United States Office of Chemical Safety and
Environmental Protection Agency Pollution Prevention
Final Risk Evaluation for
Asbestos
Part 1: Chrysotile Asbestos
Systematic Review Supplemental File:
Data Quality Evaluation of Human Health Hazard Studies:
Mesothelioma and Lung Cancer Studies
December 2020
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Table of Contents
1. Asbestos-specific evaluation criteria for epidemiologic studies 3
1.1. Rationale for asbestos-specific evaluation criteria 3
1.2. Evaluation Criteria for Epidemiological Studies: Asbestos Exposure and Lung Cancer
Health Outcome 6
1.3. Evaluation Criteria for Epidemiological Studies: Asbestos Exposure and Mesothelioma
Health Outcome 16
2. Data Evaluation of Lung Cancer Studies 28
2.1. Table of studies evaluated for asbestos exposure and lung cancer incidence 28
2.2. Data Evaluation Scoring Sheets: Lung Cancer Outcome 30
2.2.1. Epidemiology evaluation results of the South Carolina, US cohort studies on asbestos exposure and
lung cancer incidence 30
2.2.2. Epidemiology evaluation results of the Chongqing, China mining cohort studies on asbestos
exposure and lung cancer incidence 36
2.2.3. Epidemiology evaluation results of the Balangero, Italy cohort of studies on asbestos exposure and
lung cancer incidence 41
2.2.4. Epidemiology evaluation results of the North Carolina, US cohort studies on asbestos exposure and
lung cancer incidence 46
2.2.5. Epidemiology evaluation results of the Salonit Anhovo, Slovenia cohort studies on asbestos
exposure and lung cancer incidence 51
2.2.6. Epidemiology evaluation results of the Quebec, Canada cohort studies on asbestos exposure and
lung cancer incidence 55
2.2.7. Epidemiology evaluation results of the Chongqing, China textile worker cohort studies on asbestos
exposure and lung cancer incidence 60
3. Data Quality Evaluation of Mesothelioma Data Sources 65
3.1. Data Evaluation Scoring Sheets: Mesothelioma Outcome 65
3.1.1. Epidemiology evaluation results of the Quebec, Canada cohort studies on asbestos exposure and
mesothelioma incidence 65
3.1.2. Epidemiology evaluation results of the South Carolina, US cohort studies on asbestos exposure and
mesothelioma incidence 69
3.1.3. Epidemiology evaluation results of the North Carolina, US cohort studies on asbestos exposure and
mesothelioma incidence 73
References 77
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1. Asbestos-specific evaluation criteria for epidemiologic studies
1.1. Rationale for asbestos-specific evaluation criteria
For the first 10 Toxic Substances Control Act (TSCA) chemicals, a general set of study
evaluation criteria was developed. These evaluation criteria were not tailored to any specific
exposure or outcome. In the Problem Formulation step of the asbestos assessment, it was
accepted that asbestos was a known cause of lung cancer and mesothelioma, and that the purpose
of the systematic review would be the identification of studies which could inform the estimation
of an exposure-response function allowing for the derivation of an asbestos inhalation unit risk
for these two cancer sites combined. While there is also evidence that asbestos exposure is
associated with an increased risk of laryngeal and ovarian cancer, there is inadequate data for
exposure-response analyses. For the reasons described below, the study domains of exposure,
outcome, study participation, potential confounding, and analysis were further tailored to the
specific needs of evaluating asbestos studies for their potential to provide information on the
exposure-response relationship between asbestos exposure and mortality from lung cancer and
from mesothelioma (see sections L2 and 1.3).
In terms of evaluating exposure information, asbestos is unique among these first 10 TSCA
chemicals as it is a fiber and has a long history of different exposure assessment methodologies.
For mesothelioma, this assessment is also unique with respect to the impact of the timing of
exposure relative to the cancer outcome as the time since first exposure plays a dominant role in
modeling risk. The most relevant exposures for understanding mesothelioma risk were those that
occurred decades prior to the onset of cancer, and subsequent cancer mortality. Asbestos
measurement methodologies have changed over those decades; from early measurement of total
dust particles measured in units of million particles per cubic foot of air (mppcf) (by samplers
called midget impingers), to fibers per milliliter (f/ml), or the equivalent fibers per cubic
centimeter (f/cc) (where fiber samples were collected on membrane filters and the f/ml or f/cc
was measured using phase contrast microscopy (PCM) analysis of the filters). In several studies
encompassing several decades of asbestos exposure, matched samples from midget impingers
and membrane filters were compared to derive job- (or location-) specific factors allowing for
the conversion of earlier midget impinge measurements to estimate PCM measurement of
asbestos air concentrations. While some studies were able to provide these factors for specific
locations and jobs, other studies were only able to derive one factor for all jobs and locations.
The use of such data has allowed asbestos researchers to investigate the risk of asbestos and
successfully model lung cancer and mesothelioma mortality over several decades of evaluation
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(U.S. EPA. 2014. 1988. 783514). Thus, the general exposure evaluation criteria were adjusted to
be specific to exposure assessment methodologies such as midget impingers and PCM with
attention to the use of job-exposure-matrices (JEMs) to reconstruct workers' exposure histories
and the reporting of key metrics needed to derive exposure-response functions for lung cancer
and mesothelioma.
In terms of evaluating the quality of outcome information, lung cancer is relatively
straightforward to evaluate as an outcome. Specific International Classification of Disease (ICD)
codes for lung cancer have existed for the entire time period of the studies making it possible to
identify cases from mortality databases. On the other hand, there was no diagnostic code for
mesothelioma in the ICD prior to the introduction of the 10th revision (ICD-10) which was not
implemented in United States until 1999. Before ICD-10, individual researchers had to go
beyond ICD codes and generally search original death certificates for mention of mesothelioma.
Thus, the general outcome evaluation criteria were adjusted to be specific to mesothelioma and
outcome ascertainment strategies.
Mesothelioma is a very rare cancer. As noted by U.S. EPA (2014. 3827272). the "Centers for
Disease Control and Prevention estimated the death rate from mesothelioma, using 1999 to 2005
data, as approximately 23.2 per million per year in males and 5.1 per million per year in females
(CDC. 2009. 783733 )." While extremely rare, the overwhelmingly dominant cause of
mesothelioma is asbestos exposure (Tossavainen. 1997. 3081272) making the observance of
mesothelioma in a population a sentinel for asbestos exposure. It is critical to understand that the
prevailing risk model for mesothelioma models is an absolute risk model of mesothelioma
mortality which assumes there is no risk at zero exposure (U.S. EPA. 1988. 783514; Peto et al..
1982. 165; Peto. 1978. 2238688). This use of an absolute risk model is in stark contrast to the
standard use of a relative risk model for lung and other cancers. For the relative risk model, the
risk of lung cancer in an asbestos exposed population would multiply the background risk in an
unexposed population, and consideration of study quality would be the evaluation of the
comparison population. There is, however, no background risk in developing mesothelioma in an
unexposed population. As a result, no comparison population was needed to estimate the
absolute risk among people exposed to asbestos, and therefore, criteria including comparison
population were adjusted for mesothelioma.
In terms of evaluating potential confounding variables, the potential confounding section
recognized that there are both direct and indirect methods for controlling for some confounders -
specifically that methodologies involving internal comparisons in a working population may
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indirectly control for smoking and other factors assuming these factors do not vary with asbestos
exposure concentrations in the workplace. In contrast to lung cancer, mesothelioma is much
simpler to evaluate for potential confounding as chest radiation is the only other known risk
factor that could lead to mesothelioma, and this rare exposure is unlikely to be a confounder.
In terms of analysis, the evaluation criteria needed to be adapted for both mesothelioma and lung
cancer. For mesothelioma, the Peto model (Peto et al.. 1982. 165; Peto. 1978. 2238688) was
traditionally used for summary data published in the literature (U.S. EPA. 1988. 783514). so
only modeling using the Peto model by the authors, or the presentation of sufficient information
to fit the Peto model post hoc were considered acceptable. For lung cancer, a wider selection of
statistical models was acceptable, with the preference generally given to modeling that used
individual data in the analysis. Grouped data modeling would also reported but would be carried
forward to the summary only if no individual data modeling were available.
Lastly for Asbestos, studies from the same cohort were evaluated collectively to assess the
overall quality of the data collected from the cohort across all years of follow-up. This was done
to consider all information from a cohort that was presented across multiple studies as a whole.
For example, the most recent article for a cohort may not have presented the details necessary to
fully evaluate the number one domain criterion (Study Participation), whereas the first or
subsequent studies out of the cohort may have filled in data gaps.
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1.2. Evaluation Criteria for Epidemiological Studies: Asbestos
Exposure and Lung Cancer Health Outcome
Confidence Level
(Score)
Description
Selected
Score
Domain 1. Study Participation
Metric 1. Participant selection (selection, performance biases)
Instructions: To meet criteria for confidence ratings for metrics where 'AND' is included, studies must
address both conditions where 'AND' is stipulated. To meet criteria for confidence ratings for metrics
where 'OR' is included studies must address at least one of the conditions stipulated. In Metrics 3 and 4,
criteria that must be met concurrently are enclosed in parentheses and linked with an indented 'AND.'
High
(score = 1)
• For all studv tvves: All kev elements of the studv desisn are rcDortcd (e.s..
setting, participation rate described at all steps of the study, inclusion and
exclusion criteria, and methods of participant selection or case
ascertainment)
AND
The reported information indicates that selection in or out of the study (or
analysis sample) and participation was not likely to be biased (i.e., the
exposure-outcome distribution of the participants is likely representative of
the exposure-outcome distributions in the population of persons eligible for
inclusion in the study).
Medium
(score = 2)
For all studv tvves: Some kev elements of the studv desisn were not
present but available information indicates a low risk of selection bias (i.e.,
the exposure-outcome distribution of the participants is likely
representative of the exposure-outcome distributions in the population of
persons eligible for inclusion in the study).
Low
(score = 3)
• For all studv tvves: Kev elements of the studv desisn and information on
the population (e.g., setting, participation rate described at most steps of the
study, inclusion and exclusion criteria, and methods of participant selection
or case ascertainment) are not reported [STROBE checklist 4, 5 and 6 (Von
Elm et al.. 2008. 4263036)1.
Unacceptable (score
= 4)
For all studv tvves: The reported information indicates that selection in or
out of the study (or analysis sample) and participation was likely to be
significantly biased (i.e., the exposure-outcome distribution of the
participants is likely not representative of the exposure-outcome
distributions of the population of persons eligible for inclusion in the
study).
Not rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important
elements such as relevance]
Metric 2. Attrition (missing data/attrition/exclusion, reporting biases)
High
(score = 1)
• For cohort studies: There was minimal subiect loss to follow lid durins the
study (or exclusion from the analysis sample) and outcome and exposure
data were largely complete
OR
• Loss of subjects (e.g., incomplete outcome data) or missing exposure and
outcome data was adequately* addressed (as described below) and reasons
were documented when human subjects were removed from a studv (NTP.
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Confidence I.cm'I
(Scoiv)
Description
2015. 28234111.
AND
• Missing data have been imputed using appropriate methods (e.g., multiple
imputation methods), and characteristics of subjects lost to follow up or
with unavailable records are not significantly different from those of the
study participants (NTP. 2015. 28234111.
• For case-control studies and cross-sectional studies: There was minimal
subject withdrawal from the study (or exclusion from the analysis sample)
and outcome data and exposure were largely complete.
OR
• Any exclusion of subjects from analyses was adequately* addressed (as
described below), and reasons were documented when subjects were
removed from the study or excluded from analyses (NTP. 2015. 2823411).
*NOTE for all study types: Adequate handling of subject attrition can include:
Use of imputation methods for missing outcome and exposure data; reasons
for missing subjects unlikely to be related to outcome (for survival data,
censoring was unlikely to introduce bias); missing outcome data balanced in
numbers across study groups, with similar reasons for missing data across
groups.
Medium
(score = 2)
• For cohort studies: There was moderate subject loss to follow up during
the study (or exclusion from the analysis sample) or outcome and exposure
data were nearly complete.
AND
• Any loss or exclusion of subjects was adequately addressed (as described in
the acceptable handling of subject attrition in the high confidence category)
and reasons were documented when human subjects were removed from a
study.
• For case-control studies and cross-sectional studies: There was moderate
subject withdrawal from the study (or exclusion from the analysis sample),
but outcome and exposure data were largely complete
AND
• Any exclusion of subjects from analyses was adequately addressed (as
described above), and reasons were documented when subjects were
removed from the study or excluded from analyses (NTP. 2015. 2823411).
Low
(score = 3)
For cohort studies: The loss of subjects (e.g., loss to follow up, incomplete
outcome or exposure data) was moderate and unacceptably handled (as
described below in the unacceptable confidence category) (Source: OHAT).
OR
• Numbers of individuals were not reported at important stages of study (e.g.,
numbers of eligible participants included in the study or analysis sample,
completing follow-up, and analyzed). Reasons were not provided for non-
participation at each stage [STROBE Checklist Item 13 (Von Elm et al..
2008. 4263036)1.
• For case-control and cross-sectional studies: The exclusion of subjects
from analyses was moderate and unacceptably handled (as described below
in the unacceptable confidence category).
OR
• Numbers of individuals were not reported at important stages of study (e.g.,
numbers of eligible participants included in the study or analysis sample,
completing follow-up, and analyzed). Reasons were not provided for non-
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Confidence Level
(Score)
Description
Selected
Score
Darticioation at each stase 1 STROBE Checklist Item 13 (Von Elm et al..
2008. 4263036)1.
Unacceptable (score
= 4)
• For cohort studies: There was larse subiect attrition durins the studv (or
exclusion from the analysis sample).
OR
• Unacceptable handling of subject attrition: reason for missing outcome data
likely to be related to true outcome, with either imbalance in numbers or
reasons for missing data across study groups; or potentially inappropriate
application of imputation (Source: OH AT).
• For case-control and cross-sectional studies: There was larse subiect
withdrawal from the studv (or exclusion from the analysis sample).
OR
• Unacceptable handling of subject attrition: reason for missing outcome data
likely to be related to true outcome, with either imbalance in numbers or
reasons for missing data across study groups; or potentially inappropriate
application of imputation.
Not rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important
elements such as relevance]
Metric 3. Comparison Group (selection, performance biases)
High
(score = 1)
• For ALL studv tvves: Anv differences in baseline characteristics of sroiros
were considered as potential confounding or stratification variables and
were thereby controlled bv statistical analysis (Source: OHAT).
OR
• For cohort and cross-sectional studies: Kev elements of the studv desisn
are reported (i.e., setting, inclusion and exclusion criteria, and methods of
participant selection), and indicate that groups were similar (e.g., recruited
from the same eligible population with the same method of ascertainment
and within the same time frame using the same inclusion and exclusion
criteria, and were of similar ase and health status) (NTP. 2015. 2823411).
• For case-control studies: Kev elements of the studv desisn are rcDortcd
indicate that that cases and controls were similar (e.g., recruited from the
same eligible population with the number of controls described, and
elisibilitv criteria and are recruited within the same time frame (NTP. 2015.
2823411).
• For studies revortins Standardized Mortalitv Ratios (SMRs) or
Standardized Incidence Ratios (SLRs): Ase. sex (if aDDlicablc). and race
(if applicable) adjustment or stratification is described and choice of
reference population (e.g., general population) is reported.
Medium
(score = 2)
• For cohort studies and cross-sectional studies: There is onlv indirect
evidence (e.g., stated by the authors without providing a description of
methods) that groups are similar (as described above for the high
confidence rating).
• For case-control studies: There is indirect evidence (i.e.. stated bv the
authors without providing a description of methods) that cases and controls
are similar (as described above for the high confidence rating).
• For studies revortins SMRs or SLRs: Ase. sex (if aDDlicablc). and race (if
applicable) adjustment or stratification is not specifically described in the
text, but results tables are stratified bv ase and/or sex (i.e., indirect
Page 8 of 80
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( onl'idcncc l.c\cl
(Score)
Description
Selected
Scoiv
evidence); choice of reference population (e.g., general population) is
reported.
Low
(score = 3)
• For cohort and cross-sectional studies: There is indirect evidence (i.e..
stated by the authors without providing a description of methods) that
groups were not similar (as described above for the high confidence rating).
AND
• Differences between the exposure groups are not adequately controlled for
in the statistical analysis.
• For case-control studies. There is indirect evidence (i.e.. stated bv the
authors without providing a description of methods) that cases and
controls were not similar (as described above for the high confidence
rating).
AND
• The characteristics of cases and controls are not rcDortcd (Source: (NTP.
2015.2823411).
AND
• Differences in groups is not adequately controlled for in the statistical
analysis.
• For studies revortins SMRs or SIRs: Indirect evidence of a lack of
adjustment or stratification for age or sex (if applicable); indirect evidence
that choice of reference population (e.g., general population) is
inappropriate.
Unacceptable*
(score = 4)
• For cohort studies: Subiects in all exoosure aroiios were not similar
OR
• (Information was not reported to determine if participant groups were
similar 1 STROBE Checklist 6 (Von Elm et al.. 2008. 4263036)
AND
• Potential differences in exposure groups were for a factor that was related to
the outcome and not controlled for in the statistical analysis.)
OR
• (Subjects in the exposure groups had very different participation/response
rates (NTP. 2015.2823411).
AND
• Participation rates were related to exposure and outcome)
• For case-control studies: (Controls were drawn from a verv dissimilar
DODiilation than cases or recruited within verv different time frames (NTP.
2015.2823411).
AND
• Potential differences in the case and control groups were not controlled for
in the statistical analysis.)
