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Call for Evidence-Based Medicine in Medical Expert Opinions

October 30th, 2012 


Evidence-based medicine (EBM) seeks to put health care decision making on a firm epistemic foundation, rather than on the personal opinion of health care providers.  David Sackett, et al., “Evidence based medicine: what it is and what it isn’t,” 312 Brit. Med. J. 71 (1996).  EBM thus offers a therapeutic intervention, sometimes in the form of strong medicine, to the sloppy thinking, intuition, mothers’ hunches, and leveling of studies that remain prevalent in the Rule 702 gatekeeping of medical causation opinion testimony in courts.  There are some who have suggested that EBM addresses therapeutic interventions only, and not disease causation by exogenous substances or processes.  A very recent publication in the Tort Trial & Insurance Practice Law Journal provides a strong rebuttal to the naysayers and a clear articulation of the need now, more than ever, for greater acknowledgment of EBM in the evaluation of expert witness opinion testimony.  Terence M. Davidson & Christopher P. Guzelian, “Evidence-based Medicine (EBM): The (Only) Means for Distinguishing Knowledge of Medical Causation from Expert Opinion in the Courtroom,” 47 Tort Trial & Ins. Practice L. J. 741 (2012) [cited as Davidson].


Terence M. Davidson is a physician, a Professor of Surgery, and the Associate Dean for Continuing Medical Education at the University of California, San Diego School of Medicine.  Christopher P. Guzelian   is an Assistant Professor of Law at Thomas Jefferson School of Law, in San Diego, California. Davidson and Guzelian bring the Rule 702 discussion and debate back to the need for epistemic warrant, not glitz, glamour, hunches, prestige, and the like.  Their article is a valuable contribution, and the authors’ presentation and defense of EBM in the gatekeeping process is commendable.


There are some minor dissents I would offer.  For instance, in applying EBM principles to causation of harm assessments, we should recognize that there are asymmetries between determining therapeutic benefit and environmental or occupational harm.  Physicians, even those practicing EBM, may well recommend removal from a potentially toxic exposure because the very nature of their clinical judgment is often precautionary.  Tamraz v. BOC Group Inc., No. 1:04-CV-18948, 2008 WL 2796726 (N.D. Ohio July 18, 2008) (denying Rule 702 challenge to treating physician’s causation opinion), rev’d sub nom., Tamraz v. Lincoln Elec. Co., 620 F.3d 665, 673 (6th Cir. 2010) (carefully reviewing record of trial testimony of plaintiffs’ treating physician; reversing judgment for plaintiff based in substantial part upon treating physician’s speculative causal assessment created by plaintiffs’ counsel; “Getting the diagnosis right matters greatly to a treating physician, as a bungled diagnosis can lead to unnecessary procedures at best and death at worst. But with etiology, the same physician may often follow a precautionary principle: If a particular factor might cause a disease, and the factor is readily avoidable, why not advise the patient to avoid it? Such advice—telling a welder, say, to use a respirator—can do little harm, and might do a lot of good. This low threshold for making a decision serves well in the clinic but not in the courtroom, where decision requires not just an educated hunch but at least a preponderance of the evidence.”) (internal citations omitted), cert. denied, ___ U.S. ___ , 131 S. Ct. 2454, 2011 WL 863879 (2011).


The wisdom of the Tamraz decision (in the 6th Circuit) lies in its recognition of the asymmetries involved in medical decision making.  For most diseases, physicians rarely have to identify an etiology to select efficacious treatment.  This asymmetry affects the general – specific causation distinction.  A physician will want some epistemic warrant for the judgment that a therapy or medication is efficacious.  In other words, the physician needs to know that there is efficacy, even though the intervention may not be efficacious in every case.  If the risk ratio for an intervention (where the risk is cure of the disease or disorder), is greater than 1.0, and chance, bias, and confounding are eliminated as explanations for the observed efficacy, then that intervention likely goes into the physician’s therapeutic armamentarium.  The risk ratio, of course, need not be greater than two for the intervention to remain clinically attractive.  Furthermore, if the therapy is provided, and the patient improves, the determination whether therapy itself was efficacious is often not a pressing clinical matter.  After all, if the risk ratio was greater than one, but two or less, then the improvement may have been spontaneous and unrelated to therapy.


