Ethical principles of research with human subjects
Department of health & human ance & er irbs & obtain home > ohrp > regulations & policy > the belmont tionshas sub items, regulations45 cfr cehas sub items, guidancefrequently asked questions45 cfr 46 nce process en: research with children research determination ed consent igator responsibilities registration process er research y improvement activities able ical materials & ts for tions & policy archived belmont reportoffice of the l principles and guidelines for the protection of human subjects of national commission for the protection of human subjects of biomedical and behavioral : department of health, education, and : notice of report for public y: on july 12, 1974, the national research act (pub. 93-348) was signed into law, there-by creating the national commission for the protection of human subjects of biomedical and behavioral research. One of the charges to the commission was to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines which should be followed to assure that such research is conducted in accordance with those principles. In carrying out the above, the commission was directed to consider: (i) the boundaries between biomedical and behavioral research and the accepted and routine practice of medicine, (ii) the role of assessment of risk-benefit criteria in the determination of the appropriateness of research involving human subjects, (iii) appropriate guidelines for the selection of human subjects for participation in such research and (iv) the nature and definition of informed consent in various research belmont report attempts to summarize the basic ethical principles identified by the commission in the course of its deliberations. It is a statement of basic ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of research with human subjects. The department requests public comment on this al commission for the protection of human subjects of biomedical and behavioral s of the h john ryan, m. Attorney, vombaur, coburn, simmons & turtle, washington, l principles and guidelines for research involving human subjects. Basic ethical ment of risk and ion of l principles & guidelines for research involving human ific research has produced substantial social benefits. Public attention was drawn to these questions by reported abuses of human subjects in biomedical experiments, especially during the second world war. This code became the prototype of many later codes[1] intended to assure that research involving human subjects would be carried out in an ethical codes consist of rules, some general, others specific, that guide the investigators or the reviewers of research in their work. Broader ethical principles will provide a basis on which specific rules may be formulated, criticized and principles, or general prescriptive judgments, that are relevant to research involving human subjects are identified in this statement. These three are comprehensive, however, and are stated at a level of generalization that should assist scientists, subjects, reviewers and interested citizens to understand the ethical issues inherent in research involving human subjects. These principles cannot always be applied so as to resolve beyond dispute particular ethical problems. The objective is to provide an analytical framework that will guide the resolution of ethical problems arising from research involving human statement consists of a distinction between research and practice, a discussion of the three basic ethical principles, and remarks about the application of these principles. Boundaries between practice and is important to distinguish between biomedical and behavioral research, on the one hand, and the practice of accepted therapy on the other, in order to know what activities ought to undergo review for the protection of human subjects of research. The distinction between research and practice is blurred partly because both often occur together (as in research designed to evaluate a therapy) and partly because notable departures from standard practice are often called "experimental" when the terms "experimental" and "research" are not carefully the most part, the term "practice" refers to interventions that are designed solely to enhance the well-being of an individual patient or client and that have a reasonable expectation of success. By contrast, the term "research' designates an activity designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge (expressed, for example, in theories, principles, and statements of relationships). Research is usually described in a formal protocol that sets forth an objective and a set of procedures designed to reach that a clinician departs in a significant way from standard or accepted practice, the innovation does not, in and of itself, constitute research. The fact that a procedure is "experimental," in the sense of new, untested or different, does not automatically place it in the category of research. Radically new procedures of this description should, however, be made the object of formal research at an early stage in order to determine whether they are safe and effective. Thus, it is the responsibility of medical practice committees, for example, to insist that a major innovation be incorporated into a formal research project [3]. And practice may be carried on together when research is designed to evaluate the safety and efficacy of a therapy. This need not cause any confusion regarding whether or not the activity requires review; the general rule is that if there is any element of research in an activity, that activity should undergo review for the protection of human b: basic ethical principles.
