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Adverse Event Report Cheat Sheet

By James M. Beck and Mark Herrmann

A lot of things about that recent Gadolinium opinion ticked us off.  But one of the lowest of many low points was when the court ruled a causation opinion based upon FDA adverse event reports (?AERs?) was admissible in a civil trial because the FDA used AERs to assess causation administratively.  In re Gadolinium-Based Contrast Agents Products Liability Litigation, 2010 WL 1796334, at *9-11 (N.D. Ohio May 4, 2010).  Never mind that the FDA?s administrative standards (and agency standards generally) are a far cry  from those used in civil litigation.

Anyway, as we pointed out in the Gadolinium post, a lot of other courts have taken a more sensible ? not to mention scientifically valid ? approach to AERs and have excluded them, or opinions based upon them, from evidence.  Heck, even Gadolinium wouldn?t let the plaintiffs? experts base their opinions ?based on AERs alone.?  2010 WL 1796334, at *11.  For this reason we?ve decided to make exclusions of AERs from evidence (on grounds other than notice) our latest ?cheat sheet.?

Before get to the cases, however, we?ll also supply links to some relevant FDA documents.

(1) the FDA?s 1996 Annual Adverse Experience Drug Report, in which the agency states that AERs ?may not be used to calculate incidences or estimates of drug risk?;

(2) the FDA?s 2003 Pharmaceutical Safety Assessments Analysis, which characterized causation assessments based upon AERs as ?dubious,? ?inefficient,? and ?low quality?;

(3) the FDA?s current website description of its adverse event reporting system, discussing the ?limitations? of AERs and how they ?cannot be used to calculate the incidence of an adverse event in the U.S. population.?

Here goes.  It?s the usual format: a list of cases, similar to our scorecards, but only including those cases we would consider citing in support of a motion to exclude.  Like the scorecards, this cheat sheet will be updated periodically.

