MISSOURI CIRCUIT COURT
TWENTY-SECOND JUDICIAL COURT
(CITY OF ST. LOUIS)
DAYNA CRAFT, JASON STONE, DEBORAH
LARSEN, WENDY ALPER-PRESSMAN,
Individually and on Behalf of All Others
Similarly Situated,
Plaintiffs,
Case No. 002-00406-02
vs.
Division No. 6
PHILIP MORRIS COMPANIES, INC.,
a corporation, and
PHILIP MORRIS INCORPORATED,
a corporation,
Defendants.

Expert Report of Kenneth A. Mundt, Ph.D.

Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/pzkv0184

 INTRODUCTION
1.

I have been asked by Defense Counsel to evaluate the peer-reviewed,
published epidemiological literature, and other data and documents, on the
potential health effects of lower-tar cigarettes, relative to higher-tar products,
as measured by the FTC method. I have also been asked to review Plaintiffs'
and Defense experts' reports as they become available in this case, as well
as those of Dr. William Wecker and Dr. Peter Valberg from similar previous
cases.

2.

Specifically, the goals of this report include the following:
to describe the historical development of the epidemiology of health
effects associated with the reduction of cigarette tar yields over time;
to evaluate health effects of smoking lower-yield cigarettes relative to
higher-yield products;
to summarize the public health community's response to the scientific
evidence regarding the potential benefits of smoking lower yield
cigarettes;
to examine the criticisms that have been raised regarding the
epidemiological evidence on the potential benefits of lower-yield
cigarettes;

3.

•

to evaluate the rates of lung cancer overall and by major histological
group over time; and

•

to synthesize the epidemiological findings on lower-yield cigarettes and
evaluate the weight of the evidence pertaining to the health benefits of
low tar products relative to higher-tar cigarettes.

I may express additional opinions based on any new materials provided in the
case and any additional scientific literature subsequently identified or
published. I also may testify on additional topics expressed by Plaintiffs'
experts and that fall within my epidemiological expertise.
Qualifications

4.

I am by training and experience an epidemiologist. I was trained at the
master's level at the University of Massachusetts School of Public Health, and
at the doctoral level at the University of North Carolina School of Public
Health.

5.

I have extensive experience in designing, conducting, interpreting and
publishing primary epidemiological research; critically reviewing and
synthesizing the published epidemiological literature; training epidemiologists,

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 including classroom teaching, advising and chairing of Master's and Doctoral
Committees; and serving in epidemiological advisory, review and editorial
capacities at the local, national and international level.
6.

I currently serve as Adjunct Professor in the Department of Epidemiology,
University of North Carolina at Chapel Hill. For ten years (1989-1999) I
served full-time on the faculty of the Department of Biostatistics and
Epidemiology of the School of Public Health, University of Massachusetts,
where I am currently Adjunct Associate Professor and chair the Dean's
Advisory Board.

7.

I founded Applied Epidemiology, Inc., based in Amherst, Massachusetts, and
served as President until November 2003, at which time the company merged
with ENVIRON International Corporation, where I am a Principal and Director
of Epidemiology.

8.

I currently serve as an editor for two peer-reviewed scientific journals:
Advisory Editor for the International Archives of Occupational and
Environmental Health; and Associate Editor for Dose-Response. I am a peer
reviewer for these as well as several other professional journals.

9.

A copy of my current Curriculum Vitae, which provides additional details as
well as a complete list of my publications, is attached.
Substance and Basis of Opinions

10. I have comprehensively evaluated the peer-reviewed, published
epidemiological literature on lower yield cigarette use and risk of several
smoking-related diseases.
My evaluation considered primary research
studies as well as scientific reviews.
11. I have utilized standard and widely accepted methods for critically reviewing
and synthesizing the epidemiological literature.
12. In addition to the relevant peer-reviewed, published epidemiological literature,
I draw upon my education, training and professional experience to formulate
my professional opinions and conclusions, which I hold to a reasonable
degree of scientific and epidemiological certainty.