OR
• Rationale and/or methods for case and control selection, matching criteria
including number of controls per case (if relevant) were not reported
[STROBE Checklist 6 (Von Elm et al.. 2008. 4263036)1.
• For cross-sectional studies: (Subiects in all exoosure aroiios were not
similar, recruited within very different time frames, or had very different
DarticiDation/rcsDonsc rates (NTP. 2015. 2823411).
AND
• Potential differences in exposure groups were not controlled for in the
statistical analysis.)
OR
• Sources and methods of selection of participants in all exposure groups
Page 9 of 80
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Confidence Level
(Score)
Description
Selected
Score
were not rcDortcd 1 STROBE Checklist 6 (Von Elm et al.. 2008. 4263036)1.
• For studies reporting SMRs or SIRs: Lack of adjustment or stratification
for both age and sex (if applicable), race (if applicable), and calendar time
or choice of reference population (e.g., general population) is not reported.
Not rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Domain 2. Exposure Characterization
Metric 4. Measurement of Exposure (Detection/measurement/information, performance biases)
High
(score = 1)
• For all studv tvves: Quantitative estimates of exposure were consistentlv
assessed (i.e., using the same method and sampling time-frame) during
multiple time periods and using either PCM or TEM.
OR
• A combination of methods were used over time (i.e., midget
impinger, PCM or TEM), but side by side sampling and analyses
were conducted to develop appropriate conversion criteria.
AND
• For an occupational population, contains detailed employment records and
quantitative estimates of exposure using either PCM or TEM which allows
for construction of job-matrix for entire work history of exposure (i.e..
Cumulative or peak exposures, and time since first exposure).
Medium*
(score = 2)
• For all studv tvves: (Exposure was assessed durine one time oeriod but this
time period is judged to be reasonably representative of the entire study
time period.
AND
• Exposure was assessed using a combination of midget impingers, PCM,
and/or TEM measurements, but side by side sampling and analyses were
not conducted for all operations and thus there is a lack of confidence in the
conversion factors.)
OR
• For an occupational study population, contains detailed employment records
and quantitative estimates of exposure using a combination of midget
impingers and PCM or TEM measurements for only a portion of
participant's work history of exposure (i.e., only early years or later years),
such that extrapolation of the missing years is required
Low
(score = 3)
• For all studv tvves: Exposure was estimated solelv usins professional
judgement.
OR
• Exposure was directly measured and assessed using a quantitative method
other than PCM or TEM and conversion factors were not determined.
Unacceptable (score
= 4)
• For all studv tvves: There was no Quantitative measure or estimate of
exposure.
OR
• Methods used to quantify the exposure were not well defined, and sources
of data and detailed methods of exposure assessment were not reported
rSTROBE Checklist 7 and 8 (Von Elm et al.. 2008. 4263036)1.
OR
There is evidence of substantial exposure misclassification that would
significantly bias the results.
Not rated/applicable
• Do not select for this metric.
Reviewer's
[Document concerns, uncertainties, limitations, and deficiencies and anv
Page 10 of 80
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Confidence Level
(Score)
Description
Selected
Score
comments
additional comments that may highlight study strengths or important elements
such as relevance]
Metric 5. Exposure levels (Detection/measurement/information biases)
High
(score = 1)
• Do not select for this metric.
Medium
(score = 2)
• For all study tvves: The ranse and distribution of exposure is sufficient or
adeauate to develop an cxDosurc-rcsDonsc estimate (Coooer et al.. 2016.
3121908).
AND
• Reports 3 or more levels of exposure (referent group + 2 or more) or an
exposure-response model using a continuous measure of exposure.
Low
(score = 3)
For all study tvves: The ranse of exposure in the population is limited.
OR
• Reports 2 levels of exposure (e.g., exposed/unexposed)) (Cooper) (Source:
IRIS).
Unacceptable (score
= 4)
• For all study tvves: The ranse and distribution of exposure are not adeauate
to determine an exposure-response relationship (Cooper et al.. 2016.
3121908).
OR
• No description is provided on the levels or range of exposure.
Not rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Metric 6. Temporality
High
(score = 1)
• For all study tvves: The studv presents an appropriate temporality between
exposure and outcome (i.e. the exposure precedes the disease).
AND
• The interval between the exposure (or reconstructed exposure) and the
outcome is sufficiently long considering the latency of the disease (i.e.
studv follow-up is more than 15 years for luns cancer) (Lakind et al.. 2014.
2713602).
Medium
(score = 2)
• For all studv tvves: Temporality is established, but it is unclear whether
there is adequate follow-up for consideration of latency (i.e., only 10 years
of follow-up) (Lakind et al.. 2014. 2713602).
Low
(score = 3)
• For all studv tvves: The temporality of exposure and outcome is uncertain
(5-10 years).
OR
• There is inadequate follow-up of the cohort considerins the latency period.
Unacceptable
(score = 4)
• For all studv tvves: Studv lacks an established time order, such that
exposure is not likely to have occurred prior to outcome (Lakind et al..
2014. 2713602).
OR
• There was inadequate follow-up of the cohort for the expected latency
period (<5 years).
OR
• Sources of data and details of methods of assessment were not sufficiently
reported (e.g. duration of follow-up, periods of exposure, dates of outcome
ascertainment, etc.) Source: STROBE Checklist 8 (Von Elm et al.. 2008.
4263036)).
Not rated/applicable
• Do not select for this metric.
Page 11 of 80
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Confidence Level
(Score)
Description
Selected
Score
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Domain 3. Outcome Assessment
Metric 7. Outcome measurement or characterization (detection/measurement/information, performance,
reporting biases)
High
(score = 1)
• For all studv tvves: The outcome was assessed usins one or a
combination of the following well-established methods:
o Lung cancer cases confirmed by histological or cytological means
(including subtypes of lung cancer)
o ICD-10 C34 (lung and bronchus with or without C33 (trachea)
o ICD-9 (5-digit code) 162.2-162.9 or
o ICD-8 (4-digit code) 162.1 or
o ICD-7 (4-digit code) 162.1 and 163
o ICD-9 (3-digit code) 162
o ICD-8 (3-digit code) 162
o ICD-7 (3-digit code) 162 and 163
Medium
(score = 2)
• For all studv tvves: Althoush authors state thev identified luns cancer
cases they did not report the ICD codes.
Low
(score = 3)
• Do not select for this metric.
Unacceptable
(score = 4)
• For all studv tvves: Anv sclf-rcDortcd information.
OR
• Study lacks individual assessment of lung cancer (i.e., lung cancer is
assessed as a combination of cancer types, excluding lung and bronchus or
trachea).
Not
rated/applicable
• Do not select for this metric
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Metric 8. Reporting Bias
High
(score = 1)
• For all studv tvves: Luns cancer findinss are reported in the
abstract, results or discussion. Effect estimates are reported with
confidence intervals and/or standard errors, number of
cases/controls or exposed/unexposed reported for each analysis, to
be included in exposure-response analysis or fully tabulated during
data extraction and analyses (NTP. 2015. 2823411).
Medium
(score = 2)
• For all study types: All of the study's findings (primary and secondary)
outlined in the abstract, results or discussion (that are relevant for the
evaluation) are reported but not in a way that would allow for detailed
extraction (e.g., results were discussed in the text but accompanying data
were not shown).
Low
(score = 3)
• For all studv tvves: Luns cancer outcomes outlined in the methods,
abstract, and/or introduction (that are relevant for the evaluation) have not
been reported. (NTP. 2015. 2823411).
Unacceptable
(score = 4)
• Do not select for this metric.
Not
rated/applicable
• Do not select for this metric.
Page 12 of 80
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Confidence Level
(Score)
Description
Selected
Score
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Domain 4. Potential Confounding/Variable Control
Metric 9. Covariate Adjustment (confounding)
High
(score = 1)
• For all studv tvves: ADDrooriatc adjustments or explicit considerations
were made for potential confounders (e.g. age, sex, SES, race, etc.)
(excluding co-exposures, which are evaluated in metric 11) in the final
analyses through the use of statistical models to reduce research-specific
bias, including matching, adjustment in multivariate models, stratification,
or other methods that were arorouriatelv justified (NTP. 2015. 2823411).
• For Studies reporting SMRs or SIRs: Adjustments are described and
results are age-, race-, and sex-adjusted (or stratified) if applicable.
Medium
(score = 2)
• For all studv tvves: There is indirect evidence that aDDroDriatc adjustments
were made (i.e., considerations were made for primary covariates
(excluding co-exposures) and potential confounders adjustment) without
providing a description of methods.
OR
• The distribution of potential confounders (excluding co-exposures) did not
differ significantly between exposure groups or between cases and controls.
OR
• The major potential confounders (excluding co-exposures) were
appropriately adjusted (e.g., SMRs, SIRs, etc.) and any not adjusted for are
considered not to appreciably bias the results (e.g., smoking rates in an
occupational cohort are expected to be generally similar in different
departments and thus confounding by smoking is unlikely when internal
analyses are applied).
• For Studies reporting SMRs or SIRs: Indirect evidence that results are ase.
sex-, and race-adjusted (or stratified) if applicable.
Low
(score = 3)
• For all studv tvves: There is indirect evidence (i.e.. no description is
provided in the study) that considerations were not made for potential
confounders adjustment in the final analvses (NTP. 2015. 2823411).
AND
• The distribution of primary covariates (excluding co-exposures) and
potential confounders was not reported between the exposure groups or
between cases and controls (NTP. 2015. 2823411).
• For Studies reporting SMRs or SIRs: Results are ase-. race-. OR sex-
adjusted (or stratified) if applicable (i.e., if 2 or all should have been
adjusted).
Unacceptable
(score = 4)
• For all studv tvves: The distribution of potential confounders differed
significantly between the exposure groups.
AND
• Confounding was demonstrated and was not appropriately adjusted for in
the final analvses (NTP. 2015. 2823411).
• For Studies reporting SMRs or SIRs: No discussion of adjustments.
Results are not adjusted for age, sex, and race (or stratified) if applicable.
Not
rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Page 13 of 80
-------
Confidence Level
(Score)
Description
Selected
Score
Metric 10. Covariate Characterization (measurement/information, confounding biases)
High
(score = 1)
• For all studv tvves: Potential confounders (e.e. aee. sex. SES. race, etc.)
and were assessed using valid and reliable methodology where appropriate
(e.g., validated questionnaires, biomarker).
Medium
(score = 2)
• For all studv tvves: A less-established method was used to assess
confounders (excluding co-exposures) and no method validation was
conducted against well-established methods, but there was little to no
evidence that that the method had poor validity and little to no evidence of
confounding.
Low
(score = 3)
• For all studv tvves: The confounder assessment method is an insensitive
instrument or measure or a method of unknown validity.
Unacceptable
(score = 4)
• For all studv tvves: Confounders were assessed usins a method or
instrument known to be invalid.
Not
rated/applicable
• Covariates were not assessed.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important
elements such as relevance]
Metric 11. Co-exposure Confounding (measurement/information, confounding biases)
High
(score = 1)
• Do not select for this metric.
Medium
(score = 2)
• For all studv tvves: Anv co-exoosures to Dollutants that are not the tarset
exposure that would likely bias the results were not likely to be present.
OR
• Co-exposures to pollutants were appropriately measured or either directly or
indirectly adjusted for.
Low
(score = 3)
• For cohort and cross-sectional studies: There is direct evidence that there
was an unbalanced provision of additional co-exposures across the primary
study groups, which were not appropriately adjusted for.
• For case-control studies: There is direct evidence that there was an
unbalanced provision of additional co-exposures across cases and controls,
which were not appropriately adjusted for, and significant indication a
biased exposure-outcome association.
Unacceptable
(score = 4)
• Do not select for this metric.
Not
rated/applicable
• Enter 'NA' and do not score this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Domain 5. Analysis
Metric 12. Study Design and Methods
High
(score = 1)
• Do not select for this metric.
Medium
(score = 2)
• For all studv tvves: The studv desisn chosen was aDDroDriatc for the
research question.
AND
• The study uses an appropriate statistical method to address the research
question(s) (e.g.. Cox and Poisson regression for cohort studies and logistic
regression analysis for case-control studies.
Low
• Do not select for this metric.
Page 14 of 80
-------
Confidence Level
(Score)
Description
Selected
Score
(score = 3)
Unacceptable
(score = 4)
• For all studv tvves: The studv desien chosen was not aDDrooriatc for the
research question.
OR
• Inappropriate statistical analyses were applied to assess the research
questions.
Not
rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Metric 13. Statistical power (sensitivity)
High
(score = 1)
• Do not select for this metric.
Medium
(score = 2)
• For cohort and cross-sectional studies: The number of participants are
adequate to detect an effect in the exposed population and/or subgroups of
the total population.
OR
• The paper reported statistical power high is enough (> 80%) to detect an
effect in the exposure population and/or subgroups of the total population.
• For case-control studies: The number of cases and controls are adeauate to
detect an effect in the exposed population and/or subgroups of the total
population.
OR
• The paper reported statistical power was high enough (> 80%) to detect an
effect in the exposure population and/or subgroups of the total population.
Low
(score = 3)
• Do not select for this metric.
Unacceptable
(score = 4)
• For cohort and cross-sectional studies: The number of participants is
inadequate to detect an effect in the exposed population and/or subgroups of
the total population and the study was negative.
• For case-control studies: The number of cases and controls are inadeauate
to detect an effect in the exposed population and/or subgroups of the total
population and the study was negative.
Not
rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Metric 14. Reproducibility of analvses [adapted from Blettner et al. (2001. 4149692)1
High
(score = 1)
• Do not select for this metric.
Medium
(score = 2)
• For all studv tvves: The description of the analysis is sufficient to
understand precisely what has been done and to be conceptually
reproducible with access to the analytic data.
Low
(score = 3)
• For all studv tvves: The description of the analysis is insufficient to
understand what has been done and to be reproducible OR a description of
analyses are not present (e.g., statistical tests and estimation procedures
were not described, variables used in the analysis were not listed,
transformations of continuous variables (e.g. logarithmic) were not
explained, rules for categorization of continuous variables were not
Page 15 of 80
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Confidence Level
(Score)
Description
Selected
Score
presented, exclusion of outliers was not elucidated and how missing values
are dealt with was not mentioned).
Unacceptable
(score = 4)
• Do not select for this metric.
Not
rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important
elements such as relevance]
Metric 15. Statistical Models (confounding bias)
High
(score = 1)
• Do not select for this metric.
Medium
(score = 2)
• For all study tvves: The model or method for calculating the risk estimates
(e.g., odds ratios, SMRs, SIRs) is transparent (it is stated how/why variables
were included or excluded)
AND
• Model assumptions were met.
Low
(score = 3)
• For all studv tvves: The statistical model buildins process is not fullv
appropriate
OR
• Model assumptions were not met
OR
• A description of analvses is not dresent 1 STROBE Checklist 12e (Von Elm
etal.,2008. 4263036)1.
Unacceptable
(score = 4)
• Do not select for this metric.
Not
rated/applicable
• Enter 'NA' if the study did not use a statistical model.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important
elements such as relevance]
1.3. Evaluation Criteria for Epidemiological Studies: Asbestos
Exposure and Mesothelioma Health Outcome
Confidence Level
Description
Selected
(Score)
Score
Domain 1. Study Participation
Metric 1. Participant selection (selection, performance biases)
Instructions: To meet criteria for confidence ratings for metrics where 'AND' is included, studies must
address both conditions where 'AND' is stipulated. To meet criteria for confidence ratings for metrics
where 'OR' is included studies must address at least one of the conditions stipulated.
High
• For all studv tvves: All kev elements of the studv design are reported (e.g..
Page 16 of 80
-------
Confidence Level
(Score)
Description
Selected
Score
(score = 1)
•
setting, participation rate described at all steps of the study, inclusion and
exclusion criteria, and methods of participant selection or case
ascertainment)
AND
The reported information indicates that selection in or out of the study (or
analysis sample) and participation was not likely to be biased (i.e., the
exposure-outcome distribution of the participants is likely representative of
the exposure-outcome distributions in the population of persons eligible for
inclusion in the studv).
Medium
(score = 2)
•
For all studv tvves: Some kev elements of the studv desisn were not
present but available information indicates a low risk of selection bias (i.e.,
the exposure-outcome distribution of the participants is likely representative
of the exposure-outcome distributions in the population of persons eligible
for inclusion in the studv).
Low
(score = 3)
•
For all studv tvves: Kev elements of the studv desisn and information on
the population (e.g., setting, participation rate described at most steps of the
study, inclusion and exclusion criteria, and methods of participant selection
or case ascertainment) are not reported [STROBE checklist 4, 5 and 6 (Von
Elm et al.. 2008. 4263036)1.
Unacceptable (score
= 4)
•
For all studv tvves: The reported information indicates that selection in or
out of the study (or analysis sample) and participation was likely to be
significantly biased (i.e., the exposure-outcome distribution of the
participants is likely not representative of the exposure-outcome
distributions of the population of persons eligible for inclusion in the studv).
Not rated/applicable
•
Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important
elements such as relevance]
Metric 2. Attrition (missing data/attrition/exclusion, reporting biases)
High
(score = 1)
• For cohort studies: There was minimal subiect loss to follow lid durine the
study (or exclusion from the analysis sample) and outcome and exposure
data were largely complete
OR
• Loss of subjects (e.g., incomplete outcome data) or missing exposure and
outcome data was adequately* addressed (as described below) and reasons
were documented when human subiects were removed from a studv (NTP.
2015.2823411).
AND
• Missing data have been imputed using appropriate methods (e.g., multiple
imputation methods), and characteristics of subjects lost to follow up or
with unavailable records are not significantly different from those of the
studv Darticioants (NTP. 2015. 2823411).
