Document baJ01xvYjZa0br0ZGJBGb42Ey

From: Sent: To: Subject: Attach: Matt Todd <ToddM@api.org> Monday, September 13,20048:43 PM (GMT) BHRC Oversight Committee (E-mail) <benzconsort-oc@listserve.api.org>; BHRC Technical Committee (E-mail) <benzconsort-tc@listserve.api.org>; BHRC Communications Committee (E-mail) <benzconsort-cc@listserve.api.org> BHRC Communications Materials 2004-09-13_shs_funding_questions. doc; 2004-09-09_shs_main_messages. doc; 2004-0913_shs_overview.doc; 2004_Adaptable_Presentation.ppt Dear BHRC Members: Attached are updated communications documents for review and comment. Changes to these documents are noted to facilitate your review. 1) SHS Funding Questions - Changes to reflect membership funding changes, project budget, timeline, etc. 2) SHS Main Messages - Change to the end of the document on projected end date. 3) SHS Overview - Change to timing and budget portion of document. Contact information changed to include all Oversight members. 4) 2004 SHS Adaptable Presentation - Changed diagram (old on showed cases going to IPHS and exposure information come back from them) - Deleted slide listing hospitals and used "about 30" as the number - Deleted slide on funding structure and indicated $500k provided membership benefits - Anticipate completion and publications by 2007 - Updated SRP/ERP slides - Updated the format of Master document to resemble SHS website Please review and provide comments by Oct 11th. Best regards, Matt Matthew Todd Regulatory Analysis and Scientific Affairs American Petroleum Institute 1220 L Street NW Washington, DC 20005 p: (202)682-8319 f: (202)682-8031 www.api.org SH ELL-MCCLU RG-OS41 08 The Shanghai Health Study Sponsored by: Benzene Health Research Consortium SH ELL-MCCLU RG-OS41 09 Presentation Topics Shanghai Health Study Overview Shanghai Solutions Benzene Basics Current Benzene Science Shanghai Health Study Elements Shanghai Health Study Sponsors Shanghai Health Study Funding Structure Terms, Sources and Resources SHELL-MCCLURG-054110 What is the Shanghai Health Study? Clinical study to investigate the potential causes and development of Iympho-hematopoietic diseases (lymphoid organs, blood and bone marrow) as potentially related to benzene Project of Fudan University Medical Center University of Colorado Health Sciences Center Applied Health Sciences Chinese public health agencies Shanghai hospitals 3 SHELL-MCCLURG-OS4111 Shanghai Health Study Purpose To gain a quantifiable understanding of the relationship between benzene exposure and potential associated cancer risks Researchers using cutting-edge technologies to advance the understanding of benzene-induced disease 4 SHELL-MCCLURG-OS4112 Understanding Benzene: Current Science SHELL-MCCLURG-054113 Benzene Is ... A constituent of crude oil and a chemical building block A recognized human carcinogen: Acute Myelogenous Leukemia (AML) Tightly regulated although worldwide standards vary What is not currently known: benzene's impact on a molecular level; the "threshold" exposure level; whether and how associated cancers or other related diseases may be caused; and the role of genetic susceptibility 6 SHELL-MCCLURG-OS4114 Benzene Toxicity The effects of exposure to any hazardous substance depend on: dose, duration, other exposures, personal traits and habits, genetic susceptibility Co-exposure to other chemicals can also influence toxicity 7 SHELL-MCCLURG-054115 Why is Understanding Benzene Important? Benzene exposure is universal Advancing current scientific understanding of benzene exposure would be a significant contribution to health and to worker safety Understanding health effects of low-level sbCe.nieznecnee exposures would advance benzene 8 SHELL-MCCLURG-054116 Why Shanghai? Unique Study Environment Databases documenting exposure Exposure across industries Range of exposure levels Committed Collaborators Government University and hospital based researchers Community hospitals Shanghai Municipal Center for Disease Control and Prevention Institute for Public Health Supervision 9 SHELL-MCCLURG-OS4117 Unparalleled Collaboration "This study is an enormous collaborative effort, unlike anything American and Chinese researchers have ever done." Dr. Richard Irons, PhD, SHS principal investigator, professor and director of the University of Colorado's Molecular Toxicology and Environmental Health Sciences Program 10 SHELL-MCCLURG-054118 Shanghai Health Study Background Most environmental and occupational standards for benzene are based on mathematical extrapolations of cancer risk from high-level exposures to environmental concentrations These extrapolations are based on almost no knowledge of how benzene functions at a molecular level in humans 11 SHELL-MCCLURG-054119 Difficulties in Past Benzene Research Animal models do not replicate human benzene-related diseases Retrospective research Review case files of