are talking about the first block would be the redwood manufactured lots are identical to the clinical trial lots.
So, the FDA was under the assumption that the manufacturing process had been shown to be identical to actually the lots that were used in the clinical trials, which we know from the records was not correct.
Q. Were any patches manufactured in Lowman sold in the United States?
A. In the United States, I don't believe so. It was never approved for manufacturing patches in the United States. It manufactures Evra for Europe.
Q. Do you know what the changes in the dissolution specifications that were recommended by FDA?
A. Yes, I do. What would you like to know about them?
Q. What were they?
A. Okay. The FDA based that the in-vitro specifications for release of the product have dissolution at certain time periods. They specified what those should be, and they actually base that on the clinical trial information…not on the manufactured product information, since manufactured product information was not available to FDA.
So, FDA reviewing the proposed release criteria for the clinical trial patches provided what the requirements should be for release of those patches in terms of release of estrogen and norgestin over certain time periods, and I believe they included a twenty-four-hour time period, also.
So, it changed the release specifications from what had actually been used by the company.
Q. And that was a conclusion that FDA reached, as opposed to something the sponsor proposed and the FDA agreed to?
MS. PARFITT: Objection
A. I just stated it was from the FDA based on the clinical trial information. They felt that the company's release specifications were not tight enough to release a product that would perform reliably.
Q. (By Mr. Winter) How many medicines did you make this type of determination for while you were at FDA, i.e., what the dissolution specifications for the product should be?
MS. PARFITT: Objection
A. I didn't make that. And in this particular case, the medical officer didn't make that, either.
Q. (By Mr. Winter) Have you ever set the dissolution specifications for a medicine that's being manufactured?
MS. PARFITT: Objection
A. I don't think so. And, typically, it would be a person in terms of biopharmaceuticals or chemistry and manufacturing, the CMC people. We use similar types of release criteria in terms of medical devices. So, I have reviewed those in terms of medical devices and health risk assessments, but I would not accept them specifically as a medical officer.
Q. (By Mr. Winter) Would you call yourself a biomechanical engineer?
A. No.
Q. Would you–
A. And I'm assuming you mean someone who went to school and became a biomechanical engineer. No, I do not have an engineering degree.
Q. Would you call yourself an expert in statistical analysis?
A. In the use of statistical analysis in the context of what a medical officer would do to review certain things, but typically that would be a person who would be trained in statistical analysis. But using them, a medical officer has to use those.
Q. Then, I take it you're not trained specifically in doing statistical analysis?
MS. PARFITT: Objection.
Q. (By Mr. Winter) You use statistical analysis, but you are not an expert in creating it?
MS. PARFITT: Objection It misstates her testimony. I think she already answered.
A. That's the answer I have. It's not going to change.
Q. (By Mr. Winter) Do you consider yourself an expert in validating manufacturing processes?
MS. PARFITT: Objection.
A. Certain components, yes. In terms of have I had to review them and work with manufacturers and talk about how you would validate certain procedures? Yes.
I would not be a person that would come in and necessarily be the person who i
nitiated them, but I have pa

rticipated in validation and manufacturing practices, and I have reviewed validated manufacturing practices.
Q. How many manufacturing practices for a medicine have you reviewed?
A. For a medicine, not — Primarily, it would have been medical devices. They're a little more complicated than medicine.
Q. How many manufacturing processes for a transdermal product have you reviewed?
A. That would not — I don't recall the products that I've reviewed at FDA in terms of transdermal. Again, it would have been the ionic phoretic devices, looking at some of their information
Q. Would you consider the Office of Health Affairs, while you were there, to be a support office?
MS. PARFITT: Objection.
A. It was the primary clinical office, support office for the division director and the office of compliance.
Q. Have you ever heard the phrase, evidence based medicine?
A. Yes.
Q. What is your understanding of that term?
A. It would be a type of almost epidemiology, in that the best evidence would support a type of treatment versus another type of treatment.
So, they used evidence based that one treatment is better than another. It's the type of medicine that is actually being taught even in medical schools now in terms of physicians trying to determine the best types of therapy.
You can do clinical trials, but it is another form of trying to look at different types of therapies, primarily.
Q. Is it fair to say that you are not an expert in reaching a conclusion as to whether a company, in fact complied with FDA regulations?
MS. PARFITT: Objection
A. In what context? In terms of manufacturers? I mean, are you talking about when I was with the FDA, or are you talking about now? When are you talking about?
Q. (By Mr. Winter) Sitting right here.
A. Sitting right here today, I help manufacturers comply with the requirements of the FDA.
I believe the court, if you're asking had somebody violated, I believe that would be something that the court determines, whether someone has violated… and attorneys.
In terms of my helping interpret the regs and have a manufacturer comply with the regs or going through documents in the same way I looked at documents while at the FDA, looking to see if certain issues comply with the regs, I still do that. It is the same methodology I was trained to do as the support arm for the office of compliance, primarily, and also for the office of device evaluation But I'm not the final determinator. That again would be, in terms of this case, the courts and the judge.
Q. You know what the DDMac letter is?
A. Yes, sir.
Q. No DDMac letters have been issued with respect to Ortho Evra; correct?
A. Not that I've seen.
Q. I take it you've looked on FDA's website to see if there's been any posted?
A. Yes, sir.
Q. And you understand the distinction between an untitled letter and a warning letter?
A. Yes, sir.
Q. Is it fair to say that DDMac letters are generally untitled letters?
A. Usually, they are. Because the warning letter actually would make it so that you would have to sign off on general counsel, and you would have to have more of an interagency input into that warning letter.
Q. And you're not aware of any warning letters being issued by FDA with respect to Ortho Evra; correct?
MS. PARFITT: Objection What kind of warning letters are you talking about?
A. Alerts, health alerts?
MS. PARFITT: What are we talking about? It's too broad.
MR. WINTER: No, it's not.
MS. PARFITT: Object. Answer the question
MR. WINTER: You can answer the question, Doctor?
A. I haven't seen warning letters. I've seen safety letters. So, there has been safety notifications, but no warning letters that I've seen
Q. No 483's issued with respect to Ortho Evra by FDA?
A. Correct. Neither have I seen an establishment inspection report. You cant have a 483 unless there's actually been documentation that FDA's gone in and inspected
Q. That would be something that FDA chooses to do on its own initiative?
MS. PARFITT: Objection.
A. To inspect?
Q. (By Mr. Winter) Yes.
A. Yes. There's various things that can trigger an inspection Some can be that the FDA has been apprised of a safety issue.
In this particular case that the FDA may have known that this product was being manufactured with specifications that have no bearing on how it performed in humans, I don't see discussion of that from the FDA.
Typically, it can be either a planned inspection periodically, or it can be something that triggered an inspection
I'm assuming you are talking Redwood versus Puerto Rico, or where are we talking about?
Q. It could be anyplace. You could have establishment inspections to look at adverse event reporting, to look at regulatory issues, to look at manufacturing issues; correct?
A. Correct And this is a very large company in terms of Johnson and Johnson being the umbrella company.
So, there could be inspections. So, I'm sitting here specifically focused on Redwood City and Puerto Rico.
Q. Raritan, where Ortho-McNeil was located?
A. Yes, it could be there, too. So, I was limiting the world of Johnson and Johnson to specifically on this product, correct.
Q. I'm only asking you about Ortho Evra. So, I think we are on the same page there.
If I understand one of your last answers, if FDA believed there were, and I forget the phrase you used, questions about how a product was being manufactured, wouldn't FDA do an establishment inspection to look at the manufacturing processes?
MS. PARFITT: Objection
A. That's a fairly broad question in terms of this particular product, because if you notice, every time the company came in to have an interaction with the FDA, the first thing they start out with is it exhumes specs, and the labeling is appropriate, and we have no new issues, nothing unexpected.
So, when you come into FDA with a meeting like that, that is saying to the FDA that this product is under control. It is not a manufacturing issue.
So, it is being represented to the company, to the FDA over and over again that this product is within specs.
When you actually look at the documents, that's when you see, not at the FDA interaction, that the company has quite a problem in this product in terms of going from the clinical lots to the manufacturing lots.
They still, in 2007, and the deposition of the management will say they have no idea how much estrogen is being delivered. That's not the message that has been conveyed to the FDA in terms of the documents.
So, I don't pick up that that's the issue with the FDA. The FDA keeps saying why is this product not acting like we proved it? Why is it not?
So, there's parts that I am seeing that the FDA doesn't really have in their documentation that they're aware of.
Q. We talked earlier about more than 50 microgram pills and that being a higher formulation
What epidemiological studies are you aware of that says, a product having more than 35 micrograms of estrogen, but less than 50 micrograms of estrogen, has an increased risk for a venous thrombosis event?
MS. PARFITT: I'll just object to that to this extent: As you know, there were several epidemiologist designated in the litigation, and this would fall within their testimony.
To the extent you can answer that…
A. Well, number one, you mischaracterized what I said about the 50 micro. You tried to make me say that the original thing was 50 microns and less, micrograms and less.
I said 50 micrograms were actually applied to those two clinical studies that were cited by the FDA.
So, there is no m
agic number that the F.D.A has sai

d that this is safe, but there are magic numbers that the FDA has said are not safe, and those would be particularly the higher ones that are no longer marketed. So, the trend has been too low.
Now, in terms of epidemiological studies, I think there probably would be other people who are going to address those epidemiological studies. I think what we do have for this product, we know that this product is delivering more than a 35 microgram birth control pill, and we know that there are increased risks occurring. We know that the FDA is concerned about the increased risk because of the increased estrogens.
So, I think we can look at the Gic (phonetic) study, we can look at the Cole study, all of those with increased risks.
So, again, you are going to a birth control pill. This is not a birth control pill. This is a transdermal patch…different as apples and oranges.
In terms of just this product alone, we know that it is performing in a less safe fashion than a birth control pill with 35 micrograms and a birth control with 30 micrograms.
So, I think we would have to use the epidemiological studies that apply to this transdermal patch. So, I would say they support that it is not safe, that there's an increased risk.
Q. My question was very specific, Doctor. What epidemiological studies are you aware of that say that an oral contraceptive with more than 35 micrograms of estrogen has an increased risk of a venous thrombotic event than an oral contraceptive with 50 micrograms of estrogen?
MS. PARFITT: Again, I'll just object to the extent that Dr. Parisian has been proffered as an expert in the field of regulatory medicine that provides prescriptions. To the extent that she uses the field of epidemiology to interpret the information, but if you're asking her as a former medical officer, she can answer that question. As you know, there's others who have been designated. She certainly has been designated to address just this area.
A. I think I would probably rely on the experts, but I think also the labeling for the original birth control pill has a hundred and six different reference sites. Many of those address the risks of estrogen
So, just to begin with, in epidemiological studies, there are certain ones that the FDA has relied on or cited as a representative that you can have an increased risk. But again, there are epidemiologists who will be specifically addressing that
Q. You wouldn't hold yourself out as an epidemiologist; correct?
A. I have — I'm not an epidemiologist but I use epidemiology. Ive done epidemiological studies when I was at the FDA. I worked with epidemiologists to do studies. So, I have had a working use of epidemiology for the FDA.
Q. So, that working knowledge of epidemiology would have been acquired beginning sometime around 1991 through 1995?
A. Primarily, I was trained to work with my epidemiologist in that time. Actually, though, I don't want to mislead you. I went to graduate school, and I have a master's in biology, and we actually began doing statistical analysis and stuff in graduate school not for humans, but it would have been studies, pi square, and the different population studies that you would have done back in genetics.
So, it actually began there, but working with epidemiologists, helping design studies, would have began at the FDA, where I was trained to do that.
Q. If we looked at your C.V., would there be any epidemiological studies that you either authored or co-authored?
A. For the FDA, you wouldn't have written a paper. But if you look at actually an epidemiological study that I did do, that was in terms of dialysis products and ace inhibitors, that ended up with having a warning in all direct labeling about the interaction of dialysis membranes with ace inhibitors.
So, that was an epidemiological study that I began after looking at the medical literature, adverse event reports, worked with my epidemiologist We got money to be sent — money for the epidemiological study from ONB. We sent out forms. We got data, and then we designed a warning that appears in both medical devices and drugs because of that epidemiological study.
Q. Given your wealth of epidemiological experience, I'm going to come back and ask you questions.
Are you aware of any epidemiological studies that looks at women receiving an oral contraceptive with 35 micrograms of estrogen as opposed to oral contraceptive with 50 micrograms of estrogen? I want to know if you know of any epidemiological study that says there's an increased risk of venous thrombotic events.
MS. PARFITT: Mr. Winter, I think the question has been asked of her. She went through a rather lengthy explanation as to the extent of her knowledge in the field of epidemiology and how she used it and I believe the question is the same and the answer remains the same. Let's move on
Q. (By Mr. Winter) How much of your time in 2003 was spent on litigation matters?
A. 2003?
Q. Yes.
A. I don't recall.
Q. Was it seventy-five percent?
A. I don't recall what it was in 2003.
Q. 2004?
A. 2004. Off the top of my head, I don't know. I would assume it would be about that number.
Q. About seventy-five percent?
A. About seventy-five percent.
Q. 2005?
A. Probably that would be about seventy-five percent, and then 2006 would have been about eighty percent.
Q. And 2007?
A. 2007? Actually, if you took today, it would be about sixty percent.
Q. Meaning today, 2008, or today meaning —
A. Oh 2007? 2007 would have been about eighty percent. Today, 2008, it would be about sixty percent would be litigation, because I have done quite a bit for manufacturers so farther.