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 OVERVIEW OF EPIDEMIOLOGICAL PERSPECTIVE AND METHODS
13. The validity and strength of epidemiological study results depend on the
research approach, study design and data quality and completeness.
Important elements influencing the strength of evidence from an
epidemiological study include, but are not limited to, selection of proper study
design, valid ascertainment of disease, definition and accurate measurement
of exposure, timing of exposure, elimination of systematic error (bias) and
proper consideration of statistical variability leading to random error or
chance.
14. There are two basic epidemiological approaches to evaluating associations
between risk factors and disease: cohort studies in which disease rates are
compared between groups of exposed persons and a group of unexposed
persons; and case-control studies in which exposure history among
individuals with disease (cases) is compared with exposure history among
individuals without the disease (controls).
15. Case reports and case series are not epidemiological studies, but may be
useful in generating hypotheses that can be tested using appropriate
epidemiological study designs. Similarly, disease prevalence surveys and
proportionate mortality ratio (PMR) analyses of death certificate data may be
useful for generating hypotheses, but are generally unreliable for purposes of
determining causation.
16. Epidemiological studies often rely upon surrogate measures of exposure to
group individuals into qualitative exposure categories (e.g., "high," "medium,"
and "low" exposure). Studies that validly measure specific exposures for
individual study participants provide stronger evidence of an association, if it
exists, between the exposure and the disease of interest, than studies either
that employ indirect indicators or surrogates of exposure, or estimate
exposures at the group level ("ecological" evaluation).
17. Accurate timing of exposure relative to the disease process, including
consideration of a reasonable period of disease induction and disease
latency, are critical to the validity of epidemiological study results. Maximum
latency is usually described as the time elapsed between the first known or
possible exposure to the agent of interest and the diagnosis of the disease of
interest. It includes an induction period, at some (unknown) point during
which the disease is initiated, as well as a true latency period, the time
between disease initiation and clinical detection or diagnosis.
18. Exposure assessed or measured in the wrong time intervals (such as that
occurring after the disease progresses to an irreversible point) may be
irrelevant to disease causation.

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 19. In epidemiology, "bias" refers to systematic (or methodological) errors that
lead to inaccurate and potentially invalid study results. Most forms of bias
can be grouped into three broad categories: selection bias, information bias
and confounding bias. The degree to which sources of systematic error
leading to potential biases are identified and prevented in the study design, or
addressed statistically (as with confounding bias), determine the validity of
study results.
20. Selection bias results from incomplete and/or selective participation of certain
subsets of individuals in a study, resulting in distorted or even invalid results.
The degree of bias depends on the type and severity of the selective forces
acting upon the study sample.
21. Information bias results from systematic errors in questionnaire responses or
measured data, for example, leading to the misclassification of persons with
respect to exposure level or disease status.
22. Confounding bias occurs due to the failure to account for other risk factors for
the same disease outcome that are correlated with the exposure or risk factor
of interest. The effects of these other risk factors (i.e., confounders), if
appropriately identified and measured, can be controlled statistically, at least
in part. Uncontrolled confounding and residual confounding can result in
inaccurate or invalid study results.
23. Chance - or random or measurement error - can also lead to inaccurate or
invalid results. Statisticians and epidemiologists evaluate the probability that
an observed result is due to chance by applying tests of statistical
significance. Chance cannot reasonably be ruled out as an explanation for a
reported association if the results are not statistically significant. Statistical
tests are typically set to accept a 5% rate of committing a type I error, i.e.,
incorrectly identifying as statistically significant an incorrect result. Therefore,
by definition, 5% of all statistically significant results arise by chance: even in
the absence of a true underlying association, and any single result, even if
statistically significant, may not reflect a true underlying association.
24. Dose-response assessment, or the evaluation of the relationship between
estimated or actual dose of exposure, and the disease risk, (accounting for an
appropriate latency period), is a key tool of epidemiology. Such assessments
are frequently used to inform causal judgment and policy formulation.
25. Because effects of exposures at lower levels are more difficult to study, risks
identified in studies of individuals exposed at higher levels are often
mathematically extrapolated to estimate risks at lower levels of exposure. For
example, for carcinogens, EPA risk assessments assume a linear doseresponse relationship between exposure and cancer risk. Risk is assumed to
decrease monotonically with lower exposure, even if risks at such levels have
not been observed or studied epidemiologically. Examples of decision-

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 making based on higher-level exposure studies, where studies of the risks at
low-level exposures are unavailable include risks of residential radon
exposure based on studies of uranium miners or ambient air quality standards
for toxic compounds such as vinyl chloride, based on studies of vinyl chloride
production workers.
26. The determination of general causation is a judgment primarily based on a
critical review and synthesis of all available epidemiological evidence.
Epidemiological evaluation is directly relevant to human disease experience.
27. Epidemiology cannot directly demonstrate specific causation, i.e., whether
specific exposures or risk factors caused disease in a specific individual.
However, risks associated in epidemiological studies with factors considered
to be general causes of disease may reasonably be considered in inferring
specific causation among individuals similarly situated to study subjects with
respect to specific disease/diagnosis and specific exposure characteristics
including substance(s), intensity and duration.

METHODOLOGICAL ISSUES RELEVANT TO EPIDEMIOLOGIAL STUDIES OF
RISKS ASSOCIATED WITH REDUCED-YIELD CIGARETTE USE
28. The epidemiological assessment of risks associated with smoking cigarettes
with different tar levels (as measured by the FTC method) is similar to
assessments of other exposure-disease relationships, including the limitations
inherent to epidemiology as an observational science. An important issue in
assessing risks associated with cigarettes with different tar values is the
accuracy of characterizing individual smokers' tar exposures over time, given
that smokers may change brands, and that tar levels for most brands have
changed over time.
29. For a given number of cigarettes smoked per day, reductions in tar
consumption at a population level may result from manufacturers' reductions
in tar yield of cigarettes of a specific brand, from smokers of full-flavored
products switching to lower yield products, or by new smokers initiating with
lower-tar products. The latter scenario is increasingly common since the
1970's, and switching from high to lower yield brands is increasingly less
common.
30. Because actual tar dose cannot be measured in epidemiological studies,
surrogates include ever having been a smoker, age started smoking, duration
of smoking, type of cigarette smoked, FTC measurement of tar levels, and
amount smoked per day. More accurate estimation can be approximated
through the combination of measures such as duration and intensity of
smoking, resulting in "pack-years," or FTC yield and number of cigarettes per
day over time, resulting in "cumulative tar" exposures. The latter approach