1. Wolf v. Procter & Gamble Co., 555 F. Supp. 613 (D.N.J. 1982) (tampon).  Excluding AERs from evidence. AERs are inadmissible hearsay. Pre-Daubert case.
2. Richardson v. Richardson-Merrell, Inc., 649 F. Supp. 799 (D.D.C. 1986) (Bendectin).  Excluding AERs from evidence and as a basis for expert opinion.  AERs ?are neither exceptions to the hearsay rule nor data reasonably relied upon by experts in the field of making determinations of causality.? Richardson was affirmed on other grounds.  Richardson v. Richardson-Merrell, Inc., 857 F.2d 823 (D.C. Cir. 1988). Pre-Daubert case.
3. Hagaman v. Merrell Dow Pharmaceuticals, 1987 WL 342949 (D. Kan. June 26, 1987) (Bendectin).  Excluding AERs from evidence.  AERs ?are often incomplete, in that they often do not indicate whether other drugs are being taken, or whether other drugs might have caused the reported health problem.?  Many ?have been prompted by contemplated or existing litigation.?  Pre-Daubert case.
4. Martinkovic v. Bangash, 1987 WL 28400 (N.D. Ill. Dec. 18, 1987) (DTP vaccine).  AERs excluded as evidence of causation, although admissible for purposes of notice.  ?[A]necdotal reports of alleged adverse reactions are not admissible to prove the truth of the matter? and are hearsay for that purpose.  Pre-Daubert case.
5. Cosgrove v. Merrell Dow Pharmaceuticals, Inc., 788 P.2d 1293 (Idaho June 8, 1989) (Bendectin).  Affirming exclusion of AERs from evidence.  AERs ?are anecdotal in nature and should not form the basis for any conclusions, expert or otherwise? and are inadmissible hearsay.  Pre-Daubert case.
6. Peters v. Johnson & Johnson Products, Inc., 783 S.W.2d 442 (Mo. App. Jan. 23, 1990) (tampon).  Affirming exclusion of AERs from evidence.  AERs are inadmissible hearsay as ?unsolicited letters and unsubstantiated reports from alleged . . . users do not stand as to their trustworthiness.?  Pre-Daubert case.
7. DeLuca v. Merrell Dow Pharmaceuticals, Inc., 791 F. Supp. 1042 (D.N.J. April 29, 1992) (Bendectin).  Excluding expert opinion based upon AERs.  AERs ?are unreliable for determining causation? because they ?ADRs have inherent biases as they are second-or-third hand reports, are affected by medical or mass media attention, and are subject to other distortions.?  They are ?not of a type of data that are reasonably relied upon by experts . . . to make a determination of [a] causal relationship.?  DeLuca was affirmed without opinion: 6 F.3d 778 (3d Cir. 1993).  Pre-Daubert case.
8. Wade-Greaux v. Whitehall Laboratories, Inc., 874 F. Supp. 1441 (D.V.I. March 3, 1994) (Primatine).  Excluding expert opinion based upon ?[a]necdotal reports of the claimed adverse experiences? and AERs ?filed with manufacturers or regulatory authorities.?  ?[S]uch data represent anecdotal information of chance associations, do not purport to assess cause and effect and have no epidemiological significance.?  Pre-Daubert case.
9. Sprague v. Upjohn Co., CA No. 91-40035-NMG (D. Mass. May 13, 1994) (Halcion).  Excluding expert opinion based upon AERs. AERs are ?not a scientifically valid or accepted methodology for making a determination of causation or relative drug safety.?  Pre-Daubert case.  We don't have a copy of this opinion, but would like one.
10. Casey v. Ohio Medical Products, 877 F. Supp. 1380 (N.D. Cal. Feb. 28, 1995) (Halothane).  Excluding expert report based upon a study that was based upon foreign AERs.  The foreign AERs ?simply describe reported phenomena without comparison to the rate at which the phenomena occur,? ?do not isolate and exclude potentially alternative causes,? and ?do not investigate or explain the mechanism of causation.?
11. Reynolds v. Warthan, 896 S.W.2d 823 (Tex. App. March 17, 1995) (Kwell).  Affirming exclusion of AERs from evidence on grounds of danger of jury confusion.  AERs ?did not establish a causal link between [the product] and the reported symptoms; rather, they created a suspicion without any medical proof.?  ?[S]ubmission of [an AER] does not necessarily constitute an admission that the drug caused the adverse reaction.?
12. Haggerty v. Upjohn Co., 950 F. Supp. 1160 (S.D. Fla. Dec. 6, 1996) (Halcion).  Excluding expert opinion based upon AERs and ?anecdotal case reports appearing in medical literature.?  Due to the ?the inherent bias in the? AERs, they ?cannot be relied upon to form causation opinions.?  Haggerty was affirmed without opinion: 158 F.3d 588 (11th Cir. 1998).
