The drug lag and associated factors for orphan anticancer drugs in Japan compared to the United States
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The approval of orphan anticancer drugs in Japan has increased to meet high social demand. Drug lag, namely the approval lag of new drugs, is recognized as a social issue in Japan. We investigated the approval lag and its components, submission lag and review-time lag, between Japan and the United States (US) to reveal whether an approval lag still exists, and to identify potential factors that may contribute to reducing the approval lag. Anticancer drugs approved in Japan between April 2004 and November 2017 were investigated using publicly available information. Results showed that the median approval lag of orphan anticancer drugs in 2016–2017 was 727.0 days (interquartile range, IQR, 310.0–1054.3). The approval lag was significantly correlated with the submission lag (correlation coefficient = 1.00, P < 0.001) but not with the review-time lag (correlation coefficient = −0.16, P = 0.22). The submission lag was significantly longer for orphan anticancer drugs than non-orphan drugs (median, 712.5 days [IQR, 186.0–1448.3] vs. 387.0 days [92.8–1096.0], P = 0.023). External collaboration in drug development was associated with a longer submission lag (coefficient = 762.1, P = 0.017), while breakthrough therapy designation in the US was associated with a shorter submission lag (coefficient = −832.8, P = 0.035). In conclusion, we revealed that an approval lag for orphan anticancer drugs still existed in 2016–2017. A submission lag for orphan anticancer drugs was the main component affecting the approval lag, and was longer than that for non-orphan drugs. External collaboration in drug development may be a potential factor in reducing the submission lag for orphan anticancer drugs.
KeywordsCancer Orphan drug Drug lag Japan External collaboration Breakthrough therapy designation
The authors express their gratitude to Katsuya Nakano for his review of the study from a regulatory affairs viewpoint and to Makoto Tanaka for his useful suggestions.
Compliance with Ethical Standards
Conflict of Interest
Hiroki Nakayama is an employee of Astellas Pharma Inc. Naoki Matsumaru declares that he has no conflict of interest. Katsura Tsukamoto declares that he has no conflict of interest. The Global Regulatory Science laboratory is financially maintained by donations from Otsuka Pharmaceuticals Co., Ltd.
This article does not contain any studies with human participants or animals performed by any of the authors.
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