Q. Is it fair to say that this methodology you've described to me about looking at epidemiological data is something that you didn't know before you went to FDA?
MS. PARFITT: Objection to the form.
A. I think I answered that.
Q. (By Mr. Winter) I'm not sure you did.
A. Okay. Let me answer it again I did this type of studies, population studies, particularly in genetics. I also went to medical school. We did learn — Even in those days, we did learn some basic epidemiological studies, clinical trial studies. I went to the FDA in 1991, and I became involved with epidemiology in terms of designing studies, working with studies finding clinical data.
So, it would have been based on my training and experience before FDA, and then it would have been heightened in FDA.
Q. Are you aware of an adverse event that is unique to a woman using Ortho Evra as opposed to a woman taking a combination hormonal contraceptive?
MS. PARFITT: Objection
A. Well, in terms of a transdermal product, you would have skin irritation, inability to use it on her skin, also the device coming off. That wouldn't have been something that you would have in your oral contraceptive.
Allergic reactions in terms of the skin, some of the types of the properties. In terms of this, you also have — Well, there are things that would be unique to a transdermal product, that would be unique that you would not see with the pill.
Q. Can we agree that myocardial infarctions have been reported in women using hormonal contraceptives?
A. Yes. But I think the FDA made the point that the myocardial infarction in women under thirty was unique, and they had not seen that before — since the estrogen levels had not reduced in birth pills.
So, that was actually something the FDA brought up as being fairly a unique signal for this product, as opposed to oral contraceptives.
Q. Same event just happening indifferent population groups?
A. Well, in terms of the myocardial infarction in a woman under thirty, it actually is a safety signal. The same can be occurring in women
who are over thirt

y, but it would be harder to differentiate what etiology is. You don't think of myocardial infarctions in women under thirty.
So, therefore, it would be more of a red flag when you start seeing it in that age group, and you could have been seeing it in women older. It is not as likely to be as much of a red flag that something is unusual.
Q. What about pulmonary embolisms?
MS. PARFITT: Same question?
MR. WINTER: Same question
A. In terms of can you have a pulmonary embolism in women who are on birth control pills, yes. But again, seeing pulmonary embolism not as much as the myocardial infarction, but in women that are younger raises the question as to what's going on.
I think in that there were two pulmonary embolisms in the clinical trial, which is a fairly small population, thirty-two hundred women, was significant. I think the medical officer said that, too; that it's significant that a trial to get a birth control pill approved, you wouldn't typically see pulmonary embolism in those women
Q. What about the venous thrombosis?
MS. PARFITT: Can you frame the question just so we all know?
Q. (By Ms. Parfitt) Whether that would be unique or not as you have described for myocardial infarction?
MS. PARFITT: Object to form.
A. I think the myocardial infarction, particularly in women under thirty, same as when you ask me about stroke. Those are red flags that are very serious complications that you just typically don't associate with women under thirty.
It gets a little grayer with pulmonary emboli and VTE in women under thirty, because you can actually have birth control pills create those problems. That's my answer.
MS. PARFITT: John, is this a good point to break? You want to take a lunch break now?
MR. WINTER: That's fine. (A break in the proceedings was taken at this time.)
Q. (By Mr. Winter) Doctor, good afternoon
A. Good afternoon
Q. I want to spend a few minutes talking about your report.
A. Okay.
Q. How long did it take to prepare?
A. A long time. I don't remember how many hours. You can see from the size of these different documents, just the appendix and the report I don't know.
Q. Well, let's take the report itself, and then we'll talk about appendix 3, 4, 5 and 6.
A. Okay.
Q. Okay. I take it you prepared the report in its entirety?
A. Yes, sir.
Q. Unassisted?
A. Yes, sir.
Q. And would the answer be the same for appendix 3,4,5 and 6, that you prepared it exclusively?
A. Yes, sir.
Q. And the report is dated, I believe, in early 2008?
A. Yes, sir, January 4th, 2008.
Q. Was this a work-in-progress throughout the second half of 2007?
A. It would have been in December, 2007. I had already had one deposition, and there was no report for that deposition So, many of these documents, I had gone through originally for the first deposition So, this was actually the second trip through those documents to put them into a report.
Q. All right. Just so I understand chronologically, at some point you were deposed in a case called Lewis?
A. Correct.
Q. Not a requirement to have a report for that deposition?
A. Correct.
Q. And sometime between the Lewis deposition and January 4th, 2008, the report and the three appendices were prepared?
A. Is that how many appendixes? Yes, that's about right, the whole document.
MS. PARFITT: Just for the record, I think there's six appendixes.
Q. (By Mr. Winter) Well, your C.V., which is appendix 1, I didn't think would have been something that would have been prepared especially for this proceeding; correct?
A. That's correct.
Q. And then appendix 2 is your legal testimony history, which, again, would not be something specifically created for this report…maybe updated, but was an extent document, to use the word?
A. Yes, sir.
Q. So, what you prepared for this proceeding would have been the report, appendix 3, 4, 5 and 6?
A. Correct.
Q. Do you have billing records which would let us know how long it took to prepare?
A. We have billing records.
MR WINTER: We will mark this invoice as Exhibit 7.
(WHEREUPON, a certain document was marked Defendant's Deposition Exhibit No. 7, for identification as of March 11, 2008, and is attached hereto.)
Q. (By Mr. Winter) Doctor, if I'm reading Exhibit 7 correctly, you started working on your report and the appendices on December 1?
A. It looks like that yes, sir.
Q. And it continued on until January 4th of 2008?
A. Yes, sir.
Q. And if we total up the numbers in the quantity column, the Qty column —
A. Yes, sir.
Q. — we have the number of hours you spent preparing the report, plus the appendices?
A. Yes, sir.
Q. My math sometimes is good or bad but I'm counting close to a hundred and seventy hours.
A. I wont argue with that number.
Q. Now, it says — There's a reference to a James W.?
A. Parisian
Q. Parisian Is that the person who does your billing?
A. Yes, sir. That's my husband.
Q. And significant other, I was going to say?
A. That's correct. He's good with math.
Q. Did he have any role in the preparation of this report?
A. No, sir.
Q. Now, you had already gotten whatever information you needed to prepare the report from your — from the Lewis case, or whatever other material that you had been provided; correct?
A. Yes, sir. And it would have been in the documents that were copied.
Q. The two boxes or so, or three boxes that are sitting over in the comer?
A. Yes, sir.
Q. And if I understand it just so we can do this for the record, what you brought here today is the same set of materials that you produced in the Lewis case that were then copied; am I right?
A. Yes, sir. Plus, I brought you any additional documents I have.
Q. All right So, we have a new pile. But just so we're all clear, the three boxes that are over in the corner are the same boxes that were from Lewis?
A. Correct.
Q. And then you have a new pile here of material that you received both before and after you prepared your report; correct?
MS. PARFITT: Objection to the extent some may be before, some may be after, but beyond that…
Q. (By Mr. Winter) The first —
A. Those would have been after.
Q. There's just –I'm looking at a letter dated January 7th, and it's actually a copy. You got a copy of your report back?
A. Yes.
Q. And then the next document is dated February 26th, and it's a motion that the defendants filed?
A. Correct.
Q. So, just chronologically, this is after?
A. Correct.
Q. If we could quickly go through this pile, do you think you can show me what additional information you received prior to the preparation of your report, but after the documents you received in Lewis? Do you understand my question?
A. These would have been after (indicating), because I would have brought all those — If these had been mine, I would have brought them to Lewis. So, I brought the rest of my files that were not produced for Lewis.
I think one of the things in there is my deposition So, that's obvious. Those are regs. So, see, it is even a smaller pile. These are regulations that you get off FDA's website, in case we got into discussions of regulations. So, you see the pile is getting smaller.
Q. All right.
A. And this is a list of, apparently, the documents that I cited in my report. So, I got that from attorneys as to my reports. They wanted to compile a list of documents, in case they needed some for you.
Q. So, we'll mark this. But the document that I'm now holding in my hand,
this multi-page document, that
is a listing of all of– and I'm just looking at the first page upside-down– the E-mails and other internal J & J documents that you reference in your report or one of your appendices?
A. Correct.
Q. And this document was created by you, or a lawyer?
A. By a lawyer.
Q. Do you know which lawyer?
A. Their law firm (indicating). It wasn't a lawyer that created it.
Q. Someone employed by a law firm?
A. That's correct.
Q. And it would be the — Do you know which law firm?
A. Yes. This law firm, Ashcraft.
Q. And this list which we now just put separately, that was provided to you before you finalized your report, or after you finalized your report?
A. After.
Q. I take it that when we look through the rest of the pile, there is nothing that you received prior to you signing your report, but after you were deposed in Lewis?
A. No. They are not incorporated in the report. So, this would have been all after, and some of them are –One of them is from 2008 label.
Q. All right. January of 2008 label?
A. And some of them are expert reports.
Q. From the defendants?
A. Correct.
Q. All right. And then, something off of clinicaltrials.gov. Did you print this out or was this sent to you?
A. I believe this was provided to me, because I asked for it but I had already looked at the study without this, because it's actually referenced. That study is actually referenced in my report, talking about the EMEMA and the study that they had the company do in terms of the 30 microgram birth control pill versus levornorgestrel. So, this is in my report.
Q. It is one of the Chic (phonetic) studies?
A. Yes. It is the second one.
Q. And if we look at the second part of the banded group of documents here, it actually refers to that second Gic (phonetic) paper, correct.
A. Correct.
Q. And then you have a paper published in 2007; correct?
A. Correct. And it was referenced by, I believe, Dr. Dash No, wait a second. Let me make sure I'm looking at it right.
No. This is the Net 1 study that was published. I didn't have a copy of that. So, I have that.
Q. And another expert report from the defendants?
A. Yes, yes. This is more FDA. Let me get those out of there.
Q. Then there's a letter about where your report is located on a website and if anyone contacts you, what to do?
A. Yes.
Q. There's a document titled, Inhibition of Crystallization in Transdermal Devices. Did you get that one?
A. I asked for it. It was referenced in Dr. Dash's report. It is a world patent.
Q. And is that you highlighting on this exhibit?
A. Yes, sir.
Q. And why did you ask for it?
A. Because it was referenced in Dr. Dash's report, and I thought it would be something I would be wanting to see. So, I asked for it.
Q. And having had the chance to look at it did you draw any conclusions or come to any observations after reviewing this document that affects any of your opinions in this case?
MS. PARFITT: I'm going to object to the very broad nature of that question
MR. WINTER: You can answer the question, Doctor.
A. Well, it is a world patent, and it is actually dealing with transdermal ethinyl estradiol combination patch It references Dr. Whitehead, who had been involved in some of the original work for a patch trying to determine what. So, it was of interest. It doesn't change any of my opinions. I just wanted to see it, since it had been referenced.
Q. There were two documents, two single sheets of paper. One has an Exhibit 465. They may have gone together. I'm not sure.
When did you receive those documents?
A. I actually had received these documents. I had requested them yesterday, because I wanted to know exactly what had happened to Ortho Evra sales. And, so, I believe I discussed that in my report but I wanted any kind of information that was specifically for sales information
Q. And you were just looking for amount of sales?
A. No. I was just looking to see the trend in terms of users. Had the users continued to use it at the same rate as they did in 2002, or had their sales gone done. So, it was a general in terms of the sales.
Q. And the sales had gone down, looking at this exhibit; correct?
A. Correct And that had been my impression just from reading the literature, from talking to people, and I just wanted to verify that that, indeed, was true.
Q. Now, another document is an evaluation, I believe, by someone in New Zealand; correct?
A. Correct. It is two reviewers. It's a primary and a secondary reviewer for Evra to be marketed in New Zealand
Q. Now, you had seen this document before you prepared your first report, before you prepare your report; correct?
A. I had seen a document in this series of New Zealand, an interaction, and I discussed it in my report I don't believe I saw this final document. So, it actually goes through the two epidemiological studies and the final conclusion that the company made, the regulatory authority made.
So, that, if you want to ask me if that changes my opinion, it actually strengthens my opinion
Q. Can we agree that the conclusion that the reviewer in New Zealand reached is different than the conclusion that FDA reached?
MS. PARFITT: Objection.
A. No, because they're asking two different questions. In terms of the New Zealand reviewers, they had continuously said they are not going to allow marketing the product in New Zealand, and that's the initiation
The FDA has allowed the product. It has approved the product, but it has been continuously changing the label, tying to address some of the exact concerns that the New Zealand reviewers have.
So, I think what we are seeing here is the timing. New Zealand came long after the FDA's approval of the product So, they are kind of looking at things that have gone, and they reference it with other bodies, European bodies, health board authorities.
So, they are kind of, like, in a family. If you think of FDA as the first child, they're the baby. So, they're kind of looking at that They have many of the same concerns about the products and worries about the products, but they're just in a different order. They haven't approved it yet. So, they are still waiting, whereas FDA has already approved it.
