1. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 1 Presentation of Phase 2 Results Presentation of Phase 2 Results June 2-3, 2010 The Pratt & Whitney Epidemiology Study Phase 2 Incidence of Central Nervous System (CNS) Neoplasms

2. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 2 Research Teams Research Teams Univ. of Pittsburgh (Epidemiology) Gary Marsh, PhD Jeanine Buchanich, PhD Ada Youk, PhD Frank Lieberman, MD Mike Cunningham, MS Terri Washington Univ. of Illinois at Chicago (Exposure Assessment) Nurtan Esmen, PhD Steve Lacey, PhD Kathleen Kennedy, MS Roger Hancock, MCE

3. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 3 Two-Part Presentation Part 1: Overview of Phase 2 Findings (Gary Marsh) Part 2: Overview of Exposure Assessment (Nurtan Esmen)

4. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 4 Purpose of the Overall Study To investigate the earlier perception of an unusual occurrence of glioblastoma at the P&W North Haven facility

5. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 5 P&W Study Highlights Remains one of largest and most comprehensive occupational cohort studies ever done Phase 1 mortality study and Phase 2 CNS neoplasm incidence study complete and published Focus on malignant CNS neoplasms as registry data on benign neoplasms mostly not available before 2004 Final Phase 3 work needs to be done Potential not only to learn more about health in the P&W workplace but also about possible causes of brain cancer

6. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 6 What was different about Phase 2 and Phase 1 ? Phase 2 evaluated the incidence or occurrence of new cases of CNS neoplasms - Phase 1 examined deaths from CNS neoplasms The event date of interest in Phase 2 was cases’ date of diagnosis - Phase 1 used date of death Phase 2 provided first opportunity to examine incidence risk for specific CNS histologies, including glioblastoma, the histology of the North Haven index cases that prompted the overall study Phase 1 diagnostic specificity limited to “malignant brain cancer”

7. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 7 Very Large Incidence Study Population 212,513 men and women who worked in 1 of 8 P&W sites during 1952–2001 and at risk of becoming a case during 1976-2004 –North Haven (NH), East Hartford, Middletown, Rocky Hill, Cheshire, Southington – Aircraft Rd, Southington – Newell St, Manchester Foundry Incidence evaluated 1976-2004 for 21 histological categories based on CBTRUS codes –722 total CNS neoplasm cases – 489 malignant (275 glioblastoma) – 233 benign

8. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 8 Data Analysis Strategy All workers at risk 1976 - 2001 Work-related factors Plant group, pay type Year of hire, age at hire Duration of work Time since first work Non work-related factors Race, sex Age group, time period North Haven workers by study factors Combined Data Study factors Subgroups by study factors

9. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 9 Phase 2 Findings Accepted for Publication in Leading Peer- Reviewed Journal Online version- June 7, 2010 Print version- August 2010

10. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 10 Phase 2 – Results External Comparisons

11. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 11 Total Cohort Level Findings – All Malignant CNS Histology Categories We found that during the 1976-2004 study period, the total study population was diagnosed with fewer than expected cases for nearly all malignant CNS neoplasm categories examined, including glioblastoma, based on external comparisons with US and CT. We found that during the 1976-2004 study period, the total study population was diagnosed with fewer than expected cases for nearly all malignant CNS neoplasm categories examined, including glioblastoma, based on external comparisons with US and CT.

12. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 12 No Statistically Significant Elevations in Total Cohort Incidence Rates, 1976-2004, Compared with US and CT 427 20 63 275 157 8 6 27 9 26 21 # = observed cases 1.10 1.15 1.23 1.06

13. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 13 Subgroup Level Findings – Glioblastoma – CT Comparisons We found a not statistically significant overall 8% excess among “only NH” workers compared with deficits in the other plant groups We found a not statistically significant overall 8% excess among “only NH” workers compared with deficits in the other plant groups We found elevated SIRs in several subgroups of workers from the “only” and “partial” NH groups, but none was statistically significant and few consistent patterns emerged Consistent patterns unique to N. Haven workers included elevated SIRs for salaried workers and workers at risk of becoming a case in the oldest age group and latest time period

14. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 14 Glioblastoma Incidence Slightly Elevated but Not Statistically Significant in “Only NH” Group 4318 179 35

15. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 15 Glioblastoma Incidence Most Elevated but Not Statistically Significant in Salaried “Only” & “Partial” NH Groups 5123916376170162 SIR= 1.50 # = observed cases SIR= 1.03 1241 SIR = 2.17 SIR= 1.09

16. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 16 Phase 2 – Results Internal Comparisons

17. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 17 Findings for Glioblastoma - Internal Comparisons For All Workers combined, none of the study factors considered was a statistically significant predictor of risk and none of the factor subcategory-specific RRs was statistically significant For “Ever NH” workers (Only+Partial), only payroll type was a statistically significant predictor of risk due to statistically significant RR=2.04 for salary vs. (hourly + mixed) workers For “Ever NH” workers, we found little or no evidence that risk was associated with other study factors including duration of work and time since first work

18. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 18 For All Workers, Glioblastoma Risk Higher in Only and Partial N. Haven Compared with Never N. Haven 179 cases RR= 1.00 43 cases 18 cases 35 cases RR= 1.29 RR= 1.13 SIR= 1.08

19. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 19 For “Ever NH” Workers (Only + Partial), Only Payroll Type Was Statistically Significant Predictor of Glioblastoma Risk 44 cases 17 cases p <.05 SIR= 1.65 RR= 1.00 RR=2.04

20. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 20 For “Ever NH” Workers, Little Evidence That Glioblastoma Risk Associated with Duration of Work 23 cases SIR= 1.33 RR= 1.00 12 cases 11 cases 15 cases RRs adjusted for payroll type RR= 1.32 RR= 1.07

21. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 21 For “Ever NH” Workers, No Evidence That Glioblastoma Risk Associated with Time Since First Worked 5 cases RR= 1.00 16 cases 27 cases 13 cases RRs adjusted for payroll type SIR= 1.17

22. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 22 PW_Phase 1 - 22 Phase 2 – Results Other Findings

23. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 23 Detailed Evaluation of Other Malignant CNS Neoplasm Histologies Evaluated 3 categories with 25+ total cases (astrocytoma-NOS, glioma-malignant and lymphoma) using external and internal comparisons Limited to total incidence subcohort due to small numbers of plant group-specific cases Revealed no consistent evidence of trends or patterns in SIRs or RRs suggestive of an association related to P&W employment

24. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 24 How did the main results of Phase 1 and Phase 2 compare? Overall findings for cancer incidence consistent with overall findings for CNS neoplasm mortality during same 1976- 2004 study period –Reduced SMRs for “all malignant CNS neoplasms” –Reduced SMRs for “malignant brain neoplasms” Patterns of study factor-specific glioblastoma risks similar to those observed for “malignant brain cancer” in Phase 1 mortality study

25. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 25 Overall Findings Consistent for Similar CNS Neoplasm Categories in Phase 1 and Phase 2 462 381 427 275 398 SIR=.76 SIR=.77 SMR=.95 SMR=.94 SMR=.87 Phase 2 IncidencePhase 1 Mortality

26. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 26 Example: Phase 1 Findings for Malignant Brain Cancer by Payroll Type Consistent with Phase 2 Findings for Glioblastoma (1976-2004) Phase 1 – Malignant Brain Cancer Mortality Phase 2 – Glioblastoma Incidence

27. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 27 Conclusions from Phase 2 Total cohort incidence rates for malignant CNS neoplasms, including glioblastoma, were not elevated compared to US and CT general populations Glioblastoma excesses unique to certain subgroups of workers from NH may be due to work outside of P&W, non-work factors or workplace factors unique to NH not measured in the current phase of the study Glioblastoma excesses in NH will be further evaluated in Phase 3 of the study

28. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 28 P&W Epidemiology Study Upcoming Work

29. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 29 What Comes Next ? Phase 3 Completion of exposure assessment (Dr. Esmen to discuss) Re-evaluate total and cause-specific mortality in relation to detailed work history and workplace exposure information Re-evaluate incidence of malignant CNS neoplasms in relation to detailed work history and workplace exposure information

30. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 30 Estimated Timeline for Phase 3 2010 2011 Q1Q2Q3Q4Q1Q2Q3Q4 Data Analysis Article Published Public Presentations

31. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 31 Acknowledgments We gratefully acknowledge the support, cooperation and assistance of the following groups without whose help this study would not be possible: –The CT Dept. of Public Health –The Scientific Advisory Council –P&W HR and EHS personnel –The International Association of Machinists and Aerospace Workers (IAMAW) –The Communications Facilitation Workgroup

32. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 32 Questions?

33. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 1 - 33 PW_Phase 1 - 33 Part 2 Exposure Assessment

34. Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics & Epidemiology PW_Phase 2 - 34 END