Ethical Guidelines for Clinical Studies

July 30, 2003
(Amended December 28, 2004)
Ministry of Health, Labour and Welfare


TABLE OF CONTENTS


INTRODUCTION


Part I: BASIC VIEWS


1.Objectives


2.Scope of Application


3.Definitions of Terms


(1)Clinical Studies

(2)Subjects

(3)Human Specimens and Equivalent Materials

(4)Researchers and Equivalent Persons

(5)Principal Investigator

(6)Personal Information

(7)Personal Information in Possession

(8)Research Institutions

(9)Collaborative Research Institutions

(10) Institutional Review Board

(11) Informed Consent

(12) Proxy Consenters

(13) Minors

(14) Proxies

(15) Competence


Part II: RESPONSIBILITIES OF RESEARCHERS


1. Responsibilities of Researchers and Equivalent Persons

2. Responsibilities of Directors of Research Institutions

3. Responsibilities of Representatives, Directors, and Equivalent Persons of Corporations, Administrative Organs, and Equivalent Organizations that Possess Research Institutions


Part III: INSTITUTIONAL REVIEW BOARD


Part IV: INFORMED CONSENT


1. Procedure for Obtaining Informed Consent from Candidates

2. Procedure for Obtaining Informed Consent from Proxy Consenters or Equivalent Persons

3. Miscellaneous

 

Part V: SUBRULES


Part VI: REVISION


Part VII: DATE OF ENFORCEMENT




INTRODUCTION


The importance of clinical studies has been increasing with the advances in science and technology. The major objectives of clinical studies are to improve methods of preventing, diagnosing, and treating diseases, to gain better understanding of the etiology and pathophysiology of individual diseases, and to improve the quality of life of patients. Even methods that have been accepted as optimal means of preventing, diagnosing, or treating diseases need to be continually reviewed and revalidated in clinical studies in order to reconfirm their effectiveness, efficiency, convenience, and quality.

Advances in medicine often depend on clinical studies, but in every clinical study consideration of the welfare of the subjects as individuals should outweigh any consideration of scientific or social benefit.

With these points in mind, these Ethical Guidelines for Clinical Studies (EGCS) have been prepared to protect the dignity and rights of subjects as individuals and to facilitate the smooth conduct of clinical studies by researchers and equivalent persons.

The EGCS set forth principles which must be followed by researchers and equivalent persons in the conduct of clinical studies and are based on the ethical principles contained in the World Medical Association Declaration of Helsinki, the arguments made in Japan concerning the protection of personal information and the provisions of Article 8 of the Act on Protection of Personal Information (Law No. 57 in 2003). However, since clinical studies have a wide variety of forms, the EGCS provide only basic rules. It is essential that the principal investigators of each clinical study devise a study protocol that is in accordance with the basic rules and that the institutional review board assess the acceptability of the plan pursuant to the basic rules and the nature of the study planned.

All individuals involved in clinical studies are now required to follow the EGCS, in order to enable clinical studies to make a greater contribution to society with the understanding and cooperation of the general public.

 

[All research institutions to which any of the following laws or ordinances is applicable should comply with the relevant laws, ordinances, etc., in regard to the handling of personal information: (a) the Act on Protection of Personal Information, (b) the Act on Protection of Personal Information Possessed by Administrative Organs (Law No. 58 in 2003), (c) the Act on Protection of Personal Information Possessed by Independent Administrative Corporations and Equivalent Corporations (Law No. 59 in 2003), and (d) ordinances, etc., passed by local governments and equivalent organizations pursuant to Article 11 of the Act on Protection of Personal Information.



Part I: BASIC VIEWS


1. Objectives

In view of the importance of clinical studies in promoting studies in the field of medicine, the EGCS set forth principles to be followed by all individuals involved in clinical study from the standpoint of the dignity of the individual, human rights, and other ethical and scientific standpoints, with the ultimate goal of promoting appropriate clinical studies with the understanding and cooperation of the public.

 

2. Scope of application


(1) The EGCS apply to clinical studies conducted for the purpose of advancing medical care with the understanding and cooperation of the public and should be observed by all individuals involved in such studies.

The EGCS do not apply to the following:


1) Medical care intended only for diagnosis and/or treatment;


2) Studies whose conduct is governed by other laws, ordinances, or guidelines.

 

(2) The EGCS apply to clinical studies conducted both inside and outside Japan. As a rule, all individuals involved in such studies should follow the EGCS in addition to complying with the relevant laws, guidelines, etc., in the country where the study is being performed.

If the laws, ordinances, or guidelines in the country where a clinical study is being performed impose stricter regulations on the conduct of clinical studies, the study should be performed pursuant to such regulations.