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 generates some of the highest relative risks, suggesting that the FTC tar yield
is one of the best indicators of lung cancer risk.
31. Misclassification or incomplete assessment of individual lifetime exposure to
tar is likely to underestimate true exposure and therefore would tend to
artificially underestimate the benefits of lower-yield products. For example,
studies based on smokers' current brand might not accurately account for
prior smoking history, and therefore risks for those only recently switching to a
reduced-tar brand will resemble more the risks of smokers continuing to
smoke higher-level tar products. For example, misclassification of long-time
full-flavor smokers who have only recently switched to lower yield - as noted
by Dr. Wecker in his report in Schwab regarding the Harris, Thun (2004) CPS
reanalysis - will result in an underestimate of any beneficial effect of
switching.
32. Another source of potential study inaccuracy (or bias) includes possible
confounding, which is the mixing of effects from one or more risk factors with
the primary risk factor. Confounding commonly occurs due to differences in
occupational exposures, air pollution, nutritional status, etc. between
compared groups.
If measured, these factors can be evaluated and
statistically controlled, reducing or eliminating their confounding effects on the
study results. However, effective control of confounding by known risk factors
is not always possible, and control for unknown risk factors is not possible.
33. Dr. Burns in previous cases has claimed that a "self-selection" bias exists in
the epidemiological studies of lower yield cigarettes, hypothesizing that
individuals with an inherently lower risk of lung cancer self-select to smoke
lower-yield cigarettes. And any lower risk associated with lower-yield cigarette
use is therefore only an indicator of an inherently lower disease risk. If such a
bias exists, and if it is due to better education, diet, exercise or any other
exogenous factor, then these factors would be considered confounders and
could be statistically controlled (as in many studies, which tend to reject such
a "self-selection" hypothesis).
Assertions that such differences reflect
different endogenous risk profiles or genetic susceptibilities are
unsubstantiated in the peer-reviewed, published epidemiological literature.
34. As with the health effects of any exposure, differences in risk between very
small increments in exposure (e.g., 15 mg tar vs. 14 mg tar cigarettes) are
more difficult to demonstrate statistically than between larger exposure
differences (e.g., 22 mg vs. 8 mg); statistical inability to show differences in
risk between products with small gradients in tar levels does not preclude a
true difference in risk.
35. The magnitude of any benefit of switching from a higher to lower yield product
is by definition less than that of quitting, and therefore more difficult to
precisely measure. Furthermore, the benefits accruing from reductions in
exposure to tar as a result of product changes or switching to lower-yield

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 cigarettes are unlikely to be immediate, as with reductions in risk from
quitting, which reach maximal levels only after about 20 years following
quitting.
36. An example of the limited ability of a study to fully demonstrate the benefits of
lower tar cigarettes is the CPS II study - most recently re-analyzed by Harris
and Thun (2004). The CPS II study population included individuals who were
enrolled in 1982, classified based on their current smoking status and brand,
and followed for mortality through 1988. Such short follow-up is incapable of
exhibiting the actual longer-term benefits expected to become apparent after
10 or 20 or more years after switching to lower tar products.
37. Furthermore, a substantial proportion of smokers enrolled in CPS II in 1982
had initiated smoking with non-filter and higher tar yield cigarettes and may
have switched to reduced tar products by enrollment. Classification based on
current brand therefore did not properly characterize prior exposure as a
higher-yield cigarette smoker, and such misclassification would tend to
attenuate apparent benefits of reducing tar exposure.
38. Dr. Wecker also notes in his report from the Schwab case several additional
examples of misclassification of exposure in CPS II that would bias study
results. For example, many smokers of lower-yield products were likely
misclassified as "regular" smokers resulting from the lack of brand specificity
in the CPS questionnaire, i.e., whether the full flavor or "lights" version of the
brand were smoked. He further notes in his report that for many who initiated
smoking in the earlier part of the 20th century, but currently smoke a "light"
cigarette, the majority of those individual's smoking histories would have been
smoking full-flavor cigarettes.
39. For individuals switching from higher to lower yield cigarettes the benefit may
be attenuated by changes in individual smoking behavior. For example,
smokers switching to a lower-yield brand might increase the number of
cigarettes smoked per day (CPD). Furthermore, smokers may change the
puff volume, frequency, depth of inhalation, etc.
40. These suggested behavior changes among smokers who switched between
products with different yields often have been subsumed under the term
"compensation." "Compensation" is mostly used in the context of the
hypothesis that smokers try to maintain a specific level of nicotine regardless
of cigarette smoked. Under this hypothesis any change of the nicotine yield
would be counterbalanced by smoking more/less cigarettes and/or by
changing the way cigarettes are smoked. However, the epidemiological
evidence consistently demonstrates that smokers of reduced yield products
do not fully compensate and are exposed to lower levels of tar than smokers
of full-flavor cigarettes.

