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Another expert deposition from the Dicosolo Duragesic fentanyl patch lawsuit

Posted in Duragesic / Fentanyl

The expert is Robert Middleberg, P.h.D., and he covers a lot of ground in his deposition.  The issue in this case was whether a defectively designed and manufactured Duragesic fentanyl patch was responsible for the death of Adam Hendelson.  The jury found that it was, based in part upon this expert testimony.

THE VIDEOGRAPHER: We are now on the video. The time is 9:06. My name is Earle Strain from Veritext Court Reporting Company.

This deposition is being taken on May 7, 2007, at 1005 Horsham Road, Montgomeryville, PA, in the case of Hendelson vs. Johnson & Johnson.

Present for the taking of this videotape deposition are the deponent, Robert Middleberg. Counsel will now introduce themselves.

MR. DEAN: Richard Dean on behalf of the defendants.

MR. ANGWIN: Edward Angwin on behalf of the plaintiffs.

THE VIDEOGRAPHER: The court reporter is Denise Ryan. The court reporter will now swear in the witness.

ROBERT A. MIDDLEBERG, Ph.D., after having been duly sworn, was examined and testified as follows:

THE VIDEOGRAPHER: You may proceed.

EXAMINATION

BY MR. DEAN:

Q. Good morning, Dr. Middleberg.

A. Good morning, sir.

Q. You have been deposed many times before, haven't you?

A. I am afraid so.

Q. So you know the basic ground rules of the deposition procedure, don't you?

A. Yes.

Q. The only thing I would say to such a veteran witness is, and I really probably don't need to say that, but if I ever ask you a question that you don't understand, please tell me and I will rephrase it or repeat it so that it's intelligible to you, okay?

A. Yes, sir.

Q. We have marked as Exhibit 1 the Notice of Deposition in this case, and I would — you have done a report in this case, have you not, Dr. Middleberg?

A. Yes, I have.

MR. DEAN: Could you mark this as No. 2, please?

(Whereupon, Exhibit 2 was marked for identification.)

BY MR. DEAN:

Q. And, Dr. Middleberg, for the record, this is the report you prepared in this case; is that correct?

A. Yes, sir.

Q. And you were kind enough also to bring a current copy of your curriculum vitae with you; is that —

A. Yes.

Q. — here with us today?

MR. DEAN: Could you mark that as Exhibit 3, Denise?

(Whereupon, Exhibit 3 was marked for identification.)

BY MR. DEAN:

Q. And, for the record, Exhibit 3, is that curriculum vitae the current up-to-date one?

A. It appears to be, sir.

Q. Thank you.

And you have also brought with you the documents that you reviewed and/or prepared in regard to the Hendelson case; is that correct?

A. Yes, I have.

Q. And those are here in this folder, correct?

A. Yes, sir.

MR. DEAN: Denise, do you want to mark this as No. 4?

(Whereupon, Exhibit 4 was marked for identification.)

BY MR. DEAN:

Q. For the record, Dr. Middleberg, what is Exhibit 4?

A. This is a work product log. It's what we use as we work on cases to keep track of our time.

MR. DEAN: Would you mark that as 5, please?

(Whereupon, Exhibit 5 was marked for identification.)

BY MR. DEAN:

Q. What is Exhibit 5?

A. This is information from the Broward County Medical Examiner and Trauma Services, including toxicology report as well as medical examiner information as well.

Q. I see that it's marked as Deposition Exhibit 1 to the Perper deposition, correct?

A. Yes, sir.

Q. Had you seen all of this before you issued your report, which we marked as No. 2?

A. I believe — I can't say I saw all of it in its entirety, but certainly some of it, yes.

Q. Okay. Fair enough.

MR. DEAN: Could you mark these as 6, 7, and 8 and we will just do them — I will have him identify them at one time.

(Whereupon, Exhibits 6 through 8 were marked for identification.)

BY MR. DEAN:

Q. Handing you what we marked as Exhibit 6, could you identify that, please?

A. It looks like a State of Florida Certificate of Death for Adam Hendelson.

Q. And Exhibit 7 is?

A. A copy of the toxicology report from Broward County.

Q. And Exhibit 8 is?

A. It looks like the autopsy report from Broward County.

MR. DEAN: No. 9.

(Whereupon, Exhibit 9 was marked for identification.)

BY MR. DEAN:

Q. Handing you what we have marked as Exhibit 9, could you identify that for the record?

A. These are various medical records and prescription records for Adam Hendelson.

Q. Had you reviewed those before you issued your report in this case?

A. Again, I don't recollect whether I did.

Q. We will go over your report in a minute.

MR. DEAN: Could you mark that too?

(Whereupon, Exhibit 10 was marked for identification.)

MR. DEAN: Off the record — I will go back on the record.

BY MR. DEAN:

Q. Could you identify for the record what Exhibit 10 is? I'm sorry.

A. It's the report of Bruce A. Goldberger.

Q. And, Doctor, the last thing in this folder that you brought with you is the deposition of Michael Wagner and the exhibits to that deposition, correct?

A. Yes, sir.

Q. And I am not going to mark those for the record, we just identified what they are and all the lawyers have those, so I don't feel a need to mark those.

Having been through — having marked Exhibits 2 through 10 and referencing the Wagner deposition, is this the entirety of the documents you have reviewed relating to the Hendelson case?

A. Yes, sir, it is.

Q. You also brought with you a group of articles dealing with various scientific topics; is that right?

A. Yes, sir.

Q. Okay. And I am not going to take the time to mark these individually because it would just take too much time.

MR. DEAN: Why don't we mark this collectively as Exhibit 11.

(Whereupon, Exhibit 11 was marked for identification.)

