THE WORLD MEDICAL ASSOCIATION, INC.
TITLE: PROPOSED REVISION OF THE WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI
Action(s) required: Please review this document and submit comments and/or proposed amendments
Deadline: March 29, 1999
Destination: Medical Ethics Committee
153rd Council Session
15 April 1999
Initiated: March 1999 17.C/Rev1/99
THE WORLD MEDICAL ASSOCIATION, INC.
WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI (Doc. 17.C)
§1 It is the mission of the physician to promote and safeguard the health of the people. His or her knowledge and conscience are dedicated to the fulfillment of this mission.
§2 The Declaration of Geneva of the World Medical Association binds the physician with the words, "The health of my patient will be my first consideration," and the International Code of Medical Ethics declares that, "A physician shall act only in the patient's interest when providing medical care which might have the effect of weakening the physical and mental condition of the patient."
§3 The purpose of biomedical research involving human subjects is to improve diagnostic, therapeutic and prophylactic procedures and the understanding of the aetiology and pathogenesis of disease.
§4 In current medical practice most diagnostic, therapeutic or prophylactic procedures involve hazards. This fact provides both a stimulus for trying to improve these procedures and a reason for asking patients and other persons to accept the risks involved in research when they are proportionately balanced with potential benefits.
§5 The term 'research' refers to a class of activities designed to develop or contribute to the development of generalizable new knowledge. Generalizable knowledge consists of theories, principles or relationships (or the accumulation of data on which they may be based) that can be corroborated by accepted methods of scientific observation and inference.
§6 'Biomedical research involving human subjects' refers to activities in which the techniques, procedures and observations designed to contribute to the development of generalizable new knowledge are applied to human persons, to organs, tissues, cells or body fluids derived from human persons, or to records of attributes of individual persons including those prepared for purposes unrelated to research.
§7 In the treatment of a sick person with a progressive, disabling or potentially fatal disease for whom existing therapy is either not effective or not available, the physician should be free to recommend use of a new diagnostic and therapeutic measure, if in his or her judgement it offers hope of saving life, re-establishing health or alleviating suffering. Employment of such interventions, commonly called 'compassionate use' and formerly called 'clinical research,' is not properly regarded as research. However, the interventions should generally be made the objects of research designed to evaluate their safety and efficacy. Plans to employ such therapeutic interventions should be reviewed and approved by the independent research ethics committee (Article 20) unless the urgency of the situation makes it unreasonable to await such committee action.
§8 The concept termed 'clinical research' was introduced in 1953 by the World Medical Association to describe "experiments in new diagnostic and therapeutic methods" and to distinguish them from a category of activities termed 'non-clinical research' defined as "experiments undertaken to serve other purposes than simply to cure an individual." In its time this distinction served a very important purpose. However, in the 1960s, as medical researchers developed an increasing reliance on the use of the randomized clinical trial to establish the safety and efficacy of new therapies, the term, 'clinical research' was extended to attempt to embrace the conduct of randomized clinical trials. This attempt did not succeed, primarily because randomized clinical trials are not properly categorized as experiments undertaken simply to cure an individual. Rather they are complex activities that invariably include both therapeutic and non-therapeutic components. For this reason, the distinction is no longer used in this Declaration.
§9 It is essential that biomedical research involving human beings be carried out to further scientific knowledge and to alleviate human suffering. To provide guidance for all physicians participating in biomedical research involving human subjects, the World Medical Association has prepared the following recommendations. Non-physician investigators are also important in biomedical research, and the principles in this Declaration apply equally to all non-physician investigators conducting or collaborating on biomedical research involving human subjects. It must be stressed that the principles in this Declaration provide only general guidance to physicians and other investigators in all countries around the world. Physicians and other investigators are not relieved from criminal, civic and ethical responsibilities under the laws of their own countries.
§10 The World Medical Association recognizes that its authority to provide guidance is limited to the medical profession. Application of these principles to non-physician investigators depends on their ratification by the relevant organizations of professionals, their incorporation in national legislation, or both. Until such ratification or legislation occurs, physicians should refrain from collaboration in research activities that are not conducted in accordance with the principles laid down in this Declaration.
§11 Special caution must be exercised in the conduct of research which may affect the environment, and the welfare of animals used for research must be respected.
§12 Because of the changing circumstances and nature of the conduct of biomedical research over time, the principles in this Declaration should be kept under review and modified as appropriate to keep them current.
Fundamental Requirements for Conduct of Biomedical Research Involving Human Subjects
§13 Scientific basis for research
Biomedical research involving human subjects must conform to generally accepted scientific principles and should be based on adequately performed laboratory and animal research and on a thorough knowledge of the scientific literature.
