Document QX181XbzYKKEd4MdOp6b93yJE

From: Methvin, Stacy P SCC-DCA Sent: Sunday, December 17, 2006 8:38 PM To: Hofmeister, John D SHLOIL-CA Cc: Clegg, Patsy M SCC-DCSI22; Simpson, Edward J SCC-DCA/2 Subject: Shanghai Health Study - Dec 17 2006.ppt John, On Monday I will be calling you to discuss the attached slides on the Shanghai Health Study (benzene exposure analysis). I understand that you have a telecon with API later in the day where this subject will come up. There was an important meeting last week where the members of the consortium which provides funding for this project discussed the recent request for a 40% increase in funding. Shell's response is due on January 5. At this time I am inclined to approve given the conditions that have been set forth although I am surprised at the large increase in the fifth year of the study. I will be able to give you the key points of the situation and give you the opportunity to ask questions. Stacy SHELL-MCCLURG-068158 Shanghai Health Study Sponsor: Benzene Health Research Consortium Update December 2006 SHELL-MCCLURG-068159 Shanghai Health Study Program Overview - 5 Sponsors (Shell, ChevronTexaco, ExxonMobil, ConocoPhillips, BP) - Three studies shown on next slide - Benzene and leukemia/lymphoma epidemiology Benzene exposure estimation in Shanghai community. Leukemia/lymphoma epidemiology - a science based approach to understanding disease progression of a complex family of diseases: - Total contracted cost to date is $27 MM Shell's share to date is $5MM. Oversight Committee met on Dec. 13-14 to review additional request for funding up to $10.4 MM, $2 MM Shell share - Recommendation to grant $9.1 MM additional funds with conditions set for meeting program objectives, companies must respond by January 5. BP and Exxon have agreed their funding. SH ELL-MCCLU RG-068160 Study Scope: Health Effect Study of Benzene in Shanghai AML/NHL Case Control Study I AAlM DS/AML/B P Disease Progress Study Molecular Epidemiological Study of Benzene Exposure I Joint Sino-US Clinical and Molecular Laboratory ( JCML) SHELL-MCCLURG-068161 Shanghai Health Study - December 15,2006 Study Areas Desired Objectives 0 Case control 500 cases ofAML and NHL 0 Molecular Epi Biomarkers for disease 0 Disease Progression Knowledge in benzene poisoning and MDS progression to AML Current Status 425 AML / 240 NHL cases Factory worker evaluations 40 % AMLs / NHLs followed Options considered by Sponsors No additional funding Fully Fund Request Reduce risk of study not getting completed within new funding request Recommended Option Cost limited to current - $5 MM (Shell share) Shell share increased to $2MM Support additional funding if conditions met Contractual exposure if Shell does not fund Future $ increases unknown due Shell Share increased by to lack of requirements $1.7MM Reputation management End of study not guaranteed Defined end of study YE '08 SH ELL-MCCLU RG-068162 Shanghai Health Study - December 15,2006 Conditions defined by consortium in order to support additional funding: - Robust QAIQC process to be implemented; led by Dr Rice, Scientific Review Panel chair, with Dr. Wong, Case Control Study principal investigator and Judy Baldwin, professional QAIQC expert. QAIQC Team has full access to study database. - Case Control study accruals to achieve 500 AMLs and 500 NHLs or end by YE07 - whichever comes first - Progress on Disease Progression and Molecular Epi studies based on funding - Grant payments to University of Colorado tied to study progress - University of Colorado funding capped - Benzene Health Research Consortium (BHRC) to terminate YEOS - Monthly metrics on case accruals reported to Scientific Review Panel and BHRC Oversight Committee SH ELL-MCCLU RG-068163 Shanghai Health Study - December 15, 2006 Remaining Study Time Line - 2007: Complete data collection - 2008: Data analysis Closing Ceremony in Shanghai (cultural and ethics expectation) Sponsors consortium terminates - 2008-09: Publications SH ELL-MCCLU RG-068164 Shanghai Health Study Sponsor Review December 2006 SH ELL-MCCLU RG-068165 December 2006 Review Drivers for sponsoring study Accomplishments Funding challenge Elements for consideration - Technical assessment - Contracts and commitments - EA Options Recommendation SH ELL-MCCLU RG-068166 Drivers for sponsoring study Case Control: - Better dose response for benzene exposure and link to AML and NHL - Good epi data for risk assessment/regulation Disease progression: relationship of non-cancer diseases of the bone marrow and AML Molecular epi: relationship of benzene exposure and potential early indicators of exposure and effect SH ELL-MCCLU RG-068167 Accomplishments State of the art molecular diagnostic laboratory servicing the Shanghai community 7 publications 1st study to use WHO tumor classification scheme AML and NHL subtypes identified Large AML and NHL cohort identified, but not yet reached protocol estimates of 500 each Tissue bank and supporting database for cases SH ELL-MCCLU RG-068168 Funding challenge To the best of our knowledge (as of NoviDec 2006): - Total budget request from $ 26 Million to estimated $ 34 - $ 36 Million (~ added $ 2 million from Shell) - Increase due to unexpected: Staff retention difficulties. Case shortfall due to hospital(s) out of protocol compliance with respect to patient information. Extend case accrual beyond Dec 06 to Dec 07 or longer. Costs largely due to diagnostic laboratory. High end of budget range includes ~ $ 1.2 million for transition from consortium funded laboratory to independence. SH ELL-MCCLU RG-068169 Elements for Consideration Technical assessment - Full study objective closure unlikely (regardless of funding), with possible further extension requests. - Uncertain incremental added value with added funds. i.e., SMR (Standardized Mortality Ratio) - <1 - no link between exposure and effect - 1-2 - ? - >2 - link between exposure and effect - Higher than expected difficulties in exposure assessment in addition to infrastructure issues (i.e., case accrual protocol compliance). SH ELL-MCCLU RG-068170 Elements for Consideration Contracts - API/Shell contract "Joining the Research Group commits each company to pay its full portion of the total costs of the completed program." - API/University of Colorado Grant "This is grant is being provided to accomplish the research as set forth in the most recent versions of the research protocols and criteria document." EA SHELL-MCCLURG-068171 Options 1. Honor current commitment 2. Optimize cost options with alternative proposals such as stop case accrual mid 2007. 3. Support request for additional funding Seek support from DS, RDS 4. Other? SH ELL-MCCLU RG-068172 Recommendation SH ELL-MCCLU RG-068173