BY MR. DEAN:

Q. And, for the record, the first page says “Textbooks and Other References;” is that correct?

A. Yes, it does.

Q. Now, are these, for Exhibit 11, are these — well, why don't you tell me what they are rather than me try to guess.

A. They are — first is a list of textbooks and other large references that I have used not just in this case but through my career in formulating opinions. Most of the articles that are attached, journal articles, refer to various issues that I believe are salient to this case.

Again, there are articles that I have read through the years as well as others, but these are the ones that I believe are most salient and I have used at some point in my career to reach opinions that I have reached in this case.

Q. Handing you back your report, Exhibit 2, when you wrote the report, which is dated November 22nd, you listed certain things that had been supplied to you at that point, correct?

A. Yes, sir.

Q. So to the extent that we have marked anything here today that's not referenced in 1 through 5, that would be new material that you have received since you wrote the report?

A. That would be correct.

Q. Okay. Now, does this report represent the entirety of your opinions in regard to the Hendelson case?

A. Based on the information that I have been asked to review, it is, yes.

Q. Okay. And specifically one of your — you don't have any new opinions based upon the subsequent information you were provided; is that correct?

A. That's correct.

Q. You have reviewed Dr. Perper's conclusions in this case; and by that I am referencing the autopsy diagnosis that he signed?

A. Yes, sir.

Q. And his first finding was: “Combined drug overdose (cytalopram, mirtazapine, fentanyl);” do you see that?

A. Yes, sir.

Q. Do you agree with that conclusion?

A. I do agree that this was a drug overdose. From a toxicologist perspective, the — in my mind looking at the results, it is the fentanyl that is really of issue in this case.

Q. But you do agree with that opinion of the autopsy report, correct?

A. I agree that it's a drug overdose.

Q. Well, let me be clear, do you have any disagreement with what Dr. Perper has indicated there in I?

A. From his perspective, this is how from my experience how medical examiners who look at cases like this would sign them out. So, no, from that perspective, the answer is no.

Q. Now, I take it from reading your report, in Paragraph 4 at the bottom of Page 2, you agree that the heart blood level for fentanyl before the death is not reflective of the blood level for fentanyl taken six or more hours after death; is that correct?

A. Actually, that would not be correct. The —

Q. Okay. Go ahead.

A. What I would say is that we don't know in any particular case whether it is higher, the same or lower.

Q. But you do agree that there is something called postmortem redistribution and that's a little recognized phenomenon, correct?

A. Yes, sir.

Q. And what is postmortem redistribution?

A. It is something that forensic toxicologists have been aware of for I imagine at this point the better part of 20 years, where we see artifactual increases or perhaps decreases in concentrations of certain substances in dead bodies depending on where the specimens are collected from. They might be higher, they might be lower compared to where, what the values were circulating at or around the time of death, but it is very difficult to determine, if not impossible, without multiple draws of samples, whether postmortem redistribution actually occurred in a case.

Q. So to do that you would have to have you said multiple samples?

A. Yes, sir.

Q. Okay. And in this case to the best of your knowledge there was only one sample, correct?

A. Yes, sir.

Q. You say in your report the most common site for a concern for this phenomenon is the heart, correct?

A. That is correct.

Q. And that's exactly where the blood in this case was taken from, correct?

A. Yes, that's true.

Q. There are a number of — first of all, do you agree with Anderson and Muto's conclusion that fentanyl is a drug that is subject to postmortem redistribution?

A. I would agree that fentanyl can undergo postmortem redistribution, yes, sir.

Q. And are there a number of factors that affect the level of postmortem redistribution?

A. There can be, yes.

Q. And what are some of those factors, Doctor?

A. Some of the factors include how long after a person dies before an autopsy occurs, the temperature, the position of the body, what the concentration of the drug actually was in the body, and there are a host of other things.

The science behind postmortem redistribution, while there are a number of theories that are placed to try to explain it, the science really is not even today that well understood.

Q. And by that do you mean it's not possible — among other things, do you mean it's not possible to calculate with certainty how much postmortem redistribution has actually occurred in a particular individual?

A. It's not just that but you can't even state if it took place and in fact in some cases even with fentanyl, even in the paper you cited, you will find where peripheral blood, the non-heart blood, is actually higher than the heart blood. So it's all over the place. So trying to predict whether it happened is very, very difficult.

Q. So you would agree that with fentanyl, based upon what you just told me about your review of the Anderson and Muto article, which I think is a correct conclusion, that sometimes there is higher postmortem findings in femoral vessels than in heart blood?

A. There certainly can be.

Q. And so do you conclude that there can be post — from that do you conclude there can be postmortem redistribution to peripheral vessels as well as pulmonary vessels?

A. That would be one way to look at it. There are also other phenomena, pharmacological phenomena related to the distribution of a substance and where it is in its stage of elimination and there is a whole host of factors that go into this that make it very difficult.

I would say though with fentanyl, if you look at the Anderson and Muto paper and if you look at some others as well, not just theirs, it seems as though with fentanyl the higher the concentration of fentanyl that is reported say in heart blood, the greater the degree of redistribution. In a relative sense the lower the value, the closer to unity that we see heart and peripheral blood to be.

Q. Okay. Now, one of the factors you mentioned that would affect postmortem redistribution was how long after death the blood was drawn, correct?

A. It could.

Q. Okay. And would I be correct in assuming that the longer after death you take the blood sample, the more postmortem redistribution you are likely to see?

A. That's a conclusion that some people have reached based on some empirical findings, yes, sir.

Q. And do you share that conclusion?

A. Again, it's hard — it's hard to generalize in my opinion postmortem redistribution to every case. I think each case has to be looked at individually. So I am not a big proponent of making broad generalizations about it, but certainly these are observations that some people have seen.

Q. And who have — when you say some people have made that observation, can you cite me to any particular experts or authors who have reached that conclusion?

