III. CONSENT ISSUES IN HUMAN RESEARCH

"The voluntary consent of the human subject is absolutely essential." This, the first sentence of the Nuremberg Code, signals the centrality of the consent requirement in research involving human subjects (Germany [Territory under Allied Occupation], p. 181). Before the Nuremberg Code was written in 1947 as a response to the atrocities committed in the name of science by Nazi physician-researchers, statements of medical and other professional organizations apparently made no mention of the necessity of consent. Ironically, the only nations known to have promulgated regulations that established a requirement for consent to research were Prussia and Germany (Perley et al.). Subsequently, the tendency to focus on informed consent has been reinforced by public outcry over the inadequacy of consent in certain landmark cases in the United States, such as the Willowbrook Studies (1963–1966), Jewish Chronic Disease Hospital Study (1963), Tea Room Trade Study (1970), and Tuskegee Syphilis Study (1932–1972) (Katz, Capron, and Swift; Levine). Indeed, the issue of informed consent has so dominated recent discussion of the ethics of research that one might be led to think erroneously that other ethical issues (e.g., research design, selection of subjects) are either less important or more satisfactorily resolved.

This entry is concerned with the conceptual aspects of informed consent. For an extensive review of empirical studies of informed consent, see the 1999 article written by Jeremy Sugarman and Douglas C. McCrory.

Grounding of Informed Consent

The requirement for informed consent has philosophical, religious, and legal foundations.

PHILOSOPHICAL BASIS. The philosophical foundations of the requirement for informed consent may be found in several lines of reasoning (Veatch 1981; Faden, Beauchamp, and King; Brock 1987). Based on the Hippocratic admonition "to help, or at least, to do no harm," one can justify seeking consent for the benefit of the patient; to do so provides a mechanism for ascertaining what the patient would consider a benefit. Allowing individuals to decide what they consider beneficial is consistent with the perspective affirmed in U.S. public policy that competent persons are generally the best protectors of their own well-being (Brock 1987). A focus solely on patient benefit, however, would allow physicians and scientists not to seek consent when they judge that doing so might harm patients or subjects. Thus this justification alone does not suffice to establish a requirement to seek consent.

The requirement can also be justified on grounds of social benefit: The practice of seeking consent may contribute to producing the "greatest good for the greatest number" by forestalling suspicion about research, thus ensuring a subject population and increasing the efficiency of the research enterprise. Again, however, the justification fails to stand alone, because it can also be used to justify not seeking consent; the social good might be better served by avoiding the inefficient and frequently time-consuming consent process. Some commentators express concern that, carried to its extreme, the social-benefit argument might support the use of unwilling subjects, as in Nazi Germany; such a position would necessarily rest on a very limited vision of the relevant social consequences.

The firmest grounding for the requirement to seek consent is the ethical principle respect for persons, which according to the U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (hereafter, U.S. National Commission) "incorporates at least two basic ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy and thus in need of protection are entitled to such protection" (U.S. National Commission, p. 4). Although this term suggests a Kantian or deontological (a foundational ethical principle holding that the moral rightness of an action resides in the action itself without regard to its consequences) grounding of the principle, this was not the intent of the commission; a substantially similar principle, self-determination, may be grounded in rule utilitarianism deontological (a foundational ethical principle holding that the moral rightness of an action must be evaluated in terms of its consequences) (Brock, 1987). In a legal context, American jurist Benjamin Cardozo stated in 1914 that "every human being of adult years and sound mind has a right to determine what shall be done with his own body" (Katz, p. 51). To return to the Kantian approach that will be used often in this entry, this principle of respect for persons, autonomy or self-determination ensures that the research subject will be treated as an end and not merely as a means to another's end (Beauchamp and Childress). Thus the purpose of the consent requirement is not only to minimize risk but also to give persons the right to choose.

