TORTINI

For your delectation and delight, desultory dicta on the law of delicts.

EPA Research on Ultrafine Particulate Matter

June 26th, 2013

White Hat Bias

Hyping environmental and so-called toxic risk has gone on so long that many Americans have no sense of the truth when it comes to the causal consequences of personal, occupational, and environmental exposures.  Recently, I listened to a lecture given by Judge Calibresi of the Second Circuit.  In the course of talking about regulatory prohibitions and tort-law incentives, he told of his visit to the late Professor Bickel, who had then just been diagnosed with brain cancer.  In his lecture, Judge Calibresi stated that he knew that Bickel’s brain cancer was caused by his smoking, and went on to muse whether banning smoking would have saved his friend’s life.  Judge Calibresi’s ruminations upon the nature of regulation and tort law were profound; his cursory hipshot about what caused his friend’s terminal illness, juvenile.

Some years ago, a science journalist published an account of how dire predictions of asbestos deaths had not come to pass.  Tom Reynolds, “Asbestos-Linked Cancer Rates Up Less Than Predicted,” 84 J. Nat’l Cancer Instit. 560 (1992)

Reynolds quoted one scientist as saying that:

“the government’s exaggeration of the asbestos danger reflects a 1970s’ Zeitgeist that developed partly in response to revelations of industry misdeeds.  ‘It was sort of the “in” thing to exaggerate … [because] that would be good for the environmental movement’….  ‘At the time it looked like you were wearing a white hat if you made these wild estimates. But I wasn’t sure whoever did that was doing all that much good.”

Id. at 562.  Reynolds’ quote captures the nature of “white-hat” bias, a form of political correctness applied to issues that really depend upon scientific method and data for their resolution.  Perhaps the temptation to overstate the evidence against a toxic substance is unavoidable, but it diminishes the authority and credibility of regulators entrusted with promulgating and enforcing protective measures.

White-Hat Bias & Black-Hat Ethics

I recently came across a disturbing article in the Environmental Health Perspectives, a peer-reviewed journal, supported by the National Institute of Environmental Health Sciences, National Institutes of Health, United States Department of Health and Human Services.  The article detailed a case report of an individual woman experimentally exposed to ultrafine particulate matter (PM 2.5) in a test chamber.  Andrew J. Ghio, Maryann Bassett, Tracey Montilla, Eugene H. Chung, Candice B. Smith, Wayne E. Cascio, and Martha Sue Carraway, “Case Report: Supraventricular Arrhythmia after Exposure to Concentrated Ambient Air Pollution Particles,” 120 Envt’l Health Perspect. 2275 (2012) [Ghio article].  There were no controls.

The point of the case report was that a person exposed to PM 2.5, experimentally, experienced a “cardiac event,” (atrial fibrillation or AFib) which resolved after cessation of exposure.  The experiment was conducted in a federal agency facility, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Chapel Hill, North Carolina.

The authors stated that the experiment had the approval of the University of North Carolina School of Medicine Committee on the Protection of the Rights of Human Subjects. Given that the EPA has made extraordinary claims about the harmfulness of PM 2.5, including heart disease, lung disease, and cancers, and that there was no imaginable benefit to the subject from participating in the experiment, this experiment seemed dubious indeed.  The narrative of the case report, however, reveals even more disturbing information about the potential improprieties of the human experiment.

The PM Chamber

The human guinea pig was 58 years old.  Her age is significant. Although the authors claim that AFib is uncommon among those under 60, it does increase with age.  The human subject in the published experiment was close to the age at which AFib is no longer uncommon, and she was unwell to begin with.

The case report notes that the human subject had previously participated in the same exposure “protocol” without “complications.”  The report does not explain why this human subject was returning to the EPA center for being placed in a “chamber,” and being exposed sequentially to “filtered air and concentrated ambient particles (CAPs).” The implied suggestion is that she was a likely candidate to experience a “cardiac event” eventually from repeated exposures in the PM 2.5 chamber.

The “Subject”

The human subject was not well.  Although she was asymptomatic on the day of the experimental exposure to CAPs, she had a history of osteoarthritis and hypertension.  The latter condition was being treated with an angiotensin-converting enzyme inhibitor and a diuretic (10 mg. lisinopril and 12.5 mg. hydrochlorothiazide).  The subject had had surgeries for hernia repair, cholecystectomy, and knee arthroplasty. She was a little over 5 feet 6 inches tall, and obese, weighing over 230 pounds, with a 45 inch waist.

In addition to her chronic hypertension, morbid obesity, and musculoskeletal disease, the subject also had a family and personal history of heart disease.  Her father had died from a myocardial infarction, at the age of 57.  Immediately before the experimental exposure, a Holter monitor showed evidence of increased supraventricular ectopy, with 157 ± 34 premature atrial contractions/hour.

The investigators do not tell us how the experimental exposure relates to typical urban exposures, or to EPA regulatory standards, guidelines, or recommendations.  About 23 minutes after exposure to CAPs started (filter weight, 112 μg/m3; particle number, 563,912/cc), the human subject developed a “nonsustained atrial fibrillation that quickly organized into atrial flutter.”  The woman remained asymptomatic, and her EKG showed that she spontaneously reverted to a normal sinus rhythm.

