Table 1. Cross-Over Trials for Rare Diseases.

The administration of one or more experimental therapies (often including placebos) one after the other in a specified or random order to the same group of subjects.

Advantages: ○ All subjects serve as their own controls and error variance is reduced thus reducing sample size ○ All subjects receive treatment (at least some of the time) ○ Statistical tests assuming randomization can be used ○ Masking can be maintained Disadvantages: ○ All subjects receive placebo or alternative treatment at some point ○ Washout period can be lengthy or unknown ○ Cannot be used for treatments with permanent effects or in diseases that change over time