<Subrules>


1. If an ongoing clinical study started before the date of enforcement of the pre-amendment version of the Ethical Guidelines for Clinical Studies (Ministry of Health, Labour and Welfare Notification No. 255 in 2003; hereinafter called “the original EGCS", neither the amended EGCS nor the original EGCS are applicable to the study. However, it is advisable that the study also be performed appropriately in accordance with the amended EGCS.


2. As a rule, clinical studies outside Japan conducted in collaboration with foreign research institutions should be performed pursuant to the amended EGCS. If stricter guidelines are in force in the country where the collaborative foreign research institution is located, the foreign guidelines should be given priority.

However, even when the amended EGCS are stricter than the guidelines in force in the country where the collaborative foreign institution is located, the supply and handling of human specimens and equivalent materials may be conducted in accordance with the statutes, guidelines, etc., in force in that foreign country if all of the following requirements are satisfied:


(a) The amended EGCS are difficult to apply in the relevant country;


(b) The institutional view board of the Japanese research institution involved in the study and the director of the institution have authorized the following measures planned for the said country: (1) the obtaining of informed consent,
(2) the implementation of appropriate measures to protect the personal information of the individuals who supply the human specimens or equivalent materials, and (3) the obtaining of approval of the scientific and ethical validity of the study protocol in the relevant country or authorization by the relevant institutional review board or equivalent organizations in that country pursuant to the statues, guidelines, etc., in force in that country, followed by endorsement by the director of the research institution in that country.

 

3. Definitions of Terms


(1) Clinical studies

“Clinical studies" means medical studies performed on human subjects (including studies of materials and/or data derived from specifiable individuals) with the goal of improving methods of preventing, diagnosing, and treating disease, acquiring a better understanding of the etiology and pathophysiology of individual diseases, and improving the quality of life of patients.


<Subrule>


“Medical studies" encompasses not only studies in the field of medicine proper but studies related to dentistry, pharmacology, nursing, rehabilitation, preventive medicine, and health sciences.

 

(2) Subjects

“Subjects" are individuals who fall into any of the following categories:


1) Individuals for whom a clinical study is performed;


2) Individuals who are requested to participate in a clinical study;


3) Individuals who provide parts or products of the human body, such as blood, tissue, cell, body fluids, excretions, or DNA extracted from them (including from cadavers) for use in a clinical study;


4) Individuals who provide information related to diagnosis and treatment (including such information in regard to cadavers) (such information is hereinafter referred to as “medical records".

 

(3) Human Specimens and Equivalent Materials

“Human specimens and equivalent materials" means parts or products of the human body (such as blood, tissue, cell, body fluids, excretions, or DNA extracted from them, including from cadavers) and medical records (including in regard to cadavers) for use in a clinical study. They do not include tissue, cells, body fluids, excretions, and DNA extracted from them if the materials have widely accepted academic value, have been adequately studied, have been extensively used in studies and are widely available.

“Medical records"means diagnoses, names of drugs used, laboratory test data, and equivalent information collected during the course of diagnosis and treatment.

 

(4) Researchers and Equivalent Persons

“Researchers and equivalent persons" means principal investigators, directors of research institutions, and other individuals involved in clinical studies.

 

(5) Principal Investigator

“Principal investigator" means the individual who performs and supervises the clinical study at an individual research institution.

 

(6) Personal information

“Personal information" means information about a living individual which allows that individual to be identified on the basis of name, birth date, or other data contained in it (including data that can be easily linked to other information and thereby allow identification of that particular individual).

If information on a deceased individual also provides information on any living individual (blood relatives of the deceased and equivalent persons), the information concerned is regarded as personal information in regard to that living individual(s).


<Subrule>


Typical examples of personal information include not only name, birth date, address, and telephone number, but also the medical record numbers assigned to individual patients. Whether the latter information is to be regarded as personal information under the amended EGCS will be determined on an individual basis according to the circumstances in the individual case.

 

(7) Personal Information in Possession

“Personal information in possession" means personal information related to the study conducted by the researchers and equivalent persons who belong to research institutions and in regard to which the researchers and equivalent persons are entitled to make disclosures, corrections, additions, deletions, bans on utilization and deletions, and discontinuation to supply to third parties.

 

(8) Research institutions

“Research institutions" means institutions in which a clinical study is performed (including institutions that provide human specimens and equivalent materials).


<Subrule>


Typical examples of medical records are files or charts prepared for individual patients. Whether these items are to be regarded as medical records under the amended EGCS will be determined on the basis of the circumstances in each individual case.

 

(9) Collaborative Research Institutions

“Collaborative research institutions" means research institutions that are jointly engaged in a clinical study specified in a protocol (including institutions that provide human specimens and equivalent materials).

