Prof Dr Alex Burdorf Department of Public Health, Erasmus MC Rotterdam

1. The adventures of an epidemiologist giving expert evidence in asbestos litigationcompensation claims for asbestos-related diseases in the Netherlands Prof Dr Alex Burdorf Department of Public Health, Erasmus MC Rotterdam

2. Asbestos use and mesothelioma in the world Lin et al. Lancet 2007;369:844-49. Mesothelioma deaths per million people per year 0 1 2 3 4 5 Asbestos consumption (kg per head per year)

3. Asbestos and occupation

5. Asbestos products are everywhere

6. Legal turning point: Asbestos Legislation 1977 • Legislation: • - first ban on specificproducts (asbestosspraying, crocidolite) • Key developments: • - rapidly emerging scientific knowledge within Dutch HSE and 1 university • successful interference of industry, avoidance of a complete ban • (asbestos cement) • - rise of the political debate • Stakeholders: • - Government: knowledge of secondary importance in policy-making process • - Industry: active player in science, politics, and media • - Unions: initiative for complete ban on asbestos, limited perseverance

7. Legal turning point: Asbestos Legislation 1977 The battlefield in science: - no differences in opinion between (the few) academic and HSE scientists - industry actively participated in advisory bodies, eg they drafted the first brochure of the Labour inspectorate in 1971, agreed upon in the most important advisory board to government - industry actively participated in scientific meetings and research: * creating uncertainty about fibre type, friability asbestos / solid matrix, existence of safe threshold * presented evidence for adequacy of control measures (safe use) * distributed scientific articles and reports to scientists - industryactivelydefended companies in emerginglawsuits

8. First asbestos litigation cases in the Netherlands Critical arguments: - the health risk of asbestoswereunknown at the time of exposure (response: historicaldevelopment of knowledge)

9. Development of knowledge about occcupational diseases Burdorf et al. Am J Ind Med 1991

10. First asbestos litigation cases in the Netherlands Critical arguments: - the health risk of asbestoswereunknown at the time of exposure (response: historicaldevelopment of knowledge) - workingconditionswerewithin the legaloccupationallimits at the time (response: development of knowledge on control measures)

11. Development of knowledge on control measures Swuste et al. IJOEH 2004

12. Legal turning point: Supreme Court decision 1990 Legislation: Supreme Court judgement Janssen - Nefabas 1990: shift of burden of proof from victim to employer. * control measures are required from early onwards (< 1945) * asbestos companies have an international network and, thus, have access to state-of-the-art knowledge * companies have the burden of proof, not the victim The battlefield in science: - industry hired specialized lawyers, which defence was based on: * claiming there was no or uncertain scientific knowledge in the past * critical scientists are biased * lengthy scientific exchange with lawyer of victim (> 100 pages)

13. Asbestos and mesothelioma - legal debate Asbestos is only well-demonstrated cause of mesothelioma (almost 1:1 !) Thus, debates about fibre types, routes of exposure and risks Arguments: - fibre type: “low exposure to chrysotile present no detectable risk” * Bernstein et al Crit Rev Toxicol 2013;43:154-83 - time at first exposure drives the individual risk, thus, everyone exposed already at early age through environment and household products * Vecchia and Boffetta in Eur J Can Prev 2012;21:227-30 “Continued exposure at working age does not create additional risk”

14. Asbestos and mesothelioma Potential attribution: apportionment of exposure history 1. Create a complete exposure history of an exposed worker with relevant sources of exposure (different jobs & tasks, at home, in environment) 2. Use risk models to estimate risk for each source of asbestos exposure (based on epidemiological research and risk assessment models) 3. Calculate relative contribution of each source (to the overall 100% !) Price et al. Mesothelioma: risk apportionment among asbestos exposure sources. Risk Analysis 2005;25:937-43.

15. Asbestos and mesothelioma Apportionment of exposure history: (mis)use in litigation 1. Total cumulative exposure in the job (few) years is much lower than • total cumulative exposure in general environment over lifetime 2. Company is most likely not responsible for the critical exposure that has caused the mesothelioma

16. Asbestos and disease From population to individual person (with a disease !) Levels of evidence for causality of the association (ILO-list Occupational Diseases): 1. Occupational disease Disease is caused by specific agent, e.g. mesothelioma and asbestos 2. Work-related disease Disease is multi-factorial, but strong evidence that a particular agent contributes to the disease, e.g. lung cancer and asbestos 3. Diseases affecting working populations Increased occurrence of disease in some populations, but association at individual level is very uncertain, e.g. breast cancer and shift work

17. Asbestos and lung cancer Classical epidemiological evidence Classical study Relative Risk for lung cancer No smoking and no asbestos 1 Smoking 11 Asbestos 5 Smoking and asbestos 53 Cuyler Hammond et al. Asbestos exposure, cigarette smoking and death rates. Ann N Y AcadSc 1979;330:473-90.

