Abuse of
Epidemiology: Automobile Manufacturers Manufacture a Defense to Asbestos
Liability
By David S. Egilman, MD, MPH, Marion A. Billings, MSC
International Journal of Occupational and Environmental Health,
2005;11:360–371
Table omitted, see the free original:
http://www.ijoeh.com/pfds/IJOEH_1104_Egilman_02.pdf
Much of the "debate" about the relationship between asbestos exposure from
automobile brake work and asbestos-induced cancer has been fueled by studies
that have been funded by corporations with billions at stake in tort
litigation. The authors explore how asbestos-lined brake manufacturers have
corrupted medical literature to escape liability, analyzing studies funded
by these companies to enable them to claim that work with asbestos brake
linings never causes mesothelioma. They reveal how the companies have
redefined scientific criteria for the determination of cause–effect
relationships and manipulated scientific data to give the impression of an
absence of effect. But the absence of evidence is not evidence of the
absence of an effect. Key words: mesothelioma; asbestos; corruption;
occupational health; brake mechanics.
INT J OCCUP ENVIRON HEALTH 2005;11:360–371
In recent years, thousands of automobile and "shade-tree" (amateur)
mechanics have sought compensation for asbestos-related disease from
manufacturers of asbestos-lined brakes. Despite the fact that these brakes
are 40–70% asbestos, the brake manufacturers have vigorously denied that
they contributed in any way to a single case of asbestos-caused disease.1
The brake manufacturers have dismissed the fact that there is no known
threshold of exposure associated with mesothelioma (a rare cancer of the
pleura or peritoneum), and that in some cases the only documented worker
exposures are those that have occurred as a result of exposures to asbestos
from brakes.2 Rather than accept the well-established scientific facts, the
industry has funded scientists and lawyers to develop arguments and methods
for defending against lawsuits brought by workers and their household
members who have developed mesothelioma as a result of exposure to asbestos
in brakes.1,3–6 To support their arguments, the automobile manufacturers
have hired consultants to reanalyze previously published hygiene and
epidemiologic studies.4–7
Some manufacturers of asbestos-lined brakes— including GM, Ford,
Daimler–Chrysler, and Bendix— have sponsored four notable examples of such
research since the late 1990s. In 2001, Otto Wong, an epidemiologist working
for a California-based health sciences company, fired the first salvo of
their defense.6 Although Wong’s paper is couched as a critique of regulation
of exposures to asbestos-lined brakes and EPA risk assessments, Bendix (an
automobile brake manufacturer) first presented it as an expert report to
defend against a lawsuit by a worker who had been exposed to asbestos brake
linings and had contracted mesothelioma.8 Three years later other
manufacturers of asbestos-lined brakes (GM, Ford, and Chrysler) sponsored
Goodman et al. to write a second brake-related lung cancer meta-analysis
combined with a duplication of Wong’s mesothelioma analysis.5 The automobile
companies then sponsored Hessel et al. to write a third paper which was an
extension of a paper by Spirtas of the NIH that had already been included in
Goodman et al. and Wong’s metaanalysis. 4 Finally, the industry subsidized
an incomplete analysis of historical exposures to asbestos in brake work.3
These companies have spent millions of dollars to generate these
epidemiologic studies in order to refute claims of causation and thereby
avoid compensation payments to victims and their families. Accordingly, all
four papers demonstrate the use of two practices associated with the
industry’s involvement in scientific research: the redefinition of
scientific criteria for the determination of cause–effect relationships and
the manipulation of scientific data. In this paper we critique these
methods, drawing examples from the first three of the four papers cited
above. The first section delineates the process of redefinition of
scientific criteria for determination of causation, followed by a more
in-depth discussion of specific methods of scientific manipulation utilized
in the studies by Goodman et al., Wong, and Hessel. As a whole, we analyze
the value of this type of research in regard to its claims about the
relationship between exposures to asbestos during brake work and induction
of mesothelioma.