RELIGIOUS BASIS. Several fundamental tenets of the Judeo-Christian and other traditions also provide grounding for the requirement to seek consent. This tradition affirms that each human life is a gift from God and is of infinite and immeasurable worth (the "sanctity of life"). The infinite worth of the individual requires that persons treat each other with respect and not interfere in each other's lives without consent. The consent requirement can also be grounded explicitly in the notion of covenant. Seeking consent is an affirmation of the basic faithfulness or care required by the fundamental covenantal nature of human existence (Ramsey, 1970).

LEGAL BASIS. The legal grounding for the requirement for consent to research (Annas, Glantz, and Katz) is based on the outcome of litigation of disputes arising almost exclusively in the context of medical practice. There is virtually no case law on which to define the basis of the legal standards for consent to research, as distinguished from consent to practice (there is one Canadian case, Halushka v. University of Saskatchewan [1965]). The law defines, in general, the circumstances under which a patient, or by extension, a subject, may recover damages for having been wronged or harmed as a consequence of failure to negotiate adequate consent.

The legal bases for the consent requirement—which also shed light on the ethical dimensions of consent—are twofold (Annas, Glantz, and Katz). First, failure to obtain proper consent was traditionally treated as a battery action. Closely related to the principles of respect for persons and self-determination, the law of battery makes it wrong to touch, treat, or do research upon a person without the person's consent. Whether or not harm befalls the patient/subject is irrelevant: It is the unconsented-to touching that is wrong.

The modern trend in malpractice litigation is to treat cases based on failure to obtain proper consent as negligence rather than battery actions. The negligence doctrine combines elements of patient benefit and self-determination. To bring a negligence action, a patient/subject must prove that the physician had a duty toward the patient, that the duty was breached, that damage occurred to the patient, and that the damage was caused by the breach. In contrast to battery actions, negligence actions remove as a basis for the requirement for consent the simple notion that unconsented-to touching is a wrong. Rather, such touching is wrong (actionable) only if it is negligent and results in harm; otherwise, the patient/subject cannot recover damages. Under both battery and negligence doctrines, consent is invalid if any information is withheld from the patient/subject that might be considered material to the decision to give consent.

Functions of Informed Consent

In their 1975 book, Catastrophic Diseases: Who Decides What? Jay Katz and Alexander Morgan Capron identified the following functions of informed consent: promoting individual autonomy, encouraging rational decision making, avoiding fraud and duress, involving the public, encouraging self-scrutiny by the physician-investigator, and reducing the civil and/or criminal liability of the investigator and her institution.

In general, the negotiations for informed consent are designed to safeguard the rights and welfare of the subject, while documentation that the negotiations have been conducted properly safeguards the investigator and institution (Levine). The net effect of the documentation may, in fact, be harmful to the interests of the subject. Retaining a signed consent form tends to give the advantage to the investigator in any adversarial proceeding. Moreover, the availability of such documents in institutional records may lead to violations of privacy and confidentiality. Consequently, federal regulations permit waivers of the requirement for consent forms when the principal threat to the subject would be a breach of confidentiality and "the only record linking the subject and the research would be the consent document" ("Documentation of Informed Consent," pt. 46.117c).

Those who are interested in making operational the requirement for consent have a tendency to focus nearly all of their attention on the consent form. Federal regulations prescribe what information must be included in and excluded from these forms. Members of institutional review boards and researchers collaborate in a struggle to create reproachless forms. This seems to reflect an assumption that the consent form is an appropriate instrumentality through which researchers might fulfill their obligation not to treat persons merely as means. Most commentators on informed consent disagree, however, seeing consent as a continuing process rather than an event symbolized by the signing of a form; for example, Robert J. Levine (1986) characterized informed consent as a discussion or negotiation, while Katz(1984) envisioned consent as a searching conversation.