Ethical issues in research with human subjects
Basic ethical expression "basic ethical principles" refers to those general judgments that serve as a basic justification for the many particular ethical prescriptions and evaluations of human actions. Three basic principles, among those generally accepted in our cultural tradition, are particularly relevant to the ethics of research involving human subjects: the principles of respect of persons, beneficence and justice. Respect for persons incorporates at least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection. To show lack of respect for an autonomous agent is to repudiate that person's considered judgments, to deny an individual the freedom to act on those considered judgments, or to withhold information necessary to make a considered judgment, when there are no compelling reasons to do r, not every human being is capable of self-determination. The judgment that any individual lacks autonomy should be periodically reevaluated and will vary in different most cases of research involving human subjects, respect for persons demands that subjects enter into the research voluntarily and with adequate information. On the one hand, it would seem that the principle of respect for persons requires that prisoners not be deprived of the opportunity to volunteer for research. On the other hand, under prison conditions they may be subtly coerced or unduly influenced to engage in research activities for which they would not otherwise volunteer. Persons are treated in an ethical manner not only by respecting their decisions and protecting them from harm, but also by making efforts to secure their well-being. Claude bernard extended it to the realm of research, saying that one should not injure one person regardless of the benefits that might come to others. The problem posed by these imperatives is to decide when it is justifiable to seek certain benefits despite the risks involved, and when the benefits should be foregone because of the obligations of beneficence affect both individual investigators and society at large, because they extend both to particular research projects and to the entire enterprise of research. In the case of particular projects, investigators and members of their institutions are obliged to give forethought to the maximization of benefits and the reduction of risk that might occur from the research investigation. In the case of scientific research in general, members of the larger society are obliged to recognize the longer term benefits and risks that may result from the improvement of knowledge and from the development of novel medical, psychotherapeutic, and social principle of beneficence often occupies a well-defined justifying role in many areas of research involving human subjects. Effective ways of treating childhood diseases and fostering healthy development are benefits that serve to justify research involving children -- even when individual research subjects are not direct beneficiaries. Research also makes it possible to avoid the harm that may result from the application of previously accepted routine practices that on closer investigation turn out to be dangerous. A difficult ethical problem remains, for example, about research that presents more than minimal risk without immediate prospect of direct benefit to the children involved. Some have argued that such research is inadmissible, while others have pointed out that this limit would rule out much research promising great benefit to children in the future. However, they are foreshadowed even in the earliest reflections on the ethics of research involving human subjects. For example, during the 19th and early 20th centuries the burdens of serving as research subjects fell largely upon poor ward patients, while the benefits of improved medical care flowed primarily to private patients. Subsequently, the exploitation of unwilling prisoners as research subjects in nazi concentration camps was condemned as a particularly flagrant injustice. These subjects were deprived of demonstrably effective treatment in order not to interrupt the project, long after such treatment became generally t this historical background, it can be seen how conceptions of justice are relevant to research involving human subjects. For example, the selection of research subjects needs to be scrutinized in order to determine whether some classes (e. Finally, whenever research supported by public funds leads to the development of therapeutic devices and procedures, justice demands both that these not provide advantages only to those who can afford them and that such research should not unduly involve persons from groups unlikely to be among the beneficiaries of subsequent applications of the ations of the general principles to the conduct of research leads to consideration of the following requirements: informed consent, risk/benefit assessment, and the selection of subjects of research. Respect for persons requires that subjects, to the degree that they are capable, be given the opportunity to choose what shall or shall not happen to them.
Ethical issues in human research
Most codes of research establish specific items for disclosure intended to assure that subjects are given sufficient information. These items generally include: the research procedure, their purposes, risks and anticipated benefits, alternative procedures (where therapy is involved), and a statement offering the subject the opportunity to ask questions and to withdraw at any time from the research. Additional items have been proposed, including how subjects are selected, the person responsible for the research, r, a simple listing of items does not answer the question of what the standard should be for judging how much and what sort of information should be provided. One standard frequently invoked in medical practice, namely the information commonly provided by practitioners in the field or in the locale, is inadequate since research takes place precisely when a common understanding does not exist. This, too, seems insufficient since the research subject, being in essence a volunteer, may wish to know considerably more about risks gratuitously undertaken than do patients who deliver themselves into the hand of a clinician for needed care. Even when some direct benefit to them is anticipated, the subjects should understand clearly the range of risk and the voluntary nature of participation. Special problem of consent arises where informing subjects of some pertinent aspect of the research is likely to impair the validity of the research. In many cases, it is sufficient to indicate to subjects that they are being invited to participate in research of which some features will not be revealed until the research is concluded. 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. Information about risks should never be withheld for the purpose of eliciting the cooperation of subjects, and truthful answers should always be given to direct questions about the research. Care should be taken to distinguish cases in which disclosure would destroy or invalidate the research from cases in which disclosure would simply inconvenience the hension. While there is always an obligation to ascertain that the information about risk to subjects is complete and adequately comprehended, when the risks are more serious, that obligation increases. Even for these persons, however, respect requires giving them the opportunity to choose to the extent they are able, whether or not to participate in research. The objections of these subjects to involvement should be honored, unless the research entails providing them a therapy unavailable elsewhere. Respect for persons also requires seeking the permission of other parties in order to protect the subjects from harm. The person authorized to act on behalf of the subject should be given an opportunity to observe the research as it proceeds in order to be able to withdraw the subject from the research, if such action appears in the subject's best ariness. The assessment of risks and benefits requires a careful arrayal of relevant data, including, in some cases, alternative ways of obtaining the benefits sought in the research. Thus, the assessment presents both an opportunity and a responsibility to gather systematic and comprehensive information about proposed research. For the investigator, it is a means to examine whether the proposed research is properly designed. For a review committee, it is a method for determining whether the risks that will be presented to subjects are justified. For prospective subjects, the assessment will assist the determination whether or not to nature and scope of risks and benefits. The requirement that research be justified on the basis of a favorable risk/benefit assessment bears a close relation to the principle of beneficence, just as the moral requirement that informed consent be obtained is derived primarily from the principle of respect for persons. However, when expressions such as "small risk" or "high risk" are used, they usually refer (often ambiguously) both to the chance (probability) of experiencing a harm and the severity (magnitude) of the envisioned term "benefit" is used in the research context to refer to something of positive value related to health or welfare.
