Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics &...

Graduate School of Public Health Graduate School of Public Health Department of Biostatistics Department of Biostatistics Center for Occupational Biostatistics & EpidemiologyCenter for Occupational Biostatistics & Epidemiology

PW_Phase 2 - PW_Phase 2 - 11

Presentation of Phase 2 ResultsPresentation of Phase 2 Results

June 2-3, 2010June 2-3, 2010

The Pratt & Whitney The Pratt & Whitney Epidemiology Study Epidemiology Study

Phase 2 Phase 2 Incidence of Central Nervous Incidence of Central Nervous

System (CNS) Neoplasms System (CNS) Neoplasms



Research TeamsResearch Teams

Univ. of Pittsburgh (Epidemiology)Univ. of Pittsburgh (Epidemiology)Gary Marsh, PhDGary Marsh, PhD

Jeanine Buchanich, PhDJeanine Buchanich, PhDAda Youk , PhDAda Youk , PhD

Frank Lieberman, MDFrank Lieberman, MDMike Cunningham, MSMike Cunningham, MS

Terri WashingtonTerri Washington

Univ. of Illinois at Chicago (Exposure Assessment)Univ. of Illinois at Chicago (Exposure Assessment) Nurtan Esmen, PhDNurtan Esmen, PhDSteve Lacey, PhDSteve Lacey, PhD

Kathleen Kennedy, MSKathleen Kennedy, MSRoger Hancock, MCERoger Hancock, MCE



Two-Part PresentationTwo-Part Presentation

Part 1: Overview of Phase 2 Findings

(Gary Marsh)

Part 2: Overview of Exposure Assessment

(Nurtan Esmen)



Purpose of the Overall StudyPurpose of the Overall Study

To investigate the earlier perception of an To investigate the earlier perception of an unusual occurrence of glioblastoma at the unusual occurrence of glioblastoma at the P&W North Haven facilityP&W North Haven facility



P&W Study HighlightsP&W Study HighlightsRemains 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



What was different about What was different about Phase 2 and Phase 1 ?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”



Very Large Very Large IncidenceIncidence Study Population Study Population

212,513 men and women who worked in 1 of 8 P&W 212,513 men and women who worked in 1 of 8 P&W sites during 1952–2001 sites during 1952–2001 and at risk of becoming a and at risk of becoming a case during 1976-2004case during 1976-2004

– North Haven (NH), East Hartford, Middletown, Rocky Hill, North Haven (NH), East Hartford, Middletown, Rocky Hill, Cheshire, Southington – Aircraft Rd, Southington – Newell Cheshire, Southington – Aircraft Rd, Southington – Newell St, Manchester FoundrySt, Manchester Foundry

Incidence evaluated 1976-2004 for 21 histological Incidence evaluated 1976-2004 for 21 histological categories based on CBTRUS codescategories based on CBTRUS codes

– 722 total CNS neoplasm cases 722 total CNS neoplasm cases – 489 malignant (275 glioblastoma)489 malignant (275 glioblastoma)– 233 benign233 benign



Data Analysis StrategyData Analysis StrategyAll workers at risk All workers at risk 1976 - 20011976 - 2001

Work-related factorsWork-related factors

Plant group, pay typePlant group, pay type

Year of hire, age at hireYear of hire, age at hire

Duration of workDuration of work

Time since first workTime since first work

Non work-related factorsNon work-related factors

Race, sexRace, sex

Age group, time periodAge group, time period

North Haven workers by North Haven workers by study factorsstudy factors

Combined DataCombined Data

Study factors Study factors

Subgroups by study Subgroups by study factorsfactors



Phase 2 Findings Phase 2 Findings Accepted for Accepted for Publication in Publication in Leading Peer-Leading Peer-Reviewed JournalReviewed Journal

Online version-Online version-June 7, 2010June 7, 2010

Print version-Print version-August 2010August 2010

Graduate School of Public Health Graduate School of Public Health Department of Biostatistics Center Department of Biostatistics Center for Occupational Biostatistics & Epidemiologyfor Occupational Biostatistics & Epidemiology PW_Phase 1 - PW_Phase 1 - 1010

Phase 2 – Results Phase 2 – Results

External ComparisonsExternal Comparisons



Total Cohort Level Findings – All Total Cohort Level Findings – All Malignant CNS Histology CategoriesMalignant CNS Histology Categories

We found that during the 1976-2004 study period, We found that during the 1976-2004 study period, the total study population was diagnosed with fewer the total study population was diagnosed with fewer than expected cases for nearly all malignant CNS than expected cases for nearly all malignant CNS neoplasm categories examined, including neoplasm categories examined, including glioblastoma, based on external comparisons with glioblastoma, based on external comparisons with US and CT.US and CT.