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 41. Furthermore, in epidemiological studies, differences in the way individuals
smoke (depth of inhalation, puff volume, etc.) are inherently taken into
account; however, assuming such compensation occurs, it will only reduce
the magnitude of the benefit observed. Over time, more smokers initiate with
rather than switch to lower-yield cigarettes, and therefore compensation
becomes irrelevant.
42. Changes in CPD can be measured and accounted for in the analysis of
epidemiological studies of individuals switching from higher to lower tar
cigarettes; however, control for CPD has been shown epidemiologically to
have little or no impact when comparing groups of smokers smoking
cigarettes with different yields. This was clearly demonstrated in the
reanalysis of the CPS II data by Harris and Thun (2004), which, along with
other studies effectively negate this hypothesis.
43. The effect of changing tar and nicotine yield on various biomarkers has been
investigated both experimentally in studies where smokers were switched to
cigarette brands with different yields compared to their usual brand (for
example Benowitz 2005), as well as observationally in cross-sectional studies
comparing groups of smokers of different self-selected brands (for example
Hecht 2005). In general, reductions in levels of biomarkers were observed.
44. The relationships among use of lower-yield cigarettes and biological
indicators of exposure and biological indicators of early disease and risk of
disease are not well understood.
Furthermore, biological markers of
exposure and disease are subject to large individual variability in uptake,
metabolism and elimination. Nevertheless, recent epidemiological study
findings demonstrate a strong nearly linear association between increasing
serum cotinine levels and lung cancer risk (Boffetta 2006).
45. Longer range studies and studies of voluntary switchers, however, suggest
little or no increase - and even a decrease - in the number of cigarettes
smoked per day, on average, after switching to lower yield products.
46. Additional information regarding the CPD issue comes from cross-sectional
studies. More than 20 published cross-sectional studies presented results for
groups of smokers using cigarettes with different tar and nicotine yields. In
general, these studies showed that smokers of lower yield cigarettes on
average did not smoke more CPD than smokers of higher yield cigarettes.
These studies only can provide indirect evidence for or against compensatory
smoking behavior because the study populations consist of both switchers
and non-switchers.
47. The results of the cross-sectional studies were supported by my recent
analysis of the National Survey of Drug Abuse and Health (NSDUH) data
indicating that low-yield cigarette smokers smoke fewer cigarettes per day on
average than comparable smokers of regular cigarettes.

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 THE EPIDEMIOLOGY OF LOWER-YIELD CIGARETTE USE AND DISEASE
48. The study of lung cancer risks associated with cigarette smoking has
advantages over other areas of epidemiology, such as occupational and
environmental studies, in which exposures are often impossible to estimate
with any degree of accuracy. Lung cancers and heart disease (especially
myocardial infarction) are generally well defined and diagnosed, cigarette
smoking is relatively easy to characterize at an individual level; neither the
exposure nor these outcomes are rare, enhancing the statistical power of
epidemiological studies.
49. Evidence in support of the relationship between cigarette smoking and risk of
lung cancer has been available in the scientific literature for sixty years, with
studies of male lung cancer cases and controls showing an association
between smoking and lung cancer in 1950 (Wynder and Graham, 1950).
Efforts were taken to identify features of smoking associated with risk of lung
cancer, such as the amount smoked, inhalation, use of cigarette holders, filter
tips, and type of tobacco product (Doll and Hill, 1950; 1952).
50. These early case-control studies were followed by large cohort studies
conducted in Great Britain and the US, with reports from Great Britain as
early as 1954 and as recent as 2000 (Doll and Hill, 1954; Doll, 1994; Peto,
2000).
51. The studies that examined filter versus non-filtered cigarettes represented a
straightforward first step in the evaluation of "dose-response" effects of
reduced tar exposure. Epidemiological studies of filtered cigarettes have
been conducted in the US and internationally for more than thirty years.
These studies examined risk associated with different tar yields, taking into
account gender, race, increasing number of cigarettes smoked per day,
increasing duration of smoking, age started smoking, and differences in risk
by various lung cancer histologic types.
52. Subsequent studies evaluated all forms of reduction in tar yield whether
through filtration technologies, increased ventilation, tobacco formulation,
some combination of these or other technologies. These studies have shown
that smoking filtered lower tar cigarettes reduces the risk of lung cancer
compared with smoking unfiltered higher tar cigarettes.
53. A small number of studies have specifically examined the risk associated with
different categories of tar yield, as measured by the FTC method. Overall,
risks among the lowest tar categories tend to be lowest, with risk increasing
with higher tar categories; however, most have not had adequate follow-up
time to determine the magnitude of the benefit of reduced tar exposures.
Even upon quitting smoking, several years of follow-up may be required to
observe the clear benefits of long-term quitting.