people who have died Rely on inexact diagnoses Accuracy of reconstructed exposure data Guess at lifestyle and dietary habits 12 SH ELL-MCCLU RG-OS4120 How is the SHS Distinct? Prospective research Patients at participating hospitals suspected of having a lymphoid, blood or bone marrow disease will be referred to the SHS Patients' diets, environmental exposures and family histories will be recorded Patient disease progression followed at supporting hospitals 13 SHELL-MCCLURG-OS4121 Clinical Laboratory Support Sino-U.S. Joint Clinical & Molecular Lab Referral Hospitals Outside Benzene Cases Consultation SUJCML SMCDCP ~------------~ Laboratory Exposure IPHS Data Institute for Public Health Study Data Supervision Shanghai Municipal Centers for Disease Control & Prevention Case Disease Molecular Control Progression Epidemiology 14 SH ELL-MCCLU RG-OS4122 How is the SHS Distinct? Study will be able to examine primary diagnostic and medical data in real time First-hand exposure reports are more reliable than second-hand or reconstructed information State-owned databases document worker histories 15 SH ELL-MCCLU RG-OS4123 Shanghai Health Study Purpose Designed to provide mechanistic data on AML development in humans Goal to identify a more reliable basis for the extrapolation of leukemia risk associated with low-level benzene exposure 16 SH ELL-MCCLU RG-OS4124 Shanghai Solutions Unique Study Environment Unparalleled Collaboration Shanghai Health Study Genesis Rare Opportunity Shanghai Health Study Partners Shanghai Health Study Hospital Partners Sino-U.S. Joint Clinical & Molecular Lab 17 SH ELL-MCCLU RG-OS412S Unique Study Environment: Shanghai Robust data set State-maintained benzene exposure and health effects databases documented from 1970s Benzene related health effects are #2 in reported chronic occupational health hazards in China in 2001 (Source: Ministry of Public Health) Large range of exposure levels from a variety of occupational sources Regulatory authorities interest in improving benzene exposure regulation and enforcement 18 SH ELL-MCCLU RG-OS4126 Unique Study Environment: Shanghai China interested in scientific basis for improved worker-safety regulations Chinese occupational standards based on measurable human health effects Chinese Occupational Diseases Protection Law (effective May 1, 2002) Increases worker protections Specifies company role regarding worker health problems resulting from occupational exposures Benzene receiving additional scrutiny 19 SH ELL-MCCLU RG-OS4127 Unique Study Environment: Shanghai High interest in collaborating on research Technology transfers International health standards State-of-the-art lab/ equipment Shanghai hematology/pathology communities support and expertise Strong research program supports China's regulatory understanding and objectives 20 SH ELL-MCCLU RG-OS4128 Unique Study Environment: Shanghai Fudan University Medical Center Research partnership with a leading research university Community participation About 30 hospitals refer patients to the SHS Shanghai Municipal Center for Disease Prevention and Control Shanghai Institute for Public Health and Supervision 21 SH ELL-MCCLU RG-OS4129 SHS Genesis NCI/CAPM study in Shanghai Retrospective study published 1997 Raised new questions on effects of low-level benzene exposure Assessed feasibility of building on Shanghai experience Respected scientific collaborators Well-documented occupational exposure levels across variety of industries Detailed health and historical records Sufficient incidences of disease Conclusion: full study feasible Three distinct, highly integrated studies designed 22 SH ELL-MCCLU RG-OS4130 Rare Opportunity Unique data set Technological advances Early, consistent detection and diagnosis of leukemias and related diseases in Shanghai Identification of more sensitive benzene exposure biological markers Convergence of company and local Shanghai research interests 23 SH ELL-MCCLU RG-OS4131 Shanghai Partners Fudan University Medical Center Institute for Public Health Supervision Shanghai Public Health Bureau Shanghai Hematology Society Shanghai Pathology Society Shanghai Municipal Centers for Disease Control and Prevention About 30 Shanghai-area hospitals 24 SH ELL-MCCLU RG-OS4132 Sino-U. S. Joint Clinical and Molecular Laboratory 25 SH ELL-MCCLU RG-OS4133 I Benzene Basics What is Benzene Benzene Uses SH ELL-MCCLU RG-OS4134 What is Benzene? A colorless, volatile, flammable liquid with a sweet aromatic odor; A natural component of many substances including crude oil; A by-product of combustion; A chemical building block; and One of top-20 most-produced U.S. chemicals 27 SH ELL-MCCLU RG-054135 Benzene Uses Benzene is a basic petrochemical building block, widely used in the manufacture of products such as: Dyes and laundry detergents Lubricants Nylon and synthetic fibers (carpet, clothing) Pharmaceuticals