Document 3QjKOO9p1dyn7zQGozv1w8a0E
Status Report: CCIDP Exposure Assessment
Report Summary
Multiple lines of exposure assessment project work are progressing to assemble the supporting information for the qualitative and quantitative aspects of the study. The qualitative assessments are now progressing in pace with the subject accrual, for substances of concern, including benzene. The semi-quantitative and quantitative exposure assessment (EA) gOClls for benzene include more detailed data assembly, Clnd the time lines on these not unexpectedly lag accrual. Although lagging accrual, these are in control for completion when needed for detailed benzene EA in 032006. Details on the following aspects of the CCiDP EA project follow:
Study Goals Status (Fi~ll!re 1) Sludy desiSJil SLiilllilZhY \i~lgure 2) Overall timelirle (Fi:;JlJr8 3) rv1ain CC/DP EA Processes, respuilsilJliili<-:3 al1(~ l,i1ili;G (TL::Jle 1) Pilot test for the EA Matrix (Sector /\n=dys:s) Plan Forward The faculty members and graduClle students Zlssi<jil0J to the SH::, i~i'O;Xl':;, Zl~ well as the Fudan/JCML exposure Clssessrnent l83m members must be credilce] for the achievements to date, and for the successes continued work on the plan forward will assure.
Study Goals The exposure assessment strategy was originally developed for the disease progression (DP) study, but in 2H 2001 the Science Review Panel suggested that it also be applied to the CC study. A main goal of the DP study is to evaluate if the earlier disease states (e.g., benzene poisoning or aplastic anemia) are pre-requisites for subsequent development of benzene-related leukemia. The CC study has somewhat different goals, with a main aspect evaluating whether other study exposures or explanatory variClbles (e.g, viral status) 2re associated with certain diseClses (e.g., NHL) To this end, the benzene assessment is akin to a positive control by which em expected association of high level exposure with AML provides some verification of the overall exposure assessment integrity. Ordinal range assessments (no, low, medium, high exposure or with ranges such as <0.4, 0.4 to < 4,4 to 40 and> 40 mg/m3) as planned for in the protocol support these study goals.
Status Figure 1 provides a summary of the CC/OP subjects accrued, questionnaire
collection/data entry, and completion of the various EA stages. The goal for the benzene-exposed assessment progress is based on the prior to study start expected prevalence of 10% in the study subjects. Exposures other than benzene were assigned to 2631 subjects. Prevalence for the other exposures
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was not projected prior to study start. The progress continues to meet expectations of the lead team, given that developments in a few original expectations (as discussed below) required additional staffing and additional efforts for information to supplement the IPHS database.
Study Design Summary The SHS studies have several different designs and the exposure assessmelit approaches differ, with the Molecular Epidemiology stUdies designeei For extensive quantitative exposure data. The ME studies select factories for inclusion based on good records and participation in current personc:!I exposure monitoring. The protocol for the Disease Progression study anticipated significant difficulty in reaching the fully quantitative benzene assessments for the great diversity of the subjects' work histories. Thus, the protocol for the DP exposure assessment included:
Screening decision on ever/never e>:~r::sc:'l ~' h:'::-"';nr:;
Ordinal (no, low, mecJiuill , hUll ;,r ~l.; ::;.:r c;;'Js::! C
SLJojcc~s
RJngcs for- the benzene expc:=.2=! (=:!,.: ~~~ ~',,~ '''~ ~'J C'_1 ~~ .--: -1) : ~= 40 mg/m3) Quantitative by work history segri: ~I:: ~:'IC: pau,;iTl C; 2XpJ::;ur8 iur ~_._
Figure 2 illustrates the general process and decision Flow for the CC/DP EA. Figure 3 illustrates the stepwise exposure assessment information building process, where the details assembled at the lower tiers determine the feasibility of and approach for additional investigations to support the higher tier assessments. Additionally, the process involves developing qualitati'/8 Jnel quantitative exposure assessment skills in the broad study team as the work progresses.
The study subjects recruited as cases and controls from the participating hospitals come from diverse work experiences, ages, and locations around and remote from Shanghai. The upper level investigations, when they are feasible, require more time to complete. In recent discussion ';'lith SRP members on the exposure assessment, the ordinal range tier meets their maximum expectations of feasibility for the major fraction of the subjects in such a general population based case control study_ The next higher tier for quantitative benzene assessment remains a goal for a fraction of the subject, but the yield may be too low and may have too much potential for misclassification for the tier to assuredly provide data for meaningful analyses.