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 54. In 2004, the International Agency for Research on Cancer (IARC) published a
review of the epidemiological literature on cigarette tar yield and lung cancer
risk. The Monograph 83 noted that dose-response associations were seen
between increased tar levels and increased lung cancer risks. Lower risks
were associated with lower estimated tar exposures.
55. Several other diseases associated with tobacco smoking, including cancers of
sites other than the lung, non-malignant respiratory diseases, and
cardiovascular diseases (CVD) have been evaluated epidemiological^ for
possible reduction of risk with reduced yield cigarettes. A few well-conducted
studies provide additional support specifically for reduced risks for oral,
pharyngeal and oesophageal cancers, cardiovascular disease (CVD) and
chronic respiratory disease for smokers of lower yield products.
56. Evidence of decreased risk of CVD associated with lower yield cigarettes has
been reported. The largest and best-conducted study on this topic reports
clearly decreased risk of myocardial infarction (heart attacks) among users of
lower-yield (<6 mg tar) compared with high yield (>12 mg tar) cigarettes after
statistically controlling for numerous potential confounding variables (Sauer
2002).
57. Some studies have suggested reduced bladder cancer risks associated with
reduced tar exposure, but the results are less clear. Because of the long
latency period associated with chemically induced bladder cancers and the
weaker association between cigarette smoking and bladder cancers, these
studies may require larger study populations and longer follow-up to detect
clear reductions in risk associated with reduced tar exposure. A recent
review, however, noted that smokers of higher tar cigarettes had an increased
risk of bladder cancer (Pelucchi, 2006).
58. Studies of upper aerodigestive cancers, including esophageal cancer, have
also reported reduced risks associated with lower tar cigarettes (e.g., Gallus,
2003).
Lung Cancer Trends
59. The prevalence of cigarette smoking started to increase in the early 1900's,
with the peak per capita consumption of cigarettes in the US occurring around
1963. Lung cancer mortality peaked among males around 1989, some 26
years later (Wynder, 1994), consistent with the 20-40 year latency for lung
cancers.
60. Lung cancer incidence rates in the US have been decreasing among men
overall and for each of the four major histological types.
61. For women, lung cancer incidence rates have been decreasing overall, with
downward trends more apparent for large cell, squamous cell and small cell
cancers. Age-adjusted rates of lung adenocarcinomas among women overall

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 are no longer increasing, and there is recent evidence of decreasing rates
among women under 65 years of age.
62. Tobacco smoking has been associated with all major histological types of
lung cancer. Comparisons among lung cancer subtypes demonstrate the
strongest associations with tobacco for squamous and small cell cancers, and
the weakest associations with adenocarcinomas.
63. Since around 1990, lung cancer mortality rates in men in the US have
continued to drop, somewhat more rapidly than would be predicted from the
changes in total per capita consumption alone. In the UK lung cancer rates
have been declining more rapidly than would be expected from declines in
prevalence of smoking alone, which could be related to changes in cigarettes,
including reduction in tar levels (Peto, 2000).
64. Filtered cigarettes with high tar levels were common in the Australian market
between 1950 and the late 1960s. Birth cohort analyses in this population
have shown declines in age-adjusted lung cancer mortality among younger
vs. older women, despite general increases in smoking for the younger
women. It has been suggested that the reduction in lung cancer mortality
may be due to use of reduced tar products (Blizzard and Dwyer 2001).
Adenocarcinoma and Lower-tar Cigarettes
65. Among the four major lung cancer subgroups, adenocarcinomas consistently
have been shown to have the weakest association with smoking, and at one
time were considered not to be unrelated to smoking. There are many
subtypes of adenocarcinomas, and there is some evidence that part of the
weak overall relationship with smoking is due to some subtypes being related
to smoking and others not.
66. As with squamous cell carcinoma of the lung, the recent decline in
adenocarcinoma rates seen among women under age 65 are occurring
somewhat later than the decline in lung adenocarcinomas among men,
reflecting the longer latency for smoking-related adenocarcinomas than that
of other lung cancer types. A recent study of women found that the risk for
adenocarcinoma does not increase until at least 30-40 years of smoking,
while squamous or small cell carcinoma risk begins to increase after 20 years
(Kenfield, 2008).
67. A recent review of lung cancer in never smokers notes that adenocarcinoma
is the most common cell type in non-smokers, and that lung adenocarcinoma
cases are more likely to have a family history of lung cancers, pointing to
hereditary susceptibility or other factors than tobacco smoking (Subramanian,
2007).
68. Several additional risk factors for lung adenocarcinomas have been identified
including air pollution, viruses, and genetic susceptibilities. Several papers

