Response misclassification in studies on bilateral diseases.

Misclassification in binary outcomes can severely bias effect estimates of regression models when the models are naively applied to error-prone data. Here, we discuss response misclassification in studies on the special class of bilateral diseases. Such diseases can affect neither, one, or both entities of a paired organ, for example, the eyes or ears. If measurements are available on both organ entities, disease occurrence in a person is often defined as disease occurrence in at least one entity. In this setting, there are two reasons for response misclassification: (a) ignorance of missing disease assessment in one of the two entities and (b) error-prone disease assessment in the single entities. We investigate the consequences of ignoring both types of response misclassification and present an approach to adjust the bias from misclassification by optimizing an adequate likelihood function. The inherent modelling assumptions and problems in case of entity-specific misclassification are discussed. This work was motivated by studies on age-related macular degeneration (AMD), a disease that can occur separately in each eye of a person. We illustrate and discuss the proposed analysis approach based on real-world data of a study on AMD and simulated data.