0

0.2

0.4

0.6

0.8

1

1.2

1.4

Gliom

a

Anaplastic

ast

rocyt

oma

Astrocy

tom

a, NOS

Gliobla

stom

a

Oligoden

droglio

ma

Anaplastic

Olig

o.

Ependym

oma

Mix

ed G

liom

a

Gliom

o mal

ignant,

NOS

Men

ingio

ma

Lymphom

a

Neoplasm

, unspec

ified

SIR

US CT

No Statistically Significant Elevations in Total Cohort No Statistically Significant Elevations in Total Cohort Incidence Rates, 1976-2004, Compared with US and CT Incidence Rates, 1976-2004, Compared with US and CT

427427 2020 6363 275275 1515 77 88 66 2727 99 2626 2121

# = observed cases# = observed cases1.101.10

1.151.151.231.23

1.061.06



Subgroup Level Findings – Subgroup Level Findings – Glioblastoma – CT ComparisonsGlioblastoma – CT Comparisons

We found a not statistically significant overall 8% excess We found a not statistically significant overall 8% excess among “only NH” workers compared with deficits in the among “only NH” workers compared with deficits in the other plant groupsother plant groups

We found elevated SIRs in several subgroups of workers We found elevated SIRs in several subgroups of workers from the “only” and “partial” NH groups, but none was from the “only” and “partial” NH groups, but none was statistically significant and few consistent patterns statistically significant and few consistent patterns emerged emerged

Consistent patterns unique to N. Haven workers included Consistent patterns unique to N. Haven workers included elevated SIRs for salaried workers and workers at risk of elevated SIRs for salaried workers and workers at risk of becoming a case in the oldest age group and latest time becoming a case in the oldest age group and latest time periodperiod



Glioblastoma Incidence Slightly Elevated but Not Glioblastoma Incidence Slightly Elevated but Not Statistically Significant in “Only NH” GroupStatistically Significant in “Only NH” Group

1.08

0.860.76

0.57

0

0.5

1

1.5

2

SIR

-CT

Only N. Haven

Partial N. Haven

Never N. Haven

Unspecified # = observed cases

4343 1818 179179 3535



Glioblastoma Incidence Most Elevated but Not Statistically Glioblastoma Incidence Most Elevated but Not Statistically Significant in Salaried “Only” & “Partial” NH GroupsSignificant in Salaried “Only” & “Partial” NH Groups

0

0.5

1

1.5

2

2.5

Salary Hourly Mixed

SIR

-CT

Only N. Haven

Partial N. Haven

Never N. Haven

Unspecified

55 1212 3939 1616 3737 66 1717 00 1616 22

SIR= 1.50SIR= 1.50

# = observed cases# = observed cases

SIR= 1.03SIR= 1.03

124124 11

SIR = 2.17SIR = 2.17

SIR= 1.09SIR= 1.09



Internal ComparisonsInternal Comparisons



Findings for Glioblastoma - Findings for Glioblastoma - Internal ComparisonsInternal Comparisons

For All Workers combined, none of the study factors For All Workers combined, none of the study factors considered was a statistically significant predictor of risk considered was a statistically significant predictor of risk and none of the factor subcategory-specific RRs was and none of the factor subcategory-specific RRs was statistically significant statistically significant

For “Ever NH” workers (Only+Partial), only payroll type For “Ever NH” workers (Only+Partial), only payroll type was a statistically significant predictor of risk due to was a statistically significant predictor of risk due to statistically significant RR=2.04 for salary vs. (hourly + statistically significant RR=2.04 for salary vs. (hourly + mixed) workersmixed) workers