A. One particular or two particular people would be, one is Derrick Pounder, and another would be Graham Jones.

Q. Okay. Would you also agree that moving a body after death can impact the level of postmortem redistribution?

A. It has been empirically demonstrated that that can occur, yes, sir.

Q. Dr. Middleberg, isn't it the consensus of thought within the forensic toxicology community, one cannot back calculate with scientific probability to figure out what a person's drug level was before death just by looking at postmortem findings?

A. As a general rule, the answer is yes. Are there certain situations where it's more feasible and more practical and one can do it with a little more certainty than in other cases, yes, but as a general rule I would agree with what you stated.

Q. And where is it possible where you could do some calculations? You said in some cases it might be possible to do calculations. Tell me what those cases would be.

A. There would be some fairly unique cases, but oftentimes they are individuals who have been hospitalized prior to death or where there are known medication administrations over time and perhaps there has been biological monitoring over time, so really the whole situation will dictate whether it can be, but I would agree that it is difficult, but in terms of estimates, in some cases it can be done with a little greater certainty than in most of course.

Q. So where you could do a calculation would be, if I understood your answer correctly, one situation where you could do such a calculation would be if a person was hospitalized and you had blood levels before death; is that right?

A. Yes, and, again, depending on when sampling is taken postmortem, but yes.

Q. Now, turning to the last page of your report, you say — I will just read this sentence, you say: “Studies on fentanyl demonstrate that it undergoes postmortem redistribution with a reported mean ratio of heart blood to femoral blood of 1.6 (range, 0.7-4.6).” That's a figure you derived from the Anderson and Muto article, correct?

A. Yes, sir.

Q. And actually that's not a figure that — if you read Anderson and Muto, they don't ever have a sentence that say that but those are mathematical calculations you have made from that article, correct?

A. That would be correct.

Q. And so what you go on to do in your report then is, in the next sentence, is to divide the 1.6 into the 9.42 and that reduces the blood fentanyl level at least for purposes of that mathematical exercise to 5.9 nanograms, correct?

A. As an exercise, yes, sir.

Q. Okay. And obviously if you were to divide the high end of that range, the 4.6 into the 9.42, you would come out almost at exactly at 2 nanograms, would you not?

A. Mathematically, that would be correct, yes.

Q. Now, Anderson and Muto, the study, their study does not take into account the impact of the factor of time that we talked about before, does it?

A. No, sir.

Q. Because when they did their study, they didn't have any blood levels, they had no blood levels before death, correct?

A. That's correct.

Q. And their study also does not reflect postmortem — the time between death and the time the blood was taken, does it?

A. No, sir.

Q. So all they have done to come up with this ratio was to take postmortem blood from a certain number of patients, I think 30 if I remember right, and compare when they — in certain cases they had both a femoral — I'm sorry; in certain cases they had both heart and femoral and that's the formula derived from a certain subset of those 30 cases where they had both heart and femoral blood, correct?

A. Yes. In terms of a scientific endeavor, this is not a very strenuous exercise, so, yes, I would agree with you, they did.

Q. So but the point is, this ratio that they — that you calculated from their work, and I think correctly calculated, does not take into consideration the factor of time; we can agree on that?

A. Yes, sir.

Q. And we have also agreed before that generally the more time goes by, the more postmortem redistribution there would be generally, correct?

A. Well, again, it's going to vary on a case-by-case basis. Again, I would prefer not to make generalizations, but that is something that has been recognized, yes.

Q. And recognized by people you respect in the field, correct?

A. Certainly.

Q. So if we put in the time, if we assume for the sake of argument that the Anderson and Muto range but superimposed — or superimposed, took into consideration the factor of time, do you know how much time there was in this case between the death and the time the blood was drawn?

A. May I refer to —

Q. Sure, certainly. This is not a memory contest.

A. As I remember it, at least from the time he was found unresponsive, I think the autopsy occurred, if I have it correctly, not long after he was found, like maybe five, six, seven hours, in that range, if I have the right day.

Q. Okay. Do you know, do you have any idea how long he had been dead when he was found in his room?

A. No. No.

Q. Do you know whether rigor mortis had set in when he was found?

A. I don't recall reading whether he was found in rigor or not.

Q. How long does it take for rigor mortis to set in, Doctor, if you know?

A. Well, that's a variable phenomenon. I am not an expert on it but I do know from reading cases through the years and being involed in a lot of postmortem cases that there is no set time. It can be quick, it can be slow, it depends on temperature, it depends on a number of variables.

Q. Do you have any views in this case, in this specific case, as to whether postmortem redistribution was at work in Mr. Hendelson?

A. I do.

Q. And what are your views?

A. While it can't be excluded, obviously, it also can't be included.

Based on again the literature values that have been published, the concentration found in this case is not excessive in terms of an overdose, when you see people who really abuse it and get into the hundreds of nanograms per milliliter. This is in a range that while fatal in a relative sense compared to people who put on lots of patches or eat the stuff, this is on the relative scale of fatalities on the lower side, and when you look at the ratios that have been reported in terms of redistribution and in regards to those kinds of concentrations, again, the ratio approaches unity, which means femoral and heart blood are close to one another.

So with that in mind, it would be my opinion that while you can't discount redistribution given that, the likelihood that it's excessive or to a large degree is probably not great in this case.

Q. And I want to understand the bases for that opinion. I mean, we have a 9.4 reading, basically what you cite in your report is the range from Anderson and Muto —

A. Uh-huh.

Q. — and you also cite the recognition that, in your report, that heart blood is susceptible to postmortem redistribution, so I want to understand the reasons why you think it — well, strike that.

First of all, are you saying that it didn't occur in this case or that it didn't occur very much?

A. What I am saying is I can't tell you if it occurred or it didn't occur.

Q. Fair enough. Fair enough. Okay.

And that goes back to your general answer before, that except in a small number of cases you can't tell with scientific certainty whether it occurred or didn't occur; is that correct?