• For case-control studies and cross-sectional studies: There was minimal
subject withdrawal from the study (or exclusion from the analysis sample)
and outcome data and exposure were largelv complete.
OR
• Any exclusion of subjects from analyses was adequately* addressed (as
described below), and reasons were documented when subjects were
removed from the studv or excluded from analvses (NTP. 2015. 2823411).
*NOTE for all studv tvves: Adeauate handline of subiect attrition can include:
Use of imputation methods for missing outcome and exposure data; reasons
Page 17 of 80
-------
( onl'idcncc l.c\cl
(Score)
Description
Selected
Score
for missing subjects unlikely to be related to outcome (for survival data,
censoring was unlikely to introduce bias); missing outcome data balanced in
numbers across study groups, with similar reasons for missing data across
groups.
Medium
(score = 2)
• For cohort studies: There was moderate subiect loss to follow lid durine
the study (or exclusion from the analysis sample) or outcome and exposure
data were nearly complete.
AND
• Any loss or exclusion of subjects was adequately addressed (as described in
the acceptable handling of subject attrition in the high confidence category)
and reasons were documented when human subjects were removed from a
study.
• For case-control studies and cross-sectional studies: There was moderate
subject withdrawal from the study (or exclusion from the analysis sample),
but outcome and exposure data were largely complete
AND
• Any exclusion of subjects from analyses was adequately addressed (as
described above), and reasons were documented when subjects were
removed from the study or excluded from analyses (NTP. 2015. 2823411).
Low
(score = 3)
• For cohort studies: The loss of subiects (e.e.. loss to follow lid.
incomplete outcome or exposure data) was moderate and unacceptably
handled (as described below in the unacceptable confidence category)
(Source: OHAT).
OR
• Numbers of individuals were not reported at important stages of study
(e.g., numbers of eligible participants included in the study or analysis
sample, completing follow-up, and analyzed). Reasons were not provided
for non-DarticiDation at each stase 1 STROBE Checklist Item 13 (Von Elm
etal.. 2008. 4263036)1.
• For case-control and cross-sectional studies: The exclusion of subiects
from analyses was moderate and unacceptably handled (as described
below in the unacceptable confidence category).
OR
• Numbers of individuals were not reported at important stages of study
(e.g., numbers of eligible participants included in the study or analysis
sample, completing follow-up, and analyzed). Reasons were not provided
for non-DarticiDation at each stase 1 STROBE Checklist Item 13 (Von Elm
etal.. 2008. 4263036)1.
Unacceptable (score
= 4)
• For cohort studies: There was laree subiect attrition durine the studv (or
exclusion from the analysis sample).
OR
• Unacceptable handling of subject attrition: reason for missing outcome data
likely to be related to true outcome, with either imbalance in numbers or
reasons for missing data across study groups; or potentially inappropriate
application of imputation (Source: OHAT).
• For case-control and cross-sectional studies: There was larse subiect
withdrawal from the study (or exclusion from the analysis sample).
OR
• Unacceptable handling of subject attrition: reason for missing outcome data
likely to be related to true outcome, with either imbalance in numbers or
reasons for missing data across study groups; or potentially inappropriate
application of imputation.
Page 18 of 80
-------
Confidence Level
(Score)
Description
Selected
Score
Not rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important
elements such as relevance]
Metric 3. Comparison Group (selection, performance biases) [See special instructions for mesothelioma
studies in "Not rated/applicable"!*
High
(score = 1)
• For ALL study types: Anv differences in baseline characteristics of sroiros
were considered as potential confounding or stratification variables and
were thereby controlled by statistical analysis (Source: OH AT).
OR
• For cohort and cross-sectional studies: Kev elements of the studv desisn
are reported (i.e., setting, inclusion and exclusion criteria, and methods of
participant selection), and indicate that groups were similar (e.g., recruited
from the same eligible population with the same method of ascertainment
and within the same time frame using the same inclusion and exclusion
criteria, and were of similar ase and health status) (NTP. 2015. 2823411).
• For case-control studies: Kev elements of the studv desisn are rcDortcd
indicate that that cases and controls were similar (e.g., recruited from the
same eligible population with the number of controls described, and
elisibilitv criteria and are recruited within the same time frame (NTP. 2015.
2823411).
• For studies reporting Standardized Mortality Ratios (SMRs) or
Standardized Incidence Ratios (SLRs): Ase. sex (if aDDlicablc). race (if
applicable), and calendar time adjustment or stratification is described and
choice of reference population (e.g., general population) is reported.
Medium
(score = 2)
• For cohort studies and cross-sectional studies: There is onlv indirect
evidence (e.g., stated by the authors without providing a description of
methods) that groups are similar (as described above for the high
confidence rating).
• For case-control studies: There is indirect evidence (i.e.. stated bv the
authors without providing a description of methods) that cases and controls
are similar (as described above for the high confidence rating).
• For studies reporting SMRs or SLRs: Ase. sex (if aDDlicablc). race (if
applicable), and calendar time adjustment or stratification is not specifically
described (i.e., indirect evidence) in the text, but results tables are stratified
by age, sex (if applicable), race (if applicable); choice of reference
population (e.g., general population) is reported.
Low
(score = 3)
• For cohort and cross-sectional studies'. There is indirect evidence (i.e..
stated by the authors without providing a description of methods) that
groups were not similar (as described above for the high confidence rating).
AND
• Differences between the exposure groups are not adequately controlled for
in the statistical analysis.
• For case-control studies: There is indirect evidence (i.e.. stated bv the
authors without providing a description of methods) that cases and controls
were not similar (as described above for the high confidence rating).
AND
• The characteristics of cases and controls are not rcDortcd (Source: (NTP.
2015.2823411).
AND
• Differences in groups is not adequately controlled for in the statistical
analysis.
Page 19 of 80
-------
( onl'idcncc l.c\cl
(Score)
Description
Selected
Scoro
• For studies revortins SMRs or SIRs: Indirect evidence of a lack of
adjustment or stratification for age, sex (if applicable), race (if applicable),
and calendar time; or indirect evidence that choice of reference population
(e.g., general population) is inappropriate.
Unacceptable (score
= 4)
• For cohort studies: Subiects in all cxoosurc aroiios were not similar
OR
• (Information was not reported to determine if participant groups were
similar 1 STROBE Checklist 6 (Von Elm et al.. 2008. 4263036)
AND
• Potential differences in exposure groups were for a factor that was related to
the outcome and not controlled for in the statistical analysis.)
OR
• (Subjects in the exposure groups had very different participation/response
rates (NTP. 2015.2823411).
AND
• Participation rates were related to exposure and outcome.)
• For case-control studies: (Controls were drawn from a verv dissimilar
DODiilation than cases or recruited within verv different time frames (NTP.
2015.2823411).
AND
• Potential differences in the case and control groups were not controlled for
in the statistical analysis.)
OR
• Rationale and/or methods for case and control selection, matching criteria
including number of controls per case (if relevant) were not reported
TSTROBE Checklist 6 (Von Elm et al.. 2008. 4263036)1.
• For cross-sectional studies: (Subiects in all cxoosurc aroiios were not
similar, recruited within very different time frames, or had very different
DarticiDation/rcsDonsc rates (NTP. 2015. 2823411).
AND
• Potential differences in exposure groups were not controlled for in the
statistical analysis.)
OR
• Sources and methods of selection of participants in all exposure groups
were not rcDortcd TSTROBE Checklist 6 (Von Elm et al.. 2008. 4263036)1.
• For studies revortins SMRs or SIRs: Lack of adjustment or stratification
for both age, sex (if applicable), race (if applicable), and calendar time; or
choice of reference population (e.g., general population) is not reported.
Not rated/applicable
• For mesothelioma studies, a comparison population is not required, as
EPA's interest is in the absolute risk and not the relative risk. All studies of
mesothelioma allowing for evaluation of absolute risk should be labeled as
"Not rated / not applicable"
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
l)om;iin 2. Kxposurc ('hiii'iiclori/iilioii
Metric 4. .Mi'iiMiiviiK'iil ol° I'lxposuiv (l)cU'Clion/mc;isiircmcnl/inrorm;ilion, pi'Moi-miincc hhiscs)
High
(score =1)
• For all studv tvves: Quantitative estimates of exposure were consistentiv
assessed (i.e., using the same method and sampling time-frame) during
multiple time periods and using either PCM or TEM.
OR
• A combination of methods were used over time (i.e., midget impinger, PCM
Page 20 of 80
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Confidence Level
(Score)
Description
Selected
Score
or TEM), but side by side sampling and analyses were conducted to develop
appropriate conversion criteria.
AND
• For an occupational population, contains detailed employment records and
quantitative estimates of exposure using either PCM or TEM which allows
for construction of job-matrix for entire work history of exposure (i.e..
Cumulative or peak exposures, and time since first exposure).
Medium
(score = 2)
• For all studv tvves: (Exposure was assessed durins one time oeriod but this
time period is judged to be reasonably representative of the entire study
time period.
AND
• Exposure was assessed using a combination of midget impingers, PCM
and/or TEM measurements, but side by side sampling and analyses were
not conducted for all operations and thus there is a lack of confidence in the
conversion factors.)
OR
• For an occupational study population, contains detailed employment records
and quantitative estimates of exposure using a combination of midget
impingers and PCM or TEM for only a portion of participant's work history
of exposure (i.e., only early years or later years), such that extrapolation of
the missing years is required.
Low
(score = 3)
• For all studv tvves: Exposure was estimated solelv usins professional
judgement.
OR
• Exposure was directly measured (e.g., midget impinger) and assessed using
a quantitative method other than PCM or TEM and conversion factors were
not determined.
Unacceptable (score
= 4)
• For all studv tvves: There was no Quantitative measure or estimate of
exposure.
OR
• Methods used to quantify the exposure were not well defined, and sources
of data and detailed methods of exposure assessment were not reported
[STROBE Checklist 7 and 8 (Von Elm et al.. 2008. 4263036)1.
OR
• There is evidence of substantial exposure misclassification that would
significantly bias the results.
Not rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Metric 5. Exposure levels (Detection/measurement/information biases)
High
(score = 1)
Do not select for this metric.
Medium
(score = 2)
• For all studv tvves: The ranse and distribution of exposure is sufficient or
adeauate to develop an exposure-response estimate (Cooper et al.. 2016.
3121908).
Low
(score = 3)
• For all studv tvves: The ranse of exposure in the population is limited.
Unacceptable (score
= 4)
• For all studv tvves: The ranse and distribution of exposure are not
sufficient or adequate to determine an exposure-response relationship
(Cooper et al.. 2016. 3121908).
OR
Page 21 of 80
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Confidence Level
(Score)
Description
Selected
Score
• No description is provided on the levels or range of exposure.
Not rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Metric 6. Temporality
High
(score = 1)
• For all studv tvves: The studv Dresents an aDDroDriatc teniDoralitv between
exposure and outcome (i.e. the exposure precedes the disease).
AND
• The interval between the exposure (or reconstructed exposure) and the
outcome is sufficiently long considering the latency of the disease (i.e.
studv follow-up is more than 20 vears for mesothelioma) (Lakind et al..
2014. 2713602).
Medium
(score = 2)
• For all studv tvves: Temporality is established, but it is unclear whether
there is adequate follow-up for consideration of latency (i.e., only 15-20
years of follow-up) (Lakind et al.. 2014. 2713602).
Low
(score = 3)
• For all studv tvves: The temporality of exposure and outcome is uncertain
(10-15 years).
OR
• There is inadequate follow-up of the cohort considering the latency period.
Unacceptable (score
= 4)
• For all studv tvves: Studv lacks an established time order, such that
exposure is not likelv to have occurred prior to outcome (Lakind et al..
2014. 2713602).
OR
• There was inadequate follow-up of the cohort for the expected latency
period (<10 years).
OR
• Sources of data and details of methods of assessment were not sufficiently
reported (e.g. duration of follow-up, periods of exposure, dates of outcome
ascertainment, etc.) Source: STROBE Checklist 8 (Von Elm et al.. 2008).
Not rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Domain 3. Outcome Assessment
Metric 7. Outcome measurement or characterization (detection/measurement/information, performance,
reporting biases)
High
(score = 1)
• For all studv tvves: The outcome was assessed usins one or a
combination of the following well-established methods:
o Mesothelioma cases confirmed by histological or cytological means
(including subtypes of mesothelioma) and/or
o ICD-10 codes (3 digit) C45 or (4 digit) C45.x (C45.0, C45.1, C45.2,
C45.7, C45.9)
o All fields on the death certificates of cohort searched for
'mesothelioma'
o Appropriate Pre-ICD 10 codes supplemented by additional evidence
(e.g. pathology/autopsy) see Table 1 of (Kopvlev et al.. 2011)
Medium
(score = 2)
• For all studv tvves: Examined death certificates searched for
mesothelioma for pre-ICD-10 codes that include pleura, peritoneum and
site unspecified (ICD code 199)
Low
(score = 3)
• Do not select for this metric.
Page 22 of 80
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Confidence Level
(Score)
Description
Selected
Score
Unacceptable (score
= 4)
• For all study tvves: Numbers of outcome events or summary measures
were not reported (Source: STROBE Checklist 15 (Von Elm et al.. 2008)
OR
• Only pre ICD-10 codes (without additional information) were used for
ascertainment of mesothelioma.
OR
• Examined death certificates searched for mesothelioma for codes that
included only pleura and/or peritoneum
OR
• Study lacks individual assessment of mesothelioma (i.e. mesothelioma is
assessed as a combination with other cancer types, excluding lung and
bronchus or trachea)
OR
• Any self-reported information
Not rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Metric 8. Reporting
Bias
High
(score = 1)
• For all study tvves: Mesothelioma findines are reported in the abstract,
results or discussion. Effect estimates are reported with confidence
intervals and/or standard errors, number of cases/controls or
exposed/unexposed reported for each analysis, to be included in exposure-
response analysis or fully tabulated during data extraction and analyses
(NTP. 2015. 2823411). '
Medium
(score = 2)
• For all study types: All of the study's findings (primary and secondary)
outlined in the abstract, results or discussion (that are relevant for the
evaluation) are reported, but not in a way that would allow for detailed
extraction (e.g., results were discussed in the text but accompanying data
were not shown).
Low
(score = 3)
• For all study tvves: Mesothelioma outcomes outlined in the methods,
abstract, and/or introduction (that are relevant for the evaluation) have not
been reported. (NTP. 2015. 2823411).
Unacceptable (score
= 4)
• Do not select for this metric.
Not rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Domain 4. Potential Confounding/Variable Control
Metric 9. Covariate Adjustment (confounding) [See special instructions for mesothelioma studies
rated/applicable"! *
in "Not
High
(score = 1)
• For all study tvves: AoDroDriatc adjustments or explicit considerations
were made for potential confounders (e.g. age, sex, SES, race, etc.)
(excluding co-exposures, which are evaluated in metric 11) in the final
analyses through the use of statistical models to reduce research-specific
bias, including matching, adjustment in multivariate models, stratification,
or other methods that were arorouriatelv justified (NTP. 2015. 2823411).
• For Studies revortins SMRs or SIRs: Adjustments are described and
results are age-, race-, and sex-adjusted (or stratified) if applicable.
Medium
• For all study tvves: There is indirect evidence that appropriate adjustments
Page 23 of 80
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Confidence Level
(Score)
Description
Selected
Score
(score = 2)
were made (i.e., considerations were made for primary covariates
(excluding co-exposures) and potential confounders adjustment) without
providing a description of methods.
OR
• The distribution of potential confounders (excluding co-exposures) did not
differ significantly between exposure groups or between cases and controls.
OR
• The major potential confounders (excluding co-exposures) were
appropriately adjusted and any not adjusted for are considered not to
appreciably bias the results (e.g., smoking rates in an occupational cohort
are expected to be generally similar in different departments and thus
confounding by smoking is unlikely when internal analyses are applied).
• For Studies reporting SMRs or SIRs: Indirect evidence that results are ase.
sex-, and race-adjusted (or stratified) if applicable.
Low
(score = 3)
• For all study tvves: There is indirect evidence (i.e.. no description is
provided in the study) that considerations were not made for potential
confounders adjustment in the final analvses (NTP. 2015. 2823411).
AND
• The distribution of primary covariates (excluding co-exposures) and
potential confounders was not reported between the exposure groups or
between cases and controls (NTP. 2015. 2823411).
• For Studies reporting SMRs or SIRs: Results are ase-. race-. OR sex-
adjusted (or stratified) if applicable (i.e., if 2 or all should have been
adjusted).
Unacceptable (score
= 4)
• For all studv tvves: The distribution of potential confounders differed
significantly between the exposure groups.
AND
• Confounding was demonstrated and was not appropriately adjusted for in
the final analvses (NTP. 2015. 2823411).
• For Studies reporting SMRs or SIRs: No discussion of adjustments.
Results are not adjusted for age, sex, and race (or stratified) if applicable.
Not rated/applicable
• For mesothelioma studies, evaluations of potential confounders are not
required as there are few other causes of mesothelioma (zeolites, viruses,
therapeutic or diagnostic radiation) and none that are likely to be correlated
in a dose-dependent manner with asbestos. Evaluation of potential
confounding in mesothelioma studies should be labeled as "Not
rated/applicable".
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important
elements such as relevance]
Metric 10. Covariate Characterization (measurement/information, confounding biases) [See special
instructions for mesothelioma studies in "Not rated/applicable"!*
High
(score = 1)
• For all studv tvves: Potential confounders (e.s. ase. sex. SES. race, etc.)
were assessed using valid and reliable methodology where appropriate (e.g.,
validated questionnaires, biomarker).
