Clinical trials of orphan medicines.

摘要

For diseases categorised as rare because of short survival despite relatively common incidence, classic trial designs are practical, with large numbers of participants and hard outcomes such as survival. By contrast, some rare diseases affect fewer than 100 accessible patients in the European Union. For example, hyperammonaemia associated with N-acetylglutamate synthase deficiency was identified during a 20-year period from 1980 to 2001 in only 42 patients from 28 families.3 Many other rare diseases are prevalent to the extent of a few thousand people. Under such circumstances, a trial based on^ classic frequentist design and requiring enrolment of hundreds of patients is: impossible.