Document zQN8NKj7mBmo3kj59O30OvBy0

From: Sent: To: Subject: Attach: Cagen, Stuart Z SCC-CF-SS <stuart.cagen@shell.com> Thursday, June 23,2005 10:21 PM (GMT) Cagen, Stuart Z SCC-CF-SS <stuart.cagen@shell.com>; Tsai, Shan P SHLOIL-SHS <Shan.Tsai@shell.com>; Clegg, Patsy M SCC-CHSE-PC <patsy.c1egg@shell.com> FW: BHRC-TC... Handout for EA ConfCall - Fri 12110, llam EST 121004 DRAFT SHS EA ver 4.ppt Memories... Of possible use for the call tomorrow morning. Looks like there will be a combined call tomorrow, with Otto joining the call with Tom, et al at 930 am Houston time Stuart Cagen Shell Chemical LP One Shell Plaza, 910 Louisiana, Houston, TX 77002-4916 Tel: +1 713241 1407 Fax: 3325 Other Tel: +1 8326463987 Email: stuart.cagen@sheILcom Internet: http://www.sheILcom/chemicals "Business Success through HSSE Excellence" -----Original Message----From: Bruce Jarnot [mailto:jarnotb@apLorg] Sent: Thursday, December 09, 2004 5:47 PM To: benzconsort-tc@listserve.apLorg Cc: Lorraine Twerdok; Howard Feldman Subject: BHRC-TC... Handout for EA Conf Call - Fri 12/10, llam EST Attached is Tom Armstrong's handout (ppt file) for Friday morning's Exposure Assessment conference calL .. Best Regards - Bruce. -----Original Message----From: Bruce Jarnot Sent: Tuesday, December 07, 2004 10:50 AM To: benzconsort-tc@listserve.apLorg Cc: Howard Feldman Subject: BHRC-TC... REMINDER - EA Conf Call - Fri 12/10, llam EST Importance: High Benzene Health Research Consortium (BHRC) Technical Committee - REMINDER... we have a conference call scheduled this Friday, Dec 10th, to review Exposure Assessment (EA) progress in the Shanghai Health Studies with Tom Armstrong, Rob Schnatter and Yimei Zhou: Date: Friday, Dec 10 Time: 11 :OOam - 2:00pm EST Dial-in: 763/315-6900 (or toll free 866/448-6756) SH ELL-MCCLU RG-052835 PIN code: 6828319# Best Regards - Bruce. ***** Bruce M. Jarnot, PhD., DABT American Petroleum Institute Regulatory and Scientific Affairs 1220 L Street, NW (Room 1025) Washington, DC 20005-4070 phone: (202) 682-8473 fax: -8031 email: jarnotb@api.org <mailto:jarnotb@api.org> SH ELL-MCCLU RG-OS2836 Review of SHS Exposure Assessment 10 December 2004 Tom Armstrong Rob Schnatter Yimei Zhou DRAFT 1 SH ELL-MCCLU RG-OS2837 Overall Study Aims and Values Case Control (PI: Otto Wong I Fu Hua) Is NHL associated with benzene? If so, is NHL / benzene specific to NHL subtype? What is shape of dose-response curve for NHL and AML? Provide comment on NCI NHL / benzene study Disease Progression (PI: Rich Irons I Fu Hua) Does benzene-induced disease have a distinct pattern? Does benzene-induced cancer progress through requisite steps? What is shape of dose-response curve for MDS and AA? May have impact on "safe" levels Molecular Epidemiology (PI: Rich Irons I Fu Hua) What is shape of dose-response for blood effects? (Phase 1, 2A) What is earliest marker for effects? (Phase 1, 2A, 28) Does benzene induce toxicity more readily in susceptible workers? (Phase 2A, 28) Provides mechanistic insight; possible protection strategy in some settings Are there requisite steps for later markers (blood count decrements)? (Phase 2A, 28) Does benzene act on bone marrow differently than peripheral blood? (Phase 28) If so, provides insight on mechanisms, thresholds Could provide new basis for dose-response DRAFT 2 SH ELL-MCCLU RG-OS2838 Study Positives State-of-the-art lab Improved diagnostic capabilities New WHO scheme for LH disease classification enabled Tissue storage allows future research Patient population directly benefiting from improved diagnoses / treatment Reputation for diagnosis reflected by more signatory hospitals Unique resource for research Preliminary results already suggest threshold for blood effects Preliminary results suggest bone marrow changes in absence of peripheral blood Could be unique benzene signature for myelodysplasia Enhancing IH capabilities in Shanghai / China Comments / review Study obtained positive feedback at recent worldwide conference Esteemed SRP and ERB has favorably reviewed study Study may be helping to reduce benzene exposure in Shanghai DRAFT 3 SH ELL-MCCLU RG-OS2839 EA Progress Summary 10? 