Medium
(score = 2)
• For all studv tvves: A less-established method was used to assess
confounders (excluding co-exposures) and no method validation was
conducted against well-established methods, but there was little to no
evidence that that the method had poor validity and little to no evidence of
confounding.
Low
(score = 3)
• For all studv tvves: The confounder assessment method is an insensitive
instrument or measure or a method of unknown validity.
Page 24 of 80
-------
Confidence Level
(Score)
Description
Selected
Score
Unacceptable (score
= 4)
• For all studv tvves: Confounders were assessed usins a method or
instrument known to be invalid.
Not rated/applicable
• Covariates were not assessed.
OR
• Metric 9 is rated "Not applicable"
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important
elements such as relevance]
Metric 11. Co-exposure reliability (measurement/information, confounding biases) [See special instructions
for mesothelioma studies in "Not rated/applicable"!*
High
(score = 1)
• Do not select for this metric.
Medium
(score = 2)
• For all studv tvves: Anv co-exoosures to Dollutants that are not the tarset
exposure that would likely bias the results were not likely to be present.
OR
• Co-exposures to pollutants were appropriately measured or either directly or
indirectly adjusted for.
Low
(score = 3)
• For cohort and cross-sectional studies: There is direct evidence that there
was an unbalanced provision of additional co-exposures across the primary
study groups, which were not appropriately adjusted for.
• For case-control studies: There is direct evidence that there was an
unbalanced provision of additional co-exposures across cases and controls,
which were not appropriately adjusted for, and significant indication a
biased exposure-outcome association.
Unacceptable (score
= 4)
• Do not select for this metric.
Not rated/applicable
• For mesothelioma, there are no established risk factors other than exposure
to asbestos, therefore no known co-exposures are of concern. Enter 'NA'
and do not score this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Domain 5. Analysis
Metric 12. Study Design and Methods
High
(score = 1)
• Do not select for this metric.
Medium
(score = 2)
• For all studv tvves: The studv desisn chosen was aDDroDriatc for the
research question.
AND
• The study uses an appropriate statistical method to address the research
question(s) (e.g.. Cox and Poisson regression for cohort studies, logistic
regression analysis for case-control studies.
Low
(score = 3)
• Do not select for this metric.
Unacceptable (score
= 4)
• For all studv tvves: The studv desisn chosen was not aDDroDriatc for the
research question.
Not rated/applicable
• Do not select for this metric.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Metric 13. Statistical power (sensitivity) [See special instructions for mesothelioma studies in "Not
rated/applicable"! *
Page 25 of 80
-------
Confidence Level
(Score)
Description
Selected
Score
High
(score = 1)
• Do not select for this metric.
Medium
(score = 2)
• For cohort and cross-sectional studies: The number of participants are
adequate to detect an effect in the exposed population and/or subgroups of
the total population.
OR
• The paper reported statistical power high is enough (> 80%) to detect an
effect in the exposure population and/or subgroups of the total population.
• For case-control studies: The number of cases and controls are adeauate to
detect an effect in the exposed population and/or subgroups of the total
population.
OR
• The paper reported statistical power was high enough (> 80%) to detect an
effect in the exposure population and/or subgroups of the total population.
Low
(score = 3)
• Do not select for this metric.
Unacceptable (score
= 4)
• For cohort and cross-sectional studies: The number of participants is
inadequate to detect an effect in the exposed population and/or subgroups of
the total population and the study was negative.
• For case-control studies: The number of cases and controls are inadeauate
to detect an effect in the exposed population and/or subgroups of the total
population and the study was negative.
Not rated/applicable
• For mesothelioma, EPA is primarily interested in the presentation of data
collected in the study, rather than the statistical analysis. EPA will pool data
across asbestos studies to conduct for the analysis of mesothelioma risk.
Therefore, the power of individual studies will not be considered. This
metric may be marked as not rated/applicable.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important elements
such as relevance]
Metric 14. Rcnroducibilitv of analvses lad anted from Blettner et al. (2001). 41496921 ISee snccial
instructions for mesothelioma studies in "Not rated/applicable"!*
High
(score = 1)
• Do not select for this metric.
Medium
(score = 2)
• For all study tvves: The description of the analvsis is sufficient to
understand precisely what has been done and to be conceptually
reproducible with access to the analytic data.
Low
(score = 3)
• For all study tvves: The description of the analvsis is insufficient to
understand what has been done and to be reproducible OR a description of
analyses are not present (e.g., statistical tests and estimation procedures
were not described, variables used in the analysis were not listed,
transformations of continuous variables (e.g. logarithmic) were not
explained, rules for categorization of continuous variables were not
presented, exclusion of outliers was not elucidated and how missing values
are dealt with was not mentioned).
Unacceptable (score
= 4)
• Do not select for this metric.
Not rated/applicable
• For mesothelioma, EPA is primarily interested in the presentation of data
collected in the study, rather than the statistical analysis. If individual data
elements (e.g., time since first exposure, number of person-years, etc.) are
present in the study that will allow EPA to conduct its own analysis, this
metric may be marked as not rated/applicable.
Page 26 of 80
-------
( onl'idcncc l.c\cl
(Score)
Description
Selected
Scoiv
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important
elements such as relevance]
Metric 15. Sliiiisiiciil Models (coil Ton n«l ini^ bins) |Scc spcciiil instructions lor mcsothclioniii studies in "Not
r;Kc(l/;i|)|)lic;il)lc"|'
High
(score =1)
• Do not select for this metric.
Medium
(score = 2)
• For all studv tvves: The model or method for calculating the risk estimates
(e.g., odds ratios, SMRs, SIRs) is transparent (it is stated how/why variables
were included or excluded).
Low
(score = 3)
• For all studv tvves: The statistical model buildins process is not fullv
appropriate
OR
• Model assumptions were not met
OR
• A description of analyses is not dresent 1 STROBE Checklist 12e (Von Elm
etal.,2008. 4263036)].
Unacceptable (score
= 4)
• Do not select for this metric.
Not rated/applicable
• For mesothelioma, EPA is primarily interested in the presentation of data
collected in the study, rather than the statistical analysis. If individual data
elements (e.g., time since first exposure, number of person-years, etc.) are
present in the study that will allow EPA to conduct its own analysis, this
metric may be marked as not rated/applicable.
Reviewer's
comments
[Document concerns, uncertainties, limitations, and deficiencies and any
additional comments that may highlight study strengths or important
elements such as relevance]
Page 27 of 80
-------
2. Data Evaluation of Lung Cancer Studies
2.1. Table of studies evaluated for asbestos exposure and lung cancer
incidence
Study Cohort
Author, Year
HERO ID
South Carolina,
US
(Berman and Crump, 2008)
626405
(Brown et al., 1994)
3081832
(Cole etal.. 2013)
3078261
(Dement et al., 1983b)
67
(Dement and Brown, 1994a)
3094565
(Dement et al., 1994)
3081766
(Dement and Brown, 1994b)
3081783
(T.d wards el al . ) 14)
3078061
Million el ill.. Zii|2)
I247KM
(Hein et al.. 2007)
709498
(Loomis et al., 2012)
1257856
(SRC. 2019c)
5080236
(Stavner et al., 1997)
3081241
(Stavner et al., 2008)
2604140
Qinghai, China
- miners
(Wane etal.. 2012)
2572504
(Wane etal.. 2013)
2548289
(Wang et al., 2014)
2538846
Balangero, Italy
(Piolatto et al., 1990)
3082492
(Pira et al., 2009)
2592425
(Pira et al., 2017)
5060134
(Rubino et al., 1979)
178
North Carolina,
US
(Berman and CrumD, 2008)
626405
(Dement et al., 2008)
626406
Million el ill.. 2<)I2)
I247KM
(Loomis et al., 2009)
3079232
(Loomis et al., 2010)
2225695
(Loomis et al., 2012)
1257856
(Loomis el ill . 2d I1))
5100027
(SRC. 2019a)
5080241
Salonit
Anhovo,
Slovenia
(Dodic Fikfak. 2003)
3080279
(Dodic Fikfak et al., 2007)
3079664
Page 28 of 80
-------
Study Cohort
Author, Year
HERO ID
Quebec,
Canada
(Berman and Cruma 2008)
626405
(Gibbs and Lachance, 1972)
3580825
(Liddell et al., 1997)
3081408
(Liddell et al., 1998)
3081200
(Liddell and Armstrong, 2002)
3080504
(Mcdonald et al., 1993a)
3081910
(Mcdonald et al., 1993b)
3081911
(SRC. 2019b)
5080232
(Vacek. 1998)
3081118
Chongqing,
China -
asbestos
products factory
including
textiles
(Courtice et al., 2016)
3520560
(Deng et al., 2012)
2573093
(Wang et al., 2014)
2538846
(Yano et al., 2001)
3080569
Shaded rows indicate studies used for derivation of Inhalation Unit Risk (IUR).
Page 29 of 80
-------
2.2. Data Evaluation Scoring Sheets: Lung Cancer Outcome
2.2.1. Epidemiology evaluation results of the South Carolina, US
cohort studies on asbestos exposure and lung cancer incidence
Study
reference:
This cohort evaluation represents all identified publications pertaining to the South Carolina cohort of textile
workers. A full list of related papers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
C
#o
"s
o.
'3
"H
CS
a.
¦a
s
in
S3
o
.&
o
a. Setting and methods of case ascertainment were
reported in (Dement et al.. 1983b. 671 p. 422 and
(Hein et al.. 2007. 7094981 p 617. Participant
selection and inclusion/exclusion criteria varied by
study and analysis. The initial cohort consisted of
white men employed for at least one month in a
production job at the South Carolina plant between
1/1/1940 and 12/31/1965 ((Dement et al.. 1983b.
67) p 422). Subsequent analyses added non-white
men and/or women ((Stavner et al.. 1997. 30812411.
(Dement et al.. 1994. 30817661 (Brown etal.. 1994.
30818321. (Elliott et al.. 2012. 12478611, (Edwards
etal.. 2014. 30780611. (Cole et al.. 2013. 30782611.
(Hein et al.. 2007. 70949811. b. Selection in or out
of the study was based on 1) employment in
production job during designated time frame and b)
availability of necessary data (birth and hire dates;
work history; vital status). These criteria are
unlikely to result in biased subject participation.
High
0.400
0.400
Page 30 of 80
-------
Study
reference:
This cohort evaluation represents all identified publications pertaining to the South Carolina cohort of textile
workers. A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
2. Attrition
Attrition/missing data exclusions were reported in
(Dement et al.. 1983b. 67) (o. 423 and Table 1) and
(Hem et al.. 2007. 709498) (o 618 and Table 1). The
number of eligible workers and number excluded
due to incomplete work histories was not reported in
the sources reviewed. (Dement et al.. 1983b. 67) (v
422) reports that each worker was assigned a card at
hire on which was tracked the date of birth, sex,
race, and SSN, and job or department changes
throughout the career were recorded on the card;
these were used in the cohort establishment. The
suggestion is that all cohort members had complete
work histories: however. (Hem et al.. 2007. 709498)
(p 624) reported that the study was limited by
incomplete lifetime work histories. Vital status was
unknown for 2.1% of the original 1261 cohort
members, and cause of death was unknown for
5.5% of the deaths in 1975. At the 2001 follow up
(Hein et al.. 2007. 709498). vital status was
unknown for 8.6% of the larger cohort of 3072, and
cause of death was unknown for 3.9%. The latter
paper cited high rate of loss to follow-up as a
limitation of the study. Thus, loss to follow up is
judged to be moderate, and the lack of information
on number eligible and number with incomplete
work histories leads to low confidence.
Low
3
0.400
1.200
3. Comparison Group
Any differences in baseline characteristics (e.g.,
age, sex, race) were controlled by statistical analysis
((Dement et al.. 1983b. 67). a 422; (Hein et al..
2007. 709498). v 617). In (Hein et al.. 2007.
7069498) (v 617). it is reported that birth cohort was
used in statistical analysis as a surrogate for
smoking. Setting, inclusion and exclusion criteria,
and methods of participant selection are reported
((Dement et al.. 1983b. 67). a 422 and (Hein et al..
2007. 709498) o 617). and these sussest that the
groups were recruited from the same eligible
population with the same method of ascertainment
and within the same time frame using the same
inclusion and exclusion criteria.
High
1
0.200
0.200
Page 31 of 80
-------
Study
reference:
This cohort evaluation represents all identified publications pertaining to the South Carolina cohort of textile
workers. A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
a
#o
"s
N
¦e
4. Measurement of Exposure
(Dement et al.. 1983a. 66) describes the dlant
processes and the exposure estimation methods.
More than 6000 air samples obtained at the plant
from 1930 to 1975 were analyzed by PCM to yield
chrvsotile concentrations (fibers >5 um/mL: (Hein
et al.. 2007. 709498s). o 617s). Exposure
concentrations were estimated by department, job,
and time period; individual cumulative exposure
assessed using the modeled concentrations and JEM
(methods outlined in (Dement et al.. 1983a. 66)). In
2008, an updated JEM was developed to estimate
fiber size-specific exposure estimates (based on
TEM analvsis of archived samples) in (Dement et
al.. 2008. 626406s).
High
i
0.400
0.400
t5
es
~-
es
-fl
U
B
£
O
o.
UJ
5. Exposure
levels
Exposure-response relationships were developed
(see Fieure 2 and Table VIII of (Dement et al..
1983b. 67). Table 3 of (Hein et al.. 2007. 709498).
(Elliott et al.. 2012. 1247861s) see Table 2. A total of
6 cumulative exposure levels are analyzed in Table
3 of (Hein et al.. 2007. 709498).
Medium
2
0.200
0.400
6. Temporality
Temporality was established (exposure preceded
death). Exposure response analysis in initial cohort
(Dement et al.. 1983b. 67) was restricted to
individuals with at least 15 years follow up since
first employment (p 426). The longest follow-up
time for the cohort was at least 36 years (1965-
2001; (Heinetal.. 2007. 709498) o 617). Atenvear
las time was used in the analyses in (Hein et al..
2007. 709498) (d 617). In (Elliott et al.. 2012.
1247861). the assessment of the SC cohort also used
a ten year lag time (Table 2).
High
1
0.400
0.400
Outcome Assessment
7. Outcome measurement or
characterization
Lung cancer deaths (underlying and contributing
cause) were determined from the National Death
Index Plus (1979 and later; (Hein et al.. 2007.
709498) o 617) or death certificates (before 1979;
sources of certificates not specified; (Dement et al..
1983b. 67) o 422). ICD in effect at time of death
was used ((Dement et al.. 1983b. 67) v 422). Deaths
before 1979 were coded manually by a nosologist.
ICD codes 162 and 163 (trachea, bronchus, and
luns) were considered luns cancers ((Dement et al..
1983b. 67) Tables II. III. IV. VIII. XI).
High
1
0.667
0.667
Page 32 of 80
-------
Study
This cohort evaluation represents all identified publications pertaining to the South Carolina cohort of textile
reference:
workers. A full list of related naners reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Weighting
Factor
Weighted
Score
Lung cancer deaths and person-years at risk by
exposure category are reported in Table 3 of (Hcin
•S3
et al.. 2007. 709498s); luns cancer cases and person-
S
bD
vears at risk are reported in Table 1 of ffilliott et al..
2012. 1247861'). Rate ratio estimates are reported
High
i
0.333
0.333
o
with CIs in (Hcin et al.. 2007. 709498s) and ffilliott
et al.. 2012. 1247861s); coefficients forPoisson
00
regression are reported without SE in Table 2 of
ffilliott et al.. 2012. 1247861). but rate ratios with
CIs are also reported for the same models.
Analyses in (Hcin et al.. 2007. 709498s) and ffilliott
et al.. 2012. 1247861s) were adiusted for ase. sex.
race, decade of follow-up and birth cohort. No
I
adiustment was made for smokins in (Dement et al..
1983b. 67s). which could bias SMR analyses.
_
=3
However, the authors of (Dement et al.. 1983b. 67s)
~-
C
o
o
the aroiiDS. (Hein et al.. 2007. 709498s) and ffilliott
¦e
et al.. 2012. 1247861s) evaluated birth cohort as a
es
>
surrogate for smoking; lack of direct consideration
ft*)
of smoking is not likely to bias internal analysis in
¦3
an occupational cohort.
5
£
(Dement et al.. 1983b. 67s) (p 422s) reports that each
c
o
o
•-=3
worker was assigned a card at hire on which was
U
cd
N
included the date of birth, sex, and race, presumably
.5
records were used to estimate patterns of smoking in
o
O
the cohort and compared with US White males
o
(comparison group for SMR analyses). Data were
not available for all cohort members.
Page 33 of 80
-------
Study
reference:
This cohort evaluation represents all identified publications pertaining to the South Carolina cohort of textile
workers. A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
11. Co-exposure Confounding
Small amounts of crocidolite yarn were used
between 1950s and 1975, but the total quantity was
reported to be small (2000 lbs total vs 6-8 million
lbs/yr of chrysotile during that time period). In
addition, workers did not card, spun, or twist the
crocidolite; a single loom was used; and weaving
was performed wet, which minimized exposure to
crocidolite ((Hein et al.. 2007. 709498) o 616). The
distribution of this co-exposure relative to chrysotile
exposure was not evaluated, and no effort was made
to adjust fortius co-exposure. However, available
information suggests the coexposure would be
negligible relative to chrysotile exposures.
Medium
2
0.250
0.500
12. Study
Design and
Methods
Study design was retrospective cohort; Poisson
regression used for internal analyses in (YHein et
al.. 2007. 709498) o 617) and (Elliott et al.. 2012.
