TABLE 1.

Challenges to the conduct of rare disease clinical trials

Limited subjects:	1.82 PUPs per HTC per year or ~257 PUPs/y
Rare outcomes:	30% develop anti-VIII inhibitor antibody
Trial design:	Lack of novel design to conduct randomized trials in haemophilia
Competing studies:	Competition for PUPs by registries, single-arm and pharma trials
Ineligibility:	Exclusion due to past factor, bleeds, cost and competing trials
HTC organization:	Lack of unified data collection, sampling and standard of care protocol
Partnership:	Lack of foundation, industry and community support for inhibitor trials
HTC support:	Lack of personnel or sample preparation support by 40% of HTCs
Data collection:	Lack of uniform data collection, blood processing and shipping at HTC
Mechanistic studies:	Need for collaborative MD-scientist, immunology network input

HTC, haemophilia treatment centre; PUP, previously untreated patient.