Table 2. “N-of-1” Trials for Rare Diseases.

Randomized, multiple crossover trials (often includes placebo) in which an individual subject serves as her/his own control. Consecutive periods are paired and treatment order is randomized independently for each period.

Advantages ○ All subjects receive treatment (at least some of the time) ○ The benefit and side effects of the treatment are determined for the specific subjects ○ Masking can be maintained. Disadvantages ○ All subjects receive placebo or alternative treatment at some point ○ Wash out period lengthy or unknown ○ Requires that disease and outcome variables be stable or linearly progressive ○ Provides poor information on the benefits/side effects in a larger population of subjects