Document DGD1LmdJb6gDmBmpn7xoBp73M

PROGRESS REPORT January 2006 1. ANALYSIS OF DISEASE PROGRESSION FOR APLASTIC ANEMIA, MYELODYSPLASTIC SYNDROME, ACUTE MYELOGENOUS LEUKEMIA AND BENZENE POISONING IN SHANGHAI, CHINA II. MOLECULAR EPIDEMIOLOGY OF BENZENE-EXPOSED WORKERS IN SHANGHAI, CHINA III. EXPOSURE ASSESSMENT A MULTICENTER INTERNATIONAL STUDY Molecular Toxicology and Environmental Health Sciences Program Dept. of Pharmaceutical Sciences, School of Pharmacy Department of Pathology, School of Medicine University of Colorado at Denver & Health Sciences Center, Denver, CO School of Public Health, Huashan Hospital, Cancer Hospital, Fudan University Medical Center, Shanghai, China 1 SH ELL-MCCLU RG-057975 EXECUTIVE SUlVIlVIARY A. Overall Status of Budget Attached is an official summary of the overall budget for the year ending December 31,2005. In April 2005, the consortium agreed to a revised budget (Appendix A). Based on this new budget, the overall status of the budget for the second half of the 2005 calendar year is as follows: We spent $1,341,540 compared to a projected budget of $1,883,130, resulting in savings of $541,590 in funds during this period (Table 1). This savings is partly due to cost shifting of contracts from the Fudan budget to the UCHSC budget, and partly due to expenses deferred to the 2006 calendar year. Table 1. Budget Summary (Reporting Period) Budgetedl Expenditures Variance Personnel $236,350 $243,816 ($7,466) Operating Expenses $254,380 $227,940 $26,440 Subcontracts $1,264,180 $747,991 $516,189 Travel $500 $0 $500 Equipment $0 $0 $0 Indirect $127,720 $121,793 $5,927 TOTALS $1,883,130 $1,341,540 $541,590 bThe budgeted amounts are the sum of each category from Jul-05 through Dec-05. Table 2. Budget Summary (Entire Project) Budgeted2 Expenditures Variance Personnel $2,163,606 $2,179,252 ($15,646) Operating Expenses $1,726,386 $1,557,404 $168,982 Subcontracts $7,198,588 $6,621,611 $576,977 Travel $9,993 $9,098 $895 Equipment $1,383,490 $1,383,490 $0 Indirect $1,043,587 $1,002,342 $41,245 TOTALS $13,525,649 $12,753,197 $772,452 2The budgeted amounts are the sum of each category from Dec-01 through Dec-05. Subcontract Summary (Entire Project) Subcontracts Fudan University IPHS SMCDC EMBSI Children's Hospital Cincinnati Expenditures (Dec 01 - Dec 05) $4,150,117 $167,577 $153,004 $1,873,555 $277,358 2 SH ELL-MCCLU RG-057976 B. Budget Analysis Our projected costs for the remainder of the project are outlined in Table 3. Table 3. Projected Budget (Remainder of Project) Personnel Operating Expenses Subcontracts Travel Equipment Indirect TOTALS Jan1 - Jun 30 Year 2006 $236,350 $235,580 $1,454,051 $500 $0 $122,832 $2,049,913 Jul 1 - Dec 31 Year 2007 ** Year 2006 $245,804 $203,265 $160,780 $150,000 $1,229,168 $609,595 $500 $0 $0 $0 $105,845 $52,849 $1,742,097 $1,015,709 **Post-study costs budgeted only through 6/07. 3 SH ELL-MCCLU RG-OS7977 Appendix A I p@iii:iii\:@(>" Apr '05 Budget 1$ Actual 1$ $p~f@M.I!:!#i~M~$ Apr '05 Budget 1$ Actual 1$ ~MiM#~f~Miii}> Apr '05 Budget 1$ Actual .Tf~\ii!if}>' 1$ Apr '05 Budget 1$ Actual 1$ ~Mfj:ifuMf}> Apr '05 Budget Actual @:@@f}>" 1$ 1$ Apr '05 Budget 1$ Actual 1$ .r9rA4~}>' Apr '05 Budget 1$ Actual 1$ Dee-Oil Jun-021 Dec-021 Jun-031 Dec-031 Jun-041 Dec-041 Jun-051 Dec-051 Jun-061 ,1~ost-StudY thru I~otal thru post-I Dec-06 Jun-07 Study 172,140 I $ 224,883 I $ 317,665 I $ 172,140 I $ 224,883 I $ 317,665 I $ 314,703 I $ 230,328 I $ 314,703 I $ 230,328 I $ 211,016 I $ 211,016 I $ 229,260 I $ 229,260 I $ 227,260 I $ 235,437 I $ 236,350 I $ 243,816 I 236,350 I $ 245,804 I $ II 203,265 I $ 1$ 2,849,025 I 2,179,248 I 13,131 1$ 13,131 1$ 94,401 1$ 193,990 I $ 94,401 I $ 193,990 I $ 158,850 I $ 162,834 I $ 158,850 I $ 162,834 I $ 364,542 I $ 364,542 I $ 237.258 I $ 237,258 I $ 247,000 I $ 104,457 I $ 254,380 I $ 227,940 I 235,580 I $ I 160,780 I $ I 150,000 I $ 1$ 2,272,746 I 1,557,403 I 123,629 I $ 123,629 I $ -I $ -I$ 1388,452 I $ 688,452 I $ 8,429 I $ 8,429 I $ 213,291 I $ 213,291 I $ 2181 $ 2181 $ 845,8130 I $ 565.870 I $ 1.128,507 1 $ I I845,860 $ 565,870 $ 1,128,507 1 $ 3461 $ 3461 $ -I$ 105 I $ -I $ -I $ 948.696 I $ 1,420,103 I $ 1,2134,180 1$ 1,454,051 I $ 1,229,1138 I $ 948,696 I $ I1,359,315 $ 747,991 I II -I $ 500 I $ 500 I $ 500 I $ 500 I -I $ -I $ -I II 1309,595 I $ 10,491,402 1 I1$ 6,621,611 1$ 10,9931 1$ 9,0981 291,568 I $ 253,578 I $ 354,496 I $ 274,508 I $ 17,000 I $ 192,340 I $ -I II 291,568 I $ 253,578 I $ 354,496 I $ 274,508 I $ 17,000 I $ 192,340 I $ -I $ -I $ -I II II 1$ 1,383,490 I 1$ 1,383,490 I 47,922 I $ 47,922 I $ 111,4541 $ 111,454 1 $ 139,587 I $ 139,587 I $ 122,902 I $ 101,4471$ 122,902 I $ 101,447 1$ 148,709 I $ 148,709 I $ 120,408 I $ 120,408 