Archives of Environmental Health: An International Journal
ISSN: 0003-9896 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/vzeh20
Occupational Mortality in Relation to Exposure Douglas Liddell MA FIS To cite this article: Douglas Liddell MA FIS (1975) Occupational Mortality in Relation to Exposure, Archives of Environmental Health: An International Journal, 30:5, 266-267, DOI: 10.1080/00039896.1975.10666695 To link to this article: http://dx.doi.org/10.1080/00039896.1975.10666695
Published online: 02 May 2013.
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Date: 29 June 2016, At: 13:18
Letters to the Editor
Downloaded by [University of California, San Diego] at 13:18 29 June 2016
The No-Pest Strip
'fo the Editor.- The article in the December issue of the ARCHIVES (29:308, 1974) on the safety of the polyvinyl chloride resin strip in the home ends with the unwarranted conclusion that there is no hazard from the use in the home, even with prolonged exposures. !>- few months to a year is a very brIef exposure for an "animal" with a life span of 70 years. I am reminded of the assurances we received in the 1930s and 1940s that the action of asbestos in the lung was only nuisance and mechanical. Several decades and a large volume of morbidity later have shown that these bland assurances were not factual. A science teacher in Pennsylvania had a high school senior expose labo~ :atory animals to the insecticide strip In a room 3.1 meters by 3.1 meters by 3.1 meters, built of plastic. Cages of insects were killed in a few hours: less than two. The mammals did not die in a few months but their coats were affected and autopsy showed substantial darkening of the liver. None of the control animals showed these effects on autopsy. (He has not performed these experiments on humans because it is so hard to get humans to volunteer for autopsy.) Does not the principle of the insecticide strip flaunt the advice in the introduction to "Threshold Limit Values," that " ... , the best practice is to maintain concentrations of all atmospheric contaminants as low as is practical"? Although it is valuable to have an insect-free home, it hardly seems so important as to justify violating this most fundamental, decades-old, environmental rule. FRANCIS SILVER, PE Martinsburg, W Va Occupational Mortality in RelatiQn to Exposure
To the Editor.-A first report on mortality to the end of 1966 in a cohort of some 12,000 chrysotile mine 266
Arch Environ HealthlVol 30, May 1975
and mill workers of Qu'ebec, born 1891 to 1920, was published by McDonald et al' in 1971. Later reports;,3 based on mortality experience to the end of 1969, attempted to overcome shortcomings in the analysis. In preparation for possibly final analysis of mortality in the same cohort to the end of 1973, now including smoking habits, as well as exposure history, advice was sought on the best available methods. To this end, a group of statisticians met at McGill University (Montreal) in June 1974, following much preparatory work and correspondence, and a full report was circulated for comment in July to all who had been invited to participate. The following paragraphs, summarizing our discussions, may be of interest to environmental epidemiologists. The concern was with methods for analyzing mortality in a cohort of persons born in a specified period, for whom work, exposure, and smoking histories had been ascertained together with either date and cau~e of death or survival to a fixed point in time or last trace. Methods of analysis in some 40 publications were reviewed. Most used a priori reasoning (from hypothesized causes to effects) as opposed to a posteriori reasoning (from effects to correlated causal variables). The a priori approach requires that the cohort be subdivided in terms of exposure or other possible causes of death, so that the mortality experience of the subgroups can be compared. Most of the potentially acceptable published methods are variants of what Case and Lea' called comparative composite cohort analysis. "Man-years of risk" are found by summing, over all subjects in a cohort, the trace-periods measured in years. "Expected deaths" are found by applying some standard age-, year-, and cause-specific death rates to man-years of risk (better, manyears "in view"). Expected deaths from each cause of interest in each age group are summed over the period of study; observed deaths are
