3. Randomised Controlled Clinical Trial Designs

3.4. Cross-over Trial Design

Cross-over randomisation is when participants receive a sequence of different treatments (for example, the candidate compound in the first phase and the comparator/control in the second phase). Each treatment starts at an equivalent point, and each p serves as their own control. It presents some advantages, such as low variance due to treatment and control being the same participant, and the possibility of including a number of treatments. There must be a washout period between treatments – this is a period where the participant does not use any treatment. Participants must have a stable and chronic disease. Cross-over trials require fewer participants but for a longer period of time.

Image explaining cross-over trial: Participants receive a sequence of different treatments. Washout period between treatments


  • Low variance due to participant and control being the same.
  • Can include a number of treatments.

  • Requires a long-term illness as treatments are applied one after the other.
  • Carry over effects need to be avoided (washout period must be sufficiently long).