1247861) p 386.
Medium
2
0.400
0.800
13.
Statistical
power
None of the related studies report power
calculations; however, statistically significant
exposure-response relationships suggest there was
adequate power to detect the effect.
Medium
2
0.200
0.400
Analysis
14. Reproducibility of analyses
Analysis description in (Hcin et al.. 2007. 709498)
appears to be complete. Statistical tests and
estimation procedures and variables considered are
reported (YHein et al.. 2007. 709498) o 617). For
internal analyses, cumulative exposure was treated
as a continuous variable and/or partitioned into
categories with approximately equal numbers of
deaths (YHein et al.. 2007. 709498) o 617 and
footnote to Table 3). There were no variable
transformations, outlier exclusions, or imputation of
missine values. Analysis description in (Elliott et
al.. 2012. 1247861) aooears to be complete.
Statistical tests and estimation procedures and
variables considered are rcoortcd (Elliott et al..
2012. 1247861) d 386. Cumulative exposure was
analyzed as a continuous variable (Elliott et al..
2012. 1247861). d 386. No variable transformations
were reported.
Medium
2
0.200
0.400
15. Statistical
Models
Statistical models and methods are described in
detail later Dublications (see (Hein et al.. 2007.
709498) o 617-618 and (Elliott et al.. 2012.
1247861) v 386. including how variables were
included or excluded.
Medium
2
0.200
0.400
Sum of scores:
5
8
Page 34 of 80
-------
Study
reference:
This cohort evaluation represents all identified publications pertaining to the South Carolina cohort of textile
workers. A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Overall Score = Sum of Weighted Scores/Sum of Metric
Weighting Factors:
1.6
Overall
Score:
Nearest
tenth:
1.6
Overall Quality Level:
High
Study
Quality
Comment:
The reviewer agreed with this study's overall quality level.
Page 35 of 80
-------
2.2.2. Epidemiology evaluation results of the Chongqing, China
mining cohort studies on asbestos exposure and lung cancer
incidence
Study
reference:
This cohort evaluation represents all identified publications pertaining to the cohort of miners in Chongqing,
China. A full list of related naners reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
1. Participant
selection
The key elements of the study design are reported
(YWane et al.. 2013. 2548289-) d. 2. and rWane et
al.. 2012. 2572504) a 20s). All male workers
employed for at least one year in the chrysotile mine
were included in the study (participation is not
likely to be biased).
High
i
0.400
0.400
a
#o
"s
.2-
2. Attrition
There was no subject loss to follow up during the
study; outcome and exposure data were complete
(YWane et al.. 2013. 2548289) d. 2. and rWane et
al.. 2012. 2572504) v. 20).
High
i
0.400
0.400
"H
es
&
¦o
5
Tfl
3. Comparison Group
Inclusion criteria and the methods of participant
selection were reported. All subjects were recruited
from the same eligible population within the same
time frame. In studies reoortine SMRs (YWane et
al.. 2012. 2572504) v. 407. and (Wane et al.. 2013.
2548289) d. 3). the choice of a reference DODulation
is reported (based on age-specific national mortality
data for males). However, data on cause-specific
mortality data were limited (rates of 1990 and 2004
were used to correspond to periods of 1981-1995
and 1996-2006. respectively ((Wane et al.. 2012.
2572504) p. 411).
High
i
0.200
0.200
Page 36 of 80
-------
Study
reference:
This cohort evaluation represents all identified publications pertaining to the cohort of miners in Chongqing,
China. A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
Exposure Characterization
4. Measurement of Exposure
Periodic asbestos dust measurements were
available from 1984 to 1995 ((Wane et al.. 2013.
2548289s) v>.2). In 2006. additional measurements in
various workshops were Dcrformcd (YWane et al..
2013. 2548289s) v.2. (Warn et al.. 2014. 2538846) v.
120. and (Wane et al.. 2012. 2572504) v. 406);
these samples were also analyzed by TEM. Paired
samples from 1991 (using simultaneous gravimetric
and membrane filter methods) from the main
workshop only were used to define the relationship
between dust and fiber concentrations (YWane et al..
2013. 2548289) o. 2). From these data, (and usine
all periodically measured data at different
workshops), average fiber concentrations by
workshop/job were calculated. Cumulative
individual exposures were estimated as the product
of (fiber concentration at a specific workshop/job) x
(duration of iob) ((Wane et al.. 2013. 2548289) a 3
and (Wane et al.. 2014. 2538846) a 120). Side-bv-
side analyses were not conducted for all operations
or at all time points (i.e. systematic dust/fiber data
were not available: (Wane et al.. 2012. 2572504) o.
409). There were no exposure data prior to 1984.
The study authors acknowledge that there may have
been exposure misclassification based on these
estimations, but the misclassification was likely to
be non-differential ((Wane et al.. 2013. 2548289) d.
7 and (Wane et al.. 2014. 2538846) a 123).
Medium
2
0.400
0.800
5. Exposure levels
The range and distribution of exposure is sufficient
to develop and exposure-response estimate. The
Wane et al. 2014 studv ((Wane et al..
2014.2538846) o. 122) reoorts 4 levels of exposure
(referent + 3); cumulative exposures were
categorized quartiles for analyses of lung cancer
deaths.
Medium
2
0.200
0.400
6. Temporality
The study establishes appropriate temporality; the
interval between exposure and outcome is long
enoueh considerine latency of the disease ((Wane et
al.. 2013. 2548289) v. 1. (Wane et al.. 2014.
2538846) v. 119. and (Wane et al.. 2012. 2572504)
p. 406). The cohort was followed for 26 years.
High
1
0.400
0.400
Page 37 of 80
-------
Study
reference:
This cohort evaluation represents all identified publications pertaining to the cohort of miners in Chongqing,
China. A full list of related papers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
C
O
(J
5
o
S3
£
® 5
-w
o
a.
S3
y
S3
-------
Study
reference:
This cohort evaluation represents all identified publications pertaining to the cohort of miners in Chongqing,
China. A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
10. Covariate Characterization
Covariates were assessed using reliable
methodology. Vital status information was obtained
from personnel records. Information on smoking
habits and verification of occupational history was
obtained from workers or their immediate relatives
(if deceased) throush personal contact ((Wans et al..
2013. 2548289s) v. 2 and (Wans et al.. 2012.
2572504s) a 4071 The Wane et al. 2014 studv (
(Wans et al.. 2014. 2538846s) o. 120s) indicated that
vital status was obtained through follow-up and
links to death certificates and using structured
questionnaires. Although individual smoking status
information was available, information on the
duration and/or intensity of smoking was not
available.
High
i
0.250
0.250
11. Co-exposure Confounding
The members of the cohort were workers at an
asbestos mine in China. There was no evidence that
there was an unbalanced provision of co-exposures
amons exposure aroiios ((Wans et al.. 2013.
2548289s) v. 7. (Wans et al.. 2014. 2538846s) v.
123s). At least one of the studies (YWane et al.. 2013.
2548289s) d. 7s) indicated that workers senerallv
stayed with the mine for a lifetime, with little
opportunity to change jobs (making exposure to
other occupational carcinogens unlikely). Two of
the studies ((Wans et al.. 2012. 2572504s) a 406 and
(Wans et al.. 2013. 2548289s) o. 2s) indicated no
detection of tremolite (amphibole contamination <
0.1%, the limit of detection).
Medium
2
0.250
0.500
Analysis
12. Study Design and Methods
The study design was appropriate to address the
research question. Cox and/or Poisson regression
analyses were used ((Wans et al.. 2013. 2548289) v>.
3. (Wans et al.. 2014. 2538846) a 121. and (Wans
et al.. 2012. 2572504) v. 407). The Wans et al. 2012
studv ((Wans et al.. 2012. 2572504) a 407) and
Wans et al. 2014 studv ((Wans et al.. 2014.
2538846) v. 121) used Cox Drooortional hazard
models to obtain hazard ratios for lung cancer
mortality in relation to asbestos exposure
(cumulative exposure for the latter study). The
Wans et al. 2013 studv ((Wans et al.. 2013.
2548289) v. 3) used Poisson resression to estimate
relative risks for lung cancer.
Medium
2
0.400
0.800
Page 39 of 80
-------
Study
reference:
This cohort evaluation represents all identified publications pertaining to the cohort of miners in Chongqing,
China. A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
13. Statistical
power
The number of participants (cohort size =1539
workers) was large enough to detect an effect in the
exposed population. However, it was noted that
there was a relatively small number of nonsmokers
in the cohort ((Wans et al.. 2013. 2548289) a 6 and
(Wans et al.. 2012. 2572504) v. 410).
Medium
2
0.200
0.400
14. Reproducibility of
analyses
The methods used to estimate exposures were not
described in a way that would facilitate
reproducibility (string references were cited in
rWane et al.. 2013. 2548289*) a 2 and rWans et al..
2014. 2538846) v. 120 as suDDortins evidence for
dust to fiber concentration conversions). In general,
the statistical analyses used were described,
including variables used in the analyses.
Medium
2
0.200
0.400
15.
Statistical
Models
The methods used to calculate risk estimates (SMRs
and HRs) were adeauatelv described ((Wans et al..
2013. 2548289) v. 3 and (Wans et al.. 2014.
2538846) p. 121).
Medium
2
0.200
0.400
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >-2.3 and <-3
Sum of scores:
5
8.0166
Overall Score = Sum of Weighted Scores/Sum of Metric
Weighting Factors:
1.6033
Overall
Score:
Nearest
tenth:
1.6
Overall Quality Level:
High
Study
Quality
Comment:
The reviewer agreed with this study's overall quality level.
Page 40 of 80
-------
2.2.3. Epidemiology evaluation results of the Balangero, Italy
cohort of studies on asbestos exposure and lung cancer
incidence
Study
reference:
This evaluation represents all identified publications pertaining to the Balangero, Italy cohort of miners. A full list
of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
Study Participation
1. Participant selection
Subjects included men from the Balangero mine
worker cohort that were employed in an Italian
asbestos mine. The initial cohort ((Rubino et al..
1979. 178s). 02.188s) consisted of 952 men employed
between 1/1/1930 and 12/31/1965, with at least 30
calendar days' employment during that period.
Mortality data were collected from 1/1/1946 to
12/31/1975. Workers for which vital status could
not be acertained and a small number of contract
workers employed intermittently were excluded. In
the first follow-up, 1058 workers were included that
had worked at least one year between 1946 and
1987 and mortality follow-up was extended through
12/31/1987 ((Piolatto et al.. 1990. 30824921 m
810). In subseauent follow-uos ((Pira et al.. 2009.
2592425s) m 805. and (Pira et al.. 2017. 5060134V).
subjects included 1056 men from the Balangero
mine worker cohort employed between 1930 and
1990, and mortality records were evaluated though
2003 and 2014, respectively. Records were not
available between 1987 and 1990, when the mine
closed, so workers employed in 1987 were assumed
to be employed through 1990 unless they died
during that period. Additional details in the most
recent following indicated that the initial cohort
included 1182 men; the 126 excluded subjects were
contract workers, those employed <1 yr, those with
inconsistencies in data, and those known to have
died orior to 1946 (Pira et al.. 2017. 5060134s) us
558.
High
i
0.400
0.400
2. Attrition
In the most recent follow-up, study authors report
that one of the strengths of the study is low
DroDortion of subiects lost to follow-uo (Pira et al..
2017. 5060134) us 562. Loss to follow-uo was 2%
in the initial cohort (Rubino et al.. 1979. 178s). 3% in
the first follow -uD (YPiolatto et al.. 1990. 3082492).
pg 810), and 4% in the most recent follow-ups (Pira
et al.. 2009. 2592425) m 805; (Pira et al.. 2017.
5060134) ps 559.
High
i
0.400
0.400
Page 41 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Balangero, Italy cohort of miners. A full list
of related papers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
&
8
a
e
0
"S
1
o
O
The most complete data on comparison groups is
available from the most recent follow-up (Pira et al..
2017. 50601341. General population mortality rates
using the whole country from 1955 until 1980 and
specifically the Piedmont Region (where the mine is
located) from 1981 onwards (no regional rates
available prior to 1981). The 1955-1959 rates were
applied to 1946-1954 period (no available data); this
may have led to an underestimate of expected
deaths which may have showed and increased rate
during this period. Expected numbers of deaths
(overall and selected cancers) were computed using
age-specific and calendar-year-specific (5-year
categories) male death rates (Pira et al.. 2017.
5060134) pg 559. The only deviation from this was
in the first follow-up, which used national mortality
rates were for the entire follow-up period (through
1987) (Piolatto et al.. 1990. 3082492) pg. 811). In
the initial study on this cohort ((Rubino et al.. 1979.
178). pg. 189), an additional case-control study was
performed in which 5 age-matched controls were
selected at random; they were confirmed alive at the
time of death for the matched case. No details on
what population provided controls. The evaluation
is based on the cohort mortality study only, as this
was the analysis carried through the 3 follow-up
studies (Pira et al.. 2017. 5060134: Pira et al.. 2009.
2592425: Piolatto et al.. 1990. 3082492).
High
0.200
0.200
s
_o
"c5
.a
•-
0>
u
cS
•-
cS
JS
U
a
s
o
s.
H
W
O
a
x
w
S3
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Balangero, Italy cohort of miners. A full list
of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
5. Exposure levels
In the initial cohort ((Rubino et al.. 1979. 178s).
Table 8), exposure was reported as up to 100
fiber/yr or >100 fiber/year. In the follow-ups,
exposure was reported as <100 fiber/mL-yr, 100-
<400 fiber/mL-vr. and >=400 fiber/ml-vr ((Piolatto
et al.. 1990. 30824921 Table 3; (Pira et al.. 2009.
2592425s). Table 2; (Pira et al.. 2017. 50601341
Tables 3-4)
Medium
2
0.200
0.400
6. Temporality
Evaluation is based on the most recent publication,
which is has the longest follow-up period for this
cohort (follow up of the 1946-1990 cohort through
2014s) ((Pira et al.. 2017. 50601341 m 559). The
first two studies on this cohort (YRubino et al.. 1979.
178) us. 188. (Piolatto et al.. 1990. 3082492) m
811) have inadequate follow-up duration for lung
cancer (<15 years).
High
1
0.400
0.400
7. Outcome
measurement
or
characterizati
Lung cancer mortality was assessed based on death
certificate cause of death according to ICD rubrics
162/163 ((Pira et al.. 2017. 5060134). Table 1:
(Rubino et al.. 1979. 178) us 189; (Piolatto et al..
1990. 3082492) m 189).
High
1
0.667
0.667
Outcome Assessment
8. Reporting Bias
Overall SMRs plus 95% CIs for lung cancer are
reported for the initial study and all 3 follow-ups
with 95% CI values in Table 2 of the most recent
follow-uD (Pira et al.. 2017. 5060134). Luns and
pleural cancers are grouped together for the SMR
from the original study. The most recent follow-up
also reports RRs with confidence intervals for lung
cancer mortality (Table 4; (Pira et al.. 2017.
5060134)). The case-control reoort in the initial
studv lYRubino et al.. 1979. 178). Table 51 did not
include confidence intervals. The evaluation is
based on the SMR analyses carried forward in the
follow-ups and the RR analyses conducted in the
most recent follow-up.
High
1
0.333
0.333
Potential
Confound ing/V ariable
Control
9. Covariate Adjustment
SMR was stratified by age and calendar year (5-yr
categories). Onlv males were included. ((Rubino et
al.. 1979. 178) us 189; (Piolatto et al.. 1990.
3082492) ds 811; (Pira et al.. 2009. 2592425). m
806; (Piraetal.. 2017. 5060134). us 559. In the
most recent follow-up, data on smoking was limited
to 14.5% of the cohort, but the prevelance of
smoking in this subset of the cohort was comparable
to that of the eeneral male DODulation ((Pira et al..
2017. 5060134) m 562).
High
1
0.500
0.500
Page 43 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Balangero, Italy cohort of miners. A full list
of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
10.
Covariat
e
Charact
Empirical data obtained from employment records.
Smoking information was obtained from medical
records (when available).
High
i
0.250
0.250
11. Co-
exposure
Confounding
No adjustments for potential coexposures were
described. Dust identified as primarily chrysotile, no
amphibole fibers dectected, but a fibrous silicate
(balangeroite) was detected (0.2-0.5% of total
sample) ((Pira et al.. 2017. 5060134) ps 560).
Low
3
0.250
0.750
&
*5«
12. Study Design and Methods
For this retrospective cohort there is an initial study
((Rubino et al.. 1979. 178)) and 3 follow -uD studies
((Piolatto et al.. 1990. 3082492). (Pira et al.. 2009.
2592425). (Pira et al.. 2017. 5060134)). Evaluation
is based on the most recent follow-uo ((Pira et al..
2017. 5060134). us 559). in which SMRs were
calculated for entire cohort as well as based on
indicators of asbestos exposure (duration of
exposure, age at first exposure, years since first
exposure, years since last exposure, period at first
exposure, and cumulative dust exposure). RRs were
also calculated using Poisson regression. In this
recent follow-up, cohort members contributed to
person-time of observation starting 1 year after first
employment (or 1946), and ended at death, date of
last contact for those lost to follow-up, 85th
birthday, or December 31, 2014.
Medium
2
0.400
0.800
C
<
13. Statistical power
The evaluation is based on the most recent follow-
ut> ((Pira et al.. 2017. 5060134). us 516). which has
a 90% statistical power to detect a SMR of 2.0 for
lung cancer among workers with <100 fiber/mL-
years cumulative exposure (determined SMR [95%
CI] was 0.82 [0.44-1.40]; 13 deaths). The power of
the analysis for <25 fibers/mL-years cumulative
exposure was reported as "low" (determined SMR
[95% CI] was 2.40 [0.49-7.01]; 3 deaths). The
power for analyses at higher exposure levels (>=100
fiber/mL-years) was not reported.
