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. 2025 Jun;30(6):1109-1117.
doi: 10.1007/s10147-025-02756-8. Epub 2025 Apr 11.

Evaluation of drug lag and drug loss in Japan: participation in global phase III oncology trials

Kaname Shiga  1   2 , Taro Shibata  3 , Toshio Miyata  4
Affiliations

Evaluation of drug lag and drug loss in Japan: participation in global phase III oncology trials

Kaname Shiga et al. Int J Clin Oncol. 2025 Jun.

Abstract

Background: Despite efforts to mitigate drug lag, discrepancies in drug approval timelines persist between Japan and the US, and increase in unapproved drugs has become a significant challenge. This study aimed to evaluate potential drug lag and drug loss by assessing Japan's participation in global phase III multinational/multiregional clinical trials (MRCTs) targeted cancers.

Methods: Phase III MRCTs of anticancer drugs initiated between 2008 and 2022 were collected. Information of participant countries, study sponsor, study design, and cancer type were collected and analyzed by logistic regression analysis to identify factors affected Japan's participation.

Results: Of 999 phase III MRCTs, Japan's participation every 5 years increased over 15 years (2008-2012: 34.3%, 2013-2017: 51.6%, 2018-2022: 60.2%), while Japan's non-participation numbers did not change (2008-2012: 157, 2013-2017: 167, 2018-2022: 165). In the multivariate logistic regression analysis, the absence of an operational base in Japan and minor cancers were negatively associated with Japan's participation in phase III MRCTs. Japan's participation was also associated with some cancer organs and drug modalities.

Conclusion: Potential future drug lag and increases of unapproved drugs were expected to increase. Since the inclusion of Japan in MRCTs results in shorter or no approval lag, Japan should promote to make circumstances where small overseas companies can include Japan in MRCTs.

Keywords: Anticancer drug development; Drug lag; Drug loss; MRCT; Phase III.

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Conflict of interest statement

Declarations. Conflict of interest: Kaname Shiga is an employee of Janssen Pharmaceutical K.K., a subsidiary of Johnson & Johnson Innovative Medicine, Raritan, NJ, USA. Taro Shibata and Toshio Miyata have no conflict of interest.

Figures

Fig. 1
Fig. 1
Phase III multiregional clinical trials of anticancer drugs initiated between January 1, 2008, and December 31, 2022
Fig. 2
Fig. 2
Trends of participation in oncology phase III MRCTs started between 2008 and 2022. a Participation rates in oncology phase III MRCTs. b Participation numbers in oncology phase III MRCTs. c Difference in participation numbers between the US and Japan, and between East Asia Total and Japan
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References

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    1. Director of Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, MHLW (2007) Basic principles on Global Clinical Trials

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