A. Well, unless someone drew both heart blood and femoral blood or something along those lines, that would be true.

Q. Anyway, what you used — to go back to your report, what you used the Anderson and Muto equation, if I can call it that, for was a general notion as to what his blood level might have been prior to death based upon that one observation in Anderson and Muto, correct?

A. Well, again, I could have gone through lots of calculations here and I did this just as a rough sense calculation, and in that regard I would agree with you.

Q. Okay. Now, we have already established that the Anderson and Muto article compared heart blood and femoral blood after death, correct?

A. Certainly.

Q. And to even do the calculation that you — the calculation and the suggestion you do hear of the division we talked about before, getting you to 5.9 as being somehow reflective of the level at cause of death, and I know there is lots of caveats there, we have already talked about, but to even do that you would have to assume, would you not, that there is no postmortem redistribution to femoral vessels?

And I can drop back a step if that's too confusing.

A. It's not confusing. It's — again, these are just observations that they have made and whether they take that into account or not, I am not sure, but the bottom line is, I guess as you have asked the question, that would be true.

Q. That would be true.

And I don't want to be repetitive but I do want to understand your testimony, so I want to go back and ask, what is your position as to whether there is postmortem redistribution of fentanyl into peripheral vessels as a general proposition?

A. I am not — well, I guess in a technical sense it would be called redistribution. It is possible that you can get some contamination from the iliac area into femoral blood if it's not collected correctly.

Q. And I am going to go there later.

A. Okay.

Q. But it's a very simple question, do you agree that there — first of all, do you agree that there could be postmortem redistribution generally to femoral vessels?

A. Theoretically, certainly there could be.

Q. Do you agree that there could be postmortem redistribution of fentanyl to peripheral vessels?

A. Theoretically, sure.

Q. And isn't one interpretation of the Anderson and Muto article, the data you cited before where there are higher, in some instances higher femoral blood levels that there is indeed postmortem redistribution of femoral vessels of fentanyl?

A. I guess in a theoretical sense one could say yes.

Q. Okay. And you already touched on this but I want to go back and touch on it or ask you a couple questions on it, that was the 9.4 level I think you said was not particularly high in and of itself in context of cases you have seen I believe; is that fair?

A. In cases of fentanyl overdose or of deaths related to fentanyl? In a relative sense, based on how people have become overdosed on the material, I would agree with that statement, yes, sir.

Q. Let me ask it a little bit differently, isn't it true that there are lots of people walking around with fentanyl levels higher than 9.4 not in respiratory depression and perfectly healthy?

A. There are people who attain higher levels based on the amount of medication they are receiving and how they have been titered up to those concentrations, yes, sir.

Q. Have you read the Davis and Swenson article from the University of Utah?

A. I don't recall if — I don't think that one is in my data pack. I have read a lot of articles on fentanyl.

Q. I will scan through your pack in a minute here.

Now, I think you said before when you were talking to me about the 9.4, that you have seen much higher in cases of abuse; is that correct?

A. Oh, yes.

Q. What kind of levels have you seen?

A. In excess of 100 nanograms per milliliter.

Q. How do people abuse the Duragesic patch, if you know?

A. There are a lot of ways. I have seen everything from people taking the patch and removing the contents and either eating them, smoking them, putting them in their mouth and sucking on them. I have seen people swallow whole patches.

Q. How do people smoke them?

A. You just take the contents, I imagine you smear it on a cigarette and smoke it or you can put it I imagine like you would with cocaine.

I have seen people do all kinds of things, take out the contents and inject them, so…

Q. I want to go back, we know we have a 9.4 level here. In Paragraph 2 you say that a therapeutic level for a 75 patch may be as high as approximately 3 nanograms, correct?

A. Yes, sir.

Q. And so to go back again to the Anderson and Muto calculation, not going to the 4.6 at the high end of the scale but going to, if we took 3.0 and divided it into the 9.4, we'd come out slightly above a 3, wouldn't we?

A. Mathematically, that's correct.

Q. Have you done any search, and this — and if you haven't, just tell me because it may not be in your area, have you done any literature search for articles as to levels of fentanyl in living persons that would be higher than the kinds of levels you reported here?

A. Yes.

Q. What was the occasion to do that, Doctor?

A. Well, certainly in my studies of fentanyl for handling postmortem cases through the years, as well as for issues like this, you tend to collect data, what we call pharmacokinetic data, that gives us concentrations after certain amounts of administration of various substances, and certainly that's true for fentanyl as well, and I have done that.

Q. Okay. Are there any that stand out, any authors that you can recall whose reports you have read that fit in that category?

A. May I refer to my —

Q. Sure, absolutely.

A. One in particular is this article entitled: “Inter- and Intraindividual Variabilities in Pharmacokinetics of Fentanyl After Repeated 72-Hour Transdermal Applications in Cancer Pain Patients,” and the first author's last name, I will spell it, is S-O-L-A-S-S-O-L. That would be one article.

Q. Hang on.

A. Okay.

Q. Would you be kind enough just to find that in my packet and pull it out so I can take a quick look? I missed that as I was trying to find it.

Then you can just hand the whole packet back to me.

A. (Witness complies with request.)

Q. Thank you, Doctor.

A. You are welcome.

Q. And can you get me to the right page, and let's take a look at this article, pull it out.

A. Probably the easiest thing to go to would be on Page 495.

Q. The Table 4?

A. Yes, or —

Q. The graph?

A. The next page as well, Page 496.

Q. Which one would be better for us to —

A. I guess 496 looks at individuals, so that would probably be better.

Q. And what is the column that I want to look at, “Plasma Concentration At Steady State”?

A. The first one I would look at is the third column from the left, “Theoretical Rate of Absorption,” micrograms per hour, which would refer essentially to the amount, in terms of patches, and then I would go over two more columns from that that says “Plasma Concentration At Steady State.”

