2022 Volume 53 Issue 3 Pages 39-47
Our study investigated recent strategies for proof of clinical efficacy for drugs designated as particularly high medical necessities in Japan. In this study, we focused on the 129 designated drugs with small patient number approved over 6 years from 2015 to 2020 for analyzing the characteristics of proof of clinical efficacy based on the drug background, pivotal study design, and approval condition information. All pivotal studies were classified as level 1（randomized controlled trials） to level 3（single-arm studies） and analyzed by each classification. For level 3 studies, we scrutinized the types of comparators and data sources. Characteristically, cancer drug thresholds were used as comparators for efficacy explanation. 85％ cancer drug and 48％ non-cancer drugs used thresholds as comparator. Setting a threshold as a comparator is considered an effective strategy, but the data source of the threshold is the most important issue. For cancer drugs, the study results of existing drugs were mainly used as data sources, but for non-cancer drugs, it was considered necessary to promote the use of real-world data. Post-marketing clinical efficacy data were required as an approval condition for five drugs. In this strategy, a post-marketing study plan should be included from the early development stage, and close consultation with The Pharmaceuticals and Medical Devices Agency is important.
In conclusion, a hybrid strategy, such as a single-arm pivotal study with thresholds plus a post-marketing clinical plan, may facilitate drug development. To apply the hybrid strategy, preparing external control data from the early basic research stage and the post-marketing plans to accumulate clinical efficacy data in the medical practice are essential.
