Most of the lay public does not realize that many of the drugs they are prescribed were never approved by the FDA for the illness they are being treated for. After a drug is approved Doctors have great latitude in what they can prescribe for without FDA approval. Drug companies aren't supposed to but many push their drugs for purposes other than what the FDA approved the drugs for.
On the case of Neurotin an epilepsy drug, Pfizer pushed the drug big time for unapproved uses. One health care provided Kaiser said enough is enough and sued Pfizer. Below are excerpts from the Court opinion agreeing that enough is enough.
Annotation Summary for: 4-3-2013 Opinion (Kaiser Appeal)
Page 5, Highlight (Yellow):
Content: ” 2010, after a five-week trial, the jury concluded that”Kaiser prove[d] that Pfizer violated RICO with respect to itspromotion of Neurontin for” bipolar disorder, migraine, neuropathicpain,1 and dosages exceeding 1800 mg per day, and that these”violation[s] of RICO cause[d] Kaiser injury.” See In re NeurontinMktg. & Sales Practices Litig. (Kaiser Findings), No. 04-cv-10739-PBS, 2011 WL 3852254, at *1 (D. Mass. Aug. 31, 2011). “
Page 6, Highlight (Yellow):
Content: “superseded by Kaiser Findings, 2011 WL 3852254. The district court ordered defendants to pay $95,286,518 in restitution, Kaiser Findings, 2011 WL 3852254, at *2, but because this figure reflected the same damage claims encompassed by the jury verdict on Kaiser's RICO claim, the court did not add it to the jury award, id. at *60 n.25.”
Page 8, Highlight (Yellow):
Content: “In order to increase Neurontin's earning Parke-Davis began in 1995 to develop strategies to market Neurontin for off-label conditions — that is, conditions not included on the official label approved by the FDA. Id. As Parke-Davis was implementing these strategies, Pfizer acquired Warner-Lambert, and so, Parke-Davis. Id. at *5. These marketing strategies apparently worked; in the year 2003, Neurontin sales exceeded $2 billion. Id. at *6. Pfizer's Neurontin team estimated that only about ten percent of Neurontin prescriptions that year were for the FDA- approved on-label uses for epilepsy or PHN, and that more than a third of prescriptions were for the off-label uses of neuropathic pain, migraine or headache, or bipolar disorder.”
Page 9, Highlight (Yellow):
Content: ” This fraudulent marketing included, but was not limited3 to, three strategies, each of which included subcomponents: (1)direct marketing (or “detailing”) to doctors, which misrepresentedNeurontin's effectiveness for off-label indications; (2) sponsoringmisleading education informational (“CME”) supplements programs; and and (3) continuing suppressing medicalnegativeinformation about Neurontin while publishing articles in medicaljournals that reported positive information about Neurontin's off-label effectiveness. “
Page 12, Highlight (Yellow):
Content: “The district court found that “Kaiser relied on Pfizer's misrepresentations and omissions during the development of drug monographs in both June and September 1999,” id. at *29, and that Pfizer's misrepresentations “directly affected decisions about Neurontin's placement on formulary without restrictions,” id. at *30.”
Page 12, Highlight (Yellow):
Content: “Defendants stress that no physician in this case, or in the Neurontin MDL as a whole, testified that he or she prescribed Neurontin because of defendants' fraudulent off-label marketing. Id. at *32. But Kaiser presented other evidence as to causation, and evidence as to why such individual testimony was unreliable.”
Page 13, Highlight (Yellow):
Content: ” Id. Dr. Rosenthal “use[d] aggregate data andstatistical approaches to link patterns in promotional spending[ ]4 to patterns in prescribing for the drug.” Id. (internal quotationmark omitted). Her regression analysis found a causal connectionbetween the fraudulent marketing and the quantity of prescriptionswritten for off-label indications. She also testified as to whyPfizer's proposed physician-by-physician analysis of causation wasnot a scientifically valid approach to causation. “
Page 13, Highlight (Yellow):
Content: “Dr. Rosenthal used “gold standard” national Neurontin prescriptions, and employed the assumptions “Kaiser's patient population and physician distribution are similar to the national mix,” and (2) “promotional spending on off-label marketing was the same as the promotional spending on fraudulent off-label marketing.” Id. at *32-33. The district court found both assumptions to be reasonable. Id. at *32-33.”
Page 14, Highlight (Yellow):
Content: “a regression analysis on sales information spending on detailing, professional performing a regression analysis on sales information against promotional advertising, and the retail value of samples, while controlling for other variables. correlation and causation and stated that her analysis established causation by performing”
Page 15, Highlight (Yellow):
Content: “Dr. Rosenthal reasonable degree of scientific certainty that these calculations are the best way to estimate the number of prescriptions and the share of prescriptions that were affected by the alleged misconduct.” 5″
Page 15, Highlight (Yellow):
Content: “She said that self-reporting of practice that may be from physicians about patterns controversial shows both conscious reluctance and unconscious bias, which lead them to deny being influenced.”
Page 15, Highlight (Yellow):
Content: “Dr. Rosenthal utilized the standard practice of using “aggregate data and . . . statistical approaches to link patterns in promotional spending to patterns in prescribing for the drug.” Dr. Rosenthal testified that it was “neither standard nor appropriate to look physician by physician.””
Page 16, Highlight (Yellow):
Content: “The court also found that subsidiary evidence tended to causal link. For example, PMG physicians attended conferences where Neurontin was promoted for off-label uses, and after one such conference, in May 1999, new starts of Neurontin increased by 62%. Id. at *30.”
Page 19, Highlight (Yellow):
Content: “the district evidence that migraine, or at high evidence that Neurontin “there is no reliable scientific evidence that Neurontin is effective for bipolar disorder, high doses,” and that although there was evidence that Neurontin was effective in treating treating some kinds of neuropathic pain, “there is no reliable neuropathic scientific evidence to support a broad indication of neuropathic pain,” id. at *34.”
Page 21, Note (Yellow):
How did jury arrive at this number?
Page 21, Highlight (Yellow):
Content: “$47,363,092”
Page 22, Highlight (Yellow):
Content: “At the heart of law, Kaiser cannot matter the appeal is the claim that, as a matter of l meet the RICO or UCL causation requirements, and so Pfizer was entitled to a directed verdict.”
Page 22, Highlight (Yellow):
Content: “On appeal, Pfizer does not challenge the conclusions of the jury and district court that it engaged in a fraudulent scheme with respect to its promotion of Neurontin for off-label uses.”
Page 24, Highlight (Yellow):
Content: “The proximate causation question in this appeal concerns whether the chain of events between Pfizer's misrepresentations and Kaiser's payment for the prescriptions is so attenuated that, for legal and policy reasons, Kaiser's claim for recovery should be denied. The but-for causation question, incontrast, is whether, absent Pfizer's fraud, Kaiser would have paidfor fewer off-label Neurontin prescriptions. “
Page 30, Highlight (Yellow):
Content: “Here, like the defendants in Bridge, Pfizer argues that its supposed misrepresentations went to prescribing doctors, and so the causal link to Kaiser must have been broken. Even putting aside the evidence of Pfizer's direct communications to Kaiser, we think Bridge forecloses this argument. The Bridge Court rejected statutory language providing a private right of action under RICO, finding no support for it in the common law. See id. at 2139-41. We likewise find none here. the attempt to impose a direct reliance requirement on top of the”
Page 30, Highlight (Yellow):
Content: “likewise Here, Kaiser was likewise a “primary and intended victim[] of [Pfizer's] scheme to defraud.”10 Its injury was a “foreseeable”
Page 31, Highlight (Yellow):
Content: “natural consequence” of Pfizer's scheme, id. 2144 — a scheme that was designed to fraudulently inflate the number of Neurontin paid. prescriptions for which TPPs paid. scheme that was designed to fraudulently inflate the number of Neurontin prescriptions for which TPPs paid. The evidence that Pfizer had specifically targeted Kaiser for Neurontin sales in general supports the conclusion that Kaiser's injury was a natural”
Page 31, Highlight (Yellow):
Content: “consequence of Pfizer's fraudulent scheme, but such evidence was not required, given the mechanisms by which Pfizer's marketing operated. As Judge Posner stated in the Bridge case, after “The doctrine of proximate cause . . . protects the ability As Judge Posner stated in the Bridge case, plan remand: primary victims of wrongful conduct to obtain compensation . . . .” 2011). Here Kaiser was a primary victim. BCS”
Page 31, Highlight (Yellow):
Content: “Because Kaiser was both the natural and victim foreseeable victim of the fraud and the intended victim of the fraud, there is no risk of duplicative recovery.”
Page 33, Highlight (Yellow):
Content: “the core proximate causation principle of allowing compensation for those who are directly injured, whose injury was plainly foreseeable and was in fact foreseen, and were the intended victims of a defendant's wrongful conduct.12”
Page 35, Highlight (Yellow):
Content: “Pfizer now argues that because doctors exercise independent medical judgment in making decisions about prescriptions, the actions of these doctors are independent intervening intervening causes. But Pfizer's scheme relied on the expectation that physicians would base their marketing. prescribing decisions in part on Pfizer's fraudulent marketing. The fact that some physicians may have considered factors other materials than Pfizer's detailing materials in making their prescribing decisions does not add such attenuation to the causal chain as to eliminate proximate cause. Rather than showing a lack of proximate argument presents a question of proof regarding the causation, this total number of prescriptions that were attributable to Pfizer's actions. . This is a damages question.”
Page 36, Highlight (Yellow):
Content: “Holding Pfizer liable will have an effect in deterring wrongful that conduct. And the effect of that wrongful conduct was clear in foresight, not hindsight.”
Page 37, Highlight (Yellow):
Content: “would have absent such marketing. The latter type of evidence came from Dr. Rosenthal's report14 as well as inferences from other data. Pfizer has argued both that the direct reliance evidence was insufficient and that Dr. Rosenthal's aggregate evidence was inadmissible and insufficient. Pfizer's insufficiency claims rest (2) physicians caused PMG doctors to issue more Neurontin prescriptions than they”
Page 39, Highlight (Yellow):
Content: “attended a medical education conference in May 1999, new Neurontin prescriptions increased by 62 percent. Id. at *30. And significantly, when Kaiser conducted the DRUG and DUAT campaigns to reduce Neurontin usage after the negative information about Neurontin came to light, new prescriptions of Neurontin fell by about 33 percent. At the same time, such prescriptions continued to rise nationally. Id. at *31.”
Page 43, Highlight (Green):
Content: “nonetheless unreliable in this instance because it did not account for other factors that may have led a doctor to prescribe Neurontin for off-label use, particularly because the model did not include a “time trend.”15”
Page 43, Highlight (Green):
Content: “within The district court acted well within its discretion in concluding that Dr. Rosenthal's methods met the scientific validity”
Page 44, Highlight (Green):
Content: “standard under Rule 702.”
Page 44, Highlight (Green):
Content: “Pfizer's own expert witness admitted that peer-reviewed, published studies do not always contain time trends.”
Page 44, Highlight (Green):
Content: “trend would likely be a confounding variable, because its inclusionwould produce results showing that promotional spending had nostatistically significant effect on prescriptions — a conclusionthat would not comport with basic economics.”
Page 44, Highlight (Green):
Content: “Indeed, Pfizer's own expected and believed that would increase off-label prescriptions, and that its marketing had that result. The choice not to use a time trend did not make Dr. Rosenthal's methodology unreliable. Neurontin would of off-label marketing documents and testimony show that it”
Page 45, Highlight (Green):
Content: “Finally, Pfizer's argument about the 85% figure for model. of misunderstands nociceptive pain misunderstands the structure In the was fraudulent,16 then analyzed the relationship between marketing and prescriptions. Such an approach to proving injury from an underlying assumption of unlawful behavior (to be proven to the fact-finder) is well accepted in the antitrust context from which”
Page 45, Highlight (Green):
Content: “conducting her analysis, Dr. Rosenthal assumed — at plaintiffs' direction — that all off-label marketing”
Page 46, Highlight (Green):
Content: “RICO has drawn many of its causation principles.”
Page 46, Highlight (Green):
Content: “The basic thrust of Pfizer's argument argument is that Dr. Rosenthal's analysis does not provide insight into the”
Page 47, Highlight (Green):
Content: “quantity of prescriptions written as a result of Pfizer's alleged fraudulent marketing.”
Page 47, Highlight (Green):
Content: “The use of promotional spending as as a variable was a reasonable “fit” to represent Pfizer's fraud because Pfizer targeted its promotional activities toward PMG physicians and toward Kaiser itself, and the money it spent on promotion helped to implement its fraudulent publication strategy.”
Page 47, Highlight (Green):
Content: “Next, the use of national drug data was reasonable, and the district court did not abuse its discretion in so holding.”
Page 47, Highlight (Green):
Content: “this type of data is used Pfizer itself in its own strategic planning and marketing efforts.”
Page 48, Highlight (Green):
Content: “Finally, that Dr. Rosenthal's report assumed all of Pfizer's off-label marketing was fraudulent marketing is not a the basis to find that the district court erred in admitting the report.”
Page 48, Highlight (Green):
Content: “Dr. Rosenthal's analysis sought to determine whether Pfizer's marketing had a causal effect on prescribing behaviors, not whether the marketing was in fact fraudulent.”
Page 49, Highlight (Green):
Content: “b. Sufficiency of Aggregate Evidence”
Page 49, Highlight (Green):
Content: “Pfizer insists that Dr. Rosenthal's testimony cannot be into credited because it does not take into account the patient-specific, idiosyncratic decisions of individual prescribing physicians. Thus, according to Pfizer, the report was legally insufficient proof of causation.”
Page 49, Note (Yellow):
Key ruling on aggregate proof of causation in an off-label Rx case.
Page 49, Highlight (Yellow):
Content: “A tort plaintiff need not “prove a series of negatives; he doesn't have to 'offer evidence which positively exclude[s] every other possible cause of the accident.'” BCS Servs., 637 F.3dat 757 (alteration in original) (quoting Carlson v. Chisholm-MooreHoist Corp., 281 F.2d 766, 770 (2d Cir. 1960) (Friendly, J.)). “Once a plaintiff presents evidence that he suffered the sort ofinjury that would be the expected consequence of the defendant'swrongful conduct,” the burden shifts to the defendant to rebut thiscausal inference. Id. at 758. “
Page 50, Highlight (Yellow):
Content: “Pfizer's argument is a repetition of its assertion that there is an intervening cause — individual physicians' independent medical judgment — which precludes a finding of causation based on aggregate evidence. But “the burden of proving an 'intervening cause' — something which snaps the 'causal chain' (that is, operates as a 'superseding cause,' wiping out the defendant's liability) that connects the wrongful act to the defendant's injury — is on the defendant.” Id. at 757 (citation omitted). Pfizer did offer the testimony of doctors who said that their decisions to prescribe Neurontin were not influenced by Pfizer's fraudulent marketing, and the jury and district court, within their powers, rejected the argument.”
