Impact of Event‐Related Treatment Modifications in Exposure‐Response Analyses of Repeated Time‐to‐Event Data

Exposure-response (ER) analyses of repeated time-to-event (RTTE) data can be confounded when treatment modifications occur due to the event of interest. One particularly challenging scenario is when an event is preceded by an undocumented clinical worsening leading to treatment discontinuation shortly before the event. Event-related treatment modifications introduce potential reversed causality in the ER analysis and bias, as events may predict exposure, rather than exposure predicting events. W