13. Lopez v. Wyeth-Ayerst Laboratories, 1996 WL 784566 (N.D. Cal. Dec. 13, 1996) (non-swine flu vaccine).  Excluding expert report based upon ?case reports,? which were probably AERs, absent evidence that the reports ?isolate and exclude other potential causes.?  Lopez was affirmed in a non-precedential opinion.  Lopez v. Wyeth-Ayerst Laboratories, Inc., 1998 WL 81296 (9th Cir. 1998) (?anecdotal reports . . . do not attempt to isolate causes and are not intended to reach conclusions as to causation?) (in table at 139 F.3d 905).
14. Hall v. Baxter Healthcare Corp., 947 F. Supp. 1387 (D. Or. Dec. 18, 1996) (breast implants).  Excluding expert opinion based upon ?case reports or collections of case reports? which sound like AERs.  ?[C]ase reports and case studies are universally regarded as an insufficient scientific basis for a conclusion regarding causation because case reports lack controls.?
15. In re Norplant Contraceptive Products Liability Litigation, 1997 WL 80527 (E.D. Tex. Feb. 19, 1997) (Norplant).  AERs excluded from evidence on the basis of jury confusion and waste of time.  AERs are only ?marginally probative? because ?the FDA requires [defendant] to submit all adverse events reported to it without regard to whether there is any proven causal connection."
16. Saari v. Merck & Co., 961 F. Supp. 387 (N.D.N.Y. March 11, 1997) (hepatitis B vaccine).  AER about plaintiff?s case excluded from evidence.  It was ?was simply a report of what plaintiff told [the reporting doctor] about what she believed was her reaction to the vaccine.?  Reporting physician could not testify since in the AER he ?neither confirmed nor den[ied] that there is any [causal] relationship.?
17. Golod v. La Roche, 964 F. Supp. 841 (S.D.N.Y. May 20, 1997) (Tegison).  AERs excluded from evidence of causation, although admissible for purposes of notice.  ?[T]he reports may not be sufficiently reliable or relevant to be admissible on the issue of causation, [but] are relevant to [defendant?s] awareness.?
18. Merrell Dow Pharmaceuticals, Inc. v. Havner, 953 S.W.2d. 706 (Tex. July 9, 1997) (Bendectin).  Reversing admission of expert opinion based on ?case reports? (which in other Bendectin cases included AERs).  ?[P]hysicians following scientific methodology? would not ?rely on case reports to determine whether a substance is harmful.?  ?[A]necdotal . . . evidence accomplishes no more than a false appearance of direct and actual knowledge of a causal relationship.?
19. Willert v. Ortho Pharmaceutical Corp., 995 F. Supp. 979 (D. Minn. Feb. 25, 1998).  Excluding expert opinion based on ?case reports? (which might be AERs) and other ?anecdotal? evidence.  ?[T]hey simply describe reported phenomena without comparison to the rate at which the phenomena occur,? ?do not isolate and exclude potentially alternative causes,? and ?do not investigate or explain the mechanism of causation.?
20. In re Breast Implant Litigation, 11 F. Supp.2d 1217 (D. Colo. June 3, 1998) (breast implants).  Technically this case shouldn?t be here because it doesn?t involve FDA AERs, but other anectodal evidence (an expert?s individual clinical experience).  But it comes up so often ? and cites several AER cases ? that we?re including it.  ?[C]ase reports. and case studies universally are regarded as an insufficient scientific basis for a conclusion regarding causation because case reports lack controls.?
21. Allison v. McGhan Medical Corp., 184 F.3d 1300 (11th Cir. Aug. 18, 1999) (breast implants).  Affirming exclusion of expert opinion based on ?case reports? (which might be AERs).  ?Case reports and case studies are universally regarded as an insufficient scientific basis for a conclusion regarding causation because case reports lack controls.?
22. Revels v. Novartis Pharmaceuticals Corp., 1999 WL 644732 (Tex. App. Aug. 26 1999) (non-precedential), review denied (Tex. June 29, 2000) (Parlodel).  Affirming exclusion of expert opinion based upon AERs.  ?[A] study of case reports alone is a scientifically invalid manner in which to form an expert opinion.?
23. Brumbaugh v. Sandoz Pharmaceuticals Corp., 77 F. Supp. 2d 1153 (D. Mont. Sept. 27, 1999) (Parlodel).  Excluding expert opinion based upon AERs.  AERs ?do not demonstrate a causal link but instead represent coincidence.?  Their ?most significant analytical defect is that they don?t isolate and investigate the effects of alternative causation.?
