Methodological review demonstrates inconsistent usage of confounding by indication in epidemiologic literature, suggesting refined definitions to distinguish severity and protopathic bias.
Confounding by indication is a term used when a variable is a risk factor for a disease among nonexposed persons and is associated with the exposure of interest in the population from which the cases derive, without being an intermediate step in the causal pathway between the exposure and the disease. However, in the literature, the term confounding by indication is not always used consistently. The authors found three different situations in which the term has been applied or might have been used but was not: confounding by indication as protopathic bias, as confounding by severity, or as a form of selection bias. It might be helpful to limit use of the term confounding by indication to the situation in which the disease that forms the indication acts as a confounder irrespective of its severity and to apply the term confounding by severity if the severity of this disease acts as a confounder. Protopathic bias and selection bias should not be confused with these terms. The use of appropriate terms ultimately will improve communication among researchers and contribute to the clarity of their papers.
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Salas et al. (1999) studied this question.
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