 

(10) Institutional Review Board

“Institutional review board" means the advisory organization to the director of the research institution that investigates and assesses the acceptability of the start or continuation of clinical studies and other matters related to clinical studies from an ethical standpoint (a standpoint that respects the dignity and rights of individual subjects) as well as a scientific standpoint.

 

(11) Informed consent

“Informed consent" means the consent that a person who is a candidate for inclusion as a subject of a clinical study, after having been fully informed of the design of the clinical study by researchers or equivalent persons and having fully understood the significance, objective(s), method(s), etc., of the study, gives at his/her own discretion to participate in the study and to the procedure for handling the human specimens and equivalent materials.

 

(12) Proxy consenters

“Proxy consenters" means individuals who are deemed capable of acting on behalf of the intentions and interest of potential subjects of clinical studies and who have given informed consent to a researcher or an equivalent person on behalf of the subjects unable to give informed consent themselves.

 

(13) Minors

“Minors" are individuals under 20 years of age who have never been married.

 

(14) Proxies

“Proxies" are individuals who serve as legal agents for minors or adults requiring guardianship or who are entrusted with the power to represent persons in requesting notification about the purpose of utilization of personal information possessed by third parties, disclosure, correction, and other processing of such personal information, and discontinuation of utilization or supply of the personal information to a third party (hereinafter called “requests of disclosure, etc.".

 

(15) Competence

“Competence" means the ability to perform legal acts independently and in a valid manner.



Part II: RESPONSIBILITIES OF RESEARCHER

1. Responsibilities of Researchers and Equivalent Persons


(1) It is the responsibility of researchers and equivalent persons in clinical studies to protect the life, health, privacy, and dignity of each subject.

 

(2) The principal investigator, who is responsible for the study, must specify the following in the clinical study protocol: 1) the information provided to each subject, 2) the method used to obtain consent from subjects, 3) whether compensation is provided to the subjects of the clinical study (and details concerning such compensation, if any; the same in Part IV-1-(1)), and 4) other matters required to obtain informed consent.

 

<Subrules>


As a rule, every clinical study protocol should contain a statement regarding the items listed below. However, the scope of information required may be modified according to the nature of the study.


a) Subject selection policy


b) The significance, objective(s), method(s), and duration of the study; possible benefits and risks to subjects associated with participation in the study; unavoidable discomfort to subjects caused by the study; measures to be taken after completion of the study; and methods used to protect personal information related to the study (including the handling of information that allows the subject to be identified)


c) Name(s) of collaborative research institution(s)


d) Name(s) of researcher(s) and equivalent person(s)


e) Procedure for obtaining informed consent


f) The scope of information to be provided to subjects to obtain informed consent and the form used to give informed consent


g) Financial resources pertaining to the study, possible conflicts of interest, and the relationship between the researchers and other persons involved and organizations associated with the study


h) Whether compensation is given to the subjects of the study (and details of the compensation, if any)

[If it is difficult to obtain informed consent from some potential subjects]


i) Importance of conducting the study; reason why participation by the subject in the study is critical; and policy for selecting a proxy consenter or equivalent person to consent for such subjects when obtaining informed consent

 

(3) Before undertaking a clinical study, the researchers and equivalent persons must provide adequate explanations of matters related to the study to potential subjects and obtain their informed consent in writing.


<Subrule>


It is not required that every researcher and equivalent person obtain written informed consent. It is sufficient if the principal investigator acting as the representative of all of the researchers and equivalent persons obtain written informed consent from each subject.

 

(4) As a rule, the principal investigator may not start a clinical study, if he/she foresees danger in relation to the clinical study and judges that it is impossible to adequately ensure the safety of the study.


<Subrules>



1. The principal investigator must continue to obtain adequate information required to foresee danger and to ensure safety until the clinical study is completed.

2. It is particularly important for the principal investigator to ensure the safety of the clinical study once the clinical study has been started.

 

(5) The principal investigator must obtain permission from the director of the research institution to start or continue a clinical study.


<Subrules>


1. “Continuing a clinical study"means resuming a clinical study after discontinuing it for some reason.


2. “Director of the research institution"means any of the following persons:


a) Hospital Director


b) Public Health Care Center Director

 

c) Director of Laboratories, etc.


3. If the research institution is small or for some other reason, the same person is both the principal investigator and the director of the research institution, the principal investigator must use due care to satisfy the ethical requirements by requesting an examination of the study by the institutional review board of a collaborative research institution, a public service corporation, an academic society, or the like .

 

(6) The principal investigator must specify the schedule and activity involved in the clinical study when devising the clinical study protocol.

