Fig 3. Simulation of repeated measurements of depression symptom severity on the HAMD-17 among 4 patients of the initial RCT simulation (Fig 1A).

The HAMD-17 score may fluctuate over time independently of the intervention (a). While the mean HAMD-17 score may be the same across the patients, the amount of variation may differ (b). In such a scenario, within-patient variation may account for the entire variation in the observed outcome in an RCT.