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Plaintiff’s Motion in Limine Regarding Duragesic Studies

Posted in Duragesic / Fentanyl

This motion was filed by the plaintiff, and asked the court to exclude evidence of studies performed by the manufacturers of the Duragesic patch.  The plaintiff presented evidence that the studies were too unreliable to go before a jury.

Plaintiff, Lee Hendelson, moves this Honorable Court to enter an Order prohibiting Defendants, Defendants' representatives, witnesses, expert witnesses and attorneys from arguing, referring to, mentioning, alluding to, testifying, soliciting or offering in any way testimony or documents regarding or relating to the following studies:
1. Jansen Research Study of Postmortem Blood in Rabbits (1994)

Plaintiff objects and files this Motion in Limine relating to Defendants' proffered Exhibit No. 138, “Jansen Research Study of Postmortem Blood in Rabbits (1994)” as scientifically unreliable, on the ground that it is an in-house study. See Perry v. United States, supra. The bias and methodology of such studies renders them unreliable. See id. at 893 (“A scientist who has formed opinion as to the answer he is going to find before he even begins his research may be less objective than he needs to be in order to produce reliable scientific results.”). Because the study was conducted on rabbits, it is scientifically unreliable to extrapolate its results to humans. See Hall v. Baxter Healthcare Corp., 947 F. Supp. 1387, 1410 (D. Or. 1996) (“Extrapolations of animal studies to human beings are generally not considered reliable…”); Turpin v. Merrell Dow Pharms., Inc., 959 F.2d 1349, 1360 (6th Cir. 1992) (expert testimony of study excluded because the record was devoid of any clear reason that rat and rabbit studies can be extrapolated to humans). Plaintiff further objects to Exhibits 138 on the ground that the rabbit study was not published or subjected to peer review. See Daubert, Perry, McGhan Medical, supra. Plaintiff also objects to Exhibit 138 because it appears to be an incomplete portion of the results, and therefore there is a significant question regarding its scientific reliability, if any.
2. Evaporation Rate of Gel Contained in Duragesic Transdermal Fentanyl Systems (2005)

Plaintiff objects and files this Motion in Limine relating to Defendants' proffered Exhibit No. 139, “Evaporation Rate of Gel Contained in Duragesic Transdermal Fentanyl Systems,” as scientifically unreliable, on the ground that it is an in-house study made only after there was a recall of five lots of Duragesic patches. See Perry v. United States, 755 F.2d 888, 892 (11th Cir. 1985) (medical expert's findings rejected because methodology reflected predisposition to arrive at particular conclusions and there was no peer review). Plaintiff also objects to Exhibit 139 as unreliable because it was not published or subjected to peer review. Whether or not a study has been published in a peer-reviewed journal is a relevant consideration in assessing the scientific validity of a matter on which an expert opinion is premised. See Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579, 593 (1993); Allison v. McGhan Medical Corp., 184 F.3d 1300, 1313 (11th Cir. 1999) (“Peer review is significant under Daubert because scrutiny of the scientific community is a component of good science, in part because it increases the likelihood that substantive flaws in methodology will be detected.”); Perry, 755 F.2d at 892 (a study's lack of peer review provides a ground for inadmissibility as “the examination of a scientific study by a cadre of lawyers is not the same as its examination by others trained in the field of science or medicine”).

Plaintiff further objects to Exhibit 139 because correct scientific procedures have not been used. The design of Exhibit 139, the Technical Report on evaporation of Duragesic gel, cited in support of Defendants' claim that rapid evaporation of ethanol from the gel prevents fentanyl from penetrating the skin, is flawed in failing to account for differences between the laboratory conditions and home use conditions. For example, the experiment was conducted in an oven at 37° C (roughly 98.6°F). The report states (but without explaining how) that the figures used accounted for the presence of air flow in the oven, but the study does not account for the difference between the oven temperature of 37° C and skin surface temperature (about 32° C.) and the environmental temperature (room temperature is about 18-20° C). Moreover, the experiment involved a one-time application of gel, whereas leakage from a patch could be continuous, and did not consider the effect of clothing or other material covering the leaking gel. Since the experiment design is flawed, the actual evaporation time in a home setting would be much longer because the temperature of both the skin and the surrounding atmosphere are lower than the experiment temperature, and the gel may be replenished as more gel leaks from the patch. Most importantly, the report did not test or consider the effect of evaporation of ethanol on fentanyl delivery into the skin. The expert's supposition that evaporation of the ethanol would slow or stop fentanyl delivery is conjecture. It is not supported with scientific evidence. In fact, studies show that the thermodynamics of evaporation of raises the concentration of fentanyl in the gel, which creates a supersaturation of fentanyl and drives it into the skin. See Prausnitz Dec. ¶ 16, attached hereto as Exhibit “A”. Moreover, the report did not concern fentanyl delivery. Finally, Plaintiff objects to Exhibit 139 because the results are so widely varied as not to be helpful.
3. Request for Testing No. 12, BIO-OI-B0223400 (2004)

