title: Bias associated with study protocols in epidemiologic studies of disease familial aggregation.
abstract: The effect of selection bias has not been well evaluated in epidemiologic studies which focus on familial aggregation. The authors illustrate this type of bias for a reconstructed cohort study. With the reconstructed cohort design, cases and controls are first selected from the population and their relatives form the exposed and unexposed cohorts, respectively. The recurrence risk ratio (RRR) is calculated to assess and measure familial aggregation. The ways of utilizing information from relatives affects the estimate of RRR, and the authors show that a traditional method used in epidemiologic studies can yield a severely biased estimate of the RRR. However, this traditional approach can give approximately unbiased estimates under special conditions. A novel selection approach is proposed which yields an unbiased estimate of RRR. In conclusion, when relatives are identified through cases or controls, they should be included and counted in the study cohorts each time a case or control is selected, even if they or other family members have already been included.
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Bai
authors.forename: S
authors.initials: S
authors.lastname: Sherman
authors.forename: M J
authors.initials: MJ
authors.lastname: Khoury
authors.forename: W D
authors.initials: WD
authors.lastname: Flanders
mesh_terms: D015982:Bias; D001932:Brain Neoplasms / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D015984:Causality; D002985:Clinical Protocols; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D015233:Models, Statistical; D016017:Odds Ratio; D018579:Patient Selection; D015203:Reproducibility of Results; D018570:Risk Assessment