So, their actions are similar, but I think a lot of it is timing, too.
Q. FDA could have said you can't market this product anymore; correct?
MS. PARFITT: Objection.
A When?
Q. (By Mr. Winter) At any time?
A. In terms of the F.D.A–
MS. PARFITT: Same objection
A. In terms of the FDA, the last product that was withdrawn from the market was 1976 by the FDA.
As I stated in my last deposition, whether Johnson and Johnson wants to voluntarily withdraw the market because it's not profitable or they want a change, it is a different question
The FDA, in terms of removing a product from the market, it is very difficult once the product has been approved in the United States…unlike other regulatory agencies that license a product, and they actually could remove a product very quickly, but the United States cant.
Once it is approved, the FDA tends to work to try to address safety issues with labeling changes to inform — Based on the information they have, they want to inform a physician of the increased risks and let the physician and the patient make a risk versus benefit decision, but FDA doesn't typically pull products off the market.
Q. When FDA approved the last label change about two months ago —
A. Correct, 2008 labeling.
Q. To approve that label change, doesn't FDA, pursuant to the regulations, and one of them is in that pile
, have to have determined
that for the labeled indication, benefits outweigh risks?
MS. PARFITT: Objection
A. Ask it in a different way, because I don't quite understand. I see many ways that I could go with that and I don't–I want to make sure I answer your question specifically.
Q. (By Mr. Winter) For FDA to allow a product, medicine, to stay on the market, doesn't FDA have to conclude, for the labeled indication, benefits outweigh risks?
MS. PARFITT: Objection
A. For the label indication based on the information that the company has provided, the FDA has allowed the product to stay on the market.
Q. Because?
MS. PARFITT: Are you finished with the answer?
Q. (By Mr. Winter) Did you finish your answer?
A. No, I haven't. I was thinking.
Q. I'm sorry. Go ahead.
A. Because the FDA has taken the information that the company has provided and negotiated a labeling that uses the information that they've been provided by the company.
Now, what we don't have there is that we have, in terms of what I'm seeing, the manufacturer saying they don't have any clue what estrogen is being released in their depositions. And the FDA, really, I don't believe, is being provided that information, that the company would say, their executives, that they have no idea how much estrogen is being released to women
The FDA also has nothing that I've seen documented, that they've been informed that the company has no idea what the release criteria should be to get a certain type of performance in a human being.
So, based on the information the FDA is being provided, that the product is in compliance and that everything is fine and that the company knows of no problem, everything is being released in specs. Yes, the FDA has allowed the product to stay on the market trying to address the labeling in the best way they can in terms of negotiated labeling to provide information to physicians that there is an increased risk that they need to be concerned about.
That was one of the reasons I looked at marketing. The marketing of this product and the use of the product has totally changed from when it was originally approved.
The labeling is the best way the FDA has to try to inform the physician of the risk versus benefit that there actually may be a person that the product may be, you know, risk versus benefit population
So, you're asking me many things, and I'm trying not to go off into too many things. But yes, it is a fact that it is on the market. FDA has not pulled it off the market. It severely changed the labeling. The use pattern has changed. So, there's been significant changes that have occurred in the product since when it was originally approved…one of which is FDA took off from the label the amount of estrogen The product was originally approved as delivering 20 micrograms of estrogen
Now, the FDA has totally changed the labeling and say they don't have an idea of how much estrogen is being delivered
You can't compare it to a contraceptive. You could, when it was first approved.
So, there's been so many evolutions in this product that the product that was originally approved is not the product that's sitting there today, and would not be the product that a physician would have used in 2001 in terms of the risk versus benefit decision in 2008, but it is on the market.
Q. And isn't that a different conclusion than they reached in New Zealand?
MS. PARFITT: Objection.
A. No. They still say that there's an increased — Why don't we read what they said in New Zealand
Conclusion: The risk versus benefit ratio for this contraceptive patch remains unfavorable. The new data provided do not change the earlier math recommendations that this application should be deferred. Meaning, they're going to continue to watch
This product has been approved in the United States. Therefore, the FDA doesn't have the ability to defer the approval and just watch the product. They don't have the ability to ask for additional safety studies. New Zealand has asked for additional safety studies.
So, in that the FDA was the first to approve the product it normally doesn't remove a product from the market. The FDA is actually behaving consistent with what New Zealand has determined in order to try to address safety issues with product.
Q. You think FDA has tried to address the safety issues associated with Ortho Evra?
MS. PARFITT: Objection
A. With the information they've been provided, yes, that's why they've issued safety alerts. That's why the FDA publicized that they change the labeling in 2008. The company didn't. There is no Dear Doctor or Dear Healthcare Provider letter that the labeling has been changed
Q. (By Mr. Winter) Are you sure about that?
A. In terms of the FDA's website, there is not and there's none that's been produced. So, the only one who has publicized the 2008 label has been the FDA change in terms of the safety and the doubling of the risks.
Q. Did FDA ask that a Dear Doctor letter be prepared regarding the 2008 label change?
A. I would not know that. I'm just making the statement that the company has changed the labeling, and there's been no communication to doctors, other than the FDA, that the labeling has been updated to include new epidemiological information about the doubling of the risks.
Q. Okay. Now, there was a label change in 2005; correct?
MS. PARFITT: Objection Which label change?
A. There were labeling changes in 2005.
Q. (By Mr. Winter) Actually, two of them; correct?
A. Correct. So, do you want to look at the labeling changes?
Q. Well, actually, I just want to make sure I have all of them. So, there were two in 2005?
A. I believe so, yes.
Q. One in 2006, or two?
A. Well, we can look at my report.
Q. Right.
A Go through the labeling changes. You specifically want 2006. So, I'll skip that.
I don't recall offhand how many were in 2006. We have different labels. We have September 20th 2006 is a labeling change. I don't recall if there was one before that
Q. So–
A. That was announced by the FDA.
Q. And then we have the next labeling change in January of 2008, after that September one?
A. Let me make sure. That would sound about right.
(WHEREUPON, a certain document was marked Defendant's Deposition Exhibit No. 8, for identification as of March 11, 2008, and is attached hereto.)
Q. (By Mr. Winter) Doctor, I'm going to show you what's been marked as Exhibit 8. I'm going to represent to you that this is the September, 2006 Ortho Evra revised package insert.
A. All right.
Q. If you'd just take a look at the last, the very last page, you can double-check.
A. Okay.
Q. Well look at the specific information But this label change incorporated the results of the first Gic (phonetic) and the Cole EPI study?
A. Just checking.
Q. Sure. If you look at Page 43 —
A. Okay.
Q. Actually, it's the last two references, the reference section
A. Correct I see 107, 108.
Q. And if we go to Page 13 of the exhibit, and you look at that paragraph that starts, the risk of venous thromboembolism, the two references in that paragraph —
A. Yes.
Q. Those are to the first Gic (phonetic) and to the Cole study; correct?
A. Yes.
Q. And if we move to the page before, Page 12, that bolded language under the box waning is the language about the Net 1 study; correct?
A. Yes.
Q. And I'm not sure I can pull it out, but it's your recollection that the bolded language, which appears on Page 12 below the box, was part of what was added to the prescribing information in N
ovember of 2005?
A. I believe so.
Q

. Okay. Now–
A. Do we want to look at it or do we have it?
Q. I'm not sure I have the November, 2005 package insert with me. But my understanding, and correct me if I'm wrong, is that the information from Net 1 was added to the package insert in the November 2005 label change; correct?
A. Correct.
Q. Sitting here, we don't know precisely whether any of that bolded language on Page 12 may have been changed from 2005 to 2006, but Net 1 went in the package insert in November of 2005?
A. That sounds correct. It was available in 2003.
Q. And submitted to FDA twice in 2004; correct?
MS. PARFITT: Objection
A. Yes, it was submitted in, yes. It was submitted.
Q. (By Mr. Winter) Twice in 2004?
MS. PARFITT: Same objection
A. Correct. With FDA becoming aware in June of Net 1 results.
Q. (By Mr. Winter) And that's based on the way you read the documents; correct?
MS. PARFITT: Objection
Q. (By Mr. Winter) Not that you've spoken to anyone at FDA and said, we first became aware of Net 1 in June?
MS. PARFITT: Objection, mischaracterizes the testimony.
A. Well, I think the documents actually do speak for themselves, in that there is a memo of the FDA bringing forth the Net 1 study and concern about the sixty percent and the need to change this.
So, I think the documents clearly show that the FDA first became aware of it in June.
Q. (By Mr. Winter) Of 2004?
A. Correct.
Q. Now, if we were to look at Page 13, again, of Exhibit 8, can you just look at the front page?
A. Okay. Exhibit 8.
Q. And if we went back and looked at Exhibit 2 for a second, you now have in front of you Exhibit 2 and Exhibit 8; correct Doctor?
A. Yes, sir.
Q. And I've turned you to an Exhibit 2, what looks like, more or less, the same warning section of the package inserts?
A. Well, there's a whole presentation before you begin on thromboembolism You know that?
Q. Right We're going to go through that I just want to make sure that when we start this discussion, you have the warning section, generally, as that is described in the code of federal regulations, the warning section from the 2001 package insert and the warning section from the 2006 package insert.
A. All right.
Q. Okay. Now, I take it that we can agree that the box warning on cigarette smoking is the same?
A. Let me make sure. I believe it is, yes.
Q. Now, in Exhibit 8, there is the next section on the Net 1 study, which you don't find in Exhibit 2; correct?
A. Correct.
Q. And, then, there is a paragraph that starts "the risk of venous thromboembolism" in the 2006 package insert?
A. Yes.
Q. And is that same paragraph in the 2002 package insert?
MS. PARFITT: I'm going to object to package insert It refers to the labeling in Exhibit 2.
MR WINTER: Well, let's call it labeling. I'll stick with labeling.
Q. (By Mr. Winter) I can suggest to you, Doctor, the answer is no.
MS. PARFITT: Let's not suggest. Let her take a moment to read the material.
A. I'm looking, because it would be structured differently. That first paragraph isn't.
Q. (By Mr. Winter) Right. That is in Exhibit 8, and that's the results of those two epi studies; correct?
A. Right here in the first paragraph yes.
Q. Whereas, the language in Exhibit 2 was the class labeling, correct?
MS. PARFITT: Objection, objection
A. That first paragraph is unique to the epidemiological studies. This is different. This was for birth control pills. This is a comparison to birth control pills.
Q. (By Mr. Winter) The first — The paragraph starting, an increased risk of thromboembolic and thrombotic disease, in Exhibit 2 was the class labeling, correct?
A. It was the labeling, yes.
Q. Okay.
A. That we discussed this morning.
Q. Right. And the paragraph starting, the risk of venous thromboemoblism, VTE, in Exhibit 8, is a discussion of the Gic (phonetic) and Cole studies; correct?
A. Let me make sure. I actually left out some information that had been in the class labeling. They shortened some of the risk information
So, I mean, it's unique to this study, but they've actually left out some of the risk information from the class labeling
Q. FDA, whatever, result of whatever negotiations occurred, approved that correct?
A. Well, they negotiated it And, so, the FDA would have been aware that they've done that but in some ways, they've actually taken away some of the risk information
Q. And by the way, when you have a discussion about this type of label change for a product that's been on the market, not a supplemental NDA, is there a clock user fee issue?
A. Yes. In terms of a supplement with clinical data, yes.
Q. But let's say it's not a supplement with clinical data There would be no user fee clock issue; correct?
A. Well, actually when you saw the back and forth between the F.D.A., there was a clock issue, and they wanted to get it done in a timely manner.
Q. Timely manner, as opposed to a user fee, you have to decide something by a certain date, are two different things; correct?
A. Not necessarily with the FDA, because there were statements that the FDA had to bring this to closure within a certain period of time.
It's a health risk issue. So, the clock is public health So, in terms of getting an issue addressed and taken care of, there was a clock. It wasn't a user fee clock, but it was an FDA clock to try to get this addressed. This was carrying on, dragging on, and FDA wanted to have it addressed in a timely manner…different type of clock.
Q. But a clock that FDA controls?
MS. PARFITT: Objection
A. Not necessarily. At the FDA, If you have a safety issue, you are held responsible in terms of higher-ups to get the safety issue addressed within a certain period of time.
So, it's not a clock that FDA controls. It's a clock that FDA is going to be scrutinized for if they don't address it in a timely fashion
Q. (By Mr. Winter) And when they address it in a timely fashion, aren't they going to try to address it appropriately?
MS. PARFITT: Objection.
A. They're trying to negotiate the best that they can in terms of the public health.
If you have a health issue, you also want to get public information out to the public and the physicians about the issue.
The company, on the other hand, has no time clock to address it, because the longer you take, the more you sell.
So, in terms of the FDA, they're fighting a different clock. They're fighting an issue of trying to show that they're doing their job at the FDA. They're trying to protect public health. They're trying to notify physicians. They're coming out with a safety alert. They're trying to provide information to protect people, and this was also an issue that was of high publicity at that period of time. They have public concern about the risk. So, those are clocks that are ticking at the FDA, that if you are a reviewer, or you are an administrator there, you're going to be held accountable. So, there is a clock. It is not necessarily a user fee clock but it is a clock that is probably higher than a user fee clock.
