Occupational Cohort Time Scales.

PURPOSE: This study explores how highly correlated time variables (occupational cohort time scales) contribute to confounding and ambiguity of interpretation. METHODS: Occupational cohort time scales were identified and organized through simple equations of three time scales (relational triads) and the connections between these triads (time scale web). The behavior of the time scales was examined when constraints were imposed on variable ranges and interrelationships. RESULTS: Constraints on a time scale in a triad create high correlations between the other two time scales. These correlations combine with the connections between relational triads to produce association paths. High correlation between time scales leads to ambiguity of interpretation. CONCLUSIONS: Understanding the properties of occupational cohort time scales, their relational triads, and the time scale web is helpful in understanding the origins of otherwise obscure confounding bias and ambiguity of interpretation.

Bias from using occupational smoking prevalence to adjust occupational incidence cohort lung cancer mortality rates.

OBJECTIVE: To describe how smoking correction factors based on comparing worker smoking prevalence with population smoking prevalence are biased if applied to an occupational incidence cohort. METHODS: Relative rates of smoking for shorter-tenure workers derived from occupational cohort lung cancer studies were applied to incidence and prevalence population tenure distributions to calculate relative smoking estimates. RESULTS: High smoking rates in short-tenure workers have little effect on prevalent worker rates (relative smoking estimates, 1.04 and 1.02) and much larger effect in occupational incidence populations (relative smoking estimates, 1.58 and 1.21), which have a much higher proportion of short tenure-workers. CONCLUSIONS: Smoking correction estimates derived from surveys of smoking habits in prevalent workers may introduce bias when applied to incidence workers because of very different proportions of short-tenure workers (length-time biased sampling).

Exposure to beryllium and occurrence of lung cancer: findings from a cox proportional hazards analysis of data from a retrospective cohort mortality study.

OBJECTIVE: The objective was to assess highly confounded patterns in a standardized mortality ratio (SMR) analysis of lung cancer in beryllium worker cohorts. METHODS: We used Cox proportional hazards single- and multi-variate models to assess confounding and the SMR patterns. RESULTS: We confirmed the lack of association of lung cancer with time worked. We could not confirm the original study's finding of lung cancer highly associated with earlier plants and or with workers hired in the 1940s compared to the 1950s. The pattern of higher rates of lung cancer with increasing latency was attenuated when covariates were added to the model. We could not exclude that the lower SMR and hazard ratios for workers hired in the 1960s might be related to assumed lower beryllium exposures. CONCLUSION: The patterns observed provide little support for an association of lung cancer with beryllium work factors. This result is likely due to the absence in the original study of a significant overall excess of lung cancer after smoking adjustment.

Empirical evaluation of complex epidemiologic study designs: workplace exposure and cancer.

OBJECTIVE: To test whether a frequently used cohort-nested case-control study design exaggerated exposure-response relationships because of unrecognized study design bias. Our aim was to evaluate empirically the performance of this complex study design. METHODS: We applied the design from one such study to a closely related cohort using randomly selected probands as cases. Values for average exposures were assigned to probands equal to, greater than, and less than those assigned to controls (matches). RESULTS: Under certain lag scenarios, the nested study design produced higher average exposure in probands compared with their matches, even when this was clearly not the case. CONCLUSIONS: Empirical evaluation demonstrated that the study design produced a biased case-control lagged exposure difference under the null hypothesis and could not distinguish qualitatively between null and alternate hypotheses. Empirical evaluation provided a useful check on results generated from a complex study design. It gave useful insight into the behavior of the index study design that was not otherwise readily deducible.

Exposure to beryllium and occurrence of lung cancer: a reexamination of findings from a nested case-control study.

OBJECTIVE: Our aim was to reanalyze a nested case-control study of beryllium and lung cancer because we identified analysis and study design issues that could have led to the elevated odds ratios obtained in the study. METHODS: We reanalyzed the data using nontransformed exposure metrics instead of log-transformed metrics used in the publication. We identified and examined effects on estimated odds ratios of imbalances between cases and controls caused by the control selection method. RESULTS: This reanalysis found no elevated odds ratios for any exposure variable. CONCLUSION: : Our conclusions differ from the authors' interpretation that the findings are due to a causal relationship between beryllium exposure and lung cancer. Our alternative explanation is that they may be due to methodological problems that could have been controlled by closer matching of controls to cases. CLINICAL SIGNIFICANCE: This study challenges conclusions made from a large case-control study concerning beryllium-lung cancer associations. Occupational medicine practitioners may want to integrate findings from this study into advice they give beryllium-exposed workers concerned about lung cancer.

Beryllium and lung cancer: a reanalysis of a NIOSH cohort mortality study.

This analysis is motivated by recent reviews on the carcinogenicity of beryllium by the International Agency for Research on Cancer, the U.S. Environmental Protection Agency, and the American Conference of Governmental Industrial Hygienists, and reconsideration by the National Toxicology Program on its classification of the carcinogenicity of beryllium. It reanalyzes data from a 1992 publication of a cohort mortality study conducted by the National Institute of Occupational Safety and Health (NIOSH) of workers employed in seven plants producing beryllium in the United States (Ward et al., 1992). That publication reported an increased risk of lung cancer in these workers and concluded that it is most likely due to occupational exposure to beryllium compounds. This present report uses: (1) an adjustment for smoking based on more germane estimates of the association between smoking and mortality from lung cancer; (2) computations of expected lung cancer rates based on alternative comparison populations; and (3) an overall combined estimate of the findings from the individual plants based on meta-analysis. Our findings indicate lower and generally not statistically significant standard mortality ratios that are not compatible with the interpretation of a likely causal association.