Medium
2
0.200
0.400
14.
Reproducibility
of analyses
The evaluation is based on the most recent follow-
ud ((Pira et al.. 2017. 5060134)). For SMR
calculations, expected deaths were not reported for
SMRs from selected causes according to indicators
of asbestos exposure. All other relevant data are
reported in Tables 1-4.
Medium
2
0.200
0.400
Page 44 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Balangero, Italy cohort of miners. A full list
of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
15. Statistical Models
The evaluation is based on the most recent follow-
ud (YPira et al.. 2017. 5060134'). oe 5591 SMRs
were calculated for entire cohort as well as based on
indicators of asbestos exposure (duration of
exposure, age at first exposure, years since first
exposure, years since last exposure, period at first
exposure, and cumulative dust exposure). RRs were
calculated using Poisson regression.
Medium
2
0.200
0.400
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >-2.3 and <-3
Sum of scores:
5
7.1
Overall Score = Sum of Weighted Scores/Sum of Metric
Weighting Factors:
1.42
Overall
Score:
Nearest
tenth:
1.4
Overall Quality Level:
High
Study
Quality
Comment:
The reviewer agreed with this study's overall quality level.
Page 45 of 80
-------
2.2.4. Epidemiology evaluation results of the North Carolina, US
cohort studies on asbestos exposure and lung cancer incidence
Study
reference:
This evaluation represents all identified publications pertaining to the North Carolina cohort of textile workers. A
full list of related naners reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
a
#o
"s
.5-
"3
r
es
a.
1. Participant selection
a. Setting and methods of case ascertainment were
reported in (Loomis et al.. 2009. 3079232s). v>. 535-
536. Participant selection and inclusion/exclusion
criteria varied by study and analysis. Although there
were 4 plants in the cohort, exposure data were
available only for three of the four, so exposure-
response analyses were limited to these three plants.
Orieinal selection criteria rcDortcd in (Loomis et al..
2009. 3079232) d 536 foarticirants had to work at
least 1 day between 1950 and 1973) and p 539
(rarticirants excluded due to missins data), (Elliott
et al.. 2012. 1247861) evaluated a subset of the
cohort that worked >30 days during the same time
frame, b. Selection in or out of the study was based
on 1) employment in production job during
designated time frame and b) availability of
necessary data (birth and hire dates; work history;
vital status). These criteria are unlikely to result in
biased subject participation.
High
i
0.400
0.400
¦a
5
Tfl
2. Attrition
Attrition/missing data exclusions were reported in
both (Loomis et al.. 2009. 3079232) fa 539) and
(Elliott et al.. 2012. 1247861) see m 386. The
original cohort was 5770 persons; 373 workers at
plant 2 were excluded due to lack of exposure data
at this plant, 1596 were excluded due to incomplete
work histories (at department level) or non-
oroduction iobs ((Loomis et al.. 2009. 3079232) a
539). Final cohort for exposure-response analyses
was 3803. Vital status was unknown for 241 of the
3803 (6%) cohort members (suggesting moderate
loss to follow up). The subgroup evaluated in
(Elliott et al.. 2012. 1247861) consisted of 3082
subjects (excluded persons who worked <30 days);
the proportion for whom vital status was missing
was not reported for the subgroup.
Medium
2
0.400
0.800
Page 46 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the North Carolina cohort of textile workers. A
full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
3. Comparison Group
There is potential for selection bias. All plants were
subject to surveillance program that removed
workers from exposure if they developed x-ray
changes attributable to dust exposure (typical
change was pneumoconiosis). Study authors
reported that some x-ray changes are associated
with higher lung cancer risk. Thus, the surveillance
program could have selected workers at greater risk
of lung cancer for lower cumulative exposure
((Loomis et al.. 2009. 3079232s) a 542. and (Elliott
etal.,2012. 1247861) m 388.
Medium
2
0.200
0.400
a
#o
"s
N
¦e
si
-fl
U
B
4. Measurement of Exposure
Air samples were available for 3 plants covering
period from 1935 to 1986 (459 <1950; 1674 from
1950-1969. and 1287 from 1970 forward: (Loomis
et al.. 2009. 3079232). v. 536). Measurements used
impinger before 1964 and PCM thereafter; paired
and concurrent samples between 1964 and 1971
were used to relate impinger to PCM-equivalent
concentrations. Air samples were not collected
yearly, so mean PCM-equivalent concentrations
were estimated by plant, department, job, and time
oeriod usins multivariate mixed models ((Loomis et
al.. 2009. 3079232). a 536). Individual cumulative
exposure assessed using the modeled concentrations
and JEM ((Loomis et al.. 2009. 3079232). d 536);
details of JEM reported in (Dement et al.. 2008.
626406).
High
1
0.400
0.400
£
O
o.
UJ
5. Exposure
levels
Exposure-response relationships were developed
(see Table 5 of (Loomis et al.. 2009. 3079232) and
(Elliott et al.. 2012. 1247861) see Table 2). A total
of 5 cumulative exposure levels are analyzed in
Table 5 of (Loomis et al.. 2009. 3079232).
Medium
2
0.200
0.400
6. Temporality
Temporality was established (exposure preceded
death). The follow-up time was at least 30 years
(1973-2003); lag times of 0, 10, 20, and 30 years
were analyzed ((Loomis et al.. 2009. 3079232)
Table 5 and (Elliott et al.. 2012. 1247861) see Table
2).
High
1
0.400
0.400
Outcome Assessment
7. Outcome
measurement or
characterization
Lung cancer deaths (underlying or immediate cause
or other significant condition at time of death) were
determined from the National Death Index Plus
(1979 and later) or state records (before 1979).
Specific ICD codes were not reported, but ICD in
effect at time of death was used ((Loomis et al..
2009. 3079232). o 536). Deaths before 1979 were
coded manually by a nosologist.
Medium
2
0.667
1.333
Page 47 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the North Carolina cohort of textile workers. A
full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
8. Reporting Bias
Lung cancer findings are reported in abstract,
results, and discussion of kev publications ((Loomis
et al.. 2009. 3079232) and (Elliott et al.. 2012.
1247861)). Lune cancer deaths and oerson-vears at
risk by exposure category are reported in Table 5 of
(Loomis et al.. 2009. 3079232s); luns cancer cases
and person-years at risk are reported by plant in
Table 1 of ffilliott et al.. 2012. 1247861s). Rate ratio
estimates are reported with CIs in (Loomis et al..
2009. 3079232s) and (Elliott et al.. 2012. 1247861s);
coefficients for Poisson regression are reported
without SE in Table 2 of ffilliott et al.. 2012.
1247861s). but rate ratios with CIs are also reported
for the same models.
High
i
0.333
0.333
Potential Confounding/Variable Control
9. Covariate Adjustment
Analyses in (Loomis et al.. 2009. 3079232s) and
ffilliott et al.. 2012. 1247861s) were adiusted for ase.
sex, race, decade of follow-up and birth cohort. No
adjustment was made for smoking, which could bias
SMR analyses (reported in (Loomis et al.. 2009.
3079232s)s) but is not likely to bias internal analysis
in an occupational cohort (e.g., exposure-response
analyses in (Loomis et al.. 2009. 3079232s) and
ffilliott et al.. 2012. 1247861s).
Medium
2
0.500
1.000
10. Covariate
Characterization
While not specified, information on covariates
included in the analyses were likely obtained from
same sources as vital status/cause of death. Subjects
with missing hire or birth date were excluded
((Loomis et al.. 2009. 3079232s). o 539s). Smokins
information was available for <15% of the cohort.
Medium
2
0.250
0.500
11. Co-exposure
Confounding
One plant used a limited amount of amosite between
1963 and 1976 ((Loomis etal.. 2009. 3079232s). v.
536). Adjustment for this coexposure was not
possible because none of the lung cancer deaths
were among workers involved in activities using
amosite ((Loomis et al.. 2009. 3079232s). p. 539s)
Medium
2
0.250
0.500
Analysis
12. Study
Design and
Methods
Study design was retrospective cohort; Poisson
regression used for internal analyses in (Loomis et
al.. 2009. 3079232s) (a 537s) and ffilliott et al.. 2012.
1247861s) (p. 386s).
Medium
2
0.400
0.800
Page 48 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the North Carolina cohort of textile workers. A
full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
13. Statistical power
None of the related studies report power
calculations. Authors ((Loomis et al.. 2009.
3079232s). v. 541s) cite larse size of cohort (3803
who worked for at least 1 day in plants with
exoosure data lYLoomis et al.. 2009. 3079232)1;
3082 who worked at least 30 days in plants with
exoosure data (Elliott et al.. 2012. 1247861'). hieh
proportion of subjects with vital status ascertained,
and long follow-up (30+ yrs; total 124,029 person-
vears workins at least 1 dav lYLoomis et al.. 2009.
3079232)1; 100742 Dcrson-vears workins at least 30
davs (Elliott et al.. 2012. 1247861) as strengths.
Medium
2
0.200
0.400
14. Reproducibility of analyses
Analysis description in (Loomis et al.. 2009.
3079232) aooears to be complete. Statistical tests
and estimation procedures and variables considered
are reported ((Loomis et al.. 2009. 3079232) o 537-
538 and supplemental file); cumulative exposure
categories for internal analysis define quantiles of
exposure among cases (footnote to Table 5 in
(Loomis et al.. 2009. 3079232)). There were no
variable transformations, outlier exclusions, or
imputation of missing values. Analysis description
in (Elliott et al.. 2012. 1247861) aooears to be
complete. Statistical tests and estimation
procedures and variables considered are reported
(Elliott et al.. 2012) us 386. Cumulative exoosure
was analyzed as a continuous variable (Elliott et al..
2012. 1247861) us 386. No variable transformations
were reported.
Medium
2
0.200
0.400
15. Statistical Models
Statistical models and methods are described in each
Diiblication (see (Loomis et al.. 2009. 3079232) o
537-538 and (Elliott et al.. 2012. 1247861) v> 386).
including how variables were included or excluded;
siiDDlcmcntal file to Loomis et al. (2009. 3079232)
provides details of SMR computation when race
was unknown and further explanation of the Poisson
cxDOSiirc-rcsDonsc models. For (Elliott et al.. 2012.
1247861). covariates were assessed as confounders
using a 10% change in estimate method and as
effect measure modifiers using likelihood ratio test.
Medium
2
0.200
0.400
Sum of scores:
5
8.4666
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Overall Score = Sum of Weighted Scores/Sum of Metric
Weighting Factors:
1.6933
Overall
Score:
Nearest
tenth:
1.7
Page 49 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the North Carolina cohort of textile workers. A
full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
Overall Quality Level:
Medium
Study
Quality
Comment:
The reviewer agreed with this study's overall quality level.
Page 50 of 80
-------
2.2.5. Epidemiology evaluation results of the Salonit Anhovo,
Slovenia cohort studies on asbestos exposure and lung cancer
incidence
Study
reference:
This cohort evaluation represents all publications pertaining to the Slovenian cohort of asbestos-cement workers.
A full list of related naners reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
a
#o
"s
.2-
1. Participant selection
This study included 58 histologically confirmed
incident lung cancer cases from the national cancer
registrar and 290 matched controls from a cohort of
6714 workers employed at Salonit Anhovo factory
after Dec 31 1946 who worked there for at least one
day between 1964 and 1994 (pg. 263-264). DOB,
gender, and year of hire (pre-1959 or post-1959,
based on better quality of exposure data after 1959)
were used as matching factors. Five controls closest
to the birth date were selected and had to be alive at
time of diagnosis (using national mortality registrar)
(pg. 263). The follow-up begins at 1964 because the
cancer registrar data were only available in a
computerized form from 1964 onward (registry
established in 1957) (pg. 263).
High
i
0.400
0.400
t:
es
&
¦o
5
Tfl
2. Attrition
Initial study pop was 67 cases of lung cancer, 335
controls (5 controls/case) were selected based on
original. Nine cases were excluded because they
were hired prior to 1947 (a priori date cut-off;
factory was owned by Italians from 1921-1947 and
the Slovenian republic from 1947 onward), so those
45 matched controls were also excluded. This left
58 cases and 290 matched controls, (pg. 264)
Retention of 87% (58/67 cases) was characterized as
moderate subject exclusion.
Medium
2
0.400
0.800
3. Comparison
Group
Cases and controls were selected from the same
occupational cohort. Matched based on DOB,
gender, and year of hire (pre- or post-1959), (pg.
263) Controls were confirmed alive at age of
diagnosis for case. (pg. 263) Other demographics
were also similar (see Table 1, pg 264).
High
1
0.200
0.200
Page 51 of 80
-------
Study
reference:
This cohort evaluation represents all publications pertaining to the Slovenian cohort of asbestos-cement workers.
A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
4. Measurement of Exposure
A total of 1030 air measurements from factory were
available from 1961-1995 using several different
monitoring methods, including a set of 78 paired
measurements using side-by-side gravimetric and
membrane filter methods. An early publication on
this cohort bv Dodic Fikfak (2003.3080279) (vs.
171) indicates that gravimetric is a mass based
method (units of mg/m3) and the membrane filter
method is a fiber counting method (units of f/cm3).
Microscopy analysis was not described; therefore
TEM and PCM methods were likely not used.
Exposure Characterization
The non-parametric classification and regression
tree (CART) method was used to calculate
conversion factors for different combinations of
fiber type, product, and production method.
Exposure levels were measured at fixed locations
close to worker's breathing zones. Exposures were
estimated for missing years using previous or next
values (or average of both). Exposures for most
workers were based on measured exposure values in
work area. A few jobs did not have applicable air
sample measurements, and exposures were
estimated with JEM. The percentage of individuals
in the JEM group were not reported; however, study
authors state that subjects from this group were not
selected for the study, (pg. 263)
Low
3
0.400
1.200
5.
Exposur
e levels
Evaluated as dichotomous exposure definitions:
exposed/unexposed, above/below median, and
above/below 90th percentile, (pg. 263-264)
Low
3
0.200
0.600
6. Temporality
Average latency between start of employment and
diagnosis in cases was 24.9 years (pg. 264). Study
authors conducted evaluations with different latency
periods (0-15 yrs, 16-35 yrs, and >35 yrs) (pg. 263).
The primary analysis is exposure >15 years prior to
diagnosis (Table 4, pg. 266).
High
1
0.400
0.400
Outc
ome
Asse
ssme
7.
Outc
ome
meas
All cases were histologically confirmed incident
cases of primary lung cancer (pg. 263).
High
1
0.667
0.667
Page 52 of 80
-------
Study
reference:
This cohort evaluation represents all publications pertaining to the Slovenian cohort of asbestos-cement workers.
A full list of related naners reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
8. Reporting Bias
The primary analysis is limited to cases (and
matched controls) with exposure >15 years prior to
diagnosis of case (Table 4, pg. 266). The study does
not report the number of cases and controls exposed
for >15 years only. Additionally, exposure estimates
are for all years, 0-15 yr, 16-35 yr, and >35 yrs (data
are very limited for >35), separated by case and
control (Table 3, pg. 266). Based on data reporting,
it is not clear exactly which exposure-cutoff values
were used for median and 90th percentile analyses.
Medium
2
0.333
0.667
B
C
O
9. Covariate Adjustment
Matching variables of birth and gender were
included in models as covariates. The matching
factor of pre vs. post 1959 hire was also evaluated
as a potential covariate. However, a comparison of
analyses did not show evidence that pre/post 1959
hire introduced confounding, so this covariate was
not maintained in the primary analysis, (pg. 263).
Separate analyses were calculated for smokers and
non-smokers, but non-smoking population was very
small (pg. 263, 265). Logistic regression models
were adjusted for smoking (yes/no) (pg. 264). No
further covariate assessment/adjustments made
(except co-exposure, addressed in Metric 11).
Medium
2
0.500
1.000
U
3
es
10.
Cova
riate
Char
Covariates were empirical data obtained from
employment records (age, sex) (pg. 263).
High
1
0.250
0.250
•c
es
&
¦3
c
5
£
C
O
U
!§
c
• If
=3
%
Amphibole asbestos: Amphibole exposure made up
for 10% of the total asbestos exposure (pg. 261).
Detailed records allowed the estimation of separate
individual exposure histories for different forms (pg.
261). Methods indicate that models were adjusted
for confounders (pg. 263), but did not specifically
indicate whether or not final model was adjusted for
amphibole asbestos exposure.
o
a.
O
o
a
VI
0
&
-------
Study
reference:
This cohort evaluation represents all publications pertaining to the Slovenian cohort of asbestos-cement workers.
A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
12. Study Design and
Methods
Study was a case-control design. Models of
exposure and risk were adjusted for confounding
using unconditional or conditional multivariate
logistic regression (pg. 263). Matching variables
were included as covariates in unconditional models
(pg. 263). Primary evaluation used OR calculations
to determine risk from cumulative exposure
estimates using 15-year latency for main analysis
(Table 4, pg 266).
Medium
2
0.400
0.800
Analysis
13. Statistical
power
Low would be selected if it was an option. No
statistically significant findings were observed
(Table 4, pg 266); study authors attribute this to low
statistical power-confidence intervals. Low
statistical power was reported as a limitation of the
study by study authors (pg 266-267).
Medium
2
0.200
0.400
14.
Reproduci
bility of
analyses
Median and 90th percentile cutoffs were not
explicitly reported for chrysotile asbestos for >15 yr
latency analysis. Number of cases and controls
included in >15 yr latency analysis not reported.
