In a recent post¹, I noted Samuel Tarry’s valuable article² for its helpful, contrarian discussion of the importance of some scientific articles with litigation provenances. Public health debates can spill over to the courtroom, and developments in the courtroom can, on occasion, inform and even resolve those public health debates that gave rise to the litigation. Tarry provided an account of three such articles, and I provided a brief account of another article, a published meta-analysis, from the welding fume litigation.

The welding litigation actually accounted for several studies, but in this post, I detail the background of another published study, this one an epidemiologic study by a noted Harvard epidemiologist. Not every expert witness’s report has the making of a published paper. In theory, if the expert witness has conducted a systematic review, and reached a conclusion that is not populated among already published papers, we might well expect that the witness had achieved the “least publishable unit.” The reality is that most causal claims are not based upon what could even remotely be called a systematic review. Given the lack of credibility to the causal claim, rebuttal reports are likely to have little interest to serious scientists.

Martin Wells

In the welding fume cases, one of plaintiffs’ hired expert witnesses, Martin Wells, a statistician, proffered an analysis of Parkinson’s disease (PD) mortality among welders and welding tradesmen. Using the National Center for Health Statistics (NCHS) database, Wells aggregated data from 1993 to 1999, for PD among welders and compared this to PD mortality among non-welders. Wells claimed to find an increased risk of PD mortality among younger (under age 65 at death) welders and welding tradesmen in this dataset.

The defense sought discovery of Wells’s methods and materials, and obtained the underlying data from the NCHS. Wells had no protocol, no pre-stated commitment to which years in the dataset he would use, and no pre-stated statistical analysis plan. At a Rule 702 hearing, Wells was unable to state how many welders were included in his analysis, why he selected some years but not others, or why he had selected age 65 as the cut off. His analyses appeared to be pure data dredging.

As the defense discovered, the NCHS dataset contained mortality data for many more years than the limited range employed by Wells in his analysis. Working with an expert witness at the Harvard School of Public Health, the defense discovered that Wells had gerrymandered the years included (and excluded) in his analysis in a way that just happened to generate a marginally, nominally statistically significant association.

NCHS Welder Age Distribution

The defense was thus able to show that the data overall, and in each year, were very sparse. For most years, the value was either 0 or 1, for PD deaths under age 65. Because of the huge denominators, however, the calculated mortality odds ratios were nominally statistically significant. The value of four PD deaths in 1998 is clearly an outlier. If the value were three rather than four, the statistical significance of the calculated OR would have been lost. Alternatively, a simple sensitivity test suggests that if instead of overall n = 7, n were 6, statistical significance would have been lost. The chart below, prepared at the time with help from Dr. David Schwartz, of Innovative Science solutions, shows the actual number of “underlying cause” PD deaths that were in the dataset for each year in the NCHS dataset, and how sparse and “granular” these data were:

A couple of years later, the Wells’ litigation analysis showed up as a manuscript, with only minor changes in its analyses, and with authors listed as Martin T. Wells and Katherine W. Eisenberg, in the editorial offices of Neurology. Katherine W. Eisenberg, AB and Martin T. Wells, Ph.D., “A Mortality Odds Ratio Study of Welders and Parkinson Disease.” Wells disclosed that he had testified for plaintiffs in the welding fume litigation, but Eisenberg declared no conflicts. Having only an undergraduate degree, and attending medical school at the time of submission, Ms. Eisenberg would not seem to have had the opportunity to accumulate any conflicts of interest. Undisclosed to the editors of Neurology, however, was that Ms. Eisenberg was the daughter of Theodore (Ted) Eisenberg, a lawyer who taught at Cornell University and who represented plaintiffs in the same welding MDL as the one in which Wells testified. Inquiring minds might have wondered whether Ms. Eisenberg’s tuition, room, and board were subsidized by Ted’s earnings in the welding fume and other litigations. Ted Eisenberg and Martin Wells had collaborated on many other projects, but in the welding fume litigation, Ted worked as an attorney for MDL welding plaintiffs, and Martin Wells was compensated handsomely as an expert witness. The acknowledgment at the end of the manuscript thanked Theodore Eisenberg for his thoughtful comments and discussion, without noting that he had been a paid member of the plaintiff’s litigation team. Nor did Wells and Eisenberg tells the Neurology editors that the article had grown out of Wells’ 2005 litigation report in the welding MDL.