summed similarly for comparison. The standard is often taken to be national death rates, but these can be misleading when applied to an occupational cohort, particularly when they are for all (occupied and retired) men: they do not take account of such disturbing factors as socioeconomic status, selection to the cohort, and lack of diagnostic comparability. It was concluded that, at least in large cohorts, internal standards are preferable. The observed deaths in each predefined subcohort can be expressed simply as rates, which can then be summarized and analyzed. For this purpose, it is common for 00served and expected deaths to be summed over all ages at death, and a ratio obtained of total observed deaths to total expected deaths. This is "indirect" standardization-with putative associated disadvantages.' On the other hand, promising results were reported on the use of a program (Glim) based on the work of NeIder and Wedderburn." This is a particularly flexible method of fitting models, and has advantages over the program of similar principle' used for the original analysis' of the Quebec data; and more still over the test for trend used earlier by Knox and his colleagues. 8 ,o In the a posteriori approach, the dead and the living are discriminated in terms of exposure and other potential causes of death. Oldham and Rossiter!O had used maximum likelihood (ML) discriminant analysis, but another way of obtaining orthogonal discriminants was preferred. Eyssen and Liddell had used this form of reasoning in the 1974 report3 on the Quebec data. For each death from lung cancer, four controls were selected from the cohort as born in the same year as the subject and still alive at the time of his death. Total dust exposures to this time were compared for subjects against controls, and relative risks were calculated. A more sophisticated procedure, owing to Cox," was to study each death in relation to all surviving to the same age, obtaining Letters to the Editor·
Downloaded by [University of California, San Diego] at 13:18 29 June 2016
an ML weighting of exposure variables related to the probability of dying. It was considered desirable to evaluate methods of analysis on data sets simulated with known hazards: a method that could not distinguish between simulated hazards and their associated relativities was unlikely to be useful with real data. For the symposium, three simulated data sets had been prepared and some preliminary evaluation had been carried out. There was clear need for refinement, and much has been done since to obtain more realistic simulations. Hypotheses about occupational mortality are legion, and they have to be evaluated in the light of possible synergisms; differences in dust retention in the lung depending on concentration, size,and shape of fibers; ventilation in relation to effort, airway configuration, and patterns of elimination; while the effects of retained fibers may depend on factors varying between individuals, such as susceptibility, period of latency, and age at first exposure. For the examination of anyone hypothesis, information on exposure has to be treated in a specific way, and seldom will a single index be sufficient. For the a priori approach, this implies a large number of subcohorts, leading to death rates with rather large errors. Testing of more than one hypothesis would require effects to be very large for significance within the framework of simultaneous inference. '2 The a posteriori methods also require information on exposure in a variety of ways, to permit the weighing of evidence in favor of various hypotheses, including the competition of risks and lags. However, degrees of freedom are consumed much less wastefully.
Arch Environ Health IVol 30, May 1975
An approach, using both types of reasoning in sequence, and combining the best features of both, was proposed by the McGill group. The sequence would be as follows: (1) Carry out a form of a posteriori analysis to determine the "best" hypothesise es); probability (significance) statements could be made at this stage with any necessary adjustments for simultaneous inference. (2) Define subcohorts to allow quantification of each selected hypothesis and carry out an a priori analysis to obtain mortality rates for each subcohort. No testing of hypothesis is required at this stage, which is one of estimating risk. (3) Summarize the calculated rates in life-table form and compare subcohorts, again without hypothesis testing. Conciusions
The McGill approach should be tried. Of a posteriori methods, that due to Cox appeared the most flexible, and could be used for each cause of death, without loss of independence (orthogonality). Ingenuity would be required in the choice of exposure variables to allow hypotheses to be studied; however, once the choice had been made, manipulation would be objective. Any use of a priori reasoning should be based on "man-years," using internal standards where possible, coupled with analysis, for which Glim seemed admirably suited. There would remain the need for intelligent definition of subcohorts. Methods for comparing the life-tables of subcohorts are available." Evaluation of the McGill approach is in hand. DOUGLAS LIDDELL, MA FIS Professor of Medical Statistics McGill University Montreal, Canada
Participants G. Barry, MRC, Pneumoconiosis Research Unit, lJnited Kingdom, P. E. Enterline, University of Pittsburgh; 1. D. Hill, MRC, Computer Unit, United Kingdom; L. Muenz, National Cancer Institute, United States; C. E. Rossiter, MRC, Pneumoconiosis Research Unit (unable to attend); M. A. Schneiderman, National Cancer Institute (unable to attend); H. Seidman, American Cancer Society; G. E. Eyssen; F. K. Liddell (chairman) and D. C. Thomas, McGill University. J. C. McDonald, McGill University was present at the symposium.