Q. There was a lot of public awareness of this risk back in 2005 and 2006?
A. Yes. In terms of the press, in terms of the public and in terms of the FDA. There was concern that this product had gotten out on the market and there had been reports of death and reports of adverse events, particularly in young people.
So, there was a higher visibility to this issue, than some other issue at the FDA.
Q. And you would say that physicians who would
be considering prescribing this produ

ct would be similarly aware of this risk; correct?
MS. PARFITT: Objection.
A. Not necessarily, because you are also forgetting where do physicians get their information It's, oftentimes, from sales reps. That is another part of the puzzle. What is the company saying to them? If a sales rep comes into a physician, particularly an OB-GYN, and they are saying oh, they're making a big deal out of nothing. Oftentimes they will believe the sales rep. So, there's always other factors that are outside of just this label.
Q. And what evidence is there in your report that sales representatives were telling physicians, any time in 2005 and 2006, that this is nothing, don't worry about it?
A. I was giving that as a hypothetical. You were asking me what was occurring and what would physicians know.
I think one of the things that we don't have represented here is what the sales reps were saying to the physicians, because that often has a greater sway than a change in product insert.
So, that's an important piece of this. I don't have a lot of information about it but it should be considered that's probably the most important piece as to what physicians would think about this product.
You're asking me to say what physicians would think. Well, it is more complex than just the product insert as to what the physician and patients think.
Q. You're aware, or not of information disseminated by, let's call it ACOG, regarding risks associated with Ortho Evra in 2005 and 2006?
MS. PARFITT: Objection It is way too broad.
A. I don't believe I would be the one talking about what ACOG said, but yes, ACOG would be another factor.
Again, in terms of ACOG, FDA has no input into ACOG or no oversight of ACOG. It is a totally independent body that takes contributions from many manufacturers. So, it is not necessarily something that FDA has any input into.
Q. (By Mr. Winter) But they would disseminate information to people who are members, or whatever they call them, that participate in ACOG; correct?
MS. PARFITT: Objection
A. They would be free to do that, as any other medical organization would be.
Q. (By Mr. Winter) Do you think that FDA thought the information in Exhibit 8 was inadequate or inaccurate?
MS. PARFITT: Objection
A. You know, FDA approved this labeling, but it is also based on the information that FDA is being provided by the company. I've already discussed what some of those company things would be that they may not have been privy to.
So, FDA negotiated the best labeling they could with the information they had. At this study, it was actually just the Gic (phonetic) study and the Cole study that they were putting in the labeling at that time to try to address what the risk was for patients, so that physicians and women could actually make a risk versus benefits decision as to whether or not to use this product.
There are so many other birth control products that they could have chosen So, that's important information for FDA and the company to provide to them. But again, it is all based on the information being provided by the company to the FDA.
Q. If we were to look at Exhibit 8, Page 13, go back a page, please.
A. So, before we get to thromboembolic disorders; right?
Q. Correct.
A. Because we haven't gotten there yet?
Q. Right There's a paragraph in Exhibit 8 that says: In three large clinical trials. Do you see that?
A. Yes. And that appears on the other page on the Exhibit 2. It is on the page under thromboembolism.
Q. All right. I think we can read that first, that one-sentence paragraph, and look at Exhibit 2 and see that the language remained the same. It just moved up in the warning section.
MS. PARFITT: Objection, objection Read the whole paragraph Are you suggesting that the paragraph in Exhibit 2, beginning, is the same?
A. We've moved it out of underneath thromboembolism, thromboembolic disorders and other vascular problems, and it's a paragraph all by itself. It is describing the two pulmonary emboli that had occurred in the clinical trial.
And then we removed the last sentence that had been in the original about it's unknown if the risk is the same or different than oral contraceptives. So, we removed that and we have a new paragraph underneath that.
Q. And then you have practitioners prescribing Ortho Evra. Do you see that in Exhibit 8?
A. Well, again, the next paragraph was moved from under thromboembolism.
Q. Right.
A. So, that was one we discussed before about if you have any of these complications, then you should immediately stop using Ortho Evra. So, that paragraph is now moved.
Okay. Now, we're going into the practitioner. Nothing new, new statement.
Q. No. Look at the paragraph underneath the box warning in Exhibit 2, the last sentence.
A. Okay. So, all of this has been added above that.
Q. Correct And then: The use of combination hormonal contraceptives.
MS. PARFITT: Is there a question?
A. Yes.
Q. (By Mr. Winter) Is that the same in both of them, Exhibit 8 and Exhibit 2?
MS. PARFITT: The entire paragraph?
Q. (By Mr. Winter) Through to diabetes?
MS. PARFITT: Through to diabetes. Is that the same paragraph in Exhibit 8 as it is in Exhibit 2?
A. It appears to be, yes.
Q. (By Mr. Winter) And the next paragraph, the information that follows in this section through to any route remains to be determined, also appears to be the same in Exhibit 2 and Exhibit 8?
A. Yes.
Q. And then if we go to the next paragraph, throughout this labeling to refer to a text on epidemiological methods, also appears to be the same?
A. Correct.
Q. All right. And then under the heading, Thromboembolic Disorders and Other Vascular Problems, A, Thromboembolism, that paragraph starting, an increased risk of thromboembolic and thrombotic disease, continuing through, elect not to breast feed, appears to be the same?
A. Yes. So, the specific information for the Ortho Evra clinical trials have been removed from this thromboembolic disorder and put up higher in the warning, so that a physician would see it sooner.
Q. And then the next paragraph B, those two paragraphs, the chart, the paragraph starting, hormonal contraceptives, and the paragraph starting, Norgestimate through activity is greater, appears to be the same; correct?
A. Yes. They are the same records, yes.
Q. And if we do this for the paragraph labeled C, cerebral vascular diseases, the two paragraphs under that heading starting with, hormonal contraceptives and through to the risk of stroke, and then the paragraph in a large study, through to greater in older women, reference 3, is the same; correct?
A. Yes.
Q. And paragraph D, Dose-related risk of vascular disease from hormonal contraceptives, that paragraph starting with, positive association, through to, choice of hormonal contraceptives, is the same in Exhibits 2 and 8; correct?
MS. PARFITT: I'm just going to object to the extent that the documents speak for themselves. I understand you want to do this comparison back and forth between Exhibit 8 and Exhibit 2, but the objection is that the document speaks.
There's no question as to whether or not the two paragraphs read as they appear in each one of the documents.
You can go ahead and continue to answer, Doctor..
A. Yes, they're the same.
Q. (By Mr. Winter) And if we go to paragraph E, I will suggest to you that the paragraph starting, there are two studies, through higher of estrogen, that paragraph is the same, but Exhibit 2 had an additional sentence paragraph which is removed from Exhibit 8.
MS. PARFITT: And I guess the question is, is that true or is that false?
Q. (By Mr. Winter) Is tha
t true?
A. Is it
true that the paragraph was removed?
Q. Yes.
A. Yes, it's true.
Q. Now, did you attend a meeting with other experts or individuals who are experts disclosed in this litigation for plaintiffs in late 2007 in Boston?
A. No.
Q. Did you attend any meeting with other experts for plaintiffs in these proceedings where lawyers did a Power Pointe presentation the second half of 2007?
A. No.
Q. Do you remember a case, Oakberg (phonetic) versus Zimmer?
A. Yes, sir.
Q. And was your proposed opinions excluded, in whole or in part, in that case?
A. I don't know.
MS. PARFITT: Objection.
A. I don't know. I never saw a written opinion I know that all the experts were excluded, including the orthopedic surgeon
I know that I had the exact same case in Minnesota, two clients, and Judge Tunheim had no difficulty and was aware of the Oakberg decision, and those cases subsequently settled.
Q. (By Mr. Winter) What about a case, Linsley, L-i-n-s-l-e-y? Do you remember that one?
A. Yes, sir. That was a surgical mesh in New Orleans, and the judge actually did a summary judgment on that case, saying that it was a repeat surgery on the surgical mesh
So, the surgeon had already operated on the woman So, he should have had a knowledge about potential for adhesions.
So, the case was actually thrown out because the judge said that the physician should have known that but he did state that I was fine to give opinions about the FDA and issues dealing with the FDA in the decision
Q. What about issues dealing with causation and adequacy of labeling?
A. Specifically, he focused on that. In this case, it did not matter, because the surgeon was doing a repeat surgery. So, he thought labeling and the risk of causation, that he already knew, the surgeon already knew it. So, that was what the decision was about. So, labeling was not an issue in that case.
That was back in, I think, what? 2001 somewhere.
Q. Close. Good memory. Reece, what happened to you in that case?
A. Reece? I don't know which case.
Q. R-e-e-c-e.
A. Oh okay. That was a case dealing with a patient with acute pain, and whether she would be able to determine if there was muscle pain
There actually was a Daubert hearing in that case. The judge said that I was fine to give testimony about drugs and FDA issues.
The case, when I went to the Daubert hearing, the attorney had made, I guess, some kind of a settlement or something with the other side, so that the nephrologists who were involved in the case didn't appear.
So, I was talking about nephology, where I actually was not the nephology expert for that case.
So, the issue was whether I could talk about the nephology and doing testing on blood for serum creatinine, but in terms of the FDA, the judge had no problem with that. That was a federal court judge. I forget what his name was. It was in Ohio.
Q. What about adequacy of labeling in that case?
A. I don't recall what he said specifically. I think the point was specific to that case, as to whether that woman would have had a different outcome if, indeed, she had had a serum creatinine done.
So, he said I couldn't argue specifically about that particular case on causation, and I was not supposed to be the causation expert, anyway.
Q. Jacobs versus Ceasars?
A. Jacobs versus Ceasars was a man that had died on a barge, one of those casino barges, and the ceiling tile had fallen on him. He subsequently died a death, an infectious death, but the issue here is that the entire barge, all the evidence got swept away with Katrina, the hurricane. So, there really was no evidence. That was a death case. It was nothing to do with FDA.
Q. And were you allowed to give opinions or not in the case?
A. I'm not sure what happened with that case, but there wasn't any real evidence. So, it is very difficult to go into causation
Q. Would you agree that with respect to transdermals, in-vitro released tests are limited in their predictability?
A. It's a general statement, because there are so many types of transdermal products. Some are less risky than others.
This is a very narrow — In terms of Ortho Evra, it's a very narrow therapeutic range. So, it is up to each manufacturer to determine what's the appropriate release criteria.
You could actually have some transdermals that could be released totally on in-vitro data. It would be acceptable.
In this product case, the issue is that the in-vitro testing isn't really representative of what's happening in-vitro.
So, in this particular case, their own documents repeatedly discuss that there's not a good in-vitro in-utero correlation test in terms of releasing this product and being able to identify what's going to occur in a woman.
Q. Do you think the FDA takes its obligations to protect the public health seriously?
A. Of course, they do. I mean, they're actually mandated by Congress to protect the public health, but they do have restrictions as to what they're allowed to do.
For example, they cant require certain labeling changes, unless they actually have some data to support that type of a change.
They can't require safety testing. In terms of manufacturers, you have to keep a level playing field. We approved the Paducah The FDA has continued a policy that you are supposed to have a streamline of getting approval of products.
So, there are certain limitations, but I think deep down, their mandate is to protect — It's not deep down The mandate in Congress is to protect the public health, but there's certain limitations as to what they can do as an agency.
Q. Do you believe that the purpose of a label for a medicine is to equip a practitioner with available information regarding its safe use?
MS. PARFITT: Objection
A. Are you speaking just specifically about the label as a product insert or labeling in terms of marketing, promotion, advertising?
Q. I started with package insert before, and someone said let's use labels.
A. Well, that's what I want to make sure of.
Q. Yeah
A. In terms of a product insert, the requirement is that you provide certain components, one of which would be adequate instructions of use, adequate warnings, adverse events, precautions, also, if there's animal data, clinical data You give a pregnancy category in terms of the risks of the patient.
So, there's various components that are supposed to provide the intended healthcare provider with information, adequate instructions for use and adequate warnings to be able to make a risk versus benefit decision to determine whether to use a product or certain medication
Q. Do you think post marketing surveillance data is important information?
MS. PARFITT: Objection There's no context.
A. Of course, I do. I mean in terms of its requirement for every manufacturer to have post market surveillance procedures, in terms of all drug approvals, it's just a requirement of the act, and it's a requirement of the Code of Federal Regulations, and most manufacturers have standard operating procedures for post market surveillance to increase — to change their labeling, to ensure the safety of their product, that patients aren't hurt.
And, yes, post market surveillance also can be used for determination of a new efficacy. So, it's a requirement for every manufacturer, and the FDA approves products for the beginning of market, but the manufacturer stays with the product throughout the life cycle, and post market is part of monitoring that life cycle.
Q. Do you agree that the safety profile of all medicines evolve over time?
MS. PARFITT: Objection.
A. Well, what do you mean by safety profile?
MS
. PARFITT: And what do you mea

n by all medicines? Are you talking about everything that's ever been on the market from the beginning of time to now?
