Sometimes when federal courts permit dubious causation opinion testimony over Rule 702 objections, the culprit is bad lawyering by the opponent of the proffered testimony.  Allen v. Martin Surfacing, 263 F.R.D. 47 (D. Mass. 2009), may be an important example.

THE CLAIMS

Daniel Allen was the former football coach of the College of The Holy Cross, in Worcester, Massachusetts.  In spring of 2001, defendant Martin Surfacing refinished the gymnasium floor at the college.  Coach Allen was exposed to solvent fumes, including toluene fumes, during defendant’s work, as well as for a couple of months afterwards.   While exposed, Allen experienced “dizziness, headaches, and disorientation.” 263 F.R.D. at 51.  After the gym floor resurfacing was completed, Allen experienced other symptoms, such as fatigue, muscle weakness, and fasciculations in his lower limbs.  In January 2002, at the age of 45, Allen was diagnosed with amyotrophic lateral sclerosis (ALS).  Id. Allen’s condition progressed, and he died three years later, in May 2004.  Id. at 52.

Allen’s family sued for wrongful death.  The parties’ apparently agreed on the following:

• ALS occurs as a sporadic ALS, as well as “familial ALS,”
• the cause of sporadic ALS is unknown,
• Allen developed and died of sporadic ALS,
• no air sampling established overexposure to any chemical,
• there were no reliable exposure models to quantify Allen’s exposures,
• there are no known causes of sporadic ALS, and
• toluene did not cause Allen’s ALS

Remarkably, defendant lost the Rule 702 challenge to plaintiffs’ expert witnesses’ opinion testimony.  It is easy to suspect that the district judge was sleep at the gate, and that his gatekeeping was deficient.  A close read of the opinion supports the view that this was not Rule 702’s finest moment, but much more was going on to get to admissibility.

First, the plaintiffs’ counsel cleverly avoided running into a wall by avoiding a claim that toluene caused Allen’s ALS. Instead, plaintiffs’ claimed that toluene accelerated the onset of the disease.  This claim was equally dubious, but it allowed the expert witnesses to avoid a mountain of medical opinion, authoritative and well-supportive, that there is no known cause of sporadic ALS.

Second, the plaintiffs’ counsel took the initiative by filing an affirmative motion to admit the testimony of their expert witnesses.  Rather than ceding the initiative to the defendant, the plaintiffs seized the initiative and had the first and last word on admissibility.  As a result, plaintiffs were able to present and frame their witnesses’ opinions sympathetically rather than defensively.

Third, the plaintiffs had the good fortune of the defendant’s counsel’s apparent failure to find the key fallacies, invalidities, and flaws in plaintiffs’ questionable expert witness opinions.

The Allen case teaches that sometimes good lawyering can win a losing case.

The plaintiffs’ counsel retained and presented an array of expert witnesses who might be the usual suspects in a district court’s exclusion of expert witness testimony:

• L. Christine Oliver, MD
• Richard W. Clapp, Sc.D.
• Marcia H. Ratner, Ph.D
• William Ewing, C.I.H.

None of these four expert witnesses was a specialist in ALS or ALS causation; none was a neurologist; none had ever addressed ALS causation in a peer-reviewed article.  All four witnesses were frequent testifiers in tort litigation, and some have are repeat offenders when it comes to offering questionable or excludable opinion testimony.  Somehow, the defense dashed this opportunity by retaining only one expert, Dean M. Hashimoto, M.D., J.D., M.P.H., who was also not a specialist in ALS, who was not a neurologist, and who had never published anything on ALS.  And to make matters worse, the defense proceeded to challenge the plaintiffs’ expert witnesses for lack of qualifications!

The defense’s challenges to qualifications takes up a good deal of Judge Saylor’s published opinion, which illustrates the maxim that judges have short attention spans, and you should not waste the opportunity of a motion on an issue that is so easily decided against you.  The scientific issues are difficult and the temptation to avoid them is great.  By leading with an issue that will almost certainly lose, the defense wasted a valuable advocacy opportunity to show the court the fallacious reasoning in the plaintiffs’ case.  By submitting reports from only one expert witness, who had all the deficiencies claimed in the plaintiffs’ set of witnesses, the defense exhibited a duplicity that must have seriously undermined its credibility for the entire set of Rule 702 motion issues.