For “Ever NH” workers, we found little or no evidence that For “Ever NH” workers, we found little or no evidence that risk was associated with other study factors including risk was associated with other study factors including duration of work and time since first workduration of work and time since first work



For All Workers, Glioblastoma Risk Higher in Only and For All Workers, Glioblastoma Risk Higher in Only and Partial N. Haven Compared with Never N. Haven Partial N. Haven Compared with Never N. Haven

0

0.5

1

1.5

2

Never N. Haven Only N. Haven Partial N. Haven Unspecified Plant

SIR

-CT

or

RR

External Comparison (SIR)

Internal Comparison (RR)

179 cases179 cases

RR= 1.00RR= 1.00

43 cases43 cases 18 cases18 cases 35 cases35 cases

RR= 1.29RR= 1.29

RR= 1.13RR= 1.13SIR= 1.08SIR= 1.08



For “Ever NH” Workers (Only + Partial), Only Payroll Type Was For “Ever NH” Workers (Only + Partial), Only Payroll Type Was Statistically Significant Predictor of Glioblastoma Risk Statistically Significant Predictor of Glioblastoma Risk

0

0.5

1

1.5

2

2.5

Hourly + Mixed Salary

SIR

-CT

or

RR



44 cases44 cases 17 cases17 cases

p < .05p < .05SIR= 1.65SIR= 1.65

RR= 1.00RR= 1.00

RR=2.04RR=2.04



For “Ever NH” Workers, Little Evidence That Glioblastoma For “Ever NH” Workers, Little Evidence That Glioblastoma Risk Associated with Duration of Work Risk Associated with Duration of Work

0

0.25

0.5

0.75

1

1.25

1.5

< 1 yr 1 - 4 yrs 5 - 19 yrs 20+ yrs

Duration of Time Worked

SIR

-CT

or

RR



23 cases23 cases

SIR= 1.33SIR= 1.33

RR= 1.00RR= 1.00


RRs adjusted for payroll typeRR= 1.32RR= 1.32

RR= 1.07RR= 1.07



For “Ever NH” Workers, No Evidence That Glioblastoma For “Ever NH” Workers, No Evidence That Glioblastoma Risk Associated with Time Since First Worked Risk Associated with Time Since First Worked

0

0.25

0.5

0.75

1

1.25

1.5

< 20 yr 20-29 yrs 30 - 39 yrs 40+ yrs

Time Since First Worked

SIR

-CT

or

RR



5 cases5 cases

RR= 1.00RR= 1.00


RRs adjusted for payroll type

SIR= 1.17SIR= 1.17



Other FindingsOther Findings



Detailed Evaluation of Other Malignant CNS Neoplasm Histologies

Evaluated 3 categories with 25+ total cases Evaluated 3 categories with 25+ total cases (astrocytoma-NOS, glioma-malignant and (astrocytoma-NOS, glioma-malignant and lymphoma) using external and internal comparisonslymphoma) using external and internal comparisons

Limited to total incidence subcohort due to small Limited to total incidence subcohort due to small numbers of plant group-specific casesnumbers of plant group-specific cases

Revealed no consistent evidence of trends or Revealed no consistent evidence of trends or patterns in SIRs or RRs suggestive of an patterns in SIRs or RRs suggestive of an association related to P&W employmentassociation related to P&W employment



How did the main results of Phase 1 and Phase 2 compare?

Overall findings for cancer incidence consistent with overall Overall findings for cancer incidence consistent with overall findings for CNS neoplasm mortality during same 1976-findings for CNS neoplasm mortality during same 1976-2004 study period2004 study period

– Reduced SMRs for “all malignant CNS neoplasms”Reduced SMRs for “all malignant CNS neoplasms”

– Reduced SMRs for “malignant brain neoplasms”Reduced SMRs for “malignant brain neoplasms”

Patterns of study factor-specific glioblastoma risks similar to Patterns of study factor-specific glioblastoma risks similar to those observed for “malignant brain cancer” in Phase 1 those observed for “malignant brain cancer” in Phase 1 mortality studymortality study



Overall Findings Consistent for Similar CNS Overall Findings Consistent for Similar CNS Neoplasm Categories in Phase 1 and Phase 2 Neoplasm Categories in Phase 1 and Phase 2

