Orphan diseases are an heterogeneous group of 6000 disorders which span from rare cancers to genetic syndromes, to auto-immune diseases. The current definition identify as rare disease conditions with a prevalence less that 1:2000 (1999 Orphan Drug regulation); the definition of ultra rare refers to a prevalence of less than 1:1,000,000. More than 400 orphan diseases are currently treated with a drug which has a specific indication; 15 new orphan indication have been designated in 2012. In the Orphanet database (www.orphanet.org) there are 488 ongoing clinical trials registered for 304 rare diseases or group of rare diseases (most of whom are trials in cancers). The majority of the trials are driven by pharmaceutical companies with about 25% having a public sponsor.
A recent methodology workshop by the European Clinical Research Infrastructure Network (ECRIN) was dedicated to issue recommendations for performing clinical trials in rare diseases. The recommendations state to apply standard statistical methodologies, with proper sample size calculations, for rare diseases in general. For ultra rare diseases there was a suggestion to move toward adaptive licensing with re-assessment of the findings every 3 to 5 years with a systemic data collections. To enlarge enrollment international networking should be the standard despite the several difficulties now encountered with multi-national ethics committee approval, insurances, funding etc especially with studies conducted by academia. Appropriate endpoints should be applied with surrogate markers to be used only when appropriately justified and possibly validated. Registries lead by patient’s organization/academia/industries possibly, linked together, should be the ideal situation for data collection.
This lecture will describe the current challenges for running clinical trials in rare diseases in rheumatology.
Disclosure of Interest None Declared