The investigators acknowledge that there are many risk factors for AFib, and that the subject had several of them: hypertension, obesity, and possibly family history.  The woman had a history of premature atrial contractions, which may have increased her risk for AFib.

Despite this rich clinical background, the authors claim, without apparently trying very hard, that there was no “obvious” explanation for the subject’s arrhythmia while in the chamber.  They argue, however, that the exposure to PM 2.5 was causal because the arrhythmia began in the chamber, and resolved when the subject was removed from exposure.  The argument is rather weak considering that the subject may have been stressed by the mere fact of placement in a chamber, or being wired up to monitors.  See, e.g., Luana Colloca, MD, PhD, and Damien Finniss, MSc Med., “Nocebo Effects, Patient-Clinician Communication, and Therapeutic Outcomes,” 307 J. Am. Med. Ass’n 567, 567 (2012). The authors of the PM 2.5 case report acknowledge that “coincident atrial fibrillation cannot be excluded,” but they fail to deal with the potentially transient nature of AFib.

Human experimentation requires a strong rationale in terms of helping the experimental participant.  What was the rationale for this human experiment?  Here is what the EPA investigators posit:

“Although epidemiologic data strongly support a relationship between exposure to air pollutants and cardiovascular disease, this methodology does not permit a description of the clinical presentation in an individual case. To our knowledge, this is the first case report of cardiovascular disease after exposure to elevated concentrations of any air pollutant.”

Ghio at 275. The authors seemed to be saying that we know that PM 2.5 causes cardiovascular disease, but we wanted to be able to describe a person in the throes of a cardiovascular event brought on by exposure. See also Andrew J. Ghio, Jon R. Sobus, Joachim D. Pleil, Michael C. Madden, “Controlled human exposures to diesel exhaust,” 142 Swiss Med. Weekly w13597 (2012).

The Whole Truth

The Ghio article mentions only the one woman who experienced the mild, transient AFib.  A reader might wonder whether she was the only test subject.  Why was she retested after a previously incident-free experience in the chamber? How many other people were subjected to this protocol?

What is remarkable is that the authors claim not only an “association,” but causality, in a totally uncontrolled experiment, and without ruling out chance, bias, or confounding.  The article is both deficient in scientific methodological rigor, and dubious on ethical principles.

EPA – Hoisted With Its Own Petard

What I did not realize when I read this experimental case report is that the article had been a cause célèbre of the anti-regulatory right.  The EPA had walked right onto an ethical landmine by first sponsoring this research, and then by relying upon it to support a regulatory report. Steven Milloy editorialized about the EPA research, followed by a FOIA investigation. In September 2012, a regulatory watchdog group filed a lawsuit to strike an EPA report, which was based in part upon the questionable research.

Milloy’s strategy was designed to impale the EPA on the horns of a dilemma:

“I accused EPA of either: (1) conducting unethical human experimentation or exaggerating the dangers of fine airborne particulate matter (PM2.5). It must be one or the other; it can’t be neither, according to EPA’s own documents.”

Steven Milloy, “Did Obama’s EPA relaunch Tuskegee experiments?” (April 24, 2012).  The EPA had branded diesel particulate, which was used in the experiments, as “carcinogenic” and “lethal,” even from short exposures.  Accordingly, if the EPA were sincere, it should have never conducted the experiment documented in Environmental Health Perspectives.  If the agency believed that PM 2.5 was innocuous, then it unethically exaggerated and overstated its dangers.

In course of his FOIA initiative, Milloy did obtain answers to some of the questions I had from reading the Ghio article.  There were apparently about 40 human subjects, who were subjected to PM 2.5 exposure in chambers fed by diesel exhaust or other sources.  The exposure levels were upwards of 20 times what the EPA labeled a “permissible” level.  Of course, the EPA is positionally committed to a “linear, no-threshold” model of carcinogenesis, which makes any exposure to a substance it “knows” to cause cancer ethically improper.

The information from the FOIA requests puts the Ghio article in an extremely bad light.  The human subject on whom the authors reported had run about 40 other people through their chamber without ill effect, but failed to mention these cases.  The consent forms and IRB documents show that the investigators were specifically interested in “vulnerable” patients, who had diabetes, asthma, etc.  The fair inference is that the investigators wanted to provoke an anecdote that would support their causal narrative, which they believed had already been established with epidemiologic evidence.  This seems like a scientific hat trick: bad science, bad ethics, and bad publication practice.

The lawsuit did not fare well.  Predictably, it foundered on the lack of final agency action, and the lack of standing.  On January 31, 2013, Judge Anthony J. Trenga dismissed the complaint, after having previously denied a temporary restraining order.  The American Tradition Institute Environmental Law Center v. U.S. EPA, Case 1:12-cv-01066-AJT-TCB (E.D. Va. 2013).  While legally correct, the opinion is blandly devoid of any sense of ethical concern.

From a brief search, there does not appear to be an appeal to the Fourth Circuit in the works.  Of course, there were no personal injuries alleged in the ATI lawsuit, and the human subject in the Ghio article has appeared not to have sued.  Despite the lack of legal recourse, the science “right” is up in arms over EPA duplicity.  In a recent publication, Milloy and a co-author, quote former EPA Administrator Lisa Jackson, at a congressional hearing:

“Particulate matter causes premature death. It’s directly causal to dying sooner than you should.”

