Document O3qppRVd3O0879vneOJ0w233M

FILE NAME: Z< DATE: DOC#: Z< DOCUMENT DESCRIPTION :ZZZdZZZ WZZ Letter to the Editor Regulatory ToxIcology and Pharmacology xxx (2012) xxx-xxx Contents lists available at SciVerse ScienceDirect Regulatory Toxicology and Pharmacology journal homepage: www.elsevier.com/locate/yrtph Letter concerning the paper by Finley and colleagues: dx.doi.org/ 10.1016/j.yrtph.2012.05.015 Dear Dr. Gori: Having yesterday completed an invited peer-revIew of an asbestos-related paper for Regulatory Toxicology and Pharmacology, I think that it is appropnate for me to comment on the paper by Fmley and colleagues entitled "Malignant Pleural Mesothelioma in U.s. Automotive Mechal1lcs: Reported vs Expected Number of Cases from 1975 to 2007" recently publIshed online (http:// dx.dol.org/l 0.1 016/J.yrtph.2012.05.015). The authors compared the number of malignant pleural mesothelioma (MPM) cases reported in the U.S. literature among auto mechanics between 1975-2007 to an expected value derived from estimated numbers of current and former auto mechanics. A total of 106 cases categorized as mesothelioma or malignant neoplasm of the pleura were found in the literature. Using background incidence rates for MPM of 2 and 3 cases per mIllion mdlviduals per year, they estimated that a range of 278-515 cases of non-asbestos-related .MPM, respectively, would have occurred in current or former auto mechanics from 1975 to 2007. They concluded that their findings are consistent with the numerous epidemiology studies that have found no mcreased nsk of MPM in auto mechal1lcs. It IS my opinion that the analysis of Fmley and colleagues IS fatally flawed and that theIr results and conclusion are not credible. The fundamental epidemIOlogic error IS that the "cases" and "controls" were not derived from the same sampling frame and are thus not comparable. The "cases" were derived from reports in the medical lIterature of mesothelioma among automotive mechalllcs; the person-years at nsk (PYR), from whIch the expected number of cases was calculated, were computed from a population based sample of all automotIve mechanics working in the United States. The authors have thus compared the expenence of that (unknown) fraction of mechanics whose dIsease was reported in the literature to an expectatIOn based upon the entire Table 1 SensItivIty analysIs of observed vs expected case' of mesothehoma among US auto mechamcs In whIch the reportIng rate of cases In the lIterature IS vaned. Fmley et al. found 106 cases. They estImated that 500 would be expected Pubhcatlon rate 0.1% 1% 5% 10% 25% 50% 100% Actual inCIdence 1000 x 106 = 106.000 100 x 106 = 10.600 20 x 106 = 2120 10 x lOG = lOGO 4 x 106 =424 2xlOG=212 106 Expected 500 500 500 500 500 500 500 SMR 200 20 4 2 04 02 populatIOn of US mechamcs. To provide a valid comparison, the authors should have compared the total number of cases of mesothelioma among US auto mechanics (unknown) to the expectation computed from the PYR of all US auto mechal1lcs, or, compared the number of cases of mesothelioma reported III the literature to the expectation computed from the PYR of those auto mechanics described in the literature. There are enormous challenges to both these approaches, but the authors have faded in their attempt to compute a credible estImate from the hybrid approach. It will be clear to all physicians and epidemiologists that the number of cases of any condition reported m the lIterature represent only a small fraction of those actually occurring. For example, I was asked in August 2008, by a plaintiffs attorney, to reVIew a case of mesothelioma in an auto mechanic. Since that tIme. I have been asked to revIew an additional 28 cases of mesothelIoma III fnction workers. Not a sIllgle one of these 29 cases has been reported m the medical lIterature. Finley reports that he, or some of his colleagues, have been retained by defense attorneys in asbestos litigation. I estimate that there is d less than 0.1 %probability that any of the frictIOn cases that they consulted on have been reported III the literature. From our combined experience, the best estimate is that no cases of mesothelIoma among auto mechanics have been reported in the literature. The report by Finley and colleagues provides evidence that this estimate of a 0% reporting rate, based on the experience of two groups of consultants, is incorrect. It is appropriate then to undertake a senSItIvity analYSIS of how the relatIve risk of mesothelIoma among auto mechal1lcs would vary according to the reporting rate of mesothelioma cases in the literature. Table 1 shows how the mortality rate ratio, or SMR, would vary according to the proportIOn of mesothelioma cases among mechal1lcs that are actually reported in the lIterature. The Table shows that the reportmg rate would have to be somewhat over 25% for the SMR for mesothelioma to equal 1. At higher rates of reporting, the SMR falls below 1 and reaches 0.2 at the level of reportmg used by Finley and colleagues. I leave It to you and your readers to guess as to the proportion of cases of mesothelioma among US auto mechal1lcs that are reported in the literature and to extract your personal estimate of the SMR from the Table. My own guess is that less than 1 III 20 cases of MPM occurring among brake mechanics are reported m the literature. This would correspond to an SMR for pleural mesothelIoma of 4 or higher. An increased fisk of MPM in auto mechanics is consistent with the deposition and retentIOn of CanadIan asbestos fibers in the lungs of these workers (Fmkelstein, 2008). Conflict of interest The author has worked as a consultant to plamtiffs lawyers 111 asbestos litIgation. 0273-2300/$ - see front matter 2012 Elsevler Inc All fights resel ved http //c1x.c1ol org/l0 1016/J.yrtph.2012.08 016 2 Letter to the EdItor/Regulatory ToxICology and Pharmacology xxx (2012) xxx-xxx Reference FlOkelstelO, M M., 2008. Asbestos fibre concentratIOns III the lungs of brake workers. another look Ann.Occup Hyg. 52, 455-461. Murray M. Finkelstein Department of Family and Community, Medicine University of Toronto, Granovsky Gluskin Family Medicine Centre, Mt Sinai Hospital, 60 Murray Street, 4th Floor, Toronto, Ontario, Canada M5T 3L9 Fax: +1 416 7368543 E-mail address:murray.finkelstein@utoronto.ca AvaIlable online xxxx