Pesticides Plastics and resins Some types of rubbers (tires) 28 SH ELL-MCCLU RG-OS4136 Benzene Uses Element of crude oil; found in small amounts in petroleum products As a chemical building block, is transformed in the manufacturing process Eliminated as an unconverted additive to solvents and ad hesives 29 SH ELL-MCCLU RG-OS4137 Existing Benzene Know/edge Conclusions pre-1997 U.S. Regulatory Interpretation Recent Epidemiological Studies Challenges Observations on Existing Science SH ELL-MCCLU RG-OS4138 Epidemiology Conclusions pre-1997 Acute Myelogenous Leukemia (AML) associated with benzene No risk at exposures < 1ppm Clear risk at exposures> 20 ppm Insufficient data at 1-20 ppm to assess risk Some steps are not dose-dependent and are governed by a threshold mechanism All steps required for induction of cancer have not been determined 31 SH ELL-MCCLU RG-OS4139 U. S. Regulatory Interpretation Regulatory decisions based on nothreshold assumption More research needed to assess threshold assumption 32 SH ELL-MCCLU RG-OS4140 Research Challenges Accounting for multiple exposures Addressing confounding factors Exposure estimates Accuracy of medical diagnosis Analysis of results (case numbers, exposure range, etc.) 33 SH ELL-MCCLU RG-OS4141 Recent Epidemiological Studies National Cancer Institute Shanghai Study (NCI) - case-control study published in 1997 Benzene associated with AM L and Non Hodgkin's Lymphoma (NHL): unusual association with a non-AM L cancer Study design did not add to understanding of threshold (lowest exposure group was 10 ppm or less) 34 SH ELL-MCCLU RG-OS4142 Recent Epidemiological Studies Australian Institute of Petroleum's (AlP) Health Watch Study - case-control study released in 2001 Association with all leukemias, including chronic lymphocytic leukemia No association with NHL or multiple myeloma 35 SH ELL-MCCLU RG-OS4143 Observations on Current Science No definitive epidemiological evidence to define a threshold NCI and AlP studies conflict with earlier studies by associating benzene exposure with non-AML cancers SHS designed to quantitatively address these issues 36 SH ELL-MCCLU RG-OS4144 SHS Elements Case Control Study Disease Progression Study Molecular Epidemiology Quality Science Scientific Review Panels Current Status Scientific and Ethical Reviews Projected Timeline 37 SH ELL-MCCLU RG-OS414S Specific Study Goals Understand relationship, if any, between benzene exposure and development of specific hematopoietic diseases: AA, MDS, AML and NHL Causation of specific diseases/subtypes Mechanism of disease progression Dose-response relationships Identification of cofactors and confounders Identification of biomarkers of exposure and disease progression 38 SH ELL-MCCLU RG-OS4146 Study #1 - Case Control Study Prospective epidemiology study to determine risk of AML, and potentially NHL, among benzene exposed workers Data collected will allow analysis of potential other causal factors for NHL Estimate 4 to 5 years to obtain 450 AML and 450 NHL patients into study Improved exposure assessment based on historical and concurrent workplace monitoring and questionnaire 39 SH ELL-MCCLU RG-OS4147 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 non-cancer states? Research methods: medical profile developed by questionnaire and interview, work history used for exposure reconstruction, blood and urine analyzed for biomarkers of benzene exposure 40 SH ELL-MCCLU RG-OS4148 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 41 SH ELL-MCCLU RG-OS4149 Quality Science Protocols approved by external Institutional Review Boards (IRB's) Govern use of human subjects U.S. and China independently Shanghai Health Study panels International Ethics Expert Panel International Scientific Expert Panel 10 members 6 scientific disciplines Involved during entire project 42 SH ELL-MCCLU RG-OS41S0 Scientific Review Panels Cancer Mechanisms Epidemiology Biostatistics Exposure Assessment Hematology Genetic Toxicology Occupational Health Dr. Jerry M. Rice, (Chair), Georgetown University Medical Center Dr. Helmut Greim, Technical University of Munich Dr. Harvey Checkoway, University of Washington Dr. Howard Rockette, University of Pittsburgh Dr. John Cherrie, Institute of Occupational Medicine Dr. Robert F. Herrick, Harvard School of Public Health Dr. Richard Larson, University of Chicago School of Medicine Dr. Mark Minden, University of Toronto Dr. Li Guilan, Chinese Center of Disease Control and Prevention Dr. Richard Albertini, University of Vermont 43 SHELL-MCCLURG-054151 Ethics Review Panels Bioethics Dr. Jerry M. Rice (Chair), Georgetown University Medical Center Dr. Juhana Idanpaan-Heikkila (Co-Chair), Council for International Organization of Medical Sciences (CIOMS) Dr. Ellen Clayton, Vanderbilt University Dr. Paul Lombardo, University of Virginia Dr. Xu Zong-Liang, Fudan University 44 SH ELL-MCCLU RG-OS41S2 