24. Linnen v. A.H. Robins Co., 2000 WL 16769 (Mass. Super. Dec. 14, 1999) (Phentermine).  Excluding expert opinion based on ?between ten and twenty case reports? that sound like AERs.  ?[C]ase reports alone are not considered reliable scientific evidence of causation.?
25. Nelson v. American Home Products Corp., 92 F. Supp.2d 954 (W.D. Mo. March 24, 2000) (Cordarone).  Excluding expert opinion based upon AERs and possibly other case reports.  AERs ?do not demonstrate a causal link sufficient for admission to a finder of fact in court.?
26. Robinson v. Astra Pharmaceutical Products, Inc., 765 So.2d 378 (La. App. March 31, 2000) (Citanest).  AERs were ?wholly irrelevant? because they were not substantially similar to the plaintiff's situation.
27. In re Diet Drugs (Phentermine, Fenfluramine, Dexfenfluramine) Products Liability Litigation, 2001 WL 454586 (E.D. Pa. Feb. 1, 2001) (fen-phen).  Excluding expert opinion based upon AERs.  AERs ?are universally recognized as insufficient and unreliable evidence of causation.?
28. Glastetter v. Novartis Pharmaceuticals Corp., 252 F.3d 986 (8th Cir. June 8, 2001) (Parlodel).  Affirming exclusion of expert opinion based upon AERs.  Mere ?case reports? suffer from numerous flaws and are ?not scientifically valid proof of causation.?  The trial court opinion is at Glastetter v. Novartis Pharmaceuticals Corp., 107 F. Supp.2d 1015 (E.D. Mo. 2000).
29. Caraker v. Sandoz Pharmaceuticals Corp., 172 F. Supp. 2d 1046 (S.D. Ill. Sept. 12, 2001) (Parlodel).  Excluding expert opinion based upon AERs and published case reports.  AERs ?make little attempt to isolate or exclude possible alternative causes, lack adequate controls, and lack any real analysis.?
30. Cloud v. Pfizer, Inc., 198 F. Supp. 2d 1118 (D. Ariz. Nov. 21, 2001) (Zoloft).  Excluding expert opinion based upon AERs and ?retrospective case reports.?  Such items ?are merely compilations of occurrences, and have been rejected as reliable scientific evidence supporting an expert opinion.?
31. Hollander v. Sandoz Pharmaceuticals Corp., 289 F.3d 1193 (10th Cir. May 10, 2002) (Parlodel).  Affirming exclusion of expert opinion based upon AERs and other case reports.  AERs ?contain only limited information? and are ?unreliable evidence of causation.?  The trial court opinion is at Hollander v. Sandoz Pharmaceuticals Corp., 95 F. Supp.2d 1230 (W.D. Okla. 2000) (?case reports have been repeatedly rejected as a scientific basis for a conclusion regarding causation?).
32. Rider v. Sandoz Pharmaceuticals Corp., 295 F.3d 1194 (11th Cir. June 24, 2002) (Parlodel).  Affirming exclusion of expert opinion based upon AERs.  Such case reports ?are merely accounts of medical events? and ?reflect only reported data, not scientific methodology.?  They do ?not by themselves provide reliable proof of causation.?  The trial court opinion is at Siharath v. Sandoz Pharmaceuticals Corp., 131 F. Supp.2d 1347 (N.D. Ga. 2001) (case reports ?cannot establish general causation?).
33. Newton v. Roche Laboratories, Inc., 243 F. Supp.2d 672 (W.D. Tex. Dec. 5, 2002) (Accutane).  Excluding expert opinion based upon AERs.  ?[M]any other courts have soundly rejected case reports as an acceptable basis for causation.?
34. Soldo v. Sandoz Pharmaceuticals Corp., 244 F. Supp.2d 434 (W.D. Pa. Jan. 13, 2003) (Parlodel).  Excluding expert opinion based upon AERs.  AERs ?do not demonstrate a causal link but instead represent coincidence.  Case reports and ADEs are compilations of occurrences, and have been rejected as reliable scientific evidence supporting expert opinion so as to meet the requirements set forth in Daubert.?
35. Dunn v. Sandoz Pharmaceuticals Corp., 275 F. Supp. 2d 672 (M.D.N.C. Aug. 4, 2003) (Parlodel).  Excluding expert opinion based upon AERs.  AERs ?are not controlled studies, and they cannot be verified through peer review.  [AERs] often do not include information about the patient's medical history, family medical history, use of other medications or drugs, or other information that would be necessary to determine whether causation between the use of the drug and the reported adverse effect can be established. [AERs] are not scientific proof of causation.?
36. Freeman v. Hoffman-Laroche, Inc., 2004 WL 5382304 (Neb. Dist. March 18, 2004) (Accutane).  Further discovery of AER files denied.  AERs ?do[] not constitute valid scientific proof of medical causation and therefore, has little relevance in a product liability case.?
37. Skibniewski v. American Home Products Corp., 2004 WL 5628157 (W.D. Mo. April 1, 2004) (fen-phen).  AERs excluded from evidence.  AERs ?cannot be used to establish causation,? and ?are hearsay and do not fall within an exception.?