A. Are you talking about over-the-counter? Are you talking about prescription drugs?
MS. PARFITT: I'm going to object to the question That's far too broad to even be capable of being answered.
MR. WINTER: I thought there were no speaking objections here, but that's okay.
A. I want to know —
MS. PARFITT: Excuse me. There's not but when it gets into the rim of a question that exhaust all possibilities and centuries of time, I think it's only appropriate to make a speaking objection
You can answer the question, please, or attempt to.
A. Well, my question was, are you talking about over-the-counter? Because they're generally recognized as safe and effective. So, they've already been kind of put over on another shelf.
Are we talking about prescription drugs? Are we talking about — What are we talking about in terms of the safety profile? Because your safety profile would actually come from your post market your sales and the history of a product but in terms of the way the FDA looks at the safety profile, the different types of drugs are kind of treated different.
Are you talking about a grandfathered product? Are you talking about a DESI product?
Q. Do the safety profile — Does the safety profile for any prescription medicine approved by the FDA after 1968, does that safety profile evolve over time for all of those prescription medicines?
MS. PARFITT: Objection.
A. And I believe you're talking about the life cycle of the drug. Is the manufacturer required to monitor how products change, reports that you may have, update labels, if that is what you are talking about for safety profile, yes.
Q. (By Mr. Winter) And wouldn't you agree that for prescription medicines approved after 1968, that it is normal and expected to learn additional information about this medicine post marketing?
MS. PARFITT: Objection.
A. Perhaps. I mean, there's so many types of drugs.
Q. (By Mr. Winter) Do you know of any prescription medicine approved after 1968 that works, in terms of efficacy, a hundred percent of the time for a hundred percent of the patients who receive it?
MS. PARFITT: Objection, frankly, as to the relevance of every other prescription We're here to talk about Ortho Evra…not to talk about all the other medications and medicines that are available to us post 1968. So, I strongly object to that.
A. Well, the word "works" is what you threw in there, and that's efficacy. So, do I know that every drug is a hundred percent effective for everyone? Of course, I can't answer that. It's a non-answering question, and that's why every manufacturer is responsible to determine that.
We know that before DESI, a lot of those prescription products were actually eventually removed that were not effective. So, they had been approved and on the market, and then they were found subsequently to be ineffective.
Q. Would you consider an Ortho Evra patch containing 60 micrograms of ethinyl estradiol to be safe?
MS. PARFITT: Objection Is that the context?
MR. WINTER: That's the question
MS. PARFITT: Broad.
A. With the information that I've seen, are we talking about the Johnson and Johnson patch made at a particular period of time? Because if you're talking about those patches, there's some serious questions that I've raised about good manufacturing practices and the way the patch behaves in terms of release in a human being.
So, you know that's a very difficult question So, I don't really think I can answer that.
It is on the market I'm not arguing that it is on the market but whether it's safe and that any 60 microgram patch is going to be safe, I can't really say, because I have seen all of these questions about manufacturing and IMVIC. So, that's why I cannot specifically answer that.
Q. Have you looked at any data regarding lots of Ortho Evra patches used by any of the bellwether plaintiffs in this proceeding?
A. Not specifically, no.
Q. Have you looked at data from any lot for any Ortho Evra patches manufactured anywhere in the world?
MS. PARFITT: Objection.
A. In what context? Because, I mean, we know in my report I talk about the company talking about six lots, it actually had reports. And, so, there was discussion in the company.
Have I focused on specific lots, no…other than what I've discussed in my report.
Q. (By Mr. Winter) Well, that's part of the question, Doctor. Have you done any investigation regarding any lots of Ortho Evra patch sold in the United States to correlate either lack of efficacy with something in a GMP issue or an adverse event that you can associate with a GMP issue?
MS. PARFITT: Objection.
A. If terms of my report, I discuss that the company is very clearly talking about six lots that had been associated with adverse events.
So, primarily, I've relied on the company discussing that they had and that's when they began doing their design of experiment, looking at the control of the raw material. So, there's been a discussion in that.
I haven't focused on specific lots, other than what's stated in my report, discussing those lots and the issues the company brought up.
Q. As I understand, some of what you did when you were at FDA, you would do health risk assessments?
A. That would be one thing. I did 262 of those.
Q. And you would look at, for example, manufacturing records, batch records —
A. Uh-huh.
Q. — to try to trace whether something in a manufacturing process was or was not associated with a safety issue or a health risk; correct?
A. That wasn't your typical health risk assessment. That was primarily involved with, say, a company that had a consent decree, that you'd go through their manufacturing documents.
For health risk assessments, you are often relying on the company to provide you information, just like this company does to the medical officer, provide you with information to make a determination about health risks.
Some of those, we had multiple health risk assessments, and then we eventually took — Well, in Devices, you have the lovely thing of mandatory action that you take. So, we took some mandatory action against some manufacturers and went in and seized their good manufacturing, all their records, their communications, and I would look at that information, look for trending for specific lots, or software issues or different devices. But that would not be in your typical health risk assessment.
Q. And do I understand that this trending and assessment that you just described, you have not personally undertaken such analysis here with respect to Ortho Evra; correct?
MS. PARFITT: Objection The question misstates, quite frankly, her testimony for the most of the day.
A. What I've done is the process just like I would do at the FDA. In terms of putting together all the data that I would have, sometimes it would be internal documents and sometimes it wouldn't but putting it together and making a risk assessment in terms of the health, public health, and what needs to be done and what things had to be addressed by a company.
So, this is exactly the process that I would even do in terms of health risk assessment…not health hazard evaluation, but health risk assessment, and come up with a plan or recommendation for the FDA as to what needs to be done next in terms of safety, and I did that.
So, this process would really fit into that type, when I would do mandatory actions and look at the complete picture, or I would be given a task by the FDA to look at you know, the safety of some
issue and to make a recommendation
Q. Is it fair to say that there are people at the FDA who were similarly tasked with respect to Ortho Evra?
MS. PARFITT: Objection
A. Similarly tasked, no, because they wouldn't have had all of the corporate documents. They wouldn't have had all the E-mails.
There could be people who did the adverse event reporting. So, they were tasked to look at adverse events. That would have been one component that I may have done.
I don't see a person that actually had the documents that I had in terms of the kind of report. The closest you would have had would have been the medical officer. I don't see a compliance officer's report going through all the documents.
In terms of the Center for Devices, their setup is a little different than the Center for Drugs, in that I was directly related to the Office of Compliance. So, I would do this with post marketing type issues. I don't see that same structure over at the Center for Drugs. It's just a little different in terms of the way the compliance function in one center versus the other in terms of– in terms of the Safe Medical Device Act, you know that act allowed for the FDA to remove medical devices that were considered unsafe from the market
The same requirement, like, for a 518E isn't over in the Center for Drugs. So, the structure for Devices is a little different in terms of having a physician actually do this type of review of medical records and manufacturing. That's not necessarily over in Drugs.
Q. Do you think device review at FDA is more rigorous than the medicine review?
A. That's not what I said. I said the Office of Compliance is set up a little different in the Center for Drugs — Devices than it is for the Center for Drugs.
For one thing, in the FDA Center for Devices, they actually do have the ability to go and remove unreasonably safe medical devices from the market. Whereas, over in the Center for Drugs, the primary recall action that's involved in drugs is when there is a manufacturing issue, such as a component or material that was used improperly in a pill, some kind of an issue.
So, in terms of the types of recalls that have actually occurred between the two centers, they're different. So, GMP is different between the Center for
Devices and the Center for Drugs. So, there are some differences in terms of what I learned to do and the methodology obtained from the Center for Devices, but is applicable to issues over in the Center for Drugs.
I don't think there's a corollary of physicians, and I have not seen any in this case, that would have done the same role that I would have done in terms of this type of review. The closest would have been the medical officer, and he certainly didn't have all the same documents that I have here.
Q. Let me see if I understand that. Are you telling me that you're not sure if there is a counterpart to you in the medicine, GMP side of FDA, or are you saying that you know one doesn't exist?
MS. PARFITT: Objection I think it misstates what she just said.
A. I'm saying that in the whole process for the Center for Drugs, there has not been one person doing the same function that I did here, and the function that I did here, the looking at the documents and stuff, I was originally trained for in the Center for Devices, and it's not clear that there is a counterpart, because of the differences in the compliance action between the Center for Drugs and the Center for Devices.
The Center for Devices actually has a little bit more ability to close a manufacturer down for an unsafe device. The Center for Drugs doesn't tend to do that type of action. They tend to do more voluntary types of actions in terms of labeling. Also, in terms of good manufacturing, typically their good manufacturing issues are a product that may have a bad ingredient, like the Tylenol tampering, things like that where there is a risk for a lot more lots specific as opposed to an overall manufacturing type thing.
So, in terms of the different types of compliance action, there's a difference in terms — And I don't see in this whole issue anyone who would be a counterpart to the types of things that I am doing here or some of the counterparts to the things that actually would have occurred in Devices when I was over there.
So, the closest that there would be near me would be Dr. Davis doing his medical review. So, he's not necessarily compliance arm, he's an approval arm, which is a little different.
As we know, the Center for Drugs does not have the same safety arm, and that's probably where I am trying to come from. They don't have the same safety clout or arm that actually has been put into the law. It's not used much, but it's been put into the law for medical devices.
As with Vioxx and all the new changes, they're trying to improve safety. But in my Center for Devices, I was actually allowed, as a medical officer, to be more involved with certain safety issues than actually as occurring over in the Center for Drugs, and that's supported by, you know, the GAO, the OIG, the IOM. The safety arm has not been developed as much for drugs.
Does that explain?
Q. Sure. Now, when you were at FDA, you actually were not employed by FDA; correct?
A. I was a member of the United States Public Health Service, correct
Q. And approximately how much of your time was spent either reviewing autopsies or signing off on autopsies?
A. I was stationed at the Armed Forces Institute of Pathology for one day, and I would be there a half day to one day a week. So, the rest of the time, I was at the Center for Devices, Radiological Health or doing stuff for the FDA.
Q. So, four days a week? Four and a half days a week?
A. Four and a half days a week for four years, and that would be directly causation determination
MR. WINTER: You want to take a break?
MS. PARFITT: Yes. Let's take a break. (A break in the proceedings was taken at this time.)
Q. Before we broke, you referenced something, and I want to find it in your report.
You said something about six lots and E-mails or internal documents.
A Sure.
Q. I just want to make sure I know what you're talking about.
A. Okay. Page 89 of my report right above, it begins with paragraph 187.
Q. Hold on a second. The entirety of that paragraph, 187?
A. Yes. And it would be everything that's referenced. I believe there's also maybe some stuff in the — I'm not sure if it is in appendix 6, but that is what I was referencing.
Should I look in here and see if there's more in here?
Q. Sure. Let's make sure on that.
A. It would also appear in appendix 6, would be discussed on Page 159, very similar information It would be paragraph 317, I think.
Q. If I am looking at them correctly, paragraph 317 in appendix 6 and paragraph 187 in your report are identical?
A. Correct.
Q. Now, doesn't — We can take either paragraph because they're identical; right?
A. They're identical; right
Q. Now, this E-mail says — And I'll wait for you to find it.
A. Where did I say it was, again?
MR. WINTER: 187 in your report.
MS. PARFITT: Page 189.
Q. (By Mr. Winter) Then it says, for the overview. Do you see that?
A. You're in the big report now?
Q. Yeah m in paragraph 187.
A. Okay. Got it. Okay.
Q. Now, what I'm looking at is that the first sentence to that paragraph references a specific document; correct?
A. 187,yes.
Q. Okay. And if I understand how you prepared your report, if I went and looked and found document 0313-0415 to 118– to 18, excuse me, I'd find the information you extracted i
n this paragraph?
A. It should be…if I typed the numbers right.
Q. R
ight. Let's assume that you typed them correctly.
A. Okay.
Q. So, what we have is a three-page document, which you crystallized in paragraph 187; correct?
A. Well, I provided it as support for the opinion that I had before this.
Q. I understand. But just with respect to this particular paragraph, we have a three-page document, 15 to 18?
A. Correct.
Q. And you have crystallized what you believe to be pertinent, or important, or relevant, whatever word, to support your opinion in this paragraph; correct?
A. That's what I was trying to do.
Q. Technically, we probably should be putting in — You know what an ellipses is?
A. Ellipses?
Q. You know those three dots when you leave something out and you go on
A. Okay.
Q. Technically, we should have some ellipses here.
A. We do have some.
Q. Where?
A. Well, for the introduction letter and the dot, dot, dot. Sony, but I didn't put the whole thing in there.
Q. What I'm trying to understand, though, is what appears in paragraph 187, is that from the part under, for the overview? Is that a verbatim quote, or do we have some ellipses that should be there?
A. I think that is the way it actually appeared on those memos for the overview, dash, and then that. So, I think I was copying the way it was written on those pages. So, I tried to give you the pages that would support what I was trying to say.
Q. Got it. Now, under, for the overview, you see that?
A. Yes.
Q. All right. It says: All lots released for distribution have met all specifications as approved in our NDA.
Now, I take it the italics was in the original for that?
A. You know, I'm not sure, because oftentimes, I'll put, I put underlining in italics. So, I'm not sure. So, I would say that I don't know for sure. Technically, I put that in if I did that.