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 have shown an association between motor vehicle density and increased lung
adenocarcinoma incidence. Squamous cell carcinomas were found to be less
strongly associated, if at all, with motor vehicle density (Chen, 2007; Chen,
2009; Liaw, 2008).
69. Adenocarcinomas of several sites (other than the lung) have been increasing,
including sites not generally considered smoking-related. For example,
adenocarcinoma of the esophagus, which does not appear to be smokingrelated, is one of the fastest increasing cancers among white men - the group
which has in parallel demonstrated the greatest reduction in smoking
prevalence over the last decades. The leading risk factor for these
adenocarcinomas, as with cervical adenocarcinomas, is viral infection
(possibly with human papilloma virus). The proportion of adenocarcinomas of
the lung with a viral etiology is unknown.
70. Some investigators have postulated that the increase in adenocarcinomas of
the lung might be related specifically to the use of lower yield cigarettes
("lower-tar hypothesis") (Stellman 1997a; 1997b; Wynder 1988; Morabia and
Wynder 1991). Chen et al (2007) examined temporal patterns of lung cancer
rates by histologic type and cigarette consumption and found that
adenocarcinoma rates started to rise in the 1950s, while lower-tar cigarette
consumption did not start to increase until the 1970s. Therefore, the increase
in adenocarcinoma rates occurred about 20 years prior to the increase in lowtar cigarette consumption.
71. Some observers erroneously draw a connection between the increasing
proportion of adenocarcinomas among all lung cancer types, despite the clear
decline in rates of lung cancers overall and for each specific subtype, and the
increasing proportion of smokers using reduced yield products. As smokingrelated lung cancers are prevented, lung cancers less-strongly or not
associated with cigarette smoking will represent a greater proportion of all
cancers.
72. In addition to a longer latency among smoking-related adenocarcinomas,
substantial changes occurred in the histological classification scheme
gradually introduced over the last 30-40 years, and the World Health
Organization redefined the criteria for diagnosing adenocarcinomas in 1982.
These changes resulted in tumors previously classified as other cell types
(predominantly unclassified tumors and large cell carcinomas) being
reclassified as adenocarcinomas (Wu, 1986). The results of one wellconducted study that used the new criteria to re-diagnose preserved tumor
samples originally diagnosed prior to the new criteria resulted in an increase
of 94% more adenocarcinomas than originally diagnosed (Campobasso,
1993).
73. Additionally, over the last several decades diagnostic techniques and
technology have improved dramatically, allowing for smaller and more

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 peripheral tumors to be imaged, visualized internally and biopsied (leading to
more accurate histological classification). Combined, these factors would
have contributed to increasingly accurate diagnosis of adenocarcinomas over
time, and increasing rates. Nevertheless, the declining rates seen over the
last several years indicate that the true rates of lung adenocarcinomas are
decreasing.
74. In summary, the available epidemiological evidence does not support the
hypothesis that lower tar cigarettes are responsible for increased incidence of
adenocarcinomas. Some increase in lung adenocarcinoma rates has been
linked to enhanced diagnostic technologies and revised tumor classification
methods; however, the most likely explanation for the increase of
adenocarcinomas (followed by more recent declines) is that smoking-related
lung adenocarcinomas appear to have a longer latency than other types of
smoking-related lung cancers. Claims that increasing lung adenocarcinoma
rates paralleled increasing use of filtered and lower-tar cigarettes ignores this
fundamental concept. Additional hypotheses such as increased exposure to
viral agents and high historic levels of air pollution are also plausible.

PUBLIC HEALTH COMMUNITY RESPONSES TO LOWER-YIELD EPIDEMIOLOGY
75. The scientific and medical communities have recognized for decades the
health risks of smoking, and have recommended that quitting smoking is the
best approach to reducing risk.
76. Despite the general understanding that smoking is hazardous, large numbers
of people choose not to quit, and many non-smokers will take up smoking.
For these groups, public health experts had for many years encouraged those
that continue to smoke to select lower yield versus higher-yield tobacco
products. This is based on the available accumulated scientific literature, and
on the basic toxicological principal that reducing intake of toxins will reduce
disease risk.
77. In 1971, the 2nd World Conference on Smoking and Health stated that
smokers unable or unwilling to quit smoking should use low tar and nicotine
cigarettes and that tapering off, with the intention of quitting may be
accomplished by either smoking fewer cigarettes, lower tar cigarettes, or
changing patterns of smoking.
78. The 1981 Surgeon Generals' report stated: "In summary, the final estimation
of the relative risk of smoking lower 'tar' and nicotine cigarettes must be
based on a synthesis of the information derived from several methodologies.
Despite the lack of comprehensive and conclusive evidence available, the
Public Health Service policy on lower 'tar' and nicotine cigarettes must remain
unchanged. The health risks of cigarette smoking can only be eliminated by