I $ 123,438 I $ 88,121 1$ 127,720 I $ 121,793 1 122,832 I $ 105,845 I $ II 52,849 I $ 1$ 1,325,1121 1,002,343 I 648,390 I $ 1,38'1:197 I $ 1,2'19,2411 $ 1,717,169 I $ 1,077,479 I $ 2,045,114 I $ 1,535,622 I $ 2,018,301 I $ 1,883,130 1$ 2,049,313 I $ 1,742,0971 $ 1,015,709 I $ 18,332,769 I 648,390 I $ 1,381,1971 $ 1,219,247 I $ 1,717,1691 $ 1,077,584 I $ 2,045,114 I $ 1,535,622 I $ 1,787,330 I $ 1,341,540 1$ -I $ -I 1$ 12,753,1931 Original Budget Revised Budget Increase $ 14,508,000 $ 18,332,953 $ 3,824,953 4 SH ELL-MCCLU RG-057978 I. JClVIL OPERATIONS A. Progress This progress report is abbreviated because of the detailed discussion of progress given at the annual meeting in November. Case accrual for 2005 numbered 1085 subjects, bringing the total study case accrual to 1816 cases. In addition, over the course of the project to date JCML has diagnosed approximately 40 pro bono cases for individuals, mostly children, who do not qualify for inclusion in our studies. Analysis of study data and manuscript generation continues. II. lVIOLECULAR EPIDElVIIOLOGY OF BENZENE-EXPOSED WORKERS A. lVIolecular Epidemiology Phase 1 The goal of the molecular epidemiology (phase 1) study is to: (a) study retrospective benzene exposure levels vs. blood counts present in worker exam records (2000), and (b) identify candidate factories for the Phase II study. Progress to date has been made in abstracting hematology counts from physical examination data for over 1500 cases from 19 facilities, and exposure assessment has been completed for 17 of these factories. Phase 1 is scheduled for completion in 2006. B. lVIolecular Epidemiology Phase 2 The goal of the ME study is to recruit 1000 workers at different levels of benzene exposure to ME Phase 2a studies. At present 233 individuals from 3 factories have been recruited and exposure assessment has been completed for all 3 factories. Participation and recruitment of workers and facilities has been hampered by cultural based westernoriented recruitment and informed-consenting strategies that have posed difficulties. These were outlined in detail in the previous progress report. Proposed changes recently endorsed by the Ethics Review Panel are currently under IRB review. If approved, these should facilitate ongoing worker recruitment. ME Phase 2b studies have been discontinued, in part because of problems in recruitment similar to Phase 2a and in part because of our success in recruiting these workers to the DP study. This approach has resulted in characterization of a new form of MDS associated with benzene exposure which was published in 2005. III. EXPOSURE ASSESSlVIENT The challenges and issues confronting the exposure assessment (EA) team were outlined and discussed in great detail at the annual meeting. Preliminary exposure assessments continue to keep pace with the accelerated recruitment of cases to CC and DP studies. Primary goals for the short term are to purchase additional and replacement equipment necessary for factory inspections, to recruit additional qualified personnel to the EA team and to continue to engage IPHS staff in database validation and the 5 SH ELL-MCCLU RG-057979 integration of database, factory site evaluation and sector information that will be necessary for final EA matrix construction that will take place in the last half of 2006. III. ElVIERGING CHALLENGES We are encountering difficulties in the continued retention of employees currently working on the project, as well as recruitment of additional staff to supplement efforts such as exposure assessment. In the past 6 months 3 EA team members, 2 members of the JCML laboratory staff, and 1 UCHSC staff member have all resigned. In addition, several highly trained laboratory personnel at JCML as well as several high level UCHSC staff and faculty members are currently exploring alternative employment options. Several of these individuals have expertise and study experience that places them on the critical path for completion of the project. If this attrition continues, the scheduled completion of the study and data analysis will be jeopardized. The explanation for this is readily apparent to those who are familiar with the academic research environment, namely, that salary support for academic research positions is directly linked to funded research projects. At present, there are no closely related projects that utilize the skills of staff dedicated to this project that are in place. Any support or information that consortium members can provide in a timely manner on research opportunities available within the industry or related organizations would be helpful to alleviate this problem. 6 SH ELL-MCCLU RG-OS7980