Overall Timeline See Figure 4. Note that the path for the quantitative benzene assessment becomes time critical around Q2 2006. This is the time when the investigation lines converge to a consistency check and assembly of the final CCIDP EA
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matrix. Following that assembly, the assignment of final benzene exposure will be completed in a few weeks of focused effort.
Main CCIDP EA Processes
The main stages of the CCIDP process, with responsibilities and progress dates are shown in Table 1. One currently open decision hinges on whether or not broad collaboration with JPHS on the database develops. Such access was part of the original study design and expectations. The alternative of relying on the currently available extracted portions of the database will impact (to a difficult to evaluate extent) the quantitative benzene assessments. However, the assembly of the EA matrix calls on information from several lines of investigation as shown in Figure 5.
Note that the EA processes include periodic reviews and recycles of the
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assessments are pr8Iimin;:;r'/ ull~:i :,:lJl iCi:;~ roview, p:Cillil;;~ :_, :::: : ::=::~.
Pilot Test for EA Matrix (Sector Analysis)
Testing of the SA approach (completed in May 05), mainly for the shoe industry and secondarily for the rubber industry, involved: Sorting available IPHS data into industries Sorting the data into sectors within an indust,,} Adding task categories (not an IPHS data field) based on sample location
descriptions Qualitatively evaluating the frequency-concentration distributions of the
sector, task, time data Calculating preliminary summary statistics for the identified sector, task and
time categories > Assigning e:<posure to the JCrvlL subjects (n:-=17) via the SP\ based Gn the
subject's questionnaire information on industry, job, lask and time period. See Table 2 for a summary of the preliminary statistical analysis results. There are statistical treatment considerations that will be reviewed with SRP members or personnel with expertise with exposure data analysis. This work is planned in
03 05. The pilot evaluation yielded additional insights that triggered several
research efforts currently underway. These are largely covered in the following Plan Forward section. Additional coding to reduce heterogeneity in the data sets and analyses are planned before using these data for final assessment of benzene exposures. Timing of completion of such analyses is linked to whether or not further cooperative research with IPHS/CDC on the database proves possible. This IPHS/CDC agreement is particularly valuable since the database lacks the contextual information on the facility and sampling that might be
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improved upon with IPHS collaboration and access to at least selected original written reports. Further work on the currently available extracts of the IPHS
database does not seem productive if full access and collaboration with IPHS
progresses.
Plan Forward
Continued interactive planning with Fudan
team on investigative
directions, EA reviews, team development: 2H05
Access to !PHS database expanded - assure all relevant data available and
IPHS partnership in DATA REVIEW: Go/No 0305
../ If Go - Quality checks on IPHS sector data completed: 04 05-Q2 06
../ If No Go - Not Applicable
Industry Sector "History Reports" to be
histoij trends for the
sector: Current, complete by 03 06
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results: Proposed Q3 05
EA matrix for the sector completed and applied to CC/DP work
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It is expected that ALL PHASES
cone in
Fudan EA Team members.
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Figure 2. CC/DP xposure ASSeS$nl~nt ,}rc
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Table 1. Exposure Assessment Proce::ises '
~s for CC/DP Study
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includinq comparisons to IPHS data
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TABLE 2. Preliminary Statistical Summaries JL ~ Cater / 2. c_ for Shoe Industry Exposures in mg/m3
2
C\ ~j ~a Blocks
Job A General shoe making (not otherwise specified)
1970s & prior
19805
1990s+
Mean
57.3
29.7
89_1
Median Minimum Maximum
25.0 0.3 600.0
1.0 0.3 1376.7
27.4 0.3 760.0
Count
52 315 78
Job t:'
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r.tc
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2 S C. 1
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1990s
41.4
6.7 0.3 1323.5 179
Job F Assembling shoes
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1970s & prior
1980s
1990s
198C. r' ',:'1 on!"
N,
Mean
150_2
22.5
~0.1
r'p',
en
~
),-
Median Minimum
67.5 1.6 6.0 0_3 0.3 0.3
l,le:, r.A,in:
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-0
MaXimum
900.0
1199.3 593.5
r"~ :1
0
Count
38 455 f,3
Cr'l
0
Q\
0 Job C Glue mixing
f:: l :
11,
:: f-\' "
19805 Only Available Mean
191.5
1.1: "
r ',-_ ,
I,rl;d I
Median
3.4
t.led:;:
<
Minimum
0.3
:.Ii:-,ir:
0
Maximum
6964,5
I\'\a>.
Count
153
CO" 1
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