THE WITNESSES

Dr. Christine Oliver has been testifying in asbestos and other occupational lung disease cases for decades.  She is a pulmonary physician on staff at Massachusetts General Hospital, in Boston, and an associate professor of clinical medicine at the Harvard Medical School.  She is board certified in internal medicine and in occupational medicine (American Board of Preventive Medicine), and her clinical interests are asthma occupational lung disease, and health hazards of construction work.  If the defense had presented real expert witnesses in ALS causation, Dr. Oliver’s expertise would have seemed quite irrelevant.  Dr. Oliver has, as well as I can determine, never researched or published on ALS causation.  She has, however, published on “multiple chemical sensitivity,” which should give a disinterested court some pause.  See L. Christine Oliver and Alison Johnson, “Multiple Chemical Sensitivity: Reflections” (Nov. 4, 2011).

Richard Clapp, professor emeritus at the Boston University School of Public Health, is a known purveyor of dubious courtroom testimony. See, e.g., Sutera v. The Perrier Group of America Inc., 986 F.Supp. 655 (D. Mass. 1997).  He is a frequent testifier and a charter member of the surreptitiously funded SKAPP organization.  Clapp is a non-physician epidemiologist, who has never published on ALS.

Marcia Ratner Ph.D. may be best known for her possession of mace and an unlicensed gun, but she does occasionally show up in civil litigation as an expert witness.  See “Quincy District Court News,” Patriot Ledger June 09, 2010 (reporting that Ratner pleaded guilty to criminal possession of mace and a firearm).

Ratner is a postdoctoral researcher at Boston University, where she works as a neurotoxicologist.  She does not appear to have ever published a peer-reviewed paper on ALS or ALS causation.  Plaintiffs’ counsel claimed that she was researching a new drug with therapeutic potential for ALS treatment, although they were quite sketchy about details.  Ratner does not appear to hold any NIH grants for ALS drug research.

[Please see update on the discussion of Dr. Ratner at http://schachtmanlaw.com/gatekeeping-in-allen-v-martin-surfacing-postscript/]

William Ewing, an industrial hygienist, frequently testifies in asbestos litigation.  He offered no opinion on causation.

Against this field of witnesses, the defense punted on presenting its own witness with relevant expertise. Dr. Dean M. Hashimoto, the defense’s sole witness on causation, is a physician, lawyer, and has a master’s degree in occupational health.  Hashimoto has no specialized training in ALS or clinical neurology, although he serves on the Massachusetts Workers’ Compensation Board. A pubmed search  shows that Hashimoto has never published on the neurology or causation of ALS.

CAUSATION

The plaintiffs had a huge problem to avoid:  ALS has no known cause.  Counsel table could be filled up with textbooks and review articles, but perhaps the following, lengthy quote from the National Institute for Neurological Disorders and Stroke website suffices to make the point:

“What causes ALS?

The cause of ALS is not known, and scientists do not yet know why ALS strikes some people and not others. An important step toward answering that question came in 1993 when scientists supported by the National Institute of Neurological Disorders and Stroke (NINDS) discovered that mutations in the gene that produces the SOD1 enzyme were associated with some cases of familial ALS. This enzyme is a powerful antioxidant that protects the body from damage caused by free radicals. Free radicals are highly reactive molecules produced by cells during normal metabolism. If not neutralized, free radicals can accumulate and cause random damage to the DNA and proteins within cells. Although it is not yet clear how the SOD1 gene mutation leads to motor neuron degeneration, researchers have theorized that an accumulation of free radicals may result from the faulty functioning of this gene. In support of this, animal studies have shown that motor neuron degeneration and deficits in motor function accompany the presence of the SOD1 mutation.