While the most likely types of harms to research subjects are those of psychological or physical pain or injury, other possible kinds should not be and benefits of research may affect the individual subjects, the families of the individual subjects, and society at large (or special groups of subjects in society). Previous codes and federal regulations have required that risks to subjects be outweighed by the sum of both the anticipated benefit to the subject, if any, and the anticipated benefit to society in the form of knowledge to be gained from the research. In balancing these different elements, the risks and benefits affecting the immediate research subject will normally carry special weight. On the other hand, interests other than those of the subject may on some occasions be sufficient by themselves to justify the risks involved in the research, so long as the subjects' rights have been protected. Beneficence thus requires that we protect against risk of harm to subjects and also that we be concerned about the loss of the substantial benefits that might be gained from systematic assessment of risks and benefits. Only on rare occasions will quantitative techniques be available for the scrutiny of research protocols. This ideal requires those making decisions about the justifiability of research to be thorough in the accumulation and assessment of information about all aspects of the research, and to consider alternatives systematically. This procedure renders the assessment of research more rigorous and precise, while making communication between review board members and investigators less subject to misinterpretation, misinformation and conflicting judgments. Thus, there should first be a determination of the validity of the presuppositions of the research; then the nature, probability and magnitude of risk should be distinguished with as much clarity as possible. It should also be determined whether an investigator's estimates of the probability of harm or benefits are reasonable, as judged by known facts or other available y, assessment of the justifiability of research should reflect at least the following considerations: (i) brutal or inhumane treatment of human subjects is never morally justified. It should be determined whether it is in fact necessary to use human subjects at all. Iii) when research involves significant risk of serious impairment, review committees should be extraordinarily insistent on the justification of the risk (looking usually to the likelihood of benefit to the subject -- or, in some rare cases, to the manifest voluntariness of the participation). Iv) when vulnerable populations are involved in research, the appropriateness of involving them should itself be demonstrated. Just as the principle of respect for persons finds expression in the requirements for consent, and the principle of beneficence in risk/benefit assessment, the principle of justice gives rise to moral requirements that there be fair procedures and outcomes in the selection of research e is relevant to the selection of subjects of research at two levels: the social and the individual. Individual justice in the selection of subjects would require that researchers exhibit fairness: thus, they should not offer potentially beneficial research only to some patients who are in their favor or select only "undesirable" persons for risky research. Social justice requires that distinction be drawn between classes of subjects that ought, and ought not, to participate in any particular kind of research, based on the ability of members of that class to bear burdens and on the appropriateness of placing further burdens on already burdened persons. Thus, it can be considered a matter of social justice that there is an order of preference in the selection of classes of subjects (e. The institutionalized mentally infirm or prisoners) may be involved as research subjects, if at all, only on certain ice may appear in the selection of subjects, even if individual subjects are selected fairly by investigators and treated fairly in the course of research. Thus, even if individual researchers are treating their research subjects fairly, and even if irbs are taking care to assure that subjects are selected fairly within a particular institution, unjust social patterns may nevertheless appear in the overall distribution of the burdens and benefits of research. Although individual institutions or investigators may not be able to resolve a problem that is pervasive in their social setting, they can consider distributive justice in selecting research populations, especially institutionalized ones, are already burdened in many ways by their infirmities and environments. When research is proposed that involves risks and does not include a therapeutic component, other less burdened classes of persons should be called upon first to accept these risks of research, except where the research is directly related to the specific conditions of the class involved. Also, even though public funds for research may often flow in the same directions as public funds for health care, it seems unfair that populations dependent on public health care constitute a pool of preferred research subjects if more advantaged populations are likely to be the recipients of the special instance of injustice results from the involvement of vulnerable subjects. Certain groups, such as racial minorities, the economically disadvantaged, the very sick, and the institutionalized may continually be sought as research subjects, owing to their ready availability in settings where research is conducted.
