Comprehensive analysis of clinical development and regulatory submission promotion schemes for oncologic drugs as the Japanese national projects.

To reduce the delay in marketing authorization of drugs in Japan, four Japanese national projects were instituted. We examined all oncologic drugs for adult patients approved or discussed through these schemes, for the first time. All the data are publicly available. In total, 197 applications/demands (181 indications and 16 dosages/uses) were collected. As of December 31, 2015, 64 indications and 10 dosages/uses were approved as off-label drugs through these schemes without conducting additional registration trials in Japan. Furthermore, 46 indications and two dosages/uses were approved after registration trials in Japan requested by the national scheme councils. Regarding the following 23 indications of the 197 applications/demands, registration trials in Japan were commenced after the national scheme council's request: 17 hematological malignancies and six orphan solid tumors. Moreover, 54 indications and three dosages/uses, for which demands were submitted, were regarded as not a high medical priority by the national scheme council. Regarding two hematological malignancy indications, the dosage approved in foreign countries was intolerable for the Japanese patients in Japanese registration trials and this stopped the clinical development in Japan. Our analysis showed that 110 indications and 12 dosages/uses were approved in Japan through these schemes. These national projects have provided numerous therapeutic options for Japanese patients and may be meaningful for promoting clinical development and regulatory approval especially in orphan diseases in countries other than Japan.