Designing Clinical Trials to Study Rare Disease Treatment

This paper provides an overview of the design of clinical trials for rare diseases and the impact of the Orphan Drug Act on the successful study of diseases found in small, widely dispersed patient populations. Orphan drugs are defined. Randomized, placebo-control trials may not always be an option for studying orphan drugs; designs which may work better include: open protocol, open label, historical control, crossover trials, withdrawal design trials, or trials with surrogate endpoints. Each of these is discussed. The benefits of studying orphan drugs and the procedure for approval of trial design by the Food and Drug Administration are outlined.