Clinical trials and registries in haemophilia: Opponents or collaborators? Comparison of PUP data derived from different data sources

Haemophilia. 2018 May;24(3):420-428. doi: 10.1111/hae.13421. Epub 2018 Feb 13.


Introduction: The "Guideline on the clinical investigation of recombinant and human plasma-derived factor VIII products" (ClinGL) provides the requirements for the performing of clinical trials (CTs) for marketing authorization in Europe. The number of eligible previously untreated patients (PUPs) for CTs might be difficult to meet because of the concurrent development of FVIII concentrates, and additional data sources must be explored.

Aim: The extent to which CTs and the PedNet registry met relevant parameters, identified in the ClinGL, as well as inhibitor incidences were investigated in patients from both sources.

Methods: Anonymized data of eight CTs in 369 PUPs performed from 1987 to 2009 were compared with each other and with 632 PUPs (born 2000-2009) from PedNet.

Results: Clinical trials in PUPs performed for marketing authorization were too heterogeneous in their investigated parameters; therefore, a comparison of single factor concentrates was not possible. Data collection in PedNet met relevant parameters required for PUPs in accordance with the ClinGL. The overall inhibitor incidences were comparable (CT = 30.9% vs PedNet = 30.6%) when only severe haemophilia A (HA) patients from both data sources were considered.

Conclusions: Previously performed CTs in PUPs were divergent, which prevented a direct comparison of outcomes. However, this study demonstrated that data from CTs and carefully designed registries may complement each other in the establishing of sufficient safety information for single products to improve clinical insights and support regulatory decisions.

Keywords: Haemophilia A; clinical trials; inhibitor incidence; previously untreated patients; rare disease; registries.

MeSH terms

  • Clinical Trials as Topic*
  • Hemophilia A / drug therapy*
  • Hemophilia A / immunology
  • Humans
  • Information Storage and Retrieval*
  • Intersectoral Collaboration*
  • Registries*