Opinion ID: 76908
Heading Depth: 2
Heading Rank: 2

Heading: The PPA Analogy

Text: 45 In reaching his opinions about general causation, O'Donnell relies heavily on an analogy between ephedrine and phenylpropanolamine (PPA). PPA is a sympathomimetic drug that has been used widely in over-the-counter cough and cold medications and weight loss products. RALPH I. HOROWITZ ET AL., PHENYLPROPANOLAMINE & RISK OF HEMORRHAGIC STROKE: FINAL REPORT OF THE HEMORRHAGIC STROKE PROJECT (2000). The conclusions that O'Donnell draws about ephedrine by analogy from PPA are very important to his opinions, but he did not show the reliability of each of his steps in deducing Metabolife's toxicity from this analogy. This is a fatal defect under Daubert. The Daubert `requirement that the expert testify to scientific knowledge — conclusions supported by good grounds for each step in the analysis — means that any step that renders the analysis unreliable under the Daubert factors renders the expert's testimony inadmissible. ' Amorgianos v. Nat'l R.R. Passenger Corp., 303 F.3d 256, 267 (2002) (quoting In re Paoli R.R. Yard PCB Litig., 35 F.3d 717, 745 (3rd Cir.1994)). 46 When O'Donnell described how ephedrine damages blood vessels based on the PPA analogy, he stated that the longer one has exposure to a chemical, the more rigid a blood vessel becomes, and it takes time for the body to release a chemical even after the person stops taking the medicine. Thus, the drug can cause vasospasm or vasculitis and continue to cause these problems even after someone stops taking the drug. These steps are essential to his analysis of Metabolife's toxicity in general and for Plaintiffs' specific injuries. But he admitted that this theory has only been proven with PPA, not ephedrine. 47 O'Donnell cannot show that Metabolife causes vasospasm and vasculitis, which in turn causes ischemic strokes and heart attacks, except by a leap of faith. He also cannot show that Metabolife stays in the body for prolonged periods after someone stops taking it or that its effects linger. The medical articles do not support these conclusions. Speculation replaces science in this unreliable analogy between ephedrine and phenylpropanolamine. Subjective speculation that masquerades as scientific knowledge does not provide good grounds for the admissibility of expert opinions. Glastetter v. Novartis Pharm. Corp., 252 F.3d 986, 989 (8th Cir.2001). 48 According to O'Donnell, studies have shown that PPA causes vasospasm and vasculitis that lead to stroke and heart attack, and the studies also show that long-term use of the drug can cause a continuation of symptoms even after a person stops taking it. For these conclusions he relied primarily on the Hemorrhagic Stroke Project (HSP) that showed a 15-fold increase in the risk of hemorrhagic strokes in patients who took PPA as a diet supplement rather than as a cough and cold remedy. Horowitz, supra, at 2. These results, he said, should be reasonably analogized to ephedrine and especially ephedrine with caffeine. This analogy authorizes him to conclude that not only will ephedrine cause the hemorrhagic strokes demonstrated in the HSP from taking PPA, but also ischemic strokes and heart attacks. (None of the Plaintiffs in this case had hemorrhagic strokes.) Yet, he admitted that while the FDA banned PPA because of the risk of strokes, it authorized ephedrine to replace PPA in over-the-counter medications. But more importantly, the plain reading of the HSP article does not authorize O'Donnell's conclusions. 49 In 2000, the New England Journal of Medicine published the report on the Hemorrhagic Stroke Project. The report shows that the investigators devised and implemented a scientific approach to evaluate the toxicity of PPA. Id. The authors concluded that the results of the HSP suggest that PPA increases the risk for hemorrhagic strokes. For both individuals considering use of PPA and for policy-makers, the HSP provides important data for a contemporary assessment of risks associated with the use of PPA. Id. at 3. The authors draw no conclusions about ephedrine and nowhere say that ephedrine is analogous to PPA in any respect. 