All research involving human subjects should be conducted in accordance with the ethical principles contained in the current version of the Declaration of Helsinki (see Appendix 1). Three basic ethical principles should be respected, namely justice, respect for persons, and beneficence (maximizing benefits and minimizing harms and wrongs) or non-maleficence (doing no harm), as defined by the current revision of the International Ethical Guidelines for Biomedical Research Involving Human Subjects or the laws and regulations of the country in which the research is conducted, whichever represents the greater protection for subjects. All individuals involved in the conduct of any clinical trial must be fully informed of and comply with these principles (see sections 3 and 4).
Declaration of Helsinki
The current revision of the Declaration of Helsinki (Appendix 1) is the accepted basis for clinical trial ethics, and must be fully followed and respected by all parties involved in the conduct of such trials. Any departures from the Declaration must be justified and stated in the protocol. Independent assurance that subjects are protected can be provided only by an ethics committee and freely obtained informed consent.
The role of the ethics committee (or other board responsible for reviewing the trial) is to ensure the protection of the rights and welfare of human subjects participating in clinical trials, as defined by the current revision of the Declaration of Helsinki and national and other relevant regulations, and to provide public reassurance, inter alia, by previewing trial protocols, etc. (see section 2).
The ethics committee should be constituted and operated so that its tasks can be executed free from bias and from any influence of those who are conducting the trial.
The ethics committee should have documented policies and procedures as a basis for its work, which should be available to the public. These should set out the authority under which the committee is established, the number of members elected and their qualifications, a definition of what it will review, and its authority to intervene and maintain records of its activities. The documents should also state how frequently the committee will meet and how it will interact with the investigator and/or sponsor.
The investigator, or the investigator and the sponsor, must consult the relevant ethics committee(s) regarding the suitability of a proposed clinical trial protocol (including appendices and amendments) and of the methods and materials to be used in obtaining and documenting the informed consent of the subjects.
The ethics committee has an ongoing responsibility for the ethical conduct of research, and therefore must be informed of all subsequent amendments to the protocol and of any serious adverse events occurring during the trial, or other new information likely to affect the safety of the subjects or the conduct of the trial. The ethics committee should be consulted if a re-evaluation of the ethical aspects of the trial appears to be required, or if there is any doubt regarding the importance of a protocol change or new information.
Subjects must not be entered into the clinical trial until the relevant ethics committee(s) has issued its favourable opinion on the procedures. The ethics committee should give its opinion and advice in writing within a reasonable time, clearly identifying the trial protocol, itemizing the documents studied and stating the date of review. A list of those present at the committee meeting, including their professional status, should be attached.
When reviewing a clinical trial proposal, the ethics committee should consider the following:
(a) The acceptability of the investigator for the proposed trial, on the basis of sufficient information made available to the committee, in terms of his or her qualifications, experience, availability for the duration of the trial, supporting staff and available facilities.
(b) The suitability of the protocol, including the objectives of the study and the justification of predictable risks and inconveniences weighed against the anticipated benefits for the subjects and/or others, and the efficiency of its design, i.e. the potential for reaching sound conclusions with the smallest possible exposure of subjects.
(c) The means by which trial subjects will be recruited, necessary or appropriate information will be given, and consent will be obtained. This is particularly important in the case of trials involving subjects who are members of a group with a hierarchical structure or another vulnerable group (see section 3.3, (c)-(f)).
(d) The adequacy and completeness of the information, which should be written in a language and at a level of complexity understandable to everyone involved, to be given to the subjects, their relatives, guardians or, if necessary, legal representatives. All such written information must be submitted in its final form to the ethics committee.
(e) Provision, if any, for compensation or treatment in the case of death or other loss or injury of a subject, if attributable to a clinical trial, and details of any insurance or indemnity (a source of legal and financial support) to cover the liability of the investigator(s) and sponsor (see section 5.9).
(f) The appropriateness of the extent and form of payment through which the sponsor will remunerate or compensate the organization(s) and/or investigator(s) conducting the trial and the trial subjects, as required by local laws and regulations.
(g) The acceptability of any proposed amendments to the protocol that are likely to affect the safety of the subjects or the conduct of the trial.