Q. And those reflect the — those reflect the levels?

A. They do, sir.

Q. Okay. All right.

A. There are others in here.

Q. Have you read any articles that suggest that if — let's just take a 75 microgram patch, that if somebody wears a 75 microgram patch for let's say six months, that there — and they just consistently wear 75 microgram patch as it's suggested to be worn by the manufacturer, in your Exhibit 2 you suggest a level for a 75 microgram patch as high as a 3.

My question is, have you read any literature suggesting that a six-month use would result in a higher level because of build-up of fentanyl within the body?

A. Well, by definition steady state is a concentration that's reached where there — while there are still some fluctuations depending on when you draw the sample, in terms of changes of patches and things along those lines, generally you are getting what is known as a steady state condition, where the concentration remains relatively stable, within some fluctuation.

Would you necessarily expect that to happen where you would get higher concentrations, no, not necessarily.

Q. In the article, and I am not going to take the time to read it now but I will go back and read it, but in the article you just cited, were those people studied over a course of time to see whether there was a rise in fentanyl levels?

A. Yes, sir.

Q. Okay. Let's talk about citalopram for a minute. The observed level here was 0.55 milligrams per liter; is that right?

A. Yes, sir.

Q. Do you know what the expected therapeutic level would be from taking — from taking 20 milligrams of citalopram?

A. In general with citalopram, we tend to look at therapeutic concentrations being in the area of about up to about .3 milligrams per liter, and that would be in plasma or serum.

Q. Do you have Baselt, the pages on citalopram with you?

A. I do not.

Q. Okay. I am going to show it to you. This is Exhibit 8 to the deposition of Dr. Downs, and I know you haven't looked at the deposition —

A. No.

Q. — but you don't need to, but it does have the — and you are familiar with the Baselt text, correct?

A. Yes, sir.

Q. Okay. And look under the — look at the bottom of the page under “Blood Concentrations.”

A. Yes, sir.

Q. And what does Baselt say they are for the person taking the regular daily dose?

A. Steady state and depending on the dose can be up to about, he says about 107 — we are going to change units — nanograms per milliliter.

Q. And he says it goes anywhere from 45 to 107, correct?

A. That's correct.

Q. And so that would translate — I want you to — I am dangerous when I start doing this, so if I get it wrong, you tell me, okay?

A. Okay.

Q. Would that translate, the 45 translate into .045 milligrams per liter?

A..045, that's correct.

Q. Okay. So — and the 107 that he reports there would translate into .107 milligrams per liter?

A. That would be in serum or plasma, that's correct.

Q. Okay. Now, you said — the range you were giving me was a higher range of .3, correct?

A. Yes.

Q. Now, which do you believe is closer to the therapeutic range for citalopram, the figure you gave me or the ones that Baselt cited?

A. I am comfortable with the one I have cited. Baselt is a nice textbook to get started to look at concentrations but you really need to go further than — most toxicologists use it as a guide and then proceed further from Baselt.

You also have to understand, his concentrations are in serum or plasma and it is known that citalopram sequesters in red blood cells. So the concentration you would expect in whole blood would probably be higher than you would see in serum or plasma.

Q. But in any event, if we use your figure of a .3, the finding of .55 is almost double that, correct?

A. Mathematically it is, yes, sir.

Q. And if you use Baselt's figures of — it's anywhere from four to ten times higher, correct?

A. From a mathematical perspective, yes, sir.

Q. Are you familiar with any studies on the rate of postmortem redistribution in regard to citalopram?

A. There certainly are anecdotal cases that have been published where they look at different concentrations. There aren't many. There aren't many.

Q. In Adam Hendelson's case do you know whether or not the — he was taking — that he had an overdose of citalopram or whether the results we are getting are reflective of postmortem redistribution?

A. I think the best way for me to answer that is that the concentration reported is in line with concentrations that are not uncommon in postmortem situations where citalopram was not considered a cause of death or an overdose. It's even published in the literature that you can find this concentration in terms of what, if you want to call this the — call a normal postmortem concentration of citalopram, and there are a number of, again, reasons why that might occur short of postmortem redistribution.

Again, we are looking at typically a version of blood as opposed to serum or plasma, and there is at least one study that demonstrates that you would expect a higher concentration in blood — excuse me — and also you worry about not necessarily postmortem redistribution but postmortem diffusion from drugs that are orally taken as opposed to say a transdermal patch, which is not through the oral route.

So there are a number of reasons why the normal postmortem would be elevated compared to say a living person's serum or plasma. So for us when we see values like this, they are relatively normal.

Q. Well, this is a good learning experience for me because you just said something, if I heard you right, I have never heard anybody say before, and that is that you can get postmortem diffusion through an oral tablet?

A. From gastric contents.

Q. Okay. Could you briefly explain to me how that happens?

A. Well, it's simple diffusion. The theory is it's simple diffusion —

Q. Okay.

A. — across a membrane into another membrane.

Q. Okay. Fair enough. And now I will get back on track.

A. Okay.

Q. So what you have told me is that the citalopram level here is one that's consistent with other postmortem findings in other cases that you have seen regarding the drug, but my question to you is, in this individual case you cannot tell me whether the elevated level was due to an overdose or due to postmortem redistribution, can you?

A. Or a number of other factors, that's correct.

Q. Okay. Now, the mirtazapine level observed was .30 milligrams per liter, correct?

A. Yes, sir.

Q. And what is your understanding as to the therapeutic level of mirtazapine?

A. Again, in serum or plasma you can find concentrations while generally reported low, it depends on the dose that one is taking. I know in Baselt he reports relatively low concentrations but in our laboratory in our reference range that we report out for this compound, I believe we go up to about .2 milligrams per liter, again, depending on the dose that an individual is taking.