References 1. McDonald JC, McDonald AD, Gibbs GW, et al: Mortality in the chrysotile asbestos mines and mills of Quebec. Arch Environ Health 22:667686,1971. 2. McDonald JC, Rossiter CE, Eyssen G, et al: Mortality in the chrysotile producing industry of Quebec: A progress report, in Proceedings of the
Fourth International Pneumoconiosis Conference, Bucharest, 1971. Bucharest, Romania, Apimondia, 1973, pp 233-237. 3. McDonald JC, Becklake MR, Gibbs GW, et al: The health of chrysotile asbestos mine and mill workers of Quebec. Arch Environ Health 28:61-68, 1974. 4. Case RAM, Lea AJ: Mustard gas poisoning, chronic bronchitis, and lung cancer. Br J Prev Soc Med 9:62-72, 1955. 5. Liddell FDK: The measurement of occupational mortality. Br J Ind Med 17:228-233, 1960. 6. Neider JA, Wedderburn RWM: Generalized linear models. J R Stat Soc 135:370-384, 1972. 7. Berry G: Parametric analysis of disease incidence in multiway tables. Biometrics 26:572578, 1970. 8. Knox JF, Doll RS, Hill ID: Cohort analysis of changes in incidence of bronchial carcinoma in a textile asbestos factory. Ann NY Acad Sci 132:526-535, 1965. 9. Knox JF, Holmes S, Doll R, et al: Mortality from lung cancer and other causes among workers in an asbestos textile factory. Br J Ind Med 25:293-303, 1968. 10. Oldham PD, Rossiter CEo Mortality in coalworkers' pneumoconiosis related to lung function: A prospective study. Br J Ind Med 22:92-100, 1965. 11. Cox DR: Regression models and life-tables. J R Stat Soc 34:187-202, 1972. 12. Miller RG: Simultaneous Statistical Inference. New York, McGraw-Hill Book Co Inc, 1966. 13. Mantel N, Byar DP: Evaluation of response-time data involving transient states: An illustration using heart-transplant data. J Am Stat Assoc 69:81-86, 1974.
Letters to the Editor
2157
ISSN: 0003-9896 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/vzeh20
Occupational Mortality in Relation to Exposure Douglas Liddell MA FIS To cite this article: Douglas Liddell MA FIS (1975) Occupational Mortality in Relation to Exposure, Archives of Environmental Health: An International Journal, 30:5, 266-267, DOI: 10.1080/00039896.1975.10666695 To link to this article: http://dx.doi.org/10.1080/00039896.1975.10666695
Published online: 02 May 2013.
Submit your article to this journal
Article views: 1
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=vzeh20 Download by: [University of California, San Diego]
Date: 29 June 2016, At: 13:18
Letters to the Editor
Downloaded by [University of California, San Diego] at 13:18 29 June 2016
The No-Pest Strip
'fo the Editor.- The article in the December issue of the ARCHIVES (29:308, 1974) on the safety of the polyvinyl chloride resin strip in the home ends with the unwarranted conclusion that there is no hazard from the use in the home, even with prolonged exposures. !>- few months to a year is a very brIef exposure for an "animal" with a life span of 70 years. I am reminded of the assurances we received in the 1930s and 1940s that the action of asbestos in the lung was only nuisance and mechanical. Several decades and a large volume of morbidity later have shown that these bland assurances were not factual. A science teacher in Pennsylvania had a high school senior expose labo~ :atory animals to the insecticide strip In a room 3.1 meters by 3.1 meters by 3.1 meters, built of plastic. Cages of insects were killed in a few hours: less than two. The mammals did not die in a few months but their coats were affected and autopsy showed substantial darkening of the liver. None of the control animals showed these effects on autopsy. (He has not performed these experiments on humans because it is so hard to get humans to volunteer for autopsy.) Does not the principle of the insecticide strip flaunt the advice in the introduction to "Threshold Limit Values," that " ... , the best practice is to maintain concentrations of all atmospheric contaminants as low as is practical"? Although it is valuable to have an insect-free home, it hardly seems so important as to justify violating this most fundamental, decades-old, environmental rule. FRANCIS SILVER, PE Martinsburg, W Va Occupational Mortality in RelatiQn to Exposure
To the Editor.-A first report on mortality to the end of 1966 in a cohort of some 12,000 chrysotile mine 266
Arch Environ HealthlVol 30, May 1975