0

0.5

1

1.5

2

MalignantCNS

Neoplasms

MalignantBrain

Neoplasms

Glioma Glioblastoma

SM

R o

r S

IR-C

T

1952 - 2004

1976 - 2004

# = observed deaths or cases

462462 381381 427427 275275398398

SIR= .76SIR= .76 SIR= .77SIR= .77SMR= .95SMR= .95SMR= .94SMR= .94

SMR= .87SMR= .87

Phase 2 IncidencePhase 1 Mortality



Example:Example: Phase 1 Findings for Malignant Brain Cancer Phase 1 Findings for Malignant Brain Cancer by by Payroll Type Consistent with Phase 2 Findings for Payroll Type Consistent with Phase 2 Findings for

Glioblastoma (1976-2004)Glioblastoma (1976-2004)

0

0.5

1

1.5

2

2.5

Salary Hourly Mixed

SMR-

CT

Only N. Haven

Partial N. Haven

Never N. Haven

Unspecified

Salary Hourly Mixed

SIR-C

T

Phase 1 – Malignant Brain Cancer Mortality Phase 2 – Glioblastoma Incidence



Conclusions from Phase 2 Conclusions from Phase 2 Total cohort incidence rates for malignant CNS Total cohort incidence rates for malignant CNS neoplasms, including glioblastoma, were not elevated neoplasms, including glioblastoma, were not elevated compared to US and CT general populationscompared to US and CT general populations

Glioblastoma excesses unique to certain subgroups of Glioblastoma excesses unique to certain subgroups of workers from NH may be due to work outside of P&W, workers from NH may be due to work outside of P&W, non-work factors or workplace factors unique to NH non-work factors or workplace factors unique to NH not measured in the current phase of the studynot measured in the current phase of the study

Glioblastoma excesses in NH will be further evaluated Glioblastoma excesses in NH will be further evaluated in Phase 3 of the studyin Phase 3 of the study


P&W Epidemiology StudyP&W Epidemiology Study

Upcoming WorkUpcoming Work



What Comes Next ?What Comes Next ?Phase 3Phase 3

Completion of exposure assessment (Dr. Esmen Completion of exposure assessment (Dr. Esmen to discuss)to discuss)

Re-evaluate total and cause-specific Re-evaluate total and cause-specific mortalitymortality in in relation to detailed work history and workplace relation to detailed work history and workplace exposure informationexposure information

Re-evaluate Re-evaluate incidenceincidence of malignant CNS of malignant CNS neoplasms in relation to detailed work history and neoplasms in relation to detailed work history and workplace exposure informationworkplace exposure information



Estimated Timeline for Estimated Timeline for Phase 3Phase 3

20102010 20112011Q1Q1 Q2Q2 Q3Q3 Q4Q4 Q1Q1 Q2Q2 Q3Q3 Q4Q4

Data AnalysisData Analysis

Article PublishedArticle Published

Public Public PresentationsPresentations



AcknowledgmentsAcknowledgmentsWe gratefully acknowledge the support, We gratefully acknowledge the support, cooperation and assistance of the following cooperation and assistance of the following groups without whose help this study would not groups without whose help this study would not be possible: be possible: – The CT Dept. of Public HealthThe CT Dept. of Public Health– The Scientific Advisory CouncilThe Scientific Advisory Council– P&W HR and EHS personnelP&W HR and EHS personnel– The International Association of Machinists and The International Association of Machinists and

Aerospace Workers (IAMAW)Aerospace Workers (IAMAW)– The Communications Facilitation Workgroup The Communications Facilitation Workgroup



Questions?Questions?

Graduate School of Public Health Graduate School of Public Health Department of Biostatistics Department of Biostatistics Center for Occupational Biostatistics & EpidemiologyCenter for Occupational Biostatistics & Epidemiology PW_Phase 1 - PW_Phase 1 - 3333

Part 2Part 2

Exposure AssessmentExposure Assessment



END

Date post:	03-Jan-2016
Category:	Documents
Upload:	charity-boone
View:	215 times
Download:	0 times

Graduate School of Public Health Department of Biostatistics Center for Occupational Biostatistics &...

Documents