Need to know: Nuremberg Code, Declaration of Helsinki, Belmont Report, OHRP
The abuse of human subjects in research is not new. But after the horrific Nazi medical atrocities in World War II were finally exposed and judged at Nuremberg, it would seem that countries and global organizations finally took note and rendered what became classic ethical guidelines for the use of human subjects in research.
Two of those international guidelines (the Nuremberg Code , and the continuously "updated" Declaration of Helsinki ), are copied below, as well as the current U.S. federal regulations for the use of human subjects in research (OHRP - originally the OPRR regulations). The OPRR federal regulations themselves resulted from a U.S. law (the 1974 National Research Act ) that mandated the 1978 Belmont Report ). That Belmont Report is also copied below. Note that the Belmont Report issued in the formal "birth of bioethics" , and was also mandated to be used as the foundation for the revised federal OPRR regulations for the use of human subjects in research (later renamed OHRP).
Given the extensive concerns today about the exponential increase in scientific fraud and misconduct, especially in clinical trials, and the flagrant violations of "informed consent", it would do all citizens well to keep these classic documents on file somewhere, and at least be familiar with them. At least then people will be better prepared and able to identify the ethical and regulatory issues, and thus to recognize similar abuses in current research practices involving human beings. As many veteran observers of these guidelines and abuses have noted, the whole world now has become one huge clinical trial -- with no "informed consent" . You, or your family members, or the public at large could be part of an experiment and not even know it. My guess is that with the onslaught of genetic engineering (including plants, animals, humans, drugs, devices, etc.), including synthetic biology and nanotechnology, the issues surrounding ethically justified and scientifically sound research affecting human subjects will become more pertinent than ever.
Volumes and reams have been written about the following documents. The focus below, however, is on the requirements for the informed consent of the human subjects of research. However, other criteria, such as the requirement that the researcher must have mastery of the science being investigated , and that some "exceptions" to the rules are in fact unethical, etc., are worth the public's attention as well. For an extensive history and documentation of the use (or abuse) of human subjects in research, see the website of Vera Sharav, Alliance for Human Research Protection (AHRP), at: http://www.ahrp.org .
Although available from many sources on the internet (and sometimes worded slightly different from those below), the following documents are taken from the official guidebook for Institutional Review Boards (IRBs), whose appointed members make the decisions about research using human subjects: http://archive.hhs.gov/ohrp/irb/irb_appendices.htm#j6 . The gradual moves away from the details articulated in the Nuremberg Code in subsequent guidelines are stark. Please note the accurate definition of "research" as distinct from "standard medical care". " Research " can be either "experimental" or "therapeutic". These are different from " standard medical care " that has already been through several phases of "clinical research trials". Just because something is termed "therapeutic" does not mean that it is not research. Note too that most of these guidelines apply to physicians (with M.D.'s) only, not to non-physician researchers (with Ph.D.'s). Traditionally, physicians are to protect their patients from harm; researchers are to obtain "data". Note too the formal "birth of bioethics" with the 1978 Belmont Report, and the odd definitions of the three bioethical principles therein. There are no ethical guidelines or even professional Codes of Ethics for Ph.D. researchers, or for ethicists -- or for bioethicists.
U.S. Department of Health and Human Services
Office of Human Research Protection
as of June 27, 2013
[ Note that the Nuremberg Code would not allow the use of incompetent human beings in research, a restriction that was later "modified" by the Declarations of Helsinki" and the U.S. OHRP federal regulations. -- DNI]
* This means that the person involved should have legal capacity to give consent ; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment.
* The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or engages in the experiment . It is a personal duty and responsibility which may not be delegated to another with impunity .
[ Note: This Declaration is currently under review again. -- DNI]
Adopted by the 18th World Medical Assembly
Helsinki, Finland, June 1964
and amended by the
29th World Medical Assembly
Tokyo, Japan, October 1975
35th World Medical Assembly
Venice, Italy, October 1983
41st World Medical Assembly
Hong Kong, September 1989
It is the mission of the physician to safeguard the health of the people . His or her knowledge and conscience are dedicated to the fulfillment of this mission.
The Declaration of Geneva of the World Medical Assembly 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."
The purpose of biomedical research involving human subjects must be to improve diagnostic, therapeutic and prophylactic procedures and the understanding of the aetiology and pathogenesis of disease.
In current medical practice most diagnostic, therapeutic or prophylactic procedures involve hazards. This applies especially to biomedical research.
Medical progress is based on research which ultimately must rest in part on experimentation involving human subjects.