38. In re Meridia Products Liability Litigation, 328 F. Supp.2d 791 (N.D. Ohio July 7, 2004) (Meridia).  Excluding expert opinion on comparative drug risk based upon AERs.  AERs ?do not screen out alternative causes for the adverse event and often lack analysis,? are ?not scientifically valid proof of causation? and are ?irrelevant to establish a material issue of fact.?
39. McClain v. Metabolife International, Inc., 401 F.3d 1233 (11th Cir. March 2, 2005) (ephedrine).  Reversing admission of expert opinion based upon AERs.  AERs ?reflect complaints called in by product consumers without any medical controls or scientific assessment.?  ?Uncontrolled anecdotal information offers one of the least reliable sources to justify opinions about both general and individual causation.?
40. Heckstall v. Pincus, 797 N.Y.S.2d 445 (N.Y.A.D. June 16, 2005) (Bupropion).  Excluding expert opinion based upon AERs.  AERs are ?unverified listings and reporting of adverse reactions . . . [and] ?are not generally accepted in the scientific community on questions of causation.?
41. Ervin v. Johnson & Johnson, Inc., 2006 WL 1529582 (S.D. Ind. May 30, 2006) (Remicade).  Excluding expert opinion based upon AERs.  AERs ?do little more than establish a temporal association between an exposure to a drug and a particular occurrence.?  Ervin was affirmed:  Ervin v. Johnson & Johnson, Inc., 492 F.3d 901 (7th Cir. 2007), without any specific discussion of AERs.
42. Dellinger v. Pfizer Inc., 2006 WL 2057654 (W.D.N.C. July 19, 2006) (Neurontin).  Excluding expert opinion based upon AERs.  AERs ?are not scientific proof of causation.?  ?[M]any courts have recognized that adverse drug reaction case reports and other regulatory reports fail to test a causal hypothesis and therefore cannot support a causation opinion.?
43. Benkwith v. Matrixx Initiatives, Inc., 467 F. Supp.2d 1316 (M.D. Ala. Dec. 27, 2006) (Zicam).  Excluding expert opinion based upon AERs.  AERs are ?are even less persuasive than case reports? because they are ?[u]ncontrolled anecdotal information.?
44. Appleby v. Glaxo Wellcome, Inc., 2005 WL 3440440 (D.N.J. Dec. 13, 2005) (Lotronex).  Excluding AERs from evidence.  AERs are not FDA conclusions and thus have no guarantees of genuineness.  AERs ?may not be sufficiently reliable or relevant to be admissible on the issue of causation.?
45. Pauley v. Bayer Corp., 2006 WL 463866 (Pa. C.P. Jan. 26, 2006) (Baycol).  Excluding AERs from evidence.  AERs are ?not the product of laboratory research or any type of controlled study,? but ?merely the compilation of experiential reports.?  They ?are not proof of the data they contain, and do not directly bear upon the adequacy of label warnings.?  Pauley was affirmed in a non-citable memorandum opinion.  Pauley v. Bayer Corp., 2009 WL 1654592 (Pa. Super. June 12, 2009) (?the court?s limitation on the use of the AERs data at trial was appropriate, because it was anecdotal, not scientific?) (in table at 981 A.2d 331).
46. In re: Accutane Products Liability Litigation, 2007 WL 1288354 (M.D. Fla. May 2, 2007) (Accutane).  Excluding AERs from evidence. AERs ?reflect[] nothing more than an assessment of a possible relationship, not an actual relationship.?
47. In re Baycol Products Litigation, 532 F. Supp.2d 1029 (D. Minn. July 16, 2007) (Baycol).  Excluding expert opinion on comparative drug risk based upon ADEs.  ?[T]he limitations inherent in AER data? preclude any rate of error analysis and ?no evidence has been submitted to demonstrate that such an analysis is generally accepted.?
48. Ranes v. Adams Laboratories, Inc., 778 N.W.2d 677 (Iowa Feb. 5, 2010) (PPA). Affirming exclusion of expert opinion based upon AERs and published case reports.  ?[C]ase reports are merely accounts of medical events. They reflect only reported data, not scientific methodology.?  ?[T]he methodology used by the expert becomes suspect when it is only supported by case reports of limited use to the medical field.?
49. Smith v. Pfizer Inc., 2010 WL 1754443 (M.D. Tenn. April 30, 2010) (Neurontin). Excluding AERs from evidence.  AERs are not probative of causation as they have ?inherent biases as they are second-or-third hand reports, are affected by medical or mass media attention, and are subject to other distortions.?

Full post as published by Drug and Device Law on May 27, 2010 (boomark / email).