The Figure below uses a randomized comparison of medical and surgical treatments in which some very ill patients randomized to surgery died before their surgery could be organised. Should these patients be excluded from analysis? As shown in the Figure, doing that would result in an unfair bias against those allocated medical treatment from which similar very ill patients had not been excluded. To avoid bias, the challenge is to try to preserve the initial comparability of groups created using random allocation – application of a design and analysis strategy that came to be designated ‘the intention-to-treat principle’ (see Hill 1961).