In the field of biomedical research a fundamental distinction must be recognized between medical research in which the aim is essentially diagnostic or therapeutic for a patient, and medical research, the essential object of which is purely scientific and without implying direct diagnostic or therapeutic value to the person subjected to the research.
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.
Because it is essential that the results of laboratory experiments be applied to human beings to further scientific knowledge and to help suffering humanity, the World Medical Association has prepared the following recommendations as a guide to every physician in biomedical research involving human subjects. They should be kept under review in the future. It must be stressed that the standards as drafted are only a guide to physicians all over the world. Physicians are not relieved from criminal, civil and ethical responsibilities under the laws of their own countries.
[ Note: See Irving, "What is 'bioethics'?", at: http://www.lifeissues.net/writers/irv/irv_36whatisbioethics01.html ]. The 1974 National Research Act mandated that the federal government determine the "ethics" to be used in issues concerning the use of human subjects in research. Thus an 11-member National Commission to determine the ethical principles was appointed by then-DHHS Secretary Casper Weinberger. Only one of the members had a formal background in "ethics". Note the odd definitions of each of the bioethics principles. "Respect for persons" was defined in terms of "autonomy" (soon to be defined by bioethicists as the basis of "personhood"), and thus applies only to competent human subjects -- although incompetent subjects are to be "protected". "Beneficence" is defined as "the greatest good for the greatest number in society" -- a very utilitarian kind of "ethics" -- and requires all citizens to volunteer to participate in even risky experimental research "for the greater good". "Society" takes precedence over the individual. "Justice" is defined in terms of John Rawl's "Theory of Justice", i.e., "fairness" -- i.e., fairness in the distribution of the risks and benefits of research. -- DNI]
AGENCY: U.S. Department of Health, Education, and Welfare.
ACTION: Notice of Report for Public Comment.
SUMMARY: On July 12, 1974, the National Research Act (Pub. L. 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 settings.
The Belmont Report attempts to summarize the basic ethical principles identified by the Commission in the course of its deliberations. It is the outgrowth of an intensive four-day period of discussions that were held in February 1976 at the Smithsonian Institution's Belmont Conference Center supplemented by the monthly deliberations of the Commission that were held over a period of nearly four years. 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. By publishing the Report in the Federal Register, and providing reprints upon request, the Secretary intends that it may be made readily available to scientists, members of Institutional Review Boards, and Federal employees. The two-volume Appendix, containing the lengthy reports of experts and specialists who assisted the Commission in fulfilling this part of its charge, is available as DHEW Publication No. (OS) 78-0013 and No. (OS) 78-0014, for sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402.
Unlike most other reports of the Commission, the Belmont Report does not make specific recommendations for administrative action by the Secretary of Health, Education, and Welfare. Rather, the Commission recommended that the Belmont Report be adopted in its entirety, as a statement of the Department's policy. The Department requests public comment on this recommendation.
Ethical Principles and Guidelines for Research Involving Human Subjects
Scientific research has produced substantial social benefits. It has also posed some troubling ethical questions. Public attention was drawn to these questions by reported abuses of human subjects in biomedical experiments, especially during the Second World War. During the Nuremberg War Crime Trials, the Nuremberg code was drafted as a set of standards for judging physicians and scientists who had conducted biomedical experiments on concentration camp prisoners. 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 manner.
The codes consist of rules, some general, others specific, that guide the investigators or the reviewers of research in their work. Such rules often are inadequate to cover complex situations; at times they come into conflict, and they are frequently difficult to interpret or apply. Broader ethical principles will provide a basis on which specific rules may be formulated, criticized and interpreted.
Three principles, or general prescriptive judgments, that are relevant to research involving human subjects are identified in this statement. Other principles may also be relevant. 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 subjects.
This 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.
It 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 defined.
For 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. The purpose of medical or behavioral practice is to provide diagnosis, preventive treatment or therapy to particular individuals.(2) 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 objective.
When 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)
Research 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 subjects .
The 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 .
1. Respect for Persons. -- 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 . The principle of respect for persons thus divides into two separate moral requirements: the requirement to acknowledge autonomy and the requirement to protect those with diminished autonomy .
An autonomous person is an individual capable of deliberation about personal goals and of acting under the direction of such deliberation. To respect autonomy is to give weight to autonomous persons' considered opinions and choices while refraining from obstructing their actions unless they are clearly detrimental to others. 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 so.
However, not every human being is capable of self-determination. The capacity for self-determination matures during an individual's life, and some individuals lose this capacity wholly or in part because of illness, mental disability, or circumstances that severely restrict liberty. Respect for the immature and the incapacitated may require protecting them as they mature or while they are incapacitated.