Q. And I can show this to you but you obviously have just referenced Baselt and he reports — and I will be glad to show it to you — .03 to .046 milligrams per liter?

A. That sounds about right for what he has, yes.

Q. Okay. So your experience is higher, correct?

A. From a clinical perspective, yes.

Q. Now, you said “up to .2.” What is your median or mean or average? However you want to give it to me.

A. Well, the way we — as I remember it, unfortunately, we analyze for 3,000 things and I can't keep all the reference ranges in my head, but as I remember it, with mirtazapine we give a dose and then an expected concentration and we keep going down in terms of the list of doses. As they get bigger, of course the concentration range that you expect is larger.

So there really isn't a mean per se, it's more of a range starting about where Dr. Baselt starts and ending at about .2.

Q. Okay. Now, in this case the reading was .30, correct?

A. Yes, sir.

Q. And isn't it true that in Baselt he reports a toxic dose of fatality at .368? I would be glad to show this to you.

A. May I see that, please?

Q. Sure, absolutely.

A. That was a concentration — it is true. It's a concentration taken 41 hours after ingestion of 1,200 milligrams, and I believe the person lived as well.

Q. That person lived?

A. I believe — I believe so.

Q. We would have to go to that article, wouldn't we?

A. Yeah.

Q. Okay.

A. I think I may have looked at that one, I think.

Q. Okay.

A. Mirtazapine is a fairly safe drug in overdose. People have taken an awful lot of it and still have done fairly well.

Q. But you agree that it is a high reading, a .30?

A. Again, in terms of postmortem findings we see, we would put it in the quote, unquote, again, a “normal” finding for mirtazapine postmortem.

Q. Well, fair enough. But just as we talked about in regard to citalopram, in Adam Hendelson's individual case you would not know whether this .30 was a result of an overdose or of postmortem redistribution, would you?

A. No, sir.

Q. Showing you Exhibit 10, that's the report of Dr. Goldberger in this case, correct?

A. Yes, sir.

Q. And you have had a chance to review it, correct?

A. I have, sir.

Q. And do you know Bruce Goldberger?

A. I know him very well.

Q. How is it that you know him so well?

A. Professional colleagues.

Q. Okay. Is he a well respected forensic toxicologist?

A. I think so.

Q. Do you know any forensic toxicologists in Florida besides Dr. Goldberger?

A. I do.

Q. Who else do you know?

A. I know Harold Schuler, I know Mike Wagner, Lee Hearn. There are a number of them in Florida.

Q. Okay. Turning to Page 2, in the “Conclusion” section, do you have any disagreements with the first conclusion of Dr. Goldberger?

I am not going to read it all into the record. It starts out: “Comprehensive testing,” do you have any disagreement with what he says there?

A. No.

Q. In regard to question — in regard to Conclusion 2, do you have any disagreement?

A. I do, because when I looked at the data, it appears to me that they did look for clonazepam and did not find it, based on the data I received.

Q. And is that here with us?

A. I hope so.

Q. Let's try to find it.

A. Okay.

Q. Are we in the exhibits to Wagner's deposition?

A. Yes, sir, we are.

MR. DEAN: Okay. I will tell you what, since we are in that and we are going to talk about it, why don't we mark this as the next exhibit. What are we up to, 11 or 12?

(Whereupon, Exhibit 12 was marked for identification.)

BY MR. DEAN:

Q. Have you found a page in there, Doctor, that goes to that issue that you were looking for?

A. I do. Unfortunately, they are not stamped with pages or — it's about halfway through the packet. It looks like this.

Q. Could you just find it for me in here and

A. Sure, I will do my best.

Q. — and I will highlight it in yellow so I know what we are talking about.

A. I think I got lucky here, maybe. I may have come close.

Q. Okay. Do you want to put that back in front of you?

A. Sure.

Q. So we are looking at a page, at the top of it it says — well, not at the top, it's kind of an easy reference, it says: “Using ACQ method”?

A. Yes, sir.

Q. And down at the bottom there is a graph and in the upper right-hand corner of the graph it says: “Clonazepam”?

A. Yes, sir.

Q. Okay. Now, what does this sheet show?

A. It looks like they looked for clonazepam. Now, like Dr. Goldberger I am a little bit behind the eight ball here because I don't have that method, their written SOP or their method to direct me exactly how they did this, but usually when you see data like this, it means they have made an attempt to try and find the compound and could not find it.

Now, in terms of what Dr. Goldberger wrote, I would have to ask him or you would have to ask him what he means by “adequately screen for or quantify.” I guess we could get into a discussion over what “adequately” means, whether this reflects adequately in his mind or not.

Q. Okay. Does it reflect adequately in your mind?

A. It at least in my mind indicates that there is not at least a gross overdose of clonazepam here. I would expect that they would have seen it. But what I don't know, and like Dr. Goldberger, I don't know how low they can see through this method. So we are both in a similar position.

Q. Well, since we don't have their standard operating procedures we just don't know the limits of detection and things like that; is that correct?

A. Yes, sir, that's correct.

Q. Okay. Now, can you tell from this whether they made any attempt to find the metabolite?

A. No, I did not see any attempt at that.

Q. So in that regard there was just no testing for the metabolite?

A. I believe so.

Q. Okay. All right. Fair enough.

Let me draw your attention to Conclusion 3 from Dr. Goldberger's report, do you have any disagreement with that?

A. I agree with the first sentence. I do not agree with the second sentence.

Q. In regard to the second sentence, what is it that you disagree with?

A. That the blood concentration was likely less than the amount reported. That's — I am not sure how that conclusion was reached. I imagine it's based on the concept of postmortem redistribution, but, again, you don't know in any particular case that it was, that it did occur, so that it's — it was likely less than I think — I am not sure what that's based on, and, again, that this concentration is close to concentrations where the redistribution phenomenon in reports out there as close to unity might not support this conclusion.