and mill workers of Qu'ebec, born 1891 to 1920, was published by McDonald et al' in 1971. Later reports;,3 based on mortality experience to the end of 1969, attempted to overcome shortcomings in the analysis. In preparation for possibly final analysis of mortality in the same cohort to the end of 1973, now including smoking habits, as well as exposure history, advice was sought on the best available methods. To this end, a group of statisticians met at McGill University (Montreal) in June 1974, following much preparatory work and correspondence, and a full report was circulated for comment in July to all who had been invited to participate. The following paragraphs, summarizing our discussions, may be of interest to environmental epidemiologists. The concern was with methods for analyzing mortality in a cohort of persons born in a specified period, for whom work, exposure, and smoking histories had been ascertained together with either date and cau~e of death or survival to a fixed point in time or last trace. Methods of analysis in some 40 publications were reviewed. Most used a priori reasoning (from hypothesized causes to effects) as opposed to a posteriori reasoning (from effects to correlated causal variables). The a priori approach requires that the cohort be subdivided in terms of exposure or other possible causes of death, so that the mortality experience of the subgroups can be compared. Most of the potentially acceptable published methods are variants of what Case and Lea' called comparative composite cohort analysis. "Man-years of risk" are found by summing, over all subjects in a cohort, the trace-periods measured in years. "Expected deaths" are found by applying some standard age-, year-, and cause-specific death rates to man-years of risk (better, manyears "in view"). Expected deaths from each cause of interest in each age group are summed over the period of study; observed deaths are
summed similarly for comparison. The standard is often taken to be national death rates, but these can be misleading when applied to an occupational cohort, particularly when they are for all (occupied and retired) men: they do not take account of such disturbing factors as socioeconomic status, selection to the cohort, and lack of diagnostic comparability. It was concluded that, at least in large cohorts, internal standards are preferable. The observed deaths in each predefined subcohort can be expressed simply as rates, which can then be summarized and analyzed. For this purpose, it is common for 00served and expected deaths to be summed over all ages at death, and a ratio obtained of total observed deaths to total expected deaths. This is "indirect" standardization-with putative associated disadvantages.' On the other hand, promising results were reported on the use of a program (Glim) based on the work of NeIder and Wedderburn." This is a particularly flexible method of fitting models, and has advantages over the program of similar principle' used for the original analysis' of the Quebec data; and more still over the test for trend used earlier by Knox and his colleagues. 8 ,o In the a posteriori approach, the dead and the living are discriminated in terms of exposure and other potential causes of death. Oldham and Rossiter!O had used maximum likelihood (ML) discriminant analysis, but another way of obtaining orthogonal discriminants was preferred. Eyssen and Liddell had used this form of reasoning in the 1974 report3 on the Quebec data. For each death from lung cancer, four controls were selected from the cohort as born in the same year as the subject and still alive at the time of his death. Total dust exposures to this time were compared for subjects against controls, and relative risks were calculated. A more sophisticated procedure, owing to Cox," was to study each death in relation to all surviving to the same age, obtaining Letters to the Editor·
Downloaded by [University of California, San Diego] at 13:18 29 June 2016
an ML weighting of exposure variables related to the probability of dying. It was considered desirable to evaluate methods of analysis on data sets simulated with known hazards: a method that could not distinguish between simulated hazards and their associated relativities was unlikely to be useful with real data. For the symposium, three simulated data sets had been prepared and some preliminary evaluation had been carried out. There was clear need for refinement, and much has been done since to obtain more realistic simulations. Hypotheses about occupational mortality are legion, and they have to be evaluated in the light of possible synergisms; differences in dust retention in the lung depending on concentration, size,and shape of fibers; ventilation in relation to effort, airway configuration, and patterns of elimination; while the effects of retained fibers may depend on factors varying between individuals, such as susceptibility, period of latency, and age at first exposure. For the examination of anyone hypothesis, information on exposure has to be treated in a specific way, and seldom will a single index be sufficient. For the a priori approach, this implies a large number of subcohorts, leading to death rates with rather large errors. Testing of more than one hypothesis would require effects to be very large for significance within the framework of simultaneous inference. '2 The a posteriori methods also require information on exposure in a variety of ways, to permit the weighing of evidence in favor of various hypotheses, including the competition of risks and lags. However, degrees of freedom are consumed much less wastefully.