The disclosure lapses and oversights by Wells and the younger Eisenberg proved harmless error because Neurology rejected the Wells and Eisenberg paper for publication, and it was never submitted elsewhere. The paper used the same restricted set of years of NCHS data, 1993-1999. The defense had already shown, through its own expert witness’s rebuttal report, that the manuscript’s analysis achieved statistical significance only because it omitted years from the analysis. For instance, if the authors had analyzed 1992 through 1999, their Parkinson’s disease mortality point estimate for younger welding tradesmen would no longer have been statistically significant.

Robert Park

One reason that Wells and Eisenberg may have abandoned their gerrymandered statistical analysis of the NCHS dataset was that an ostensibly independent group³ of investigators published a paper that presented a competing analysis. Robert M. Park, Paul A. Schulte, Joseph D. Bowman, James T. Walker, Stephen C. Bondy, Michael G. Yost, Jennifer A. Touchstone, and Mustafa Dosemeci, “Potential Occupational Risks for Neurodegenerative Diseases,” 48 Am. J. Ind. Med. 63 (2005) [cited as Park (2005)]. The authors accessed the same NCHS dataset, and looked at hundreds of different occupations, including welding tradesmen, and four neurodegenerative diseases.

Park, et al., claimed that they looked at occupations that had previously shown elevated proportional mortality ratios (PMR) in a previous publication of the NIOSH. A few other occupations were included; in all their were hundreds of independent analyses, without any adjustment for multiple testing. Welding occupations⁴ were included “[b]ecause of reports of Parkinsonism in welders [Racette et al.,, 2001; Levy and Nassetta, 2003], possibly attributable to manganese exposure (from welding rods and steel alloys)… .”⁵ Racette was a consultant for the Lawsuit Industry, which had been funded his research on parkinsonism among welders. Levy was a testifying expert witness for Lawsuit, Inc. A betting person would conclude that Park had consulted with Wells and Eisenberg, and their colleagues.

These authors looked at four neurological degenerative diseases (NDDs), Alzheimer’s disease, Parkinson’s disease, motor neuron disease, and pre-senile dementia. The authors looked at NCHS death certificate occupational information from 1992 to 1998, which was remarkable because Wells had insisted that 1992 somehow was not available for inclusion in his analyses. During 1992 to 1998, in 22 states, there were 2,614,346 deaths with 33,678 from Parkinson’s diseases. (p. 65b). Then for each of the four disease outcomes, the authors conducted an analysis for deaths below age 65. For the welding tradesmen, none of the four NDDs showed any associations. Park went on to conduct subgroup analyses for each of the four NDDs for death below age 65. In these subgroup analyses for welding tradesmen, the authors purported to find only an association only with Parkinson’s disease:

“Of the four NDDs under study, only PD was associated with occupations where arc-welding of steel is performed, and only for the 20 PD deaths below age 65 (MOR=1.77, 95% CI=1.08-2.75) (Table V).”

Park (2005), at 70.

“Adjusted for age, race, gender, region and SES. Model contains multiplicative terms for exposure and for exposure if age at death <65; thus MOR is estimate for deaths occurring age 65+, and MOR, age <65 is estimate of enhanced risk: age <65 versus age 65+”

In other words, Park looked to see whether welding tradesmen who died at a younger age (below age 65) were more likely to have a PD cause of death than welding tradesmen who died an older age (over age 65). The meaning of this internal comparison is totally unclear, but it cannot represent a comparison of welder’s with non-welders. Indeed, every time, Park and his colleagues calculated and reported this strange odds ratio for any occupational group in the published paper, the odds ratio was elevated. If the odds ratio means anything, it is that younger Parkinson’s patients, regardless of occupation, are more likely to die of their neurological disease than older patients. Older men, regardless of occupation, are more likely to die of cancer, cardiovascular disease, and other chronic diseases. Furthermore, this age association within (not between) an occupational groups may be nothing other than a reflection of the greater severity of early-onset Parkinson’s disease in anyone, regardless of their occupation.

Like the manuscript by Eisenberg and Wells, the Park paper was an exercise in data dredging. The Park study reported increased odds ratios for Parkinson’s disease among the following groups on the primary analysis:

biological, medical scientists [MOR 2.04 (95% CI, 1.37-2.92)]

clergy [MOR 1.79 (95% CI, 1.58-2.02)]

religious workers [MOR 1.70 (95% CI, 1.27-2.21)]

college teachers [MOR 1.61 (95% CI, 1.39-1.85)]

social workers [MOR 1.44 (95% CI, 1.14-1.80)]

As noted above, the Park paper reported all of the internal mortality odds ratios for below versus above age 65, within occupational groups were nominally statistically significantly elevated. Nonetheless, the Park authors were on a mission, and determined to make something out of nothing, at least when it came to welding and Parkinson’s disease among younger patients. The authors’ conclusion reflected stunningly poor scholarship:

“Studies in the US, Europe, and Korea implicate manganese fumes from arc-welding of steel in the development of a Parkinson’s-like disorder, probably a manifestation of manganism [Sjogren et al., 1990; Kim et al., 1999; Luccini, et al., 1999; Moon et al., 1999]. The observation here that PD mortality is elevated among workers with likely manganese exposures from welding, below age 65 (based on 20 deaths), supports the welding-Parkinsonism connection.”