Studies also have focused on the role of glutamate in motor neuron degeneration. Glutamate is one of the chemical messengers or neurotransmitters in the brain. Scientists have found that, compared to healthy people, ALS patients have higher levels of glutamate in the serum and spinal fluid. Laboratory studies have demonstrated that neurons begin to die off when they are exposed over long periods to excessive amounts of glutamate. Now, scientists are trying to understand what mechanisms lead to a buildup of unneeded glutamate in the spinal fluid and how this imbalance could contribute to the development of ALS.

Autoimmune responses—which occur when the body’s immune system attacks normal cells—have been suggested as one possible cause for motor neuron degeneration in ALS. Some scientists theorize that antibodies may directly or indirectly impair the function of motor neurons, interfering with the transmission of signals between the brain and muscles.

In searching for the cause of ALS, researchers have also studied environmental factors such as exposure to toxic or infectious agents. Other research has examined the possible role of dietary deficiency or trauma. However, as of yet, there is insufficient evidence to implicate these factors as causes of ALS.

Future research may show that many factors, including a genetic predisposition, are involved in the development of ALS.”

NINDS – “Amyotrophic Lateral Sclerosis (ALS) Fact Sheet.”

As a result, the plaintiffs adopted a strategy of confession and avoidance; they renounced any claim that they were asserting a causal claim.  Instead, they insisted that they were “merely” claiming that toluene exposure had accelerated the onset of sporadic ALS in Coach Allen.  This mere claim, however, was actually a causal claim in disguise, and the district judge was taken in by the ruse.  If plaintiffs were claiming that toluene can accelerate the onset of ALS by a meaningful period of time (years), then they were making a causal claim, legally and scientifically.  A shift in the age of onset of a sporadic disease is a causal claim, and it requires supporting evidence, not hand waving.

PLAUSIBLE MECHANISM

One scientist could postulate a reasonable mechanism even for a sporadic disease.  Professional journals and textbooks are filled with such speculation.  These postulations are part of science in that they inform research hypotheses and funding, but they are not conclusions of causality.  The quote above from the NINDS discusses the lack of an anti-oxidizing enzyme and glutamate toxicity as potential mechanisms in familial ALS, but even there, the authors are appropriately modest in avoiding a claim to know the pathogenesis of familial ALS.

The plaintiffs’ approach was to take the suggestion of a mechanism, misrepresent it as a known mechanism, and then claim that toluene activated glutamate toxicity and exercised an oxidizing effect on neurons. The plaintiffs’ team had no basis for claiming that short-term exposure to solvents, or toluene specifically, translated into a toxicity to the relevant human motor neurons that are involved in ALS.  It is a long stretch from suggesting a mechanism to documenting the mechanism to be actually at work in producing, or accelerating, a disease in humans.

A typical statement, from the Yale School of Medicine, Division of Neurology, in 2012:

“Why the motor neurons begin to die is still unknown. Recent evidence, however, have implicated glutamate excitotoxicity, free radical toxicity, and mitochondrial dysfunction as possible mechanisms, and this is an area of active research.”

“Amyotrophic Lateral Sclerosis (ALS)” (emphasis added).   See also Adams and Victor’s Principles of Neurology 1157-58 (7th ed. 2001) (noting that the pathogenesis of ALS and similar motor neuron diseases is not known).

The district judge seemed mesmerized by Ratner’s having providing a biologically plausible theory for tying ALS progression to toluene exposure.  263 F.R.D. at 60.  Judge Saylor stated that the defense did not address any flaw in Ratner’s methodology other than to point out that her theory was not supported by epidemiology.  The court seemed to equate providing a plausible theory with establishing a scientific conclusion.  More to the point, the court was truly asleep at its gatekeeping task because Ratner’s theory actually presupposed that she knew that Coach Allen was going to develop ALS in any event, only not as early as 2001.  The court faulted the defense for not showing that Ratner’s (and the other plaintiffs’ witnesses’) theory was unreliable, but the burden was on the plaintiffs to show reliability.  Id.  The court not only faulted the defense for carrying a burden it did not have, but it overlooked the very telling criticisms of Ratner’s theories of acceleration and mechanism.