Given their dependent status and their frequently compromised capacity for free consent, they should be protected against the danger of being involved in research solely for administrative convenience, or because they are easy to manipulate as a result of their illness or socioeconomic condition. 1] since 1945, various codes for the proper and responsible conduct of human experimentation in medical research have been adopted by different organizations. Department of health, education, and welfare codes for the conduct of social and behavioral research have also been adopted, the best known being that of the american psychological association, published in 1973. The fact that some forms of practice have elements other than immediate benefit to the individual receiving an intervention, however, should not confuse the general distinction between research and practice. Even when a procedure applied in practice may benefit some other person, it remains an intervention designed to enhance the well-being of a particular individual or groups of individuals; thus, it is practice and need not be reviewed as research. 3] because the problems related to social experimentation may differ substantially from those of biomedical and behavioral research, the commission specifically declines to make any policy determination regarding such research at this time. Rather, the commission believes that the problem ought to be addressed by one of its successor t created by office for human research protectionscontent last reviewed on march 15, up for ohrp sign up for updates, please click the sign up button for human research protections. Wootton parkway, suite crimination ch ethics review orating l standards and procedures for research with human ch ethics govern the standards of conduct for scientific researchers. It is important to adhere to ethical principles in order to protect the dignity, rights and welfare of research such, all research involving human beings should be reviewed by an ethics committee to ensure that the appropriate ethical standards are being upheld. Discussion of the ethical principles of beneficence, justice and autonomy are central to ethical who manual (section xv. Defines research with human subjects as 'any social science, biomedical, behavioural, or epidemiological activity that entails systematic collection or analysis of data with the intent to generate new knowledge, in which human beings:Are exposed to manipulation, intervention, observation, or other interaction with investigators either directly or through alteration of their environment; individually identifiable through investigator's collection, preparation, or use of biological material or medical or other rds and operational guidance for ethics review of health-related research with human participants pdf, ational ethical guidelines for biomedical research involving human subjectscouncil for international organizations of medical sciences. Pdf, medical association: declaration of an group on ive 2001/20/ec of the european parliament and of the council pdf, l of europe (oviedo convention - protocol on biomedical research). Council: the ethics of research related to healthcare in developing research ethics review committee (erc). The erc reviews all research projects, involving human participants supported either financially or technically by a proposal to the research ethics review committee (erc). The erc reviews all research projects, involving human participants supported either financially or technically by a proposal to the health ethics ment of information, evidence and health l standards and procedures for research with human mmes and region of the south-east asia eastern mediterranean western pacific up for who ch ethics review orating l standards and procedures for research with human ch ethics govern the standards of conduct for scientific researchers. The erc reviews all research projects, involving human participants supported either financially or technically by a proposal to the health ethics ment of information, evidence and health l standards and procedures for research with human mmes and region of the south-east asia eastern mediterranean western pacific up for who in medicine university of washington school of h a. Atrocities committed by nazi physicians on jewish prisoners during world war ii prompted an international tribunal, convened in the city of nuremberg, germany between 1945-1946, to elaborate 10 principles, called the nuremberg code, by which research involving human subjects should be governed. Publication of the nuremburg code in 1947 ushered in the modern era of research ethics, which mandated balancing the advancement of science with the rights and welfare of humans who serve as research nuremburg, a multitude of regulations and policy statements have been developed by domestic and international bodies. These regulatory guidance documents, including the world medical association declaration of helskinki (world medical association); the belmont report and the federal regulations at 45 cfr 46 and 21 cfr 50 share a common purpose: to protect the autonomy, safety, privacy, and welfare of human research subjects. Within institutions where clinical research is conducted, responsibility for the interpretation and application of these ethical principles and regulations rests with committees comprised of scientist and non-scientists, called institutional review boards for the protection of human subjects (irbs). Ethical principles applied to research with human belmont report, which provides the ethical foundation for research regulations and guides irb deliberations, was generated by a federally commissioned group of scientists, physicians, ethicists, and philosophers and published in 1979. The three primary ethical principles cited in belmont are: autonomy, beneficence, and my refers to the right of an individual to determine what activities they will or will not participate in. The cornerstone of protecting autonomy is the informed consent process, whereby an investigator provides a potential research participant with full disclosure about the nature of the study, the risks, benefits and alternatives, and an extended opportunity to ask questions before deciding whether or not to participate.
