title: Clinical trial designs to obtain marketing authorization of drugs for haematological malignancy in Japan, the EU and the US.
abstract: Differences in regulatory actions between Japan, the European Union (EU) and the United States (US) regarding the approval date and primary endpoints of pivotal trials have never been analysed comprehensively. This study aimed to examine such differences in haematological malignancy indications not only in applications for new molecular entity agents but also in supplemental applications for additional indications. A total of 101 haematological malignancy indications were examined for 58 drugs. Only 30 indications were approved by the regulatory agencies of all three regions with 25, 9 and 67 indications being first approved in Japan, the EU and the US, respectively. Regarding the 18 indications approved only in the US, 13 were approved based on results of single-arm trials. The approval of all nine indications approved first in the EU was based on results of comparative trials. The primary endpoints were different between the EU and the US in 4 of 49 indications approved by both regulatory agencies, all of which were approved earlier in the US than in the EU. This analysis shows that the US Food and Drug Administration has taken the most active attitude to acceptance of surrogate endpoints in single-arm trials. Therefore, not only shorter review time but also this attitude may lead to earlier approval in US.
authors.affiliation: Division of Genetic Therapeutics, The Advanced Clinical Research Centre, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Sumimasa
authors.initials: S
authors.lastname: Nagai
authors.affiliation: Division of Genetic Therapeutics, The Advanced Clinical Research Centre, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D002986:Clinical Trials as Topic; D017277:Drug Approval / Q000379:methods*; D023381:Endpoint Determination; D005062:European Union; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D007564:Japan; D040541:Marketing / Q000592:standards*; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration
keywords: clinical trials; haematological malignancy; regulation