EXCUSES – EPIDEMIOLOGY

Plaintiffs’ expert witnesses had a welter of excuses as to why there was no epidemiologic data to support their theories.  The absence of statistical significance, according to plaintiffs’ expert witnesses does not mean that a study should be disregarded.  Id. at 58.  Their claim is superficially true, but a study not disregarded does not necessarily support a causal inference, either alone or conjunction with other such studies. Similarly, plaintiffs’ claim that flawed studies should not be disregarded is also a half truth.  A flawed study may lead to a much better one, which can support valid inferences.  Flawed studies are thus part of the scientific process because they may lead to a self-correcting triangulation of the truth, but there is little to recommend relying upon flawed studies to support scientific conclusions of causality.  Nevertheless, the district court appeared to swallow these half truths, whole.

Ratner also advanced a claim that the acceleration theory had not been subjected to epidemiologic analysis because of “funding limitations, as most funding goes toward finding treatment or cures for the disease, not towards finding what accelerates the course of the disease.”  Id. at 59 n. 14.  The district court repeats this excuse without critical thought.  If a commonly used solvent such as toluene accelerated the onset of a terrible disease such as ALS by decades, such a putative effect would be amenable to epidemiologic analysis and would be a source of incredible concern and funding efforts by the NIH, NINDS, NIEHS, and other granting agencies and organizations.  Despite excusifying verbiage, Ratner maintained that there were no epidemiologic data that refuted her novel acceleration.  Id. at 59.  Of course, if her excuses were taken seriously, then this absence of refutation was fairly irrelevant, but in any event, this supposed absence could not support the reliability of Ratner’s inferences or conclusions.

The defense focused on the lack of short-term exposures in epidemiologic studies, and also the lack of statistical significance in some studies.  What appears to have been missing from both sides was a comprehensive analysis of the available epidemiologic data.  If long-term exposure were associated with earlier age of onset of ALS, or even a greater risk of ALS, then it would have given some support to Ratner’s novel theory.  The defense appeared to punt on the epidemiology by claiming its irrelevance.  It might have been helpful to point out internal as well as external validity issues to the court.

As for both sides citing different studies, and no side presenting a comprehensive view of the epidemiologic evidence, the court could have given some consideration to the ethical considerations of the incomplete presentation:

“Basis of Expert Medical Testimony

The testimony of an expert medical witness should be founded on a thorough and critical review of the pertinent medical and scientific facts, available data, and relevant literature.”

Ethical Guidelines for Occupational and Environmental Medicine Physicians Serving as Expert Witnesses (Oct. 25, 2007).

DIFFERENTIAL DIAGNOSIS

The plaintiffs’ claim that they were not asserting causation was disingenuous.  As noted above, acceleration of onset is a form of causation.  Of course, exposure to a neurotoxic material, with some symptoms, might have made Allen more aware of other symptoms, and so the time to diagnosis was abbreviated.  The plaintiffs, however, were claiming more than earlier ascertainment; they claimed the toluene exposure caused an underlying disease process to accelerate.

Oliver actually went further and performed an invalid differential etiologic analysis. Oliver reviewed medical records and claimed to have applied “differential diagnosis to the review.”  Id. at 63. This claim was quite bogus because there was no dispute that Allen had and died of ALS, but the district court was beguiled.  Having ruled out family history, Oliver claimed to then rule out other “putative causes” of ALS:  “pesticides and agricultural chemicals containing solvents, 60-hertz magnetic fields, and welding fumes.”  Id. at 63.  In one fell swoop, Oliver created several known causes to be ruled out, and then ruled them out in Allen’s case.  This is remarkable given that NINDS and most of medical sciences does not recognize any known or putative causes of sporadic ALS, and that Oliver failed to rule out the one potential cause that some scientists take seriously:  cigarette smoking.  See, e.g., Hao Wang, Éilis J. O’Reilly, Marc G. Weisskopf, Giancarlo Logroscino, Marji L. McCullough, Michael Thun, Arthur Schatzkin, Laurence N. Kolonel, Alberto Ascherio, “Smoking and risk of amyotrophic lateral sclerosis: a pooled analysis of 5 prospective cohorts” 68 Arch. Neurol. 207 (2011); A. Alonso, G. Logroscino, M.A. Hernán, “Smoking and the risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis,” 81 J. Neurol. Neurosurg. & Psychiatry 1249 (2010); F. Fang & W. Ye, “Smoking may be considered an established risk factor for sporadic ALS,” 74 Neurology 1927 (2010).