Q. But in the sense he is saying it's possibly in the therapeutic range, you've already told me that if — obviously this is a mathematical result, but if you divide 4.6 by 9.4, you are going to get in the therapeutic range, are you not?

A. If you choose to use — of course —

Q. Right, right.

A. — if you choose to use the 4.6.

Q. So in that sense you wouldn't disagree because he used the word “possibly,” correct?

You would agree that it's possibly in the therapeutic range under the Anderson and Muto equation that you yourself cite?

A. Well, I guess it becomes semantics. All things are possible of course, but the preface that he uses to get to that conclusion is that the blood concentration at the time of death was likely less than the amount reported, which would then possibly put it in the therapeutic concentration.

Q. Well —

A. And that's where we would disagree.

Q. And so your position is we just don't know in this individual case of Mr. Hendelson whether there was postmortem redistribution or not; is that your position?

A. We do not know for sure but, again, when you look at the data, not just from Muto and Anderson but from others, concentrations that are toxic, fatal, but on the lower end of the scale, the redistribution tends to hover close to unity.

Q. And you say that Anderson and Muto stands for that proposition?

A. Well, if you look at — you have to pick through their data, but there is another paper within the packet I gave you that sort of supports that as well.

Q. And which paper is that, Dr. Middleberg?

A. It would be the one by — if you would like, I could find it for you.

Q. It's probably easier.

A. Martin, Woodall and McLellan.

Q. Oh, is that that arterial paper?

A. It is, sir.

Q. Oh, I know that paper. Okay. It's highlighted here.

So is that some derivations that you have made or is it something on the face of the document that I can —

A. Actually, if I can find it.

It's actually on Page 608.

Q. Okay.

A. And it's the second sentence down where it says: “Peripheral” —

Q. Wait, wait, second sentence down, which paragraph?

A. Oh, I'm sorry, first column, last paragraph.

Q. Okay. I thought that's where you were reading.

Go ahead.

A. Second sentence down, it says: “Peripheral blood fentanyl concentrations” — talking about four cases — “ranged from 8 to 28, with an average heart to peripheral blood ratio of 1.13, the range is 1.11 to 1.14.”

Q. And is this from Anderson and Muto or from their study? If you know.

A. I believe this — I believe this is their study, I believe.

Q. Okay. And the reason I — and you are probably right, look at the next sentence. I think in the next sentence they are referencing Anderson and Muto.

A. Yeah, so I think this is independent of that.

Q. Okay. All right.

And drawing you back to Dr. Goldberger's report, Conclusion 4, do you agree with that conclusion?

A. Absolutely.

Q. And you have so testified before, have you not?

A. Yes, sir.

Q. You've been identified also as an expert witness in a case called Evans and I am going to take a very short deposition of you in a few minutes in that case when we finish this one, but are you currently working on other Duragesic cases?

A. I have been asked to consult on a number of them and I believe there is only one other case that I am aware of that I have been retained on other than these two.

Q. Is that by Dr. Angwin or by somebody else?

A. I think it is.

Q. And what is the name of that case?

A. I believe it's Luce, L-U-C-E.

Q. Okay.

A. Maybe Mr. Angwin can confirm that.

MR. ANGWIN: Yes, he has already provided a report and we have already settled that case.

MR. DEAN: Okay.

MR. ANGWIN: It's also sometimes called Davis. The decedent is Luce but the plaintiff is Davis.

MR. DEAN: I am with you.

BY MR. DEAN:

Q. You have testified in other Duragesic cases for attorneys other than Mr. Angwin's firm in the past, correct?

A. Yes.

Q. Have you ever reviewed a Duragesic case brought to you by an attorney representing a claimant and refused to testify in that case?

A. Yes.

Q. What was that case?

A. Well, the one case that comes to mind is one that was in Texas recently, and, unfortunately, the name of it escapes me.

Q. What was the base — putting the name of the case aside, what was the basis upon which you refused to testify?

A. I thought the analytical data did not support the finding and, as I remember it, I don't even — I didn't even think that the finding was one that would support what was being contended.

Q. And the reason —

MR. ANGWIN: I can give you specifics on the case if you'd like.

BY MR. DEAN:

Q. And the reason —

MR. DEAN: I can give you more.

MR. ANGWIN: I mean, depending on which case it was.

BY MR. DEAN:

Q. And the reason for that was that they had one out of four calibrators which were functioning, correct?

A. It was a lot more than that from an analytical perspective.

Q. What else was it?

A. It was one out of four calibrators, the data was very, very poor, just the way it looked, and I don't think it was interpreted properly, and in terms of an analytical interpretation, but I also don't think it may have been interpreted properly from a toxicological perspective.

Q. And you told the attorneys in that case that you would not testify in that case, correct?

A. I did.

Q. And that case was called Thompson, and it was from Mr. Tommy Fibbich, correct?

A. I think “Thompson” rings a bell. The attorney's name —

MR. ANGWIN: I think he dealt with Fletch Trammell.

THE WITNESS: That rings a bell.

BY MR. DEAN:

Q. So Mr. Trammell was at that point in time associated with Mr. Fibbich and he was the one you communicated those thoughts to, correct?

A. Yes, sir.

Q. Okay. All right. Any other cases other than that where you have looked at the Duragesic file and refused to testify?

A. From a consultancy perspective, there have been an awful lot of cases that I have looked at that I don't think have merit.

Q. Okay. Just so we are clear, this question states the obvious, but your company, NMS, has not done any laboratory work in this case, correct?

A. I don't believe so.

Q. Your opinions here are simply based upon your review of work done by other laboratories, correct?

A. Yes, sir.

Q. Have you at any time in your professional career performed any independent research studies on postmortem redistribution?

