and respecting patient subjects and volunteers, with scientific innovation and medical progress through research, is brought up again.
Paragraph 9 has not raised a great deal of debate, but it is important in that it sets up a minimal standard that all physicians worldwide should follow, specifically, distinguishing that “No national ethical, legal or regulatory requirement should be allowed to reduce or eliminate any of the protections for human subjects set forth in this Declaration.” This is emphasized in the WMA 2003 statement, which included that “In some cases the law mandates unethical conduct. The fact that a physician has complied with the law does not necessarily mean that the physician has acted ethically. When the law is in conflict with medical ethics, physicians should work to change the law. In circumstances of such conflict, ethical responsibilities supersede legal obligations.”
Controversies of Paragraphs 29 of the Edinburg (2000) revision: Are patient subjects worse off in the clinical trial than they were before? The Somerset West, South Africa (1996), revision was the first in which the use of placebo in clinical trials was described. The wording of this 1996 version—“The potential benefits, hazards and discomfort of a new method should be weighed against the best current diagnostic and therapeutic methods”—was changed in the 2000 version to state that “The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists.” The 2000 version completely removed the 1996 statement that “In any medical study, every patient—including those of a control group, if any—must be assured of the best proven diagnostic and therapeutic method.”
The first controversy brings into question the definition of the “best current” therapeutic methods. Indeed, “best current” could mean either in existence globally, best used in practice globally, or best available within the local community. Then there is the question of even the word “best”—does this refer to the most effective, the least toxic, a weighing of the two, or simply the most widely used and therefore best studied and understood? With personalized medicine on the horizon, arguments today may additionally question, “best” for whom—the general population of patients with the condition under study, or for the individual patient?
Additionally, an ensuing outcry of protest following the release of the Edinburgh (2000) version was that this paragraph appears to disallow the use of placebo as a control where there is a proven treatment, which led to the WMA issuing a clarification on paragraph 29. The clarification described the use of a placebo as acceptable where there is a scientifically compelling reason, or where the subject is at no increased risk of serious or irreversible harm, for example, when the condition under study is a minor one. However, the clarification itself continues to fall under question, for example, in the use of the connector “or.” It is argued, for example, by R. Macklin in her 2003 paper “Future Challenges for the Declaration of Helsinki” that the connector used should be “and” since the statement, as it is written, suggests that a scientifically compelling reason may supersede or justify an increased risk of serious or irreversible harm to the subject.
Nonetheless, counterarguments exist, for example, that paragraph 5 covers the issue stating that “considerations related to 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.