Current SHS Status State-of-the-art laboratory constructed on Fudan University campus Built according to international standards Lab will support the project, Shanghai medical community and remain at Fudan Technology transfers Chinese staff receiving training at University of Colorado U.S. researchers working with Chinese colleagues and government officials on methodologies, questionnaires, processes, etc. 45 SH ELL-MCCLU RG-OS41S3 Scientific and Ethical Review Status Fudan University IRB - final approval Nov 01 External International Scientific Review Panel - final approval Jan 02 External Ethics Review Panel - final approval Feb 02 University of CO IRB - final approval May 02 Applied Health Sciences - final approval 02 46 SH ELL-MCCLU RG-OS41S4 SHS Projected Timeline Questionnaire development, pilot testing in progress, 2002 Key laboratory personnel trained, 2002 Laboratory complete, 2003 Laboratory opening, summer 2003 Case recruitment began - 4th quarter, 2003 1600 benzene exposed workers, 400 controls Time necessary to identify qualified patients Length of study may be extended if required Research, analysis expected 2003-2007 Results published as studies completed 47 SH ELL-MCCLU RG-054155 I SHS Sponsors I SH ELL-MCCLU RG-OS41S6 Who is Sponsoring the SHS? 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 Other participants welcome Project Administrator: American Petroleum Institute 49 SH ELL-MCCLU RG-OS41S7 Why Industry Sponsors? SHS goal to provide an accurate understanding of how benzene works on a molecular level in humans Advanced understanding of benzene-induced disease could lead to development of effective disease prevention strategies Would allow a more finely calibrated assessment of potential health effects Provide best protection for workers and public 50 SH ELL-MCCLU RG-OS41S8 Why Industry Sponsors? Worldwide, benzene occupational exposure regulatory standards vary widely O.Sppm in Malaysia; 1.0ppm in U.S.; 10ppm in Japan American Conference of Governmental Industrial Hygienists recommends O.Sppm Industry has long sponsored benzene research 51 SH ELL-MCCLU RG-OS41S9 SHS Funding Structure SH ELL-MCCLU RG-OS4160 SHS Funding Structure $21.08 million program total for all costs over approximately 5 years needed to complete study. Costs highest during first years (laboratory construction and equipment, training). Minimum contribution of $500k for full membership and participation 53 SHELL-MCCLURG-054161 SHS Funding Structure 0 irect costs pDrai.vtaaccyo;llection and analysis with procedures to protect Procedures and training for data collection in participating clinics; Constructing, training, staffing state-of-the-art hematology laboratory; Laboratory operations for research and clinical tests; and Operations for 5 years estimated to identify study cases Administrative costs Internal and external communications and coordination; API project administration, travel; off-site meetings 54 SH ELL-MCCLU RG-OS4162 Conclusions SH ELL-MCCLU RG-OS4163 Conclusions PRESENTER: SELECT AUDIENCE General Recruitment - Funding Recruitment - Technical 56 SH ELL-MCCLU RG-OS4164 Conclusions Study will advance benzene science Sponsors funding study Product stewardship Corporate social responsibility goals Anticipate completion and major publications by 2007 Results will add to accepted body of scientific research on benzene Referenced by government, industry decision-makers 57 SH ELL-MCCLU RG-054165 Additional Sponsors Needed Responsibility to understand the health impacts of your products Commitment to worker health, safety Need for most advanced science possible 58 SH ELL-MCCLU RG-OS4166 Terms, Sources and Resources SH ELL-MCCLU RG-OS4167 Terminology AA AML Biomarker Epidemiology Histology NHL 60 SH ELL-MCCLU RG-OS4168 Acronyms API - American Petroleum Institute AlP - Australia Institute of Petroleum IRB - Institutional Review Board CAPM - Chinese Academy of Preventive Medicine IPHS - Institute for Public Health Supervision (China) NCI - National Cancer Institute (U.S.) SUJCML - Sino-U.S. Joint Clinical and Molecular Lab SMCDCP - Shanghai Municipal Center for Disease Control and Prevention USEPA - U.S. Environmental Protection Agency 61 SH ELL-MCCLU RG-OS4169 Sources American Council of Government Industrial Hygienists Agency for Toxic Substances and Disease Registry ToxFAQs, U.S. Department of Health and Human Services American Petroleum Institute International Agency for Research on Cancer United States Environmental Protection Agency University of Colorado Cancer Center, Denver, CO 62 SH ELL-MCCLU RG-OS4170 For More Information Template: Add your contact information here. Lorraine Twerdok, BHRC Administrator 202.682.8344 twerdokl@api.org 63 SHELL-MCCLURG-OS4171 For More Information Patsy Clegg, Chair, Oversight Committee pmclegg@shell.com Patrick Beatty, Chair, Technical Committee patrickbeatty@chevrontexaco.com