Comparison of global versus Asian clinical trial strategies supportive of registration of drugs in Japan.
The number of worldwide and Asian multiregional clinical trials (MRCTs) submitted for Japanese New Drug Applications increased markedly between 2009 and 2013, with an increasing number performed for simultaneously submission in the USA, EU, and Japan. Asian studies accounted for 32% of MRCTs (14/44 studies) and had comparatively small sample sizes (<500 subjects). Moreover, the number of Japanese subjects in Asian studies was 2.1- to 13.4-fold larger than the sample size estimated using the method described in Japanese MRCT guidelines, whereas the ratio for worldwide studies was 0.05- to 4.9-fold. Before the introduction of this guidelines, bridging or domestic clinical development strategies were used as the regional development strategy in accordance with ICH E5 guidelines. The results presented herein suggest that Asian studies were conducted when the drug had already been approved in the US/EU, when phase 3 clinical trials were not be planned in the USA/EU, when there was insufficient knowledge of ethnic differences in drug efficacy and safety, or when Caucasian data could not be extrapolated to the Japanese population. New strategies with Asian studies including the Japanese population could be conducted instead of Japanese domestic development strategy.
Department of Drug Development and Regulatory Science of Pharmacy, Keio University, Tokyo, Japan.
Mari
M
Shirotani
Tatsuo
T
Kurokawa
Koji
K
Chiba
D001208:Asia; D044466:Asian People; D017326:Clinical Trials, Phase III as Topic / Q000592:standards; D018849:Controlled Clinical Trials as Topic / Q000592:standards / Q000639:trends; D004305:Dose-Response Relationship, Drug; D017277:Drug Approval; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D057217:Economic Development; D005062:European Union; D006801:Humans; D038622:Internationality; D007564:Japan; D015337:Multicenter Studies as Topic / Q000592:standards / Q000639:trends; D017410:Practice Guidelines as Topic; D012107:Research Design / Q000639:trends; D014481:United States; D044465:White People
D015507:Drugs, Investigational
Asian studies; globalization of clinical trials; multiregional clinical trial; regulatory science