Park (2005) at 73.

Stunningly bad because the cited papers by Sjogren, Luccini, Kim, and Moon did not examine Parkinson’s disease as an outcome; indeed, they did not even examine a parkinsonian movement disorder. More egregious, however, was the authors’ assertion that their analysis, which compared the odds of Parkinson’s disease mortality between welders under age 65 to that mortality for welders over age 65, supported an association between welding and “Parkinsonism.” 

Every time the authors conducted this analysis internal to an occupational group, they found an elevation among under age 65 deaths compared with over age 65 deaths within the occupational group. They did not report comparisons of any age-defined subgroup of a single occupational group with similarly aged mortality in the remaining dataset.

Elan Louis

The plaintiffs’ lawyers used the Park paper as “evidence” of an association that they claimed was causal. They were aided by a cadre of expert witnesses who could cite to a paper’s conclusions, but could not understand its methods. Occasionally, one of the plaintiffs’ expert witnesses would confess ignorance about exactly what Robert Park had done in this paper. Elan Louis, one of the better qualified expert witnesses on the side of claimants, for instance, testified in the plaintiffs’ attempt to certify a national medical monitoring class action for welding tradesmen. His testimony about what to make of the Park paper was more honest than most of the plaintiffs’ expert witnesses:

Q. My question to you is, is it true that that 1.77 point estimate of risk, is not a comparison of this welder and allied tradesmen under this age 65 mortality, compared with non-welders and allied tradesmen who die under age 65?

A. I think it’s not clear that the footnote — I think that the footnote is not clearly written. When you read the footnote, you didn’t read the punctuation that there are semicolons and colons and commas in the same sentence. And it’s not a well constructed sentence. And I’ve gone through this sentence many times. And I’ve gone through this sentence with Ted Eisenberg many times. This is a topic of our discussion. One of the topics of our discussions. And it’s not clear from this sentence that that’s the appropriate interpretation. *  *  *  However, the footnote, because it’s so poorly written, it obscures what he actually did. And then I think it opens up alternative interpretations.

Q. And if we can pursue that for a moment. If you look at other tables for other occupational titles, or exposure related variables, is it true that every time that Mr. Park reports on that MOR age under 65, that the estimate is elevated and statistically significantly so?

A. Yes. And he uses the same footnote every time. He’s obviously cut and paste that footnote every single time, down to the punctuation is exactly the same. And I would agree that if you look for example at table 4, the mortality odds ratios are elevated in that manner for Parkinson’s Disease, with reference to farming, with reference to pesticides, and with reference to farmers excluding horticultural deaths.

Deposition testimony of Elan Louis, at p. 401-04, in Steele v. A. O. Smith Corp., no. 1:03 CV-17000, MDL 1535 (Jan. 18, 2007). Other less qualified, or less honest expert witnesses on the plaintiffs’ side were content to cite Park (2005) as support for their causal opinions.

Meir Stampfer

The empathetic MDL trial judge denied the plaintiffs’ request for class certification in Steele, but individual personal injury cases continued to be litigated. Steele v. A.O. Smith Corp., 245 F.R.D. 279 (N.D. Ohio 2007) (denying class certification); In re Welding Fume Prods. Liab. Litig., No. 1:03-CV-17000, MDL 1535, 2008 WL 3166309 (N.D. Ohio Aug. 4, 2008) (striking pendent state-law class actions claims)

Although Elan Louis was honest enough to acknowledge his own confusion about the Park paper, other expert witnesses continued to rely upon it, and plaintiffs’ counsel continued to cite the paper in their briefs and to use the apparently elevated point estimate for welders in their cross-examinations of defense expert witnesses. With the NCHS data in hand (on a DVD), defense counsel returned to Meir Stampfer, who had helped them unravel the Martin Wells’ litigation analysis. The question for Professor Stampfer was whether Park’s reported point estimate for PD mortality odds ratio was truly a comparison of welders versus non-welders, or whether it was some uninformative internal comparison of younger welders versus older welders.

