A crossover design is a clinical study design in which each participant receives several treatments in succession – typically the investigational medicinal product and a comparator. In contrast to a parallel-group design, each participant serves as their own control, which eliminates inter-individual variability and considerably reduces the required sample size.
The simplest crossover design is the 2×2 design: group 1 receives treatment A first, then treatment B; group 2 receives B first, then A. A washout period between the treatment periods is required to minimise carry-over effects (residual effects of the first treatment on the second period). The washout duration should be at least five times the half-life of the investigational medicinal product.
Crossover designs are particularly suitable for pharmacokinetic studies (bioequivalence, dose-finding in Phase I) and for conditions that are stable and reversible (e.g. pain, hypertension). They are not suitable for curative treatments (irreversible change in health status) or for conditions with high spontaneous variability. For CROs, crossover studies are a standard design for PK/PD studies and early phases. Regulatory reference: ICH E9, EMA Bioequivalence Guideline (CPMP/EWP/QWP/1401/98 Rev. 1).