Some persons are in need of extensive protection , even to the point of excluding them from activities which may harm them; other persons require little protection beyond making sure they undertake activities freely and with awareness of possible adverse consequence. The extent of protection afforded should depend upon the risk of harm and the likelihood of benefit . The judgment that any individual lacks autonomy should be periodically reevaluated and will vary in different situations.
In most cases of research involving human subjects, respect for persons demands that subjects enter into the research voluntarily and with adequate information . In some situations, however, application of the principle is not obvious. The involvement of prisoners as subjects of research provides an instructive example. 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 . Respect for persons would then dictate that prisoners be protected. Whether to allow prisoners to "volunteer" or to "protect" them presents a dilemma . Respecting persons, in most hard cases, is often a matter of balancing competing claims urged by the principle of respect itself.
2. Beneficence. -- 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 . Such treatment falls under the principle of beneficence. The term "beneficence" is often understood to cover acts of kindness or charity that go beyond strict obligation. In this document, beneficence is understood in a stronger sense, as an obligation. Two general rules have been formulated as complementary expressions of beneficent actions in this sense: (1) do not harm and (2) maximize possible benefits and minimize possible harms .
The Hippocratic maxim "do no harm" has long been a fundamental principle of medical ethics. 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. However, even avoiding harm requires learning what is harmful; and, in the process of obtaining this information, persons may be exposed to risk of harm. Further, the Hippocratic Oath requires physicians to benefit their patients "according to their best judgment." Learning what will in fact benefit may require exposing persons to risk. 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 risks.
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 procedures.
The principle of beneficence often occupies a well-defined justifying role in many areas of research involving human subjects. An example is found in research involving children . 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. But the role of the principle of beneficence is not always so unambiguous. 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 . Here again, as with all hard cases, the different claims covered by the principle of beneficence may come into conflict and force difficult choices.
3. Justice . -- Who ought to receive the benefits of research and bear its burdens ? This is a question of justice, in the sense of "fairness in distribution" or "what is deserved ." An injustice occurs when some benefit to which a person is entitled is denied without good reason or when some burden is imposed unduly. Another way of conceiving the principle of justice is that equals ought to be treated equally . However, this statement requires explication. Who is equal and who is unequal? What considerations justify departure from equal distribution? Almost all commentators allow that distinctions based on experience, age, deprivation, competence, merit and position do sometimes constitute criteria justifying differential treatment for certain purposes. It is necessary, then, to explain in what respects people should be treated equally.
There are several widely accepted formulations of just ways to distribute burdens and benefits . Each formulation mentions some relevant property on the basis of which burdens and benefits should be distributed. These formulations are (1) to each person an equal share , (2) to each person according to individual need , (3) to each person according to individual effort, (4) to each person according to societal contribution , and (5) to each person according to merit .
Questions of justice have long been associated with social practices such as punishment, taxation and political representation. Until recently these questions have not generally been associated with scientific research. 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. In this country, in the 1940's, the Tuskegee syphilis study used disadvantaged, rural black men to study the untreated course of a disease that is by no means confined to that population. These subjects were deprived of demonstrably effective treatment in order not to interrupt the project, long after such treatment became generally available.
Against 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.g., welfare patients, particular racial and ethnic minorities, or persons confined to institutions) are being systematically selected simply because of their easy availability, their compromised position, or their manipulability, rather than for reasons directly related to the problem being studied . 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 research.
Applications 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.
1. Informed Consent . -- 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. This opportunity is provided when adequate standards for informed consent are satisfied.
While the importance of informed consent is unquestioned, controversy prevails over the nature and possibility of an informed consent. Nonetheless, there is widespread agreement that the consent process can be analyzed as containing three elements: information, comprehension and voluntariness .
Information. 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, etc.
However, 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 . Another standard, currently popular in malpractice law, requires the practitioner to reveal the information that reasonable persons would wish to know in order to make a decision regarding their care . 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 . It may be that a standard of "the reasonable volunteer" should be proposed: the extent and nature of information should be such that persons, knowing that the procedure is neither necessary for their care nor perhaps fully understood, can decide whether they wish to participate in the furthering of knowledge . Even when some direct benefit to them is anticipated, the subjects should understand clearly the range of risk and the voluntary nature of participation.
A 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 investigator.
Comprehension. The manner and context in which information is conveyed is as important as the information itself. For example, presenting information in a disorganized and rapid fashion, allowing too little time for consideration or curtailing opportunities for questioning , all may adversely affect a subject's ability to make an informed choice.
Because the subject's ability to understand is a function of intelligence, rationality, maturity and language , it is necessary to adapt the presentation of the information to the subject's capacities. Investigators are responsible for ascertaining that the subject has comprehended the information. 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 . On occasion, it may be suitable to give some oral or written tests of comprehension .