Plaintiff objects and files this Motion in Limine relating to Defendants' proffered Exhibit No. 140, “Request for Testing No. 12, BIO-OI-B0223400,” as scientifically unreliable, on the ground that it is an in-house study made only after there was a recall of Duragesic patches. See Perry v. United States, supra. The bias and methodology of such studies renders them unreliable. See id. at 893 (“A scientist who has formed opinion as to the answer he is going to find before he even begins his research may be less objective than he needs to be in order to produce reliable scientific results.”). In this study, Duragesic patches were applied to some rabbits and Duragesic gel was applied directly to other rabbits. Because the study was conducted on rabbits, it is scientifically unreliable to extrapolate its results to humans. See Hall v. Baxter Healthcare Corp., 947 F. Supp. 1387, 1410 (D. Or. 1996) (“Extrapolations of animal studies to human beings are generally not considered reliable…”); Turpin v. Merrell Dow Pharms., Inc., 959 F.2d 1349, 1360 (6th Cir. 1992) (expert testimony of study excluded because the record was devoid of any clear reason that rat and rabbit studies can be extrapolated to humans). In addition, it does not appear to be a finished study. It consists of a description of the experimental methods, an event log, and partial results. Of the graphs, tables, and calculation sheets listed in the raw data index, only one raw graph is included, and there is no discussion of the results. Plaintiff further objects to Exhibits 140 on the ground that the rabbit study was not published or subjected to peer review. See Daubert, Perry, McGhan Medical, supra. Plaintiff also objects to Exhibit 140 because it appears to be an incomplete portion of the results, and therefore there is a significant question regarding its scientific reliability, if any.

Plaintiff further objects to Exhibit 140 as scientifically unreliable on the ground that the methodology employed in the rabbit study was unreliable. Use of rabbit skin as a model for human skin is not generally accepted because rabbit skin is generally considered a poor model for human skin permeability and is rarely used in peer-reviewed literature or in the field of transdermal drug delivery testing. See Prausnitz Dec, ¶ 27. Also, the rabbit study did not evaluate the comparison of rabbit skin to human skin, disclose the method by which the rabbit hair was shaved, or clearly state other conditions of the study. Plaintiff also objects to Exhibit 140 on the ground that the design of the rabbit study was flawed for the purpose for which Defendants used it. Defendants cite the study to suggest that rapid evaporation of Duragesic gel will prevent absorption of fentanyl through human skin, but the experiment involved a one-time application of Duragesic gel to uncovered rabbit skin. It did not account for the actual conditions that would be present if a person were using a leaking patch; no account was taken of the likelihood of gel leaking under clothing or under a patch. See ¶ 27 of Prausnitz Dec. Moreover, how accurately fentanyl absorption via human skin is represented by shaved rabbit skin was not evaluated in the study. Finally, the result of the study is anomalous. The rabbit study result – that rabbits exposed to Duragesic gel did not receive therapeutic doses of the drug – is inconsistent with a studies published in peer-reviewed journals, presented at international conferences and disclosed in issued patents clearly showing that fentanyl applied to the skin using an evaporating solvent is extensively absorbed into the skin. See ¶¶ 15, 21, 27 of Prausnitz Dec.
4. Pharmacokinetic Profile of D. TRANS (Fentanyl) System in Rabbits

Plaintiff objects and files this Motion in Limine relating to Defendants' proffered Exhibit No. 142, “Phamacokinetic Profile of D. TRANS (Fentanyl) System in Rabbits,” as scientifically unreliable, on the ground that it is an in-house study made only after there was a recall of Duragesic patches. See Perry v. United States, supra. The bias and methodology of such studies renders them unreliable. See id. at 893 (“A scientist who has formed opinion as to the answer he is going to find before he even begins his research may be less objective than he needs to be in order to produce reliable scientific results.”). In this study, Duragesic patches were applied to some rabbits and Duragesic gel was applied directly to other rabbits. Because the study was conducted on rabbits, it is scientifically unreliable to extrapolate its results to humans. See Hall v. Baxter Healthcare Corp., 947 F. Supp. 1387, 1410 (D. Or. 1996) (“Extrapolations of animal studies to human beings are generally not considered reliable…”); Turpin v. Merrell Dow Pharms., Inc., 959 F.2d 1349, 1360 (6th Cir. 1992) (expert testimony of study excluded because the record was devoid of any clear reason that rat and rabbit studies can be extrapolated to humans). In addition, it does not appear to be a finished study. It consists of a description of the experimental methods, an event log, and partial results. Of the graphs, tables, and calculation sheets listed in the raw data index, only one raw graph is included, and there is no discussion of the results. Plaintiff farther objects to Exhibits 142 on the ground that the rabbit study was not published or subjected to peer review. See Daubert, Perry, McGhan Medical, supra. Plaintiff also objects to Exhibit 142 because it appears to be an incomplete portion of the results, and therefore there is a significant question regarding its scientific reliability, if any.

