Comparison of the Quality of Phase Ⅲ Non-commercial Clinical Trials in Japan, the United States, and the United Kingdom before the Implementation of the New Japanese Clinical Trials Act

Abstract

Recent research misconduct, represented by the valsartan scandal, has raised questions about the quality of non-commercial trials not for regulatory approval in Japan. Unlike in the US and Europe, non-commercial clinical trials are not regulated by law in Japan, which was believed to be a reason why quality could not be guaranteed. However, until now, few studies have compared the quality of clinical studies among countries. In this study, the quality of Japanese non-commercial phase Ⅲ trials before the implementation of the Clinical Trials Act (CTA) in 2018 was compared with Western non-commercial trials registered in the database using study design as quality indicators. The study found a lower proportion of randomized, controlled trials (RCTs) (70％ in Japan, 89％ in the US, and 88％ in the UK) and fewer blinded designs (46％ in Japan, 59％ in the US, and 52％ in the UK) in non-commercial trials in Japan. Single-arm trials not for either cancer or rare diseases, which are usually considered low quality because of a lack of fair comparison, were more common in Japan (82％) than in the US (76％) and the UK (50％). In terms of endpoint setting, most non-commercial trials in Japan had surrogate endpoints, with only a few trials using true endpoints (5％) compared to the US (24％) and the UK (40％). A comparison of these quality indicators in Japanese non-commercial trials before and after the CTA implementation showed no increases in the proportion of RCT and blinded designs, but an increase in the proportion of trials using true endpoints and appropriate use of single-arm design. In conclusion, the lack of legal regulation in Japan may have indirectly affected the quality of non-commercial phase Ⅲ trials in Japan at the time. Implementation of the CTA has contributed to some quality improvements, but the effect is limited at present.