The present study investigated the effect of tea catechins on the immune function in elderly subjects using a catechin-rich beverage. Twenty Japanese individuals aged over 65 years participated in the study after written informed consent was obtained. The present single-arm pilot study was conducted for an intervention period of two weeks, after one week of abstinence from consuming tea/catechin-rich products. Participants consumed one bottle of the catechin-rich beverage (total catechins, 540 mg in 350 mL) every morning. The participants' immune function including the change in natural killer (NK) cell activity (％) from before to after intervention were evaluated. Pearson's correlation coefficient (r) was calculated to investigate the correlation between NK cell activity before intervention and change in NK cell activity. The study participants appropriately consumed the catechin-rich beverage every day without any adverse event. The mean NK cell activity at baseline was 41.7 (standard deviation, 23.1). After the intervention, NK cell activity increased in 17 participants (85.0％), and the estimated mean of the differences indicated a statistically significant increase (17.1; 95％ confidence interval, 9.7 to 24.5). No significant changes in C-reactive protein and interleukin-6 levels were observed. Moreover, pre-intervention NK cell activity correlated significantly with the ratio of post- to pre-intervention NK activity (r＝−0.63). Although further studies using a parallel-group and comparative design are required to clarify the effect of tea catechins on the immune function, our results suggest that catechin consumption may enhance or maintain NK cell activity in the elderly.

Clinical trials using adaptive designs (AD) are more flexible in study design and implementation compared to conventional fixed designs. In the US, the draft guidance document “Adaptive Design Clinical Trials for Drugs and Biologics” was issued by the FDA in 2010, and many studies using AD have been performed. On the other hand, the situation of practical application of AD to clinical trials in Japan has not been reported and no guidance has been issued. We investigated the use of AD in both Japan and the US by searching public clinical trial registration databases in both countries. Four databases were used for searching clinical trials carried out in Japan, and one database for the US. We included clinical trials using AD registered between January 1, 2013 and December 31, 2017. Twenty-four AD trials conducted in Japan and 97 conducted in the US were identified. The AD were used mainly in the early phase of clinical development. Of the 24 trials conducted in Japan, 23 were sponsored by pharmaceutical companies. In particular, AD were frequently used in clinical trials led by global pharmaceutical companies and overseas affiliate of Japanese companies. In the US, the numbers of domestic AD trials and multi-national AD trials were almost the same, and some of them were led by academic institutions. These findings suggest that Japanese companies have limited experience in using AD, and that AD are not yet popular in Japan. Efforts to enhance understanding of AD, such as issuing guidance by regulatory authorities in Japan, are needed to promote diffusion of efficient clinical development using AD.

Background: Risks associated with conducting clinical trials include occurrence of unintended adverse events which could potentially cause health impairment of study participants.Therefore mechanisms by which patients are compensated for trial-related injury must exist. However, the actual situation of such compensation has not been adequately surveyed, especially for investigator-initiated clinical trials (IITs).

Objectives: To examine the actual situation of managing compensation in IITs.

Methods: A web-based questionnaire survey was conducted in 2017. Responses were obtained from institutional review boards (IRBs) for good clinical practice (GCP)-regulated studies and from ethics committees (ECs) for government guideline-regulated studies.

Findings: Main findings were as follows: (1) 5 of 21 (24％) IRBs and 7 of 22 (32％) ECs responded that they had a written institutional policy or procedural document; (2) 9 of 21 (43％) IRBs and 1 of 22 (5％) ECs responded that they had prepared an explanation sheet concerning compensation for research subjects, and 4 of 21 (19％) IRBs and 1 of 22 (5％) ECs had prepared an explanation sheet in the case of occurrence of injury; (3) only 1 of 21 (5％) IRBs and 2 of 22 (9％) ECs responded that they had a compensation-specific assessment mechanism separately from IRB/EC ; (4) only a few institutions responded that they had financial resource for compensation separately from insurance; (5) information on cases of awarding monetary compensation was obtained.

Conclusion: Institutional operation manual and information sheet for research subjects concerning compensation for trial-related injuries are not adequately prepared, but several institutions have produced these documents. One issue is that institutional mechanism to assess the need for compensation is rarely established. Further survey is required to elucidate the actual situation of managing compensation in IITs.

Background: The use of big data/real-world data (BD/RWD) is expected to be a new option for evidence generation in drug development. Pharmaceutical companies are considered to be a group of key drivers to promote widespread use of BD/RWD in Japan. However, little is reported about the current status of the use of BD/RWD for drug development in Japan.

Objective: This study was conducted to reveal the current usage of BD/RWD by pharmaceutical companies in Japan and their current organization structure, with the aim to gain insight on the challenges and future perspective of BD/RWD in Japan.

Methods: A questionnaire survey was conducted on 66 pharmaceutical companies affiliated with Japan Pharmaceutical Manufacturers Association from 16 to 31 October 2018. The survey consisted of two parts: Questionnaire 1 investigated the current usage of BD/RWD in drug development in Japan, and Questionnaire 2 investigated the current organization structure.

Results: Of 52 companies that responded to Questionnaire 1, 30 companies (57.7％) were currently using BD/RWD for drug development in Japan for various purposes, 29 of which (96.7％) planned to continue using BD/RWD. Of 28 companies that responded to Questionnaire 2 and currently using BD/RWD, 9 companies (32.1％) had established divisions or organizations for internal management of BD/RWD, and 14 companies (50.0％) had standard operation procedures or guidance for handling legal and regulatory aspects associated with the use of BD/RWD for drug development in Japan.

Conclusion: BD/RWD is currently used for various purposes in drug development in Japan. However, the proportion of companies currently using BD/RWD for drug development is limited to approximately 50％. Proactive involvement of pharmaceutical companies toward the use of BD/RWD for drug development in Japan together with further industry-government-academia harmonization for environment improvement are awaited.

The implementation of “Ethical Guidelines for Medical and Health Research Involving Human Subjects” and “Clinical Trials Act” is expected to improve the quality and reliability of clinical trials, however, as comprehensive understanding of each regulation is necessary, the burden of conducting and reviewing a research is increasing for both researchers and review board members. As we sought information on the international trends, we noticed the U.S. developed and publicized “NIH-FDA Clinical Trial Protocol Template (v1.0 7 Apr 2017)” (NIH-FDA Template) to be useful and decided to translate into Japanese and compare with the Japanese regulations. We also developed our own Template, using the NIH-FDA Template as a referral. Some contents or instructions in the NIH-FDA Template which either was an international standard or U.S. standard, was not compatible with the Japanese regulation. Thus, we devised our own Templates with both international consistency and coordination to Japanese regulations. In this paper, we will outline the whole project, discuss the distinct aspect of NIH-FDA Template, examine the difference between Japanese regulations and explain the elements unique to our own Templates.