Rare diseases : a new Public Health concept
The European Commission on Public Health defines rare diseases as ‘life-threatening or chronically debilitating diseases which are of such low prevalence that special combined efforts are needed to address them.’ The term low prevalence is defined as less than 1 in 2,000 persons. It is estimated that between 5,000 and 8,000 distinct rare diseases exist today, affecting 6% to 8% of the population, 24 to 36 million people in the European Community. 80% of rare diseases have identified genetic origins, others result from infections, allergies or are due to degenerative and proliferative causes. Rare diseases are characterized by a broad diversity of disorders and symptoms across diseases and also across patients suffering from the same disease. Therefore, it is impossible to develop a Public Health policy specific to each rare disease. A global approach to rare diseases is consequently required for establishing policies dealing with scientific and biomedical research, drug research and development, industry policy, training, social benefits, hospitalization and outpatient treatment.
An orphan drug is a pharmaceutical agent specifically developed to treat a rare medical condition, referred to as an orphan disease. Orphan drugs follow the same regulatory development path as other pharmaceutical products, with studies focusing on pharmacokinetics, pharmacodynamics, dosing, stability, safety and efficacy. However, some statistical burdens are lessened in an effort to maintain development momentum. For example, orphan drug regulation generally acknowledges that it may not be possible to test 1,000 patients in a phase III clinical trial, given the number of afflicted persons.
The standard approach to clinical trials and a need for alternatives
Even though the available population of potential research participants does not allow the conduct of adequately powered randomized clinical trials (RCTs), there is a need for facilitating the development and availability of high quality, ethically researched, and appropriately authorized medicines in pediatric rare diseases, without subjecting children to unnecessary trials. Historically, drug developers and federal regulators have been worried of small clinical trials, primarily because of their low statistical power and generalizability. New approaches to protocol design are presently needed for trials with small sample sizes that can assess the potential therapeutic efficacy of drugs, biologics, devices, and other medical interventions.