e t o u q Report of the HEI Diesel r o Epidemiology Panel - PowerPoint PPT Presentation

e t o u q Report of the HEI Diesel r o Epidemiology Panel (Part II): e Diesel Epidemiology and t i c Lung Cancer t o n Introduction and Framing o Katherine Walker, Health Effects Institute D

e Outline t o u q • A short history of diesel exhaust, r o epidemiology and risk assessment e • A tale of 2 studies t i c • A project design t o • A panel n • A charge o D • HEI’s evaluation approach 2

e A short history : Diesel exhaust, t o epidemiology and risk assessment u q • Two decades of systematic reviews (IARC, WHO, EPA, etc) associate exposures to older technology diesel engine r o exhaust with increased rates of lung cancer e t • However, setting risk-based quantitative standards or i c guidelines limited by exposure assessments t o • 1999 HEI Report recommended against n use of the then available epidemiologic o studies in railroad workers and in teamsters D for quantitative risk assessment 3

e A short history: t o Research Needs for Quantitative Risk Assessment u (HEI 1999, 2002 ) q • Measures of diesel constituents Better measures of r exposure o • Valid chemical markers of the complex mix of diesel exhaust emissions. • Specific biomarkers of diesel exposures, health outcomes, and e susceptibility • More use of personal monitors, area monitors placed where diesel t Better models of exposure is likely to occur, and current and historical data regarding i c exposure emission sources. reliable estimates of past emissions and of factors affecting historical • exposures …… t • Exposures should be adequately and accurately characterized with o Better study designs respect to magnitude, frequency, and duration, rather than solely by for exposure-response duration of employment. n Exposures should be close to levels of regulatory concern, including a • range of exposures to provide a base for understanding the relation between exposure and health effects. o • Errors and uncertainties in exposure measurements should be D quantified where possible; These should be fully reported to users, and taken into account in both • 4 power calculations and exposure–response analyses. Cigarette smoking must be controlled for in any study of risk factors for • this disease. • A cohort study subset that uses a case-control or case-cohort design with smoking histories will strengthen the interpretation of results.

e A short history : t o IARC re-classifies diesel exhaust as Group 1 u q r o e t i … c t KEY COMPONENTS: o The US Truckers Study and Diesel Exhaust in Miners Study (DEMS) • n CAVEATS: • Based on animal and human studies with old technology diesel exhaust o • IARC noted substantial (>98%) improvements in new technology diesel, but D • Only new technology diesel study: HEI’s Advanced Collaborative Emissions Study 5 (ACES) • Suggest relevance of their review where fleet turnover incomplete or slow (as in less developed countries)

e A tale of 2 studies: t o u q r o e t i c t o National Cancer Institute/ National Institute of Occupational Safety and Health (NCI/NIOSH) n o D 6

e DEMS and Truckers: Overview t o u DEMS Truckers q Design Cohort and Nested Case- Cohort Control r Questionnaire Yes, individual level risk No o factors e Population 8 U.S. non-metal mines 139 U.S. Trucking terminals (limestone, trona, salt, t i potash) c 12,315 miners: 31,135 worker: 96% male, 88% white t 100% male, 85% white o Lung cancer 198 lung cancer cases, 563 779 lung cancer cases n controls matched on mine, sex, race, and birth year o End of follow-up 1997 2000 D Metric of Respirable elemental carbon Submicron Elemental 7 personal (REC) ≤3.5 µg/m3 Carbon (SEC) ≤ 1 µg/m3 exposure

e DEMS and Truckers: Range of Exposures t o u q r o e t i c t o n o D 8

e Truckers Main results t o u q Entire Cohort • Main Models Hazard Ratio=1 r • Cumulative o exposure • 5-year lagged e • Adjustment t i for duration of c work – healthy t Excluding Mechanics worker effect o n o D 9

e t DEMS Main Results: Case-Control o u q All Subjects r Odd’s Ratio=1 o e t i c t o n o D 10 Silverman et al. 2012