The one certainty available to the defense is that it had the same dataset that had been used by Martin Wells in the earlier litigation analysis, and now by Robert Park and his colleagues in their published analysis. Using the NCHS dataset, and Park’s definition of a welder or a welding tradesman, Professor Stampfer calculated PD mortality odds ratios for each definition, as well as for each definition for deaths under age 65. None of these analyses yielded statistically significant associations. Park’s curious results could not be replicated from the NCHS dataset.

For welders, the overall PD mortality odds ratio (MOR) was 0.85 (95% CI, 0.77–0.94), for years 1985 through 1999, in the NCHS dataset. If the definition of welders was expanded to including welding tradesmen, as used by Robert Park, the MOR was 0.83 (95% CI, 0.78–0.88) for all years available in the NCHS dataset.

When Stampfer conducted an age-restricted analysis, which properly compared welders or welding tradesmen with non-welding tradesmen, with death under age 65, he similarly obtained no associations for PD MOR. For the years 1985-1991, death under 65 from PD, Stampfer found MORs 0.99 (95% CI, 0.44–2.22) for just welders, and 0.83 (95% CI, 0.48–1.44) all welding tradesmen.

And for 1992-1999, the years used by Park (2005), and similar to the date range used by Martin Wells, for PD deaths at under age 65, for welders only, Stampfer found a MOR of 1.44 (95% CI, 0.79–2.62), and for all welding tradesmen, 1.20 (95% CI, 0.79–1.84)

None of Park’s slicing, dicing, and subgrouping of welding and PD results could be replicated. Although Dr. Stampfer submitted a report in Steele, there remained the problem that Park (2005) was a peer-reviewed paper, and that plaintiffs’ counsel, expert witnesses, and other published papers were citing it for its claimed results and errant discussion. The defense asked Dr. Stampfer whether the “least publishable unit” had been achieved, and Stampfer reluctantly agreed. He wrote up his analysis, and published it in 2009, with an appropriate disclosure⁶. Meir J. Stampfer, “Welding Occupations and Mortality from Parkinson’s Disease and Other Neurodegenerative Diseases Among United States Men, 1985–1999,” 6 J. Occup. & Envt’l Hygiene 267 (2009).

Professor Stampfer’s paper may not be the most important contribution to the epidemiology of Parkinson’s disease, but it corrected the distortions and misrepresentations of data in Robert Park’s paper. His paper has since been cited by well-known researchers in support of their conclusion that there is no association between welding and Parkinson’s disease⁷. Park’s paper has been criticized on PubPeer, with no rebuttal⁸.

Almost comically, Park has cited Stampfer’s study tendentiously for a claim that there is a healthy worker bias present in the available epidemiology of welding and PD, without noting, or responding to, the devastating criticism of his own Park (2005) work:

“For a mortality study of neurodegenerative disease deaths in the United States during 1985 – 1999, Stampfer [61] used the Cause of Death database of the US National Center for Health Statistics and observed adjusted mortality odds ratios for PD of 0.85 (95% CI, 0.77 – 0.94) and 0.83 (95% CI, 0.78 – 0.88) in welders, using two definitions of welding occupations [61]. This supports the presence of a significant HWE [healthy worker effect] among welders. An even stronger effect was observed in welders for motor neuron disease (amyotrophic lateral sclerosis, OR 0.71, 95% CI, 0.56 – 0.89), a chronic condition that clearly would affect welders’ ability to work.”

Robert M. Park, “Neurobehavioral Deficits and Parkinsonism in Occupations with Manganese Exposure: A Review of Methodological Issues in the Epidemiological Literature,” 4 Safety & Health at Work 123, 126 (2013). Amyotrophic lateral sclerosis has a sudden onset, usually in middle age, without any real prodomal signs or symptoms, which would keep a young man from entering welding as a trade. Just shows you can get any opinion published in a peer-reviewed journal, somewhere. Stampfer’s paper, along with Mortimer’s meta-analysis helped put the kabosh on welding fume litigation.

Addendum

A few weeks ago, the Sixth Circuit affirmed the dismissal of a class action that was attempted based upon claims of environmental manganese exposure. Abrams v. Nucor Steel Marion, Inc., Case No. 3:13 CV 137, 2015 WL 6872511 (N. D. Ohio Nov. 9, 2015) (finding testimony of neurologist Jonathan Rutchik to be nugatory, and excluding his proffered opinions), aff’d, 2017 U.S. App. LEXIS 9323 (6th Cir. May 25, 2017). Class plaintiffs employed one of the regulators, Jonathan Rutchik, from the welding fume parkinsonism litigation).