When Representative, now Senator, Edward J. Markey asked, “How would you compare [the benefits of reducing airborne PM2.5] to the fight against cancer?” Jackson answered hyperbolically:

“If we could reduce particulate matter to healthy levels, it would have the same impact as finding a cure for cancer in our country.”

Steve Milloy & John Dale Dunn, “Environmental Protection Agency’s Air Pollution Research: Unethical and Illegal?” 17 J. Am. Phys. & Surg. 109 (2012) (quoting Jackson).  The FOIA and other background materials from this EPA posturing can be found on one of Milloy’s websites.

Sadly, I found the answers raised by the Ghio article only because of the anti-regulatory activism of Milloy and the American Tradition Institute.  The white-hat bias remains a potent force in regulatory agencies, and in scientific laboratories.

A Cautionary Tale on How Not to Sponsor a Scientific Study for Litigation

June 21st, 2013

Weitz & Luxenberg P.C. v. Georgia-Pacific

Earlier this month, the First Department of the New York Appellate Division upheld a trial court’s ruling that a former manufacturer of an asbestos-containing product, Georgia-Pacific LLC (G-P), must produce underlying data from eight published research studies, funded by the company.  These studies apparently addressed health outcomes from the use of the company’s product, a joint compound, or from its chrysotile asbestos component.  The trial court had also ordered an in camera review of various other documents on G-P’s privilege log.  Weitz & Luxenberg P.C. v. Georgia-Pacific LLC, 2013 WL 2435565, 2013 NY Slip Op 04127 (June 6, 2013)

The appellate court accepted that G-P had funded the eight studies as part of its legal defense to asbestos personal injury litigation.  The studies at issue involved recreating G-P’s asbestos-containing joint compound to assess biopersistence and pathogenicity of its (past) chrysotile content.  According to the Appellate Division’s opinion, G-P was closely involved in the development of the published articles.  G-P’s Director of Toxicology and Chemical Management, Stewart Holm, became a contractor to provide “consulting services” to G-P’s in-house counsel.  Both Holm and in-house counsel were involved in pre-publication review of the articles.

G-P claimed attorney-client and work-product privilege to resist production of documents that reflected communications with consulting experts or legal staff.  The Special Master directed an in camera review of documents on G-P’s privilege log, and the production of the underlying data and materials from the studies.  The motion court refused G-P’s motions to vacate the Special Master’s recommendations, and to reconsider.

The trial and appellate court rulings seem fairly straightforward except that the appellate court omitted serious consideration of the existence and scope of the privilege, and focused upon the applicability of the crime-fraud exception.  This exception requires that the legal advice, sought to be protected, involves some fraudulent scheme or wrongful conduct, but the court seemed all too willing to engage in an analysis of the applicability of the exception before it considered whether the privilege applied in the first place.   

The Appellate Division held that the plaintiffs had made a sufficient “showing of a factual basis adequate to support a good faith belief by a reasonable person that in camera review of the materials may reveal evidence to establish the claim that the crime-fraud exception applies.” Slip op. at 4.  Here is how the appellate court described the plaintiffs’ claim that the attorney-client privilege had been lost:

Holm co-authorized nearly all of the studies, which were intended to cast doubt on the capability of chrysotile asbestos to cause cancer. On the two articles that he did not co-author, he [*4]and GP’s counsel participated in lengthy ‘WebEx conferences’ in which they discussed the manuscripts and suggested revisions. Despite this extensive participation, none of the articles disclosed that GP’s in-house counsel had reviewed the manuscripts before they were submitted for publication. Two articles falsely stated that ‘[GP] did not participate in the design of the study, analysis of the data, or preparation of the manuscript’. For articles lead-authored by David M. Bernstein, Ph.D., and co-authored by Holm, the only disclosure was that the research was ‘sponsored’ or ‘supported’ by a grant from GP. The articles did not disclose that Holm was specially employed by GP for the asbestos litigation or that he reported to GP’s in-house counsel. Furthermore, there were no grant proposals, and Dr. Bernstein was hired by GP on an hourly basis. Nor did the articles reveal that Dr. Bernstein has been disclosed as a GP expert witness in NYCAL since 2009, that he had testified as a defense expert for Union Carbide Corporation in asbestos litigation, or that he had been paid by, and spoken on behalf of, the Chrysotile Institute, the lobbying arm of the Quebec chrysotile mining industry. Although GP belatedly endeavored to address the inadequacies of certain of its disclosures, its corrections failed to acknowledge its in-house counsel’s participation and did not make clear that Dr. Bernstein’s testimony as an expert witness preceded the publication of the first GP reformulated joint compound article in 2008.”

The court was obviously concerned that G-P in-house counsel was involved in the publication process, and that this involvement was not disclosed. Slip at 4, citing United States v. Philip Morris USA, Inc., 449 F. Supp. 2d 1 (D. D.C. 2006) (applying fraud-crime exception to tobacco industry), aff’d in relevant part, 566 F.3d 1095 (D.C. Cir. 2009), cert. denied, 130 S.Ct. 3501 (2010).