Populations presumed to have diminished autonomy, by virtue of impaired cognition (for example, children, cognitively-impaired elderly, or mentally ill subjects) or of circumstance (for example prisoners or seriously ill people) are considered to be vulnerable populations. Maximizing potential benefits is predicated on sound experimental design, thus research proposals must undergo rigorous scientific review before proceeding to the irb for ethical review. The principle of justice requires that those who undertake the burdens of research must be likely to benefit from the research, and is a principle often violated by the export of clinical trials to underdeveloped ing ethical research primary concern of the investigator should be the safety of the research participant. Protecting subject safety requires the investigator to use all available information to identify potential risks to the subject, to establish means of minimizing those risks, and to continually monitor the ongoing research for adverse events experienced by subjects. The investigator must be prepared to stop the study if serious unanticipated risks are scientific investigator must obtain informed consent from each research participant. There are regulations and guidance documents that govern exceptions to the requirement to obtain informed consent, for example in cases of emergency or if the subject is unconscious and thereby unable to give investigator must protect the subjects’ privacy and confidentiality. Researchers must have mechanisms in place to prevent the disclosure of, or unauthorized access to, data that can be linked to a subject’s individual investigator must consider how adverse events will be handled. A true null hypothesis should exist at the onset regarding the outcome of the trial, that is, if a new intervention is being tested against the currently accepted treatment, the investigator should be genuinely uncertain which approach is ents of ethically valid informed consent for the appreciation that informed consent is at the crux of human subjects protection, it is not surprising that the regulations reflect extensively upon the necessary elements of the consent document itself as well as on the informed consent process. For an informed consent to be ethically valid, the following components must be present:Disclosure: the informed consent document must make clear that the study is a research study, and not clinical therapy. The potential participant must be informed as fully as possible of the nature and purpose of the research, the procedures to be used, the expected benefits to the participant and/or society, the potential of reasonably foreseeable risks, stresses, and discomforts, and alternatives to participating in the research. The informed consent document must also disclose what compensation and medical treatment are available in the case of a research-related injury. The document should make it clear whom to contact with questions about the research study, research subjects' rights, and in case of tanding: the participant must understand what has been explained and must be given the opportunity to ask questions and have them answered by someone fully conversant in the study particulars. Consent forms for multinational research must be translated into the respective language for each participating country and back-translated to verify ariness: the participant's consent to participate in the research must be voluntary, free of any coercion or inflated promise of benefits from participation. In the event that there is a question about competence, mental status exams may be t: the potential human subject must authorize his/her participation in the research study, preferably in writing. No investigator may involve a human being as a subject in research covered by this policy unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. Review of research: full-board, expedited, and exempt board: clinical trials that expose subjects to more than minimal risk must be reviewed by the irb at a convened meeting of the full board. Studies that qualify for expedited review are those that present no more than minimal risk to subjects, and involve only procedures commonly done in clinical settings, such as taking hair, saliva, excreta or small amounts of blood. A study that qualifies for expedited review is held to the same ethical standards of autonomy, beneficence and justice that are used in full board review, but the approval process may take less : some research with humans can be designated as exempt from irb review. Research that is part of a routine educational experience, or in which participants will be anonymous or effectively de-identified falls into this category and may be granted a certificate of exemption. The proposal must still be reviewed by a member of the irb to assign exempt status, but the application process may be considerably t the university irb if you have questions about the category under which your study deception of subjects allowed when doing research? Using deception jeopardizes the integrity of the informed consent process and could harm participants, as well as eroding trust between the public and researchers. In some instances deception is necessary to conduct the research: for example, a study of how the decision-making practices of physicians affect their practice of medicine might be presented as a study of "communication behaviors. They will require an in-depth justification of why deception is necessary for the study and the steps that will be taken to safeguard participants, including a plan to debrief subjects at the end of the research.
Form of deception of subjects can occur if the terms of the informed consent are violated by the investigator or other scientists. For example, if a subject consents to have their blood sample evaluated for markers of diabetes and the investigator or other scientists use the blood sample for purposes unrelated to diabetes research, the subject has effectively been deceived about the nature of their research participation and they have been denied autonomous agency over their own actions. The havasupai tribe illustrates the ethical pitfalls and legal consequences of biological sample sharing without explicit prior consent (drabiak-syed, 2010).