REDEFINITION OF SCIENTIFIC CRITERIA FOR DETERMINATION OF CAUSE–EFFECT
RELATIONSHIPS
This method, first developed by the tobacco industry, involves two parts.9
First, industry lawyers and scientists redefine the type and amount of
"proof" required to legally establish causation.9 This is done by derogating
unfavorable classes of evidence that are unfavorable to industries’
litigation and regulatory positions and insisting that evidence that does
not exist or is favorable to industry is most important or essential to
establish a cause–effect relationship in court. For example, when a suspect
carcinogen is found to cause cancer in human epidemiologic studies but not
in animals, companies argue that animal studies are required to prove
causation. 9 On the other hand when animal studies are positive and human
epidemiology is incomplete or negative, companies argue that human evidence
is required before the government can regulate the substance and before
workers and others can be compensated.9
For example, tobacco companies argue that human epidemiologic studies cannot
establish causation but instead only establish some "non-definitive"
association between exposure to tobacco smoke and cancer.10 They have argued
that epidemiologic studies cannot distinguish a genetic link between the
propensity to smoke and the propensity to contract cancer.10 This critique
of human epidemiologic studies is true, but irrelevant since there is no
biologic basis for such speculation. On the other hand, when early
researchers failed to induce cancer in animals that were exposed to tobacco
smoke, tobacco companies insisted that only animal inhalation studies could
"prove" causation.10 After the now-famous beagle studies, these companies
emphasized the importance of mechanistic understanding as a causal
requirement. 10 They then argued that unless one could explain exactly how
tobacco smoke caused cancer they had no "scientific proof" of causation.10
Some chemical manufacturers have made comparable epistemological arguments
when studies of their products have followed a similar fact pattern. In the
early 1970s, for example, when researchers failed to induce cancer in
animals following benzene exposure, industry expert witnesses stated that
these missing animal data were required to establish that a substance was a
human carcinogen.11,12
The second element of this method is industry’s insistence on direct causal
evidence related to specific forms of exposure in individual cohorts of
workers. Human epidemiology is often lacking for most chemical- exposure
cancer effects. Most chemical companies, therefore, argue that these missing
"animal or other studies," or human studies in which the exposed workers are
exposed to the substance in question only (a virtual impossibility), are
required to establish proof of a cause–effect relationship. In the latter
case, industry argues that animal and in vitro studies are rendered invalid
as evidence of causation.9 Since cancer effects have long latent periods and
workers are generally subject to potential confounding exposures, these
studies are rare and easily criticized.9 When clear epidemiologic evidence
of causation exists, as is the case of the relationship between asbestos and
mesothelioma, companies and their experts have argued that before an injured
worker can even file a claim for compensation two epidemiologic studies in
similarly exposed individuals that find a statistically significant doubling
of the risk must be published in peer-reviewed journals.13 Some Texas courts
have accepted this argument and even appear to require the publication of
human epidemiologic studies for subgroups of particular industries with
statistically significant rate ratios above two before a worker can even
file a lawsuit.14 Greenland calls the use of this criteria a "methodologic
error that has become a social problem."15
These stringent legal requirements can be contrasted with the normal
physician practice of assigning causation based on an analysis of all
available evidence with no specific rate ratio or statistical
requirements.16 In general, practicing physicians attribute lung cancer
causation to tobacco smoking if there is evidence of a history of smoking
any cigarettes, regardless of brand, for often unspecified time frames prior
to disease diagnosis. 9 Practicing physicians would not check to see whether
a published, peer-reviewed paper showed that smoking ten cigarettes per day
caused a statistically significant doubling of the risk of contracting lung
cancer prior to making the determination that a patient’s smoking had caused
or contributed to his or her cancer. Physicians also take for granted that
all brands smoked contributed to disease causation even in the absence of
studies evaluating individual brands.
The asbestos-product manufacturers and their experts have constructed an
epistemological straw man, asserting that epidemiologic evidence of
causation is required in each and every worker cohort that has a documented
excess exposure to a harmful substance before evidence of causation can be
presented in court. Companies argue that, to prove causation, both the type
of asbestos and the nature of exposure (same job, not just comparable
exposure) must be clearly documented in an epidemiologic study as having a
causal effect on the development of cancer.13 Even the tobacco companies
have not gone so far as to argue that an expert cannot assert that Virginia
Slims cause a specific lung cancer subtype (e.g., bronchogenic cancer) in
women absent an epidemiologic study of smokers of that particular cigarette
showing a statistically significant twofold increased risk in that
particular cohort of female smokers for that particular subtype of lung
cancer. Yet the asbestos companies and their experts argue that separate
cohort studies are needed to establish causation for the same disease for
each fiber type and each product composed of that fiber despite the fact
that almost all workers are exposed to more than one fiber type from more
that one product.13
As a result, companies and their experts attempt to show that exposures to
asbestos from their product are somehow "different" or even irrelevant.
Manufacturers argue that exposures to asbestos from their products are
quantitatively or qualitatively unlike other asbestos exposures. 13 For
example, asbestos in their products is "bound" or "degraded" or "decomposed"
or "results in too low an exposure" to cause mesothelioma.13 Unfortunately,
some courts have adopted aspects of this reasoning. 17 In the case of
chrysotile asbestos—the only fiber type that industry still claims does not
cause mesothelioma— the argument that the particular type of asbestos in a
company’s product is different from other types is now generally recognized
as the "amphibole hypothesis." 18–23 It is important to note that product
manufacturers who used amosite fiber made similar arguments by claiming that
there was insufficient epidemiologic evidence to establish that amosite
caused mesothelioma.24
MANIPULATION OF SCIENTIFIC DATA— META-ANALYSIS AND EXPOSURE DATA
MISREPRESENTATION
Manipulation of scientific data and misuse or reinterpretation of standard
scientific reasoning is ubiquitous in the automobile industry–sponsored
asbestos studies. The most common are: selection of inappropriate studies
for re-analysis, selective presentation of study data, non-differential
exposure-determination bias, inadequate sample size, comparison of an
exposed cohort with an inappropriate control group, and misuse of confidence
intervals. Here we present these strategies, illustrated with specific
examples from the Bendix, Ford, General Motors, and Daimler– Chrysler
studies.
