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‘Experts ‘Frye’d On Tylenol-Cirrhosis Link

December 12, 2011 in  News

New York Law Journal

Prior columns have elaborated on the ripening of New York law regarding judicial screening, or “gatekeeping,” of the reliability of expert testimony.Particularly after the New York Court of Appeals’ pivotal October 2006 decision in Parker v. Mobil Oil Corp.,2  courts and lawyers were alerted to a remarkably clear, yet substantially nuanced, road map on approaching questions of experts’ reliability. Clear road maps, however, do not mean the roadways to be traveled are always straight or smoothly paved or sans obstacles or detours. Complexities can intrude to distract or divert attention from or obfuscate the quest for true reliability in the particular expert’s methodology, foundational predicates and opinions. Our Sept. 16 column dealing with reliability concerns when experts use or misuse scientific articles sets forth examples.3

On paper, the reliability-policing rules seem simple enough. If novel scientific evidence is involved, New York’s application of the Frye “general acceptance” test has the judge determine “whether the accepted techniques, when properly performed, generate results accepted as reliable within the scientific community generally.” If the answer is “no,” the testimony flunks and is precluded or excluded. If the answer is “yes,” the proponent of the novel expert opinion has survived the threshold test but must also meet a second reliability standard—one I have called the “foundational reliability” question.

In Parker, the Court said the Frye inquiry is “separate and distinct from the admissibility question applied to all evidence—whether there is a proper foundation—to determine whether the accepted methods were appropriately employed in a particular case.” Parker clarified that the focus moves “from the general reliability concerns of Fryeto the specific reliability of the procedures followed to generate the evidence proffered and whether they establish a foundation for the reception of evidence at trial.” Indeed, in the Parker case itself, which claimed that a gas station attendant’s leukemia was caused by exposure to benzene in gasoline, the Court said that no particular novel methodology was at issue for which “general acceptance” needed to be determined. Rather, the issue was foundational reliability, “an inquiry…more akin to whether there is an appropriate foundation for the experts’ opinions.” The question in Parker was not a Frye issue but whether the methodologies “lead to a reliable result.”

Thus, when novel scientific evidence is involved, the opponent of the proffered expert opinion may throw, and the proponent may have to dodge, a “one-two punch,” first Frye’s “general acceptance” hurdle and, then, if necessary, the “foundational reliability” obstacle. When the scientific evidence is not novel, however, reliability-policing goes forward nonetheless since the foundational reliability requirement must be met. In Parker, the plaintiff’s experts, although highly qualified in their respective fields, “failed to demonstrate that exposure to benzene as a component of gasoline caused [Mr.] Parker’s AML.”

Although the New York courts have not adopted the federal Daubert gatekeeping standard,4 the Court of Appeals in Parker referred in its footnote 4 to federal case law on how much precise exposure information a toxic tort plaintiff needs to prove and stated: “We recognize that these cases employ a Daubert analysis. However, they are instructive to the extent they address the reliability of an expert’s methodology.” Thus, although the Frye test governs the reliability issue in novel science cases, federal case law employing Daubert analysis may be “instructive” on the foundational reliability issue courts have to grapple with in all expert testimony cases where reliability concerns are properly raised.

Tylenol Case

A comprehensive gatekeeping decision offering salient points and valuable insights was issued on Nov. 22 by the Appellate Division, Second Department, in Ratner v. McNeil-PPC Inc.,5  a case in which it was claimed that plaintiff’s ingestion of the common medication, Tylenol, caused liver cirrhosis. In an opinion authored by Justice John M. Leventhal, the court concluded that the trial judge properly granted defendant’s motion to preclude plaintiff’s expert testimony relating to plaintiff’s theory of medical causation and for summary judgment dismissing the complaint. Since the appellate opinion is informative, we briefly review highlights here.