What Appellate Division appeared to overlook is whether the attorney-client privilege applied in the first place.  In her initial recommendation, Special Master Laraine Pacheco gave careful consideration to the logically prior question whether the disputed materials were “legal” such that any privilege even attached to the disputed materials in the first place. See Recommendation of Special Master at 3, citing United States Postal Serv. v. Phelps Dodge Ref. Corp., 852 F. Supp. 156, 160 (E.D.N.Y. 1994) (“Defining the scope of the privilege for in-house counsel is complicated by the fact that these attorneys frequently have multi-faceted duties that go beyond traditional tasks performed by lawyers. . . . Needless to say, the attorney-client privilege attaches only to legal, as opposed to business, services. The communication must be made to the attorney acting in her capacity as counsel. If the communication is made to the attorney in her capacity as a business adviser, for example, it ought not be privileged”); In re Grand Jury Subpoena, 599 F.2d 504, 511 (2d Cir. 1979) (“Participation of the general counsel does not automatically cloak the investigation with legal garb”). The Special Master seemed to think that there was no privilege, which stood in need of an exception.

The Special Master also noted that no privilege attaches to materials that were intended for ultimate publication: 

 “New York of course accepts the unremarkable proposition that if a client communicates to the lawyer with the intent that the communication is to be released to the public, that communication is not privileged.”

Recommendation at 3, citing In re New York Renu with Moistureloc Prod. Liability Litig. , 2008 U.S. Dist. LEXIS 88515, at *5, 14 (D.S.C. May 8, 2008) (applying New York law) (relying on Michael M. Martin, et al., New York Evidence Handbook  318 (2d ed. 2002)).  Furthermore, there was a question whether G-P had waived its privilege claim by selectively producing some documents that it wanted to put into the record of the case.  Id.  The Special Master’s points appear important and persuasive, but the Appellate Division skipped over them in order to address the exception, which assumes that the privilege applies in the first place.

American Law Institute (ALI), The Law Governing Lawyers § 68 (1998). The mere participation of in-house counsel is not dispositive of the question.  The privilege applies to communications made for the purpose of obtaining legal advice. In-house lawyers are often consulted for advice on non-legal issues.  Courts have thus been drawn in to controversies over sorting out whether the communication was engaged in for purpose of obtaining “legal assistance.” ALI § 72. The law acknowledges that communications may have multiple purposes and motives, but the predominant function of the communication must relate to legal advice if it is to retain its privileged status. ALI § 72, comment c.

In Burton v. R.J. Reynolds Tobacco Co., both the magistrate and district judges accepted, as a general principle:

 “An analysis of scientific data may be the subject of a privileged communication. To establish that such communications are protected by the attorney-client privilege there must be a connection between the scientific information which is the subject of the communication and the rendering of legal advice.”

200 F.R.D. 661, 668 (D. Kan. 2001). The court, however, proceeded to analyze the disputed claims of privilege and rejected most of them on grounds that the attorney communications were not in response to requests for legal advice. For instance, the court rejected the claim of privilege for a memorandum, written by an RJR scientist who assisted RJR patent lawyers as a scientific paralegal. The RJR scientist commented on “patentability,” but the court found that the document primarily concerned scientific research with no connection to the rendering of legal advice. Id. at 670. Even stingier was the court’s interpretation of a memorandum from RJR’s CEO to its general counsel, which discussed outside counsel’s recommendation that the company “should fund additional medical research in order to gain additional facts that [it]] can use to defend [itself] against [its] critics.” The court characterized the referenced advice as relating to public relations advice, not legal counsel. Id. at 672.

In the Vioxx MDL, Judge Fallon struggled with the issue whether many of activities of in-house counsel were truly “legal,” especially when the attorney communications were comments and edits of “scientific reports, articles accepted for publication in noted journals, and research proposals,” or word choice comments in scientific articles and study proposals. In re Vioxx Prods. Liab. Litig., 501 F.Supp. 2d 789, 800, 802 (E.D.La. 2007)(“We could not see the legal significance of these comments… .”).

Merck advanced a theory that the pharmaceutical industry was so pervasively regulated that the court should assume that its in-house lawyers were providing legal advice in making such comments and edits. Special Master Rice, a noted privilege scholar appointed to review the privilege claims, and Judge Fallon, never accepted Merck’s blanket rationale, although they did acknowledge that some service, initially appearing to be non-legal (such as “commenting upon and editing television ads and other promotional materials”) could in fact be legal advice when understood in the context of the pharmaceutical industry’s regulatory framework. Id. (citing Vodra et al., “The Food and Drug Administration’s Evolving Regulation of Press Releases: Limits and Challenges,” 61 Food & Drug L.J. 623 (2006)).

Concerned that such a blanket justification would seriously curtail discovery, the Special Master and the MDL Court insisted that Merck, in claiming a privilege, carry its burden to show that each document was, in fact, a confidential communication of legal advice. Id. The Special Master professed to be receptive to Merck’s evidence that, in the context of the highly regulated pharmaceutical industry, in-house counsel’s extensive changes and commentary to technical and scientific matters were legal services. Id. at 811-12.  Judge Fallon, quoting from the Special Master Rice’s report, noted that:

 “The responsive communication from the attorney is protected only to the extent that the response reveals the content of the client’s prior confidential communication.”

