Haemophilia registries to complement clinical trial data: a pious hope or an urgent necessity?

Keipert, Christine; Berg, H. M. Van Den; Keller‐Stanislawski, Brigitte; Hilger, A.

doi:10.1111/hae.13015

Cited by 4 publications

(5 citation statements)

References 10 publications

(15 reference statements)

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“…However, common data elements are a prerequisite. In addition, considering the limited sample size of prelicensure studies, postmarketing surveillance of factor VIII products in large, well‐characterized and unselected cohorts is deemed to be important to further characterize the safety profile of individual products . Our combined analysis demonstrates that large cohorts are needed to investigate subtle, but potentially meaningful differences among various products.…”

Section: Discussionmentioning

confidence: 99%

Recombinant factor VIII products and inhibitor development in previously untreated patients with severe haemophilia A: Combined analysis of three studies

et al. 2019

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Introduction Standard treatment of congenital haemophilia A is based on replacement therapy with coagulation factor VIII (FVIII) products. A major complication of FVIII therapy is the occurrence of IgG alloantibodies (inhibitors) that neutralize FVIII activity. Aim The aim of the analysis was estimating the risk of high‐titre inhibitor associated with the second‐generation full‐length product compared to third‐generation full‐length product and other recombinant FVIII (rFVIII). Methods We conducted a combined analysis of individual patient data from three large studies in previously untreated patients (PUPs) with severe haemophilia A. Results A total of 1109 PUPs were treated from 1993 to 2013 including 787 PUPs treated from 2004 onwards (primary analysis cohort). A total of 322 patients (29.0%) developed an inhibitor, of which 192 (17.3%) a high‐titre inhibitor. In the primary analysis set, 29.9% of patients developed an inhibitor and 17.2% a high‐titre inhibitor. The combined analysis indicated a lower risk of high‐titre inhibitor development for the third‐generation rFVIII product compared to the second‐generation rFVIII product (primary analysis: adjusted hazard ratio (HR) = 0.72, 95% CI: 0.49 to 1.06). Adjusted HR for all inhibitor development was significantly lower for the third‐generation product compared to the second‐generation product. Conclusion The trend of an increased risk of inhibitor development in PUPs for one recombinant product illustrates that extrapolation from one recombinant factor VIII product to other products might not be justified.

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Section: Discussionmentioning

confidence: 99%

Recombinant factor VIII products and inhibitor development in previously untreated patients with severe haemophilia A: Combined analysis of three studies

et al. 2019

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“…The restriction in patient availability has been controversially debated for decades . An international workshop organized by the European Medicines Agency (EMA) was held in 2015 to investigate whether haemophilia registries can provide valuable data for regulatory purposes . One of the outcomes of this workshop was that the reporting structures from registries to regulators must be developed as well as the possibility for registries to demonstrate an appropriate quality assurance level of data entry and maintenance.…”

Section: Resultsmentioning

confidence: 99%

“…Further harmonization of data collected in CTs and registries is needed to avoid methodological constraints and differences in design and realization . Clarification of the legal ownership of registry data (or patient data in general) and access to these data must be addressed to improve clinical insights and support regulatory decisions . Data derived from registries should not be regarded as opponents to CTs but as important complementary data sources after MA.…”

Section: Resultsmentioning

confidence: 99%

“…28 An international workshop organized by the European Medicines Agency (EMA) was held in 2015 to investigate whether haemophilia registries can provide valuable data for regulatory purposes. 29 One of the outcomes of this workshop was that the reporting structures from registries to regulators must be developed as well as the possibility for registries to demonstrate an appropriate quality assurance level of data entry and maintenance. Several largescale epidemiological studies and a randomized controlled trial were published 10,11,[30][31][32][33][34][35] and intensively discussed with the result that it is difficult to conclude statistically significant outcomes for single products.…”

Section: Is the Inhibitor Development Observed In Cts And Pednet Comentioning

confidence: 99%

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

Keipert

Jonker

Berg³

et al. 2018

Haemophilia

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“…These schemes vary in the detail of the information collected and the length of time they have been in existence. Although traditionally the regulatory authorities depended on clinical trials for adverse event reporting, there is a move that could result in registry data being accepted in the future [35].…”

Section: Specialized Haemophilia National Schemesmentioning

confidence: 99%

The current state of adverse event reporting in hemophilia

Vulpen

Saccullo

Iorio

et al. 2016

Expert Review of Hematology

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Text word count: 3827; abstract word count: 187; number of tables: 5; number of references: 73.2 Abstract Introduction: Replacement of the missing clotting factor is the mainstay of haemophilia treatment. Whilst historically many haemophilia patients were infected with blood-borne viruses transmitted via plasma-derived products, nowadays the formation of alloantibodies against the missing clotting factor is the main adverse event of treatment.Areas covered: This paper provides an overview of the current national and international adverse event reporting systems, what these surveillance schemes taught us about side effects of the products presently in use, and elaborates on how to adapt these systems to the challenges we face with the changing treatment landscape.Expert commentary: Treatment of inherited bleeding disorders was accompanied by severe complications in the past, resulting in major morbidity and mortality. Current products are much safer, but still require monitoring via efficient safety surveillance systems. Adverse events are reported in national and international systems. With many new products entering the market, as well as non-factor replacement therapies, new safety issues may arise. It is important to identify potential adverse events early by making surveillance systems suitable to pick up unknown or unexpected effects, and to recognize and communicate patterns of adverse events rapidly.

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Haemophilia registries to complement clinical trial data: a pious hope or an urgent necessity?

Cited by 4 publications

References 10 publications

Recombinant factor VIII products and inhibitor development in previously untreated patients with severe haemophilia A: Combined analysis of three studies

Recombinant factor VIII products and inhibitor development in previously untreated patients with severe haemophilia A: Combined analysis of three studies

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

The current state of adverse event reporting in hemophilia

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