Ed Murphy, API Group Director of Industry Operations and Downstream murphy@api.org Lorraine Twerdok, BHRC Administrator twerdol@api.org 64 SH ELL-MCCLU RG-OS4172 SHANGHAI HEALTH STUDY Overview Purpose: To gain an accurate understanding of the relationship between benzene exposure and the risk of certain hematopoietic diseases. This study is an important element in the product stewardship programs of participating companies. It could also lead to improved, health-based regulatory (e.g., ambient air, water & occupational) standards worldwide, by providing the regulatory and scientific communities with additional information for more accurate assessment of the risks from exposure to benzene. A unique set of circumstances in Shanghai enabled investigators to launch this meaningful benzene research. These include a database of occupational exposures, and qualified coinvestigators influential in local scientific medical, and regulatory establishments. Therefore, questions that have complicated benzene health risk assessment for decades may be addressed in Shanghai. The Studies: The program involves three inter-related studies: Case-Control Study - A hospital-based case control study investigating the potential relationship between benzene exposure and both Non-Hodgkins Lymphoma (NHL) and Acute Myelogenous Leukemia (AML), including an attempt to quantify the potency of the AML response. Disease Progression Study - A hospital/clinic-based investigation of the potential relationship between non-cancer diseases of the bone marrow and AML to determine if effects on bone marrow progress through non-cancer stages to an ultimate leukemia. This study is also attempting to define the shape of the dose response for possible "precursor" diseases and could result in characterization of unique identifiers of benzene-induced AML. Molecular Epidemiology Study - Investigating if there is a quantitative relationship between benzene exposure and potential early indicators of both exposure and effect in a focused population of workers. The investigators are leading experts in their fields, coming from such well-known institutions as the University of Colorado Health Sciences Center and Fudan University Medical Center. The combined studies apply cutting-edge, 21 st century technologies in ways that will not only advance our understanding of benzene-induced disease, but may also identify potential prevention strategies for benzene-induced disease in individuals. Benefits: Information gained from this project may have direct relevance for worldwide regulatory standards designed to protect workers and the general population from benzeneinduced disease. These include air and water quality standards, as well as hazardous waste and site remediation standards. These studies will assist contributing companies in achieving the highest product stewardship goals and in oversight of their risk management programs. Challenges: The proposed studies meet several technical, ethical, and cultural/political challenges. Technical - In order to stand up to scientific scrutiny, studies must be large, well-managed, and incorporate the latest technology. State-of-the-art research is absolutely necessary to make real progress in developing sound benzene risk assessments. To that end, a Scientific Review Panel made up of leading experts from a number of fields relevant to these studies has reviewed and endorsed the research protocols. Additionally, the protocols have been reviewed by Use of Human Subjects Committees (Institutional Review Board or IRB) both in the US and China. September 13, 2004 - 1- SH ELL-MCCLU RG-OS4173 SHANGHAI HEALTH STUDY Overview Ethical - To address ethical issues posed by the study, the protocols have undergone a thorough analysis to ensure that they meet international standards for research involving humans, including for example insuring that the subjects and the communities benefit from participating in the study; that confidentiality is preserved, and that participants are fully informed about the research to give their informed consent. An Ethics Panel is part of the oversight for the project. It includes bioethicists from the U.S., China and Europe. Cultural/Political- A key to this program's success is local partnerships. Collaborators on these studies include researchers from the Medical School at Fudan University, the Institute for Public Health Supervision, and the Shanghai Municipal Centers for Disease Control and Prevention (the latter two are responsible for occupational exposure monitoring and enforcement in Shanghai). Costs: The estimated costs for the project were derived after careful consideration of all of the technical, ethical, and political issues. (inflation has been incorporated into the estimate). Item Cost Estimate $2,28 $15,92 Funding: Funding for the project is being provided by a consortium of interested