Introduction: The recent revision of the Declaration of Helsinki strengthened the ethical obligation to provide compensation for harm of research subjects. However, the actual status of providing compensation has rarely been disclosed, especially in the situation of investigator-initiated clinical trials (IITs).

Objectives: To figure out the actual situation of compensation for injured subjects of IITs in Japan and to identify the necessary steps to fulfill the ethical obligation of compensation.

Method: We conducted two types of surveys of compensation in IITs in Japan over the past five years. A: questionnaire survey delivered to 1,700 institutions on (1) number and paid amount of compensation cases; number and amount of contract fees paid to insurance companies; and (2) institutional management system of compensation cases. B: complementary survey to the item (1) of the survey A, at two institutions, on contract fees paid to and insurance paid from insurance companies.

Result: In the survey A, we found only two cases of compensation provided, but could not find any serious cases claiming payment from insurance companies, although we could not exclude possibility of undisclosed cases. In the survey B, at the two institutions, a substantial amount of contract fees has been paid to insurance companies without claiming insurance payment; however, the total amount for each institution is less than that expected for one case of a serious injury. Also we found that there remain several points to improve the institutional management system of compensation in IITs in Japan.

Conclusion: To provide appropriate compensation for injured subjects of IITs, we need to develop an institutional management system, along with a system to gather statistical information of compensation cases, to achieve proper resource allocation. This system should also provide education for investigators and support staff to manage injury cases.