the well-being of the subject should take preference over the interests of science and society.” This is in fact the major principle ensured by the first major revision in 1975. Other counterarguments break this same principle in that valuable research may be prevented, or that placebo-controlled trials actually lower overall societal risks by requiring smaller sample sizes and shorter follow-up times, thereby exposing fewer members of the community to the inherent risks.
Controversies of Paragraph 30 of the Edinburg (2000) revision: Are patient subjects worse off after the clinical trial than they were during the trial? The other most controversial paragraph of the Edinburgh (2000) revision of the Helsinki Report, although certainly not the only one, is paragraph 30. This paragraph speaks to the obligation of follow-up with patients after the conclusion of the study. It states: “At the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study.” As discussed in the book The Principles of Biomedical Ethics by Tom Beauchamp and James Childress, in times prior to this revision, the paradigm of ethical analysis centered around the risks and burdens of research and the need to protect subjects participating in clinical research. But this revision in paragraph 30 and also in paragraph 19 reflects a shift in paradigm whereby ethical analysis includes another important core, namely, that of fair access to participation in research and to the findings of that research.
With such a far-reaching change, a workgroup was called by the WMA to consider whether any clarifications were needed. While the workgroup concluded that no amendment or clarification was needed, it also raised some criticisms, especially around what exactly were the obligations to the clinical trial subject patients after the trial was over. One view was that this imposes too great a burden on the researchers, especially when the subject patients had no access to treatment before the trial. The argument for this side is that if there is no treatment access beforehand, then after the trial, there is comparatively no change, that is, nothing lost. However, on the other side, supporting paragraph 30, it is argued that the harm added is additional distress to patients whose treatments are halted post-trial when they are returned to their pre-trial “no access” status.
Despite any of the controversies, the Declaration of Helsinki is referred to as the “most widely recognized source of ethical guidance for biomedical research,” as declared at the World Medical Association’s 2003 Annual Assembly Scientific Session.
The Belmont Report
The Belmont Report was written in 1979, long after the Nuremberg Code and the original Helsinki Report were published. Its purpose was to present a succinct summary of the ethical guidelines for research involving human subjects. It was the result of intensive discussions over four days, during which time a commission comprised of 11 persons—medical doctors, PhD scientists, and lawyers—met at the Smithsonian Institution’s Belmont Conference Center. The Belmont Report presents three important principles for ethical research: (1) respect for persons, (2) beneficence, and (3) justice. These principles are presented in many U.S. academic institutions to researchers taking part in fieldwork and clinical studies, acknowledging the boundaries between clinical practice and research.
Such boundaries were also a source of discussion during the Nuremberg Trials. In general, clinical practice today refers to interventions designed to treat individual patients for the purposes of providing diagnoses, preventative treatments, or therapeutic treatments in order to relieve some ailment and enhance their wellness. On the other hand, clinical research refers to experiments conducted in accordance with the scientific method, which has defined objectives, tests a hypothesis, provides conclusions, and contributes in some way to medical knowledge. The three principles of the Belmont Report acknowledge these differences and refer specifically to ethical conduct in clinical research.
Two moral requirements constitute the first of the three principles, respect for persons. These requirements are that each subject should be treated as an individual, autonomous agent, and that those subjects who are vulnerable (e.g., children) or have diminished autonomy (e.g., those with a mental disability) should and must be protected. In practice, respect for persons calls for informed consent of the participants/patient subjects in the clinical trials, which itself has three elements to meet the requirement that subjects participate voluntarily with sufficient understanding about the research, its goals, and what is required of them. The three elements of informed consent are (1) information, (2) comprehension, and (3) voluntariness.
1 Information refers to specific items to be disclosed to potential participants, including the research procedure, the purpose of the research and of each procedure, the risks and anticipated benefits, any alternative procedures, and the opportunity for the subject to ask questions or to withdraw from participation at any time. Information may also include how subjects are selected, a brief background on the researchers, and anything else deemed important to the study. However, the Belmont Report also allows for incomplete disclosure under the following justifications: “In all cases of research involving incomplete disclosure, such research is justified only if it is clear that (1) incomplete disclosure is truly necessary to accomplish the goals of the research, (2) there are no undisclosed risks to subjects that are more than minimal, and (3) there is an adequate plan for debriefing subjects, when appropriate, and for dissemination of research results to them.” Nonetheless, these statements are followed by another, which specifically declares that risks should never be withheld for the purpose of eliciting subjects, and fully honest answers should always be given to questions asked of the researchers by the subjects.
2 Comprehension refers to the requirement of adaptable manner and context in which information is presented to the subject based on their ability to understand, which may be variable, considering level of intelligence, rationality, maturity, and language. The Belmont Report requires that it is the investigators’ responsibility and obligation to determine that the subject fully understands the information given to him/her and that special provision be given when comprehension may be limited.
3 Finally, voluntariness refers to the agreement of the subject to participate in the research with the requirement that such consent is valid only if voluntarily given, free of coercion, undue influence, and after the first two elements of the first principle Respect for Persons are met.
The second principle of beneficence is an assessment of the risks and benefits of the clinical research. This includes an examination of the experimental design and whether the risks to the subjects participating in the research are justified, taking into account several considerations listed in the report. The first two of these considerations are that “brutal or inhumane treatment of human subjects is never morally justified; and that risks should be reduced to those necessary to achieve the research objective. It should be determined whether it is in fact necessary to use human subjects at all.” Beneficence is also an obligation of the subjects themselves to determine. They must assess for themselves whether the research is of sufficient benefit to them or the community and, thus, whether they should participate.
The final principle required in the Belmont Report is that of justice, which refers to the specific selection of subjects to participate in the clinical research. Two levels are required to be considered in the selection of subjects: the social level and the individual level. Researchers must be fair in that they should not choose patients who are “in their favor” for beneficial research, or “undesirable” patients to take part in research that may carry a higher risk. On the social level, justice requires distinction between classes of subjects in order to not place a further burden on already burdened classes of subjects. This requires, for example, that the class of “adults” should be chosen for participation in a study before “children.”
Today, the Belmont Report serves as the main reference for U.S. institutional review boards, which were established in compliance with the Declaration of Helsinki.
Conclusion