oil and chemical companies. It is anticipated to take five years to complete the project. The costs will be highest in the first years of the project. For More Information: Please contact anyone of the following individuals. Patsy Clegg Brian Doll Patrick Beatty, PhD Don Burnett, PhD Michael Johnston Lorraine Twerdok, PhD Bruce Jarnot, PhD Shell Chemical ExxonMobil ChevronTexaco BP ConocoPhillips API API Q9:l~y,~1~gK@~1]._~lJ._~_Qm brian.e.doll@exxonmobil.com Qatrickbeatty@chevrontexaco.com burnettdmial,bo. com mike. d.Johnston@conocoQhilliQs.com twerdokl@aQi.org jarnotb@aQi.org 713-241-2521 703-846-2515 510-242-7037 630-420-5093 281-293-4468 202-682-8344 202-682-8473 September 13, 2004 - 2- SH ELL-MCCLU RG-OS4174 Final 9/9/2004 SHANGHAI HEALTH STUDY Main Messages As part of their ongoing individual product stewardship and safety and health programs, a consortium of petroleum and chemical companies is sponsoring a scientifically rigorous research project to further the current understanding of the human health effects of benzene. The research project's purpose is to gain a more refined understanding of the relationship between benzene exposure and associated cancer risks. The studies utilize cutting edge, state-of-the-art technologies to advance the scientific knowledge of benzene-induced disease and potential prevention strategies. This new approach to better define the risks from benzene exposure could impact future decisions on health-based air, water and occupational standards for benzene worldwide. While benzene is recognized as a human carcinogen, what is not understood is how cancer or other related diseases may be caused, the interactions that may occur between benzene and genetic material, and the role biomarkers may play in adding to existing knowledge. The study is a project of Fudan University Medical Center, the University of Colorado Health Sciences Center, and Applied Health Sciences (an independent U.S. research firm). Other key participants in China include the Shanghai Municipal Center for Disease Prevention and Control and the Shanghai Institute for Public Health and Supervision. The research program has met the rigorous requirements of three separate Independent Review Boards; the research program has also attained the approval of two separate and independent scientific and ethical review panels. Finally, the research also meets the Council for International Organizations of Medical Sciences (CIOMS) guidelines for medical research involving human subjects. The scientific and ethical review panels will remain involved as consultants throughout the project; permission to adjust the research protocols in any way also requires prior review and approval from each institution's Independent Review Board. Study sponsors are committed to seeing that the Shanghai Health Study in as open a manner as possible consistent with ensuring the investigators' research independence in conducting the study, analyzing the data, and publishing their conclusions. The sponsors' goal is for the study to contribute to the accepted body of scientific research on benzene consulted by decision makers in government and industry. A state-of-the-art clinical and molecular laboratory is being built on the Fudan Medical University campus. The laboratory supports the research project and the Shanghai medical community and will remain at Fudan once the project is completed. This sustainable technology transfer is an important aspect of the project design. The data from a wide range of benzene exposures in Shanghai, China provides a rare opportunity to conduct meaningful research on the health effects of human exposure to benzene. The unique historical database combined with cooperation of local regulatory authorities and the partnership with scientists in Shanghai form the basis for an exciting scientific collaboration. The joint Sino-U.S. benzene research and analysis is projected to take about five years. Results will be published, with final publications anticipated in 2007/8. SH ELL-MCCLU RG-OS417S Shanghai Health Study Background Information DRAFT Q: Who are the funders? A: Current funders (as of Oct. 2002): BP ChevronTexaco ConocoPhillips ExxonMobil Shell Chemical Additional funding from Marathon The American Petroleum Institute is the project administrator. Q: How were the funders selected? A: A consortium of petroleum and chemical companies are sponsoring the SHS as part of their ongoing individual product stewardship and corporate responsibility programs. Others with a similar interest in the health effects of benzene are welcome to join the consortium. Q: How much will the SHS cost? A: $21.08 million program total for all costs including: operations for five years estimated to identify case studies; staff training, data collection, and analysis; study revisions recommended by the scientific and ethics panels; patient privacy protections; constructing a state-of-the-art laboratory at Fudan University in China; and laboratory operations for research and clinical tests. - The on-site lab provides cutting edge technologies and diagnostic capabilities without necessitating shipping human tissue samples to the U. S. for testing. Q: Are funding shares equal? 