Of course, Oliver, and the entire plaintiffs’ expert witness team failed to rule out the most obvious, most prevalent explanation for Allen’s ALS:  unknown.

GENETIC SUSCEPTIBILITY

Ratner testified “to a reasonable degree of scientific certainty that Allen was genetically predisposed to develop ALS and would have developed and died from ALS later in his life.”  263 F.R.D. at 61.  This assertion was truly an incredible, unsupported, unverifiable, and unfalsifiable statement.  If a drug company ever made a similarly unsupported claim in an electronically transmitted document, the Department of Justice would prosecute it for wire fraud.  United States v. Harkonen, 2010 WL 2985257 (N.D. Calif. 2010).

The parties had essentially stipulated that Allen did not suffer from familial ALS, and neither Ratner nor anyone else identified any gene that was responsible for his “susceptibility.”  The district court, of course, did not report how Ratner could possibly have known that Allen was going to develop ALS, only at some unspecified date later than the date when Allen first became aware of signs and symptoms of motor neuron disease.  The district court announced that plaintiffs’ expert witnesses were not propounding “junk science,” but perhaps the heavy perfume helped masquerade the garbage.

POST HOC ERGO PROPTER HOC

The court conclusorily noted, without explanation, that the temporal relationship between exposure and disease manifestation would allow a conclusion of causality:

“Finally, after interpreting the data within a chronological context, the clinician may conclude that the patient’s disease is a neurotoxic illness.”

Id. at 61.  The court appears to accept the temporal pattern as sufficient in itself, or with other information, to support the conclusion.  This reasoning is fallacious.

AGE OF ONSET

Allen developed ALS when he was 45 years old.  Ratner reasoned that the average age of onset was 60, and Allen developed his disease “much earlier than would be expected”; therefore toluene accelerated the onset of Allen’s disease.  Id. at 61. The problem is that there is no “therefore” that can reasonably be claimed in the court’s sentence.

Most publications put the mean and median of age of ALS onset around 55 years, but even if the court were to accept Ratner’s reference to 60 as correct, surely the court recognized that half the cases therefore occurred below the age of 60.  The question of course is the variability in age of onset, and the court’s opinion is silent about the scatter or distribution of age-of-onset data.  Ratner’s reasoning was prima facie invalid unless there was additional information to show a very narrow distribution of age of onset around the mean.  It is difficult to discern whether the defense made this point, but Ratner could not have supported this counterfactual claim.

Here is what the ALS association has to say about the issue:

“Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 at the time of diagnosis. However, cases of the disease do occur in persons in their twenties and thirties.”

“Who Gets ALS.”

Ratner essentially conceded that her argument was vacuous and invalid.  When confronted at her deposition about whether age of onset greater than the mean would have changed her opinion, she emphatically denied its relevance:

“My opinion would be the same even if that guy died at 60 instead of 75 and had history of this exposure … but you wouldn’t have bothered to depose me in that case… . Somebody else has moved down from where they are to here. But it may not result in a lawsuit, and I wouldn’t be here, because— I wouldn’t be here.”

Ratner Deposition at 172-3.