Selective Presentation of Exposure Data
In his article, Wong outlines the "lack of exposure" argument as described
in the previous section.6 In doing so, however, he fails to report studies
indicating that work with asbestos brake linings leads to exposures that
have resulted in asbestos cancers in other occupational and non-occupational
settings.25 Wong not only ignores exposure studies whose results contradict
his industry position; he also misrepresents the results of the studies he
does report. He states that "studies have shown that brake lining dust
contains little recognizable chrysotile fibers" and extrapolates from a few
studies to claim that current exposures are "extremely low."6 It is true
that only some studies have examined decomposed (used) brakes; the heaviest
exposure to asbestos occurs during the sanding and grinding of new brakes.25
Of course, current exposures do not reflect past exposures or risk. Studies
of workers’ previous job activities reveal exposure levels hundreds of times
higher than current permissible limits.25 Wong cites some "data" from a 1987
Finnish study by Kauppinen and Korhonen by listing average fiber
concentrations as <0.05 fibers/cc.26 This study also found, however, that
the grinding of brake linings produced asbestos concentrations as high as
125 fibers/cm3. Kauppinen and Korhonen reported exposures up to 8.2 f/cm3
during the cleaning of passengercar drum brakes using a compressed air jet
to remove brake dust.26 (Unfortunately this is still a common practice in
many nations, including the United States.) Average concentrations were
between 0.1 and 0.2 f/cm3 for truck and bus repair. The only data point Wong
chose to report from this study represented average exposures during
passenger-car repair. Contrary to Wong’s misleading data selection and
analysis, this study demonstrated that average asbestos concentrations in
Finland may comply with TWA limits, but also showed that peak exposures
often exceeded the OSHA excursion limit.26
Wong also selectively excerpts information from a paper by Agudo et al.,
whom he quotes stating, "Overall, 37% of cases of mesothelioma in our
population are attributed to a sure (or almost sure) occupational exposure
to asbestos and this proportion comes up to 62% when occupations with any
probability of exposure are included." In turn, Wong concludes that "this
observation underscores the high proportion of malignant mesothelioma cases
not related to occupational exposure."6 Wong makes this assertion but omits
Agudo et al.’s subsequent qualifying sentence, which states, "Around 40% of
cases of mesothelioma in our population could be due to causes other than
occupational exposure to asbestos, although possibility of other
occupational exposures in non-traditionally hazardous scenarios cannot be
ruled out."
Manipulation of Meta-analysis: Inappropriate Study Selection and
Selective Presentation of Data
Industry researchers can often influence results by careful selection of the
epidemiologic studies they decide to evaluate. Studies favored by the
industry perspective (those with negative results in regard to the
relationship between exposure and cancers) are included, and others are
ignored or derogated and then excluded. Goodman et al. and Wong reanalyzed a
series of epidemiologic studies, claiming that they failed to find an
association between brake work and an increased incidence of
mesothelioma.5,6 Both, however, disregard numerous methodologic problems in
the individual studies they chose to incorporate in their analyses and
ignore study limitations noted by the original authors. Furthermore, these
authors selectively omit key information that undermines their conclusions
and evidence.
Goodman et al. first attempt to evaluate the quality of 11 studies with
potentially relevant information about the relationship between brake work
and mesothelioma. The authors use a self-created 11-point scale to evaluate
the studies (the rating system allowed for negative scores). The highest
ranked study—one of two purported "studies" based on "personal
communications" by Goodman and Hessel themselves—garners a 5, out of 9. The
scores for the rest of the studies included in the meta-analysis are
unimpressive: 3, 4, 1, 4, 1, and 2, out of 9. Goodman et al. excluded
studies that scored minus 1 (the rating system allowed for negative scores)
but none of the included studies achieved a passing grade of 60% based on
normal academic standards. Goodman et al. seem to believe that evaluating
the studies in such a way somehow mitigates their underlying methodologic
errors and inadequacies. Unfortunately, revealing errors is not the same as
fixing them, and these studies, which were never designed to assess
mesothelioma risk to brake-exposed workers, are beyond repair.
After this elaborate quality evaluation, Goodman et al. performed a
meta-analysis using the same studies that Wong had reviewed three years
before. They excluded two cohorts. The first of these was a study of 685
automobile mechanics that reported two mesotheliomas. 27 The second found a
statistically significant excess of mesothelioma in mechanics with a
reported rate ratio.28
Furthermore, Goodman and his colleagues present the data entirely out of
context. The original authors of the underlying studies did not design them
to examine the specific issue of exposure to asbestos during brake work and
subsequent incidence of mesothelioma. The extraction, therefore, of
occasional study participants who happen to be automobile mechanics not only
lacks statistical power but cannot be independently used as concrete
evidence proving the absence of a relationship between a complicated
exposure and a potential outcome. Due to the inherent difficulty in
determining asbestos exposure (especially in the case of brake work due to
the large number of amateur brake jobs and part-time brake work that can
easily go unnoticed when determining exposure) cohort studies must be
specifically designed to address the issue of mesothelioma among those
exposed to brake dust. Until such studies are conducted, it is wrong to
conclude that epidemiologic studies fail to establish a relationship between
brake work and asbestos-induced cancer. The converse, however, is not true.