Whether or not negotiations for informed consent to research should be conducted according to different standards than consent to practice is controversial. In a 1974 article, Alvan R. Feinstein observed that it is the custom to adhere to a double standard: "An act that receives no special concern when performed as part of clinical practice may become a major ethical or legal issue if done as part of a formally designed investigation" (p. 331). In his view there is less need for formality in the negotiations for informed consent in a relationship in which the interests of research and practice are conjoined—for example, as in research conducted by a physician-investigator who has the aim of demonstrating the safety and/or efficacy of a nonvalidated therapeutic maneuver—than when the only purpose of the investigator–subject relationship is to perform research. Capron, on the other hand, asserted in a 1972 publication: "Higher requirements for informed consent should be imposed in therapy than in investigation, particularly when an element of honest experimentation is joined with therapy"(p. 574). Levine (1986) concluded that patients are entitled to the same degree of thoroughness of negotiations for informed consent as are subjects of research. Patients, however, may be offered the opportunity to delegate some (but not all) decision-making authority to a physician, whereas subjects should rarely be offered this option. The most important distinction is that the prospective subject should be informed that in research, in contrast with practice, the subject will be at least in part a means and perhaps primarily a means to an end identified by someone else.

Two Interpretations of the Consent Requirement

Interpretations of the meaning and application of informed consent reflect a tension between respecting the autonomy of persons and protecting them from harm. Hans Jonas(1970) and Paul Ramsey (1970) have developed a covenantal model in which subjects are respected and protected by ensuring that they give truly informed consent. Benjamin Freedman (1975) stressed the legally competent individual's freedom of choice, whether or not the choice is informed.

For Jonas and Ramsey, the consent requirement is derived from the duty to treat persons as ends, not merely as means. In research, subjects are used as means to the end of acquiring knowledge. (In Jonas's terms, they are "sacrificed" for the collective good.) Such use of persons is justified only if the subjects so identify with the purposes of the research that they will those purposes as their own ends. Only then are they not being used, but instead they have become, in Ramsey's term, "co-adventurers." The consent requirement thus affirms a basic covenantal bond between the researcher and the subject and ensures respect for the subject as an end, not merely a means.

To establish a true covenant, the subject's consent must be informed. Only subjects who genuinely know the purposes and appreciate the risks of research can assume those risks and adopt those purposes as their own ends. Ideal subjects, therefore, would be researchers themselves (Jonas). The less one understands the risks and identifies with the purposes of research, the less valid is one's consent. Jonas therefore established a "descending order of permissibility" for the recruitment ("conscription") of volunteers. Both Ramsey and Jonas restrict the use of subjects unable to consent or to understand what is involved, permitting the use of such subjects only in research directly related to their own condition (Jonas) or their own survival and well-being (Ramsey).

This interpretation reflects certain assumptions that can be challenged. First, while neither Jonas nor Ramsey focused exclusively on patients as subjects, their approach appears to be influenced largely by the medical practice model. That approach may not be adequate to deal with research not based on the medical practice model—for example, social-science research.

Second, while Ramsey argued that it is wrong to use a person in research without consent irrespective of risk (because one can be wronged without being harmed), he nonetheless appears to share with Jonas the assumption that most research is risky and involves sacrifice on the part of the subject. In fact, most research does not present risk of physical or psychological harm; rather, it presents inconvenience (e.g., of urine collection) and discomforts (e.g., of needle sticks) (Levine). Even Phase I drug testing, which involves the first administration of new drugs to humans and is usually assumed to be highly risky, has been estimated to present subjects with risks slightly greater than those involved in secretarial work and substantially less than those assumed by window washers and miners (Levine).

But the most important challenge is Freedman's (1975) alternative interpretation and use of the basic principles. Like Jonas and Ramsey, Freedman derived the consent requirement from the duty to have respect for persons. Unlike Jonas and Ramsey, however, he interpreted the requirement of respect for competent persons to allow the possibility of a "valid but ignorant" consent.