§14 Qualifications of investigators
Biomedical research involving human subjects should be conducted only by persons having the requisite scientific competence. If there is risk of physical or psychological injury to the subjects, or if they are patients who require continuing clinical care, responsibility for their well-being should rest with a professional having the appropriate medical or other clinical qualifications.
§15 Balance of risks and benefits
Biomedical research involving human subjects cannot legitimately be carried out unless the importance of the objective is in proportion to the inherent risk to the subject. The risks of procedures or interventions that are performed with the intent and reasonable probability of providing direct health-related benefit to patient-subjects may be justified in part by the anticipated benefit to the patient-subjects. The risks of all other procedures and interventions must be justified exclusively in terms of the anticipated benefit to society.
§16 Altruistic participation in research
Every biomedical research project involving human subjects must be preceded by careful assessment of the risks to the subjects and anticipated benefits to the subjects or to others. Concern for the interests of the subject must always prevail over the interests of science and society. Persons may, however, elect to participate as subjects in research protocols in which there is no prospect of direct health-related benefit to themselves. In such cases, their motivation may be primarily or exclusively an altruistic wish to advance the interests of science and society.
§17 The rights of research subjects
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 any negative impact of the study on the subject's physical or mental health.
§18 Access to health care
In any biomedical research protocol every patient-subject, including those of a control group, if any, should be assured that he or she will not be denied access to the best proven diagnostic, prophylactic or therapeutic method that would otherwise be available to him or her. This principle does not exclude the use of placebo or no-treatment control groups if such are justified by a scientifically and ethically sound research protocol.
§19 Controlled clinical trials
The central ethical and scientific justification for conducting a controlled clinical trial in which the outcome measures are either death or disability is that there is within the expert clinical community genuine uncertainty or otherwise irreconcilable controversy as to which of the two or more interventions or procedures to be compared is superior. This justification criterion applies equally to clinical trials in which the control group will receive placebo or no active treatment. When the outcome measures are neither death nor disability, placebo or other no-treatment controls may be justified on the basis of their efficiency.
Scientific and Ethical Review of Research Protocols.
§20 Independent research ethics committees
The design and performance of each proposal to conduct research involving human subjects should be clearly formulated in a protocol that should be transmitted to a specially appointed committee independent of the investigator and the sponsor for its consideration, guidance and approval. This research ethics committee, which should operate in conformity with the laws and regulations of the country in which the research is to be carried out, is charged to determine that plans to conduct research are in accordance with the standards set forth in this Declaration. The committee should have the authority to monitor the conduct of research, when appropriate, to assure continuing compliance with these standards.
§21 Ethical considerations and conflicts of interest
Each research protocol should contain a statement of the ethical considerations involved and an assurance of the investigators' plans to comply with the principles set forth in this Declaration. Each investigator should disclose to the research ethics committee any and all of his or her actual or potential financial or other pertinent conflicts of interest.
Informed Consent and Selection of Research Subjects
§22 Informed consent
Unless otherwise specified in this Declaration, each potential subject must be adequately and objectively informed about the aims, methods, anticipated benefits and potential hazards of the study and the discomfort it may entail. Potential subjects must be made aware of all reasonable alternatives to those procedures or interventions that are performed with the intent and reasonable probability of providing direct health-related benefit to the subjects. There must be no coercion, constraint, duress, unjustified deception or undue influence. Material inducements should be limited to reimbursement for out-of-pocket expenses and normal levels of compensation for time, inconvenience or discomfort. The subject should be informed that he or she is at liberty to abstain from participation in the study and that he or she is free to withdraw his or her consent to participate at any time without jeopardizing his or her medical care and without loss of any other benefits to which he or she is entitled.
§23 The investigator's responsibilities
The investigator is responsible for assuring the adequacy of informed consent from or on behalf of each subject. Although the investigator may delegate another appropriately qualified person to obtain consent from prospective subjects, the responsibility for assuring that adequate consent has been accomplished remains with the investigator. When obtaining informed consent, the investigator should be particularly cautious if the subject is in a dependent relationship to him or her or may consent under duress. In some cases of this type, it may be preferable if the informed consent were to be obtained by a qualified person who is either not engaged in the investigation, independent of the dependent relationship, or both.
§24 Documentation of informed consent
In most research the subject's informed consent should be documented in writing. The requirement for written documentation may be waived by the research ethics committee in certain circumstances such as when the research involves only slight risk, when the procedures to be used are customarily used in the practice of medicine without documentation of consent, or when a signed consent document would create an unwarranted risk of a breach of the subject's confidentiality.
