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Manganese Meta-Analysis Further Undermines Reference Manual’s Toxicology Chapter

October 15th, 2012

Last October, when the ink was still wet on the Reference Manual on Scientific Evidence (3d 2011), I dipped into the toxicology chapter only to find the treatment of a number of key issues to be partial and biased. See “Toxicology for Judges – The New Reference Manual on Scientific Evidence” (Oct. 5, 2011).

The chapter, “Reference Guide on Toxicology,” was written by Professor Bernard D. Goldstein, of the University of Pittsburgh Graduate School of Public Health, and Mary Sue Henifin, a partner in the law firm of Buchanan Ingersoll, P.C. In particular, I noted the authors’ conflicts of interest, both financial and ideological, which may have resulted in an incomplete and tendentious presentation of important concepts in the chapter. Important concepts in toxicology, such as hormesis, were omitted completely from the chapter. See, e.g., Mark P. Mattson and Edward J. Calabrese, eds., Hormesis: A Revolution in Biology, Toxicology and Medicine (N.Y. 2009); Curtis D. Klaassen, Casarett & Doull’s Toxicology: The Basic Science of Poisons 23 (7th ed. 2008) (“There is considerable evidence to suggest that some non-nutritional toxic substances may also impart beneficial or stimulatory effects at low doses but that, at higher doses, they produce adverse effects. This concept of “hormesis” was first described for radiation effects but may also pertain to most chemical responses.”)(internal citations omitted); Philip Wexler, et al., eds., 2 Encyclopedia of Toxicology 96 (2005) (“This type of dose–response relationship is observed in a phenomenon known as hormesis, with one explanation being that exposure to small amounts of a material can actually confer resistance to the agent before frank toxicity begins to appear following exposures to larger amounts. However, analysis of the available mechanistic studies indicates that there is no single hormetic mechanism. In fact, there are numerous ways for biological systems to show hormetic-like biphasic dose–response relationship. Hormetic dose–response has emerged in recent years as a dose–response phenomenon of great interest in toxicology and risk assessment.”).

The financial conflicts are perhaps more readily appreciated. Goldstein has testified in any number of so-called toxic tort cases, including several in which courts had excluded his testimony as being methodologically unreliable. These cases are not cited in the Manual. See, e.g., Parker v. Mobil Oil Corp., 7 N.Y.3d 434, 857 N.E.2d 1114, 824 N.Y.S.2d 584 (2006) (dismissing leukemia (AML) claim based upon claimed low-level benzene exposure from gasoline) , aff’g 16 A.D.3d 648 (App. Div. 2d Dep’t 2005); Exxon Corp. v. Makofski, 116 S.W.3d 176 (Tex.App.–Houston [14th Dist.] 2003, pet. denied) (benzene and ALL claim).

One of the disappointments of the toxicology chapter was its failure to remain neutral in substantive disputes, unless of course it could document its position against adversarial claims. Table 1 in the chapter presents, without documentation or citation, a “Sample of Selected Toxicological End Points and Examples of Agents of Concern in Humans.” Although many of the agent/disease outcome relationships in the table are well accepted, one was curiously unsupported at the time; namely the claim that manganese causes Parkinson’s disease (PD). Reference Manual at 653.This tendentious claim undermines the Manual’s attempt to remain disinterested in what was then an ongoing litigation effort. Last year, I noted that Goldstein’s scholarship was questionable at the time of publication because PD is generally accepted to have no known cause. Claims that manganese can cause PD had been addressed in several reviews. See, e.g., Karin Wirdefeldt, Hans-Olaf Adami, Philip Cole, Dimitrios Trichopoulos, and Jack Mandel, “Epidemiology and etiology of Parkinson’s disease: a review of the evidence. 26 European J. Epidemiol. S1, S20-21 (2011); Tomas R. Guilarte, “Manganese and Parkinson’s Disease: A Critical Review and New Findings,” 118 Environ Health Perspect. 1071, 1078 (2010) (“The available evidence from human and nonhuman primate studies using behavioral, neuroimaging, neurochemical, and neuropathological end points provides strong support to the hypothesis that, although excess levels of [manganese] accumulation in the brain results in an atypical form of parkinsonism, this clinical outcome is not associated with the degeneration of nigrostriatal dopaminergic neurons as is the case in PD.”).

More recently, three neuro-epidemiologists have published a systematic review and meta-analysis of the available analytical epidemiologic studies. What they found was an inverse association between welding, a trade that involves manganese fume exposure, and Parkinson’s disease. James Mortimer, Amy Borenstein, and Lorene Nelson, “Associations of welding and manganese exposure with Parkinson disease: Review and meta-analysis,” 79 Neurology 1174 (2012).

Here are the summary figures from the published meta-analysis:

The Fourth Edition should aim at a better integration of toxicology into the evolving science of human health effects.

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Hop on Pop Redux – Watson Case

October 3rd, 2012

Last month, Maxwell Kennerly of the Beasley Firm in Philadelphia posted about the Watson case in his blog. See Max Kennerly, “The Science And Law Behind The $7 Million Microwave Popcorn Lung Jury Verdict” (Sept. 20, 2012). This case has attracted a lot of attention, as it well should. See “It’s Alimentary, My Dear Watson” (Sept. 20, 2012); and “Good’s Expert Witness Opinion Not Good Enough in Tenth Circuit” (Sept. 8, 2012).

Kennerly is correct that we should not lump the Watson case with other frivolous cases, such as the infamous McDonald’s hot-coffee spill case. I suppose people can debate whether McDonald’s sold their coffee at too-high a temperature, but most civilized people can agree that McDonald’s makes bad coffee, and that everyone should be careful what they put between their legs, regardless of temperature.

Watson represents a paradigmatic tort case, involving exposure and diagnostic issues common to many toxic tort cases. Mr. Watson was a mega-consumer of microwavable popcorn, flavored with diacetyl. We can assume for discussion that diacetyl can cause bronchiolitis obliterans in factory workers who are exposed at relatively high levels. There are, however, other causes, as well as idiopathic cases. Two uncertainties overlapped in the Watson case: diagnosis and exposure assessment. A treating physician pondered a differential diagnosis between hypersensitivity pneumonitis (HP) and bronchiolitis obliterans (BO). As a carpet cleaner, Watson had occupational exposures that might well have caused HP. Indeed, in August 2006, an open lung biopsy requested by his treating physicians, by pathologists at University Hospital, at the University of Colorado, interpreted Watson’s lung pathology as HP. In 2010, Professor Eugene Mark, a well-known pulmonary pathologist at Harvard Medical School, interpreted the pathology as “in keeping with hypersensitivity pneumonitis.” Although Dr. Mark was consulting for the defense in this case, he is not a frequent testifier, and his few forays have been almost always for plaintiffs in asbestos cancer cases. To my understanding, none of the pathologists testified at the trial.

Despite the pathology report, Watson’s treating physician, Dr. Cecile Rose, advocated that the correct diagnosis was BO. She wrote a letter to NIOSH, and other federal agencies, in which advanced her diagnosis, although she did not mention the hospital pathology. Regulators and lawyers became involved. NIOSH measurements of diacetyl in Watson’s home were below the level of detection. Another set of diacetyl measurements taken by Watson’s legal team reported levels close to that of the industrial workers who sustained BO from workplace exposure to diacetyl. The plaintiffs’ expert witnesses relied upon these measurements suggesting high exposure. Just before trial, the defense renewed its Rule 702 motion, challenging the plaintiffs’ exposure level evidence. The defendant’s motion sought preclusion of the plaintiffs’ expert witnesses’ reliance upon data generated by an Innova Model 1312 Photoacoustic Multi-Gas Monitor. The court denied this motion, with leave to raise it at trial, and also precluded mention of the testing in front of the jury until the evidentiary matter is resolved. Order of June 22, 2012. I do not know how the court handled this important evidentiary issue at trial, and no analysis of the case is possible until this part of the story is told.

What can be said now, hypothetically, is that if the plaintiffs had no reliable evidence of high exposure, there was precious little in the exposure data to support Watson’s treating physician’s argument for BO, over HP. The treating clinician did not settle on the BO diagnosis until she had the dubious exposure data. The pathology reports consistently favored the HP diagnosis.

Watson is the third consumer diacetyl case litigated to date. The Newkirk case resulted in the 702 exclusion of plaintiffs’ expert witness, Dr. Egilman. Newkirk v. ConAgra Foods, Inc., 727 F. Supp. 2d 1006 (E.D.Wash. 2010), aff’d, 438 Fed.Appx. 607 (9th Cir. 2011). See also Egilman v. ConAgra Foods, Inc., No. 10-35667, U.S. Court of Appeals for the Ninth Circuit (Sept. 5, 2012; unpublished memorandum) (refusing personal appeal of expert witness who claimed defamation and “wrongful exclusion” by district court). A second case was tried to a jury verdict for the defense, and the appellate court upheld the judgment for the defense. Khoury v. Conagra Foods, Inc., 368 S.W.3d 189 (Mo. Ct. App. 2012).

Kennerly argues that Watson had proof! Referring to “evidence” as “proof” is a hyperbolic conceit of lawyers; I am sure have used the expression, as well. Outside the legal world, proofs and demonstrations are the work of geometers and mathematicians; factual propositions are usually more modestly shown or suggested by evidence. The “proof” that Kennerly cites is the testimony of Watson’s treating physician, Dr. Cecile Rose, MD, MPH, “a published expert and researcher of occupational pulmonary diseases,” who testified that the basis for her opinion:

“relates mainly to the fact that his lung disease has stabilized with the cessation of use of the product and exposure to the inhalants related with that product. The fact that there was no other causal explanation for his lung condition and the fact that the clinical findings in his lung disease were similar to those that occurred in workers who were exposed to butter flavoring also support that opinion.”

