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These designs represent an important step toward stratified therapy, but N-of-1 trials [14] are the purest form of pragmatic patient-centered design [15]. N-of-1 trials are multiple-period, crossover experiments comparing two or more treatments within individual patients. They are the optimal design to estimate individual treatment effects directly and to identify the best treatment for each individual patient in each specific setting. The Journal of Clinical Epidemiology has recently published a number of articles reviewing the main features and applications of N-of-1 trials [16]. - www.jclinepi.com