Crossover design

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In a crossover design, each participant is randomized to a sequence of two or more treatments therefore the participant is used as his or her own control.  Crossover trials produce within participant comparisons, whereas parallel designs produce between participant comparisons.  For example, in the simplest case, participants are randomised to receive either intervention A followed by intervention B or randomised to intervention B followed by intervention A.  This design is called a two-period crossover design.

Crossover trials can be used to investigate chronic conditions, such as asthma, where the objective is to investigate the participants’ short term response to therapy.  The condition must also be stable, so that the circumstances at the beginning of each period are more likely to be the same. Clearly, not all interventions can be studied in crossover designs.  For example, comparing surgical procedures or evaluating long term outcomes such as 5 year survival where it is impossible to crossover to another intervention.

The advantage of using crossover trials is a more precise estimate of the treatment effect and therefore the trial requires fewer participants.  The disadvantages are the difficulty in avoiding carryover effects (the influence of the first treatment phase ‘carrying over’ to the second treatment phase), patient withdrawals complicating interpretation and analysis, and difficulties with assigning adverse events which occur in later treatment phases to the appropriate intervention.  See Further reading for more details.

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Illustrative example - From the BMJ

Forty nine participants were randomised to follow either a margarine or butter diet for six weeks.  At the end of his period, participants were crossed over to the other intervention for six weeks.  Outcomes were measured every four days throughout the study.  (Chisholm A, Mann J, Sutherland W et al. Effect on lipoprotein profile of replacing butter with margarine in a low fat diet: randomised crossover study with hypercholesterolaemic subjects. BMJ 1996; 312: 931-4)

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Further reading

Sibbald B, Roberts C.  Understanding controlled trials: Crossover trials BMJ 1998; 316: 1719-20.

Senn SJ.  Cross-over trials in clinical research. Chichester: John Wiley, 1993. 

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This page was last updated 18th April 2005.