Declaration of Baltimore

Guideline 10: Equitable distribution of burdens and benefits (p. 29)

"... Special justification is required for inviting vulnerable individuals and, if they are selected, the means of protecting their rights and welfare must be particularly strictly applied." (p. 29) [A, B] [DD, EE, II, LL]


"General considerations. ...Equitable distribution of the burdens and benefits of research participation is generally more difficult when the intended subjects include vulnerable individuals or groups. Classes of individuals traditionally considered vulnerable are those with limited capacity or freedom to consent. They are the subject of specific guidelines in this document and include children, persons who because of mental or behavioral disorders are incapable of giving informed consent, and prisoners. Ethical justification of their involvement usually requires that investigators satisfy ethical review committees that: [A, B[ [DD, EE]

- the risks attached to research that is not intended to benefit individual subjects will be minimal, unless an ethical review committee authorizes a slight increase above minimal risk; (p. 30) (emphasis ours) (other points noted) [E, G] [GG, II, MM]

"Other vulnerable social groups. ... Other groups or classes may also be considered vulnerable. They include residents of nursing homes, people receiving welfare benefits or social assistance and other poor people and the unemployed, patients in emergency rooms, some ethnic and racial minority groups, homeless persons, nomads, refugees, and patients with incurable disease. To the extent that these and other classes of people have attributes resembling those of classes identified as vulnerable, the need for special protection of their rights and welfare should be considered." (p. 31) [A] [EE]

Guideline 12: Safeguarding confidentiality (p. 35)


"General considerations: The Declaration of Helsinki, Article I.6, states: "the right of the research subject to safeguard his or her integrity must always be respected. Every precaution should be taken to respect the privacy of the subject and to minimize the impact of the study on the subject's physical and mental integrity and on the personality of the subject." (p. 35) (emphasis ours) [A, J] [GG]

Guideline 13: Right of subjects to compensation (p. 36)

Research subjects who suffer physical injury as a result of their participation are entitled to such financial or other assistance as would compensate them equitably for any temporary or permanent impairment or disability. In the case of death, their dependents are entitled to material compensation. The right to compensation may not be waived. [J, K, L, M] [NN]


"Equitable compensation. Compensation is owed to subjects who sustain significant physical injury from procedures performed solely to accomplish the purposes of research. Justice requires that every subject of biomedical research be automatically entitled to fair compensation for any such injury. Compensation is generally not owed to research subjects who suffer expected or foreseen adverse reactions from investigational therapies or other procedures performed to diagnose or prevent disease. Such reactions are not different in kind from those that occur in medical practice. (p. 36-37) [J, K, L, M] [NN]

"Subjects should not be required to waive their rights to compensation or to show negligence or lack of a reasonable degree of skill on the part of the investigator in order to claim compensation. The informed consent process or form should contain no words that would absolve an investigator from responsibility in the case of accidental injury, or that would imply that subjects would waive their legal rights, including the right to seek compensation for injury." (p. 37) [I, J, K, L, M] [KK, NN]

Guideline 14: Constitution and responsibilities of ethical review committees (p. 37)


"Scientific review. The Declaration of Helsinki, Article I.1, states that "biomedical research involving human subjects must conform to generally accepted scientific principles and should be based on adequately performed laboratory and animal experimentation and on a thorough knowledge of the scientific literature." [FF]

"Committees competent to review and approve scientific aspects of clinical trials must be multi-disciplinary ... (p. 38)

"Risks and benefits. The Declaration of Helsinki forbids the imposition of unwarranted risks on human research subjects. Article I.4 requires that "the importance of the objective is in proportion to the inherent risk to the subject..." (p. 39) (emphasis ours) [E, G, J] [GG, II, MM]

"In Phases II and III of drug testing ..., when benefits are intended for the subjects and they are reasonably likely to be realized, it is permissible to involve members of vulnerable groups and persons with limited capacity to consent. However, as required by the Declaration of Helsinki, Article II.3, "every patient - including those of a control group, if any - should be assured of the best proven diagnostic and therapeutic method." Therefore, if there is already an approved and accepted drug for the condition that a candidate drug is designed to treat, placebo for controls usually cannot be justified. (p. 39) (emphasis ours) [F, G, J] [DD, EE]

"Ethical justification to begin a randomized clinical trial also meets the requirement of Article II.3. The therapies ... to be compared must be regarded as equally advantageous to the prospective subjects: there should be no scientific evidence to establish the superiority of one over another. Moreover, no other intervention must be known to be superior to those being compared in the clinical trial, unless eligibility to participate is limited to persons who have been unsuccessfully treated with the other superior intervention or to persons who are aware of the other intervention and its superiority and have chosen not to accept it. (p. 39-40) (emphasis ours) [E, G, J] [DD]