RULE 702 ANALYSIS

The district court recognized the novelty of Ratner’s analysis, but opined that Ratner, Oliver, and Clapp had provided sufficient cumulative evidence to support their theories.  263 F.R.D. at 61.  The trial court apparently conducted a Rule 702 hearing, over three days. Both sides filed what appears to have been extensive briefing and affidavits.  There are some huge gaps in the reasoning of the plaintiffs’ expert witnesses, and in the district court’s opinion.  Perhaps those gaps could be filled in with volumes of testimony.  My unscientific opinion is to doubt it. Although the plaintiffs should have had the burden of showing admissibility, the defendant had the practical burden of illustrating the analytical gaps, ipse dixit, fallacies, and invalid inferences that were before the court.  The defense may have indeed pointed out such problems, which were fulsomely present, but the district court’s opinion does not report the obvious defense arguments.  Without more background information, it is difficult to evaluate comprehensively the court’s or the defense’s handling of the scientific issues that were clearly before the court on the Rule 702 motions.  What is clear from what the district court reports is, however, sufficient to document an unsatisfactory judicial review of the evidence discussed.

In the last post, I discussed an important article by Professors Davidson and Guzelian, on the legal implications of evidence-based medicine (EBM).  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].

Their criticism of the deficiencies in current gatekeeping practice cries out for reform of much current judicial practice.  Education of the judiciary in EBM would be helpful to both plaintiffs and defendants in civil cases, as well as prosecutors and defendants in criminal cases.  I will leave for another day a discussion of whether the boundary between knowledge and “mere opinion” is so easily discernible.

Although the authors’ call for EBM in judicial decisions is timely and needed, I noted my dissent to their assessment of one defense expert witness’s specific causation opinion in the hormone therapy litigation. Davidson and Guzelian criticize one district judge for having admitted the challenged testimony of a defense expert witness, Dr. Blaustein, who opined that (1) estrogen + progesterone combination post-menopausal hormone replacement therapy (CHRT) has not been shown to cause breast cancer, and (2) there is no generally accepted method for determining a cause of a woman’s breast cancer.  Cross v. Wyeth Pharms., Inc., CASE NO.: 8:06-cv-429-T-23AEP, 2011 U.S. Dist. LEXIS 89078; 2011 WL 3498305 (M.D. Fla. 2011) (Merryday, J.).

Here is how Davidson & Guzelian put the matter:

“Blaustein also opined that there is no generally accepted method for diagnosing specific medical causation—that is, whether a medical intervention or treatment, even if it is known to generally cause a result ‘X’ (e.g., breast cancer), caused a particular patient’s result ‘X’. Blaustein’s statement, accepted by the judge as befitting of presentation to the jury, is ‘simply false’.”

The claim that Blaustein’s statement is “simply false” is pretty strong for both general and specific causation, and partially explains my initial dissent.  The prestige of the Women’s Health Initiative (WHI), a large, randomized, clinical meta-trial of  CHRT, with its finding of an increased risk for breast cancer among women, certainly has made Dr. Blaustein’s opinion on general causation a distinctly minority view.  There are, however, some careful authors who have challenged the findings of the WHI on grounds of internal and external validity.  See, e.g., Samuel Shapiro, Richard Farmer, Helen Seaman, J. C. Stevenson, “Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies: part 2. The Women’s Health Initiative: estrogen plus progestogen,” 37 J. Family Planning & Reproductive Health Care 165, 165 (2011) (“HRT with estrogen plus progestogen may or may not increase the risk of breast cancer, but the WHI did not establish that it does.”).  In any event, given the state of the science, most defendants would hedge their position on general causation even if they stopped short of saying it was not established.  Still, the validity concerns may cause us to have some doubts that the conclusions drawn from the WHI and other studies are truly “knowledge.”

Professor Guzelian has persuaded me that their indictment of Blaustein’s opinion on specific causation is correct, at least technically.  There are, to be sure, a few genetic causes of breast cancer, such as the BrCa 1, and 2, genes, which can cause breast cancer, and which, if present in a particular woman, would constitute an adequate description of the cause of that woman’s cancer.  Blaustein claimed that there is no generally accepted method for attributing an individual woman’s breast cancer to known causes, and Davidson and Guzelian are correct that Blaustein’s claim is, therefore, “simply false.”