Low
3
0.200
0.600
15.
Statistical
Models
Logistic regression models were constructed for
each of the following dichotomous exposure
definitions: ever/never, above/below median, and
above/below 90th percentile (pg. 263-264).
Medium
2
0.200
0.400
Sum of scores:
5
9.1334
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >-2.3 and <-3
Overall Score = Sum of Weighted Scores/Sum of Metric
Weighting Factors:
1.8267
Overall
Score:
Nearest
tenth:
1.8
Overall Quality Level:
Medium
Study
Quality
Comment:
The reviewer agreed with this study's overall quality level.
Page 54 of 80
-------
2.2.6. Epidemiology evaluation results of the Quebec, Canada
cohort studies on asbestos exposure and lung cancer incidence
Study
reference:
This evaluation represents all identified publications pertaining to the Quebec, Canada cohort of miners. A full list
of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
a
#o
"s
1. Participant selection
Some details of the setting (e.g., the mine locations
and production quantities, but no description of the
facilities and exposure conditions) are provided in
(Liddell et al.. 1997. 3081408-) (o 14): additional
information mav be available in Gibbs and
Lachance (1972. 3580825) (cited as the source of
the exposure assessment), but no pdf was available
in HERO at the time of evaluation. Participant
selection, inclusion/exclusion criteria, case
ascertainment, and participation at each level are
described in detail ((Liddell et al.. 1997. 3081408).
p 14-16). Selection into the cohort was based on a)
male sex; b) birth year between 1890 and 1920; b)
employment at the Thetford Mines or Asbestos
mine/mill or factory for at least one month.
Participant selection and participation were not
likely to be biased based on these criteria.
High
i
0.400
0.400
o.
'3
"H
es
a.
¦a
5
Tfl
2. Attrition
Numbers of subjects lost to follow up are reported
in (Liddell et al.. 1997. 3081408). Table 4; there it is
reported that a total of 1138/10918 (-10%) were
lost to follow-up. No information comparing the
demographics or exposure of those lost to follow up
to the study subjects was located in the six selected
HERO IDs. Missing data were not imputed;
however, censoring of survival data is unlikely to
introduce bias. This level of attrition is considered
to be moderate.
Medium
2
0.400
0.800
3. Comparison Group
Internal analysis was reported only in the nested
case-control studv in Liddell et al. (1998. 3081200)
(ORs in Table 4). Most of the publications (see
(Liddell et al.. 1997.. 3081408) d 18; Liddell and
Armstrong (2002. 3080504) d 9) reported SMR
analyses using age- sex- and calendar year (5 year
intervals) -adjusted general population (Quebec
when available, or Canada for earlier time periods)
mortality rates as the comparison group. No
adjustment for race was made.
Medium
2
0.200
0.400
Exposure
Character
ization
4.
Measurem
ent of
Exposure
Exposure levels measured exclusively using midget
immnser ((Liddell et al.. 1997. 3081408). d 17) and
conversion factors were not determined (based on
review of the six selected HERO IDs).
Low
3
0.400
1.200
Page 55 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Quebec, Canada cohort of miners. A full list
of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
5. Exposure levels
Cumulative exposure-response relationships were
developed (see for example Table 8 of (Liddcll et
al.. 1997. 3081408)). A total of 7 cumulative
exposure levels (exposure through age 55) are
reported in Table 8 of (Liddcll et al.. 1997.
3081408); inLiddell and Armstrong (2002.
3080504). 10 exposure levels are reported in Table
5.
Medium
2
0.200
0.400
6. Temporality
Temporality was established (exposure preceded
death), and there was adequate follow-up for
consideration of latency. Of the total cohort of
10918 men, 6415 were still employed when the
cohort was first established in 1966, and follow up
extended to 1992 ((Liddell et al.. 1997. 3081408) d
15). Entry into the cohort was restricted to men born
between 1891 and 1920 ((Liddell et al.. 1997.
3081408) v 15). so the vounsest subiects at the end
of follow up were 72 years old. There was no
indication in the studies reviewed that the operations
at Thetford or Asbestos had ceased at any point
during the follow up time.
High
1
0.400
0.400
C
S
5«
5«
5«
<
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Quebec, Canada cohort of miners. A full list
of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
10. Covariate Characterization
Information on sex and birth date or age at first
employment were recorded from personnel records
in 1966 and reviewed and/or corrected during
subseauent analyses ((Liddell et al.. 1997.
13081408s) o 14-15). No information on race of
cohort members was located in any of the 8 selected
HERO IDs. A questionnaire was administered in
1970 to obtain smoking histories; subjects still
living completed the questionnaires (99.6% of 6583
men alive completed their own questionnaires), and
proxies provided the information for deceased
subjects (for 90% of those who died after 1950;
(Liddell et al.. 1997. 13081408) u 18). Each subiect
was assigned to the smoking category in which his
response placed him at the time of the questionnaire
((Liddell et al.. 1997. 13081408) o 18). A total of
891 questionnaires, mostly completed by proxies,
were judged unreliable and the subjects omitted
from analyses that considered smokins ((Liddell
and Armstrong. 2002. 3080504) d 7). While the
methods to assess potential confounders were not
validated, there is little indication that the methods
had poor validity.
Medium
2
0.250
0.500
11. Co-exposure Confounding
Liddell et al. (1997. 13081408) (o 33) reports that
analysis of fibers in the lungs of workers in the
Quebec industry showed higher levels of tremolite
fibers than chrysotile fibers, especially at the
Thetford mines. On d 34. Liddell et al. (1997.
13081408) states that the chrvsotile produced in
Quebec may be contaminated not only with
tremolite but with other amohibole fibers. Liddell
and Armstrong (2002. 3080504) (o 8) rcoorts that
the Thetford mines complex had "more substantial"
tremolite contamination than the mine and mill at
Asbestos, and suggests that it is therefore desirable
to analyze the sites separately. None of the 8
selected HERO IDs provided quantitative estimation
of the degree of contamination. Thus, there is no
information to indicate how the co-exposure may
have been distributed across cohort members and/or
its relationship to chrysotile exposure. It is possible
that additional information is available in Gibbs and
Lachance (1972. 3580825). which is cited as the
source of the JEM and exposure assessment, but no
pdf was available in HERO at the time of
evaluation.
Low
3
0.250
0.750
Page 57 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Quebec, Canada cohort of miners. A full list
of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
12. Study
Design and
Methods
Study design was retrospective cohort. Poisson
regression used in some analyses (Liddell and
Armstrong (2002. 3080504) d. 8) but not others.
Liddell et al. (1998. 3081200) reported a nested
case-control study within the cohort and used
conditional logistic regression
Medium
2
0.400
0.800
13. Statistical power
Power calculations were not reported. The number
of participants was sufficient to detect an effect
(statistically significant association reported in
Vacek (1998. 3081118"»"». However, manv of the
studies did not report statistical significance or
confidence intervals for calculated SMRs (see for
example Tables 8 and 10 of Liddell et al. (1997.
3081408V).
Medium
2
0.200
0.400
Analysis
14. Reproducibility of analyses
The analysis description varied by study. This
metric is rated based exclusively on the description
in Liddell et al. (1997. 3081408). which is based on
the combined longest follow up and largest
population. The effect estimation methods in this
paper were reported (p. 18-19), but the rules for
cumulative exposure categorization (as shown in
Tables 7 and 8) were not reported. There were no
variable transformations or outlier exclusions, and
no true statistical analyses (CIs were not reported
for the SMRs).
Low
3
0.200
0.600
15. Statistical Models
Liddell et al. (1997. 3081408) did not include anv
statistical models per se (effect estimates calculated
as SMRs = O/E without CIs). Liddell et al. (1998.
3081200) rcDortcd a nested case-control studv
within the cohort and used conditional logistic
regression. 90% Confidence intervals were
estimated from the regression on the assumption
that the regression coefficients are normally
distributed; no information on whether assumptions
were met was orovided. Liddell and Armstrong
(2002. 3080504) provided detailed description of
statistical models (p 8-9) but did not describe model
assumptions or whether they were met.
Low
3
0.200
0.600
Sum of scores:
5
9.5834
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >-2.3 and <-3
Overall Score = Sum of Weighted Scores/Sum of Metric
Weighting Factors:
NA
Overall
Score:
Nearest
tenth:
NA
Overall Quality Level:
Low
Page 58 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Quebec, Canada cohort of miners. A full list
of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
Study
Quality
Comment:
This study's overall quality rating was downgraded during conflict resolution between primary review and QA/QC
review. Downgrading was due to lack of PCM or TEM-equivalent exposure estimates and potentially significant co-
exposure to tremolite or other amphiboles. Note: The original calculated score for this study was 1.9.
This value is not presented above because the final rating was changed based on professional judgement.
Page 59 of 80
-------
2.2.7. Epidemiology evaluation results of the Chongqing, China
textile worker cohort studies on asbestos exposure and lung
cancer incidence
Study
reference:
This evaluation represents all identified publications pertaining to the Chongqing, China cohort of textile workers.
A full list of related papers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
1. Participant selection
The key elements of the study design are reported.
The fixed cohort is well-established. The inclusion
criteria were clearly specified (male workers
registered with the plant by January 1 1972,
employed for at least one \ car: Dens et al. (2012.
2573093s) v. 82 and Courtice et al. (2016. 3520560)
p. 370). Workers with cardiopulmonary disease, or
those employed after January 1 1972 were excluded.
The reported information indicates that selection
into/out of the study was not likely biased.
High
i
0.400
0.400
a
#o
"s
o.
'3
"H
es
Q*
2. Attrition
There was minimal loss of subjects at follow-up.
The 2016 study (conducted 37 years after
establishment of the cohort) reported that 577 of
586 workers (99%) were successfully followed
throueh 2008 (Courtice et al. (2016. 3520560) a
370). Therefore, exposure and outcome data were
largely complete.
High
i
0.400
0.400
¦o
5
Tfl
3. Comparison Group
Inclusion criteria and the methods of participant
selection were reported. All subjects were recruited
from the same eligible population within the same
time frame. In the Wang et al. 2012 study reporting
SMRs rand RRs: (Wane et al.. 2014. 2538846) d.
121), the choice of a reference population is
reported (based on age-specific national mortality
data for males). However, data on cause-specific
mortality data were limited (rates of 1990 and 2004
were used to correspond to periods of 1981-1995
and 1996-2006. respectively. The Courtice et al.
(2016. 3520560) (v. 375) used the lowest
continuous cumulative exposure category (i.e.,
members of the same cohort in the lowest exposure
quartile) as the reference group.
High
i
0.200
0.200
Page 60 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Chongqing, China cohort of textile workers.
A full list of related papers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
C
#o
"s
N
¦e
t5
es
~-
es
-fl
U
5
O
o.
O
Oh
X
W
c
52
cd
Asbestos dust measurements were available starting
in 1955 (Courtice et al. (2016. 35205601 p.371.
Deng et al. (2012. 25730931 p. 82). Starting in 1999,
samples were also analyzed by phase contrast and/or
electron scanning microscopy (Courtice et al. (2016.
3520560} p. 371. Deng et al. (2012. 25730931 p.
82). Paired gravimetric and membrane filter samples
from 1999 and 2002 ( Courtice et al. (2016.
3520560) p. 371. (Wang et al.. 2014. 2538846) p.
120) or from 1999, 2002, and 2006 (Deng et al.
(2012. 2573093) p. 82) were used to define the
relationship between dust and fiber concentrations.
From these data, (and using periodically measured
data), average fiber concentrations by job
type/exposure area were calculated. Studies for this
cohort ((Wang et al.. 2014. 2538846) p. 120 and
Deng et al. (2012. 2573093) p. 82) indicate that
conversion from dust to fiber concentrations
required log transformation of the paired samples
(the distribution of paired samples was positively
skewed). Individual cumulative exposures were
estimated as the product of (fiber concentration at a
specific workshop/job) x (duration of job) (Courtice
et al. (2016. 3520560) p.371. Deng et al. (2012.
2573093) p. 82). There were no exposure data prior
to 1955; exposure was assumed to be the same as
the earliest time measurement in 1955 (Courtice et
al. (2016. 3520560) p. 371). There was also no
samples for administration or rear service workers;
these groups were assumed to belong in the lowest
cumulative exposure group (Courtice et al. (2016.
3520560) p. 371). The lack of detailed exposure
information and the use of recent (since 1999)
samples to convert to historical measurements since
1955 are limitations of the study (Courtice et al.
(2016. 3520560) p. 375-376). In addition, workers
may have been additionally exposed to chrysotile at
home (from spinning; Courtice et al. (2016.
3520560) p. 376). The study authors acknowledge
that there may have been exposure misclassification
based on these estimations, but the misclassification
was likely to be non-differential.
Medium
0.400
0.800
Page 61 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Chongqing, China cohort of textile workers.
A full list of related papers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
5. Exposure levels
The range and distribution of exposure is sufficient
to develop and exposure-response estimate. The
Courtice et al. 2016 studv (Courtice et al. (2016.
3520560) v. 375) reoorts 4 levels of cxoosurc
(referent + 3); cumulative exposures were
categorized into quartiles for analyses of lung
cancer deaths.
Medium
2
0.200
0.400
6. Temporality
The study establishes appropriate temporality; the
interval between exposure and outcome is long
enough considering latency of the disease. The
cohort was followed for 35 vears (Dens et al. (2012.
2573093s) d. 811. 26 vears ((Wans et al.. 2014.
25388461 a 1191 and 37 vears ( Courtice et al.
(2016. 35205601 d. 3701. The studv bv Dene et al.
2012 (Dens et al. (2012. 25730931 v. 831
incorporated lag periods of 5 or 10 years into the
models. The Courtice et al. 2016 studv (Courtice et
al. (2016. 35205601 a 3711 also used exposure
lagged by 10 years to account for effects of disease
latency. The cohort experienced an average of 41
vears since initial c\ do sure (Courtice et al. (2016.
35205601 p. 3761.
High
1
0.400
0.400
C
S
5«
5«
5«
«<
i
7. Outcome measurement or
characterization
The Wans et al. 2014 Dublication ((Wans et al..
2014. 25388461 a 1201. does not reoort ICD codes
corresponding to lung cancer. However, the studies
bv Dens et al. 2012 (Dens et al. (2012. 25730931 v.
821 and Courtice et al. 2016 (Courtice et al. (2016.
35205601 v. 3701 clearlv identify luns cancers
included for analyses by ICD code (ICD-10
C33/C34). About half of the cancer cases were
verified pathologically (biopsy or autopsy); others
were diagnosed by CT scan and clinical
manifestations (Courtice et al. (2016. 35205601 o.
370).
High
1
0.667
0.667
O
(J
5
O
8. Reporting Bias
Lung cancer findings are reported in the results. In
the Wans et al. 2012 studv ((Wans et al.. 2012.
2572504) v. 122). SMRs and hazard ratio data (with
95% confidence intervals) were complete. The
Courtice et al. 2016 studv (Courtice et al. (2016.
3520560) v. 375) provides hazard ratios and 95%
confidence intervals for lung cancer mortality using
cumulative exposure categorized into 4 groups (as a
continuous variable).
High
1
0.333
0.333
Page 62 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Chongqing, China cohort of textile workers.
A full list of related papers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
=3
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Chongqing, China cohort of textile workers.
A full list of related papers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
12. Study Design and Methods
The study design (cohort) was appropriate to
address the research question. In the Deng et al.
2012 studv (Dene et al. <7012. 2573093-) a 81).
Poisson regression analyses was used to fit models
(log-linear, log-quadratic, power, additive relative
risk and categorical) to estimate relationships
between cumulative exposure and mortality from
luns cancer. The Wans et al. 2012 studv ((Wans et
al.. 2012. 2572504) a 407) used Cox orooortional
hazard models to obtain hazard ratios for lung
cancer mortality in relation to cumulative asbestos
exposure. The studv bv (Courtice et al. (2016.
3520560) v. 371) estimated cxDOSiirc-rcsDonsc
relationships using Cox proportional hazard models.
Medium
2
0.400
0.800
&
*5«
13. Statistical
power
The number of participants (cohort size = 577
workers) was sufficiently large to detect an effect in
the exposed population. However, it was noted that
there was a relatively small number of nonsmokers
in the cohort (Dens et al. (2012. 2573093) p. 86).
Medium
2
0.200
0.400
13
c
<
14. Reproducibility of
analyses
The methods used to estimate exposures were not
described in a way that would facilitate
reproducibility; a process "similar" to those in other
studies was cited (Courtice et al. (2016. 3520560) o.
371) or a strins of references was provided ((Wans
et al.. 2014. 2538846) a 120) for dust to fiber
concentration conversions. In general, the statistical
analyses used were described, including variables
used in the analyses.
Medium
2
0.200
0.400
15. Statistical Models
The data analysis section of the Deng et al. paper
(Dens et al. (2012. 2573093) v>. 83) describes the
analyses used in detail (including calculations,
model considerations, variables). The methods used
to calculate risk estimates (HRs) in Wang et al.
2014 were adeauatelv described ((Wans et al..
2014. 2538846) v. 121). In the Courtice et al. 2016
studv (Courtice et al. (2016. 3520560) v. 371). the
methods used to generate HRs were briefly
described (i.e. age included as a time dimension for
Cox proportional hazard modeling).
Medium
2
0.200
0.400
Sum of scores:
5
6.85
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >=2.3 and <=3
Overall Score = Sum of Weighted Scores/Sum of Metric
Weighting Factors:
1.37
Overall
Score:
Nearest
tenth:
1.4
Page 64 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Chongqing, China cohort of textile workers.