Q. Okay. And then there's a sentence that talks about six specific lot numbers associated with spontaneous post marking reports of VTE?
A. Yes.
Q. We don't know whether you highlighted that?
A. I will state that I don't know offhand.
Q. Now, has — Have you, or are you aware of anyone determining whether any of the bellwether plaintiffs in this proceeding got a patch from one of these lots?
A. I haven't seen that documentation I haven't been asked to do that and that would be one of the things you would wonder about, but what I have here is what you see here.
Q. The next sentence says: The lots were reviewed, and there were no deviations associated with them that would affect product quality.
A. That's what they're saying. They're saying they all met specs.
Q. Now, did you — Are you aware, or did you take any steps to challenge the veracity of that assertion?
A. No.
Q. Okay. Now,then the next part of that sentence, and the assay and impurity results from testing retained samples are within the approved product specifications.
Again, are you aware of anyone, or did you yourself take any steps to challenge or confirm the veracity of that statement?
MS. PARFITT: Objection, compound.
A. No. I wasn't specifically asked to look at that.
Q. (By Mr. Winter) And then there's a risk assessment?
A. Yes. And that's their term.
Q. All right. And then there's a data assessment?
A. Correct.
Q. And then with in the data assessment, there's a sentence, the third sentence in the first paragraph there: The batch records for those lots have been reviewed.
A. Right.
Q. And the "those" refers back to those six lots?
A. I believe so, yes.
Q. Have been reviewed, and there were no deviations associated with the lots that would adversely effect product quality. And then it goes on, the assay and the purity results, ellipses.
I take it that we can assume that what you left out was the same language that appeared in the overview?
A. It would have been language that would not have been contributing to the point I was trying to make here, because this isn't one point in an opinion This is point F, and the support for that opinion that I was trying to make.
Q. I understand that. But you specifically reference this, and this is why I want to ask you about it.
A. Right. It would have been that I stopped typing. It's a lot of typing, and it didn't contribute one way or the other.
Q. Now, the next paragraph says: All lots released to distribution have been within specifications as approved in our NDA. Post approval changes have been the subject of either a supplemental, another abbreviation, to our approved NDA or included in the annual report, most recent filed January, 2004.
Did you, or are you aware of anyone testing the veracity of that statement?
MS. PARFITT: Objection
A. No.
Q. (By Mr. Winter) Now, if we could just go over to the next paragraph, 188.
A. Okay.
Q. Quick question You see the last sentence of that paragraph sixty-one lots of U.S. commercial patches are out of trend?
A. Yes.
Q. Were any of those lots released for sale?
A. I do not believe they were. I'm not sure, though, but from what I understand, I do not believe they were, and I would use the testimony of Mr. Audet, A-u-d-e-t.
Q. Can we take a minute and have you look through your report to see if there's any other discussion about either these six lots or any similar lots that you associate with either post marketing, spontaneous reports or lack of efficacy?
A. Now, the lack of efficacy is a different question In terms of this is the only documentation I found where the company was discussing that they actually had adverse events associated with six lots that they could identify the number.
So, if I had more like that, I would have provided that. But now efficacy, I haven't seen specific lots focused on for efficacy, and that would be pregnancy. But we have reports all through the lots that there are issues with pregnancy. So, that would be your adverse event reporting and a different issue.
But in terms of focusing on six lots, those were the once I saw focused on by the company.
Q. To go back to something you were explaining to me about the device side of FDA, and the review over manufacturing and the controls that you described to me —
A. Well, okay. Go ahead. Ask your question
Q. You know what I'm generally referring to. Was what you were describing something that applied, or applies, excuse me, to 510K devices, or PMA devices, or both?
A. Both And it would all be that what I was describing comes from the Food, Drug and Cosmetic Act. It would be the same type of process and requirements that would have been required for both drug and devices. So, it's a generic issue.
In that center, because there were so few medical officers, I actually got to be involved more with labeling issues and manufacturing issues than I would if I had been a medical officer just sitting in the Center for Drugs just reviewing drug charts.
Because, as you know, there's three hundred physicians in Cedar and there were ten over in Devices. Therefore, they tended to use us a little different in terms of interpretation of the act, and labeling and compliance issues, or they tended to use me more in that center.
Q. Well, I appreciate that. The question, I just want to make sure I understood it. The question didn't go to how you were utilized.
I'm trying to understand that the framework you were describing as the controller over manufacturing processes and the ability to have someone stop selling a device applied both to 510K devices and PMA devices?
A. Yes.
Q. Okay.
A. As you know, those are rarely used, just like over in drugs. But in terms of the sa
fe medical device, it actually a

pplies to 510K, PDP and PMA.
Q. People always ask this question. Do we have any new opinions not reflected in your expert report?
A. Not really. I mean, when you take all of this, I mean, you have, you know, we have, and we are including the expert report, plus all the appendices.
Q. I will — I didn't mean to exclude that.
So, if we take the totality of your six appendices and your report, is there anything new?
A. Is there anything new? I think the only thing new would be the New Zealand report I agree with it. It just strengthens my opinion. So, it is not a new opinion
The 2008 labeling wasn't in my report because it hadn't existed then, but it doesn't change my opinion So, those would be the only two new factors.
I've looked at the different reviews from the defense. They don't change my opinion So, the opinion stays the same, fairly, between all of these documents and everything I've reviewed.
Q. Are you critical of the 2008 label?
A. I think —
MS. PARFITT: Objection to the form.
A. The word, critical, I'm not critical. I'm not critical of anything. I'm just talking about that, you know, I've raised a lot of points in terms of manufacturing issues and of the information that the company knows, and that may not be conveyed in the labeling.
The FDA again negotiated the best labeling they could. They included the second study that the EMEA asked for, in terms of the low-dose of birth control pills.
So, the FDA is, again, in the same process of negotiating, trying to create a labeling that adequately warns a physician of risks versus benefits, based on the information they have.
But, on the same time, we know that the management does not know what the estrogen release is from a transdermal patch in 2007. We know that Audet talked about they don't have a valid in-vitro, in-vivo correlation, which the FDA doesn't seem to be fully aware of.
So, I'm seeing more than necessarily is reflected in that labeling, and that nature, the FDA hasn't been necessarily given all the same information I have in this process.
Q. For example, that E-mail that you referred to with respect to paragraph 187?
A. You mean about the six lots?
Q. Yes.
A. I haven't seen that in information that has been conveyed to the FDA, specifically.
Now, we have had meetings where they have discussed design, experiments, trying to look at materials.
Some of the discussions about the changes in the materials and the need to control the raw materials isn't necessarily something that I have seen conveyed to the FDA fully.
Q. At least in what you reviewed?
A. In what I've reviewed, and I've given you exactly everything that I've reviewed. I would look at other documents, if you had documents you wanted me to look at now.
Q. There's actually one or two more. So, I didn't want to disappoint you. If I could just confirm something, on paragraph 186 of your report, there's a discussion about toward the middle of that paragraph, 61 out-of-trend lots and 15 out-of-specification lots.
Do you see that?
A. Yes, sir.
Q. That's probably your bold language or italics?
A. I think it was — It may be. I think I was trying to take it as the quote. They're not my words, but I'm not sure how that came about.
Q. Is it your understanding that neither the 61 out-of-trend lots, nor the 15 out-of-specification lots were released for sale and use?
A. I believe — Isn't that the same in 1987? Don't they talk about — Well, You just asked me about 61 lots.
Q. I just want to make sure that it is paragraph 188, Doctor.
A. Right. When we just went through 187, didn't we talk about 61 lots?
Q. It's in paragraph 188, Doctor.
A. No, I know. I know where you are. I'm talking about the 61 lots. I'm going by what the company has stated, and I don't have any evidence that those were necessarily, but I do not know what happened to the 15 Evra lots.
Q. I was trying to be helpful, Doctor, and sometimes I fail. If you look at paragraph 188 of your report, you see the 61 lots there?
A. Yes.
Q. To the best of your knowledge, are we talking the same 61 lots in 186 as we are in 188?
A. I believe we are.
Q. Okay.
A. That's why I was looking for those 61 lots.
Q. Sometimes I'm marginally helpful.
By the way, you would expect if someone is doing quality assurance, I think that's the phrase, and finds lots are of spec, you would expect those lots not to be sold; correct?
MS. PARFITT: Objection
A. Correct, and that's why I wanted to make sure. Because I know there was some actual testing using those out-of-trend lots, but they were not commercially released
Q. (By Mr. Winter) Now, to the best of your knowledge, there's not going to be a plaintiff who received patches from one of those lots?
A. That's a different question I don't know.
(WHEREUPON, a certain document was marked Defendant's Deposition Exhibit No. 9, for identification as of March 11, 2008, and is attached hereto.)
Q. (By Mr. Winter) Could you just take a look at Exhibit 9. You may have seen this in a different format but I take it that you did review the medical officer's review for Ortho Evra?
A. Yes, sir.
Q. And if we look at the last page of Exhibit 9, your understanding, we had three different people from the Division of Reproductive and Urologic Drug products sign off on this review?
A. Yes, sir.
Q. And then we talked about this this morning. You had Dr. Houn — I think that's how you pronounce her — review the review?
A. Correct and concur.
Q. Now, this report does discuss the results of the 014 Study; correct?
A. Yes, it does, as is understood by Dr. Davis, and that's discussed in my report, too.
Q. And this report does discuss the two reports of pulmonary embolism; correct?
A. Yes, sir.
Q. And I think if we go to Page 51 of the report, we have the summary of Dr. Davis' review of both the literature and the reports from the clinical studies of Ortho Evra on the question of thromboembolic risks; correct?
MS. PARFITT: Objection, mischaracterization
A. We have a summary, but his primary discussion is on the progestin He is under the impression, when it got approved, that the estrogen was known, that it was 20 micrograms.
So, his summary here is because of the new molecular entity, which is the progestin So, that's what his primary focus is in this summary; is that they approved a new progestin and a discussion of risk, because you have risks associated with VTE with a progestin, too. So, that's what his focus is on, yes.
Q. And I apologize if I asked you this before, but you're making inferences and judgements about what was in Dr. Davis' mind.
You didn't talk to him about this; did you?
MS. PARFITT: Objection.
A. No. I'm reading what he wrote here in terms of the FDA, medical officers follow one medical officer. They don't stay static.
And, so, to read this, if I was the next medical officer up to take this report or this product, he has made it very clear that he was concerned, and he spoke throughout the report and the review about using progestin His focus is not the estrogen, because the estrogen is low.
So, his concern is the VTE risk of the progestin, which they don't know whether it is a second generation or third generation, and that's what he's stating here. He states that the label should clearly reflect the safety concern about the potential risks about venothromboembolism in every user, and he's also going on and on about th
e progestin throughout his review.
Q. We are talki

ng about a risk of VTE; right?
A. Correct You can have a risk of VTE with both, estrogen and the progestin The third generations, the labeling about risks is associated with the progestin, not the estrogen, because estrogen is a low dose.
And, so, his focus has been on his concern with those two PE's due to the progestin. It's the new progestin that has never been used before.
He assumes the estrogen is low, and the company has told them it's low. 014 has told them, you know, it's 20 micrograms. It's a done deal when it comes to estrogen It should be a low dose. So, the concern is the new progestin.
Q. Did he agree with the company's calculation of the PEARL index for this product?
MS. PARFIT: Objection.
A. In this summary, he didn't state in the summary. He discussed that somewhere else when he talked about efficacy.
Obviously, it was approved. So, they met the PEARL index requirement that the company wanted in order to get it approved, and I think that's Page 49.
Q. (By Mr. Winter) Have you independently tried to determine whether or not Dr. Davis' assessment of the efficacy data presented by the sponsor was correct?
MS. PARFITT: Objection
A. He approved it but there had subsequently been public hearings or advisory committees to try to discuss the future of birth control products, including rings and transdermal patches, what should be the indexes used for approval of a pregnancy product particularly in a real life situation
So, at this time, with the information he had he approved it but there's been subsequent discussions trying to determine if there was perhaps a better way or a more representative way to approve these types of products.
Q (By Mr. Winter) Have you gone out and tried to do whatever type of calculation, real world or the way done by Dr. Davis and the sponsor, for PEARL index for Ortho Evra?
A. I don't think — I was never asked to do that and I believe there would probably be other people that would talk about that epidemiologists and people who would discuss that. I mean, the fact is, it is approved.
Q. Whether or not another epidemiologist or someone else would do it, I take it you haven't independently gone out and tried to calculate a PEARL index for Ortho Evra?
MS. PARFITT: Objection to the extent that she has not been asked to — She has not been proffered as an expert in this case as an epidemiologist or someone who has been asked to calculate PEARL index and to opine on those matters.
Q. (By Mr. Winter) Well, appreciating that, Doctor, Dr. Davis is looking at efficacy and safety when he does his medical review; correct?
A. Primarily efficacy, because the safety has already been established with being able to bridge to the birth control pills.
Q. And in a regulatory context, he looks at whatever data he's given and makes a judgment as to whether or not there's efficacy; correct?