This is the same Dr. Rose who wrote to several federal regulatory agencies, to present a tendentiously abridged clinical case report of a patient with BO, who consumed thousands of bags of microwave diacetyl-flavored popcorn. Even with the serious omissions of information, and the problematic exposure measurements, Dr. Rose hedged in her attribution:

“It is difficult to make a causal connection based on a single case report. We cannot be sure that this patient’s exposure to butter flavored microwave popcorn from daily heavy preparation has caused his lung disease. However, we have no other plausible explanation. Given the public health implications of this possibility, we wanted to alert you to our concerns.”

To be sure, this is nothing like the McDonald’s coffee-spill case. This is a case of questioned and questionable science. Kennerly is correct; there is nothing frivolous about the Watson case. If the diagnosis were correct, and the exposure measurements were accurate, this case would raise very serious public concerns for consumer exposure to diacetyl. If the antecedents of the BO diagnosis are incorrect, then the judicial system has been snookered, again. The view from over 2,600 kilometers away suggests that the antecedent conditions were unlikely.

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Siracusano Dicta Infects Daubert Decisions

September 22nd, 2012

Gatekeeping is sometimes intellectually challenging, but the challenge does not excuse sloppy thinking. Understandably, judges will sometimes misunderstand the relevant science. The process, however, allows the public and the scientific community to see what is happening in court cases, rather than allowing the critical scientific reasoning to be hidden in the black box of jury determinations. This transparency can and should invite criticism, commentary, corrections, and consensus, when possible.

Bad legal reasoning is much harder to excuse. The Supreme Court, in Matrixx Initiatives, Inc. v. Siracusano, 131 S. Ct. 1309 (2011), unanimously affirmed the reversal of a trial court’s Rule 12(b)(6) dismissal of a securities fraud class action. The corporate defendant objected that the plaintiffs failed to plead statistical significance in alleging causation between Zicam and the loss of the sense of smell. The Supreme Court, however, made clear that causation was not required to make out a claim of securities fraud. It was, and would be, sufficient for the company’s product to have raised sufficient regulatory concerns, which in turn would bring regulatory scrutiny and action that would affect the product’s marketability.

The Supreme Court could have disposed of the essential issue in a two page per curiam opinion. Instead the Court issued an opinion signed by Justice Sotomayor, who waxed carelessly about causation and statistical significance, which discussion was not necessary to the holding. Not only was Justice Sotomayor’s discussion obiter dicta, but the dicta were demonstrably incorrect. Matrixx Unloaded (Mar. 29, 2011).

The errant dicta in Siracusano has already led one MDL court astray:

“While the defendant repeatedly harps on the importance of statistically significant data, the United States Supreme Court recently stated that ‘[a] lack of statistically significant data does not mean that medical experts have no reliable basis for inferring a causal link between a drug and adverse events …. medical experts rely on other evidence to establish an inference of causation.’ Matrixx Initiatives, Inc. v. Siracsano, 131 S.Ct. 1309, 1319 (2011).”

Memorandum Opinion and Order at 22, In re Chantix (Varenicline) Products Liability Litigation, MDL No. 2092, Case 2:09-cv-02039-IPJ Document 642 (N.D. Ala. Aug. 21, 2012)[hereafter cited as Chantix]. See Open Admissions for Expert Witnesses in Chantix Litigation.

It was only a matter of time before the Supreme Court’s dictum would be put to this predictably erroneous interpretation. See “The Matrixx Oversold” (April 4, 2011). Within two weeks, the error in Chantix propagated itself in another MDL case, with another trial court succumbing to the misleading dicta in Justice Sotomayor’s opinion. See Memorandum in Support of Separate Pretrial Order No. 8933, Cheek v. Wyeth Pharm. Inc. (E.D.Pa. Aug. 30, 2012)(Bartle, J.).

In Cheek, Judge Harvey Bartle rejected a Rule 702 challenge to plaintiffs’ expert witness’s opinion. I confess that I do not know enough about the expert witness’s opinion or the challenge to assess Judge Bartle’s conclusion. Judge Bartle, however, invoked the Matrixx decision for the dubious proposition that:

“Daubert does not require that an expert opinion regarding causation be based on statistical evidence in order to be reliable. Matrixx Initiatives, Inc. v. Siracusano, 131 S. Ct. 1309, 1319 (2011). In fact, many courts have recognized that medical professionals often base their opinions on data other than statistical evidence from controlled clinical trials or epidemiological studies. Id. at 1320.”

Cheek at 16. The Cheek decision is a welter of non-sequiturs. The fact that in some instances statistical evidence is not necessary is hardly a warrant to excuse the lack of statistical evidence in every case. The truly disturbing gaps in reasoning, however, are not scientific, but legal. Siracusano was not a “Daubert” opinion; and Siracusano does not, and cannot, support the refusal to inquire whether statistical evidence was necessary in a causation opinion, in main part because causation was not at issue in Siracusano.

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Bipartisan Junk Science – Pork-Barrel Causation

September 19th, 2012

Despite the hand waving and finger pointing, junk science is embraced by both political parties in the United States, when it suits their purposes. Both parties want to have God and science on their sides.

Congress created September 11th Victim Compensation Fund, 49 USC § 40101, also known as the James Zadroga 9/11 Health and Compensation Act (P.L. 111-347) (signed into law in January 2011). The Act was a touching acknowledgement of the dedication and sacrifices of first responders to the World Trade Center and Pentagon victims of an Islamic jihad. Being a victim, however, implies that the harm to be compensated was caused by the attack and its consequences. The New York politicians soon learned that causality can be turned into a very malleable concept.

The law allocated over $4 billion for medical screening and treatment of fire fighters, policemen, emergency responders, and survivors. Most of the covered conditions were acute onset respiratory and mental disorders caused by gases, fumes, dusts, and stresses, to which the workers were exposed. The law also made the director of CDC’s National Institute for Occupational Safety and Health (NIOSH), the head of a World Trade Center Health Program, which could add new conditions to the list of compensable diseases, based upon a review of scientific evidence.

In September 2011, several New York congressmen and Senators petitioned the director, citing flimsy or non-existent scientific evidence, to add cancer to the list. Senators Kirsten Gillibrand (D-NY) and Charles Schumer (D-NY), and Representatives Carolyn Maloney (D-NY), Jerrold Nadler (D-NY), Peter King (R-NY), Charles Rangel (D-NY), Nita Velazquez (D-NY), Michael Grimm (R-NY), and Yvette Clark (D-NY), made their request, citing R. Zeig-Owens, M. Webber, C.B. Hall, et al., “Early assessment of cancer outcomes in New York City firefighters after the 9/11 attacks: an observational cohort study,” 378 Lancet 898 (2011).

This is pork barrel politics masquerading as sympathy for putative victims. The Zeig-Owens study reported a non-statistically significant standardized incidence ratio for all cancer, of either 1.10 (95% CI 0.98–1.25), with a comparison group of the generalized U.S. male population, or 1.19 (95% CI 0.96–1.47), with unexposed firefighters as a comparison group, and corrected for possible surveillance bias. Of course, given that there is no disease of cancer, the composite end point is not particularly meaningful.

Here are the authors’ (including Dr. Prezant’s) published interpretation of the data:

“We reported a modest excess of cancer cases in the WTC-exposed cohort. We remain cautious in our interpretation of this finding because the time since 9/11 is short for cancer outcomes, and the reported excess of cancers is not limited to specific organ types. As in any observational study, we cannot rule out the possibility that effects in the exposed group might be due to unidentified confounders.”

Zeig-Owens, at 898. The Zeig-Owens study did not support any conclusions of causality between the workers’ exposures in 2001, and any type of cancer. See NIOSH Report Sets Up Run on September 11th Victim Compensation Fund by Non-Victims.

The WTC Health Program director requested recommendations from the program’s Scientific – Technical Advisory Committee (STAC), whether to add cancer generally, or any particular kind of cancer, to the Zadroga Act’s list of compensable conditions. In April 2012, the STAC made its recommendations, essentially relying upon likely exposures, without any consideration of individual dose, duration, latency, and without any serious consideration of the available epidemiologic evidence.

The STAC claimed that the Lancet study reported statistically significant excesses of cancer; it did not. The Committee also failed to come to grips with the biological implausibility of excess rates of solid malignant tumors presenting within less than a decade since exposure:

“Given that cancer latencies for solid tumors average 20 years or more, it is noteworthy that the published FDNY study of fire fighters showed a statistically significant excess in all-site cancer with only 7 years of follow-up.”

In June 2012, NIOSH director, Dr. Howard, reported that he was inclined to accept the STAC’s recommendation, but held open a public comment period. See Anemona Hartocollis, “Sept. 11 Health Fund Given Clearance to Cover Cancer,” N.Y. Times (June 8, 2012). Not surprising, given the political pressure, the WTC Health Program director promulgated his final rule to include 50 types of cancer, including many that occurred less often than expected in the Zeig-Owens study.

This decision ignores appropriate scientific methodology for reaching causal conclusions. Worse than its intellectual shabbiness, the decision insults the true victims of the jihad terrorism.

The rule is effective October 12, 2012.

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The Supreme Court’s Unsteady Gatekeeping Pre-Daubert

September 8th, 2012

Some writers assert that the United States Supreme Court did not wade into the troubled waters of medical causation and expert witness testimony until it decided Daubert v. Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993). Actually, the Court swam in these stormy waters in admiralty and FELA cases, at least up through the 1950’s.