Plaintiff further objects to Exhibit 142 as scientifically unreliable on the ground that the methodology employed in the rabbit study was unreliable. Use of rabbit skin as a model for human skin is not generally accepted because rabbit skin is generally considered a poor model for human skin permeability and is rarely used in peer-reviewed literature or in the field of transdermal drug delivery testing. See Prausnitz Dec, ¶ 27. Also, the rabbit study did not evaluate the comparison of rabbit skin to human skin, disclose the method by which the rabbit hair was shaved, or clearly state other conditions of the study. Plaintiff also objects to Exhibit 142 on the ground that the design of the rabbit study was flawed for the purpose for which Defendants used it. Defendants cite the study to suggest that rapid evaporation of Duragesic gel will prevent absorption of fentanyl through human skin, but the experiment involved a one-time application of Duragesic gel to uncovered rabbit skin. It did not account for the actual conditions that would be present if a person were using a leaking patch; no account was taken of the likelihood of gel leaking under clothing or under a patch. See ¶ 27 of Prausnitz Dec. Moreover, how accurately fentanyl absorption via human skin is represented by shaved rabbit skin was not evaluated in the study. Finally, the result of the study is anomalous. The rabbit study result – that rabbits exposed to Duragesic gel did not receive therapeutic doses of the drug – is inconsistent with a studies published in peer-reviewed journals, presented at international conferences and disclosed in issued patents clearly showing that fentanyl applied to the skin using an evaporating solvent is extensively absorbed into the skin. See ¶¶ 15, 21, 27 of Prausnitz Dec.

In addition, each of the foregoing studies and any related testimony subject to Plaintiff's Motion in Limine is inadmissible because: (1) the studies are not competent or reliable evidence; (2) the studies are not relevant because they do not tend to make the existence of any fact that is of consequence to the determination of the action more probable or less probable than it would be without the evidence, as required under Federal Rules of Evidence 401 and 402; and (3) the probative value, if any, of the studies and related opinion testimony is substantially outweighed by the danger of unfair prejudice, confusion of the issues, or misleading the jury, in violation of Federal Rule of Evidence 403.

Accordingly, before any proceedings have been had in the presence of the jury and prior to the voir dire examination of the jury panel, before the impaneling of any jury, or selection of any jury, and before the introduction of any evidence, Plaintiff files this Motion in Limine to exclude Exhibits 138, 139, 140 and 142 and any related opinion testimony. Plaintiff respectfully moves this Court to instruct opposing counsel not to mention, refer to, or attempt to introduce evidence, within the hearing of any member of the jury panel, either in voir dire or at any time during trial, upon reading of the pleadings, upon a settlement of the case, or by questions or interrogation of any witness, or in argument or by objections or sidebar remarks, in the presence of the jury or otherwise, regarding any of the studies identified in this Motion, either directly or indirectly, or to refer to or interrogate any witness or otherwise apprise the jury of any of the studies until each study has been first called to the Court's attention out of the presence and hearing of the jury and the Court rules as to Plaintiff's motion to exclude each such study and any opinion testimony referring or relating to such study. Plaintiff further moves the Court to instruct defense counsel to apprise each of their respective witnesses of the contents of this motion so that Plaintiff's Motion in Limine and this Court's rulings thereon not be violated or circumvented by or through any witness.

Also, in support of this Motion, Plaintiff states that in the event any of the excluded opinion testimony regarding the studies or the studies themselves are made known to the jury, even if objection to such matters are sustained by the Court, Plaintiff will be irreparably prejudiced and injured to the extent that not even proper instruction to the jury to disregard such improper testimony or studies will remove the resulting prejudice or injury to Plaintiff. As such, by granting this motion, the Court can properly handle these issues outside of the jury's presence.

DATED: May 21, 2007.