Figure 1. Example Patient Timelines for the Primary (Intention-to-Treat) and Secondary (Per-Protocol) Analysis.

A, All patients shown are distinct and were classified on the basis of their treatment initiation within a 14-day exposure regimen ascertainment window that is incident with respect to each patient’s first record of metastasis. Notably, this analysis is agnostic to adherence and patients were followed-up from the end of the exposure regimen ascertainment window until occurrence of an outcome or censor event. Additionally, multiple records for each study drug could occur within the ascertainment window, as observed in patients D and H. B, Patients 1 to 4 are cloned and assigned to each treatment strategy on initiation of a study drug. Patient 1 adhered perfectly to the exposure treatment strategy and experienced the outcome event; therefore, all person-time observations were contributed to the exposed group. Patient 1 also contributed a small amount of person-time to the comparator group, as the patient’s treatment history was aligned with the comparator treatment strategy for some follow-up time prior to initiation of D₃. Patient 2 in the exposed group was censored on initiation of a cancer treatment that is not a part of their assigned regimen (D_x) and did not contribute person-time to the comparator group, since D₃ is not a component of the comparator regimen. Patient 3 in the exposed group was censored at the end of the 21-day interval because that is the point at which the patient’s treatment history was no longer adherent with the exposure strategy. Patient 4 in the comparator group had a treatment history that was compatible with the comparator strategy and experienced an outcome event but is censored in the exposed group due to a lack of adherence with the exposed treatment strategy. Notably, if an event occurred during an interval of follow-up time that was compatible with both treatment strategies, the outcome was attributed to both groups.