A. Correct. And the company determined that they wanted to use only the PEARL index as being their primary end point.
So, he would look at their end point calculation He would also have the FDA statistical people look at the end point calculations and determine if the company has meet what they said would be their efficacy point for getting approved.
Q. And I take it that we can agree that the statisticians at FDA check the sponsors data?
MS. PARFITT: Objection.
A. For the PEARL index, they would have looked at that information, and the company only used the PEARL index for efficacy. They didn't make any other claim. They didn't get approved on any other requirement. They just said the PEARL index.
Q. And statisticians at FDA verified the data as it relates to the PEARL index, and Dr. Davis looked at whatever information was given to him, and he agreed that that efficacy point the PEARL index, was met; correct?
MS. PARFITT: Objection.
A. Obviously, for them to approve it they met the index, because that was all they were going to get approved on, was that index.
Q. (By Mr. Winter) And three years from now, two years from now, who knows when, we could have a different regulatory system for what would be an end point for efficacy for an oral contraceptive, if I'm understanding your last answer about five minutes ago?
MS. PARFITT: Objection.
A. There's still discussion. I don't think the FDA has determined if they are going to change from the PEARL index or not I haven't seen anything to that. It is just they wanted advice as to other mechanisms to test for efficacy.
A new manufacturer may come along and have a different mechanism that they want to get approved with, and they could put that forth. So, it's not static. The end point can change.
Q. But today, the end point is a PEARL index?
MS. PARFITT: Objection, asked and answered.
A. Today, their end point is a PEARL index. Other manufacturers may want to use a different index, but the industry has been using the PEARL index.
Q. (By Mr. Winter) I'm going to take two pages and mark them as Exhibit 10.
(WHEREUPON, a certain document was marked Defendant's Deposition Exhibit No. 10, for identification as of March 11, 2008, and is attached hereto.)
Q. (By Mr. Winter) Before we talk about these, Doctor, you're familiar with the Med Watch form?
A. Yes, sir.
Q. And Med Watch forms, I think they're called 3500s?
A. 3500 A, Form 3500 A.
Q. And not to oversimplify, but even in a clinical trial and in a post marketing setting, sponsors submit Med Watch forms; correct?
A. Correct.
Q. And you have two separate Med Watch forms in front of you that have been marked Exhibit 10. Have you seen them before?
A. I believe I have, yes.
Q. And they're for the two reports of pulmonary embolism and the phase three studies; correct?
A. I believe so, yes, in IND 5488.
Q. And we can go back and find the document, but that's the IND for Ortho Evra; correct?
A. Yes.
Q. And were both of them submitted to FDA the day the information was received by the sponsor?
MS. PARFITT: I'm just going to object to the extent that I believe there are some additional Med Watch reports, John, for the same two PEs that have not been produced to the doctor. You have given her one. I believe there are additional Med Watch forms for the same two PEs. Do you have those, as well?
MR. WINTER: Was that the nature of an objection?
MS. PARFITT: It was. It actually was an objection I'm not sure she's being provided the complete document.
In answer to your question, yes, it is an objection
Q. (By Mr. Winter) Doctor, it is pretty easy. Look at the top of each page. Is it 1 of 1 and of l?
A. Page 1 of 1, yes.
Q. And look at the second page.
A. l of 1.
Q. All right. Aren't these the initial reports for each of those?
MS. PARFITT: Objection
A. Well, they're reports and they're 1 of 1, but I think there are other reports that subsequently went in, and I think that's what the issue is.
Q. (By Mr. Winter) These are the initial reports for each of those PEs; correct?
MS. PARFITT: Objection.
A. Well, the reason I'm looking at it is because I know that one of them actually was listed originally as pleurisy (sic), and then the clot came out later. I believe there's more than one report, as I'm looking at this.
Q. (By Mr. Winter) I think the question was whether or not there were additional reports. I will agree with you that there are additional reports.
A. Okay.
MS. PARFITT: Additional reports for these same two persons?
Q. (By Mr. Winter) Sure, supplemental reports. But aren't these the initial reports for these two patients?
MS. PARFITT: My o
bjection is simply this: You're sh

owing her initial reports for two PE clinical trial patients, and what you are not showing her, you have not provided would be the entire report for both of those two PEs.
I think it is unfair I think it is misleading and I think it is improper. That's my objection
A. Actually, I think I discuss these adverse events in here. I was just pulling out my comments on the adverse events, these two, to see what I have.
Q. (By Mr. Winter) Can I make this pretty simple, Doctor?
MS. PARFITT: No, no, no. Let her find the page and report where she has discussed it. She said she was looking for that. Let her find it.
(An off-the-record discussion was held.)
MS. PARFITT: To shorten this, I can show her the report. Do you have a problem with that?
MR. WINTER: It doesn't matter.
MS. PARFITT: Your discussion report is around Page 54.
THE WITNESS: Thank you
MS. PARFITT: Your report, Page 54, paragraph one, with counsel's permission 113, around there.
A. All right. Okay. Paragraph 13, and 113 is where I've written about it. And you talk about subject — Okay. I guess you should ask your question
Q. (By Mr. Winter) Why don't we go to the first page of this exhibit You have the first page of the exhibit?
A. Yes, sir.
Q. If we look — These are all boxes here. The date received by manufacturer, July 7th, 1998. Do you see that?
A. Uh-huh
Q. And the date of the report is July 7th, 1998. Do you see that, box 4?
A. Yes.
Q. And box, in box 7, it's checked initial. Do you see it?
A. Yes. I'm just looking at it, because I have — I think this is — I want to make sure I have the right woman here.
Q. This is the patient who had the elective surgery.
A. Right. I just want to make sure I have the right report. Because the first report I have, the initial report was filed June 24, 1998, which is different than this, which would have been her–
Q. Actually, you have the date of the event confused, Doctor.
A. That's what I'm trying to look at here. The report has been received on July 7th. The complaint was assigned.
Okay. Go ahead. Now, you had a question?
Q. What we have, the first page of Exhibit 10 is the initial report for the patient described in paragraph 113 of your report; correct?
A. Correct.
Q. And what I had asked you a few minutes ago was that this report was submitted to FDA the day it was received by the sponsor?
MS. PARFITT: Objection
A. Well, that's what I'm looking at. You have a date received by the manufacturer. I'm looking for a date received by the FDA.
Normally, it's multiple pages. Do we have a date that it was received by the FDA? Date of the report, yes, but do we have anything to show that it was received? Because it actually has an odd number. We have the manufacturers number, but we don't have the FDA's number, the adverse event report for the FDA.
Q. Who would put the FDA number on it? The sponsor or FDA?
A. The FDA.
Q. All right.
A. And I was wondering do we have any documentation that the FDA put a number on it.
Q. You would have to look at the FDA database; wouldn't you?
A. Correct. So, you're asking me the day it was received, and I cant tell you the day it was received because there's nothing to show that it actually was received.
Q. My question was, the date it was received by the sponsor and the date of the report are the same; correct?
A. Well, the date of the report and the date of received by the manufacturer, correct, they are the same, 4 and 4.
Q. Okay. Now, if we go to the second page of Exhibit 10, can you confirm for me, first, that the patient described — the second page of Exhibit 10 is the patient described in paragraph 115.
A. Okay. What's the question?
Q. Well, have you confirmed that, South African patient?
A. Yes, I know, South African patient, 28-year-old woman, diagnosed with pleuritis on August 26th, which is what it says, received on September 29th 1998 by J & J.
Is there a question?
Q. We got the same report?
A. It seems to be, yes.
Q. And Page 2 is the initial report for this patient who was in 2003; correct?
A. Yes.
Q. And the adverse events described are pleurisy and embolism pulmonary; correct?
A. Yes.
Q. And date of report and date received by manufacturer are the same, September 29, 1998; correct?
A. Correct.
Q. You have a tab 7 to your report, the documents you reviewed?
A. Do I have a tab 7? I think I do, yes.
Q. Now, the pages aren't numbered. So –Oh, they are. I'm sorry. Do you have it?
A. Yes, sir. Right here (indicating).
Q. Could you look at the Page 30. Do you have it?
A. Yes, sir.
Q. There are a series of FDA letters in the middle of that page?
A. Yes, sir.
Q. None of them relate to Ortho Evra; correct?
A. Oh, no. They're related in terms of Johnson and Johnson doing a search of other issues, letters that may have been for the company.
I assume you're talking about the warning letters, because there are some communications in there that are two people.
Q. Well, if I started at what is in the column, Exhibit 48, and then not that they are all sequential, but going down to 39, actually to 55, none of those relate to Ortho Evra; correct?
A. I don't believe so, not specifically to Ortho Evra. They would be Ortho Diagnostic or some other component.
Q. Now, this 39, and if I'm testing your recollection, you need to tell me. Does 39 relate to Ortho Evra?
A. I don't remember what 39 is.
Q. If we went to Page 41, do any of those letters relate to Ortho Evra?
A. Not — No, not necessarily. They say exactly who they go to. The only ones there, I think, is the Ortho-McNeil. I don't think it is Ortho Evra.
Q. And if we were to look at Page 40.
A. Uh-huh
Q. There is an Ortho-McNeil Pharmaceutical awarding letter dated April 21, 1997. Does that relate to Ortho Eva?
A. No.
Q. Do any of the other letters on Page 40 relate to Ortho Evra?
A. Offhand, I don't believe so. I was doing a search of everything that would have been found for the company.
Q. Now, if you go to Page 43, you have a heading, FDA LETTER PACKET. Do you see that?
A. Yes.
Q. What does that relate to?
A. I don't know offhand. Those would, again, be letters that I have that I found.
Q. Is this appendix 7 something you created?
A. No. As I said today, it would be documents that I cited in my report someone else created.
Q. Well, see, that's why I'm a little confused. Because when I looked at your report, none of the letters on Page 43 are cited. So, that's what I'm trying to understand here.
A. Okay. I think I provided everything that I have. So, I believe you actually got my complete file of everything that I had sent. If you had my hard drive and all the information on it, that's what you got. So, you have everything, more than you wanted.
Q. More than I wanted?
A. Right. You've got it all, my complete file.
Q. And I take it, if we just go to Page 44–
A. Uh-huh.
Q. You went on FDA's website and pulled every letter to the Johnson and Johnson company?
A. Yes.
MS. PARFITT: Objection.
Q. (By Mr. Winter) Now, on Page 44, there's, toward the bottom, a September 15, 2004 letter to Ortho-McNeil. Do you see that?
A. Yes.
Q. That has — Does that have anything to do with Ortho Evra?
A. I don't believe so.
Q. Again, not that I want to play a memory game, but do you know what that letter relates to?
A. I don't know what that letter relates to. Ortho-McNei
l has had so many other products. If th

ere had been a warning letter, it would have been cited in my report specifically for Ortho Evra.
Q. I appreciate that. If you could look at Pages 46 and 45, do we have all of the medical literature that you have reviewed, say, for the article that you recently had to prepare your report?
A. Well, you would have all that I've cited, and all that I saved would be listed here, primarily. I mean, you can't say that these are all the articles I've ever looked at, but these would be the articles that I've actually saved in my files that I have. If I would have referenced other — Any articles that I was citing would be referenced in that So, you have more than what I've cited, probably, in my report.
Q. Okay. Have you looked at any of the ACOG guidelines for the prescription of hormonal contraceptives?
A. Not recently, not specifically for this case, I assume there would be many OB-GYNs involved in this litigation that would probably discuss ACOG. Are you going to give me some to look at?
Q. Well, if you're telling me that you didn't look at any to prepare this report and you would say you need to ask an OB-GYN about them, then I'd say no.
But if you're going to say, yes, then I'll show you one. You decide.
A. I don't think I would be the one asked about ACOG…not that I don't want to look at them. I think that it would be — I don't want to mislead you. I wouldn't be the person, probably, asked to address ACOG.
Q. Give me about three minutes, Doctor. I have to check two things. Why don't we take a three-minute break, and then we'll wrap this up.
A. Okay.
(A break in the proceedings was taken at this time.)
Q. (By Mr. Winter) What advertising or promotional material concerning Ortho Evra did you review?
A. I don't have any, I believe, in terms of my report.
Q. I don't think so. I just want to confirm that you haven't looked at any advertising or promotional material concerning Ortho Evra for purposes of your report or your opinions in this matter?
MS. PARFITT: With the exception of perhaps there was that one sales document there that you looked at a little bit earlier that showed whether or not sales were going up or down, that was it.
(WHEREUPON, a certain document was marked Defendant's Deposition Exhibit No. 11, for identification as of March 11, 2008, and is attached hereto.)
Q. (By Mr. Winter) What's been marked as Exhibit 11 is a two-page document that we talked about earlier of sales figures for Otho Evra for periods of time from 2002 through, I believe, 2007.
Is that the totality of anything relating to promotion or marketing that you looked at?
A. There's also one E-mail where a salesperson is talking about the impact on sales in terms of the change in sales. It's in my report.
There's also a discussion of the change in the labeling, what the change in the labeling would do in terms of making it a second tier.
So, there's marketing discussions. It is very limited, but it is in my report. Those are the documents I've seen I believe that would be around opinion number 5.