To paraphrase Karl Popper, finding a thousand white swans does not prove
that all swans are white; the discovery of a single black swan disproves
that hypothesis.29 This is particularly true when a researcher is relying on
studies of all bird species (all SIC codes) to determine the color of swans
(risk in brake workers). As Lemen has shown, there are plenty of black swans
in the context of asbestos-induced cancer; he has documented more than 220
published cases of mesothelioma in users of friction products.25
The automobile manufacturers have spent millions of dollars to reanalyze
studies that were never designed to determine mesothelioma risk in brake
mechanics. On the other hand, they have access to a cohort of their own and
their dealers’ workers, whose work involves the installation and repair of
brakes. They are perfectly situated to use other demographically similar
employees who work at these same facilities as a control population. In many
cases they have access to medical and workers’ compensation records that
would allow them to efficiently conduct such a study. Why haven’t they done
so?*
*Or perhaps their lawyers have already conducted such a study and kept it
secret. As has been noted, in tobacco litigation, company lawyers often
contract with experts to conduct studies. If the studies are unfavorable the
company does not have to produce these in litigation. The brake
manufacturers’ lawyers have funded and actually helped conduct some studies
related to brake exposures.30,31
Wong and Goodman et al. both exclude evidence from other epidemiologic
studies that contradict their conclusions. Hansen, for example, examined the
mortality of automobile mechanics and found an excess mortality from
mesothelioma.32 The study reported a single case of mesothelioma over a
ten-year period among approximately 20,000 automobile mechanics, yet,
because of the rarity of the disease, the authors concluded that, "asbestos
exposure is known to occur during the replacement of brake linings, and the
single case of pleural mesothelioma is an indication that this exposure has
not been negligible."
Differential Exposure-determination Bias
In his meta-analysis Wong relied primarily on case– control studies that
were fraught with problems of differential exposure-determination bias.
Asbestos exposure is difficult to determine since many individuals are
unaware of their exposures, especially in secondary cases in which an
individual might inhale asbestos fibers from the clothing of a spouse or
parent returning home from asbestos-related work. In the case of brake work,
many individuals engage in part-time or amateur mechanic work, yet otherwise
engage in other careers and may therefore be classified as unexposed if
determination is based on a classical epidemiologic determination of
"regular occupation." Of course the direction of any potential or actual
bias is a key issue in analyzing its potential effect on the results of a
study. Random exposure misclassification biases results towards the null.
However, as we discuss below, in this case, because exposure is more often
missed in the exposed cohort, the misclassification is likely to lead to an
inverse relationship between exposure and disease.
In the case of mesothelioma, in which the time between diagnosis and death
is usually a matter of months, retrospective study designs such as case–con-
trol studies often require the interviewing of surrogates (spouse, children,
etc) to determine exposure. Direct interviews of cases or controls are far
more likely to uncover prior brake exposure than are interviews with
surrogates. Individuals who did not work primarily as automobile mechanics
are likely to be misclassified as unexposed if surrogate interviewees are
unaware of any part-time or amateur brake work done earlier in life. Since
mesothelioma cases are more likely to be deceased at the time of interview
than controls, a differential exposure-determination bias may show that the
"exposed" have less risk than the unexposed. Nextof- kin interviews are
particularly subject to this result, since brake exposures often occur among
"shade tree," occasional, or even high school mechanics in automobile repair
courses. These exposures are more likely to be reported by patients
themselves than by relatives, particularly children of patients. In many of
the studies the researchers determined exposure from direct interview of
controls, in comparison with greater reliance on interviews with survivors
of mesothelioma patients. Next-of-kin interviews were therefore used more
often to estimate exposure in mesothelioma patients than in controls. Since
direct interviews are more likely to elicit a history of exposure to brakes
than next-of-kin interviews, brake exposures are systematically more likely
to be recorded for controls than cases. Goodman et al. acknowledge the
problem of next-of-kin interview bias but omit any discussion of the fact
that the consequence of this bias is a result showing that brake work
protects against mesothelioma. This phenomenon is demonstrated by the fact
that most of the studies Wong and Goodman et al. selected had rate ratios of
less than one. Wong’s overall point estimate was 0.90 (95% confidence
interval 0.66–1.23), while Goodman et al. determined that exposure to brake
dust produced a statistically significant and important reduction in the
rate of mesothelioma of 0.67 (95% confidence interval 0.53–0.84) in all
studies combined.†
†They found combined RRs of 0.92 (95% CI 0.55–1.56) in Tier I studies and
0.81 (95% CI 0.52–1.28) Tier II studies.
The finding that brake work reduces the risk of mesothelioma is a sign of
systematic error in this meta-analysis, because exposure to asbestos brakes
cannot reduce the risk of developing mesothelioma by 33%. That is, however,
what these selected meta-analyzed data showed.