Beginning in 1985, plaintiff ingested Tylenol and Extra Strength Tylenol as needed to relieve migraine headaches, never exceeding the maximum recommended dosage. Acetaminophen is the sole active ingredient of the over-the-counter analgesic. In 1997 she underwent a liver biopsy based on symptoms of “portal hypertension,” but established cirrhosis was not shown. In 2001 an MRI indicated she had “microndular cirrhosis.” In July 2004 she underwent liver transplant surgery. Later, she was diagnosed with liver conditions called “incomplete septal cirrhosis” (ISC) and “hepataportal sclerosis” (HPS), an uncommon condition.

Defendant manufactures and sells Tylenol. Plaintiff sued for negligence, failure to warn, defective design, breach of warranties and a violation of the General Business Law. During discovery four experts were identified to testify on behalf of plaintiff. Two were prepared to set forth the theory that acetaminophen caused her liver cirrhosis. The experts asserted that acetaminophen was a known hepatoxin, a substance harmful to the liver. Repeated exposure can cause chronic inflammation that can lead to scarring of the liver which, in turn, may cause cirrhosis. The experts relied on medical studies, plaintiff’s liver pathology slides, clinical history and biopsy reports.

Expert D, a gastroenterologist and a hepatologist, would testify that toxic effects of acetaminophen could be seen at doses “only slightly greater than recommended therapeutic doses.” Further, some persons, those who are fasting, malnourished or “predisposed” are at a greater risk of toxicity, even at therapeutic doses. After “ruling out other possibilities” and “using techniques consistent with those used in his practice,” D concluded that acetaminophen caused the cirrhosis. D also relied on four case studies performed on mice and rats.

Expert T, a pathologist and professor of hepatopathology, planned to testify how exposure to hepatoxins can result in toxic hepatitis, then to hepatic fibrosis and liver cirrhosis. He would rely on scientific literature. He also reviewed plaintiff’s liver slides and noticed a regression of scarring coinciding with plaintiff’s discontinuation of the product. Expert R, a pharmacologist, was to testify about inadequate warnings as well as the ability of defendant to eliminate the hepatoxicity by adding an ingredient called methionine. Expert P, a former chief medical officer with the Food and Drug Administration would testify that defendant downplayed the potential risks and failed to safely design, test and label Extra Strength Tylenol.

Defendant moved to preclude the expert testimony on medical causation and for summary judgment. Defense expert W, a physician specializing in hepatology and cell biology, in an affidavit, conceded that acetaminophen is toxic to the liver in overdose and can cause failure in massive overdose. But, the theory that long-term acetaminophen use at therapeutic doses can cause cirrhosis was not generally accepted in the medical and scientific communities. W asserted that plaintiff’s experts’ opinions were based on a faulty conclusion regarding the nature of her diagnosis. W criticized the reliance on medical literature consisting almost exclusively of case reports and animal studies involving overdose. Such data about overdoses “could not be extrapolated” to explain the cause of the plaintiff’s condition. W supplemented his affidavit with two medical articles concluding that acetaminophen was safe in therapeutic doses, even for individuals suffering from liver disease.

Plaintiff opposed the motion arguing that there was nothing novel in the methodologies employed by her experts. A Frye hearing was therefore unnecessary. Experts T, D, R and P urged that the drug caused the disease. The trial judge, noting that almost all of the case reports involved ingestion of doses greater than the recommended dose, or involved a patient with a disease other than cirrhosis, concluded that plaintiff’s novel premise that normal ingestion caused cirrhosis failed to satisfy the evidentiary requirements of Frye.

Speculative Theory

The Appellate Division restated the Frye rule quoting from prior precedents. The test typically considers the admissibility of new scientific tests, techniques or  processes.6  It has also been used to determine admissibility of expert testimony based on new social and behavioral theories. However, where there is no novel or innovative science involved, or where the tendered scientific deduction has been deemed generally accepted as reliable, “there remains a separate inquiry applied to all evidence.” This inquiry is “whether there is a proper foundation to determine whether the accepted methods were appropriately employed in a particular  case.”7