A full list of related papers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
Overall Quality Level:
High
Study
Quality
Comment:
The reviewer agreed with this study's overall quality level.
3. Data Quality Evaluation of Mesothelioma Data Sources
3.1. Data Evaluation Scoring Sheets: Mesothelioma Outcome
3.1.1. Epidemiology evaluation results of the Quebec, Canada
cohort studies on asbestos exposure and mesothelioma
incidence
Study
This evaluation represents all identified publications pertaining to the Quebec, Canada cohort of miners. A full list
reference:
of related papers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
Some details of the setting (e.g., the mine locations
and production quantities, but no description of the
facilities and exposure conditions) are provided in
Liddell et al. <1997. 3081408-) (o 14): additional
information mav be available in Gibbs and
o
O
Lachance (1972. 3580825) (cited as the source of
"S
the exposure assessment), but no pdf was available
"3
in HERO at the time of evaluation. Participant
r
u
selection, inclusion/exclusion criteria, case
High
1
0.500
0.500
a.
Oh
o
ascertainment, and participation at each level are
¦a
described in detail ((Liddell et al.. 1997. 3081408).
s
Tfl
Ph
p 14-16). Selection into the cohort was based on a)
male sex; b) birth year between 1890 and 1920; b)
employment at the Thetford Mines or Asbestos
mine/mill or factory for at least one month.
Participant selection and participation were not
likely to be biased based on these criteria.
Page 65 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Quebec, Canada cohort of miners. A full list
of related naners reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
2. Attrition
Numbers of subjects lost to follow up are reported
inLiddell et al. (1997. 3081408). Table 4; there it is
reported that a total of 1138/10918 (-10%) were
lost to follow-up. No information comparing the
demographics or exposure of those lost to follow up
to the study subjects was located in the eight
selected HERO IDs. Missing data were not imputed;
however, censoring of survival data is unlikely to
introduce bias. This level of attrition is considered
to be moderate.
Medium
2
0.500
1.000
3. Comparison
Group
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
4. Measurement of
Exposure
Exposure levels measured exclusively using midget
impineer (Liddell et al. (1997. 3081408). p 17) and
conversion factors were not determined (based on
review of the eisht selected HERO IDs). In (Berman
and Catnip. 2008. 626405). a sinsle conversion
factor is applied to all operation for estimation of
equivalent exposure concentrations.
Medium
2
0.400
0.800
a
"c5
.a
~-
(J
si
~-
si
-fl
5. Exposure levels
Cumulative exposure-response relationships were
developed (see for example Table 9 of Liddell et al.
(1997. 3081408)). A total of 6 cumulative exposure
levels (exposure through age 55) are reported in
Table 9 of Liddell et al. (1997. 3081408). (Berman
and CrumD. 2008. 626405) reports Km estimate for
mesothelioma exposure-response.
Medium
2
0.200
0.400
U
B
£
o
o.
UJ
6. Temporality
Temporality was established (exposure preceded
death), and there was adequate follow-up for
consideration of latency. Of the total cohort of
10918 men, 6415 were still employed when the
cohort was first established in 1966, and follow up
extended to 1992 (Liddell et al. (1997. 3081408) p
15). Entry into the cohort was restricted to men born
between 1891 and 1920 (Liddell et al. (1997.
3081408) p 15). so the vounsest subiects at the end
of follow up were 72 years old. There was no
indication in the studies reviewed that the operations
at Thetford or Asbestos had ceased at any point
during the follow up time.
High
1
0.400
0.400
Page 66 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Quebec, Canada cohort of miners. A full list
of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
Outcome Assessment
7. Outcome
measurement or
characterization
Mesothelioma cases post-1966 were identified via
examination of "all related clinical, biopsy, and
nccroDSY records" (Liddcll et al. (1997. 3081408) o
16).
High
i
0.667
0.667
8. Reporting
Bias
Rate estimates by exposure level are reported
without CI estimates (e.g.. Table 9 in Liddell et al.
(1997. 3081408)). (Berman and Crumo. 2008.
626405) reoorts Km estimate for mesothelioma
exposure-response data.
Medium
2
0.333
0.667
Potential Confounding/Variable Control
9. Covariate
Adjustment
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
10. Covariate
Characterization
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
11. Co-exposure
Confounding
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
Analysis
12. Study
Design and
Methods
Study design was retrospective cohort. Poisson
regression used in some analvses (Liddell and
Armstrong (2002. 3080504) d. 8) but not others.
AoDroDriatc statistical method was used in (Berman
and Crumo. 2008. 626405)
Medium
2
1.000
2.000
13. Statistical
power
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
Page 67 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the Quebec, Canada cohort of miners. A full list
of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
14.
Reproducibility
of analyses
(Bcrman and CruiriD. 2008. 626405s) reports Km
estimate for mesothelioma exposure-response.
Not Rated
NA
NA
NA
15. Statistical
Models
(Bcrman and CruiriD. 2008. 626405s) rcoorts Km
estimate for mesothelioma exposure-response.
Not Rated
NA
NA
NA
High: >=1 and <1.7
Medium: >=1.7 and
<2.3
Low: >=2.3 and <=3
Sum of scores:
4
6.4334
Overall Score = Sum of Weighted Scores/Sum of Metric
Weighting Factors:
NA
Overall
Score:
Nearest
tenth:
NA
Overall Quality Level:
Medium
Study
Quality
Comment:
This study's overall quality was downgraded during conflict resolution between primary review and QA/QC review.
Downgrading due to lack of PCM or TEM-equivalent exposure estimates and potentially significant co-exposure to
tremolite or other amphiboles. Note: The original calculated score for this study was 1.9. This value is not presented
above because the final rating was changed based on professional judgement
Page 68 of 80
-------
3.1.2. Epidemiology evaluation results of the South Carolina, US
cohort studies on asbestos exposure and mesothelioma
incidence
Study
reference:
This cohort evaluation represents all identified publications pertaining to the South Carolina cohort of textile
workers. A full list of related papers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
C
"s
.5-
"3
r
es
&
¦O
5
Tfl
e
o
•-=3
O
O
•e
C3
Ph
a. Setting and methods of case ascertainment were
reported in (Dement et al.. 1983b. 671. p. 422 and
(Hein et al.. 2007. 7094981. pg 617. Participant
selection and inclusion/exclusion criteria varied by
study and analysis. The initial cohort consisted of
white men employed for at least one month in a
production job at the South Carolina plant between
1/1/1940 and 12/31/1965 ((Dement et al.. 1983b.
67) p 422). Subsequent analyses added non-white
men and/or women ((Stavner et al.. 1997. 30812411.
(Dement et al.. 1994. 30817661. (Brown etal.. 1994.
30818321. (Elliott et al.. 2012. 12478611. (Edwards
etal.. 2014. 30780611. (Cole et al.. 2013. 30782611.
(Hein et al.. 2007. 70949811. b. Selection in or out of
the study was based on 1) employment in
production job during designated time frame and 2)
availability of necessary data (birth and hire dates;
work history; vital status). These criteria are
unlikely to result in biased subject participation.
High
0.500
0.500
Page 69 of 80
-------
Study
reference:
This cohort evaluation represents all identified publications pertaining to the South Carolina cohort of textile
workers. A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
2. Attrition
Attrition/missing data exclusions were reported in
(SRC. 2019c. 5080236s). (Dement et al.. 1983b. 67)
(a 423 and Table 1) and (Hein et al.. 2007.709498).
see pg 618 and Table 1. The number of eligible
workers and number excluded due to incomplete
work histories was not reported in the sources
reviewed. ((Dement et al.. 1983b. 67) v 422) reoorts
that each worker was assigned a card at hire on
which was tracked the date of birth, sex, race, and
SSN, and job or department changes throughout the
career were recorded on the card; these were used in
the cohort establishment. The suggestion is that all
cohort members had complete work histories;
however. ((Hein et al.. 2007. 709498) us 624)
reported that the study was limited by incomplete
lifetime work histories. Vital status was unknown
for 2.1% of the original 1261 cohort members, and
cause of death was unknown for 5.5% of the deaths
in 1975. At the 2001 follow lid (Hem et al.. 2007.
7094981 vital status was unknown for 8.6% of the
larger cohort of 3072, and cause of death was
unknown for 3.9%. The latter paper cited high rate
of loss to follow-up as a limitation of the study.
Thus, loss to follow up is judged to be moderate,
and the lack of information on number eligible and
number with incomplete work histories leads to low
confidence.
Low
3
0.500
1.500
3. Comparison
Group
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
Exposure Characterization
4. Measurement of Exposure
(Dement et al.. 1983a. 66) describes the dlant
processes and the exposure estimation methods.
More than 6000 air samples obtained at the plant
from 1930 to 1975 were analyzed by PCM to yield
chrvsotile concentrations (fibers >5 um/mL) (Hein
et al.. 2007. 709498s). us 617. Exposure
concentrations were estimated by department, job,
and time period; individual cumulative exposure
assessed using the modeled concentrations and JEM
(methods outlined in (Dement et al.. 1983a. 66). In
2008, an updated JEM was developed to estimate
fiber size-specific exposure estimates (based on
TEM analysis of archived sainnles) in (Dement et
al.. 2008. 626406s).
High
1
0.400
0.400
Page 70 of 80
-------
Study
reference:
This cohort evaluation represents all identified publications pertaining to the South Carolina cohort of textile
workers. A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
5. Exposure
levels
(Bcrman and Cm hid. 2008. 626405s) reoorts Km
estimate for mesothelioma exposure-response data
obtained from the primary investigators for this
cohort.
Medium
2
0.200
0.400
6. Temporality
Temporality was established (exposure preceded
death). (Hem et al.. 2007. 709498s) d 618 reoorts
number of years between first employment and
death for one of the 3 mesothelioma cases (~50
years). The other two cases had been identified in an
earlier analvsis (Dement et al.. 1994. 3081766); that
paper reported latency periods of 37 and 34 years
for those cases.
High
1
0.400
0.400
Outcome Assessment
7. Outcome
measurement or
characterization
ICD-10 code C45 used to identify mesothelioma
cases after 1998; to identify earlier cases, death
certificates were reviewed for any mention of
mesothelioma ((Hein et al.. 2007. 709498) d 617).
High
1
0.667
0.667
8. Reporting
Bias
None of the publications reports exposure-response
information for mesothelioma: however (Berman
and Cmmd. 2008. 626405) reoorts Km estimate for
mesothelioma exposure-response data obtained
from the primary investigators for this cohort.
Low
3
0.333
1.000
Potential Confounding/Variable Control
9. Covariate
Adjustment
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
10. Covariate
Characterization
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
11. Co-exposure
Confounding
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
Page 71 of 80
-------
Study
reference:
This cohort evaluation represents all identified publications pertaining to the South Carolina cohort of textile
workers. A full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
12. Study
Design and
Methods
Studv desisn was retrospective cohort (Hcin et al..
2007. 709498s) and the aDDroDriatc statistical method
was used in (Bcrman and Cm mo. 2008. 626405').
Medium
2
1.000
2.000
&
*5«
13. Statistical
power
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
c
<
14.
Reproducibility
of analyses
(Bcrman and Cmmo. 2008. 626405s) reoorts Km
estimate for mesothelioma exposure-response data
obtained from the primary investigators for this
cohort.
Not Rated
NA
NA
NA
15. Statistical
Models
(Bcrman and Cmmo. 2008. 626405s) reoorts Km
estimate for mesothelioma exposure-response data
obtained from the primary investigators for this
cohort.
Not Rated
NA
NA
NA
Sum of scores:
4
6.8667
High: >=1 and <1.7
Medium: >=1.7 and <2.3
Low: >-2.3 and <-3
Overall Score = Sum of Weighted Scores/Sum of Metric
Weighting Factors:
1.7167
Overall
Score:
Nearest
tenth:
1.7
Overall Quality Level:
Medium
Study
Quality
Comment:
The reviewer agreed with this study's overall quality level.
Page 72 of 80
-------
3.1.3. Epidemiology evaluation results of the North Carolina, US
cohort studies on asbestos exposure and mesothelioma
incidence
Study
reference:
This evaluation represents all identified publications pertaining to the North Carolina cohort of textile workers. A
full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
Study Participation
1. Participant selection
a. Setting and methods of case ascertainment were
reported in (Loomis et al.. 2009. 3079232s). a 535-
536. Participant selection and inclusion/exclusion
criteria varied by study and analysis. Although there
were 4 plants in the cohort, exposure data were
available only for three of the four, so exposure-
response analyses were limited to these three plants.
Orieinal selection criteria rcDortcd in (Loomis et al..
2009. 3079232) d 536 (narticirants had to work at
least 1 day between 1950 and 1973) and p 539
(narticirants excluded due to missine data), (Elliott
etal.,2012. 1247861) evaluated a subset of the
cohort that worked >30 days during the same time
frame, b. Selection in or out of the study was based
on 1) employment in production job during
designated time frame and b) availability of
necessary data (birth and hire dates; work history;
vital status). These criteria are unlikely to result in
biased subject participation.
High
i
0.500
0.500
2. Attrition
Attrition/missing data exclusions were reported in
(YSRC. 2019a. 5080241) d. 1). ((Loomis et al..
2009. 3079232) v. 539) and (Elliott et al.. 2012.
1247861) vs. 386. The orieinal cohort was 5770
persons; 373 workers at plant 2 were excluded due
to lack of exposure data at this plant, 1596 were
excluded due to incomplete work histories (at
department level) or non-uroduction iobs ((Loomis
et al.. 2009. 3079232) a 539). Final cohort for
exposure-response analyses was 3803. Vital status
was unknown for 241 of the 3803 (6%) cohort
members (suggesting moderate loss to follow up).
The subaroiiD evaluated in (Elliott et al.. 2012.
1247861) consisted of 3082 subiects (excluded
persons who worked <30 days); the proportion for
whom vital status was missing was not reported for
the subgroup.
Medium
2
0.500
1.000
3. Comparison
Group
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
Page 73 of 80
-------
Study
This evaluation represents all identified publications pertaining to the North Carolina cohort of textile workers. A
reference:
full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
(SRC. 2019a. 5080241) reoorts air concentrations
and exposure duration by interval of TSFE. Air
samples were available for 3 plants covering period
from 1935 to 1986 (459 <1950; 1674 from 1950-
%
1969. and 1287 from 1970 forward: (Loomis et al..
in
O
2009. 3079232s). p. 536). Measurements used
X
W
impinger before 1964 and PCM thereafter; paired
and concurrent samples between 1964 and 1971
"H
were used to relate impinger to PCM-equivalent
Medium
2
0.400
0.800
§
concentrations. Air samples were not collected
a
a
yearly, so mean PCM-equivalent concentrations
exposure.
High rating applies to cases assessed with ICD10.
« 2 .2
For some analyses, the authors pooled these cases
s
I s
5 5«
6 fi
III
o « C
3 a £
with cases coded to cancer of the pleura in ICDs 6-
9, which is not considered a reliable measure of
High
1
0.667
0.667
a d
J? 0®
O
o 3 y
mesothelioma outcome. (SRC. 2019a. 5080241)
^ SI
S o
reports cases assessed with ICD10 by interval of
TSFE
Page 74 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the North Carolina cohort of textile workers. A
full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
8. Reporting Bias
(SRC. 2019a. 5080241) provides mesothelioma
cases and person-years at risk by interval of TSFE,
including separate reporting of those assessed by
ICD10. Mesothelioma cases (with detail of those
assessed by ICD10) reported by employment
duration in Table 4 of (Loomis et al.. 2009.
3079232s) (2 coded cases with 5-10 vears
employment and 1 coded case each with 10-20 and
20-30 years employment). SMR with CI reported in
Table 3 (Loomis et al.. 2009. 3079232). and in
(SRC. 2019a. 5080241). (Loomis et al.. 2009.
3079232) reoorts number in cohort, total PY of
follow-up, and median duration employment. In
(Elliott et al.. 2012. 1247861). Table 1 reoorts
cohort characteristics including age at entry, age at
first employment, person years at risk, cumulative
exposures, for the subset of workers who were
employed at least 30 days (by NC plant and for the
whole NC cohort).
High
i
0.333
0.333
Potential Confounding/Variable Control
9. Covariate
Adjustment
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
10. Covariate
Characterization
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
11. Co-exposure
Confounding
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
Analysis
12. Study
Design and
Methods
Study design was retrospective cohort and SMR
analvsis was oerformed. (Loomis et al.. 2009.
3079232)
Medium
2
1.000
2.000
Page 75 of 80
-------
Study
reference:
This evaluation represents all identified publications pertaining to the North Carolina cohort of textile workers. A
full list of related DaDers reviewed during this evaluation are listed in Table 2.1.
Domain
Metric
Comments
Qualitative
Determination
Metric Score
Metric
Weighting
Factor
Weighted
Score
13. Statistical
power
Not applicable for mesothelioma studies
Not Rated
NA
NA
NA
14.
Reproducibility
of analyses
(SRC. 2019a. 5080241) provides individual data
elements allowing independent analysis
Not Rated
NA
NA
NA
15. Statistical
Models
(SRC. 2019a. 5080241) provides individual data
elements allowing independent analysis
Not Rated
NA
NA
NA
High: >=1 and <1.7
Medium: >=1.7 and
<2.3
Low: >=2.3 and <=3
Sum of scores:
4
6.1
Overall Score = Sum of Weighted Scores/Sum of Metric
Weighting Factors:
1.525
Overall
Score:
Nearest
tenth:
1.5
Overall Quality Level:
High
Study
Quality
Comment:
The reviewer agreed with this study's overall quality level.
Page 76 of 80
-------
Asbestos
References
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