Other Bias Issues
The study conducted by Agudo and others, published in 2000, demonstrates how
differential exposure determination can bias results when exposure histories
of cases (who are dead or too sick to be interviewed directly) are more
likely to be determined by surrogate interviews than are exposure histories
for controls.33 Forty-four percent of cases were deceased at the time of the
study, and thus researchers determined their exposures through family-member
interviews. Among the control group, however, the researchers directly
interviewed all but one participant. Cases, therefore, may have been less
likely to be classified as exposed, which would bias the resulting risk
ratios to be less than one. In addition, the researchers considered only
occupations that had been held for at least six consecutive months, meaning
that workers with exposures from part-time or amateur brake jobs were
omitted. This random misclassification biased the results of the study
towards the null. The authors also assumed without question that brake work
puts an individual at risk for asbestos exposure, by placing brake mechanics
in the "risk of exposure" category in their analysis. The rate ratio for
this entire category of asbestos-exposed workers was elevated, at 2.59, but
the analysis of a small number of individuals within the category of at-risk
occupations (i.e., the brake mechanics) cannot lead to any sound
conclusions.
The study published in 1994 by Spirtas and others provides additional
evidence that exposure-determination bias is a real threat to study
validity.34 In the study, younger cases had a higher attributable risk for
mesothelioma from asbestos exposure than did older cases. This is likely to
have resulted from more accurate exposure assessment among younger
individuals, who were better able to remember more recent exposure events.
Spirtas et al. did not include independent analyses of the members of the
cohort who reported "brake lining work or repair" (105 of 741) because of
the high rate of multiple asbestos exposures in this group.34 Unlike the
authors of the original study, Wong fails to note these non-brake exposures
or the original authors’ exclusion of these workers, and relies on these
rejected data in his meta-analysis.6
The automobile manufacturers paid Hessel et al. to "update" the Spirtas
cohort and reanalyze its brakeworker data in 2004.4 The results of the
analysis presented by Hessel and colleagues reveal the methodologic problems
with the use of the NIH data set. First, the analysis of Hessel et al.
indicated that non-occupational brake work prevented workers from developing
mesothelioma (regression beta was –0.184). In addition, their analysis found
that higher levels of exposure to asbestos among workers performing
occupational brake work were more protective (regression beta was –0.307).
In other words, these authors found a dose– response relationship between
exposure to asbestoslined brakes and reduced risk of mesothelioma. Of
course, brake work cannot reduce workers’ risk for contracting mesothelioma,
and it certainly can’t do this in a "dose"-dependent manner. The
unbelievable dose– response relationship is further evidence that the study
suffered from systematic error. Hessel and his colleagues also examined six
other job categories of asbestos-exposed workers, all of whom have been
found to have developed asbestos-induced mesothelioma or other
asbestos-related disease in other studies, including workers exposed to
asbestos insulation in furnace or boiler installation or repair,35,36
building demolition, 37,38 plumbing or heating repair,39,40 elevator
installation or repair,41 production of asbestos textiles, and production of
paper products.42–45 In contrast to previous cohort studies, Hessel et al.
found no increased risk of mesothelioma in workers performing these jobs.
They found elevated odds ratios for shipbuilding and repair work (OR 6.04,
CI 3.74–9.75) and insulation work (OR 3.38, CI 2.20–5.17). While elevated,
these odds ratios are orders of magnitude lower than those found in cohort
studies of these same two groups. For example, Selikoff found that about 10%
of insulators died from mesothelioma, giving an approximate rate ratio of
1,000.46 Thus, unless one is willing to believe that brake work protects
against mesothelioma and that previous cohort studies of other job
categories are wrong, Hessel et al. have provided results indicating that
their method biases results to the null and/or reverses actual effects of
exposure, turning harmful exposures into beneficial ones.
Teschke et al. used an occupation-classification scheme that may also have
biased results towards the null.47 The authors stated, "In addition,
grouping of occupations was likely to result in non-differential
misclassification, usually biasing risk estimates to the null value." Wong
omitted this critical fact. The study is also another example of
differential exposure-determination bias—the authors determined exposure
histories for 13.6% of controls’ histories of exposure were obtained through
next-of-kin interviews, compared with 33% of cases. The study also had a
higher non-participation rate among controls, which could lead to selection
bias, and interviewers were not blinded to the case–control status of the
interviewee, possibly leading to interviewer bias.
The Woitowitz and Rodelsperger study focused solely on the issue of a
relationship between automobile mechanic work and mesothelioma.48 Part of
this study is of no value in determining the relationship between any
asbestos exposure and mesothelioma because the authors used lung cancer
patients as controls. Exposure status is likely to be similar among the
control group and the cases, which would lead to little discernable
difference in risk between the two groups, despite any real association that
may exist between brake work and mesothelioma. Since asbestos exposure is a
well-known risk factor for lung cancer, any mesothelioma case–control study
with lung cancer patients as the control group will almost certainly produce
results at or below the null. This study demonstrates this effect well,
since the researchers used "population controls" as well as lung cancer
patients as controls. The odds ratio (OR) for "hospital controls" was 0.75,
almost half that for population controls, 1.32. Rather than report both
results, Wong presented an average OR of 0.87. Goodman et al. published both
ORs but included only the lower average in their meta-analysis.5,6
McDonald and McDonald conducted a case–control study, published in 1980,
examining mesothelioma cases from Canada and the United States.49 Like the
Woitowitz and Rodelsperger study, this study relied on an inappropriate
control group; control subjects were patients in cases diagnosed by
pathologists in which "pulmonary metastases were present from a
non-pulmonary malignant tumor."48,49 For example, the control group may have
included patients who had died from mesothelioma or other asbestos-induced
malignancies such as laryngeal or colon cancer.50,51 The choice of such
controls biased results towards the null. In addition, the study reviewed
occupational status only ten years prior to death. Since mesothelioma has a
minimum latency period of about ten years, this study did not necessarily
address any subject’s most relevant exposures. McDonald et al. subsequently
compared lung-fiber burdens between control and mesothelioma patients and
found no statistically significant difference between the amounts of
chrysotile, amosite or crocidolite. 52 This is further evidence that
controls were not adequately chosen, since they were clearly exposed to as
much asbestos as the 99 mesothelioma patients. This misclassification biases
the results to the null.
