It takes time and effort to keep all our scorecards and cheat sheets up to date. So we fell all over ourselves when a Reed Smith associate, Kevin Hara, offered to update our cheat sheed on adverse event reports. The result is this guest post. As you might guess, Kevin works out of the RS San Francisco office. As with all guest posts, Kevin is due all the credit (and blame, if any) for what follows. The AER cheat sheet has been simultaneously updated to include the case descriptions in Kevin's post.
As the San Francisco Giants completed their biennial foray deep into the playoffs, on their way to a third World Series title in the last five seasons, it makes us think of Adverse Event Reports (“AERs”) and Medical Device Reports. How exactly do we relate baseball to AERs? The Giants have managed to advance to the World Series with a seemingly rhythmic frequency, in 2010, 2012, and again this year. Baseball fans even joke that because 2014 is an even numbered year, that was why the Giants won. Are the two things related? Do people really believe that the digits on the calendar determine the fate of the Bay Area baseball franchise? Or is it simply a coincidence, and not a cause and effect relationship? Is it not more likely that consistently good pitching, defense, and timely hitting along with good management are reason that the Giants are winning, and it just happens to fall on even numbered years (although until last night the Kansas City Royals of course disagreed)? Although Kevin Costner’s soliloquy in Bull Durham captures the idea that baseball players in general take superstition to the extreme, and might argue that the Giants’ success is as simple as the calendar year, the answer of course, is yes, there is much more to the analysis.
A similar analogy can be drawn between using AERs as evidence of causation in pharmaceutical drug and medical device litigation. There are numerous other potential explanations that may be more likely and one simply cannot draw a conclusion that a drug or device caused an adverse event based on AER data. The publicly available FDA Adverse Event Reporting System “FAERS,” launched on September 10, 2012, clearly cautions that “[t]he appearance of a drug on this list does not mean that FDA has concluded that the drug has the listed risk. It means that FDA has identified a potential safety issue, but it does not mean that FDA has identified a causal relationship between the drug and the listed risk.”
However, when required to submit evidence establishing medical causation of their injuries, plaintiffs in drug and device cases frequently attempt to submit expert opinions that rely heavily on AERs. As this blog has reported before, here, and here, AERs, often referred to as case reports, are not reliable indicia of causation. A recent decision, Wendell v. Johnson & Johnson, which the blog covered here, underscored the fact that anecdotal evidence is not a reliable source of medical causation. 2014 WL 2943572, at *3-5 (N.D. Cal. June 30, 2014). Although the experts in Wendell “cite[d] a handful of studies and case reports discussing possible causes of HSTCL, none of these purports to show that the specific combination of drugs prescribed to [plaintiff] actually causes HSTCL.” Id. at *5 (emphasis added). This straightforward application of the law of medical causation is elegant in its simplicity – if the plaintiff cannot show that the medicine, or in this case – combination of medicines – is even capable of causing the alleged injury, the defendant (rightly so) prevails.
Baseball appears to be a beautiful and simple game when played well, but as anyone who has tried to hit a ball traveling more than 95 miles per hourwill tell you, there are few things more difficult. Indeed, a hitter in the major leagues who succeeds merely one third of the time is not just good but great. Therefore, just like the Giants’ winning ways are not simply a product of even numbers, but relate instead to numerous other factors such as pitching, defense, hitting, favorable matchups, managerial decisions, and even human error (although, as last night proved, replay review certainly helps), an injury or disease may have many possible explanations, or may instead be idiopathic. There is much more to the outcome of the Major League Baseball playoffs than a single factor. And that is precisely why courts should not infer causation from case reports.
With all that as prologue, here are the latest case updates to the blog’s adverse event report cheat sheet:
Chapman v. Procter & Gamble Distributors, LLC, 766 F.3d 1296 (11th Cir. Sept. 11, 2014) (Fixodent). Affirming exclusion of causation testimony because reliance on “generalized case reports, hypotheses, and animal studies are insufficient proof of general causation,” because such information “could mislead the jury by causing it to consider testimony that was insufficient by recognized primary methodologies to prove using [denture cream] causes myelopathy.”
Wirt v. Sec'y of Health & Human Services, No. 11–118V S, 2014 WL 1911421 (Fed. Cl. Apr. 18, 2014) (HPV vaccine). Adverse event data alone, “without the opinion of a medical expert and/or medical records showing a causal connection between vaccination and injury, is not proof of a causal connection,” and is insufficient to establish that a product caused a particular disease.