50 The authors likewise do not say that PPA is associated with ischemic stroke or heart attack or that one can analogize that because PPA may cause hemorrhagic strokes, it also causes ischemic strokes and heart attacks. Furthermore, the authors do not attempt to explain the physiological mechanism by which PPA causes strokes. Although O'Donnell contends that the PPA analogy supports his opinions that ephedrine causes vasospasm or vasculitis, nowhere in the HSP study do the authors assert this about PPA, much less about the ephedrine/caffeine combination. This study offers no support for O'Donnell's opinions. 51 But another methodological problem undermines O'Donnell's analogical approach. As Dr. Eaton explains: even small differences in chemical structure can sometimes make very large differences in the type of toxic response that is produced. See Eaton, supra, at 10-11. Likewise, as this court noted in Rider v. Sandoz Pharm. Corp., 295 F.3d 1194 (11th Cir.2002), [e]ven minor deviations in chemical structure can radically change a particular substance's properties and propensities. Id. at 1201 (citing Glastetter v. Novartis Pharm. Corp., 252 F.3d 986, 990 (8th Cir.2001)). O'Donnell failed to show that the PPA analogy is valid or that the differences in chemical structure between PPA and ephedrine make no difference. He simply assumes its validity without offering any scientific evidence. As he said, one presumes the same effect by drugs in the same class until proven otherwise. Such presumptions do not make for reliable opinions in toxic tort cases. (As Dr. Hakim admitted, if one product had the same effect as another product, it would be the same product.) 52 The court addressed drug analogies in detail in Rider where plaintiffs sued Sandoz claiming that they suffered postpartum hemorrhagic strokes from ingesting Parlodel to suppress lactation after childbirth. Id. at 1196. Plaintiffs' experts in that case followed an analogical approach similar to O'Donnell's. They testified that Parlodel (bromocriptine) is a member of a class of drugs known as ergot alkaloids, and that ergot alkaloids can cause vasoconstriction, which suggests that Parlodel causes vasoconstriction. Id. at 1198. Animal studies also suggest that Parlodel causes vasoconstriction. Id. Vasoconstriction can cause high blood pressure and ischemic stroke. Id. Because Parlodel can cause vasoconstriction, which causes high blood pressure resulting in ischemic stroke, it can also cause hemorrhagic stroke. Id. Thus, Parlodel caused plaintiffs' hemorrhagic strokes, according to Plaintiffs' experts. Id. 53 This drug analogy is stronger than O'Donnell's because in Rider the experts analogized from the same drug and also had some partial support for their theory from animal studies. 295 F.3d at 1200-02. O'Donnell, on the other hand, compares one drug, PPA, to a different drug, ephedrine, to reach his opinions that not only does ephedrine cause hemorrhagic stroke, as reported about PPA, it also causes ischemic stroke and heart attack. (Hemorrhagic stroke occurs when a blood vessel ruptures. Ischemic stroke occurs because of decreased blood flow to the brain.) The court in Rider properly rejected the testimony because of the unreliable analogy. Id. As the court stated, [e]vidence suggest[ing] that [a chemical] may cause ischemic stroke does not apply to situations involving hemorrhagic stroke. This is `a leap of faith' supported by little more than the fact that both conditions are commonly called strokes. Id. at 1202. 54 Finally, on O'Donnell's analogy methodology, he agreed that: [t]here is a tendency in the literature, particularly in government monographs, to lump together all ephedrine alkaloids. Doing so is both foolish and misleading as it implies that the toxicity of all enantiomers is equivalent, which is clearly not the case. After agreeing with this statement, he went on to say that it's not predictable. 55 This lack of predictability, O'Donnell's use of an unreliable analogy and his inclination to draw overreaching conclusions from self-limiting medical articles, show the speculative nature of his opinions. As Judge Posner explained: the courtroom is not the place for scientific guesswork, even of the inspired sort. Law lags science; it does not lead it. Rosen v. Ciba-Geigy Corp., 78 F.3d 316, 319 (7th Cir.1996).