Both Wong and Goodman et al. ignore other studies that reveal mesothelioma
risk to brake-manufacturing workers. Since these authors base their argument
for lack of risk on fiber length and the general issue of whether or not
chrysotile can ever cause mesothelioma, they are clearly relevant. And while
they are also compromised by numerous methodologic and other problems, they
do show increased rates of mesothelioma in brake manufacturing workers.53,54
Dodson has critiqued the "short fiber" argument elsewhere.55 The risk to
brake-manufacturing workers is relevant to the question of risk to
brake-repair workers, since the fiber used in the manufacture of brakes is
the same length as that in new brakes. If there is relevance to the
shortfiber argument at all, it relates to exposures from used brakes.
Brake-repair workers are exposed to fibers from both new and used brakes
from tooling parts as well as blow-out of brake-wear dust.
In 1982, McDonald and Fry published results of a study of a Connecticut
chrysotile asbestos brake-manufacturing factory and concluded that, "The
failure to find a single mesothelioma among 1469 deaths in 4738 employees of
the largest and oldest asbestos factory in the state suggests that
chrysotile in the manufacture of friction products was not responsible for
the problem." 54 In a study of three plants including the Connecticut plant,
McDonald et al. reported "only" 0.4 cases of mesothelioma per 1,000
individuals in chrysotile asbestos factories over the course of
approximately 40 years [1/100,000 or 10 per million per year]. They then
asserted that, "This finding supports much other evidence that amphibole are
mainly responsible for mesothelioma whereas chrysotile has little or no
mesothelioma-producing potential."54 The authors present this evidence,
however, without discussing the expected population rate for comparison.
Teta et al. report an expected rate of 2.2 cases per million each year for
the total population and 4 per million for Connecticut. 56 Comparisons with
expected population rates are also problematic, since at least half of all
mesothelioma cases are caused by occupational exposures to asbestos. The
unexposed expected rate is no higher than 1 per million.57 For a true
comparison to be drawn, it would have to be with only those cases that were
not occupational, since the risk of mesothelioma among automobile mechanics
should not be compared with the risk of workers in other occupations known
to cause the disease, but with those who were not occupationally exposed.
The rate reported by McDonald et al. is therefore at least more than double
the expected rate. McDonald’s data thus support the claim that chrysotile
asbestos causes mesothelioma.
The McDonalds’ research suffered from other, more serious problems. In 1983,
Teta et al. described findings from the state of Connecticut cancer registry
and reported three mesothelioma deaths in the same Connecticut factory and
during the same time frame used in the McDonald study.56 One year after the
publication of Teta’s paper, in 1984, McDonald et al. published their
"final" report on the plant. This "final" report, however, did not report
the full data from the original cohort, which included both men and women,
but reported data from the male portion of the cohort only.58 Two "missed
cases" occurred in women who were members of McDonald’s cohort.59 McDonald
et al. reported that they had found not a single case of mesothelioma in
this plant and failed to mention the cases Teta cited from the state of
Connecticut registry.53 In their 1982 paper, McDonald and Fry claimed their
data were reliable, in large part due to the existence of the very same
registry. They stated, "The opportunity for recognition of mesotheliomas was
also very good at the chrysotile friction materials plant, as the state of
Connecticut has maintained a renowned cancer register." 54 Clearly this
would hold true only if the authors had checked the registry prior to the
publication of their paper; unfortunately, it appears that they had not done
so.59,60 Teta et al. claim they informed them of the discrepancy and in 1986
McDonald tried to explain the omission away.59 McDonald stated that she and
her colleagues omitted the cases because mesothelioma had not been indicated
on two of the deceaseds’ death certificates, the primary measure of outcome
in their study, and that they excluded the third case because he had
terminated work prior to the beginning date of their study.59 However, in
1986, by the time McDonald had commented on these discrepancies, at least
two other cases of mesothelioma in the plant had been reported on death
certificates (see Table 1, cases 1 and 2). Both fit the initial cohort
definition and the first left employment before there was any alleged
amphibole use. These cases occurred after the termination date of the
McDonald study. We are now aware of at least six additional mesothelioma
cases in workers from the plant, four of whom had no other possible
exposures to asbestos (Table 1). At least four of these cases are known to
the main sponsors of the McDonalds’ research, since members of the Quebec
Asbestos Mining Association (QAMA) were sued by three of them. Therefore,
there were a total of at least nine mesotheliomas in this factory, which
used chrysotile until 1957 only.‡
‡Some anthophyllite was used beginning in 1957, and about 400 pound of
crocidolite were used experimentally in the laboratory from 1964 to 1972.53
Perhaps by unfortunate coincidence, all of these cases occurred before or
after the beginning and ending dates of the McDonalds’ studies or the
diagnoses were not reported on the death certificates.
