Referent sampling, family history and relative risk: the role of length-biased sampling

Abstract

Familial risk of disease is often assessed using case control studies based on referent databases. A referent database is a collection of family histories of cases typically assembled as a result of one family member being diagnosed with disease. This sampling scheme is equivalent to sampling families proportional to their size. The larger the family, the greater the probability of finding the family in the referent registry. This phenomena is known as length-biased sampling. The consequence of this kind of sampling is to bias the regression estimate associated with family history. The estimate is typically inflated in comparison to what is true for the actual population.