 

(7) The principal investigator is required to have adequate expert knowledge and clinical experience for appropriate implementation of the clinical study.


<Subrule>


When a clinical study that may affect human health (a so-called “interventional study" is performed on human subjects, appropriate advice should be sought from physicians with adequate clinical experience. This provision does not apply if a physician with adequate clinical experience is participating in said study.

 

(8) When performing a clinical study, researchers and equivalent persons must follow generally accepted scientific rules and their activity must be based on the scientific literature, other science-related information, and adequate experimental data.

 

(9) Researchers and equivalent persons must use due care when performing a clinical study that may affect the environment or that involves animals.

 

(10) The principal investigator must report serious adverse events and other information required to conduct a survey to ensure the appropriateness and reliability of a clinical study to the director of the research institution.

 

(11) When a clinical study is undertaken jointly by two or more research institutions, the principal investigator of each research institution must report serious adverse events that occur during the study to the principal investigator of each of the other research institutions participating in the study.

 

(12) The principal investigator must discontinue or complete the clinical study if he/she judges that the danger involved outweighs the benefits expected from the study, or if the results already obtained from the study are adequate.


<Subrules>


1. It is advisable that the principal investigator continue to be familiar with presentations and publications concerning the study concerned (hereinafter called “information on presentations, etc." made in Japan and foreign countries until the study is completed, and that he/she reports such information to the director of the research institution.


2. When a clinical study is undertaken jointly by two or more research institutions, it is advisable that the principal investigator of a research report information on presentations, etc., to the principal investigators of each of the other research institutions involved.


3. When a clinical study is discontinued or completed, the principal investigator must report its discontinuation or completion to the director of the research institution. If the study has been discontinued for emergency reasons (e.g., a judgment that the danger arising from the study outweighs the benefits expected from the study), the principal investigator must immediately report its discontinuation to the director of the research institution.

 

(13) The principal investigator has the following responsibilities related to the protection of personal information.


1) The principal investigator must implement necessary and appropriate supervision of researchers and equivalent persons who handle personal information, to ensure safe control of the personal information related to the study.


<Subrule>


It is advisable that the principal investigator cooperate with the director of the research institution to ensure procedures, facilities, systems, etc., for strict control of personal information.


2) If handling of all or part of the personal information is assigned to a contractor, the principal investigator must implement necessary and appropriate supervision of the contractor, to ensure safe control of the assigned personal information by the contractor.


<Subrule>


“Necessary and appropriate supervision"means inserting explicit provisions about measures deemed necessary by the assignor for safe control of personal information into the assignment contract and checking for implementation of these provisions by the contractor.


3) The principal investigator must keep the following information related to the personal information in possession accessible to the subjects of the clinical study (“making the information accessible to the subjects"includes immediately responding to subjects' requests).


i) Names of the researchers and equivalent persons or the research teams involved in the study;


ii) All purposes of utilization of personal information (this provision does not apply to the cases specified in the subrules below);


iii) Procedure for responding to requests for disclosure, etc.;


iv) Addresses to which claims or questions are to be sent.


<Subrules>


The provision in Part II-1-(13)-3) does not apply if:


a) Informing the subject of any purpose of utilization or making any purpose public may adversely affect the life, health, property, or other rights or interests of the subject or any third party;


b) Informing the subject of any purpose of utilization or making any purpose public may adversely affect the rights or due interests of the principal investigator involved;


c) Informing the subject of any purpose of utilization or making any purpose public may compromise smooth cooperation of the research institution with the operation undertaken by organs of the state or local governments pursuant to statutes;


d) Any purpose of utilization of personal information is already obvious because of the circumstances under which the information was collected.


4) If the subject or his/her proxy has requested disclosure of the subject's identifiable information in possession, as a rule the principal investigator must immediately disclose said information in writing or by other means agreed upon with the person who has made the request.

If the subject's identifiable information is not possessed by the research institution, the principal investigator must inform the person who has requested it of that fact.

If any of the following apply to disclosure of the information requested, the principal investigator may refuse disclosure of all or part of the information concerned:


a) Disclosure may adversely affect the life, health, property, or other rights or interests of the subject or any third party;


b) Disclosure may seriously compromise appropriate pursuit of the tasks related to the clinical study by the researchers and equivalent persons;


c) Disclosure violates any other statute.

If the principal investigator has decided not to disclose all or part of the personal information requested, then, as a rule, he/she must inform the subject of that decision without delay. As a rule, then the principal investigator must make an effort to provide the reason for this decision.

If any other statute contains a provision about disclosure of personal information in possession, that provision must be followed.


5) As a rule, disclosure of personal information which contains medical records must be in accordance with the guidelines prepared by the Director General of the Health Policy Bureau of the Ministry of Health, Labour and Welfare (MHLW).