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 quitting. For those who continue to smoke, some risk reduction may result
from a switch to lower 'tar' and nicotine cigarettes, provided that no
compensatory changes in style of smoking occur."
79. In 1989, the American Cancer Society published informational booklets on
smoking that reiterated the fact that smoking cessation is the best way to
reduce cancer risk, however, individuals not able to quit are advised to switch
to brands with the lowest possible tar and nicotine content particularly
because those who smoke low tar/nicotine cigarettes find it easier to quit
altogether than high tar/nicotine smokers. In 1992, a similar publication
advised men who could not quit to reduce the number of cigarettes smoked,
or to switch to a lower yield product.
80. In 1996, an editorial in the British Medical Journal advocated for a "global
cigarette" of 12 mg tar and 1 mg nicotine by 2000, as a means to reduce lung
cancer risk, particularly in developing countries where higher yield cigarettes
are typically smoked (Gray, 1996). In 2001, the European Union issued a
directive indicating that by January 1, 2004, all cigarettes circulated, marketed
or manufactured in member states would have tar yields no greater than 10
mg and nicotine no greater than 1 mg.
81. Australia limited the tar content of cigarettes beginning as early as 1982 (in
negotiated agreements with the tobacco industry) with a cap of 18 mg tar per
cigarette, which was reduced further to 14 mg in 1988 before subsequently
being regulated in 1995 at 16 mg. Blizzard and Dwyer (2001) have shown
that lung cancer rates among Australian women have declined, which they
attribute to reduced-tar cigarettes, despite an increase in prevalence and
average duration of smoking.
82. Scientists and public health officials supported efforts to produce less
hazardous cigarettes through reduction in tar content and improved filters, in
addition to further reductions in lung cancer risk through education, smoking
cessation and reduced initiation. The Institute of Medicine (IOM, 2001)
described possible strategies for tobacco harm reduction that include
manufacturing changes that continue to reduce toxicants in cigarette smoke.
83. In an apparent reversal of the established position recommending reduction
of tar exposure through selecting lower-yield cigarettes, the National Cancer
Institute (Monograph 13, conclusion 3 of Chapter 4) states: "Existing disease
risk data do not support making a recommendation that smokers switch
cigarette brands. The recommendation that individuals who cannot stop
smoking should switch to low yield cigarettes can cause harm if it misleads
smokers to postpone serious efforts at cessation."
84. While it is true that smoking lower yield cigarettes does not eliminate smoking
risks, NCI's conclusion contradicts a substantial body of epidemiological
evidence demonstrating benefits of reducing tar exposure.

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 MONOGRAPH 13. CHAPTER 4
85. Chapter 4 of Monograph 13 states as its purpose: "This chapter is focused
on answering the question: 'Have changes in cigarette manufacture and
design over the last 50 years resulted in a meaningful public health benefit to
human smokers?' This overall question has two related but distinct research
questions. First, has the risk per cigarette smoked been changed by these
product modifications; and second have the net adverse consequences of
smoking for the population been changed by these product modifications."
[sic] The authors claim that "From the public health perspective, the latter is
the more relevant question."
86. Chapter 4 presents brief reviews of the epidemiological literature on
reduced-tar cigarettes and risk of lung cancer, cardiovascular disease, and
chronic respiratory symptoms and disease. It concludes, "Studies published
in the epidemiological literature support a difference in lung cancer and
possibly heart disease risks, between populations of individuals who smoke
filtered or lower yield cigarettes compared with individuals who smoke
unfiltered or higher yield cigarettes."
87. However, the authors further and contradictorily conclude that "Given the
variability of these results, the potential for confounding and in the analysis
[sic], and the difficulty of examining the continually changing cigarette
product, it is difficult to conclude from these data that there is a clearly
demonstrable harm reduction that is due to the use of filtered or lower yield
cigarettes in comparison to unfiltered or higher yield cigarettes."
88. Chapter 4 is critical of the epidemiology studies as not accounting for
switchers likely increasing the number of cigarettes smoked per day with
lower yield cigarettes. An evaluation of the epidemiological studies included
in Chapter 4 (and several apparently overlooked) indicates that some papers
either directly addressed the "cigarettes per day bias" by controlling for
cigarettes per day at baseline (prior to switching) or demonstrated no
difference when comparing adjusted with unadjusted results. Other studies
demonstrated that not all smokers increased the number of cigarettes
smoked. For those who did increase the number, some benefit of reduced
tar remained (Lubin, 1984b; Augustine, 1989). Several of the Chapter 4
reviewers criticized the extent to which the "cigarettes per day" bias was
used to dismiss the findings of previously conducted epidemiological studies.
89. Based on materials produced by the University of California at San Diego as
part of discovery in another tobacco litigation case, Dr. William Wecker has
attempted to replicate and evaluate several new analyses presented in
Chapter 4 that do not appear in the peer-reviewed published literature. In
the process, Dr. Wecker identified a number of errors and inconsistencies.
Dr. Wecker's re-analyses, however, were consistent with the balance of the
published science demonstrating some benefit of lower yield cigarettes.