In 1953, Mr. Sentilles, a marine engineer, was thrown to the deck of his ship, and washed off deck, by a wave. He became ill with tuberculosis, and he brought a person injury action (for “maintenance and cure”) against vessel owner. Inter-Caribbean Shipping Corp. v. Sentilles, 256 F.2d 156 (5th Cir. 1958). The vessel owner defended on the theory that the plaintiff’s diabetes pre-disposed him to TB, and that the plaintiffs’ expert witnesses were equivocal in their conclusions of causality or aggravation. The jury nonetheless found for the plaintiff.

The judgment entered on a jury verdict for the seaman was reversed by the Fifth Circuit, which found the plaintiffs’ expert witnesses’ testimony inadequate to support submission of the case to the jury:

“The rule as to the medical testimony respecting causation which is required to take a case to a jury has been thus stated:

It appears to be well settled that medical testimony as to the possibility of a causal relation between a given accident or injury and the subsequent death or impaired physical or mental condition of the person injured is not sufficient, standing alone, to establish such relation. By testimony as to possibility is meant testimony in which the witness asserts that the accident or injury `might have’, `may have’, or `could have’ caused, or `possibly did’ cause the subsequent physical condition or death or that a given physical condition (or death) `might have,’ `may have,’ or `could have’ resulted or `possibly did’ result from a previous accident or injury — testimony, that is, which is confined to words indicating the possibility or chance of the existence of the causal relation in question and does not include words indicating the probability or likelihood of its existence.”

Id. (internal citations omitted).

The Supreme Court granted a writ of certiorari, heard argument, and reversed the Court of Appeals. Sentilles v. Inter-Caribbean Shipping Corp., 361 U.S. 107 (1959). In announcing the Court’s opinion, Justice Brennan voiced the remarkable doctrine that the jury could find reasonable probability when the expert witnesses could not:

“The jury’s power to draw the inference that the aggravation of petitioner’s tubercular condition, evident so shortly after the accident, was in fact caused by that accident, was not impaired by the failure of any medical witness to testify that it was in fact the cause. Neither can it be impaired by the lack of medical unanimity as to the respective likelihood of the potential causes of the aggravation, or by the fact that other potential causes of the aggravation existed and were not conclusively negated by the proofs. The matter does not turn on the use a of particular form of words by the physicians in giving their testimony. The members of the jury, not the medical witnesses, were sworn to make a legal determination of the question of causation. They were entitled to take all the circumstances, including the medical testimony into consideration. Though this case involves a medical issue, it is no exception to the admonition that, ‘It is not the function of a court to search the record for conflicting circumstantial evidence in order to take the case away from the jury on a theory that the proof gives equal support to inconsistent and uncertain inferences. The focal point of judicial review is the reasonableness of the particular inference or conclusion drawn by the jury. * * * The very essence of its function is to select from conflicting inferences and conclusions that which it considers most reasonable. * * * Courts are not free to reweigh the evidence and set aside the jury verdict merely because the jury could have drawn different inferences or conclusions or because judges feel that other results are more reasonable.’”

Id. at 109-10. Justice Brennan thus ignored equally venerable precedent that juries are not free to speculate, and he failed to consider how the jury in this case could reach a determination in the face of conflicting evidence, and without ruling out alternative causes.

Sentilles was decided before the enactment of the Federal Rules of Evidence, and there was no challenge to the plaintiff’s expert witnesses’ testimony under the Frye doctrine. Another crucial difference, of course, is that Sentilles was an isolated case, not likely to recur frequently in the federal courts. With the rise of product liability law, and the emergence of epidemiology as a basis for inferring causality, the federal courts would soon see mass exposure situations resulting in mass torts. Dubious expert witness testimony resulting in dubious judgments of causation would attain much greater notoriety, for the expert witnesses, for the trial bar, and for the courts that tolerated the results.

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David Egilman’s Methodology for Divining Causation

September 6th, 2012

If the Method Yields An Erroneous Conclusion, then the Method is Wrong

David Stephen Egilman wanted very much to testify in a diacetyl case. One judge, however, did not think that this was such a good idea, and excluded Dr. Egilman’s testimony. Newkirk v. Conagra Foods, Inc. 727 F.Supp. 2d 1006 (E.D. Wash. 2010).

Egilman was so distraught by being excluded that he sought to file a personal appeal to the United States Court of Appeal. See “Declaration of David Egilman, M.D., M.P.H., in Support of Opposition to Motion for Order to Show Cause Why Appeal Should Not Be Dismissed for Lack of Standing.” (Attached: Egilman Motion Appeal Diacetyl Exclusion 2011 and Egilman Declaration Newkirk Diacetyl Appeal 2011.)

Egilman improvidently, if not scurrulously, attacked the district judge for having excluded Egilman’s proffered testimony. If Egilman’s attack on the trial judge were not sufficiently odd, Egilman also claimed a right to intervene in the appeal by advancing the claim that the Rule 702 exclusion hurt his livelihood. Here is how Egilman put the matter:

“The Daubert ruling eliminates my ability to testify in this case and in others. I will lose the opportunity to bill for services in this case and in others (although I generally donate most fees related to courtroom testimony to charitable organizations, the lack of opportunity to do so is an injury to me). Based on my experience, it is virtually certain that some lawyers will choose not to attempt to retain me as a result of this ruling. Some lawyers will be dissuaded from retaining my services because the ruling is replete with unsubstantiated pejorative attacks on my qualifications as a scientist and expert. The judge’s rejection of my opinion is primarily an ad hominem attack and not based on an actual analysis of what I said – in an effort to deflect the ad hominem nature of the attack the judge creates ‘straw man’ arguments and then knocks the straw men down, without ever addressing the substance of my positions.”

Egilman Declaration at ¶ 11.

The Ninth Circuit, unmoved by the prospect of an impoverished Dr. Egilman, denied his personal appeal, and affirmed the district court’s exclusion. Newkirk v. Conagra Foods, Inc., 438 Fed. Appx. 607 (9th Cir. 2011).

In his appellate papers, Egilman did not stop at simply citing his pecuniary interest. With no sense of false shame or modesty, Egilman recited what a wonderful expert witness he has been. Egilman suggested that courts have been duly impressed by his views on the scientific assessment of causation:

“My views on the scientific standards for the determination of cause-effect relationships (medical epistemology) have been cited by the Massachusetts Supreme Court (Vassallo v. Baxter Healthcare Corporation, 428 Mass. 1 (1998)):

‘Although there was conflicting testimony at the Oregon hearing as to the necessity of epidemiological data to establish causation of a disease, the judge appears to have accepted the testimony of an expert epidemiologist that, in the absence of epidemiology, it is “sound science…. to rely on case reports, clinical studies, in vivo tests and animal tests.” The judge may also have relied on the affidavit of the plaintiff’s epidemiological expert, Dr. David S. Egilman, who identified several examples in which disease causation has been established based on animal and clinical case studies alone to demonstrate that “doctors utilize epidemiological data as one tool among many”.’”

Egilman Declaration at p.5-6.

We may excuse Dr. Egilman, a non-lawyer, for incorrectly referring to a non-existent court. Massachusetts does not have a “Supreme Court,” but the quoted language did indeed come from the Supreme Judicial Court of Massachusetts, in Vassallo v. Baxter Healthcare Corporation, 428 Mass. 1, 12, 696 N.E.2d 909, 917 (1998).

The Massachusetts court’s suggestion that there was conflicting testimony at the “Oregon hearing,” about the need for epidemiologic evidence is itself rather bizarre. The Oregon hearing was the Rule 702 hearing before Judge Jones, of the District of Oregon. Judge Jones appointed four technical advisors to assist him in ruling on the defendants’ motions to exclude plaintiffs’ causation opinions. One of the appointed advisors was an epidemiologist. More important, the plaintiffs’ counsel presented the testimony of an epidemiologist, Dr. David Goldsmith. The Massachusetts court did not, and indeed, could not cite the Oregon District Court’s opinion, or the underlying record, for any suggestion that epidemiologic testimony was not needed to show a causal relationship between silicone breast implants and the development of autoimmune disease. See Hall v. Baxter Healthcare Corp., 947 F. Supp. 1387 (D. Or. 1996). Judge Jones made his views very clear: epidemiology was needed, but lacking, in the plaintiffs’ case. The argument that epidemiology was unnecessary came from Dr. Egilman’s report, and the plaintiffs’ counsel’s briefs.

There is more, however, to the disingenuousness of Dr. Egilman’s citation to the Vassallo case. The Newkirk court, in receiving his curious affidavit, would not likely know that Vassallo was a silicone gel breast implant case, and one may suspect that Dr. Egilman wanted to keep the Ninth Circuit uninformed of his role in the silicone litigation. If Dr. Egilman submitted an affidavit in connection with the so-called Oregon hearings, which took place during the summer of 1996, it was not a particularly important piece of evidence. Egilman is not mentioned by name in the Hall decision, even though the district court clearly rejected the plaintiffs’ witnesses and affiants, in their efforts to make a case for silicone as a cause of autoimmune disease.

A few months after the Oregon hearings, Judge Weinstein, in the fall of 1996, along with other federal and state judges, held a “Daubert” hearing on the admissibility of expert witness opinion testimony in breast implant cases, pending in New York state and federal courts. Plaintiffs’ counsel suggested that Egilman might testify, but ultimately he was a no show. After the New York hearings, Judge Weinstein granted, sua sponte, partial summary judgment against all plaintiffs’ claims of systemic immune-system injury. In re Breast Implant Cases, 942 F. Supp. 958 (E.&S.D.N.Y. 1996).

