That conditioning on a common effect of exposure and outcome may cause selection, or collider-stratification, bias is not intuitive. We provide two hypothetical examples to convey concepts underlying bias due to conditioning on a collider. In the first example, fever is a common effect of influenza and consumption of a tainted egg-salad sandwich. In the second example, case-status is a common effect of a genotype and an environmental factor. In both examples, conditioning on the common effect imparts an association between two otherwise independent variables; we call this selection bias.

Better understanding of biases related to selective prescribing of, and adherence to, preventive treatments has led to improvements in the design and analysis of pharmacoepidemiologic studies. One influential development has been the “active comparator, new user” study design, which seeks to emulate the design of a head-to-head randomized controlled trial. In this review, we first discuss biases that may affect pharmacoepidemiologic studies and describe their direction and magnitude in a variety of settings. We then present the historical foundations of the active comparator, new user study design and explain how this design conceptually mitigates biases leading to a paradigm shift in pharmacoepidemiology. We offer practical guidance on the implementation of the study design using administrative databases. Finally, we provide an empirical example in which the active comparator, new user study design addresses biases that have previously impeded pharmacoepidemiologic studies.

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Objectives To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. Design Multinational retrospective cohort study of cancer mortality. Setting Cohorts of workers in the nuclear industry in 15 countries. Participants 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. Main outcome measurements Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. Results The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv ( < 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. Conclusions These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Study queStionIs protracted exposure to low doses of ionising radiation associated with an increased risk of solid cancer?