Freedman proposed that striving for fully informed consent is generally undesirable and that what is required is valid consent, not necessarily informed consent. To be valid, consent must be responsible and voluntary. Thus valid consent "entails only the imparting of that information which the patient/subject requires in order to make a responsible decision" (Freedman, p. 34). A choice based on less or other information than another responsible person might consider essential is not necessarily a sign of irresponsibility. Overprotection is a form of dehumanization and lack of respect; for example, to classify persons as incompetent to protect them from their own judgment is the worst form of abuse.

This approach also has several weaknesses. Much hinges on what is taken to be a responsible choice. Freedman suggested that responsibility is a dispositional characteristic and is to be judged in terms of the person, not in terms of a particular choice. There can be still, however, an element of paternalism introduced in judging another to be an irresponsible person. Moreover, this approach may not provide sufficient protection for those subjects who tend too readily to abdicate responsibility for choice, or who lack sufficient capacity or information to choose prudently.

It is clear that debates over the interpretation of informed consent depend on interpretations of the basic ethical principle of respect for persons and the extent to which that principle requires protection from harm or respect for autonomy.

Informed Consent: Conditions and Exceptions

According to the Nuremberg Code, to consent to participate in research one must:

1. be "so situated as to be able to exercise free power of choice";
2. have the "legal capacity" to give consent;
3. have "sufficient … comprehension" to make an "enlightened" decision; and
4. have "sufficient knowledge" on which to decide (Germany [Territory under Allied Occupation], p. 181).

More recent discussion emphasizes the knowledge or information component of consent—hence the term "informed consent" (Katz). The Nuremberg Code's focus on freedom of choice rather than on the quantity or quality of information transmitted is represented by its use of the term voluntary consent, instead of informed consent. It is worth recalling that a demand for informed consent at the expense of other styles of self-determination such as Freedman's responsible choice is not necessarily respectful of persons. Most commentators agree that compromise on any one of the four conditions specified by the Nuremberg Code jeopardizes the ethical acceptability of the consent.

"FREE POWER OF CHOICE." The Nuremberg Code proscribes "any element of force, fraud, deceit, duress, overreaching, or other ulterior forms of constraint or coercion" (Germany [Territory under Allied Occupation], p.181) in obtaining consent. Any flagrant coercion—for instance, when competent, comprehending persons are forced to submit to research against their expressed will—clearly renders consent invalid. There may be more subtle or indirect "constraints" or "coercions" when prospective subjects are highly dependent, impoverished, ignorant, or "junior or subordinate members of a hierarchical group" (CIOMS, p. 65). Some argue that consent obtained from such persons violates the intent of the Nuremberg Code. This argument has been posed most sharply with respect to prisoners and other institutionalized populations, because institutionalization often involves both dependency and impoverishment. (Biomedical research involving prisoners as subjects has become quite rare since 1976 when the U.S. National Commission recommended very stringent standards for its justification [Dubler and Sidel 1989].) Some argue that consent to participate in research is not valid when it is given(1) to procure financial reward in situations offering few alternatives for remuneration; (2) to seek release from an institution either by evidencing "good behavior" or by ameliorating the condition for which one was confined; or(3) to please physicians or authorities on whom one's continued welfare depends (Branson).

But in his contribution to a 1976 U.S. National Commission report, Cornel R. West argued that such indirect forms of constraint do not constitute coercion in a strict sense and thus do not render consent involuntary. "Coercion," says West, consists in a threat to render one's circumstances worse if one does not do something. Hence, a threat to withdraw basic necessities of existence, or in some other way to render a prison inmate's situation worse if he declines to participate in research, would constitute coercion and render consent invalid. Similarly, to condition release from prison upon participation would constitute coercion, because it would make the inmate's situation worse by removing normal alternatives for seeking release. But the provision of better living conditions in exchange for participation in research does not constitute a threat to make conditions worse; rather, it is an enticement to make conditions better. While enticement and bribery can invalidate consent by undermining the rational grounds for choice, they do not undermine the voluntariness of the choice (Cohen). Similarly, a desire to get well or to favorably influence institutional authorities is not an ulterior constraint in the strict sense of the Nuremberg Code, though it may be a very real psychological constraint.