A. Short of casework, the answer is no.

Q. What do you mean by “short of casework”?

A. Handling cases where we do both femoral and cardiac blood.

Q. So — okay; I understand.

So other than that, the answer is no, correct?

A. That is correct.

Q. Okay. Have you ever written a paper on postmortem redistribution?

A. I don't think so, no.

Q. Have you ever lectured on postmortem redistribution?

A. Yes.

Q. Where?

A. I lecture to students about it and I lecture — at Thomas Jefferson University and Medical School.

Q. And when you say you lecture, is it part of a — some other general topic or do you lecture specifically on postmortem redistribution?

A. It's generally part of a lecture on forensic toxicology.

Q. And when you give that lecture, are you like a visiting lecturer where you come into a particular class and —

A. No; I have an appointment at the university.

Q. Do you teach a regular class?

A. I do.

Q. And how — do you teach one every semester?

A. Not every semester, no, sir.

Q. How often do you teach it?

A. The main course that I teach for graduate students is in the summer. It starts — it runs from June to September, I believe, and I have been doing that for about 10 years.

Q. And do you do that every summer?

A. I do.

Q. Okay. How often does that class meet?

A. Once a week, three hours a day.

Q. Okay. And in the course of that class you have lectured on postmortem redistribution, correct?

A. Yes, sir.

Q. Any other occasions when you would have lectured on postmortem redistribution?

A. Yes.

Q. What are they?

A. I also lecture to the medical students, I teach toxicology to the medical students, which is in the fall of each year, and I also have an appointment at a local university here called Arcadia University that has a master's program in forensic science, and it would be within there too.

Q. And, again, let's go to the medical school class that you teach the medical students, how often does that class meet?

A. Well, it's a long course. I only give three lectures. That's what is allotted to toxicology.

Q. Okay. So it's a general course of some type within which there is a subset of three lectures on toxicology and you give those lectures, correct?

A. Yes, sir.

Q. And one of the topics you cover in one of those three lectures is postmortem redistribution?

A. It's not extensive for sure in that class. It's a brief mention.

Q. Okay. I was going to ask, in that class it's pretty limited, right?

A. Extremely.

Q. Let's go back to the class you teach in the summer, how much time would you spend on postmortem redistribution, lecturing in that class?

A. Within the — certainly less than an hour.

Q. Who are the primary authors that you would look to if you wanted to read articles about postmortem redistribution?

A. Well, I actually brought three papers that refer to that, and I can tell you the authors from them —

Q. Sure.

A. — from these papers, and there are others as well, and I will mention their names also, one of the seminal papers is by Prouty, P-R-O-U-T-Y, and Anderson, that's William Anderson, another paper is by Derrick Pounder, P-O-U-N-D-E-R, and then there is a group from France, and I will spell this for you —

Q. Hang on a minute; the group from France, make sure it's the same one here, “Mechanisms Underlying Postmortem Redistribution of Drugs: A Review”?

A. Yes, sir.

Q. Okay. So you view that as a reliable source of information regarding postmortem redistribution, correct?

A. Well, again, it's a piece of information that I use in formulating opinions. Is it reliable? It's, again, a treatise that I think has good information in it.

Q. Have you ever read an article by Hilberg entitled: “Postmortem Drug Redistribution: Human Cases Related to Results in Experimental Animals”?

A. I am sure I have read it but it's not one that just comes to the fore.

Q. Fair enough.

And you do know Graham Jones, correct?

A. Of course.

Q. And you are familiar with his work on postmortem redistribution, aren't you?

A. I am familiar with at least one of his articles.

Q. And would you agree that he is well respected in the field of forensic toxicology?

A. Without question.

Q. Do you know Yale Caplan?

A. I do.

Q. How do you know Yale Caplan?

A. As a professional colleague. We sit on the board of directors of the American Board of Forensic Toxicology together and I have just known him for a long time.

Q. Would you agree that he is well respected in the field of forensic toxicology?

A. I would.

Q. Would you agree that at the time of his death Mr. Hendelson was on a number of drugs which were CNS depressants other than Duragesic?

A. For forensic toxicologists the word “number” is a relative thing. I have seen people that have 15 or 20 things.

In terms of this individual, he has a couple, a couple others that I think are relevant in this case.

Q. And relevant in what sense?

A. In that they are CNS depressants.

Q. Well, what other CNS depressants was he on that you are familiar with?

A. Well, certainly the citalopram.

Q. What else?

A. There is a trace amount of diphenhydramine, D-I-P-H-E-N-H-Y-D-R-A-M-I-N-E, and there is also a trace amount of diazepam, D-I-A-Z-E-P-A-M, and metabolite.

Q. As a forensic toxicologist are you familiar with something called “the concomitant effect of drugs”?

A. Of course.

Q. And what is that?

A. Is that we talk about drugs that behave similarly having what is known as an at least additive effect, if not a potentiative effect, depending on what effect we are talking about.

Q. Right, right.

And here, in Mr. Hendelson's case, a number of these CNS depressant drugs that he was on could cause respiratory depression, correct?

A. If you are looking at the prescription records, the answer is, that is, yes. I was focusing on when I gave my previous answer based on the toxicology findings alone.

Q. Fair enough. And I was talking in terms of concomitant effects now in regard to respiratory depression. Are you with me?

A. Yes, sir.

Q. And would it be fair to say that there is a general concern when somebody is on Duragesic about them not being prescribed drugs which have concomitant effects on respiratory depression?

A. Certainly it's a concern. It's a concern not just obviously with Duragesic but any CNS depressants, combining any of them, sure.

Q. Are you aware that on the label on Duragesic it says that if a patient is on other CNS depressants, it should be reduced by one-half?

A. I am aware.

Q. And based upon your review of these records, can you make any determination as to whether the other CNS depressants were indeed reduced by one-half of their therapeutic level?

A. I don't know. I do not know.