Special provision may need to be made when comprehension is severely limited -- for example, by conditions of immaturity or mental disability . Each class of subjects that one might consider as incompetent (e.g., infants and young children, mentally disable patients, the terminally ill and the comatose) should be considered on its own terms. 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 . Such persons are thus respected both by acknowledging their own wishes and by the use of third parties to protect them from harm.
The third parties chosen should be those who are most likely to understand the incompetent subject's situation and to act in that person's best interest . 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 interest .
Voluntariness. An agreement to participate in research constitutes a valid consent only if voluntarily given . This element of informed consent requires conditions free of coercion and undue influence. Coercion occurs when an overt threat of harm is intentionally presented by one person to another in order to obtain compliance. Undue influence , by contrast, occurs through an offer of an excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain compliance . Also, inducements that would ordinarily be acceptable may become undue influences if the subject is especially vulnerable .
Unjustifiable pressures usually occur when persons in positions of authority or commanding influence -- especially where possible sanctions are involved -- urge a course of action for a subject . A continuum of such influencing factors exists, however, and it is impossible to state precisely where justifiable persuasion ends and undue influence begins . But undue influence would include actions such as manipulating a person's choice through the controlling influence of a close relative and threatening to withdraw health services to which an individual would otherwise be entitle.
2. Assessment of Risks and Benefits. -- 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 participate .
The 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. The term " risk " refers to a possibility that harm may occur . 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 harm.
The term " benefit " is used in the research context to refer to something of positive value related to health or welfare . Unlike, "risk," "benefit" is not a term that expresses probabilities . Risk is properly contrasted to probability of benefits, and benefits are properly contrasted with harms rather than risks of harm . Accordingly, so-called risk/benefit assessments are concerned with the probabilities and magnitudes of possible harm and anticipated benefits . Many kinds of possible harms and benefits need to be taken into account. There are, for example, risks of psychological harm, physical harm, legal harm, social harm and economic harm and the corresponding benefits . 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 overlooked.
Risks 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 research .
The Systematic Assessment of Risks and Benefits. It is commonly said that benefits and risks must be " balanced " and shown to be " in a favorable ratio ." The metaphorical character of these terms draws attention to the difficulty of making precise judgments. Only on rare occasions will quantitative techniques be available for the scrutiny of research protocols. However, the idea of systematic, nonarbitrary analysis of risks and benefits should be emulated insofar as possible .
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. The method of ascertaining risks should be explicit, especially where there is no alternative to the use of such vague categories as small or slight risk. 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 studies.
Finally, 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. (ii) 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. Risk can perhaps never be entirely eliminated, but it can often be reduced by careful attention to alternative procedures . (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 . A number of variables go into such judgments, including the nature and degree of risk, the condition of the particular population involved, and the nature and level of the anticipated benefits . (v) Relevant risks and benefits must be thoroughly arrayed in documents and procedures used in the informed consent process .
3. Selection of Subjects. -- 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 subjects.
Justice 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.g., adults before children) and that some classes of potential subjects (e.g., the institutionalized mentally infirm or prisoners) may be involved as research subjects, if at all, only on certain conditions.
Injustice 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 injustice arises from social, racial, sexual and cultural biases institutionalized in society. 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 subjects.
Some 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 benefits .
One 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.
[ Note: The above Belmont Report was also mandated by the 1974 National Research Act to be used as the foundation for the new federal OPRR (later OHRP) regulations for the use of human subjects in research, and the following OHRP federal regulations are currently in use . Note the "exceptions". In fact, the Secretary of DHHS has the authority to waive certain informed consent requirements, even with the opposition of the President or members of Congress. Among many other problems and concerns, note also the false scientific definitions inserted into the original OPRR regulations (admittedly done so by Richard Doerflinger of the USCCB) and preserved continuously to the present OHRP regulation updates. The two false scientific definitions are "fetus" and "pregnancy" , both erroneously defined as "beginning at implantation". "Fetus" is also defined as the "product of conception " (which usually means "fertilization", or "sexual reproduction", fusion of sperm and oocyte). In the real world, implantation takes place about a week after the new human embryo begins to exist at the beginning of fertilization in the woman's fallopian tube, and by implantation is about a week old (consisting of about 100+ cells at the blastocyst stage of development). Therefore a woman is really already pregnant before implantation in normal sexual relations. And a "fetus" is accurately defined as the developing human being beginning at 9 weeks post-fertilization (when the "fetal period" begins) until birth. Also, the "product of conception " applies only to sexually reproduced human beings; it does not apply to any a-sexually reproduced human beings (i.e., reproduced without the immediate use of any sperm or oocytes), e.g., all cloned or otherwise genetically engineered human beings a-sexually reproduced naturally in vivo (identical twins) or a-sexually reproduced artificially in vitro in IVF/ART research laboratories or "infertility" clinics.