Other commentators, however, are less concerned with a sharp distinction between coercion and other forms of constraint or undue influence (Levine; CIOMS). Even outside such total institutions as prisons there are many situations in which junior or subordinate members of hierarchical groups may be exploited or manipulated. Such persons may assume that their willingness to consent to research may be rewarded by preferential treatment or that their refusals could provoke retaliation by those in positions of authority in the system. Whether or not such assumptions are justified, it is the assumptions themselves that make such persons susceptible to manipulation. Examples of such persons are medical or nursing students, subordinate hospital and laboratory personnel, employees of pharmaceutical firms, and members of the military services. Other persons whose dependency status can be exploited include residents of nursing homes, people receiving welfare benefits, patients in emergency rooms, and those with incurable diseases.

Apart from those populations identified by regulations and ethical codes as requiring special protection—fetuses, children, prisoners, and those who are incompetent by reason of mental incapacity—there is no clear consensus about how to respond to the problems presented by those whose capacity to consent may be limited by virtue of their dependency status. For example, whereas some medical schools have policies that forbid the involvement of medical students as research subjects, others have required investigators to invite them to participate in certain complex projects, reasoning that their highly sophisticated understanding of the risks, benefits, and purposes of such projects ensures a high quality of consent (Levine). Involvement of medical students, it is further argued, is consistent with Jonas's "descending order of permissibility" and contributes to their socialization into the medical profession.

While most regulations and ethical codes proscribe undue material inducements, there is no consensus on what this means. Some commentators argue that in most cases in which competent adults are recruited to serve as subjects in research that presents only slight increases above minimal risk, the role of the research subject is similar to that of an employee (Levine). Consequently, the amounts of cash payments or other material inducements can be determined by ordinary market factors. Others protest that because participation in research entails selling one's body as opposed to selling one's labor the role of the research subject might be considered more akin to commercial sex work than to any other type of employment (Wartofsky). According to this view, research subjects should not be paid at all; rather, they should be motivated by altruism.

Attempts to regulate the amounts of permissible material inducements are inevitably problematic (Levine). Setting the rates at a low level results in inequitable distribution of the burdens of participation among those who have no opportunities to earn more money for each unit of their time. Higher rates may overwhelm the capacity of the impoverished to decline participation.

In multinational research it is essential to evaluate the ethical acceptability of material inducements in the light of the gift-exchange traditions of the culture or community in which the research is to be carried out (CIOMS).

COMPETENCE AND COMPREHENSION. The Nuremberg Code requires both "legal capacity" to consent (often called competence) and "sufficient understanding" to reach an "enlightened" decision. Definitions of competence often include elements of comprehension, for example, to evaluate relevant information, to understand the consequences of action, and to reach a decision for rational reasons (Stanley and Stanley).

ASSESSMENTS OF INCOMPETENCE. The various standards employed for assessing competence are variations of four basic themes (Appelbaum, Lidz, Meisel):

1. Reasonable outcome of choice. This is a highly paternalistic standard in that the individual's right to self-determination is respected only if she makes the "right" choice—that is, one that accords with what the competency reviewer either considers reasonable or presumes a reasonable person might make.
2. Factual comprehension. The individual is required to understand, or at least be able to understand, the information divulged during the consent negotiation.
3. Choice based on rational reasons. Individuals must demonstrate a capacity for rational manipulation of information. They may, for example, be required to show that they not only understand the risks and benefits but also have weighed them in relation to their personal situations.
4. Appreciation of the nature of the situation. Individuals must demonstrate not only comprehension of the consent information but also the ability to use the information in a rational manner. Furthermore, they must appreciate that they are being invited to become research subjects and what that implies.

While there is disagreement as to the grounds for assessing incompetence, most commentators agree that such assessments are limited in several ways (Faden, Beauchamp, and King). First, a judgment of incompetence may apply to only certain areas of decision making, for example, to one's legal but not to one's personal affairs. Second, confinement to a mental institution is not in itself equivalent to a determination of incompetence. Third, some people are legally competent but functionally incompetent, whereas others are legally incompetent but functionally competent.

The Nuremberg Code does not permit the use of subjects lacking legal capacity or comprehension. Most subsequent codes and discussions allow their use with certain restrictions: for example, that mentally competent adults are not suitable subjects, that the veto of a legally incompetent but minimally comprehending subject is binding, and that consent or permission of the legal guardian must be obtained (Levine).

In its 1982 report, Making Health Care Decisions, the U.S. President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (hereafter, U.S. President's Commission) wrote that "decisionmaking capacity requires, to a greater or lesser degree: (1) possession of a set of values and goals; (2) the ability to communicate and understand information; and(3) the ability to reason and deliberate about one's choices"(p. 57). Moreover, individuals may have sufficient capacity to make some decisions but not others (Brock; Kopelman). In the words of the U.S. President's Commission:

Since the assessment [of capacity] must balance possibly competing considerations of well-being and self-determination, [one should] take into account the potential consequences of the patient's decision. When the consequences for well-being are substantial, there is a greater need to be certain that the patient possesses the necessary level of capacity.… Thus a particular patient may be capable of deciding about a relatively inconsequential medication, but not about the amputation of a gangrenous limb. (U.S. President's Commission, p. 60)

PROXY CONSENT. The debate between Paul Ramsey and Richard A. McCormick over the legitimacy of proxy consent to authorize the participation of an incompetent person in research is one of the classics in the brief history of bioethics. Adopting the battery argument, Ramsey claimed that the use of a nonconsenting subject is wrong whether or not there is risk, simply because it involves an unconsented touching. Unconsented touching is not wrongful, however, when the guardian judges it is for the good of the incompetent individual. Hence, proxy consent may be given for the use of nonconsenting subjects in research only when it includes therapeutic interventions related to the subject's own recovery (Ramsey, 1970).

Ramsey acknowledged, however, that benefit does not always justify unconsented touching; such touching of a competent adult is wrong even if it benefits that person. Why, then, can benefit be presumed to justify such touching for a child (or other subject unable to give consent)? McCormick proposed that the validity of such interventions rests on the presumption that the child, if capable, would consent to therapy. This presumption in turn derives from a child's obligation to seek therapy, an obligation that the child possesses simply as a human being (McCormick, 1974). Because children have an obligation to seek their own well-being, it is presumed that they would consent if they could, and thus presumed also that proxy consent on their behalf would not violate respect for them as persons.

By analogy, McCormick suggested that, as members of a moral community, children have other obligations to which one would presume their consent and give proxy consent on their behalf. One such obligation is to contribute to the general welfare when such contribution requires little or no sacrifice. Hence, nonconsenting subjects may be used in research not directly related to their own benefit so long as the research fulfills an important social need and involves no discernible risk. Ramsey countered this argument with respect to children, claiming that McCormick's position fails to recognize that children are not adults with a full range of duties and obligations. Instead, they have rights that must be protected by adults (Ramsey, 1976).

Adopting this premise about the nature of the child as a moral being, Freedman drew different conclusions. Because a child is not a moral being in the same sense as an adult, he argued, the concept of wrongful touching does not apply. The child has no right to be left alone but only a right to be protected. Hence, Freedman concluded that the only relevant moral issue is the risk involved in the research, and, like McCormick, that children could be used in research unrelated to their therapy, provided it presents them no discernible risk. Thus, the debate centers on the status of the child (a paradigmatic incompetent) as a moral being and on interpretations of the requirements of respect for persons.

Although disagreements persist over both standards of competence and the use of incompetent subjects, one issue seems to have been settled by the U.S. National Commission in several of its reports (Levine). Parents, guardians, and, in some cases, other responsible relatives may give permission (a term that often replaces "proxy consent") to involve an incompetent in research if there is no more than minimal risk, if incompetents who are capable of giving their assents (knowledgeable agreements that do not meet the legal standards for informed consent) do so, and if certain other criteria are satisfied. If there is more than minimal risk, the standards for ethical justification of the involvement of incompetents are more stringent.