Given how cursory and conclusory the trial court’s opinion is, Davidson and Guzelian’s derision is, however, relatively uncharitable.  We can probably credit the plaintiff’s counsel with sufficient entrepreneurial savvy to have not pressed the claims of a woman who had a known genetic cause of breast cancer.  And we can similarly credit the defense counsel with sufficient intelligence not to have overlooked the presence of such a gene if it were present.

With genetic causes taken out of the equation, Blaustein’s opinion seems fairly unremarkable.  Even if the criticism of the trial court’s refusal to preclude Dr. Blaustein’s testimony on general causation were correct under Federal Rule of Evidence 702, Davidson and Guzelian have failed to make their case against the trial court, and Dr. Blaustein, on specific causation.

Here is what Davidson and Guzelian have to say about Blaustein’s specific causation opinion:

“EBM has documented and catalogued the best practices regarding how to diagnose whether generally applicable evidence-based conclusions hold for specific patients.⁵¹ Moreover, even if in a specific case it were plausible to assert that it is impossible to reach a specific causation conclusion for a particular patient’s condition using the scientific method, that is very different than saying that there is no scientific method for analyzing specific causation. According to EBM’s strictures, Blaustein’s proposed blanket denial of the possibility of specific causation should have been precluded from his testimony.⁵²”

Davidson at 757. The footnotes in this passage are to the section of an article on evidence-based toxicology, which deals with attribution of an adverse drug reaction.  Philip Guzelian et al., “Evidence-Based Toxicology: A Comprehensive Framework for Causation,” 24 Human & Experimental Toxicol. 161, 190-91 (Table 9) (2005) (presenting “an overview of evidence-based specific causation diagnostic criteria”). Putting aside the very substantial differences between cancer causation and the general run of adverse drug reactions, we can see that the proposed criteria for specific causation in the referenced article contain this extremely important criterion:

“No good alternative candidate (unexplained exacerbation or recurrence of underlying illness).”

Id.  Specific causation in a breast cancer case falls outside this criterion because most cases of breast cancer (with the exception of the genetic cases mentioned above) have no identifiable risk factor.  Dr. Blaustein’s opinion on specific causation — that there is no generally accepted method for attributing breast cancer to exogenous cause(s) — seems then exactly on point, even on the EBM criteria for specific causation urged by the authors.

In Cross, the trial court does not provide any insight into the basis for the plaintiffs’ challenge to Blaustein’s specific causation opinion, and I am aware of none.  The trial court does not give us any particulars of the plaintiff’s use of CHRT or development of breast cancer, and there is no suggestion that she had an extraordinarily high risk (say > 10-fold increase, which I have never seen reported, in any event).

The plaintiffs did not attempt to infer causation from risk.  Perhaps they thought better of it, or perhaps one of their testifying epidemiologists, Dr. Graham Colditz, refused to support such an inference:

“Knowledge that a factor is associated with increased risk of disease does not translate into the premise that a case of disease will be prevented if a specific individual eliminates exposure to that risk factor. Disease pathogenesis at the individual level is extremely complex. As Rose stated, a preventive measure that brings large benefits to the community offers little to each participating individual [3]. Accordingly, epidemiology must be harnessed to identify the population level strategies that will reduce the burden of illness.”

Graham A. Colditz, “From epidemiology to cancer prevention: implications for the 21st Century,” 18 Cancer Causes Control 117, 118 (2007).  Professor Colditz’ view is hardly unique; there are many similar refusals to base an inference of specific causation upon an increased risk, whether or not that increased risk is quantified as a relative risk greater than two.  The late David Freedman, who was the co-author of the chapters on statistics in all three editions of the Reference Manual on Scientific Evidence, was also a naysayer when it came to transmuting risk into cause:

“The scientific connection between specific causation and a relative risk of two is doubtful. *** Epidemiologic data cannot determine the probability of causation in any meaningful way because of individual differences.”