At the New York hearings, plaintiffs’ counsel again attempted to make an epidemiologic case, and once again called Dr. David Goldsmith. Marshaling the evidentiary display that Egilman would have presented had he shown up in New York, Dr. Goldsmith’s testimony did not go well. At one point, Judge Weinstein interrupted and offered his interim assessment of Dr. Goldsmith and the plaintiffs causation case:

THE COURT: Why are you presenting this witness, for epidemiological purposes?

MR. GORDON: That’s correct.

THE COURT: And I can tell you for epidemiological purposes, based on the only testimony I have seen, he doesn’t meet my standard of anybody who can be helpful to a jury, not because he isn’t a great epidemiologist, I’m sure he is, but because the data he is relying on admittedly is almost useless. I’m not going to go forward with a trial on this kind of haphazard abstract without any basic definition or explication.

Transcript at p.159:7-18, from Nyitray v. Baxter Healthcare Corp., CV 93-159 (E.D.N.Y. Oct. 9, 1996)(pre-trial hearing before Judge Jack Weinstein, Justice Lobis, and Magistrate Cheryl Pollak). In his semi-autobiographical writings, Judge Jack B. Weinstein elaborated upon his published breast-implant decision, with a bit more detail about how he viewed the plaintiffs’ expert witnesses. Judge Jack B. Weinstein, “Preliminary Reflections on Administration of Complex Litigation” 2009 Cardozo L. Rev. de novo 1, 14 (2009) (describing plaintiffs’ expert witnesses in silicone litigation as “charlatans”; “[t]he breast implant litigation was largely based on a litigation fraud. … Claims—supported by medical charlatans—that enormous damages to women’s systems resulted could not be supported.”)

When Judge Weinstein began to create a process for the selection of Rule 706 court-appointed expert witnesses, plaintiffs’ counsel rushed to have Judge Pointer take control over the process. Because Judge Pointer believed that there must be some germ of validity in the plaintiffs’ case, the plaintiffs were hoping that his courtroom, the center of MDL 926, would be a more favorable forum than Judge Weinstein’s withering skepticism. Ultimately, Judge Pointer, through a select nominating committee, appointed appointed expert witnesses, in the fields of toxicology, immunology, rheumology, and epidemiology. MDL 926 Order No. 31 (Appointment of Rule 706 Expert Witnesses).

Each of the four witnesses prepared, presented, and defended his or her own report, but all the reports soundly rejected plaintiffs’ causation theories. Laural L. Hooper, Joe S. Cecil, and Thomas E. Willging, Neutral Science Panels: Two Examples of Panels of Court-Appointed Experts in the Breast Implants Product Liability Litigation (Fed. Jud. Ctr. 2001).

In the United Kingdom, the British Minister of Health ordered an independent review of the breast implant controversy, which led to the formation of the Independent Review Group (IRG) to evaluate the causal claims that were being made by claimants and advocates. The IRG concluded that there was no demonstrable risk of connective tissue disease from silicone breast implants. Independent Review Group, Silicone Breast Implants: The Report of the Independent Review Group 8, 22-23 (July 1998).

In 1999, The Institute of Medicine delivered its assessment of the safety of silicone breast implants. Again, the plaintiffs’ theories were rejected. Stuart Bondurant, Virginia Ernster, and Roger Herdman, eds., Safety of Silicone Breast Implants (1999).

Still, Egilman persisted. As late as 2000, Egilman was posting his breast-implant litigation report at his Brown University website. His conclusion, however awkwardly worded, was clear enough:

“Although a prospective, large epidemiological study investigating atypical symptoms and disease would clearly contribute to underestimating of the strength of association between silicone breast implants and disease, the available epidemiologic evidence is suggestive of a causal association for silicone breast implants and atypical connective tissue diseases and scleroderma.”

David S. Egilman, “Breast Implants and Disease” (2000) (“For purposes of this report SBI induced disease is considered an iatrogenic environmental disease.”) (<http://209.67.232.40/brown/implants/sbi.html> lasted visited on Mar. 28, 2000).

Sometime after 2000, Egilman developed a sensitivity to being associated with the plaintiffs’ side of the silicone litigation. In 2009, Dr. Laurence Hirsch, published an article critical of Egilman’s disclosures of conflicts of interest, in some of his published articles. Hirsch struck a sensitive nerve in mentioning Egilman’s involvement in the breast implant litigation:

“Egilman reports having testified for plaintiffs in legal cases involving asbestosis, occupational lung disease, beryllium poisoning, silicone breast implants and connective tissue disease (characterized as the epitome of junk science91), selective serotonin reuptake inhibitor and suicide risk, atypical antipsychotics and metabolic changes, and selective COX-2 inhibitors and cardiovascular disease, an amazing breadth of medical expertise.”

Laurence J. Hirsch, “Conflicts of Interest, Authorship, and Disclosures in Industry-Related Scientific Publications: The Tort Bar and Editorial Oversight of Medical Journals,” 84 Mayo Clin. Proc. 811, 815 (2009).

Egilman apparently besieged Dr. Hirsch and the Mayo Clinic Proceedings with his protests, and it seems that he was able to induce the author or the journal into a “correction”:

“Dr Egilman has not testified in court in breast implant and connective tissue disease, or in antidepressant or antipsychotic drug cases.”

Laurence J. Hirsch, “Corrections,” 85 Mayo Clin. Proc. 99 (2010). But this correction is itself incorrect because Dr. Egilman testified over the course of three days, in court, in the same Vassallo v. Baxter Healthcare case he holds up as having embraced his causal “principles.” The Vassallo case involved allegations that silicone had caused systemic autoimmune disease, an allegation that was ultimately shown to be meritless by the MDL court’s neutral expert witnesses, as well as the Institute of Medicine.

Perhaps this history helps explain Dr. Egilman’s coyness in what he told the Newkirk appellate court about his involvement in the Vassallo case. More likely is that Dr. Egilman understands, all too well, the logical implications of his being wrong in the breast implant litigation. If his vaunted method leads to an erroneous conclusion, then the method must be wrong. It is a simple matter of modus tollens.

Posted in Causation, Expert Witnesses, Rule 702, Scientific Evidence | Comments Off on David Egilman’s Methodology for Divining Causation

Open Admissions for Expert Witnesses in Chantix Litigation

September 1st, 2012

Chantix is medication that helps people stop smoking. Smoking kills people, but make a licensed drug and the lawsuits will come.

Earlier this month, Judge Inge Prytz Johnson, the MDL trial judge in the Chantix litigation, filed an opinion that rejected Pfizer’s challenges to plaintiffs’ general causation expert witnesses. Memorandum Opinion and Order, In re Chantix (Varenicline) Products Liability Litigation, MDL No. 2092, Case 2:09-cv-02039-IPJ Document 642 (N.D. Ala. Aug. 21, 2012)[hereafter cited as Chantix].

Plaintiffs claimed that Chantix causes depression and suicidality, sometimes severe enough to result in suicide, attempted or completed. Chantix at 3-4. Others have written about Judge Johnson’s decision. See Lacayo, “Win Some, Lose Some: Recent Federal Court Rulings on Daubert Challenges to Plaintiffs’ Experts,” (Aug. 30, 2012).

The breadth and depth of error of the trial court’s analysis, or lack thereof, remains, however, to be explored.

STATISTICAL SIGNIFICANCE

The Chantix MDL court notes several times that the defendant “harped” on this or that issue; the reader might think the defendant was a music label rather than a pharmaceutical manufacturer. One of the defendant’s chords that failed to resonate with the trial judge was the point that the plaintiffs’ expert witnesses relied upon statistically non-significant results. Here is how the trial court reported the issue:

“While the defendant repeatedly harps on the importance of statistically significant data, the United States Supreme Court recently stated that ‘[a] lack of statistically significant data does not mean that medical experts have no reliable basis for inferring a causal link between a drug and adverse events …. medical experts rely on other evidence to establish an inference of causation.’ Matrixx Initiatives, Inc. v. Siracsano, 131 S.Ct. 1309, 1319 (2011).”

Chantix at 22.

Well, it was only a matter of time before the Supreme Court’s dictum would be put to this predictably erroneous interpretation. See “The Matrixx Oversold” (April 4, 2011).

Matrixx involved a motion to dismiss the complaint, which the trial court granted, but the Ninth Circuit reversed. No evidence was offered; nor was any ruling that evidence was unreliable or insufficient at issue. The Supreme Court affirmed the Circuit on the issue whether pleading statistical significance was necessary. Matrixx Initiatives took this position in the hopes of avoiding the merits, and so the issue of causation was never before the Supreme Court. A unanimous Supreme Court held that because FDA regulatory action does not require reliable evidence to support a causal conclusion, pleading materiality for a securities fraud suit does not require an allegation of causation, and thus does not require an allegation of statistically significant evidence. Everything that the Court said about statistical significance and causation was obiter dictum, and rather ill-considered dictum at that.

The Supreme Court thus wandered far beyond its holding to suggest that courts “frequently permit expert testimony on causation based on evidence other than statistical significance.” Matrixx Initiatives, Inc. v. Siracsano, 131 S.Ct. 1309, 1319 (2011) (citing Wells v. Ortho Pharm. Corp., 788 F.2d 741, 744-745 (11th Cir.1986)). But the Supreme Court’s citation to Wells, in Justice Sotomayor’s opinion, failed to support the point she was trying to make, or the decision that the trial court announced in Chantix.

Wells involved a claim of birth defects caused by the use of spermicidal jelly contraceptive. At least one study reported a statistically significant increase in detected birth defects over the expected rate. Wells v. Ortho Pharmaceutical Corp., 615 F. Supp. 262 (N.D.Ga. 1985), aff’d, and rev’d in part on other grounds, 788 F.2d 741 (11th Cir.), cert. denied, 479 U.S.950 (1986). Wells is not an example of a case in which an expert witness opined about causation in the absence of a scientific study with statistical significance. Of course, finding statistical significance is just the beginning of assessing the causality of an association; the Wells case was and remains notorious for the expert witness’s poor assessment of all the determinants of scientific causation, including the validity of the studies relied upon.

The Wells decision was met with severe criticism in the 1980s. The decision was widely criticized for its failure to evaluate the entire evidentiary display, as well as for its failure to rule out bias and confounding in the studies relied upon by the plaintiff. See, e.g., James L. Mills and Duane Alexander, “Teratogens and ‘Litogens’,” 15 New Engl. J. Med. 1234 (1986); Samuel R. Gross, “Expert Evidence,” 1991 Wis. L. Rev. 1113, 1121-24 (1991) (“Unfortunately, Judge Shoob’s decision is absolutely wrong. There is no scientifically credible evidence that Ortho-Gynol Contraceptive Jelly ever causes birth defects.”). See also Editorial, “Federal Judges v. Science,” N.Y. Times, December 27, 1986, at A22 (unsigned editorial); David E. Bernstein, “Junk Science in the Courtroom,” Wall St. J. at A 15 (Mar. 24,1993) (pointing to Wells as a prominent example of how the federal judiciary had embarrassed the American judicial system with its careless, non-evidence based approach to scientific evidence). A few years later, another case in the same judicial district, against the same defendant, for the same product, resulted in the grant of summary judgment. Smith v. Ortho Pharmaceutical Corp., 770 F. Supp. 1561 (N.D. Ga. 1991) (supposedly distinguishing Wells on the basis of more recent studies).

Neither the Justices in Matrixx Initiatives nor the trial court in Chantix can be excused for their poor scholarship, or their failure to note that Wells was overruled sub silentio by the Supreme Court’s own subsequent decisions in Daubert, Joiner, Kumho Tire, and Weisgram. And if the weight of precedent did not kill the concept, then there is the simple matter of a supervening statute: the 2000 amendment of Rule 702, of Federal Rules of Evidence.

CONFUSING REGULATORY ACTION WITH CAUSAL ASSESSMENTS

The Supreme Court in Matrixx Initiatives was careful to distinguish causal judgments from regulatory action, but then went on in dictum to conflate the two. The trial judge in Chantix showed no similar analytical care. Judge Johnson held that the asserted absence of statistical significance was not a basis for excluding plaintiffs’ expert witnesses’ opinions on general causation. Her Honor adverted to the Matrixx Initiatives dictum that the FDA “does not apply any single metric for determining when additional inquiry or action is necessary.” Matrixx, 131 S.Ct. at 1320. Chantix at 22. Judge Johnson noted

“that ‘[n]ot only does the FDA rely on a wide range of evidence of causation, it sometimes acts on the basis of evidence that suggests, but does not prove, causation…. the FDA may make regulatory decisions against drugs based on postmarketing evidence that gives rise to only a suspicion of causation’. Matrixx, id. The court declines to hold the plaintiffs’ experts to a more exacting standard as the defendant requests.”

Chantix at 23.

In the trial court’s analysis, the difference between regulatory action and civil litigation fact adjudication is obliterated. This, however, is not the law of the United States, which has consistently acknowledged the difference. See, e.g., IUD v. API, 448 U.S. 607, 656 (1980)(“agency is free to use conservative assumptions in interpreting the data on the side of overprotection rather than underprotection.”)

As the Second Edition of the Reference Manual on Scientific Evidence (which was the out-dated edition cited by the court in Chantix) explains:

“[p]roof of risk and proof of causation entail somewhat different questions because risk assessment frequently calls for a cost-benefit analysis. The agency assessing risk may decide to bar a substance or product if the potential benefits are outweighed by the possibility of risks that are largely unquantifiable because of presently unknown contingencies. Consequently, risk assessors may pay heed to any evidence that points to a need for caution, rather than assess the likelihood that a causal relationship in a specific case is more likely than not.”

Margaret A. Berger, “The Supreme Court’s Trilogy on the Admissibility of Expert Testimony,” in Reference Manual On Scientific Evidence at 33 (Fed. Jud. Ctr. 2d. ed. 2000).

CONCLUSIONS VS. METHODOLOGY

Judge Johnson insisted that the “court’s focus was solely on the principles and methodology, not on the conclusions they generate.” Chantix at 9. This insistence, however, is contrary to the established law of Rule 702.

Although the United States Supreme Court attempted, in Daubert, to draw a distinction between the reliability of an expert witness’s methodology and conclusion, that Court soon realized that the distinction was flawed. If an expert witness’s proffered testimony is discordant from regulatory and scientific conclusions, a reasonable, disinterested scientists would be led to question the reliability of the testimony’s methodology and its inferences from facts and data, to its conclusion. The Supreme Court recognized this connection in General Electric v. Joiner, and the connection between methodology and conclusions was ultimately incorporated into a statute, the revised Federal Rule of Evidence 702:

“[I]f scientific, technical or other specialized knowledge will assist the trier of fact to understand the evidence or to determine a fact in issue, a witness qualified as an expert by knowledge, skill, experience, training or education, may testify thereto in the form of an opinion or otherwise, if

the testimony is based upon sufficient fact or data,

the testimony is the product of reliable principles and methods; and

the witness has applied the principles and methods reliably to the facts.”

When the testimony is a conclusion about causation, the Rule 702 directs an inquiry into whether that conclusion is based upon sufficient fact or data, and whether that conclusion is the product of reliable principles and methods. The court’s focus should indeed be on the conclusion as well the methodology claimed to generate the conclusion. The Chantix MDL court thus ignored the clear mandate of a statute, Rule 702(1), and applied dictum from Daubert, superseded by Joiner, and an Act of Congress. The ruling is thus legally invalid to the extent it departs from the statute.

EPIDEMIOLOGY

For obscure reasons, Judge Johnson sought to deprecate the need to rely upon epidemiologic studies, whether placebo-controlled clinical trials or observational studies. See Chantix at 25 (citing Rider v. Sandoz Pharm. Corp., 295 F.3d 1194, 1198-99 (11 Cir.2002)). Of course, the language cited in Rider came from a pre-Daubert, pre-Joiner, case, Wells v. Ortho Pharm. Corp., 788 F.2d 741, 745 (11th Cir.1986) (holding that “a cause-effect relationship need not be clearly established by animal or epidemiological studies”). This dubious legal lineage cannot support the glib dismissal of the need for epidemiologic evidence.

WEIGHT OF THE EVIDENCE (WOE)

According to Judge Johnson, plaintiffs’ expert witness Shira Kramer considered all the evidence relevant to Chantix and neuropsychiatric side effects, in what Kramer described as a “weight of the evidence” analysis. Chantix at 26. In her report, Kramer had written that determinations about the weight of evidence are “subjective interpretations” based upon “various lines of scientific evidence. Id. (citing and quoting Kramer’s report). Kramer also claimed that every scientist “brings a unique set of experiences, training and expertise …. Philosophical differences exist between experts…. Therefore, it is not surprising that differences of opinion exist among scientists. Such differences of opinion are not necessarily evidence of flawed scientific reasoning or methodology, but rather differences in judgment between scientists.” Id.

Without any support from scientific literature, or the Reference Manual on Scientific Evidence, Judge Johnson accepted Kramer’s explanation of a totally subjective, unprincipled approach as a scientific methodology. Not surprisingly, Judge Johnson cited the First Circuit’s embrace of a similar vacuous embrace of a WOE analysis in Milward v. Acuity Specialty Products Group, Inc. 639 F.3d 11, 22 (1st Cir. 2011). Chantix at 51.

CHERRY PICKING

Judge Johnson noted, contrary to her earlier suggestion that Shira Kramer had considered all the studies, that Kramer had excluded data from her analysis. Kramer’s basis for excluding data may have been based upon pre-specified exclusionary principles, or they may have been completely ad hoc, as were the lack of weighting principles in her WOE analysis. In its gatekeeping role, however, the trial court expressed complete indifference to Kramer’s selectivity in excluding data. “Why Dr. Kramer chose to include or exclude data from specific clinical trials is a matter for cross-examination.” Chantix at 27. This indifference is an abdication of the court’s gatekeeping responsibility.

POWER

The trial court attempted to justify its willingness to mute defendant’s harping on statistical significance by adverting to the concept of statistical power:

“Oftentimes, epidemiological studies lack the statistical power needed for definitive conclusions, either because they are small or the suspected adverse effect is particularly rare. Id. [Michael D. Green et al., “Reference Guide on Epidemiology,” in Reference Manual on Scientific Evidence 333, 335 (Fed. Judicial Ctr. 2d ed. 2000)… .

Chantix at 29 n.16.

To be fair to the trial court, the Reference Manual invited this illegitimate use of statistical power because it, at times, omits the specification that statistical power requires not only a level of statistical significance to be attained, but also a specified alternative hypothesis to assess power. See Power in the Courts — Part One; Power in the Courts — Part Two. The trial court offered no alternative hypothesis against which any measure of power was to be assessed.

Judge Johnson did not report any power analyses, and she certainly did not report any quantification of power or lack thereof against some specific alternative hypothesis. Judge Johnson’s invocation of power was just that – power used arbitrarily, without data, evidence, or reason.