Davidson and Guzelian do not fully recognize this asymmetry, which leads the authors into error.  They give an example in which a defense expert witness proferred a personal opinion about general causation of breast cancer by post-menopausal hormone replacement therapy, which opinion is undermined and contradicted by a judgment reached with EBM principles.  See Cross v. Wyeth Pharm., Inc., 2011 U.S. Dist. LEXIS 89078, at *10 (M.D. Fla. Aug. 10, 2011).  Fair enough, but Davidson and Guzelian then claim that the errant defense expert had no basis for claiming that there was no generally accepted basis for “diagnosing specific medical causation.” Davidson at 757.  The authors go even further and claim that the defense expert’s statement is “simply false.” Id.


I would suggest that the authors have gotten this dead wrong.  In this sort of case, the plaintiff’s expert witness is usually the one casting about for a basis to support specific attribution.  The authors offer no basis for their judgment that the defense expert witness is wrong, or lacks a basis for his specific causation judgment. The poor, pilloried defense expert was, in the cited case, opining that there was no way to attribute a particular patient’s breast cancer to her prior use of post-menopausal hormone replacement therapy.  Putting aside the possibility of long-term use (with risk ratio greater than 2.0), the expert’s opinion is reasonable. General causation does not logically or practically imply specific causation; they are separate and distinct determinations.  Perhaps a high risk ratio might justify a probabilistic inference that the medication caused the specific patient’s breast cancer, but for many HRT-use factual scenarios, the appropriate risk ratio is two or less.  If there is some other method Davidson and Guzelian have in mind, they should say so. The authors miss an important point, which is that EBM sets out to provide a proper foundation for judgments of causality (whether of therapeutic benefit or harm), but it often does not have the epistemic foundation to provide a resolution of the individual causation issue. In medicine, there often is simply no need to do so.




One other nit.  The authors briefly discuss statistical significance, citing the Supreme Court’s recent foray into statistical theory.  Davidson at 747 & n. 14 (citing Matrixx Initiatives, Inc. v. Siracusano, 131 S. Ct. 1309, 1321 (2011)).  In their explanatory parenthetical, however, the authors describe the case as “holding that a lack of statistical significance in a pharmaceutical company’s results does not exempt the company from material disclosure requirements for reporting adverse events during product testing.”  Id.  


Matrixx Initiatives held no such thing; the Supreme Court was faced with an adequacy of pleadings case. No evidence was ever offered; nor was there any ruling on the reliability or insufficiency of evidence of causation. Matrixx Initiative’s attempt to import Rule 702 principles of reliability into a motion to dismiss on the pleadings was seriously misguided. Even assuming that statistical significance was necessary to causation, regulatory action did not require a showing of causality. Therefore, statistical significance was never necessary for the plaintiffs’ case. Second, the company’s argument that the adverse event reports at issue were “not statistically significant” was fallacious because adverse event reports, standing alone, could not be “statistically significant” or “insignificant.” The company would need to know the expected base rate for anosmia among Zicam users, and it would need to frame the adverse event reports in terms of an observed rate, so that the expected and observed rates could be compared against an assumption of no difference. Third, the class plaintiffs had alleged considerably more than just the adverse events, and the allegations taken together deserved the attention of a reasonable investor.  Bottom line:  the comments that the Court made about the lack of necessity for statistical significance were pure obiter dictum.


Highlighting these two issues in the Davidson & Guzelian article should not detract from the importance of the authors’ general enterprise. There is an aversion to examining the “epistemic warrant” behind opinion evidence in federal court gatekeeping.  Anything that treats that aversion, such as Davidson & Guzelian’s article, is good medicine.

				


				
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Origins of the Relative Risk of Two Argument for Specific Causation

				October 20th, 2012 

				

					
In an unpublished paper, which Professor Susan Haack has presented several times over the last few years, she has criticized the relative risk [RR] >2 argument.  In these presentations, Haack has argued that the use of RR to infer specific causation is an example of flawed “probabilism” in the law.  Susan Haack, “Risky Business:  Statistical Proof of Individual Causation,” in Jordi Ferrer Beltrán, ed., Casuación y atribución de responsibilidad (Madrid: Marcial Pons, forthcoming)[hereafter Risky Business]; Presentation at the Hastings Law School (Jan. 20, 2012);  Presentation at University of Girona (May 24, 2011).  Elsewhere, Haack has criticized the use of relative risks for inferring specific causation on logical grounds.  See, e.g., Susan Haack, “Warrant, Causation, and the Atomism of Evidence Law,” 5 Episteme 253, 261 (2008)[hereafter “Warrant“];  “Proving Causation: The Holism of Warrant and the Atomism of Daubert,” 4 J. Health & Biomedical Law 273, 304 (2008)[hereafter “Proving Causation“].  (See Schachtman, “On the Importance of Showing Relative Risks Greater Than Two – Haack’s Arguments” (May 23, 2012) (addressing errors in Haack’s analysis).


In “Risky Business,” Haack describes the RR > 2 argument as the creation of government lawyers from the litigation over claims of Guillain-Barré syndrome (GBS), by patients who had received swine flu vaccine.  Like her logical analyses, Haack’s historical description is erroneous.  The swine flu outbreak of 1976, indeed, had led to a federal governmental immunization program, which in turn generated claims that the flu vaccine caused GBS.  Litigation, of course, ensued.  The origins of the RR > 2 argument, however, predate this litigation.


GBS is an auto-immune disease of the nervous system.  The cause or causes of GBS are largely unknown. In the GBS vaccine cases, the government took the reasonable position that treating physicians or clinicians have little or nothing to contribute to understanding whether the swine-flu vaccine can cause GBS or whether the vaccine caused a particular patient’s case.  Cook v. United States, 545 F. Supp. 306 (N.D. Cal. 1982); Iglarsh v. United States, No. 79 C 2148, 1983 U.S. Dist. Lexis 10950 (N.D. Ill. Dec. 9, 1983).  The government did, however, concede that cases that arose within 10 weeks of vaccination were more likely than not related on the basis of surveillance data from the Centers for Disease Control.  After 10 weeks, the relative risk dropped to two or less, and thus the plaintiffs who developed GBS 10 weeks, or more, after immunization were more likely than not idiopathic cases (or at least non-vaccine cases).  See Michael D. Green, “The Impact of Daubert on Statistically Based Evidence in the United States,” Am. Stat. Ass’n, Proc. Comm. Stat. Epidem. 35, 37-38 (1998) (describing use of probabilistic evidence in the GBS cases).


Haack’s narrative of the evolution of the RR > 2 argument creates the impression that the government lawyers developed their defense out of thin air.  This impression is false.  By the time, the Cook and Iglarsh cases were litigated, the doubling of risk notion had been around for decades in the medical literature on radiation risks and effects.  Ionizing radiation had been shown to have genetic effects, including cancer risk, in the 1920’s.  By the time of the Manhattan project, radiation was a known cause of certain types of cancer. Although there was an obvious dose-response relationship between radiation and cancer, the nature of the relationship and the existence of thresholds were not well understood.  Medical scientists, aware that there were background mutations and genetic mistakes, thus resorted to a concept of a “doubling dose” to help isolate exposures that would likely be of concern.  See, e.g., Laurence L. Robbins, “Radiation Hazards:  III. Radiation Protection in Diagnostic Procedures,” 257 New Engl. J. Med. 922, 923 (1957) (discussing doubling dose in context of the medical use of radiation).


By 1960, the connection between “doubling dose” and a legal “more likely than not” evidentiary standard was discussed in the law review literature.  See, e.g., Samuel D. Estep, “Radiation Injuries and Statistics: The Need for a New Approach to Injury Litigation,” 59 Mich. L. Rev. 259 (1960).  If the doubling dose concept was not obviously important for specific causation previously, Professor Estep made it so in his lengthy law review article.  By 1960, the prospect of litigation over radiation-induced cancers, which had a baseline prevalence in the population, was a real threat.  Estep described the implications of the doubling dose:




“This number is known technically as the doubling dose and has great legal significance under existing proof rules.”




Id. at 271. 


* * *




“The more-probable-than-not test surely means simply that the trier of fact must find that the chances that defendant’s force caused the plaintiff’s injuries are at least slightly better than 50 percent; or, to put it the other way, that the chances that all other forces or causes together could have caused the injury are at least no greater than just short of 50 percent. Even if such an analysis is inapplicable to other types of cases, in those cases in which the only proof of causal connection is a statistical correlation between radiation dose and injury, the only just approach is to use a percentage formula. This is the case with all nonspecific injuries, including leukemia. Under existing rules the only fair place to draw the line is at 50 percent. These rules apply when the injury is already manifested as of the time of trial.”




Id. at 274.


The RR >2 argument was also percolating through the biostatistical and epidemiologic communities before the Cook and Iglarsh cases.  For instance, Philip Enterline,  a biostatistician at the University of Pittsburgh, specifically addressed the RR > 2 argument in a 1980 paper:




“The purpose of this paper is to illustrate how epidemiologic data can be used to make statements about causality in a particular case.”  


* * *


“In summary, while in a given instance we cannot attribute an individual case of disease to a particular occupational exposure, we can, based on epidemiologic observation, make a statement as to the probability that a particular occupational exposure was the cause.  Moreover, we can modify this probability by taking into consideration various aspects of a particular case.”  




Philip Enterline, “Attributability in the Face of Uncertainty,” 78 (Supp.) Chest 377, 377, 378 (1980).


About the time of the Cook case, the scientific media discussed Enterline’s suggestion for using epidemiologic data to infer specific causation.  See, e.g., Janet Raloff, “Compensating radiation victims,” 124 Science News 330 (1983).  Dr. David Lilienfeld, son of the well-known epidemiologist Abraham Lilienfeld, along with a lawyer, further popularized the use of attributable risk, derived from a relevant RR to quantify the probability that an individual case is causally related to an exposure of interest.  See David Lilienfeld & Bert Black, “The Epidemiologist in Court,” 123 Am. J. Epidem. 961, 963 (1986) (describing how a relative risk of 1.5 allows an inference of attributable risk of 33%, which means any individual case is less likely than not to causally related to the exposure). 


In the meanwhile, the RR argument picked up support from other professional epidemiologists.  In 1986, Dr. Otto Wong explained that for many common cancers, tied to multiple non-specific risk factors, probabilistic reasoning was the only way to make a specific attribution:




“In fact, all cancers have multiple causes. Furthermore, clinical features of cancer cases, caused by different risk factors, are seldom distinguishable from one another. Therefore, the only valid scientific way to address causation in a specific individual is through use of probability.”




Otto Wong, “Using Epidemiology to Determine Causation in Disease,” 3 Natural Resources & Env’t 20, 23 (1988).  The attributable risk [AR], derived from the RR, was the only rational link that could support attribution in many cases:




“For AR [attributable risk] to be greater than 50% (more likely than not), RR has to be greater than 2.  Thus, for any exposure with a RR of less than 2, the cancer cannot be attributed to that exposure according to the ‘more likely than not’ criterion.  That is, that cancer is ‘more likely than not’ a background case.”


***


“The epidemiologic measure for probability of causation is attributable risk, which can be used to determine whether a particular cause in an individual case meets the ‘more likely than not’ criterion.”




Id. at 24.


In 1988, three Canadian professional epidemiologists described the acceptance of the use of epidemiologic data to attribute bladder cancer cases in the aluminum industry. Ben Armstrong, Claude Tremblay, and Gilles Theriault, “Compensating Bladder Cancer Victims Employed in Aluminum Reduction Plants,” 30 J. Occup. Med. 771 (1988).


The use of the RR > 2 argument was not a phenomenon limited to defense counsel or defense-friendly expert witnesses.  In 1994, a significant textbook, edited by two occupational physicians who were then and now associated with plaintiffs’ causes, explicitly embraced the RR argument. Mark R. Cullen & Linda Rosenstock, “Principles and Practice of Occupational and Environmental Medicine,” chap. 1, in Linda Rosenstock & Marc Cullen, eds., Textbook of Clinical Occupational and Environmental Medicine 1 (Phila. 1994) [Cullen & Rosenstock].


