RESUMEN
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.
Asunto(s)
Ensayos Clínicos Controlados como Asunto , Aprobación de Drogas , Drogas en Investigación/uso terapéutico , Internacionalidad , Estudios Multicéntricos como Asunto , Proyectos de Investigación , Asia , Pueblo Asiatico , Ensayos Clínicos Fase III como Asunto/normas , Ensayos Clínicos Controlados como Asunto/normas , Ensayos Clínicos Controlados como Asunto/tendencias , Relación Dosis-Respuesta a Droga , Drogas en Investigación/administración & dosificación , Drogas en Investigación/efectos adversos , Drogas en Investigación/farmacocinética , Desarrollo Económico , Unión Europea , Humanos , Japón , Estudios Multicéntricos como Asunto/normas , Estudios Multicéntricos como Asunto/tendencias , Guías de Práctica Clínica como Asunto , Proyectos de Investigación/tendencias , Estados Unidos , Población BlancaRESUMEN
The required number of Japanese subjects was compared between the Bridging (BG) filing strategy described in ICH-E5 for drugs approved from 1998 to 2012, in which foreign phase 3 results were used together with a BG study conducted to confirm optimum Japanese dose, and global clinical trial (GCT) strategies in which the number was simulated from the foreign phase 3 studies. The simulated number from the GCT strategy was smaller than that of the BG, suggesting that the GCT strategy could be expected to reduce Japanese clinical trial costs. However, two exceptions were found, namely for preventive drugs and drugs for children, because of the large scales of foreign phase 3 studies.