飯島 祥彦

In 2018, we conducted a study on 121 ethics review committee offices in Japan to examine the state of "central review" in non-interventional studies and discern any challenges regarding its introduction. Of the 452 offices that were invited to participate, 121 responded (26.8% response rate), and 35 (28.9%) had records of furnishing contracting agreements with ethical reviews by other research institutions. The merits of central reviewing include easing the burden on ethics review committees, improving the quality level and consistency of ethical reviews, and enhancing the efficiency in conducting them. The demerits include increased administrative overheads and work for researchers, such as preparing application forms and checking institutional requirements, and a lack of clarity regarding who is responsible for conducting the research, which makes it is less desirable for institutions to have their own ethics review committees. This study revealed that the comprehensive introduction of central review in non-interventional studies continues to encounter many hurdles, and promoting central review requires overcoming these challenges one at a time. The Ethical Guidelines for Medical and Health Research Involving Human Subjects will be revised in 2021 to require central review as a part of ethical reviews for non-interventional studies. In the future, central reviews of non-interventional studies will need to be of high quality and conducted efficiently, and this will require research institutions to utilize relevant central review guidelines and checklists.

Clinical issues involving ethical dilemmas arise daily and confound physicians as they provide medical care. These dilemmas require difficult decisions as physicians must respect patients' values, lifestyles, and freedom of choice while protecting life and promoting health. This is made more challenging as values and lifestyles become more diverse, making third-party support necessary to accommodate the wishes of stakeholders, particularly patients. Collaborative work is important for addressing clinical ethics issues. Government agencies and professional organisations should discuss individual cases as public policy concerns and release guidelines based on their deliberations. Medical institutions should refer to such guidelines in their own discussions on ethically challenging cases. This is not the case today as each organisation creates its own guidelines; there is no consensus on how clinical ethics committees or consultations should be conducted. Support systems that are public in nature are needed to protect patients' rights and freedoms in medical care.

We investigated the differences in Japanese and United States medical and legal professional opinions on ethical support for clinical ethical issues using the refusal of blood transfusions on the grounds of religious principles as an example of a clinical ethical issue. In ethical support systems for medical institutions in Japan, 95.0% of "clinical training designation hospitals" have hospital ethics committees, and 63.1% have medical safety divisions; clinical ethical support is provided in accordance with their scale and function. In terms of clinical ethical support limits the discretion of physicians, 59.2% of lawyers responded "No" and 54.4% of doctors responded "Yes". In addition, on the feasibility of government or academic guidelines in clinical practice, 37.7% of lawyers responded "Yes" and 63.0% of doctors responded "No". In terms of "relative transfusion-free" policy, 83.2% of lawyers and 76.8% of doctors responded that it is "unavoidable," while 81.6% of U.S. committee heads responded that it is a "violation of rights." In terms of hospital transfers due to a hospital being unable to treat patients refusing blood transfusion, 62.6% of lawyers reported that it is "unavoidable" while 57.1% of U.S. committee heads reported that it "should be avoided". The results of this study indicate that medical and legal professionals and U.S. ethics committee heads recognize clinical ethical issues in slightly different ways.

The survey involves examining the applications from 142 institutions that have consented to make available all certification applications from 2015 and 2016 to a research project for building a certification system for an ethics committee run by the Agency for Medical Research and Development. The number of certified institutions is 20 (14.1%). In the applications from uncertified institutions, there are cases in which requirements of ethics guidelines are unmet, and there is insufficient information provided on regulation and procedure. An analysis of the committee members who can contribute as members of the general public (general public committee members) has indicated that the number of committee members who do not belong to an institution in which an ethics committee is instituted (external committee members) is 41 (95.7%) among the certified institutions and 224 (84.5%) among the uncertified institutions. The proportion of general public committee members drawn internally from institutions tends to be higher among uncertified institutions. While a separate committee examined conflicts of interest in research in 19 certified institutions (95.0%), such conflicts were found in 41 uncertified institutions (33.9%) by the ethics committee. The survey confirms that the challenge lies in increasing the number of external committee members and in further improving the system to manage conflicts of interest, and the education and training regime.

Clinical research is guided by ethical principles promulgated in several statements, principally the Nuremberg Code, the Helsinki Declaration of the World Medical Association etc. In Japan, clinical research of medical products, principally trial of new pharmaceutical products is regulated by GCP (good clinical practice). Other types of clinical research are regulated by some ethical guidelines for clinical researches. The result is a regulatory position that is a complex combination of legislation and ethical guidelines. In the Ethical Guideline for Clinical Studies revised in 2008, clinical research is classified into intervention research and observational research. When researchers plan clinical research, they must determine the type of clinical research and appropriate ethical guideline for the type of clinical research. Advances in health informatics and genetic research have produced a new and very rich body of raw material for clinical research in the form of gene banks and genome-wide association study etc. The use of human tissue and medical information in the course of clinical research raises issues under the ethical regulations for research with human subjects.

A 65-year-old female patient with liver cirrhosis complicated with hepatocellular carcinoma (HCC) was treated with oral administration of 5'-DFUR (600 mg/day). The titer of serum α fetoprotein gradually decreased, and reduction of the hepatic tumor size was observed by abdominal computed tomography (CT) following 5'-DFUR treatment. HCC was obviously diminished since the start of 5'-DFUR administration and almost disappeared in fifteen months. This case suggests the treatment with 5'-DFUR for hepatocellular carcinoma is completely effective.