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Semin Thromb Hemost 2015; 41(08): 855-859
DOI: 10.1055/s-0035-1564799
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Assessment of Clotting Factor Concentrates—Pivotal Studies and Long-Term Requirements

H. Marijke van den Berg
1   Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
,
Flora Peyvandi
2   Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
3   Department of Pathophysiology and Transplantation, Università degli studi di Milano, Milan, Italy
› Author Affiliations
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Publication History

Publication Date:
19 October 2015 (online)

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Abstract

Assessment of quality in terms of safety and efficacy of clotting factor concentrates (CFCs) is very important for all new therapeutic products. In rare diseases this is often complicated due to small number of trial participants. In hemophilia, an extra complication is the large impact previous treatments have on both the risk on inhibitors and the overall response to bleedings. For new CFCs, safety needs to be evaluated against inhibitor risk whereas efficacy is primarily judged against the most common clinical manifestations of the disease, namely, bleeding into joints and muscles. In this article the challenges are described for hemophilia that recruits patients globally. Recommendations of ISTH are discussed; these propose to substitute the single-arm prelicensure study with a two-stage approach, which considers epidemic and endemic incidence rate, and might increase the feasibility of studying multiple new products in populations with rare disease without compromising the assessment of product safety and efficacy. We also suggest that the annual bleeding rate (ABR) is an unreliable predictor of efficacy. The response to treatment highly depends on the current disease status of every patient participating in a clinical trial. The phenotype of patients with hemophilia is highly influenced by previous treatment history. Patients with severe hemophilia of the same age can demonstrate a different response to treatment.

Keywords

clotting factor concentrate - safety - efficacy - short-term - long-term
 

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