"For each randomized clinical trial there should be a data and safety monitoring committee, responsible for monitoring the data obtained in the course of a study and for making recommendations to the sponsors and investigators about modifying or terminating the study, or about amending the informed-consent process or form. Such recommendations are made in response to the committee's detection of adverse events of which the nature, frequency or magnitude had not been anticipated by the investigators or sponsors as they planned the study, or of evidence that one of the therapies or preventive measures being tested in the clinical trial is superior to another. During the planning stage of a clinical trial, stopping-rules should be established to guide the data and safety monitoring committee in determining when it should recommend termination of the study. (p. 40) (emphasis ours) [I,L] [MM]

"National or local review. Review committees may be created under the aegis of national or local health administration, national medical research councils or other nationally-representative bodies. In a highly centralized administration, a national review committee may be constituted for both the scientific and the ethical review of research protocols ..." [H, O] [QQ]

"Committee membership. Local review committees should be so composed as to be able to provide complete and adequate review of the research activities referred to them. They should include physicians, scientists and other professionals, such as nurses, lawyers, ethicists and clergy, as well as lay persons qualified to represent the cultural and moral values of the community. The membership should include both men and women. Committees that often review research directed at specific diseases or impairments ... should consider the advantages of including as members or consultants patients with such diseases or impairments. Similarly, committees that review research involving such vulnerable groups as children, students, aged persons or employees should consider the advantages of including representatives of, or advocates for, such groups. (p. 40-41) [H] [OO, PP]

"Need for particularly stringent review requirements. The requirements of review committees should be particularly stringent in the case of proposed research involving ... persons with mental or behavioral disorders, ... and other vulnerable social groups, and in the case of invasive non-clinical research... (p. 41) [A, B] [DD, EE, GG, PP]

"Sanctions. Should sanctions become necessary, they should be directed at the non-compliant investigators or sponsors. They may include fines or suspension of eligibility to receive research funding, to use investigational therapies, or to practice medicine. Refusal to publish the results of research conducted unethically, as prescribed in the Declaration of Helsinki, Article I.8, may be considered, as may refusal to accept unethically obtained data submitted in support of an application for drug registration ... (p. 42) (emphasis ours) [C, I, K, N] [KK, NN]

"Publications of reports of the results of research involving human subjects should include, when appropriate, a statement that the research was conducted in accordance with these guidelines. Departures, if any, from these guidelines should be explained and justified in the report submitted for publication. (p. 42) (emphasis ours) [C, I, K, N]

"Information to be provided by investigators. Whatever the procedure adopted for ethical review, such review should be based on a detailed protocol comprising: (all emphases ours) (not all points included) [KK]

"Information should also be included to establish:


Because persons with mental illness are vulnerable (whether competent or incompetent), and thus should be provided with special procedures and precautions when they are used in neurobiological research in order to protect their human rights and physical as well as psychological welfare, the following list of issues of concern are provided for further discussion, in order to facilitate the further refinement of the CIOMS (and similar) research guidelines:

(Issues included in the first draft of the Declaration of Baltimore:)

(Issues graciously submitted by commentators on the first draft of the Declaration of Baltimore:)


1 For purposes of clarity and uniformity, the relevant sections of the first draft of the Declaration of Baltimore have been set within the context of the most recent CIOMS 1993 international guidelines on the use of human subjects in research. Copies of those guidelines will be provided to all participants of the Conference. [Back]

2 International Ethical Guidelines for Biomedical Research Involving Human Subjects, prepared by the Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the World Health Organization (WHO) (Geneva: 1993). Appreciation is expressed to Robert J. Levine, M.D., for distribution of this document to us. Dr. Levine was the co-chairman of the CIOMS Steering Committee which helped to draft these Guidelines, and of the Conference on Ethics and Research on Human Subjects - International Guidelines. [Back]

3 World Medical Association Declaration of Helsinki, adopted by the 18th World Medical Assembly (Helsinki, Finland: June 1964); and amended by the 29th World Medical Assembly (Tokyo, Japan: October 1975), the 35th World Medical Assembly (Venice, Italy: October 1983), and the 41st World Medical Assembly (Hong Kong, China: September 1989). [Back]

4 Persons with mental illnesses and behavioral disorders have been declared to belong to a "vulnerable group" by the National Commission, the President's Commission, the Declaration(s) of Helsinki, and the CIOMS Guidelines. [Back]

5 Relevant sections of the CIOMS document have been selected, and attempts have been made to list them in context as much as possible in this short draft. Most of these sections are so listed in affirmation of the relevant principles or guidelines. Some have been listed which are not automatically affirmed, and which may require further discussion and refinement. [Back]

1, 2,