Intention-to-treat analysis (revision 5)

Intention-to-treat analysis includes every randomised participant in the group to which they were assigned, regardless of whether they received the assigned treatment, adhered to it, or completed the trial. Its purpose is to preserve the comparability that randomisation created.^[1]

The alternative — analysing only those who completed as assigned — breaks that comparability, because completion is not random. Participants who stop because a treatment is not working, or because it is poorly tolerated, differ systematically from those who continue.^[2]

Intention-to-treat generally produces a more conservative estimate than a per-protocol analysis, and it answers a different question: what happens when treatment is offered, rather than what happens when it is taken as directed.^[2] Which question a trial should answer depends on the comparison it was designed to make.^[3]

Randomisation makes the groups comparable on everything, measured and unmeasured. Any post-randomisation selection — dropping non-completers, excluding non-adherers, analysing by treatment actually received — reintroduces confounding by the very factors that led to the selection.^[2]

The classic demonstration is that adherence itself predicts outcome even in a placebo arm: participants who take placebo reliably do better than those who do not, because adherence is a marker for other health-related behaviour. An analysis conditioning on adherence therefore finds an effect where none exists.^[2]

The practical consequence is that a striking difference between an intention-to-treat and a per-protocol result is informative about differential dropout rather than about the treatment.^[1]