Quiz 6, Module Confounding
6. Lawn/garden pesticide use was significantly associated with breast cancer after adjusting for age, level of education, and other combined pest group (OR=1.34, 95% C.I. 1.11-1.63). Given that investigators also determined that a host of other factors (e.g., age of menarche, oral contraceptive use, and family history of breast cancer) did not meet the criteria for confounders, can the authors conclude that they have removed all sources of confounding in the examination of this association?
- Yes. Investigators have examined all potential risk factors for the outcome, adjusted for necessary confounders, and can be fully confident that their estimate is free of confounding.
- No. Authors did not adjust for family history of breast cancer, a known risk factor, and thus the association reported may be biased.
- Yes. Because authors conducted a case-control study, most of the confounding was removed in the design stage of the analysis because cases and controls are comparable on risk factors.
- No. Investigators can never be fully confident that confounding is eliminated in an observational study.
Answer (a) —
incorrect:
We can never be absolutely sure that our estimates are unbiased. First, it is unlikely that all measured confounders were measured without any error. For example, in the Teitelbaum et al. (2007) study, individuals self-reported on history of oral contraceptive use. It is likely that women were not 100% accurate in their memory of length of oral contraceptive use and exact dose, and thus the measurement of this variable is less than perfect. Further, there may be unmeasured confounding affecting the association. In an observational study such as this case-control study, we can never be sure that we have measured all confounders of the association. However, experimental studies such as RCT design, when sufficiently large, are capable of creating, on average, comparability between exposed and unexposed on all measured as well as unmeasured confounders by randomization of exposure.
Answer (b) —
incorrect:
The investigators reported that adjusting for history of breast cancer did not appreciably affect the results of the study. That is, among those with a history of breast cancer, the association between lawn/garden pesticide use and breast cancer was not different than: a) those without a history of breast cancer, and b) the crude estimate unadjusted for family history of breast cancer. Thus, family history of breast cancer (as measured) did not contribute to confounding of the association between lawn/garden pesticide use and breast cancer.
Answer (c) —
incorrect:
Cases and controls are never comparable on all risk factors for the outcome. Matching of cases to controls on age was used to remove confounding by age, but there may be many more measured and unmeasured risk factors which were not matched that need to be controlled.
Answer (d) —
correct:
We can never be absolutely sure that our estimates are unbiased. Residual confounding is confounding that remains even after many confounding variables have been controlled. It can occur if there is systematic error in the measurement of the confounders, if there are unmeasured confounders that have not been controlled, or if confounders were classified into categories that are too broad (Aschengrau & Seage, pp. 300-301).