1[not, how they are allocated? A: Funding shares for start-up were determined by size and sector. Currently, a contribution of $500,000 provides full membership benefits (see table at end of document). Q: Apart from financial commitments, ifour organization were to join, what are the membership requirements? A: Current members can serve on three separate committees -communications, oversight or technical. The oversight committee makes budgeting, resource and other major decisions; the technical committee follows progress of the research; SHS Funding Questions September 13, 2004 SH ELL-MCCLU RG-OS4176 FINAL and the communications committee helps with external communications about the project. Q: Would it be possible to join the SHS as a partial member? 1[so, how would that be decided? A: The Oversight Committee would need to consider that request. Marathon has been admitted as a partial member. They are invited to participate in the Annual Meeting and receive the investigator's periodic updates. Q: Why are petroleum andpetrochemical companies the only funders? A: The petrochemical industry has long taken a lead role in researching benzene health effects. However, any interested company or group is invited to participate. Q: Wouldn't the American Petroleum Institute and their European counterpart (CONCA WE) be a logical source for additional funds? A: All of the current funders are API and CONCAWE members. For a variety of reasons, member companies often fund and manage major research initiatives in a separate resource consortium rather than through the association. However, the sponsors do think the project should be of interest to other companies, industries and sectors and would like to see funding diversified. Q: Were other funders solicited? A: Yes and active outreach continues. Q: Iithey said no, why should I be interested? A: Each company has to set its own priorities and interests. And I can't address the decisions other companies have made. Obviously, since my company is funding the project (ALTfor API staff: since I'm closely involved with..) we think it is important for understanding the health effects of benzene, which is an important part of our product stewardship responsibilities. Q: Whyare the original project supporters seeking additional funding? A: We believe this project is of general interest to all companies who produce or handle benzene. We'd like to see as many of them as possible them directly involved. Q: What is the benefit to me to join the study at this point? Won't the study be conducted anyWay? A: Study sponsorship allows you the opportunity to engage in constructive dialogue on these issues with the people actively searching for worker safety solutions. It will help ensure your company has a solid understanding of the project, beyond the summaries presented in the anticipated peer-reviewed publication of the study SHS Funding Questions September 13, 2004 2 SH ELL-MCCLU RG-OS4177 FINAL results. And it will clearly demonstrate to your employees, customers and shareholders that you agree you have a responsibility to actively study and understand your products. Q: Your company was involved in designing the project; at this point my company wouldn't have input to the research. So why should we join now? A: First, the research was designed by Drs. Richard Irons and Otto Wong. Sponsoring companies established an Ethics Review Board and a Scientific Review Panel, both of which had extensive input to the project. These bodies endorsed the study design. While the initial sponsors had a lot to do with that process, they did not control the study design. As a result, we think we will make a sound contribution to the science of benzene health effects. [As appropriate, repeat reasons for joining.] Q: Is there a role for non-government and/ or government organizations in the SHS? A: We would welcome the opportunity to brief others on the project and to keep in touch with them on future progress. Approved Sponsorship Privileges for New Funding Sponsors Privileges Oversight Committee Technical Committee Budget Committee Communications Committee SRP/ERP Study Updates Website access Financial Reports Identified as sponsor on publications, posters and meeting presentations Annual Meeting <$500,000 X Observer X Invite to participate X -J -J -J Second tier acknowledgement: "With additional funding by .. " Observer $500,000 I share Participant Participant Participant Participant X -J -J -J Full Participant SHS Funding Questions September 13, 2004 3 SH ELL-MCCLU RG-OS4178