David Freedman & Philip Stark, “The Swine Flu Vaccine and Guillaine-Barré Syndrome:  A Case Study in Relative Risk and Specific Causation,” 64 Law & Contemporary Problems 49, 61 (2001).

The plaintiffs’ challenge to Blaustein’s claim that there was no “generally accepted” method for specific causal attribution took the form of advancing their own “method”:  differential diagnosis. At face value, the plaintiffs’ use of differential diagnosis to advance a claim of specific causation is “simply false.”  There was no dispute about diagnosis, and no differential diagnosis at issue.  Unfortunately, courts have permitted lawyers to corrupt the meaning of differential diagnosis and contend that it covers something akin to differential etiology.

Davidson and Guzelian, in their reference back to an earlier article on evidence-based toxicology, embrace differential etiology as a method of specific case attribution.  I agree that there is really no dispute about the logically validity of such reasoning, generally.  The logic of differential etiology is simple.  If you can specify all the known causes of a disease, and eliminate all but one cause, then you have ruled in the specific cause.  Logically, this is an iterative disjunctive syllogism, also known as the process of elimination.  The syllogism requires an exhaustive statement of disjuncts, with the negation of all but one:

A v B v C v D

~A and ~B and ~ C.

Therefore, D.

In “The Adventure of the Beryl Coronet,” Sir Arthur Conan Doyle had his famous detective, Sherlock Holmes, articulate this method in ordinary English, with a bit more flair:

“It is an old maxim of mine that when you have excluded the impossible, whatever remains, however improbable, must be the truth.”

Arthur Conan Doyle, The Penguin Complete Sherlock Holmes 315 (Penguin 1981). The process of elimination was a mainstay of Holmes’ forensic thought:

“Eliminate all other factors, and the one which remains must be the truth.”

“The Sign of the Four,” chap. 1 (“The Science of Deduction”), in Arthur Conan Doyle, The Penguin Complete Sherlock Holmes at 92 (Penguin 1981).

The problem of course is, for a disease such as breast cancer, is that one of the disjuncts has been, and will remain, for some time: the proposition that this case is “idiopathic” or “sporadic.” The plaintiffs in Cross did not advance any plausible method for eliminating this disjunct.  As a result, they can never arrive at a conclusion that CHRT was a cause of Ms. Cross’s breast cancer.  The closest they can get to their desired conclusion with this “method,” once they have eliminated genetic causes, is a conclusion that:

The case is idiopathic OR the case resulted from CHRT.

This conclusion is not really a conclusion at all, but an indeterminate statement, which would be quite unhelpful to the trier in deciding the case. Furthermore, as the case is described by the trial court’s opinion, the plaintiffs did not even attempt a quantification of the probability of each of these two disjuncts.  Thus, the plaintiffs failed to offer any substantial evidence that a jury could believe to find in their favor on specific causation.  The trial court was correct to reject the challenge to Dr. Blaustein’s specific causation opinion, but the court should have granted the defendants’ challenge to the plaintiffs’ expert witnesses, who had no method at all on the crucial element of specific causation.

Interestingly, one of the plaintiffs’ better arguments against Dr. Blaustein was that he was, as a clinician, unqualified to opine on causation.  Cross, *9.  The trial court did not elaborate on the argument other than to point out that plaintiffs had emphasized that Dr. Blaustein relied upon his “unquantifiable and untested clinical experience.” Cross, *10. The courts have been remarkably resistant to the argument that physicians are generally unqualified to interpret scientific evidence of causation.  Sadly, there is a good deal of empirical evidence to show that physicians are not particularly well trained in statistics or in interpreting clinical research.  See, e.g., Donna Windish, Stephen Huot, and Michael Green, “Medicine Residents’ Understanding of the Biostatics and Results in the Medical Literature,” 298 J. Am. Med. Ass’n 1010, 1010 (2007) (“Most residents in this study lacked the knowledge in biostatistics to interpret many of the results in published clinical research.”).

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.

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.