Q. I think I know what you're talking about, Doctor, but I guess the question is, is there some promotional brochure, some sales aid, some advertisement, some TV ad that you've looked at and have an opinion about that is in your report?
A. No. It would be only what I was just talking about. There is the discussion about the impact on sales and the change in the labeling and then the decrease in sales in terms of this marketing sheet as to the sales. So, it's primarily been on sales…not on promotion and marketing.
Q. And it's actually on total sales…not a sales effort; correct?
A. Other than that one E-mail that the person had discussing the change in sales and the types of patients who would continue to use their products.
Q. And if I'm remembering correctly, you saw Exhibit 11 after you prepared your report; correct?
A. Correct.
Q. Okay. Now, I believe, if you look at paragraph 58 of your report — Do you have it?
A. Yes, sir.
Q. You reference an evaluation done by someone at FDA on Net 1 in 2005; correct?
A. Correct.
Q. So, can we agree that people at FDA reviewed Net 1 in its entirety, at least by some point in August of 2005?
MS. PARFITT: Object to form.
A. They did review — They did review Net 1, and there's a discussion at the end of his review as to whether it is comparable to the United States product or to the European product, but there was a review done by the pharmacology people at FDA in August of 2005.
Q. (By Mr. Winter) And the fact that there's a report, which you give a Bates range to from the FDA production, in your mind, is positive evidence that someone at FDA, in fact, looked at Net 1?
MS. PARFITT: Objection.
A. No. People had looked at Net 1 before that in terms of the interaction at that meeting and, also, in the May, 2004 package.
But when an official person, who was a pharmacology type person, reviewed it that would have been August of 2005.
Q. (By Mr. Winter) When was the 017 Study submitted to FDA, the final report?
A. Well, the 017, we discuss that in here.
MS. PARFITT: John, if you don't have a problem, could you reference the page we're on?
MR. WINTER: Sure. It's Page 40.
THE WITNESS: Page 40 in the appendix?
MS. PARFITT: In the appendix, it is Page 12, and Page 40 in your report.
Thank you, John, I appreciate it.
A. So, that would be — We're discussing paragraph 80, 81, 82, and you want specifically the last date for 017?
Q. (By Mr. Winter) The question, Doctor, is, when was the final study report for the 017 Study submitted to FDA, based on your review of whatever information you looked at?
A. I'm trying to find you. Okay. It was not prior to the NDA approval. It was after the NDA approval. I'm trying to find a date. The letter that Dr. Polo sent to the FDA in the footnote on Page 41.
So, if you go to paragraph 179 in appendix 6, it talks about the abbreviated summary where it was submitted, and a letter of October 1st, 2001, and that's the abbreviated study report. You're asking the complete report.
Q. What I'm trying to understand, Doctor — Had you completed your answer?
A. Yes.
Q. Okay. Don't want to interrupt you.
But if you look at the second sentence of paragraph 179.
A. Okay.
Q. As I read that, based on what you reviewed, the full study report in three volumes was submitted on October 1, 2001, and actually the first two volumes were the 017 Study, and 018 was volume 3. Have I got it right?
A. I believe you do have it right
Q. Okay.
A. But wait a second. If you go October 1st, 2001, it was an abbreviated study report, volumes 7 and 8 of the NDA.
So, you're right. In October 1st, 2001, I completed three volumes.
Q. As I read your report, there was an — There were abbreviated summaries at some point in time, but based on what you reviewed, two volumes, which is the best you could determine, where the entire report was submitted on October 1, 2001 to FDA; correct?
A. I don't know if this is correct, because I think there was an abbreviated study report, and that was in volumes 7 and 8 of the NDA. There was a later submission, and I don't — I don't know if I have the right date there where they provided the complete, but it was after NDA approval.
Q. Okay. And, actually, you don't have any page references to that paragraph So, you're thinking that may be a typo?
A. It may be, because if you look at the other one with the POE number, that would be — that would have been the letter from Ram
on (phonetic) Polo submitting the abbreviated stu

dy report.
So, there may be a typo in there, because it actually came, I believe — the full report came after the NDA. So, there was an abbreviated safety summary.
Q. Can we just make sure we agree on one thing, if we have a typo here.
The full NDA was submitted in December of 2000? Does that sound right?
A. Yes.
Q. And you would have volumes 6, 7 and 8 in the NDA submitted in December of 2000; correct?
A. Yes.
Q. So, could it be, and I'm just — You know, if we're starting to guess, then we're starting to guess.
Is it that the October 1 in the first sentence is wrong and the October 1 in the second sentence is right, or is it the other way around?
A. That's what I was trying to figure out a minute ago.
We know that the abbreviated summary was what was reviewed by the FDA before they approved the NDA, and the complete summary, I believe, actually came after or near the time of approval. So, I'm not sure where the original typo is.
Q. Okay. Now, sitting here, are you of the view that whenever the 017 report and its two volumes was submitted to FDA, it was not reviewed by people at FDA?
A. No. What has not ever been cited has been the findings of 017 in terms of the difference to the birth control pills, and that's what the point is. It may be submitted somewhere in some manner, but in terms of the FDA, they've never expressed an awareness of the findings in terms of the relation of Ortho Evra versus birth control pills, in terms of the estrogen delivery, which actually is very similar to the findings of Net 1.
So, the information in the 017 really reflects Net 1. So, why was FDA concerned about Net 1 in 2004, if they fully had been aware of the increased risks with 017.
And when you look at investigators' brochures, there's discussion of 017, but never 017's relationship to birth control pills in terms of the two times, three times findings as found in 017.
So, 017 is a study that is really not addressed by FDA. It's not addressed by the company when talking to clinical investigators, and it really preceded the Net 1 study.
It was a study that had not originally been planned to have been done, but was done by the company. It seems as if the FDA was given an abbreviated summary. You have Dr. Abrams talking about not providing it fully to the FDA, not discussing it with the FDA, because it really is a significant study that is not reflected in any of the information the FDA has.
Q. Significant in your mind; correct?
A. Well, no. It's significant into the evolution of this product The FDA made the labeling be changed with the Net 1 when they did a comparison of Ortho Evra versus the birth control pill, and they found that the estrogen was elevated.
Now, they had this same information at the time they did 017, which was before approval.
So, it supports that the company actually was aware that there was a difference in the estrogen delivery before they even were approved, that subsequently became apparent with Net 1.
So, everything that we changed the labeling to with Net 1 could have been done before the product was even approved, or it could have been considered by the FDA before approval.
So, what we have is the information about safety and estrogen delivery is delayed until we have the Net 1 labeling changes in 2004.
So, the Net 1 information in 2004 is not new. It's old. It had been available in the 017 and never really brought out in the labeling. Because the labeling was approved as equal to a birth control pill, and obviously 017 shows that it isn't equal to a birth control pill in terms of the estrogen delivery.
Q. You've looked at the final report for 017?
A. For the 017, yes, in terms of the report that the company has for 017, and it's striking. 017 data is very important.
I think Dr. Polo was asked, well, why didn't you tell the FDA? Well, the FDA didn't ask for it So, we didn't show it to them.
There's a whole discussion in the report about 017. So, it may be somewhere available to the FDA, but the FDA, the medical officers and the label really never reflected 017.
Q. Isn't the data from the oral contraceptive part of 017 dramatically lower than all other oral contraceptive data at that time, and that the Ortho Evra data is very consistent with what all the clinical studies show for that product?
MS. PARFITT: Objection
A. That's the company's interpretation, that all of a sudden, these products that have been marketed have this incredibly different profile than they have ever had before, and Ortho Evra has stayed up high That doesn't make sense. These are all marketed products.
Why, all of a sudden, would every one that they pick all of a sudden have a totally different estrogen delivery. And if you look at 017's data, it's actually very consistent with what happens with Net 1 and what we are talking about years later in terms of the delivery of estrogen
So, the 017 data was consistent with actually what appeared — you know, when the EMEA made them do a similar study. So, it's very consistent, and 017 actually foreshadowed what had happened in 2004.
Q. That's your interpretation as opposed to the company's interpretation of the same data?
MS. PARFITT: Objection It's her opinion based on facts.
A. It's my opinion and it's also Dr. Abrams' opinion If you look at his reticence about not wanting to describe it not wanting it to be in the pharmacokinetic portion of the labeling, not wanting to have to answer that.
So, Dr. Abrams is very consistent with my opinion in terms of the value of 017. Also, you have the expert from Europe, Dr. Givall (phonetic). He said you have to have transparency with this data. It is very important He had already approved Ortho Evra for Europe. He saw this data, and he also agreed with me that it was very dramatic data that really significantly impacted the safety of this product. He wanted it to be published. He wanted it to be transparent, and the employees' management have never published that data.
So, the data for 017, basically, has not been shown in any way…in an article, in the labeling, anywhere.
So, I don't think it is my opinion. I think — It is my expert opinion, looking at the documents, but it is also supported by the, you know, the expert from Europe, from New Zealand that saw the data, complete 017 data and would not approve the product because they considered it was not safe.
So, I think my opinion is consistent with all the other opinions that are out there.
Q. Let me just see if I understand. Do you believe that today, FDA has not looked at the complete data for 017?
A. I believe that I have not seen documentation to show that FDA has been fully apprised of 017, because it very much reflects the same information that they objected to with Net 1. And, so, I think that if you want to show me documentation that they actually looked at 017, that would be fine, but I have seen nothing to support that they have actually looked at the full meaning of 017…particularly when the company told them that the value — the data was not of any value in terms of their communication, that it was so rapidly equilibrating, that this information, we weren't going to use it.
So, the company told FDA that that was not valid information, but I don't think that's held up in terms of the performance of this product and later testing.
Q. So, let me just make sure I understand.
Your view is that the company says 017 is not valid or valuable data for the following reasons, lets FDA know that, and no one from FDA has gone and actually looked at 017 to see if the representation was accurate?
MS. PARFITT: Objection That completel
y misstates her testimony, completely
misstates her testimony.
A. No. When FDA was being informed that 017 was not–
MS. PARFITT: And you've answered the question. If you want to try it again, the question has been fully responded to.
Q. (By Mr. Winter) No. You can answer the question.
A. When 017 was originally put in, and in the context of the way that it was provided to the company the FDA was not aware that the product was not under control. They did not know that the estrogen levels was actually very elevated.
And, so, in the context of the way it was provided, in that the company, you know, informed the FDA that this information wasn't of value and the way it was presented and it was downplayed and abbreviated, report was given, that was the context 017 was given
I don't see that 017 has been brought up at other meetings to be discussed with the FDA. So, taken in the context it was originally given, it makes sense.
Now when you look at the whole product line and you look at — Well, there's a period of time when the product was actually being manufactured with questionable estrogen delivery and good manufacturing practices, then, it would probably have been a different issue if it was presented to FDA in that context.
But I think you can't separate it from the way it was actually presented to FDA, as if this company has everything under control, this product has met specs and it's perfectly safe. So, it was actually produced to the FDA early on in the product, but it was not clearly developed to the FDA, you know, this impact, when Net 1 came to surface. We actually had this data back here with 017.
Q. So, your view is that no one from FDA went back and checked any of that data when they —
MS. PARFITT: Objection.
Q (By Mr. Winter) — had this revelation about Net 1?
MS. PARFITT: Objection, misstates the testimony.
A. I think, and I stated that there has been no documentation, one way or the other, from the FDA, but it certainly doesn't appear in any of the labeling, in any of the communications, any of the information, that the FDA does focus on Net 1.
Net 1 has almost the same type of information as 017. So, the FDA has put their emphasis on Net 1, which suggests they are not fully aware of the information that they had in 017.
Now, if you want to show me documents where FDA has looked at 017 and has made some statements, at this point in time, I see nothing that has shown that FDA has consciously gone back and looked at 017, or been told to by the company that it actually had very interesting information in terms of oral contraceptives and a patch
Q. (By Mr. Winter) How much of that is inference and opinion based on your wealth of experience at FDA? How much of that is actually fact…I went back and checked, and they never looked at it?
MS. PARFITT: Objection This question has been asked
You're coming at it a lot of different ways. Just because you phrase your question a little differently doesn't mean it's precisely the same question You've asked that. She's answered it. There's nothing more she can add.
MR. WINTER: She didn't answer my question
MS. PARFITT: She has answered that question You've asked it many different ways. Because you are not real pleased with her response, you just try to get at it a little different way.
The question has been asked and answered. It is getting late in the day. If you've got a new question, let's go with it but she's answered that question
MR. WINTER: She didn't answer this question
MS. PARFEITT: If you have anything to add to it add to it. If you don't say you've answered the question completely.
A. I've answered the question completely.
MR. WINTER: All right Thank you, Doctor. I have nothing further.
Actually, we have to mark some exhibits. We've got to mark three more exhibits, 12, 13, and 14.
Exhibit 12 would be the New Zealand assessment…paraphrasing. Exhibit 13 would be the Inhibition of Crystallization in Transdermal, and 14 would be this document that has all sorts of numbers of exhibits on it. I can't do a better job of describing this.
(WHEREUPON, a certain document was marked Defendant's Deposition Exhibit Nos. 12, 13 & 14 for identification as of March 11, 2008, and is attached hereto.)
(FURTHER AFFIANT SAITH NOT)