100-200? DRAFT 4 SH ELL-MCCLU RG-052840 Deliverables Associated with Each Study Molecular Epidemiology Scope Phase 1: Phase 2A: Phase 2B: 2000 workers 1000 workers 200 workers EMBSI Activities I Deliverables Design Questionnaires Design Training of staff Abstraction forms Factory selection Exposure assessment QA/QC Statistical analysis Publication assistance Presentations assistance Status Complete Complete Complete Complete In progress In progress In progress Future Future Future Actual Effort +5% (see CC) 2X (see CC) Future Future Future DRAFT 5 SH ELL-MCCLU RG-OS2841 Deliverables Associated with Each Study (cont'd) Disease Progression I Case Control Planned Scope BZ poisoning cases: Aplastic anemia: MDS: AML: NHL: Controls: Total: 50 250 300 600 600 3600 5400 EMBSI Activities I Deliverables Design Questionnaires design Training of staff - Quest. administrators - Clinical coordinators - Exposure Assessment Control selection Exposure assessment QA/QC Some statistical analysis (DP) Some publications (DP) Some presentations (DP) Status Complete Complete Complete Complete Complete Complete Complete In progress In progress Future Future Future Actual Effort +20% +60-70% Retune +30% " + 20-30% " +20-30% +2-3X In progress Future Future Future DRAFT 6 SH ELL-MCCLU RG-OS2842 EMBSln imeline [ .a.C -e-l,l EMBSI $ Plan $ Actual - Na c -e-l,l - 21i2 K 132 K Ii 718 K 624 K - (") a Ol :::J - "a<t C -e-l,l ~ 1,213K 1,192K 1,576K 1,533K Project Milestones Protocols approved Agreements with Fudan, CDC,IPHS Lab & Studies Start Field testing, ME Pilots Lab& Studies Start EMBSI Planned Work Protocols: write, review, approve EMBSI Actual Work Protocol write, review, approve Staffing, EA support materials, training Troubleshoot, Monitor, Reviews Design & ov,:::.rsight for EA - AMLlNHL Study (2) Questionnaire development Staffing, EA support materials, training (1) l Design & OVerSight for EA - AMLlNHL Study "I ;~~::::hoot, Monnor, " JCML Database for EA (3): ------------------------------------------.~.i Questionnaire development (4) ;-----------------------------------------------+i~i EMBSI reviews CDC lab & I provides lab QA support(5) Import delays (Chines regulation driven) IPHS Role Change EA crew to Comments Agreements & revisions with Fudan, IPHS, CDC Fudan recruiting EA questionnaires _________________________________________________________.~ YZ begins support SARS Turnover Notes: (1) Extended due to project start delays, changing agreements and Fudan staff reassignments (2) Added per SRB request and budget increased (3) Need identified by PI Team DRAFT (4) Extended due to add in of AMLlNHL Study EA support (5) Unanticipated need covered by EMBSI New IH Lab EA Reviews, EA Committee, Local management issues 7 SH ELL-MCCLU RG-052843 EMBSl-=.. imeline Forward P)a n IJ') o C -e-l,l EMBSI $ Current Plan-1 ,650K $ Proposed Plan -1,650K Does not include XOM sweat equity Project Milestones Current Project Milestones Proposed oco Io"- C -e-l,l C -e-l,l -2,OOOK -2,300K End case accrualI End EMB?I contract I'-2800K 3,200K Begin analyses : iPublications drafted End case accrua Begin analyse , Publications drafted End EMBSI contract EMBSI Current Planned Work Troubleshoot, Monitor, Reviews ~i Analyses DP, ME & P4blications prepared EMBSI Proposed Work Troubleshoot, Monitor, Reviews Additional on-site technical & management ~ Analyses DP, ME & -----------''----------i+~ Publications ~ repared (facilitate increased technical resourcing, me:ntoring, communication; EA QA oversight, facilitate on-going Fudan/lPHS co~tributions) I Analytical QA support I I DRAFT 8 SH ELL-MCCLU RG-OS2844 SHS EMBSI BUDGET 1800000 1600000 1400000 1200000 .~ CI) > 1000000 cu ::::J E ::::J 800000 0 600000 400000 200000 o Y./ /.,r/ ./ ././ ./ ./ /."........./. / . / ..... ..... / . , / ' . ,/'./..... / ./ .....""/ ...../ . /. ./" ,,/ ./ ; //.//,,/,// ..... / / . /..... / ,..,.././" ./ ./ .................. .......... ~./ ././ /././. ./ .....,..,.."../...... / ./ ./ ././ /./.".......,," ././ ~....../ ...............,," ~ ~ ~~~ ~~ ~~~ ~ ~ ~ ~ ~~ ~ ~ ~ c:;0~" ~o~ ')0-~' ~rS:-' ~1;\' ').s.' c:;0~" ~o~ ')0-~' ~rS:-' ~1;\' ').s.' c:;0~" ~o~ ')r:" ~rS:-' ~1;\' ').s.' c:;0~' Month DRAFT -Spent - Control Budget 9 SH ELL-MCCLU RG-052845 Exposure Assessment Options Review of strategies and study impacts DRAFT 10 SH ELL-MCCLU RG-052846 Case Control Studies Tiered Design: Expectation of Fewer Subjects Completed at Higher Tiers Robust database, site visits, task data, retro EA skills Quantitative & Pattern of Exposure SH ELL-MCCLU RG-OS2847 CC / DP Exposure Assessment Design Hospital recruitment, cases of BP 1 (10/year) AA 2 (50/year) MDS 3 (GO/year) AML 4 (120/year), NHL 5 (120/year) Actual 8/day Questionnaires L...{) 1080 /year, 5/day ~ ~ Initial exposure assessment - work history, -IPHS database - facility records, - Other I Two matched controls selected per case Fudan Exposure Assessment Team Clarify or Verify & characterize main exposures No or? v Construct Detailed Exposure Assessment Job - facility - exposure - time matrix I Yes Fudan Exposure Assessment Committee I Exposure reconstruction - historic measurements, history of changes in methods, facilities, materials, etc. - retrospective estimation - physical recreation DRAFT I Exposure surveys - facility summaries - worker or surrogate exposure monitoring - air samples - biological monitoring SH ELL-MCCLU RG-052848 EA Tiers: Design Basis for SH Studies Case Control Studies DP Case Series (1) AMLlNHL, Broad DP (1) Quantitative -Quantitative doseresponse -Links to studies used in risk assessments -Quantitative doseresponse -Links to studies used in risk assessments ME Studies (2) Phase 1 Phase 2A Underway as planned Quantitative dose-response Phase 2B Links to studies used in risk assessments SemiQuantitative Ranks Qualitative Ranks -Semi-Quant. "dose" response -Semi-Quant. causal link -Semi-Quant. link to studies used in risk assessments Group differences in risk -Semi-Quant. "dose" response -Semi-Quant. causal link -Semi-Quant. link to studies used in risk assessments Group differences in risk -Semi-Quant. "dose" response -Semi-Quant. causal link -Semi-Quant. link to studies used in risk assessments Ever Exposed Never exposed Association with disease Association with disease Note 1: For the CC/OP studies, all tiers have a "certainty" rating and these generally decrease at the higher tiers Note 2: "lower tiers" not planned or needed in the ME studies. Semi-quantitative ranks may be applied in some factories for Phase 1, but full quantitative assessment planned. DRAFT 13 SH ELL-MCCLU RG-052849 CC/DP Studies - Bz EA Impact Analysis Stop Point Quantitative Semi Quantitative 0- 0.3 mg/m3 0.3 to 3 3to 40 > 40 Qualitative range No Low Medium High Study Impact Discussion -Best evidence of causal links -Data for use in risk assessment -Currently planned for -10% of subjects -Requires additional investigative effort for site reviews, additional retrospective EA skills, robust analysis of IPHS database and other quantitative data sources -Most difficult tier to complete -Costs - medium - high -Probability of Success -low -Value -high -Improved evidence of causal links -Semi-quant. link to quantitative risk assessments -Work site screening visits -Difficulty - medium -Costs - medium -Probability of Success - medium -Value - medium -Risks by groups for stronger information or possible causal link for diseases of concern -Difficulty - low - medium -Costs -low -Probability of Success - high -Value - low-medium Read Here to Top Everexposed,never exposed -Only potential relationship of benzene or other exposures to diseases of concern -Questionnaire driven -Difficulty - low -Probability of Success - high -Value -low SH ELL-MCCLU RG-052850 Go-forward Options DRAFT 15 SHELL-MCCLURG-052851 Many Factors Lead to Project Success Cultural & Political Management Technical Resourcing I 16 SH ELL-MCCLU RG-OS28S2 Opportunities Action Item #1 yz assignment to Shanghai and more EA support Expected Benefits EA staff morale, productivity, leadership; understanding Fudan / IPHS drivers, EA qualifications, less EA staff resource diversion Implementor EMBSI #2 Fund extension of the study Increase subject numbers, more insight on disease mechanisms (from ME/DP), more power for case control less chance of spurious findings Oversight Committee #3 Re-engage IPHS More efficient factory selection, EA, more insight on IPHS database limitations PI's #4 Further support the Fudan team Continuous Improvement of PI Oversight Committee collaboration, YZ effectiveness, post- study prob. of lab utilization #5 Periormindependent QAlQC audits of Fudan IH laboratory and field (questionnaire EA) work Ensure data integrity Member CO's, external resource DRAFT Enabler Technical/Oversight Committees FU's support PI involvement in EA Technical/Oversight Committees Factory access through IPHS PA/Member Companies Technical/Oversight Committees Technical Committee 17 SH ELL-MCCLU RG-052853 Recommendations: Maintain Full Scope of SHS Continue Planned Quantitative EA for CC/OP Studies Continue Recruitment of Subjects for ME liB Maximizes Value of Study Results for Risk Assessments Requires Extension through 2007 Requires Additional $3.3M Funding DRAFT 18 SH ELL-MCCLU RG-OS28S4