The editors of this textbook were also the authors of the introductory chapter, which discussed the RR > 2 argument.  The first editor-author, Mark R. Cullen,  is now a Professor of Medicine in Stanford University’s School of Medicine.  He is a member of the Institute of Medicine (IOM). Professor Cullen has been involved in several litigations, almost always on the plaintiffs’ side.  In the welding fume litigation, Cullen worked on a plaintiff-sponsored study of Mississippi welders.  Linda Rosenstock was the director for the National Institute for Occupational Safety and Health (NIOSH) from 1994 through 2000. Dr. Rosenstock left NIOSH to become the dean of the University of California, Los Angeles School of Public Health.  She too is a member of the IOM.  Here is how Cullen and Rosenstock treat the RR > 2 argument in their textbook:




“In most workers’ compensation and legal settings, one of the physician’s roles in OEM [occupational and environmental medicine] practice is to establish whether or not it is probable (greater, than 50% likelihood) that the patient’s injury or disease is occupationally or environmentally related. Physicians, whose standards of scientific certainty are usually considerably higher than those of the legal field (for example, often at the 95% level that an observed association did not occur by chance), need to appreciate that a disease may be deemed work related (i.e., in legal jargon, with medical certainty or more probable than not) even when there remains significant uncertainty (up to 50%) about this judgment.


Epidemiologic or population-based data may be used to provide evidence of both the causal relationship between an exposure and an outcome and the likelihood that the exposure is related to the outcome in an individual case. *** Although they are not fully conclusive, well-performed and interpreted epidemiologic studies can play an important role in determining the work-relatedness of disease in a person, using some of the additional guidelines below.”


***


“The concept of attributable fraction, known by many names, including attributable risk and etiologic fraction, has particular utility in determining the likelihood of importance of a hazardous exposure. Although these numbers refer to risks in groups, as shown in the following section, reasonable extrapolations from these numbers can often be made about risks in individuals.”




Cullen & Rosenstock at 13. Cullen & Rosenstock work through an easy example and discuss its implications:




“For example, if all the members of a population are exposed to a factor, and there is a RR of 5 of disease in relation to the factor, then the PAR = 80% (= (5 – 1)/5 X 100). If exposures and other population characteristics are similar in a second population, then it also can be assumed that this factor will account for 80% of cases of the disease. A short conceptual leap can be made to individual attribution:  if an affected individual is similar (e.g., in age and gender) to those in the population and is similarly exposed (e.g., similar duration, intensity, and latency), then there is an 80% likelihood that the factor caused the disease in that individual.”


***


“By this reasoning of assuming that all in a population are exposed and the relative risk is greater that [sic] 2, then the PAR [population attributable risk] is greater than 50% (where PAR = (2 – 1)/2 X 100%).  Accordingly, if an affected individual is similar to the population in a study that has demonstrated a RR ≥  2, then the legal test (that there is a greater than 50% likelihood that the factor caused disease) can be met.”


***


“In cases in which the relative risks are stable (i.e., very narrow confidence intervals) and the patient is typical of the population studied, one can state these individual attributable risks with some assurance that they are valid estimates. When the studies are of limited power or give varying results, or if the patient’s exposure cannot be easily related to the study population., caution in using this method is appropriate.”




Cullen & Rosenstock at 13-14. Cullen and Rosenstock embraced probabilistic evidence because they understood that antipathy to probabilistic inference meant that there could be no rational basis for supporting recoveries in the face of known hazards that carried low relative risks (greater than 2).  The “conceptual leap” these authors described is small compared to the unbridgeable analytical gaps that result from trying to infer specific causation from clinicians’ hunches.

				


				
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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.


 


 


 


 

				


				
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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


    

  1. the testimony is based upon sufficient fact or data,
    2. 

  2. the testimony is the product of reliable principles and methods; and
    3. 

  3. the witness has applied the principles and methods reliably to the facts.”
    4. 





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.

				


				
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