In re Vioxx Prods. Liab. Litig., 501 F.Supp. 2d 789, 795 (E.D.La. 2007).  As a result, an attorney’s transmission to the client of information obtained from third-parties is not privileged. Id. at 796. Similarly, the derivative nature of the privilege may lead to a refusal to apply it to in-house lawyers’ line edits of a non-privileged document, which was circulated to other corporate employees outside the legal department. Id.

The Vioxx analysis shows that the presumption that in-house or outside (or out-house) counsel are writing to provide legal advice, in response to client communications can be lost.  When the communications at issue are not for the purpose of providing legal advice, there may well be no protection under the attorney-client privilege.  In re Vioxx Prods. Liab. Litig., 501 F.Supp. 2d 789, 797 n. 12 (E.D. La. 2007)(quoting Special Master Rice, who was quoting from his treatise at § 7.28). See also . In re Seroquel Prods. Liab. Litig., 2008 WL 1995058, at* 6- 7 (M.D. Fla. 2008) (rejecting “pervasive regulation” theory, and relying heavily upon Judge Fallon’s analysis in Vioxx).

The Appellate Division’s enthusiasm for accepting the existence of the privilege in Georgia-Pacific, and to except its application by the crime-fraud exception, is deeply troubling because the court left unclear exactly what G-P’s crime or fraud was.  Perhaps G-P had failed to disclose some of the above-quoted facts in its discovery, but the anemic disclosures are all-too-common in most publications.  They are hardly a crime.  No provision of the penal code was cited.  Although some of the suggested conduct is unseemly, it is not clearly a fraud.

The only supposed falsehood was that “[t]wo articles falsely stated that ‘[GP] did not participate in the design of the study, analysis of the data, or preparation of the manuscript’.”  Slip op. at 4.  The recited “good faith” belief does not suggest that G-P designed or analyzed the studies.  It is unclear whether G-P’s in-house counsel’s participation in a Webex conference realistically could be considered “preparing” a manuscript.  The court’s vague accusations leave unclear exactly what G-P did to design the study, analyze the data, or prepare the manuscript.  Such vague accusations would hardly pass the strictures of Federal Rule of Civil Procedure 9(b) (“Fraud or Mistake; Conditions of Mind. In alleging fraud or mistake, a party must state with particularity the circumstances constituting fraud or mistake.”)

Work Product Protection

The Appellate Division’s decision was on firmer ground with respect to rejecting G-P’s asserted work-product protection for attorney mental impressions, writings, trial preparation materials, and the like.  As the court noted, there is a strong public interest in having disputes resolved on the basis of complete, accurate information.  Slip op. at 6, citing In re American Tobacco Co., 880 F.2d 1520, 1529 (2d Cir 1989).  Of course, in the American Tobacco case, the Second Circuit upheld a subpoena (previously quashed by New York state courts) against Dr. Selikoff’s Environmental Sciences Department, at the Mt. Sinai School of Medicine.

In the case on appeal, the court noted that G-P had admitted to commissioning the studies in anticipation of litigation, and to having its trial counsel or its expert witnesses use the studies at trial.  Slip op. at 6.  The appellate court also held that the plaintiffs’ substantial need for the underlying data and related materials, and the prejudice from being denied access, were obvious.  The appellate court cast a broad, but not an unlimited net, for materials that would have to be produced.  “[T]he data, protocols, process, conduct, discussion, and analyses underlying these studies” must be produced, but not “any internal communications that portray its attorneys’ or consultants’ notes, comments or opinions.” Slip op. at 7.  The court identified the rationale for requiring production:

 “A significant expenditure of time and money would be required to duplicate the studies, if they could be exactly duplicated at all, whereas scrutiny of the underlying data may provide a permissible manner in which to attack the findings that would be consistent with the intent of the CMO to minimize the cost of and streamline discovery.”

Id.  Indeed, the lesson of the American Tobacco case, cited by the court, is that a party’s need and entitlement to underlying data and materials trumps even an independent researcher’s claim of “scholar’s privilege” or proprietary interest in data.  Litigants are entitled to everyman’s and everywoman’s evidence, even if they are scientists.  Courts may have to fashion protection to protect some of the scientists’ interests, but the wholesale denial of access to underlying data from published studies is, and should be, a relic of the past.

It is reflective of the Zeitgeist that the appellate court couched some of its rationale in corporation bashing:

 “Large corporations often invest strategically in research agendas whose objective is to develop a body of scientific knowledge favorable to a particular economic interest or useful for defending against particular claims of legal liability.”

Slip op. at 6, quoting from In re Welding Fume Prods. Liability Litig., 534 F.Supp. 2d 761, 769 n.10 (N.D. Ohio 2008). Well the litigation industry, a.k.a. the plaintiffs’ bar, similarly invests in its research agenda, as evidenced in any number of litigations, including asbestos, silicone, welding cases, etc.  More important, the plaintiffs’ bar has powerful interest proxies, such as support groups, labor unions, so-called public-interest groups, and captured governmental agencies, which are frequently involved in advocacy science.  The need for access to underlying data, protocols, questionnaires, research materials is not limited to plaintiffs or defendants in litigation.

Eight Articles

A Pubmed search turned up exactly eight articles for <S.E. Holm and asbestos>.  Two of the articles at issue did not have Holm as an author, so the following list is not identical to the eight articles at issue.