CONFIDENCE INTERVALS

As with the invocation of statistical power, the trial also invoked the concept of confidence intervals to suggest that such intervals provide a more refined approach to assessing statistical significance:

“A study found to have ‘results that are unlikely to be the result of random error’ is ‘statistically significant’. Reference Guide on Epidemiology, supra, at 354. Statistical significance, however, does not indicate the strength of an association found in a study. Id. at 359. ‘A study may be statistically significant but may find only a very weak association; conversely, a study with small sample sizes may find a high relative risk but still not be statistically significant.’ Id. To reach a ‘more refined assessment of appropriate inferences about the association found in an epidemiologic study’, researchers rely on another statistical technique known as a confidence interval’. Id. at 360.”

Chantix at 30 n.17. True, true, but immaterial. The trial court, again, never carries through with the direction given by the Reference Manual. Not a single confidence interval is presented. No confidence intervals are subjected to this more refined assessment. Why have more refined assessments when even the cruder assessments are not done?

OPEN ADMISSIONS IN SCHOOL OF EXPERT WITNESSING

The trial court somehow had the notion that all it had to do was state that every disputed fact and opinion went to the weight not the admissibility, and then pass to a presumably more scientifically literate jury. To be sure, the court engaged in a good deal of hand waving, going through the motions of deciding a contested issues. Not only did the Judge Johnson smash poor Pfizer’s harp, Her Honor unhinged the gate that federal judges are supposed to keep. Chantix declares that it is now open admissions for expert witnesses testifying to causation in federal cases. This is a judgment in search of an appeal.

Posted in Causation, Expert Witnesses, Rule 702, Scientific Evidence, statistical evidence | Comments Off on Open Admissions for Expert Witnesses in Chantix Litigation

Eighth Circuit Holds That Increased Risk Is Not Cause

August 4th, 2012

The South Dakota legislature took it upon itself to specify the “risks” to be included in the informed consent required by state law for an abortion procedure:

(1) A statement in writing providing the following information:
* * *
(e) A description of all known medical risks of the procedure and statistically significant risk factors to which the pregnant woman would be subjected, including:
(i) Depression and related psychological distress;
(ii) Increased risk of suicide ideation and suicide;
* * *

S.D.C.L. § 34-23A-10.1(1)(e)(i)(ii). Planned Parenthood challenged the law on constitutional grounds, and the district court granted a preliminary injunction against the South Dakota statute, which a panel of the Eight Circuit affirmed, only to have that Circuit en banc reverse and remand the case for further proceedings. Planned Parenthood Minn. v. Rounds, 530 F.3d 724 (8th Cir. 2008) (en banc).

On remand, the parties filed cross-motions for summary judgment. The district court held that the so-called suicide advisory was unconstitutional. On the second appeal to the Eight Circuit, a divided panel affirmed the trial court’s holding on the suicide advisory. 653 F.3d 662 (8th Cir. 2011). The Circuit, however, again granted rehearing en banc, and reversed the summary judgment for Planned Parenthood on the advisory. Planned Parenthood Minnesota v. Rounds, Slip op. July 24, 2012 (en banc)[Slip op.].

In support of the injunction, Planned Parenthood argued that the state’s mandatory suicide advisory violated women’s abortion rights and physicians’ free speech rights. The en banc court rejected this argument, holding that the required advisory was “truthful, non-misleading information,” which did not unduly burden abortion rights, even if it might cause women to forgo abortion. See Planned Parenthood of Southeastern Pennsylvania v. Casey, 505 U.S. 833, 882-83 (1992).

Risk ≠ Cause

Planned Parenthood’s success in the trial court turned on its identification of risk (or increased risk) with cause, and its expert witness evidence that causation had not been accepted in the medical literature. In other words, Planned Parenthood argued that the advisory required disclosure of a conclusive causal “link” between abortion and suicide or suicidal ideation. See 650 F. Supp. 2d 972, 982 (D.S.D. 2009). The en banc court, on the second appeal, sought to save the statute by rejecting Planned Parenthood’s reading. The court parsed the statute to suggest that the term “increased risk” is more precise and limited than the umbrella term of “risk,” standing alone. Slip op. at 6. The statute does not define “increased risk,” which the en banc court noted had various meanings in medicine. Id. at 7.

Reviewing the medical literature, the en banc court held that the term “increased risk” does not refer to causation but to a much more modest finding of “a relatively higher probability of an adverse outcome in one group compared to other groups—that is, to ‘relative risk’.” Id. The en banc majority seemed to embroil itself in some considerable semantic confusion. One the hand, the majority, in a rhetorical rift proclaimed that:

“It would be nonsensical for those in the field to distinguish a relationship of ‘increased risk’ from one of causation if the term ‘risk’ itself was equivalent to causation.”

Id. at 9. The majority’s nonsensical labeling is, well, … nonsensical. There is a compelling difference in assessment of risk and causation. Risk is an ex ante concept, applied before the effect has occurred. Assessment or attribution of causation takes place after the effect. Of course, there is a sense of risk or “increased risk,” which is epistemologically more modest, but that hardly makes the more rigorous use of risk as an ex ante cause, nonsensical.

The majority, however, is not content to leave the matter alone. Elsewhere, the en banc court contradicts itself, and endorses a view that risk = causation. For instance, in citing to a civil action involving a claimed causal relationship between Bendectin and a birth defect, the Eighth Circuit reduces risk to cause. See Slip op. at 26 n. 9 (citing Brock v. Merrell Dow Pharms., Inc., 874 F.2d 307, 312 , modified on reh’g, 884 F.2d 166 (5th Cir. 1989)). The en banc court’s “explanatory” parenthetical explains the depths of its confusion:

“explaining that if studies establish, within an acceptable confidence interval, that those who use a pharmaceutical have a relative risk of greater than 1.0—that is, an increased risk—of an adverse outcome, those studies might be considered sufficient to support a jury verdict of liability on a failure-to-warn claim.”

This reading of Brock is wrong on two counts. First, the Fifth Circuit, in Brock, and consistently since, has required the relative risk greater than 1.0 to be statistically significant at the conventional significance probability, as well as other indicia of causality, such as the Bradford Hill factors. So Brock and its progeny did not confuse or conflate risk with cause, or dilute the meaning of cause such that it could be satisfied by a mere showing of an increased relative risk.

Second, Brock itself made a serious error in interpreting statistical significance and confidence intervals. The Bendectin studies at issue in Brock were not statistically significant, and the confidence intervals did not include a measure of no association (relative risk = one). Brock, however, in notoriously incorrect dicta claimed that the computation of confidence intervals took into account bias and confounding as well as sampling variability. Brock v. Merrill Dow Pharmaceuticals, Inc., 874 F.2d 307, 311-12 (5th Cir. 1989)(“Fortunately, we do not have to resolve any of the above questions [as to bias and confounding], since the studies presented to us incorporate the possibility of these factors by the use of a confidence interval.”)(emphasis in original). See, e.g., David H. Kaye, David E. Bernstein, and Jennifer L. Mnookin, The New Wigmore – A Treatise on Evidence: Expert Evidence § 12.6.4, at 546 (2d ed. 2011); Michael O. Finkelstein, Basic Concepts of Probability and Statistics in the Law 86-87 (2009)(criticizing the over-interpretation of confidence intervals by the Brock court); Schachtman, “Confidence in Intervals and Diffidence in the Courts” (Mar. 4, 2012).

The en banc majority’s discussion of the studies of abortion and suicidality make clear that the presence of bias and confounding in a study may prevent inference of causation, but they do not undermine the conclusion that the studies show an increased risk. A conclusion that the body of epidemiologic studies was inconclusive, and that it failed to “to disentangle confounding factors and establish relative risks of abortion compared to its alternatives,” did not, therefore, render the suicide advisory about risk or increased risk unsupported, untruthful, or misleading. Slip op. at 20. Indeed, the en banc court provided an example, outside the context of abortion, to illustrate its meaning. The en banc court’s use of the example of prolonged television viewing and “increased risk” of mortality suggests that the court took risk to mean any association, no matter how likely it was the result of bias or confounding. See id. at 10 n. 3 (citing Anders Grøntved, et al., “Television Viewing and Risk of Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality, 305 J. Am. Med. Ass’n 2448 (2011). The en banc majority held that the advisory would be misleading only if Planned Parenthood could show that the available epidemiologic studies conclusively ruled out causation. Slip op. at 24-25.

The Suicide Advisory Has Little Content Because Risk Is Not Cause

The majority decision clarified that the mandatory disclosure does not require a physician to inform a patient that abortion causes suicide or suicidal thoughts. Slip op. at 25. The en banc court took solace in its realization that physicians’ reviewing the available studies could provide a disclosure that captures the difference between risk, relative risk, and causation. In other words, physicians are free to tell patients that this thing called increased risk is not concerning because the studies are highly confounded, and they do not show causation. Id. at 25-26. Indeed, it would be hard to imagine an ethical physician telling patients anything else.

Dissent

Four of the Eight Circuit judges dissented, pointing to evidence that the South Dakota legislators intended to mandate a disclosure about causality. Slip op. at 29. Putting aside whether the truthfulness of the suicide advisory can be saved by reverting to a more modest interpretation of risk or of increased risk, the dissenters appear to have the better argument that the advisory is misleading. The majority, however, by driving its wedge between causation and increased risk have allowed physicians to explain that the advisory has little or no meaning.

NOCEBO

The nocebo effect is the dark side of the placebo effect. As pointed out recently in the Journal of the American Medical Association, nocebos can induce harmful outcomes because of the expectation of injury from the “psychosocial context or therapeutic environment” affecting patients’ perception of their health. Luana Colloca & Damien Finniss, “Nocebo Effects, Patient-Clinician Communication, and Therapeutic Outcomes,” 307 J. Am. Med. Ass’n 567, 567 (2012). It is fairly well accepted that clinicians can inadvertently prejudice health outcomes by how they frame outcome information to patients. Colloca and Finniss note that the negative expectations created by nocebo communication can take place in the process of obtaining informed consent.

