An important principle in clinical trials is that the analysis must take into account the level at which randomization occurred. In most circumstances the number of observations in the analysis should match the number of ‘units’ that were randomized. In a simple parallel group design for a clinical trial, participants are individually randomized to one of two intervention groups, and a single measurement for each outcome from each participant is collected and analysed. However, there are numerous variations on this design. Authors should consider whether in each study:
groups of individuals were randomized together to the same intervention (i.e. cluster-randomized trials);
individuals undergo more than one intervention (e.g. in a cross-over trial, or simultaneous treatment of multiple sites on each individual); or
there are multiple observations for the same outcome (e.g. repeated measurements, recurring events, measurements on different body parts).
There follows a more detailed list of situations in which unit-of-analysis issues commonly arise, together with directions to relevant discussions elsewhere in the Handbook.