1. Exposures from chrysotile-containing joint compound: evaluation of new model relating respirable dust to fiber concentrations.

Brorby GP, Sheehan PJ, Berman DW, Bogen KT, Holm SE.

Risk Anal. 2013 Jan;33(1):161-76.

2. More on the dynamics of dust generation: the effects of mixing and sanding chrysotile, calcium carbonate, and other components on the characteristics of joint-compound dusts.

Berman DW, Brorby GP, Sheehan PJ, Bogen KT, Holm SE.

Ann Occup Hyg. 2012 Aug;56(7):852-67.

3. Chamber for testing asbestos-containing products: validation and testing of a re-created chrysotile-containing joint compound.

Sheehan PJ, Brorby GP, Berman DW, Bogen KT, Holm SE.

Ann Occup Hyg. 2011 Aug;55(7):797-809.

4. Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure.

Bernstein DM, Rogers RA, Sepulveda R, Donaldson K, Schuler D, Gaering S, Kunzendorf P, Chevalier J, Holm SE.

Inhal Toxicol. 2011 Jun;23(7):372-91.

5. Potential artifacts associated with historical preparation of joint compound samples and reported airborne asbestos concentrations.

Brorby GP, Sheehan PJ, Berman DW, Bogen KT, Holm SE.

J Occup Environ Hyg. 2011 May;8(5):271-8.

6. The pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite asbestos following short-term inhalation exposure: interim results.

Bernstein DM, Rogers RA, Sepulveda R, Donaldson K, Schuler D, Gaering S, Kunzendorf P, Chevalier J, Holm SE.

Inhal Toxicol. 2010 Sep;22(11):937-62.

7. Re-creation of historical chrysotile-containing joint compounds.

Brorby GP, Sheehan PJ, Berman DW, Greene JF, Holm SE.

Inhal Toxicol. 2008 Sep;20(11):1043-53.

8. A biopersistence study following exposure to chrysotile asbestos alone or in combination with fine particles.

Bernstein DM, Donaldson K, Decker U, Gaering S, Kunzendorf P, Chevalier J, Holm SE.

Inhal Toxicol. 2008 Sep;20(11):1009-28.


I thank William Ruskin for calling my attention to this interesting case in his blog post about the Weitz & Luxenberg v. Georgia-Pacific case.

Federal Rule of Evidence 106 Applied to Statistical Evidence

June 18th, 2013

Watching your expert witness harassed by an unfair crossexamination, without protection from the trial judge, is one of the most frustrating, annoying, and enraging events in trial.  Not so long ago, I had the experience of having a lawyer put a chart together during his crossexamination of an expert witness. The crossexaminer took the upper bound of each confidence interval, and asked “Based upon this study, the true relative risk could be as high as X?”  When the witness, naturally and properly pointed out that the study data were also compatible with a relative risk as low as Y, the lower bound of the confidence interval, the crossexaminer whined that the witness was not being responsive, with the trial court’s chiming in to curb the expert’s reasonable desire to have a complete, correct answer.

Watching events such as this crossexamination has led me to believe that there really should be a rule of completeness for statistical evidence.  If sampling is random and unbiased, a point estimate may be the best estimate of the true value of a mean or a proportion, but that estimate may be rather crummy if the random error is large.  Presenting the sample statistic without some idea of the standard error seems wrong, but is there a remedy?

Statistical evidence did not play much of a role in the development of common law evidence, but the law is concerned with the sort of contextual accuracy that was being abused by the crossexamination of the expert witness, above.  The Federal Rules provide for completeness in at least two contexts.  Federal Rule of Evidence 106 provides:

Remainder of or Related Writings or Recorded Statements

If a party introduces all or part of a writing or recorded statement, an adverse party may require the introduction, at that time, of any other part — or any other writing or recorded statement — that in fairness ought to be considered at the same time.”

A similar rule governs depositions presented in court.  Federal Rule of Civil Procedure 32(a)(4).

As the Advisory Committee notes to Rule 106 point out, Rule 106 is based upon two basic considerations:

“The first is the misleading impression created by taking matters out of context. The second is the inadequacy of repair work when delayed to a point later in the trial. …  The rule does not in any way circumscribe the right of the adversary to develop the matter on cross-examination or as part of his own case.”

Rule 106, Advisory Committee Notes (internal citations omitted).

When “in fairness” should an omitted portion be considered contemporaneously?  Here is how the Seventh Circuit put the matter in the more mundane context of a writing:

“To determine whether a disputed portion is necessary, the district court considers whether

(1) it explains the admitted evidence,

(2) places the admitted evidence in context,

(3) avoids misleading the jury, and

(4) insures fair and impartial understanding of the evidence.”

United States v. Velasco, 953 F.2d 1467, 1475 (7th Cir.1992).

Presentation of a point estimate should be accompanied by a measure of its variability; “[w]henever possible, an estimate should be accompanied by its standard error.” Reference Manual on Scientific Evidence at 117-18 (2d ed. 2000).  Similarly, trial courts should be vigilant against permitting a party to use the upper or the lower bound of a confidence interval to paint a misleading picture of “what the evidence shows.”