<Subrule>


The guidelines prepared by the Director General of the Health Policy Bureau of the Ministry of Health, Labour and Welfare referred to in Part II-1(13)-5) are the Guidelines for Supply and Other Handling of Medical Records announced with the notification by the Health Policy Bureau Director General of the MHLW entitled, “Notice on the Guidelines for Supply and Other Handling of Medical Records"(Health Policy Bureau Notification No. 0912001, September 12, 2003).


6) The principal investigator must comply with due and acceptable requests by subjects or their proxy in regard to the correction or other processing of personal information in possession or in regard to discontinuation of utilization or third party supply of the information.

If discontinuation of utilization or third party supply of the information is difficult for reasons such as great expense and if there is an alternative means of protecting the rights and interests of the subject, this provision does not apply.


<Subrule>


If the principal investigator has done any of the following in regard to all or part of the personal information in possession in response to a request by the subject or his/her proxy in accordance with Part II-1(13)-6), as a rule the principal investigator must inform the subject immediately.


a) Corrected or other processed it


b) Decided to refuse to correct or otherwise process it


c) Discontinued utilization


d) Decided to refuse discontinuation of utilization


e) Discontinued supply to a third party


f) Decided to refuse discontinuation of third party supply

 

7) When the principal investigator informs a subject or proxy of his/her decision to refuse a request by the subject or his/her proxy regarding disclosure, etc., or to take a measure different from the one requested, as a rule he/she must endeavor to explain the reason for such a decision to the subject.


8) When the subject or his/her proxy has made a request for disclosure, etc., the principal investigator may ask the subject or the proxy to present information sufficient to specify the personal information requested. However, the principal investigator must take measures for the convenience of the subject or the proxy (e.g., supply of information that will help the subject or proxy specify the personal information possessed by the research institution) to enable the subject or the proxy to easily and precisely request disclosure, etc.


<Subrule>


The principal investigator must establish a uniform procedure to deal with requests for disclosure, etc., related to the clinical study, in order to reduce the burden on subjects or proxies when making such requests.

 

(14) The researchers and equivalent persons have the following responsibilities related to the protection of personal information.


1) When the outcome of a clinical study is made public, the researchers and equivalent persons must take measures to ensure that the subject is not identified by the information published.


<Subrule>


When the data on some of the subjects are presented at professional conferences or in journals, deletion of the subjects' name, birth date, address, etc., will make the subjects unidentifiable. If it is difficult to make the subjects unidentifiable when reporting their data, consent must be obtained from the subjects concerned.


2) The researchers and equivalent persons may not use the personal information beyond the extent required to achieve the purposes of utilization specified in the informed consent document, unless additional consent is obtained from the subject in advance.


3) Before modifying the purposes of utilization of personal information related to the clinical study (excluding the situations specified in Part II-1(14)-4)), the researchers and equivalent persons must inform the subject of the planned modification and obtain the subject's consent (this provision does not apply under the circumstances specified below in the subrule).


<Subrule>


The provision set forth in Part II-1(14)-3) does not apply if:


a) The modification is made pursuant to statutes;


b) The modification is necessary for the protection of the life, health, or property of individuals and it is difficult to obtain the consent of the subject
concerned;


c) The modification is particularly necessary to improve public health or to promote the sound growth of children and it is difficult to obtain the consent of the subject concerned;


d) Obtaining the subject's consent may compromise smooth cooperation between the research institution and the operation undertaken pursuant to statutes by organs of the state, local governments, or their contractors;


4) As a rule, the researchers and equivalent persons must inform the subject any modification of the purposes of utilization of personal information related to the clinical study, if the modification is reasonable in relation to the scope of the original purposes of utilization;


5) When the researchers and equivalent persons have obtained personal information as a result of taking over a clinical study from other researchers or equivalent persons, they may not use the personal information beyond the extent required to achieve the original purposes of utilization, unless additional consent is obtained from the subjects concerned;


6) Personal information may not be obtained by falsehood or other fraudulent means;


7) The researchers and equivalent persons must endeavor to keep the personal information (related to the clinical study) accurate and up to date within the extent necessary to achieve the purposes of utilization;


8) The researchers and equivalent persons must take necessary and appropriate measures to ensure safe control of the personal information they handle, such as measures to prevent leakage, loss, or damage of the information.

Furthermore, out of respect for the dignity of the deceased and the feelings of the blood relatives of the deceased, the researchers and equivalent persons must take measures similar to those taken in regard to personal information to ensure safe control of information related to the deceased, such as the measures to prevent leakage, loss, or damage of the information;


9) The researchers and equivalent persons may not supply any personal information related to the clinical study to any third party without prior consent of the subjects concerned. (This provision does not apply under the circumstances specified in the subrules.)