Citing Parker, among other precedents, the court said that, when the experts offer no novel test or technique, but intend to testify about a novel theory of causation, where such opinion is supported by generally accepted scientific methods, “it is proper to proceed directly to the foundational inquiry of admissibility, which is whether the theory is properly founded on generally accepted scientific methods or principles.” Here, the plaintiff’s experts did not utilize any novel scientific techniques or evidence, but they did seek to set forth “the novel theory that therapeutic acetaminophen use caused the plaintiff’s liver cirrhosis primarily based on the fact that acetaminophen is a hepatoxin and that certain case studies suggest a relationship between acetaminophen and cirrhosis.”8

The court observed that deductive reasoning or “extrapolation,” even in the absence of medical texts or literature supporting a plaintiff’s theory of causation under identical circumstances, can be admissible “if it is based upon more than mere theoretical speculation or scientific hunch.” Indeed, deduction, extrapolation, drawing inferences from existing data, and analysis are not novel methodologies and are accepted stages of the scientific process.Nevertheless, where there is “simply too great an analytical gap between the data and the opinion proffered,” the opinion should be rejected.10

Here the court found that the data upon which the plaintiff’s experts relied was insufficient to support their novel theory of medical causation, “rendering that theory speculative.” Each of the case reports or observational studies plaintiff’s experts used did not overcome the “analytical gap” between the scientific data and the experts’ theory of causation, a gap “widened by the contrary scientific articles concluding that acetaminophen is safe in therapeutic doses, even for individuals suffering from liver disease.”

Moreover, plaintiff did not offer any clinical or epidemiological data or peer reviewed studies showing a causal link between therapeutic use and liver cirrhosis. In the absence of such evidence, plaintiff had to set forth other scientific evidence “based on accepted principles.” The methodology employed by the experts, primarily based on case studies, was “fundamentally speculative.” The court emphasized that when an expert seeks to introduce a novel theory of medical causation without relying on a novel test or technique, “the proper inquiry begins with whether the opinion is properly founded on generally accepted methodology, rather than whether the causal theory is generally accepted in the relevant scientific community.” Here that burden was not met.11


The omnipresent struggle to assure that only reliable and relevant expert testimony gets to the jury is robustly addressed by New York courts using Frye analysis in novel science and technology cases augmented by penetrating inquiry into foundational reliability in all cases. Although the objective is clear and the legal road map is lucid, in practice, nuanced tensions are presented. For example, is there a distinction in determining causation when a new drug is involved as opposed to one popularly used for 50 years? The dynamics in given cases call for diligent gatekeeping efforts. The Appellate Division’s Ratner decision helps readers understand not only the rules but some of the nuances.

Michael Hoenig is a member of Herzfeld & Rubin.


  1.  Hoenig, Judicial Gatekeeping: ‘Frye,’ ‘Foundational Reliability,'” New York Law Journal, Feb. 11, 2008, p. 3; “‘Parker,’ ‘Frye’ and Gatekeeping of Experts: an Update,” NYLJ, June 17, 2009, p.3.
  2.  7 N.Y. 3d 434 (2006).
  3.  Hoenig, “Testifying Experts and Scientific Articles: Reliability Concerns,” NYLJ, Sept. 16, 2011, p. 3 (citing prior articles on experts’ use of unreliable hearsay, scientific papers questioning the reliability of biomedical articles, and reporting serious shortcomings even in those that were peer reviewed).
  4.  See Fed. R. Evid. 702; Daubert v. Merrell Dow Pharmaceuticals Inc., 509 U.S. 579 (1993); General Elec. Co. v. Joiner, 522 U.S. 136 (1997); Kumho Tire Co. v. Carmichael, 526 U.S. 137 (1999).
  5.  2011 NY Slip Op 08575 (2d Dept., Nov. 22, 2011).
  6.  Ratner, Id., Slip Op, at p. 10.
  7.  Id., Slip Op, at p. 11.
  8.  Id., Slip Op, at p. 12.
  9.  Id., Slip Op, at p. 12—13 (citing and discussing Zito v. Zabarsky, 28 A.D.3d 42) (extrapolation or deduction warranted where theory pertains to new drug) and citing other cases.
  10.  Id., Slip Op, at p. 13 (quoting from General Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997)).
  11.  Id., Slip Op, at pp. 15—16.