 

Power in the Reference Manual for Scientific Evidence

June 15th, 2013

The Third Edition of the Reference Manual on Scientific Evidence (2011) [RMSE3ed] treats statistical power in three of its chapters, those on statistics, epidemiology, and medical testimony.  Unfortunately, the treatment is not always consistent.

The chapter on statistics has been consistently among the best and most frequently ignored content of the three editions of the Reference Manual.  The most recent edition offers a good introduction to basic concepts of sampling, random variability, significance testing, and confidence intervals.  David H. Kaye & David A. Freedman, “Reference Guide on Statistics,” in RMSE3ed 209 (2011).  Kaye and Freedman provide an acceptable non-technical definition of statistical power:

“More precisely, power is the probability of rejecting the null hypothesis when the alternative hypothesis … is right. Typically, this probability will depend on the values of unknown parameters, as well as the preset significance level α. The power can be computed for any value of α and any choice of parameters satisfying the alternative hypothesis. Frequentist hypothesis testing keeps the risk of a false positive to a specified level (such as α = 5%) and then tries to maximize power. Statisticians usually denote power by the Greek letter beta (β). However, some authors use β to denote the probability of accepting the null hypothesis when the alternative hypothesis is true; this usage is fairly standard in epidemiology. Accepting the null hypothesis when the alternative holds true is a false negative (also called a Type II error, a missed signal, or a false acceptance of the null hypothesis).”

Id. at 254 n.106

The definition is not, however, without problems.  First, it introduces a nomenclature issue likely to be confusing for judges and lawyers. Kaye and Freeman use β to denote statistical power, but they acknowledge that epidemiologists use β to denote the probability of a Type II error.  And indeed, both the chapters on epidemiology and medical testimony use β to reference Type II error rate, and thus denote power as the complement of β, or (1- β).  See Michael D. Green, D. Michal Freedman, and Leon Gordis, “Reference Guide on Epidemiology,” in RMSE3ed 549, 582, 626 ; John B. Wong, Lawrence O. Gostin, and Oscar A. Cabrera, Abogado, “Reference Guide on Medical Testimony,” in RMSE3ed 687, 724.  This confusion in nomenclature is regrettable, given the difficulty many lawyers and judges seem have in following discussions of statistical concepts.

Second, the reason for introducing the confusion about β is doubtful.  Kaye and Freeman suggest that statisticians usually denote power by β, but they offer no citations.  A quick review (not necessarily complete or even a random sample) suggests that many modern statistics texts denote power as (1- β).  See, e.g., Richard D. De Veaux, Paul F. Velleman, and David E. Bock, Intro Stats 545-48 (3d ed. 2012); Rand R. Wilcox, Fundamentals of Modern Statistical Methods 65 (2d ed. 2010).  At the end of the day, there really is no reason for the conflicting nomenclature and the likely confusion it engenders.  Indeed, the duplicative handling of statistical power, and other concepts, suggests that it is time to eliminate the repetitive discussions, in favor of one, clear, thorough discussion in the statistics chapter.

Third, Kaye and Freeman problematically refer to β as the probability of accepting the null hypothesis when elsewhere they more carefully instruct that a non-significant finding results in not rejecting the null hypothesis as opposed to accepting the null.  Id. at 253.  See also Daniel Rubinfeld, “Reference Guide on Multiple Regression,“ in RMSE3d 303, 321 (describing a p-value > 5% as leading to failing to reject the null hypothesis).

Fourth, Kaye and Freedman’s discussion of power, unlike most of their chapter, offers advice that is controversial and unclear:

“On the other hand, when studies have a good chance of detecting a meaningful association, failure to obtain significance can be persuasive evidence that there is nothing much to be found.”

RMSE3d at 254. Note that the authors leave open what a legal or clinically meaningful association is, and thus offer no real guidance to judges on how to evaluate power after data are collected and analyzed.  As Professor Sander Greenland has argued, in legal contexts, this reliance upon observed power (as opposed to power as a guide in determining appropriate sample size in the planning stages of a study) is arbitrary and “unsalvageable as an analytic tool.”  See Sander Greenland, “Nonsignificance Plus High Power Does Not Imply Support Over the Alternative,” 22 Ann. Epidemiol. 364, 364 (2012).

The chapter on epidemiology offers similar controversial advice on the use of power:

“When a study fails to find a statistically significant association, an important question is whether the result tends to exonerate the agent’s toxicity or is essentially inconclusive with regard to toxicity.93 The concept of power can be helpful in evaluating whether a study’s outcome is exonerative or inconclusive.94  The power of a study is the probability of finding a statistically significant association of a given magnitude (if it exists) in light of the sample sizes used in the study. The power of a study depends on several factors: the sample size; the level of alpha (or statistical significance) specified; the background incidence of disease; and the specified relative risk that the researcher would like to detect.95  Power curves can be constructed that show the likelihood of finding any given relative risk in light of these factors. Often, power curves are used in the design of a study to determine what size the study populations should be.96

Michael D. Green, D. Michal Freedman, and Leon Gordis, “Reference Guide on Epidemiology,” RMSE3ed 549, 582.  Although the authors correctly emphasize the need to specify an alternative hypothesis, their discussion and advice are empty of how that alternative should be selected in legal contexts.  The suggestion that power curves can be constructed is, of course, true, but irrelevant unless courts know where on the power curve they should be looking.  The authors are correct that power is used to determine adequate sample size under specified conditions, but again, the use of power curves in this setting is today rather uncommon.  Investigators select a level of power corresponding to an acceptable Type II error rate, and an alternative hypothesis that would be clinically meaningful for their research, in order to determine their sample size. Translating clinical into legal meaningfulness is not always straightforward.

