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.

To select a drug suitable for a patient from drugs with the same indication, scientific and objective comparative evaluation of drug information is important. However, some of the secondary sources comparing drugs with the same indication lack scientific accuracy. For example, among proton pump inhibitors (PPIs) approved in Japan, benzimidazole derivatives, such as omeprazole, esomeprazole, lansoprazole, and rabeprazole, possess similar chemical structures and inhibit the gastric mucosal parietal cell proton pumps by similar irreversible mechanisms.

However, contrary to this scientific fact, there are secondary sources stating that only rabeprazole is reversible.

Hence, this study aimed to demonstrate the importance of gathering and examining drug information from a scientific and objective perspective by clarifying the background to the interpretation that only rabeprazole is reversible in secondary sources. We conducted a comprehensive survey of the descriptions of the inhibitory mechanism of rabeprazole in the package inserts and the interview forms of the brand-name drug, Pariet^®, along with all the 23 generic versions of rabeprazole. Additionally, we also investigated the reference papers of each description. Furthermore, we compared the descriptions in the package inserts and the interview forms of the four brand-name PPIs. It was observed that several documents described rabeprazole as the only reversible PPI. Moreover, only Pariet^® (rabeprazole) was described as “glutathione may restore enzyme activity” in the interview form among the four brand-name PPIs. However, it is clear from their chemical structures that all the benzimidazole-derivative PPIs, including rabeprazole, have the same mechanism of action. Thus, the widespread notion that only rabeprazole is reversible is possibly because “recovery of enzyme activity” is indicated only for rabeprazole among the four brand-name PPIs. Thus, there is a risk that drug information may be misinterpreted depending on how it is read. Overall, it is important to objectively and scientifically examine the description of drug information when determining the appropriate drug for a patient.