Unfortunately, there is no discussion of nocebo effects in the Eight Circuit’s decision. Planned Parenthood might well consider the role the nocebo effect has on the risk-benefit of an informed consent disclosure about a risk that really is not a risk, or is not a risk in the sense that it is a factor that will result in the putative cause, but rather only something that is under study and which cannot be separated from many confounding factors. Surely, physicians in South Dakota will figure out how to give truthful, non-misleading disclosures that incorporate the mandatory suicide advisory, as well as the scientific evidence.

Posted in Causation, Risk and Risk Factor, Scientific Evidence, statistical evidence | Comments Off on Eighth Circuit Holds That Increased Risk Is Not Cause

Viagra, Part II — MDL Court Sees The Light – Bad Data Trump Nuances of Statistical Inference

July 8th, 2012

In the Viagra vision loss MDL, the first Daubert hearing did not end well for the defense. Judge Magnuson refused to go beyond conclusory statements by the plaintiffs’ expert witness, Gerald McGwin, and to examine the qualitative and quantitative evaluative errors invoked to support plaintiffs’ health claims. The weakness of McGwin’s evidence, however, appeared to encourage Judge Magnuson to authorize extensive discovery into McGwin’s study. In re Viagra Products Liab. Litig., 572 F. Supp. 2d 1071, 1090 (D. Minn. 2008).

The discovery into McGwin’s study had already been underway, with subpoenas to him and to his academic institution. As it turned out, defendant’s discovery into the data and documents underlying McGwin’s study won the day. Although Judge Magnuson struggled with inferential statistics, he understood the direct attack on the integrity of McGwin’s data. Over a year after denying defendant’s Rule 702 motion to exclude Gerald McGwin, the MDL court reconsidered and granted the motion. In re Viagra Products Liab. Litig., 658 F. Supp. 2d 936, 945 (D. Minn. 2009).

The basic data on prior exposures and risk factors for the McGwin study was collected by telephone surveys, from which the information was coded into an electronic dataset. In analyzing the data, McGwin used the electronic dataset and not the survey forms. Id. at 939. The transfer from survey forms to electronic dataset did not go smoothly; about 11 patients were miscoded as “exposed“ when their use of Viagra post-dated the onset of NAION. Id. at 942. Furthermore, the published article incorrectly stated personal history of heart attack as a “risk factor ”; the survey inquired about family not personal history of heart attack. Id. at 944.

The plaintiffs threw several bombs in response, but without legal effect. First, the plaintiffs claimed that the study participants had been recontacted and the database had been corrected, but they were unable to document this process or the alleged corrections. Id. at 433. Furthermore, the plaintiffs could not explain how, if their contention had been true, McGwin would have not committed serious violations of his university’s institutional review board’s regulations with respect to deviations from the original protocol. Id. at 943 n.7.

Second, the plaintiffs argued that the underlying survey forms were “inadmissible ” and thus the defense could not use them to impeach the McGwin study. Some might think this a duplicitous argument, utterly at odds with Rule 703 – rely upon a study but prevent use of underlying data and documents to explain that the study does not show what it purports to show. The MDL court spared the plaintiffs the embarrassment of ruling that the documents on which McGwin had based his study were inadmissible, and found that the forms were business records and admissible under Federal Rule of evidence 803(6). The court could have gone further to point out that McGwin’s reliance upon hearsay in the form of his study, McGwin 2006, opened the door to impeaching the hearsay relied upon with other hearsay. See Rule 806.

When defense counsel sat down with McGwin in a deposition, they found that he had not undertaken any new analyses of corrected data. Plaintiffs’ counsel directed him not to do so. Id. at 940-41. But then after the deposition was over, McGwin submitted a letter to the journal to report a corrected analysis. Pfizer’s counsel obtained the letter in response to their subpoena to McGwin’s university, the University of Alabama, Birmingham. Mirabile dictu; now the increase risk appeared limited to only to the defendant’s medication, Viagra!

The trial court was not amused. First, the new analysis was no longer peer reviewed, and the court had placed a great deal of emphasis on peer review in denying the first challenge to McGwin. Second, the new analysis was no longer that of an independent scientist, but was conducted and submitted as a letter to the editor, while McGwin was working for plaintiffs’ counsel. Third, the plaintiffs and McGwin conceded that the data were not accurate. Last, but not least, the trial court clearly was not pleased that the plaintiffs’ counsel had deliberately delayed McGwin’s further analyses until after the deposition, and then tried to submit yet another supplemental report with those further analyses. In sum:

“the Court finds good reason to vacate its original Daubert Order permitting Dr. McGwin to testify as a general causation expert based on the McGwin Study as published. Almost every indicia of reliability the Court relied on in its previous Daubert Order regarding the McGwin Study has been shown now to be unreliable. Peer review and publication mean little if a study is not based on accurate underlying data. Likewise, the known rate of error is also meaningless if it is based on inaccurate data. Even if the McGwin Study as published was conducted according to generally accepted epidemiologic research and did not result from post-litigation research, the fact that the McGwin Study appears to have been based on data that cannot now be documented or supported renders it inadmissibly unreliable. The Court concludes that under Daubert, Dr. McGwin’s opinion, to the extent that it is based on the McGwin Study as published, lacks sufficient indicia of reliability to be admitted as a general causation opinion.”

Id. at 945-46. The remaining evidence was the Margo & French study, but McGwin had previously criticized that study as lacking data that ensured that Viagra use preceded onset of NAION. In the end, McGwin was left with bupkes, and the plaintiffs were left with even less.

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McGwin 2006 Was Also A Pain in the Rear End for McGwin

The Rule 702 motions and hearings on McGwin’s proposed testimony had consequences in the scientific world itself. In 2011, the British Journal of Ophthalmology retracted McGwin’s 2006 paper. “Retraction: Non-arteritic anterior ischaemic optic neuropathy and the treatment of erectile dysfunction, ” 95 Brit. J. Ophthalmol. 595 (2011).

Interestingly, the retraction was reported in the Retraction Watch blog, “Retractile dysfunction? Author says journal yanked paper linking Viagra, Cialis to vision problem after legal threats.” The blog treated the retraction as routine except for the hint of “legal pressure”:

“One of the authors of the paper, a researcher at the University of Alabama named Gerald McGwin Jr., told us that the journal retracted the article because it had become a tool in a lawsuit involving Pfizer, which makes Viagra, and, presumably, men who’d developed blindness after taking the drug:

‘The article just became too much of a pain in the rear end. It became one of those things where we couldn’t provide all the relevant documentation [to the university, which had to provide records for attorneys].’

Ultimately, however, McGwin said that the BJO pulled the plug on the paper.”

Id. The legal threat is hard to discern other than the fact that lawyers wanted to see something that peer reviewers almost never see – the documentation underlying the published paper. So now, the study that formed the basis for the original ruling against Pfizer floats aimlessly as a derelict on the sea of science. McGwin is, however, still at his craft. In a study he published in 2010, he claimed that Viagra but not Cialis use was associated with hearing impairment. Gerald McGwin, Jr, “Phosphodiesterase Type 5 Inhibitor Use and Hearing Impairment,” 136 Arch. Otolaryngol. Head & Neck Surgery 488 (2010).

Where are Senator Grassley and Congressman Waxman when you need them?

Posted in Causation, Data Sharing, Expert Witnesses, Rule 702, statistical evidence, Underlying Data | Comments Off on Viagra, Part II — MDL Court Sees The Light – Bad Data Trump Nuances of Statistical Inference

Love is Blind but What About Judicial Gatekeeping of Expert Witnesses? – Viagra Part I

July 7th, 2012

The Viagra litigation over claimed vision loss vividly illustrates the difficulties that trial judges have in understanding and applying the concept of statistical significance. In this MDL, plaintiffs sued for a specific form of vision loss, non-arteritic ischemic optic neuropathy (NAION), which they claimed was caused by their use of defendant’s medication, Viagra. In re Viagra Products Liab. Litig., 572 F. Supp. 2d 1071 (D. Minn. 2008). Plaintiffs’ key expert witness, Gerald McGwin considered three epidemiologic studies; none found a statistically significant elevation of risk of NAION after Viagra use. Id. at 1076. The defense filed a Rule 702 motion to exclude McGwin’s testimony, based in part upon the lack of statistical significance of the risk ratios he relied upon for his causal opinion. The trial court held that this lack did not render McGwin’s testimony and unreliable and inadmissible Id. at 1090.

One of the three studies considered by McGwin was his own published paper. G. McGwin, Jr., M. Vaphiades, T. Hall, C. Owsley, ‘‘Non-arteritic anterior ischaemic optic neuropathy and the treatment of erectile dysfunction,’’ 90 Br. J. Ophthalmol. 154 (2006)[“McGwin 2006”]. The MDL court noted that McGwin had stated that his paper reported an odds ratio (OR) of 1.75, with a 95% confidence interval (CI), 0.48 to 6.30. Id. at 1080. The study also presented multiple subgroup analyses of men who had reported Viagra use after a history of heart attack (OR = 10.7) or hypertension (OR = 6.9), but the MDL court did not provide p-values or confidence intervals for the subgroup analysis results.

Curiously, Judge Magnuson eschewed the guidance of the Reference Manual on Scientific Evidence, in dealing with statistics of sampling estimates of means or proportions. The Reference Manual on Scientific Evidence (2d ed. 2000) urges that:

“[w]henever possible, an estimate should be accompanied by its standard error.”