DeGidio v. Centocor Ortho Biotech, Inc., 3 F. Supp.3d 674 (N.D. Ohio Mar. 11, 2014) (Remicade). Excluding expert testimony under Daubert, where there was “no question that plaintiffs’' experts based their general-causation opinions solely on case reports” because “[c]ase reports make little attempt to screen out alternative causes for a patient's condition,” and simply describe phenomena without comparison to background rates, either “in the general population or in a defined control group; do not isolate and exclude potentially alternative causes; and do not investigate or explain the mechanism of causation.
Berman v. Stryker Corp., No. 11 C 1309, 2013 WL 5348324 (N.D. Ill. Sept. 24, 2013) (prosthetic knee). Reliance on Manufacturer and User Facility Device Experience (“MAUDE”) medical device adverse event reports alone was inappropriate basis to infer causation are because “such reports can contain inaccurate and non-validated data,” and “[d]enominator data are missing which makes evaluation of the incidence or prevalence of reported events impossible.”
Trainer v. Sec’y of Health & Human Services, No. 10–865V, 2013 WL 4505803 (Fed. Cl. July 24, 2013) (hepatitis A vaccine). Finding “no causal link” between” the product and the alleged harm where the claimant attempted to rely on case reports and anecdotal evidence because “there are too many unknown variables that make such raw information inherently unreliable.”
Klein v. TAP Pharmaceutical Products, Inc., 518 F. Appx. 583 (9th Cir. May 14, 2013) (Lupron). Affirming exclusion of adverse event reports, as they “were hearsay reports of uncertain reliability, lacking information relevant to causation.”
Rhodes v. Bayer Healthcare Pharmaceutical, Inc., No. 10–1695, 2013 WL 1289050 (W.D. La. Mar. 26, 2013) (Avelox). GrantingDaubert motion to exclude expert testimony because “reliance on adverse event reports is also unimpressive, as such reports do not demonstrate the requisite degree of reliability.”
In re Aredia & Zometa Products Liability Litigation, 483 F. Appx. 182 (6th Cir. June 5, 2012) (bisphosphonate drugs). Affirming grant of summary judgment. Expert testimony was properly excluded as unreliable because general causation expert admitted that he could not “establish causation [based on 2] case reports, but simply a ‘very close association.’”
In re Denture Cream Products Liability Litigation 795 F. Supp.2d 1345 (S.D. Fla. June 13, 2011) (Fixodent). Expert testimony on general causation was unreliable because there was “no evidence that Plaintiffs’ experts or the case reports they rely on [were] systematic in considering other plausible hypotheses and excluding background risk.” AERs are “unreliable, as a general matter,” due to “inconsistencies in case definition,” which “limit[ed] the evidentiary value of the case reports to support an inference of causation.”
In re Zicam Cold Remedy Marketing, Sales Practices, & Products Liability Litigation., No. 09–md–2096–PHX–FJM, 2011 WL 798898 (D. Ariz. Feb. 24, 2011) (Zicam). The FDA’s “AERs data and the agency’s reports are not admissible bases” for expert causation opinions. Such reports “reflect complaints called in by product consumers without any medical controls or scientific assessment,” and are “uncontrolled anecdotal information [which] is not the foundation of a reliable causation methodology.”
Toni’s Alpacas, Inc. v. Evans, No. 09–cv–02045–REB–CBS, 2010 WL 3730382 (D. Colo. Sept. 16, 2010) (fiber supplement). Rejecting anecdotal reports as foundation for proof of causation, since they do not isolate and exclude alternative causes and lack controls.
Kilpatrick v. Berg, Inc., 613 F.3d 1329 (11th Cir. Aug. 12, 2010) (pain pump). Affirming that case study was an unreliable basis for expert testimony because it did not contain statistical analysis and did not draw medically valid conclusions. The excluded expert “acknowledged that case reports . . . are ‘way down at the very bottom as far as medical strength of an article’ and cannot establish medical causation,” because of a “multitude of factors that could have caused” the alleged injuries.
Hendrix v. Evenflo Co., Inc., 609 F.3d 1183 (11th Cir. June 22, 2010) (child restraint system). Affirming exclusion of expert testimony. “Case studies and clinical experience, used alone and not merely to bolster other evidence, are also insufficient to show general causation.”