In a footnote, the authors of the epidemiology chapter note that Professor Rothman has been “one of the leaders in advocating the use of confidence intervals and rejecting strict significance testing.” RMSE3d at 579 n.88.  What the chapter fails, however, to mention is that Rothman has also been outspoken in rejecting post-hoc power calculations that the epidemiology chapter seems to invite:

“Standard statistical advice states that when the data indicate a lack of significance, it is important to consider the power of the study to detect as significant a specific alternative hypothesis. The power of a test, however, is only an indirect indicator of precision, and it requires an assumption about the magnitude of the effect. In planning a study, it is reasonable to make conjectures about the magnitude of an effect to compute study-size requirements or power. In analyzing data, however, it is always preferable to use the information in the data about the effect to estimate it directly, rather than to speculate about it with study-size or power calculations (Smith and Bates, 1992; Goodman and Berlin, 1994; Hoening and Heisey, 2001). Confidence limits and (even more so) P-value functions convey much more of the essential information by indicating the range of values that are reasonably compatible with the observations (albeit at a somewhat arbitrary alpha level), assuming the statistical model is correct. They can also show that the data do not contain the information necessary for reassurance about an absence of effect.”

Kenneth Rothman, Sander Greenland, and Timothy Lash, Modern Epidemiology 160 (3d ed. 2008).  See also Kenneth J. Rothman, “Significance Questing,” 105 Ann. Intern. Med. 445, 446 (1986) (“[Simon] rightly dismisses calculations of power as a weak substitute for confidence intervals, because power calculations address only the qualitative issue of statistical significance and do not take account of the results already in hand.”)

The selective, incomplete scholarship of the epidemiology chapter on the issue of statistical power is not only unfortunate, but it distorts the authors’ evaluation of the sparse case law on the issue of power.  For instance, they note:

“Even when a study or body of studies tends to exonerate an agent, that does not establish that the agent is absolutely safe. See Cooley v. Lincoln Elec. Co., 693 F. Supp. 2d 767 (N.D. Ohio 2010).  Epidemiology is not able to provide such evidence.”

RMSE3d at 582 n.93; id. at 582 n.94 (“Thus, in Smith v. Wyeth-Ayerst Labs. Co., 278 F.Supp. 2d 684, 693 (W.D.N.C. 2003), and Cooley v. Lincoln Electric Co., 693 F. Supp. 2d 767, 773 (N.D. Ohio 2010), the courts recognized that the power of a study was critical to assessing whether the failure of the study to find a statistically significant association was exonerative of the agent or inconclusive.”)

Here Green, Freedman, and Gordis shift the burden to the defendant and make the burden one of absolute certainty in the product’s safety.  This is not a legal standard. The cases they cite amplify the error. In Cooley, for instance, the defense expert would have opined that welding fume exposure did not cause parkinsonism or Parkinson’s disease.  Although the expert had not conducted a meta-analysis, he had reviewed the confidence intervals around the point estimates of the available studies.  Many of the point estimates were at or below 1.0, and in some cases, the upper bound of the confidence interval excluded 1.0.  The trial court expressed its concern that the expert witness had inferred “evidence of absence” from “absence of evidence.”  Cooley v. Lincoln Elec. Co., 693 F. Supp. 2d 767, 773 (N.D. Ohio 2010).  This concern, however, was misguided given that many studies had tested the claimed association, and that virtually every case-control and cohort study had found risk ratios at or below 1.0, or very close to 1.0.  What the court in Cooley, and the authors of the epidemiology chapter in the RSME3d have lost sight of, is that when the hypothesis is repeatedly tested, with failure to reject the null hypothesis, and with point estimates at or very close to 1.0, and with narrow confidence intervals, then the claimed association is probably incorrect.  See, e.g., Anthony J. Swerdlow, Maria Feychting, Adele C. Green, Leeka Kheifets, David A. Savitz, International Commission for Non-Ionizing Radiation Protection Standing Committee on Epidemiology, “Mobile Phones, Brain Tumors, and the Interphone Study: Where Are We Now?” 119 Envt’l Health Persp. 1534, 1534 (2011) (“Although there remains some uncertainty, the trend in the accumulating evidence is increasingly against the hypothesis that mobile phone use can cause brain tumors in adults.”).

The Cooley court’s comments have some validity when applied to a single study, but not to the impressive body of exculpatory epidemiologic evidence that pertains to welding fume and Parkinson’s disease.  Shortly after the Cooley case was decided, a published meta-analysis of welding fume or manganese exposure demonstrated a reduced level of risk for Parkinson’s disease among persons occupationally exposed to welding fumes or manganese.  James Mortimer, Amy Borenstein, and Lorene Nelson, “Associations of welding and manganese exposure with Parkinson disease: Review and meta-analysis,” 79 Neurology 1174 (2012).