§25 Waiver of consent
When permitted by applicable law, the requirement for informed consent may be waived by the independent research ethics committee. Such waiver may be appropriate in research that presents little or no threat to the rights and welfare of research subjects as exemplified by use of anonymous tissue samples for research purposes and in certain other types of research in such fields as epidemiology and policy evaluation. It may also be justified in research in emergency situations in which patient-subjects have temporary or enduring loss of decisional capacity and interventions or procedures must be initiated before informed consent can be obtained from patient-subjects or their legally authorized representatives. In the latter case the research ethics committee may require special procedures to protect the rights and welfare of the research subjects.
§26 Research involving women
Women who are biologically capable of becoming pregnant should not be excluded from research for which they are otherwise eligible unless participation entails exposure to substances likely to be dangerous to a fetus (e.g., known or suspected mutagens or teratogens). Involvement of pregnant or breastfeeding women should generally be postponed until suitable pre-clinical and preliminary clinical studies have provided a basis for advising such women of the nature, probability and magnitude of anticipated effects on them, the fetus and the nursling. When appropriate, prospective subjects should be advised of risks to the fetus or nursling and on what they can do to minimize such risks.
§27 Research involving vulnerable subjects
Vulnerable subjects need special protection of their rights and welfare to ensure that they do not bear more than their fair share of the burdens of participation in research. Involvement of vulnerable persons rather than competent consenting adults as research subjects requires special ethical justification. Groups of vulnerable persons include but are not limited to those who are legally incompetent by virtue of their status (e.g., children) or individual condition (e.g., cognitive impairment by mental disease); those who lack the capacity to comprehend (e.g., persons for whom Western concepts of disease causation are unknown); and those with limited freedom to exercise free power of choice (e.g., institutionalized or incarcerated persons and junior or subordinate members of hierarchical groups). The inclusion of vulnerable subjects in biomedical research is most readily justified in the context of research designed to develop new diagnostic, prophylactic or therapeutic modalities for classes of vulnerable subjects (e.g., children or persons with mental diseases) or the basic knowledge upon which such developments can be based; such research must necessarily involve members of the relevant vulnerable groups as subjects.
§28 Subjects who are incapable of valid consent
For a prospective research subject who is legally incompetent, the investigator must obtain informed consent from the legally authorized representative in accordance with applicable law. For prospective subjects who are incapable of valid consent but not adjudicated incompetent, investigators may rely on the permission of a responsible relative or other appropriate person to the extent allowed by applicable law and approved by the research ethics committee. Persons who are partially capable of valid consent should generally be invited to assent to the extent of their capability; such assent should generally be supplemented with the permission of the responsible relative or other appropriate person.
Responsibilities of Physicians and Other Investigators
§29 Protecting research subjects
It is the duty of physicians and other investigators to remain the protectors of the life and health of those persons on whom biomedical research is being carried out. The responsibility for the health of the human subject must never rest solely on the subject of the research, even though the subject has given consent to participate in the study.
§30 Oversight of research
Physicians and other investigators conducting research involving human subjects should cease any study in which the hazards are found to be disproportionate to the benefits, and they should terminate the involvement of any individual subject if, in their judgment, continued participation in the research may be harmful to that individual. Fulfilling these responsibilities in some studies (e.g., double-blind, controlled clinical trials) may require the establishment of an independent data and safety monitoring committee.
§31 Responsibility for medical services
Investigators should inform prospective patient-subjects about the extent of the investigators' responsibility to provide medical services during the course of the research. Health care professionals who are also investigators should specify whether they are serving only as investigators or as both treating professionals and investigators. Those who serve in the combined roles of investigator and treating professional have a special obligation to protect the rights and welfare of the patient-subjects.
Data Management and Publication of Results
§32 Recording and preserving research results
Investigators who conduct biomedical research should record their findings and observations fully and accurately and preserve them for subsequent examination or future use as necessary and appropriate, while safeguarding the privacy of information about the subjects. Investigators should not misinform anyone about any aspect of the research.
§33 Validity of research reports and conflicts of interest
In publishing the results of their research, investigators are obliged to report the methods, results, conclusions, and interpretation of their research fully and accurately, to remain accountable for future inquiry into their work, and to disclose to others any actual or potential financial or other pertinent conflicts of interest they may have had.
§34 Adherence to this Declaration
Any published reports of research involving human subjects should include a statement from the investigators that the research was conducted in accordance with the principles laid down in this Declaration. Variances from these principles should be explained and justified in the report. Editors are obligated to consider carefully the justification for any variances from these principles in deciding whether to accept or reject the report for publication.