18. Asbestos and lung cancer - legal debate Asbestos is less important than smoking ! Thus, debates about relative contribution of asbestos exposure and of fibre types (again) Arguments: - fibre type: “low exposure to chrysotile present no detectable risk” * Bernstein et al Crit Rev Toxicol 2013;43:154-83 - smoking is much more important than asbestos, hence, no compensable disease

19. Asbestos and lung cancer Epidemiological measures of attribution Population attributable = proportion of lung cancer cases in the population fraction that is attributable to the exposure of interest Smoking PAF = 0.89 Asbestos PAF = 0.55 Smoking and asbestos PAF = 0.94

20. Asbestos and lung cancer Is population attributable fraction useful ? YES, for public health purposes the best measure (population level!) NO, not for assessment at individual level Please note that  PAFs easily exceed 1 (mutual adjustment required): Smoking PAF = 0.89 Asbestos PAF = 0.55 Smoking and asbestos PAF = 0.94

21. Asbestos and lung cancer Epidemiological measures of attribution (etiological approach) Attributable fraction = proportion of lung cancer cases among exposed that is attributable to the exposure Smoking AF = 0.91 Asbestos AF = 0.80 Smoking and asbestos AF = 0.98 RR = relative risk, R = disease rate

22. Asbestos and lung cancer Is attributable fraction useful ? YES, for assessment of probability that disease among exposed persons is caused by that exposure Please note: -  AFs can easily exceed 1 - AF often depends on the level of (cumulative) exposure, thus, AF increases with higher exposure - howtocompare AF of different causes?

23. Asbestos and lung cancer Incorrect use of measure of attribution Probability to die of lung cancer during lifetime Not exposed to asbestos 8% Exposed to asbestos (RR=1.35) 10.8% Risk difference is 10.8% - 8% = 2.8%. Thus, likelihood that lung cancer is caused by asbestos is 2.8% (= negligible) Classical mistake: estimation of prior probability to contract a particular disease, versus estimation of posterior probability whether the disease is caused by exposure

24. Asbestos and lung cancer Legal application of measures of attribution Casus: A 65 year old construction worker has been diagnosed with lung cancer. He has worked with asbestos-cement products. He files a claim for compensation. Questions: Which measure of attribution is justified ? What is interpretation of attribution ? How do different jurisdictions deal with attribution ?

25. Asbestos and lung cancer Use of measure of attribution (yes - no decision) Cumulative exposure Relative Risk of lung cancer 25 - 100 fibres/ml-years 2.00 (1997 Helsinki criteria) By use of lower estimate of 25 fibres/ml-years: Attributable fraction = (2 - 1) / 2 = 0.50 = 50% Thus, if cumulative exposure > 25 fibres/ml-years then attribution > 50%, thus, disease is caused primarily by asbestos (compensation system in Germany, Belgium, and other countries)

26. Asbestos and lung cancer Use of measure of attribution (proportional liability) Cumulative exposure Relative Risk of lung cancer 25 - 100 fibres/ml-years 2.00 1. risk = 1 fibre/ml-year will increase risk by 1% (upper estimate) 2. estimate cumulative exposure, eg. 35 fibre/ml-years (shipyard worker) 3. calculate relative risk; 35 * 1% = 35%, thus RR = 1.35 4. Calculate attributable fraction = 1.35 - 1 = 26% 1.35 Schaier-De Schelde ruling 1999

27. Asbestos and lung cancer Complications: the role of smoking 1. Multiplicative effect of asbestos and smoking (Riskasbestos * Risksmoking) ? 2. Quitting smoking will reduce risk of lung cancer considerably (crude estimation is elimination of risk after 20-30 years) Quitting asbestos exposure will probably also reduce risk of lung cancer 3. Epidemiological evidence is largely based on results among smokers (up to 1960s, smoking prevalence among men > 80%) Reid et al. The risk of lung cancer with increasing time since ceasing exposure to asbestos and quitting smoking. Occup Environ Med 2006;63:509-12. Sandén et al. The risk of lung cancer and mesothelioma after cessation of asbestos exposure: a prospective cohort study of shipyard workers. Eur Respir J 1992;5:281-5

28. Epidemiology and litigation 1. Use of appropriate measure of attribution: - attributable fraction - relevant for work-related disease 2. Understanding the correct use of the appropriate measure of attribution: - risk on disease  disease due to exposure - conditional probability (on disease status!) 3. Interpretation of attribution: - all or nothing (> 50%) - proportional liability

29. Risk management in the Netherlands a.burdorf@erasmusmc.nl