Study designs for rare diseases

The development and marketing of new drugs for rare diseases, the so called orphan drugs, means a great challenge for all who participate in the health care system:  As the number of probands is very small and rare disorders are often very heterogeneous in age and disease severity, it is often very difficult or even impossible to show a statistically firm evidence of efficacy. For the approval procedure of an orphan drug the standard placebo-controlled, double-blind clinical trial is often inappropriate, therefore other study designs or other parameter as for example a biomarker have to be used in order to proof a clinical efficacy of the study drug. There are many study designs that have been used in rare diseases such as for example cross-over design, N-of-1 design and adaptive randomization designs. A novel blind start design was applied in a clinical trial in patients with mucopolysaccharidosis VII, an ultra-rare lysosomal disorder. Before performing a clinical trial for an orphan disease, the type of study design should be carefully selected, as the all these different study designs have advantages and disadvantages.