Death certificates, in general, are often inadequate means of determining a
mesothelioma diagnosis, due to the strong possibility of other related
conditions’ becoming the primary causes of death (e.g., cardiac arrest) and
because mesothelioma is frequently misdiagnosed. Mesothelioma was not added
as a specific ICD code until 1968.61 The study was conducted in the 1970s,
mostly examining data from prior decades, in which mesothelioma was a
lesser-known disease that was frequently not accurately diagnosed. In
addition, the Connecticut registry was an excellent source of data for a
comparison of expected and plant rates. To make the data compatible, the
registry should have been used to determine the mesothelioma rates for the
plant workers. Had they done so, McDonald et al. would not have missed the
two mesothelioma cases that occurred during their selected observation
period. Of course, the most important result of the exposure to chrysotile
at this plant is the death of nine workers from mesothelioma in a population
of about 4,500 workers. Although the McDonalds et al. stressed the
importance of this cohort in asserting that chrysotile did not cause
mesothelioma, these nine cases provide additional evidence that chrysotile
causes mesothelioma.
Despite the fact that Teta is a co-author of one of the
brake-manufacturer–funded papers and works for the company that generated
three of these papers, the brake-manufacturer–funded researchers failed to
use any of these studies or data to assess the hazard of exposure to
chrysotile-lined brakes.5,6 Other industry-funded researchers have also
failed to use this information in assessing chrysotile risks. Recently,
Crump and Berman completed a risk assessment for asbestos for the EPA.63 To
some extent this was an update of a previous assess- ment they had done for
the Asbestos Information Association, an asbestos industry lobby and public
relations front, in 1984.64 Berman and Crump ignored the published
mesothelioma cases from the friction plant that McDonald had acknowledged in
1986, and based their dose–response analysis on the assumption that there
were no cases in that plant,
Perhaps the most interesting of the changes between the 1986 KL value
estimates and the current KL value estimates involves the friction products
plant in Connecticut (McDonald et al. 1984). Although a relatively small,
positive exposureresponse was estimated from this study in the 1986 Health
Effects Update, the best current estimate is that this is essentially a
negative study (no excess risk attributable to asbestos).63
Teta served as an official reviewer of Berman and Crump’s paper, and
although the omitted cases were noted in 1983, along with the need for
further follow-up on this cohort, Teta recommended that the EPA adopt the
Berman–Crump model before the cohort follow-up was performed.65 The
Berman–Crump model did not incorporate these 1983 data, and we have reported
our partial follow-up of this population in this paper. Berman and Crump
also relied on dose estimates from QAMA studies about which the authors
themselves stated, "It remains doubtful, however, whether conversion [of
particle dose estimates, the only measure of exposure in the QAMA studies]
to a fibre equivalent can have much epidemiological validity."66
Inadequate Sample Size
Because of the broad nature of most of the studies, examining mesothelioma
risks among many different occupational groups, the numbers used by Wong
from each study (i.e., the number of garage mechanics in each study) is
usually less than 25. Hessel et al. (the highest- rated study in Goodman et
al.’s re-analysis) reports an OR for brake workers based on only two cases
after "controlling" for insulation and shipbuilding exposure and on a single
case after controlling for all other potential asbestos exposures. Any
conclusions relative to safety based on these tiny sample sizes are
reckless.
Use of Inappropriate Control Group
It is extremely difficult to find a comparable control group for
hospitalized mesothelioma cases. Due to the rarity of the condition,
mesothelioma cases are often referred to large medical centers. Some
hospital controls who do not have "rare" diseases will not reflect the true
demographics of the desired denominator population. Patients with
mesothelioma are often referred from rural or suburban to urban hospitals
for diagnosis or treatment. Patients from these urban environments are
likely to be overrepresented in the control group and are more likely to
have been exposed to brakes than the rural or suburban neighbors of the
cases (controls that more accurately reflect the demographics of the cases).
This effect helps explain how all but one of the studies Wong and Goodman et
al. analyzed found that brake work reduced the risk of the development of
mesothelioma.
Misuse of Confidence Intervals
Almost all of the studies reviewed report confidence intervals that include
a rate ratio greater than one.5,6 When risk ratios are being calculated on
small samples, point estimates cannot be considered particularly accurate,
and examination of confidence intervals is more important in determining
risk. Wong and Goodman et al., however, mention these confidence intervals
only in passing and base their entire analysis on point estimates.
DISCUSSION
Despite the clear methodologic problems with the abovementioned studies used
in their meta-analyses, Goodman et al. and Wong present them as
unquestionable evidence of the absence of an association between brake work
and mesothelioma.5,6 None of the studies used was designed specifically to
examine this association, bringing in the possibility that unknown
confounders could be at play. Despite this, Wong presents the studies under
the heading of "Epidemiologic Studies of Mesothelioma among Auto Mechanics"
and Goodman et al. title their paper, "Mesothelioma and Lung Cancer among
Motor Vehicle Mechanics: A Meta-analysis." As we have shown, a study that is
not designed specifically to determine brakework exposure is likely to be
fraught with bias due to the complexity of exposure determination.
