Prompt versus Delayed Triple Therapy in COPD: Solutions to Time-Related Biases in Observational Studies.

Background: Recent observational studies have reported that prompt initiation of single-inhaler triple therapy after a COPD exacerbation is more effective than delayed initiation. We show that their study design, by "peeking into the future" to define the timing of treatment initiation, introduces time-related biases, particularly protopathic bias. These biases can be avoided using the "cloning" approach to emulate a randomized trial approach.