An Overall Project Design: e t o Diesel Epidemiology Project II u q Charge Questions r o Appoint Panel e t • Selected Analyses of DEMS Evaluation i analytical data sets c Public t workshop o n Draft report o Peer D Review 11 Final • Summer We are here Report 2015

e A Charge t o u q 1. Reviewing the findings of the 1999 HEI Special Report on epidemiology and risk assessment r o 2. For recent epidemiologic studies, reviewing their design, data, and exposure estimates, … analyzing such data as needed. e t 3. Exploring whether the data from these new studies enables analyses to i extend concentration–response relationships to lower ambient c concentrations t 4. Identifying data gaps and sources of uncertainty. o n 5. Making recommendations about extension or further analyses of existing data sets. o D 6. Making recommendations, if necessary, about the design of new studies that would provide a stronger basis for risk assessment. 12

e A Panel: Diesel Epidemiology Project t o u q Daniel Krewski, PhD, Chair Professor and Director of the R. Samuel McLaughlin Centre for Population Health Risk Assessment at the University of Ottawa r Director, Occupational Cancer Research Centre, Cancer Care o Paul Demers, PhD Ontario and Professor, Dalla Lana School of Public Health, University of Toronto e Professor Emeritus, Department of Mechanical Engineering, David Foster, PhD t University of Wisconsin Madison i c Joel Kaufman, MD, MPH Professor, Environmental and Occupational Health Sciences, Medicine and Epidemiology; School of Public Health and School of Medicine, University of Washington t o Professor and Associate Chair, Department of Environmental Jonathan Levy, ScD Health, Boston University School of Public Health n Associate Professor, Department of Epidemiology, University Charles Poole, ScD, MPH of North Carolina School of Public Health o University Professor of Statistics, Canada Research Chair in Nancy Reid, PhD D Statistical Theory and Applications, University of Toronto 13 Martie van Tongeren, PhD Director, Centre for Human Exposure Science, Institute of Occupational Medicine, Edinburgh, Scotland, UK Professor, Department of Work Environment, University of Susan R. Woskie, PhD, CIH Massachusetts-Lowell.

e Panel evaluation approach t o u q • Internal Panel Deliberations April 2013 to September 2014 • Review of each study r o • Review of published commentaries on both studies and investigator responses e t • Public Workshop and Presentations – March 6, 2014 i c • DEMS: Silverman, Stewart, Vermeulen, Attfield • Truckers: Garshick t o • EMA-led Consortium: Crump and Moolgavkar • Risk Assessors/Managers: Cogliano/EPA; Park/NIOSH; n Rodricks/Environ Corp. o • Analyses in DEMS analytical data sets: D • Replication of main results 14 • Evaluation of smoking, radon and other analyses

Panel Evaluation Process: e t o Analyses of DEMS data u q Analytical data sets Additional opportunities r • Case-control variables • Linkage available o through further • Cohort variables e application National • Obtained by application to t Center for Health NCI and NIOSH, with IRB i c Statistics Research Data approval Center • In secure facility at U of t o Ottawa • Extensive underlying • By data use agreement, n mine and job data cannot be linked collected by authors o • Exposure data sets: • Obtained by EMA by FOIA downloadable on-line from D • Now available to public NIOSH website 15

e Evaluation Approach (Cont’d) t o u “ Reanalysis of the DEMS Nested-case q “Diesel engine exhaust and lung control study of lung cancer and cancer mortality ---time-related diesel exhaust: suitability for r factors in exposure and risk” quantitative risk analysis” o Crump et al. (2015) * Moolgavkar et al. (2015)* e • Cohort analytical dataset • Case-control (linked to cohort) t i • 6 Alternative REC estimates and • Time-dependent exposure c exposure assignments modeling with TSCE model • Alternative variable selection for t main CPH models • Subset analysis with only- o • Control for cumulative radon underground workers n (WLMs) • Individual mine-by-mine • Alternative tests for trend o analysis of risk using TSCE and • Subset analysis with only- underground workers CPH models D • “leave one out” analysis of 16 individual mines * Funded by consortium of companies led by the Engine Manufacturers Association

NRC Paradigm: e t o Quantitative risk assessment u q Research-Based Risk Assessment Risk Management Data Streams r o IARC, others Regulatory Human options • Experimental e Epidemiology • t Hazard Identification Evaluate Animal i c consequences of Mechanistic options Characterization of Risk Public health • t Pharmacokinetic and Uncertainty o • Economic Absorption, • • Social Exposure-Response distribution, n • Political Assessment metabolism, excretion • Other • Dosimetry modeling o D Agency decisions Exposure measurements, and actions predictions, 17 Exposure Assessment biomonitoring Stakeholder input