The World Trade Organization issued a ruling on the matter in September
2000, after extensive expert testimony led to a conclusion that chrysotile
asbestos does produce a real risk of mesothelioma to mechanics. 67 The
ruling allowed European countries to ban the use of asbestos-containing
brakes. Both papers omit this information as well.
After publication of Wong’s paper but before the publication of that of
Goodman et al., considerable evidence emerged from studies conducted in
Australia by Leigh et al. supporting an association between automobile
mechanic work and mesothelioma. Of the approximately 6,000 individuals in
Australia’s extensive mesothelioma death registry, 1.2% were automobile
mechanics.68–70 For many, the only source of asbestos exposure was
brakelining repair.68,69 In a number of individuals examined, only
chrysotile asbestos fibers were found, indicating that chrysotile exposure
alone can cause malignancy.69
On the whole, Wong and Goodman et al. fail to adequately address the issue
of the relationship between brake work and mesothelioma. The small numbers
of individuals pulled from larger studies, from which Wong reports risk
ratios to support his argument, lack statistical power as well as
epidemiologic meaning due to the large amount of potential bias. The
meta-analyses begin to the address the problem of a lack of statistical
power. However, since the data used for the analysis are handpicked from the
literature to the exclusion of contrary evidence, and those that are
included are likely to suffer from various types of bias, the results
reported are not reliable. Until prospective cohort studies specifically
designed to determine asbestos exposure from brakelining installation and
repair are conducted, definite conclusions about the magnitude of this risk
cannot be made. It is clear that a risk exists.25
Moreover, the entire argument addressed by these analyses, regarding the
risks of chrysotile, is specious in light of the following undisputed facts:
1. Chrysotile causes lung cancer.72
2. Chrysotile causes asbestosis.72–74
3. Chrysotile used in the United States is contaminated with tremolite—an
amphibole.75
4. Products made from chrysotile contain tremolite.76
5. Chrysotile is concentrated in the pleura.77
6. Populations with mixed exposures to amphiboles and chrysotile have double
the rate of mesothelioma of those exposed to amphibole alone.78–80
7. Brake-repair workers get substantial airborne asbestos exposures from
grinding brake and clutch parts and blowing out dust from brake
assemblies.25
Almost all brake workers have had some exposure to amphibole with, or as
well as, chrysotile. Thus, even if chrysotile alone is not a cause of
mesothelioma it acts synergistically with amphiboles to increase the
incidence of this cancer.
CONCLUSION
The methods utilized by the asbestos and related industries— the
redefinition of scientific criteria for determining cause–effect
relationships and the manipulation of scientific data and scientific
inferences—have obscured the true picture regarding asbestos exposure and
mesothelioma. In contrast to their experts’ opinions, the relationship
between exposure to asbestos and mesothelioma has long since been recognized
by the brake-industry executives who retained Goodman et al. and Wong.5,6 In
his 1973 private presidential address to brake manufacturers, Ike Weaver,
the Chairman of the Asbestos Study Committee of the Friction Materials
Standards Institute, an industry trade organization, noted the importance of
this phenomenon:
I know of no way any of us
can be absolutely sure that his friction products, regardless of whether
they are sold as original equipment or on the replace- ment market, will not
be subjected to additional operations or alterations in the field that could
result in excessive exposure of workers or bystanders to airborne asbestos
fibre. I have been appalled to learn of a number of instances where this
problem has occurred, and some of these cases involved people that certainly
might have been expected to know better. . . .
If this kind of thing occurs in fabrication operations of major OE [original
equipment] customers, it appears to me there can be no argument about the
need for educational measures to reduce chances of unnecessary exposure
during grinding, drilling, or cutting operations. To those who argue that
labeling or other types of warning need not apply to replacement materials
because fabricators or appliers handling replacement quantities are exposed
relatively intermittently, I say emphatically this just ain’t necessarily
so! Large volume replacement users present major potential hazards, and even
small job shops can needlessly expose people to high fibre concentrations if
operations are performed without controls.81
Despite the secret industry acknowledgement of risk and high exposures,
Goodman et al. and Wong manipulate epidemiologic science to conclude that
exposure to asbestos from brakes does not induce asbestosrelated
malignancies. As we and others have noted, absence of evidence is not
evidence of absence; in other words, failing to find an association does not
provide any evidence that an association does not exist.82 Once it is
generally accepted that a substance can cause disease in humans, all that is
required to establish causation is documentation of exposure to that
substance. For example, the OSHA benzene standard did not require
epidemiologic evidence of cancer risk in every sector covered by the
standard.83 In the case of vinyl chloride, chemical companies themselves
removed the compound as a propellant in hair sprays based on animal studies
alone because of the risk of unlimited liability.84 The asbestos industry
and the automobile industry, rather than hiding behind a "dust cloud" of
misleading science, should do the same and stop using asbestos in brakes
worldwide.
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