Arch Environ Health IVol 30, May 1975
An approach, using both types of reasoning in sequence, and combining the best features of both, was proposed by the McGill group. The sequence would be as follows: (1) Carry out a form of a posteriori analysis to determine the "best" hypothesise es); probability (significance) statements could be made at this stage with any necessary adjustments for simultaneous inference. (2) Define subcohorts to allow quantification of each selected hypothesis and carry out an a priori analysis to obtain mortality rates for each subcohort. No testing of hypothesis is required at this stage, which is one of estimating risk. (3) Summarize the calculated rates in life-table form and compare subcohorts, again without hypothesis testing. Conciusions
The McGill approach should be tried. Of a posteriori methods, that due to Cox appeared the most flexible, and could be used for each cause of death, without loss of independence (orthogonality). Ingenuity would be required in the choice of exposure variables to allow hypotheses to be studied; however, once the choice had been made, manipulation would be objective. Any use of a priori reasoning should be based on "man-years," using internal standards where possible, coupled with analysis, for which Glim seemed admirably suited. There would remain the need for intelligent definition of subcohorts. Methods for comparing the life-tables of subcohorts are available." Evaluation of the McGill approach is in hand. DOUGLAS LIDDELL, MA FIS Professor of Medical Statistics McGill University Montreal, Canada
Participants G. Barry, MRC, Pneumoconiosis Research Unit, lJnited Kingdom, P. E. Enterline, University of Pittsburgh; 1. D. Hill, MRC, Computer Unit, United Kingdom; L. Muenz, National Cancer Institute, United States; C. E. Rossiter, MRC, Pneumoconiosis Research Unit (unable to attend); M. A. Schneiderman, National Cancer Institute (unable to attend); H. Seidman, American Cancer Society; G. E. Eyssen; F. K. Liddell (chairman) and D. C. Thomas, McGill University. J. C. McDonald, McGill University was present at the symposium.
References 1. McDonald JC, McDonald AD, Gibbs GW, et al: Mortality in the chrysotile asbestos mines and mills of Quebec. Arch Environ Health 22:667686,1971. 2. McDonald JC, Rossiter CE, Eyssen G, et al: Mortality in the chrysotile producing industry of Quebec: A progress report, in Proceedings of the
Fourth International Pneumoconiosis Conference, Bucharest, 1971. Bucharest, Romania, Apimondia, 1973, pp 233-237. 3. McDonald JC, Becklake MR, Gibbs GW, et al: The health of chrysotile asbestos mine and mill workers of Quebec. Arch Environ Health 28:61-68, 1974. 4. Case RAM, Lea AJ: Mustard gas poisoning, chronic bronchitis, and lung cancer. Br J Prev Soc Med 9:62-72, 1955. 5. Liddell FDK: The measurement of occupational mortality. Br J Ind Med 17:228-233, 1960. 6. Neider JA, Wedderburn RWM: Generalized linear models. J R Stat Soc 135:370-384, 1972. 7. Berry G: Parametric analysis of disease incidence in multiway tables. Biometrics 26:572578, 1970. 8. Knox JF, Doll RS, Hill ID: Cohort analysis of changes in incidence of bronchial carcinoma in a textile asbestos factory. Ann NY Acad Sci 132:526-535, 1965. 9. Knox JF, Holmes S, Doll R, et al: Mortality from lung cancer and other causes among workers in an asbestos textile factory. Br J Ind Med 25:293-303, 1968. 10. Oldham PD, Rossiter CEo Mortality in coalworkers' pneumoconiosis related to lung function: A prospective study. Br J Ind Med 22:92-100, 1965. 11. Cox DR: Regression models and life-tables. J R Stat Soc 34:187-202, 1972. 12. Miller RG: Simultaneous Statistical Inference. New York, McGraw-Hill Book Co Inc, 1966. 13. Mantel N, Byar DP: Evaluation of response-time data involving transient states: An illustration using heart-transplant data. J Am Stat Assoc 69:81-86, 1974.
Letters to the Editor
2157
