The assesment and control of non-differential and differential exposure misclassification in a case-control study of breast cancer

This research study was designed to investigate some of the methodological issues involved in the design, conduct and analysis of a case-control study. The overall objective was to determine the reliability and validity of exposure data collected in a nested casecontrol study of breast cancer (N=l,177). The study was designed specifically to determine if the retrospective (post-diagnostic) reports of exposure provided by the cases and the controls were systematically different, to assess the impact of any resulting exposure misclassification on the estimates of relative risk, and (most importantly) to develop and to evaluate a 'Validity Scale' as a possible design standard for the measurement and the statistical control of differential exposure misclassification in future case-control studies. To answer these questions, exposure information was collected prospectively and retrospectively by means of a self-administered questionnaire. When the retrospective (post-diagnostic) and prospective (pre-diagnostic) exposure assessments were compared, the reported levels of exposure were assessed to be both reliable and consistent, although some inconsistencies (i.e., random exposure misclassification) were noted. The data provided no strong and conclusive evidence that the knowledge of diagnosis (i.e., case versus control status) resulted in the differential reporting of past exposure and antecedent events by the cases and the controls. To determine the impact of exposure misclassification on the estimates of association, the prospective and retrospective odds ratios and their 95% confidence intervals were compared. Both the pre- and post-diagnostic odds ratios were found to be comparable. Therefore, the odds ratio (OR) estimates for the various study factors had not been biased towards or away from the null value (OR=1.00) by either the systematic overreporting or the underreporting of exposure by the cases and the controls. Furthermore, these data did not provide empirical evidence for the existence of either nondifferential or differential exposure misclassification. This was apparently the first study to explore directly the impact of different control groups on the estimates of association, and in particular, whether or not a particular control group would have a tendency to bias odds ratio estimates. Two control groups were recruited for the case-control comparisons ~ healthy controls (i.e., women with a normal mammogram) and anamnestically equivalent controls (i.e., women with an abnormal mammogram but no breast cancer). Correlation, Kappa and McNemar analyses reported similar levels of agreement and inconsistency between the prospective and retrospective reports of exposure among the three study comparison groups. The results suggested that no advantage was obtained by using a control group which was anamnestically equivalent to the cases (except for diagnosis) that is, had experienced the same trauma (an abnormal mammogram), had experienced the same diagnostics to determine a diagnosis, and the same motivation to participate in the research study, and to report their past exposures both completely and reliably. In addition, within the context of this research study, an 'Exposure Data Validity Scale' as conceptualized by Raphael (1987) was designed, implemented and evaluated as a design strategy for the measurement and the control of differential exposure misclassification (i.e., recall bias). Overall, the validity scale appeared to be an effective means of assessing the propensity of the cases and the controls to report past exposures differently, and whether or not the estimates of effect have been subject to distortion (bias) as a result of differential exposure misclassification (i.e., recall bias). Replication studies will be required to determine both the utility and effectiveness of an 'Exposure Data Validity Scale' as a design strategy to be included routinely in future case-control studies.Graduate and Postdoctoral StudiesGraduat