Page 50, Highlight (Yellow):
Content: “that they prescribed Neurontin for on Pfizer's misrepresentations statistical analysis. Not so. The existence of some doctors who purportedly were not influenced by Pfizer's misinformation would not defeat the inference that this misinformation had a significant influence on prescribing decisions which injured Kaiser. Indeed, Dr. Rosenthal noted the scientific invalidity of looking to physician-by-physician accounts of their prescribing decisions. aggregate evidence presented by Kaiser was a task for the jury and district court. on stated that Pfizer also argues that its testimony from doctors who relying on without misrepresentations “falsified” Kaiser's for off-label uses without Weighing the individual testimony presented by Pfizer against the”
Page 51, Note (Yellow):
Ct looks to fact company spent the money on the marketing to support use of aggregate proof.
Page 51, Highlight (Yellow):
Content: “demonstrated “correlation” and not “causation.” But if information could not be expected to affect a single decisionmaking, the company's choice to undertake the campaign would be inexplicable. Cf. id. at 758 (“The object [the defendants'] conspiracies was to obtain liens that would otherwise go to [the plaintiffs and other] bidders — there could be no other reason for wanting to pack the room in violation of the County's rule. . . . How likely is it that [plaintiffs] lost no bids to bidders who had 13 arms in the room but should have had only three?”). Pfizer next argues that the Rosenthal report merely if Pfizer's doctor's marketing”
Page 51, Note (Yellow):
Rejects argument precedent is against use of aggregate proof. Cases cited do undercut courts holding.
Page 52, Highlight (Yellow):
Content: ” To begin, the district court in Eli Lilly grantedclass certification on the former (excess pricing) claim, and theSecond Circuit reversed on that basis. See id. at 133. Bycontrast, the claimed injury to Kaiser resembles the latter (excessquantity) theory. The Second Circuit found a lack of but-forcausation only on the excess pricing theory, because doctors do notgenerally consider the price of a drug when they make prescribingdecisions. Id. at 133-34. On the other hand, doctors wouldcertainly consider information about the efficacy of a drug whendeciding whether to prescribe it for their patients. “
Page 54, Highlight (Yellow):
Content: “Courts' treatment of aggregate evidence is not as Pfizer the use of such aggregate evidence represents. Earlier we cited to reason to show causation under several causes of action. action. We see no reason specific subset of RICO o reach a different conclusion for the specific subset of RIC claims based on fraudulent marketing.”
Page 54, Highlight (Yellow):
Content: “And to the extent that some district courts may have endorsed Pfizer's position that aggregate evidence is legally insufficient to prove but-for causation, we disagree, at least on the facts of this case.”
Page 56, Highlight (Yellow):
Content: “standard Pfizer argues that the proper standard was the standard FDA governing the practice of medicine, not the standard for approval.21 practice, clinical approval.21 In clinical Pfizer argues, FDA-type trials own their are not dispositive; instead, physicians rely on their experience, other doctors' positive clinical experiences, and other”
Page 57, Highlight (Yellow):
Content: “evidence.”
Page 57, Highlight (Yellow):
Content: “Randomized controlled studies like DBRCTs are widely accepted as “ideally suited” for showing causation and as a “good measure of the treatment effect.” D. Kaye & D. Freedman, Reference on Scientific Evidence 211, 218, 220 (3d ed. 2011). Where, as Center, Reference Manual”
Page 58, Highlight (Yellow):
Content: “indicate numerous here, DBRCTs indicate that a drug is ineffective, that provides powerful scientific evidence of inefficacy, particularly as compared to anecdotal experiences, which can be tainted by the placebo effect.”
Page 58, Highlight (Yellow):
Content: “evidence As one [in medical ineffective unless it's proven otherwise.” a null hypothesis that the drug is no more effective than placebo. In this case, DBRCTs repeatedly showed that there was not enough evidence to reject the null hypothesis for the indications at issue. See Kaiser Findings, 2011 WL 3852254, at *35-45. Pfizer's claimed evidence of Neurontin's efficacy came from less convincing sources. in this witness this trial testified, “the default position [in medical decisionmaking] is that a drug is Experiments start with”
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