RMSE 2d ed. at 117-18. The new third edition again conveys the same basic message:

“What is the standard error? The confidence interval?

An estimate based on a sample is likely to be off the mark, at least by a small amount, because of random error. The standard error gives the likely magnitude of this random error, with smaller standard errors indicating better estimates.”

RMSE 3d ed. at 243.

The point of the RSME‘s guidance is, of course, that the standard error, or the confidence interval (C.I.) based upon a specified number of standard errors, is an important component of the sample statistic, without which the sample estimate is virtually meaningless. Just as a narrative statement should not be truncated, a statistical or numerical expression should not be unduly abridged.

The statistical data on which McGwin was basing his opinion was readily available from McGwin 2006:

“Overall, males with NAION were no more likely to report a history of Viagra … use compared to similarly aged controls (odd ratio (OR) 1.75, 95% confidence interval (CI) 0.48 to 6.30. However, for those with a history of myocardial infarction, a statistically significant association was observed (OR 10.7, 95% CI 1.3 to 95.8). A similar association was observed for those with a history of hypertension though it lacked statistical significance (OR 6.9, 95% CI 0.8 to 63.6).”

McGwin 2006, at 154. Following the RSME‘s guidance would have assisted the MDL court in its gatekeeping responsibility in several distinct ways. First, the court would have focused on how wide the 95% confidence intervals were. The width of the intervals pointed to statistical imprecision and instability in the point estimates urged by McGwin. Second, the MDL court would have confronted the extent to which there were multiple ad hoc subgroup analyses in McGwin’s paper. See Newman v. Motorola, Inc., 218 F. Supp. 2d 769, 779 (D. Md. 2002)(“It is not good scientific methodology to highlight certain elevated subgroups as significant findings without having earlier enunciated a hypothesis to look for or explain particular patterns.”) Third, the court would have confronted the extent to which the study’s validity was undermined by several potent biases. Statistical significance was the least of the problems faced by McGwin 2006.

The second study considered and relied upon by McGwin was referred to as Margo & French. McGwin cited this paper for an “elevated OR of 1.10,” id. at 1081, but again, had the court engaged with the actual evidence, it would have found that McGwin had cherry picked the data he chose to emphasize. The Margo & French study was a retrospective cohort study using the National Veterans Health Administration’s pharmacy and clinical databases. C. Margo & D. French, ‘‘Ischemic optic neuropathy in male veterans prescribed phosphodiesterase-5 inhibitors,’’ 143 Am. J. Ophthalmol. 538 (2007). There were two outcomes ascertained: NAION and “possible” NAION. The relative risk of NAION among men prescribed a PDE-5 inhibitor (the class to which Viagra belongs) was 1.02 (95% confidence interval [CI]: 0.92 to 1.12. In other words, the Margo & French paper had very high statistical precision, and it reported essentially no increased risk at all. Judge Magnuson cited uncritically McGwin’s endorsement of a risk ratio that included ‘‘possible’’ NAION cases, which could not bode well for a gatekeeping process that is supposed to protect against speculative evidence and conclusions.

McGwin’s citation of Margo & French for the proposition that men who had taken the PDE-5 inhibitors had a 10% increased risk was wrong on several counts. First, he relied upon an outcome measure that included ‘‘possible’’ cases of NAION. Second, he completely ignored the sampling error that is captured in the confidence interval. The MDL court failed to note or acknowledge the p-value or confidence interval for any result in Margo & French. The consideration of random error was not an optional exercise for the expert witness or the court; nor was ignoring it a methodological choice that simply went to the ‘‘disagreement among experts.’’

The Viagra MDL court not only lost its way by ignoring the guidance of the RMSE, it appeared to confuse the magnitude of the associations with the concept of statistical significance. In the midst of the discussion of statistical significance, the court digressed to address the notion that the small relative risk in Margo & French might mean that no plaintiff could show specific causation, and then in the same paragraph returned to state that ‘‘persuasive authority’’ supported the notion that the lack of statistical significance did not detract from the reliability of a study. Id. at 1081 (citing In re Phenylpropanolamine (PPA) Prods. Liab. Litig., MDL No. 1407, 289 F.Supp.2d 1230, 1241 (W.D.Wash. 2003)). The magnitude of the observed odds ratio is an independent concept from that of whether an odds ratio as extreme or more so would have occurred by chance if there really was no elevation.

Citing one case, at odds with a great many others, however, did not create an epistemic warrant for ignoring the lack of statistical significance. The entire notion of cited caselaw for the meaning and importance of statistical significance for drawing inferences is wrong headed. Even more to the point, the lack of statistical significance in the key study in the PPA litigation did not detract from the reliability of the study, although other features of that study certainly did. The lack of statistical significance in the PPA study did, however, detract from the reliability of the inference from the study’s estimate of ‘‘effect size’’ to a conclusion of causal association. Indeed, nowhere in the key PPA study did its authors draw a causal conclusion with respect to PPA ingestion and hemorrhagic stroke. See Walter Kernan, Catherine Viscoli, Lawrence Brass, Joseph Broderick, Thomas Brott, Edward Feldmann, Lewis Morgenstern, Janet Lee Wilterdink, and Ralph Horwitz, ‘‘Phenylpropanolamine and the Risk of Hemorrhagic Stroke,’’ 343 New England J. Med. 1826 (2000).

The MDL court did attempt to distinguish the Eighth Circuit’s decision in Glastetter v. Novartis Pharms. Corp., 252 F.3d 986 (8th Cir. 2001), cited by the defense:

‘‘[I]n Glastetter … expert evidence was excluded because ‘rechallenge and dechallenge data’ presented statistically insignificant results and because the data involved conditions ‘quite distinct’ from the conditions at issue in the case. Here, epidemiologic data is at issue and the studies’ conditions are not distinct from the conditions present in the case. The Court does not find Glastetter to be controlling.’’

Id. at 1081 (internal citations omitted; emphasis in original). This reading of Glastetter, however, misses important features of that case and the Parlodel litigation more generally. First, the Eighth Circuit commented not only upon the rechallenge-dechallenge data, which involved arterial spasms, but upon an epidemiologic study of stroke, from which Ms. Glastetter suffered. The Glastetter court did not review the epidemiologic evidence itself, but cited to another court, which did discuss and criticize the study for various ‘‘statistical and conceptual flaws.’’ See Glastetter, 252 F.3d at 992 (citing Siharath v. Sandoz Pharms.Corp., 131 F.Supp. 2d 1347, 1356-59 (N.D.Ga.2001)). Glastetter was binding authority, and not so easily dismissed and distinguished.

The Viagra MDL court ultimately placed its holding upon the facts that:

‘‘the McGwin et al. and Margo et al. studies were peer-reviewed, published, contain known rates of error, and result from generally accepted epidemiologic research.’’

In re Viagra, 572 F. Supp. 2d at 1081 (citations omitted). This holding was a judicial ipse dixit substituting for the expert witness’s ipse dixit. There were no known rates of error for the systematic errors in the McGwin study, and the ‘‘known’’ rates of error for random error in McGwin 2006 were intolerably high. The MDL court never considered any of the error rates, systematic or random, for the Margo & French study. The court appeared to have abdicated its gatekeeping responsibility by delegating it to unknown peer reviewers, who never considered whether the studies at issue in isolation or together could support a causal health claim.

With respect to the last of the three studies considered, the Gorkin study, McGwin opined that it was too small, and the data were not suited to assessing temporal relationship. Id. The court did not appear inclined to go beyond McGwin’s ipse dixit. The Gorkin study was hardly small, in that it was based upon more than 35,000 patient-years of observation in epidemiologic studies and clinical trials, and provided an estimate of incidence for NAION among users of Viagra that was not statistically different from the general U.S. population. See L. Gorkin, K. Hvidsten, R. Sobel, and R. Siegel, ‘‘Sildenafil citrate use and the incidence of nonarteritic anterior ischemic optic neuropathy,’’ 60 Internat’l J. Clin. Pract. 500, 500 (2006).

Judge Magnuson did proceed, in his 2008 opinion, to exclude all the other expert witnesses put forward by the plaintiffs. McGwin survived the defendant’s Rule 702 challenge, largely because the court refused to consider the substantial random variability in the point estimates from the studies relied upon by McGwin. There was no consideration of the magnitude of random error, or for that matter, of the systematic error in McGwin’s study. The MDL court found that the studies upon which McGwin relied had a known and presumably acceptable ‘‘rate of error.’’ In fact, the court did not consider the random or sampling error in any of the three cited studies; it failed to consider the multiple testing and interaction; and it failed to consider the actual and potential biases in the McGwin study.

Some legal commentators have argued that statistical significance should not be a litmus test. David Faigman, Michael Saks, Joseph Sanders, and Edward Cheng, Modern Scientific Evidence: The Law and Science of Expert Testimony § 23:13, at 241 (‘‘Statistical significance should not be a litmus test. However, there are many situations where the lack of significance combined with other aspects of the research should be enough to exclude an expert’s testimony.’’) While I agree that significance probability should not be evaluated in a mechanical fashion, without consideration of study validity, multiple testing, bias, confounding, and the like, handing waving about litmus tests does not excuse courts or commentators from totally ignoring random variability in studies based upon population sampling. The dataset in the Viagra litigation was not a close call.

Posted in Causation, Reference Manual on Scientific Evidence, Rule 702, statistical evidence | Comments Off on Love is Blind but What About Judicial Gatekeeping of Expert Witnesses? – Viagra Part I