In a crossover trial, what practice helps mitigate carryover effects between treatment periods?

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Carryover effects happen when the effects of one treatment linger into the next period in a crossover trial. The best way to prevent this is to include a sufficient washout period between treatment periods, allowing the drug to be eliminated and its effects to subside before the next treatment begins. The length of the washout should reflect the drug’s pharmacokinetics, often lasting several half-lives, so that residual concentrations are negligible and measurements in the subsequent period reflect only the current treatment. While randomizing the order of treatments can help balance period effects, it doesn’t address lingering drug effects if the washout is too short. Increasing sample size affects power but not residual bias, and open-label or nonrandomized assignment introduces other issues without solving carryover.