<Subrules>


1. The provision set forth in Part II-1(14)-9) does not apply in the following situations:


a) When the information is supplied pursuant to statutes;


b) When supplying the information is necessary to protect the life, health or property of individuals and it is difficult to obtain the consent of the subjects concerned;


c) When supplying the information is particularly necessary to improve public health or to promote the sound growth of children and it would be difficult to obtain consent of the subject concerned;

 

d) When obtaining subjects' consent may compromise smooth cooperation between the research institution and the operation undertaken pursuant to statutes by organs of the state, local governments, or their contractors.


2. The following situations are not considered to constitute supply of personal information to third parties under the provision set forth in Part II-1(14)-
9):


a) Assignment by researchers and equivalent persons of all or part of the personal information handling to contractors, within the extent required to achieve the purposes of utilization;


b) When supply of personal information is associated with a business takeover because of a merger or other reasons;


c) When personal information is utilized jointly with other persons and the subject is informed in advance or has easily access to knowledge about the joint utilization, the type of personal information utilized jointly, the scope of persons allowed to utilize the information, purposes of utilization, name or title of the persons responsible for control of the personal information concerned (If the researchers or equivalent persons change the purposes of joint utilization of personal information or the name or title of the persons responsible for control of the personal information, they must inform the subject in advance of the planned modification or provide the subject with easy access to the plan of modification).


10) The researchers and equivalent persons must endeavor to appropriately and quickly respond to claims or inquiries made by subjects and equivalent persons about the handling of personal information related to the clinical study.

 

(15) Even after completion of the clinical study, the principal investigator must make an effort to ensure that the subjects have access to the best preventive, diagnostic, and therapeutic methods identified by the clinical study concerned.

 

2. Responsibilities of Directors of Research Institutions


(1) Thorough consideration for ethics

The director of each research institution must ensure that researchers and equivalent persons in a clinical study (excluding the director of the research institution concerned) thoroughly understand the need to respect the dignity and rights of individual subjects and protect their personal information when conducting the clinical study, so that the clinical study undertaken at the institution does not give rise to ethical, legal, or social problems.


(2) Organizing the institutional review board

The director of each research institution must organize an institutional review board to access the acceptability of the clinical study protocol in light of the amended EGCS and other matters necessary for the pursuit of the clinical study. If it is impossible to organize an institutional review board because of the small size of the research institution or for other reasons, arranging an examination by the institutional review board of a collaborative research institution, a public service corporation, an academic society or the like, shall satisfy this requirement.


<Subrule>


If the research institution has a committee that plays a role similar to that of an institutional review board (irrespective of what the committee is called), it is acceptable to re-organize that committee into one that satisfies the amended EGCS instead of newly organizing an institutional review board.

 

(3) Examination at the institutional review board

If the principal investigator has reported information required to perform a survey to ensure the appropriateness and reliability of the clinical study pursuant to provision 1(10) of the amended EGCS, the director of the research institution must report the fact to the institutional review board. If the principal investigator has asked for approval to start or continue a clinical study pursuant to provision 1(5), or if the principal investigator has reported serious adverse events pursuant to provision 1(10), the director of the research institution must immediately ask the opinion of the institutional review board concerning the acceptability of starting or continuing the clinical study or the other matters related to the clinical study.


<Subrules>


1. When a clinical study is undertaken jointly by two or more research institutions, as a rule, the director of each research institution involved must obtain authorization of the protocol from its own institutional review board.


2. When a clinical study is undertaken jointly by two or more research institutions, the director of each research institution involved must submit information on the status of protocol approval, informed consent from subjects, etc., at other participating research institutions when asking the opinion of the institutional review board about the acceptability of starting or continuing the study concerned.

 

(4) Approval by the director of the research institution

The director of each research institution must make the necessary discretion as to whether to approve the start or continuation of the clinical study concerned and discretions about other matters related to the study, with due respect to the opinions of the institutional review board. The director of the research institution may not approve the start or continuation of a study that has been judged to be unacceptable by the institutional review board.


<Subrule>


The director of the research institution may approve the start of a clinical study on an emergency basis without seeking the opinions of the institutional review board, if he/she judges the study to be indispensable to the prevention or control of a public health hazard. In such situations the director of the research institution must seek the opinions of the institutional review board after having issued approval of the study. If the institutional review board advises modifying or discontinuing the study, the director of the research institution must instruct the principal investigator to modify or discontinue the study concerned.

 

(5) Disclosure of the clinical study protocol, etc.

The director of each research institution must endeavor to make the protocol and outcome of each clinical study public.

 

3. Responsibilities of Representatives, Directors, and Equivalent Persons of Corporations, Administrative Organs, and Equivalent Organizations that Possess Research Institutions


(1) Responsibilities related to protection of personal information


1) The representatives, directors, or equivalent persons of the corporations, administrative organs, and equivalent organizations that possess research institutions hereinafter referred to as “representatives of organizations" must ensure that personal information be protected during pursuit of the clinical study at their institutions.


2) The representatives of organizations may issue directions required for supervision to the director or equivalent person of the research institution concerned if he/she judges that they are required to ensure appropriate measures for the protection of personal information.


3) The representatives of organizations may assign the power or operation of the matters defined below related to their responsibilities to the director or another appropriate person of the research institution concerned in accordance with the rules set forth by the research institution concerned.

 

(2) Measures for safe control of personal information

The representatives of organizations must take necessary and appropriate organizational, personal, physical, and technical measures for safe control of personal information.

Out of respect for the dignity of the deceased and the feelings of the blood relatives of the deceased, the representatives of organizations must also take necessary and appropriate organizational, personal, physical, and technical measures for safe control of information on the deceased in a way similar to that for personal information.

 

(3) Establishing a system to deal with claims, inquiries, etc.

For appropriate and quick responses to claims, inquiries, etc., the representatives of organizations must endeavor to establish a system to deal with claims, inquiries, etc., from subjects and other persons, by organizing a unit that accepts claims, inquiries, etc., preparing a manual on the procedures for dealing with claims, inquiries, etc., and taking other measures.

 

(4) Collection of fees, etc.

The representatives of organizations may collect fees for the services they render in response to requests for notification of the purposes of utilization of personal information possessed by the organizations or requests for disclosure of personal information in possession. The representatives or organizations must set reasonable fees, taking into account the actual cost of rendering such services.

 

Part III: INSTITUTIONAL REVIEW BOARD

 

(1) When the director of the research institution has sought the opinion of the institutional review board as to whether a clinical study protocol satisfies the amended EGCS and in regard to other matters related to the clinical study, the institutional review board must examine the questions and answer them in writing from an ethical and scientific standpoint.

 

(2) The institutional review board must be appropriately composed and operated so that each matter can be examined in a fair and neutral manner from an inter-disciplinary and multi-dimensional standpoint by members of the board representing various viewpoints.


<Subrules>


1. The institutional review board must be composed of experts in natural sciences (medicine, medical care, etc.), experts in cultural or social sciences (law, etc.), and individuals representing the general public. Some board members must be from outside the institution concerned. The board must be composed of members of both sexes.


2. When the board examines or votes on any issue, at least one member representing the natural sciences and one member representing either the cultural or social sciences or the general public must be in attendance at the meeting.


3. Individuals involved in the clinical study to be examined (e.g., the director of the research institution) may not participate in the examination or voting on the clinical study concerned, however, they may attend the meeting and provide explanations when requested by the board.

 

(3) Members of the institutional review board may not disclose any information that they acquire during their activity as members of the board to any third party without due cause. This same provision also applies after members have resigned.

 

(4) The institutional review board may conduct investigations to ensure the appropriateness and reliability of ongoing or completed clinical studies.


Part IV: INFORMED CONSENT


<Subrules>


When requesting informed consent from candidate for subjects, the information below must first be given to the candidate, or his/her proxy consenter or equivalent person. The scope of the information given may vary with the nature of the clinical study concerned.


a) Participation in the study is optional;


b) Not giving consent to the study will not cause any disadvantage to the candidate;


c) A subject or his/her proxy consenter or equivalent person may rescind informed consent at any time after giving it without sustaining any disadvantage;


d) The reason why the individual was selected as candidate for a subject of the study;


e) The significance, objective(s), method(s), and duration of the study;


f) Name(s) and positions(s) of researcher(s) and equivalent person(s);


g) Expected outcome of the study, benefits and risks possibly arising from participation in the study, unavoidable discomfort associated with participation in the study, and measures to be taken after completion of the study;


h) The right of the subject to obtain or access information pertaining to the protocol and methods of the clinical study concerned, if the subject or his/her proxy consenter or equivalent person so desires, unless it interferes with the protection of the personal information of other subjects or compromises ensuring the novelty of the study;


i) The possibility that the results of the study will be supplied to other organizations, subject to verification by the institutional review board as to the appropriateness of the handling of personal information, the nature of the recipient of the information, and how the information supplied will be utilized;


j) The possibility that patent rights, etc., may be derived from the results of the study, and identification of the party who will possess such rights;


k) The possibility that the results of the study will be published after measures are taken to make the subjects unidentifiable;


l) Financial resources pertaining to the study, possible conflicts of interest, and the relationship between the researchers and equivalent persons and the organizations related to the study;


m) Whether compensation will be provided for participation in the study (and details of the compensation, if any);


n) Information on whom to contact if the subject has any inquiries, complaints, etc.

[If it is difficult to obtain informed consent from some subjects]


o) Information on the importance of conducting the study and the reason why participation by the subject in the study is critical.

 

1. Procedure for Obtaining Informed Consent from Candidates


(1) Researchers and equivalent persons must provide candidates for the subjects of the planned clinical study with adequate explanations concerning the objective, methods, and financial resources of the study, possible conflicts of interest, relationship between the researchers and equivalent persons and the organizations related to the study, possible benefits and risks associated with participation in the study, unavoidable discomfort caused by the study, measures to be taken after completion of the study, whether compensation will be provided for participation in the study, and other necessary items of information.

 

(2) Researchers and equivalent persons must exercise due care to ensure the free exercise of discretion by the candidate if the candidate is in an unfavorable position for economic, medical, or other reasons.

 

(3) Researchers and equivalent persons must confirm that the candidate has understood the explanations given pursuant to provision (1) and must obtain written informed consent given at the candidate's own discretion.

 

(4) Researchers and equivalent persons must explain to the candidate his/her right to rescind informed consent at any time without causing any disadvantage to the candidate.


<Subrule>


It is advisable to use a leaflet to explain the subject's right to rescind informed consent.

 

2. Procedure for Obtaining Informed Consent from Proxy Consenters or Equivalent Persons


<Subrules>


1. Situations in which informed consent may be obtained from the subject's proxy consenter or equivalent person are specified below. How such situations should be handled is also described. In every such situation, the principal investigator must state the importance of the study, reason(s) why participation of the subject in the study is critical, and the policy for selecting the proxy consenter or agent in the clinical study protocol, and must obtain approval of the protocol by the institutional review board and then by the director of the research institution.


a) If the candidate is objectively rated as being unable to give valid informed consent for reasons of sickness, etc.


b) If the candidate is a minor. Also, if the candidate is a minor, researchers or equivalent persons must provide adequate explanations in a manner that can be understood by the candidate and endeavor to obtain his/her understanding. If the minor is 16 years of age or older, informed consent should be obtained both from the proxy consenter or equivalent person and from the candidate himself/herself.

[If it was impossible to obtain informed consent while the candidate was alive]


c) Situations in which participation in the study does not contradict the explicit intention of the candidate expressed while alive.


2. In general, researchers and equivalent persons must consider the composition of the subject's family and situation confronting the subject, and select an individual who can represent the subject's intentions and interests from among the individuals listed below. The policy used to select a proxy consenter or equivalent person must be specified in the clinical study protocol.


a) Voluntary guardian, persons in parental authority, guardian of an adult, guardian of a minor, or curator/assistant, if any;


b) The candidate's spouse, adult child, parent, adult siblings, adult grandchild, grandparent, blood relative residing in the same household, or the like.


3. In general, researchers and equivalent persons must consider the composition of a deceased candidate's family and the situation of the dead candidate confronted while alive, and then select an individual who can represent the deceased candidate's intentions from among the individuals listed below. The policy used for selection of a proxy consenter or equivalent person must be specified in the clinical study protocol.


a) Deceased candidate's spouse, adult child, parent, adult sibling, adult grandchild, grandparent, blood relative residing in the same household, or the like.

 

(1) If it is impossible for a candidate whose participation is critical to a clinical study to give informed consent, researchers and equivalent persons may obtain informed consent from the subject's proxy consenter or equivalent person, subject to approval by the institutional review board and the director of the research institution concerned.

 

(2) If a minor or an individual who appears to be incompetent is concluded to be capable of understanding the meaning of participation in the clinical study, researchers and equivalent persons must obtain informed consent both from the proxy consenter or equivalent person and from the candidate himself/herself.

 

3. Miscellaneous

If informed consent by the candidate or proxy consenter has not been obtained in regard to the use of a given human specimen or equivalent material for clinical study, as a rule the specimen or material may not be used for clinical study unless informed consent is obtained from the candidate or proxy consenter in accordance with the method or procedure set forth in the amended EGCS (this provision does not apply to cases approved by the institutional review board).



Part V: SUBRULES

 

Matters required for enforcement of the amended EGCS will be set forth separately as subrules.

 

Part VI: REVISION

 

Whenever required, or by July 30, 2008, the amended EGCS will be reviewed and revised as needed.

 

Part VII: DATE OF ENFORCEMENT

 

The amended EGCS will go into effect on April 1, 2005.


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