20.2.2 Crossover Trials
In a crossover trial, participants receive more than 1 of the treatments under investigation, usually in a randomly determined sequence, and with a prespecified amount of time (a “washout period”) between sequential treatments. The participants and the investigators are generally blinded to the treatment assignment (double-blinded). This experimental design is often used for evaluating drug treatments. Each participant serves as his or her own control, thereby eliminating variability when comparing treatment effects and reducing the sample size needed to detect a significant effect. Most considerations of parallel-design randomized trials apply. Rather than indicating which participants were assigned to which condition, the CONSORT flow diagram should indicate how many were assigned to each sequence of conditions. Other information important to this study design includes possible carryover effects (ie, effect of intervention persists after completion of the intervention) and length of washout period (intervention effects should have ended completely before crossover to the other treatment). If the actual period of crossover differs from the original study protocol, how and why decisions were made to cross over to the alternate treatment and when the crossover occurred should be stated. The treatment sequence should be randomized to ensure that investigators remain blinded and that no systematic differences arise because of treatment order. Otherwise, unblinding is likely, treatment order may confound the analysis, and carryover effects will be more difficult to assess. The amount of time between each intervention (the washout period) should also be prespecified. If carryover effects are significant, or if a washout period with no treatment is undesirable or unethical, a parallel-group design (possibly with a larger sample size) may be necessary.