Thus these federal regulations (1) would not consider women "pregnant" before the already existing embryo implants into her uterus. (2) They would not cover any a-sexually reproduced human embryos or fetuses at any age. All a-sexually reproduced human embryos and fetuses would not be "human subjects" needing protection and legally disappear. (3) They are falsely claiming that it is the fetus that implants into her uterus -- which is absurd, since it is the "embryo" at the blastocyst stage of development that implants into her uterus. The developing human being is not considered a "fetus" until 9 weeks post-fertilization . (4) Therefore these federal regulations would not legally recognize even the sexually reproduced ("conception") developing human being during the embryonic period at all as a "human subject of research" from fertilization until the end of the 8th week post-fertilization . Even the "human embryo" sexually reproduced is not a "human subject of research" needing protection and legally simply disappears. [See Irving: FERTILIZATION and IMPLANTATION of the Early Human Embryo: Accurate Scientific Resources (May 8, 2013), at: http://www.lifeissues.net/writers/irv/irv_212accurateresources1.html ; also, "Individual testimony before the NIH Human Embryo Research Panel" (March 14, 1994); reprinted in Linacre Quarterly , 61(4):82-89 (Nov. 1994), at: http://www.lifeissues.net/writers/irv/irv_32individualtestimony.html ; PMID: 11652834 [PubMed - indexed for MEDLINE]; also, "Invited Submission: Maryland state proposed statute for research using "decisionally incapacitated" human subjects: The legalization of normative bioethics theory" ; submitted to State of Maryland Attorney General J. Joseph Curran, Jr., and Asst. Attorney General Jack Schwartz, in response to the Initial Report of the Attorney General's Research Working Group (June 30, 1998); submitted to the State of Maryland General Assembly, March 1999, at: http://www.lifeissues.net/writers/irv/irv_70incapacitated1.html ]. The current U.S. federal regulations for the use of human subjects in research are the following:]
Appendix 4 (U.S. Federal Guidelines): The Federal Policy and 45 CFR 46 (see page 3 of original document for beginning, page 8 re "informed consent"): http://www.hhs.gov/ohrp/humansubjects/regbook2013.pdf.pdf
Except as provided elsewhere in this policy, 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 . An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence . The information that is given to the subject or the representative shall be in language understandable to the subject or the representative . No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the investigator, the sponsor, the institution or its agents from liability for negligence .
(a) Basic elements of informed consent. Except as provided in paragraph (c) or (d) of this section, in seeking informed consent the following information shall be provided to each subject :
(b) Additional elements of informed consent. When appropriate, one or more of the following elements of information shall also be provided to each subject:
(c) An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth above, or waive the requirement to obtain informed consent provided the IRB finds and documents that:
(d) An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth in this section, or waive the requirements to obtain informed consent provided the IRB finds and documents that:
(e) The informed consent requirements in this policy are not intended to preempt any applicable federal, state, or local laws which require additional information to be disclosed in order for informed consent to be legally effective.
(f) Nothing in this policy is intended to limit the authority of a physician to provide emergency medical care, to the extent the physician is permitted to do so under applicable federal, state, or local law. (Approved by the Office of Management and Budget under Control Number 0990-0260.) [56 FR 28012, 28022, June 18, 1991, as amended at 70 FR 36328, June 23, 2005]
(a) Except as provided in paragraph (c) of this section, informed consent shall be documented by the use of a written consent form approved by the IRB and signed by the subject or the subject's legally authorized representative . A copy shall be given to the person signing the form.
(b) Except as provided in paragraph (c) of this section, the consent form may be either of the following:
(c) An IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either:
(Approved by the Office of Management and Budget under Control Number 0990-0260.) [56 FR 28012, 28022, June 18, 1991, as amended at 70 FR 36328, June 23, 2005]
[[NOTE again that both "fetus" and "pregnancy" are extremely mis-defined in the next section as "beginning at implantation". -- DNI]]
Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research Source: 66 FR 56778, Nov. 13, 2001, unless otherwise noted.
(c) Fetus means the product of conception from implantation until delivery .
(d) Neonate means a newborn.
(e) Nonviable neonate means a neonate after delivery that, although living, is not viable.
(f) Pregnancy encompasses the period of time from implantation until delivery . A woman shall be assumed to be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery.