Document 2qJMMEbKVbRB3p6jYw5MoxEQr

Shanghai Health Study Review and Update Shell Steering Team 16 November 2004 November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068090 Shanghai Health Study Benzene Toxicology and Regulations Shanghai Health Study (SHS) providing an opportunity to clarify scientific issues Status of the study Benzene Health Research Consortium Organization Shell participation Current challenges Shell Steering Team November 15,2004 Patsy Clegg SHELL-MCCLURG-068091 Benzene Toxicology & Regulations Benzene Toxicology Toxic chemical management : 1. Hazard Identification what are the hazards, regardless of exposure? 2. Risk Characterization dose response - what is a safe dose? November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068092 II I think ynu should be n10re ""p'll' -l"e n' i.::1te fatt- t''e~.2l~. . Cl". .i> .. L lIt: .' ..... l' . a 1-r-ffi . "tTtl)' '. II November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068093 Benzene Toxicology & Regulations Benzene Toxicology - the hazard Benzene Is .. - A recognized - known - human carcinogen Acute Myelogenous Leukemia (AML) November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068094 Benzene Toxicology & Regulations Benzene Toxicology - Risk Characterization The effects of exposure depend on: - dose - duration - other exposures - personal traits and habits - genetic susceptibility November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068095 Benzene Toxicology & Regulations Benzene Toxicology - Previous Study Summaries Pre-1997 - Acute Myelogenous Leukemia (AML) associated with benzene Not seen at exposures < 1ppm Clear observations at exposures> 20 ppm Insufficient data at 1-20 ppm to clearly assess risk - All steps required for induction of cancer have not been determined November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068096 Benzene Toxicology & Regulations Benzene Toxicology - Previous Study Summaries National Cancer Institute (NCI) Shanghai Study - Case-control study published in 1997 - Benzene associated with AML and Non Hodgkin's LYlDpholDa (NHL): unusual association with a nonAML cancer - Study design did not add to understanding of threshold (lowest exposure group was 10 ppm or less) November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068097 Benzene Toxicology & Regulations Benzene Toxicology - Previous Study Summaries Australian Institute of Petroleum (AlP) Health Watch Study - Case-control study released in 2001 - Association with allleukelDias, including chronic lymphocytic leukemia (CLL) - Leukemia association reported at lower exposure levels than prior studies. - No association with NHL or multiple myeloma November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068098 Benzene Toxicology & Regulations Benzene Toxicology Summary Known: - Acute Myelogenous Leukemia New studies information - Non-Hodgkin Lymphoma - All leukemias - Cancers associated at lower exposures than previously recognized November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068099 Benzene Toxicology & Regulations Benzene Regulations - Work place exposure Benzene Is .. - Tightly regulated although worldwide standards vary: Work place exposure levels in the range of 0.4 - 10 ppm Regulations in the US via the Clean Air Act might limit community levels to as low as 40 ppt. November 15,2004 Patsy Clegg SHELL-MCCLURG-068100 Shanghai Health Study An Opportunity SHS designed to qualitatively and quantitatively address these issues: What other Lymphoid or Hematopoietic Diseases might be associated with benzene exposure? At what exposure level/threshold are there effects? What is the progression of disease from exposure to cancer? Are there biomarkers to help identify exposure and potential disease? November 15,2004 Patsy Clegg SHELL-MCCLURG-068101 Shanghai Health Study An Opportunity Purpose: To gain a quantifiable understanding of the relationship between benzene exposure and potential development of associated hematopoietic diseases/cancer risks - Researchers using cutting-edge technologies to advance the understanding of benzene-induced disease November 15,2004 Patsy Clegg SHELL-MCCLURG-068102 Shanghai Health Study is 3 Studies AML/NHL Case Control Study I AA/MDS/AML/BP Disease Progress Study Molecular Epidemiological Study of Benzene Exposure I Joint Sino-US Clinical and Molecular Laboratory CJCML) November 15,2004 Patsy Clegg SHELL-MCCLURG-068103 Joint Sino-US. Clinical and Molecular Laboratory November 15,2004 Patsy Clegg SHELL-MCCLURG-068104 Joint Sino-US. Clinical and Molecular Laboratory -State-of-the-art laboratory on Fudan University campus - Meets international standards - Supports the study, Shanghai medical community and will remain at Fudan -Technology transfers - Chinese staff trained at University of Colorado - U.S. researchers working with Chinese colleagues and government officials November 15,2004 Patsy Clegg SHELL-MCCLURG-068105 Referral Hospitals Outside Cases Factories Clinical Laboratory Support L I JCML Laboratory Consultation Exposure r SMCDPC SMIPHS Case Control Disease Progression Molecular Epidemiology November 15,2004 Patsy Clegg SHELL-MCCLURG-068106 Shanghai Health Study An Opportunity SHS Elements: 3 Studies - Case Control Study - Disease Progression Study - Molecular Epidemiology Quality Science Study Participants Study Timeline November 15,2004 Patsy Clegg SHELL-MCCLURG-068107 Shanghai Health Study An Opportunity Study #1 - Case Control Study Prospective epidemiology study to determine risk of AML and NHL, among benzene exposed workers Data collected will allow analysis of potential other causal factors for NHL Estimate 4-5 years to obtain 450 AML and 450 NHL patients into study Improved exposure assessment based on historical and concurrent workplace monitoring and questionnaire November 15,2004 Patsy Clegg SHELL-MCCLURG-068108 Shanghai Health Study An Opportunity Study #2 - Disease Progression Prospective study on relationship of non-cancer bone marrow disease and benzene-induced AML - Is benzene-induced AML different from spontaneous AML by unique cellular markers? - Does AML involve a progression through one or more noncancer states? Research methods: - questionnaires, interviews, review work histories - examine blood, breath, urine study/evaluate potential biomarkers November 15,2004 Patsy Clegg SHELL-MCCLURG-068109 Shanghai Health Study An Opportunity Study #3 - Molecular Epidemiology Prospective study of establish quantitative relationship between exposure and effect - Do low benzene exposures cause blood effects? - Is there an association of blood effects and genetic susceptibility? - Do biomarkers of exposure accurately reflect workplace exposures? Healthy workers at sites with varying levels of benzene exposure will participate; extensive lab work, including genetic tests, will be conducted November 15,2004 Patsy Clegg SHELL-MCCLURG-068110 Shanghai Health Study An Opportunity Quality Science Institutional Review Boards (IRBs) approved Protocols - Govern use of human subjects - u.s. and China independently Shanghai Health Study Panels - International Ethics Review Panel 4 members representing 3 global regions - International Scientific Review Panel 10 members; 6 scientific disciplines - Involved during entire project November 15,2004 Patsy Clegg SHELL-MCCLURG-068111 Shanghai Health Study An Opportunity Principal Investigators Study Participants Dr. Richard Irons, U of Colorado Health Sciences Center Dr. Otto Wong, Applied Health Sciences Dr. Fu Hua, Fudan University Collaborators ExxonMobil Biomedical Sciences Chinese Participants Fudan University School of Medicine 30 area Shanghai hospitals Shanghai Municipal Center for Disease Prevention Shanghai Hematology Society Shanghai Pathology Institute for Public Health Supervision Shanghai Public Health Bureau Internal Review Boards U of Colorado, Fudan University, Applied Health Sciences November 15,2004 Patsy Clegg SHELL-MCCLURG-068112 SHS Timeline 2001 - Consortium established to fund the study; Protocols reviewed 2002 - Questionnaire development, pilot testing;Key laboratory personnel trained 2003 - Laboratory completed; 1st Annual Meeting; Case recruitment began 4th quarter 2004 - Preliminary data; 2nd Annual Meeting; International Benzene Symposium Presentations 2005 -7 2007 - Research, data analysis; Results published as studies completed November 15,2004 Patsy Clegg SHELL-MCCLURG-068113 SHS - Current Status Study structure is a big success - 2 annual meetings held - Scientific & Ethics Review Panels engaged Study is progressing - In year 2 of anticipated 4-year study - Laboratory is operating smoothly - Cases being accrued - 30 Shanghai hospitals referring cases Study presentations - International Benzene Symposium, Munich, Oct 2004 - Papers to be published November 15,2004 Patsy Clegg SHELL-MCCLURG-068114 SHS - Major Accomplishments Set the standard for epidemiology studies Study being conducted using WHO cancer classifications for the first time Study infrastructure November 15,2004 Patsy Clegg SHELL-MCCLURG-068115 Benzene Health Research Consortium SHS Sponsors A consortium of petroleum and chemical companies concerned about understanding the human health effects of benzene - BP - ChevronTexaco - ConocoPhillips - ExxonMobil - Shell Chemical - with additional funding from Marathon Ashland - Project Administrator: American Petroleum Institute November 15,2004 Patsy Clegg SHELL-MCCLURG-068116 Benzene Health Research Consortium Structure Oversight Committee 1.. RI.Technlecal/Communlcatlon ecrultment L ga1 - Finance Scientific Review Panel Ethics Review Panel APCO Steptoe & Johnson API Administrative Support November 15,2004 Patsy Clegg SHELL-MCCLURG-068117 Benzene Health Research Consortium Shell Participation Consortium leadership positions: Patsy Clegg Stuart Cagen Shan Tsai Sarah Colletti Oversight Committee Chair Technical Vice-Chair Finance Committee Chair Adjunct Professor, Fudan University Communications Committee November 15,2004 Patsy Clegg SHELL-MCCLURG-068118 Shell Intentions for Proj ect and Outreach Shell intentions based on: - Product stewardship needs for hazard and risk clarity. - Protecting reputation - in China and around the world. - Protect relationships/investments in China. - Meet commitment to transparency and ethics. - Protect credibility of project and participants. - Raise awareness and understanding of the project. - Secure buy-in and constructive feedback into the process. November 15,2004 Patsy Clegg SHELL-MCCLURG-068119 Current Challenges Short Term: Getting the study done - Exposure Assessment - Operating costs Longer Term - Laboratory Sustainability & Disengagement November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068120 Current Challenges Exposure AssesslDent is a greater challenge than expected - Quality & capability of resources on the ground in China - Cooperation of Chinese agencies November 15,2004 Patsy Clegg SHELL-MCCLURG-068121 Current Challenges Budget IlDpiications - Current Budget: - Request for additional $: 20.8 MM 3.3 MM Budget Solution Proposals - Funding reallocation: - Additional Funding sought: - BP - ILSI - Study prioritization: 0.6 MM? 1.7MM ? ? November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068122 Current Challenges Laboratory Sustainability & Disengagement - Lab belongs to Fudan University; Expecting university decision as to management by year end. - Uncertainty as to future role of lab after study concludes. - Consortium is working on options November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068123 Current Challenges Conclusions: Ensure that a robust study is completed Continue efforts to reprogram and reallocate funds Lab sustainability November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068124 SHS - Shell Steering Team Business SOPUS External Affairs Issue Management Legal Finance HSE Medical Nancy Sullivan, Business sponsor - Emeritus Stacy Methvin, Americas Base Chemicals VP Contracts and Funding Harshad Topiwala, APME Base Chemicals VP Business Focal Point Bill Colquhoun, EUAF Base Chemicals VP David Sexton, Portfolio Planning & Development Nick Wood, EA Manager for Shell in China Sarah Colletti, EA Manager for the Americas John Schmid Tarita Samuel Susan Tholstrup, HSE sponsor Patsy Clegg, Oversight Committee Stuart Cagen, Technical & Finance Committees Shan Tsai, Technical Committee November 15,2004 Patsy Clegg SH ELL-MCCLU RG-06812S SHS - Shell Steering Team Charter PURPOSE: The purpose of the Shell Steering Team is Set the strategy Provide guidance to Shell staff on the Benzene Health Research Consortium committees Provide internal Shell communication on the progress of the study Issue Management Provide resources to support the study November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068126 SHS - Shell Steering Team Path Forward: Next Meeting Next communication November 15,2004 Patsy Clegg SH ELL-MCCLU RG-068127