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 90. The conclusions of Chapter 4 are not compatible with the weight of evidence
based on the published epidemiological literature. For example, conclusion
2 states: "Cigarettes with low machine-measured yields by the FTC method
are designed to allow compensatory smoking behaviors that enable a
smoker to derive a wide range of tar and nicotine yields from the same
brand, offsetting much of the theoretical benefit of a reduced-yield cigarette."
The literature, however, indicates that compensation is incomplete. Further,
most smokers switching brands do not increase the number of cigarettes
smoked per day and smokers of low-yield products tend to smoke fewer
cigarettes per day than smokers of regular cigarettes, resulting in overall
reductions in exposure.
91. Another example is conclusion 4, which states: "Widespread adoption of
lower yield cigarettes by smokers in the United States has not prevented the
sustained increase in lung cancer among older smokers." This has not been
substantiated. Low yield products may have attenuated the steep rise in
lung cancer rates seen in other countries prior to the widespread use of
reduced tar products. Further, older smokers included in the early studies
(including CPS I and II) would have had substantial smoking histories prior
to lower yield products being introduced to the market, leading to sustained
increased risks. On the other hand, and as suggested by Peto, the rates
among younger ages might be declining faster because of reduced tar
cigarettes.
92. Another example is conclusion 5, which states: "Epidemiological studies
have not consistently found lesser risk of diseases, other than lung cancer,
among smokers of reduced yield cigarettes. Some studies have found
lesser risks of lung cancer among smokers of reduced yield cigarettes.
Some or all of this reduction in lung cancer risk may reflect differing
characteristics of smokers of reduced-yield compared to higher-yield
cigarettes." While again acknowledging that the literature demonstrates a
benefit of reduced yield - at least for lung cancers - the authors then
attempt to attribute the benefit to "differing characteristics" of different
products. This is not substantiated. To the contrary, the published literature
consistently documents a benefit of lower yield cigarettes with respect to
lung cancers even when taking into account a broad range of these "differing
characteristics." Sound epidemiological studies have also demonstrated
substantial reductions in risk of other smoking-related cancers (such as
laryngeal and bladder cancers) and myocardial infarction.
93. Conclusion 6 states: "There is no convincing evidence that changes in
cigarette design between 1950 and the mid 1980s have resulted in an
important decrease in the disease burden caused by cigarette use either for
smokers as a group or for the whole population." The efforts to discredit this
body of evidence, including the suggestion of various biases and the "new"
analyses presented in Chapter 4, have not been adequately tested or
scientifically substantiated. Despite these efforts, substantial and convincing

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 epidemiological evidence exists, some of which is presented in Chapter 4,
demonstrating important reductions in risk associated with reduced cigarette
yields.
94. Overall, Chapter 4 contributes no new valid scientific perspectives on the
epidemiology of lower-yield cigarettes. Many of my observations and
criticisms are similar to those raised by some of the original reviewers of
Monograph 13.

CONCLUSIONS
95. Critical review and synthesis of the epidemiological evidence available to
date indicate that changes in cigarettes over the past 50 years have resulted
in reduced tar exposures, and that this has resulted in lower - but by no
means eliminated - risks of some smoking-related diseases. Observed
dose-response relationships between tar exposure and disease risks are
compatible with the basic toxicological, epidemiological and public health
principle that reduction in exposure to known human hazards reduces
disease risk.
96. Efforts by Plaintiffs' experts to discredit the available epidemiological
evidence relevant to the health risks associated with lower-tar cigarettes including those expressed in Monograph 13 and their expert reports and
publications - fail to address the totality of relevant evidence and largely
remain unsubstantiated.
97. While the benefits of large reductions in tar exposure, as may be achieved
through filtration, are more clearly demonstrated, it is reasonable to expect
that smaller reductions in exposure to hazardous substances in tobacco
smoke will be accompanied by additional, but small reductions in disease
risks. Although small reductions in exposure to hazardous substances may
be accompanied by small reductions in risk, from a public health
perspective, such reductions over large numbers of individuals can lead to
important population-level public health benefits. This is also the rationale
behind regulatory efforts to reduce exposure to air pollutants, workplace
chemical hazards, and consumer product contaminants - all of which are
presumed to reduce human disease risks that are usually unmeasured or
unmeasureable.
98. The weight of the scientific evidence, based on my critical review of the
published, peer-reviewed epidemiological literature and taking into
consideration of Plaintiffs' experts' claims of bias and alternative hypotheses,
indicates that there are health benefits, not limited to reduced lung cancer
risks, of reduced-tar cigarettes, including Lights.

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 99. I understand that I may be asked to review and comment on additional
information that becomes available, including testimony and opinions of
plaintiffs' expert witnesses and documents used to support those opinions,
to the extent the information relates to my opinions and expertise. I am also
told that I may be asked to offer opinions in response to the opinions of
plaintiffs' rebuttal experts in this case, if allowed, including in the form of a
surrebuttal report.

^^6$^^-^—
Kenneth A. Mundt, Ph.D.

si/zc I 10
26 February 2010

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