DISCLOSURE OF INFORMATION. The Nuremberg Code requires that the subject be told "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 (Germany, [Territory under Allied Occupation], p. 182)." These requirements have been modified by subsequent codes and regulations. U.S. federal regulations require:

1. a statement of the purpose of the research and a description of its procedures;
2. a description of foreseeable risks and discomforts;
3. a description of benefits;
4. disclosure of appropriate alternatives, if any;
5. a statement of the extent of confidentiality;
6. an explanation of the availability of medical treatment for injury and compensation for disability;
7. an explanation of whom to contact for answers to questions; and
8. a statement that participation is voluntary and that neither refusal to participate nor withdrawal at any time will result in a loss of benefits to which the subject is otherwise entitled ("General Requirements" 1993).

The regulations further specify six additional elements of information to be provided when appropriate:

1. additional risks to the subject or to the fetus if the subject becomes pregnant;
2. circumstances in which a subject's participation may be terminated without his consent;
3. additional costs to the subject that may result from participation;
4. the consequences of a subject's decision to withdraw and procedures for orderly termination of participation;
5. a commitment to divulge significant new findings developed during the research that may relate to the subject's continued willingness to participate; and
6. the approximate number of subjects in the study.

Finally, the regulations forbid use of any exculpatory language through which the subject or her representative is made to waive any of their legal rights or that releases of the investigator, sponsor, or institution from liability for negligence.

While these requirements have the force of law, they are by no means exhaustive of possible standards for disclosure. To them one might add the following: a clear invitation to participate in research, distinguishing maneuvers required for research purposes from those necessary for therapy; an explanation of why the particular person is invited (selected); a suggestion that the prospective subject might wish to discuss the research with another person; and an identification of the source of funding for the research. Robert M. Veatch (1978) would add the names of members of any review boards that had approved the research and an explanation of the right, if any, to continue receiving treatments found useful. In short, there is no universal agreement on standards for disclosure of information or on what it takes for a person to have sufficient knowledge to give informed consent.

Those who agree on the need for disclosure of information in a particular category—the risks, for example—often disagree on the nature of the information that must be made known. The Nuremberg Code requires explication of hazards "reasonably" to be expected. Does this include a very slight chance of a substantial harm, or a substantial chance of a very slight harm? Neither the quality nor the probability of the risks to be divulged has been clearly determined legally.

Disagreements over particulars arise in part from disagreements about underlying standards: Is disclosure to be determined by (1) general medical practice or opinion, (2) the requirements of a reasonable person, or (3) the idiosyncratic judgment of the individual? While the legal trend may be shifting from the first to the second, it may be argued that only the third, the subjective standard, is truly compatible with the requirement of respect for the autonomy of the individual person (Faden, Beauchamp, and King; Veatch, 1978).

Yet even those who adopt the subjective standard disagree as to its implications. As noted earlier, Freedman(1975) held that the idiosyncratic judgment of the individual is overriding, to the point that the prospective subject can choose to have less information than a "reasonable" person might require. Veatch (1978), however, argued that anyone refusing to accept as much information as would be expected of a "reasonable person" should not be accepted as a subject.

In the context of medical practice, two exceptions to the requirement for informed consent are recognized—emergency exception and therapeutic privilege. The former, which permits the doctor to proceed without delay to administer urgently required therapy in emergencies, is reflected in a limited form in two provisions of the regulations of the U.S. Food and Drug Administration: (1) In some "lifethreatening" emergencies in which informed consent is "infeasible," physician-investigators are authorized to employ investigational drugs and devices for therapeutic purposes (Levine). (2) In carefully defined circumstances, research designed to evaluate the safety and efficacy of investigational drugs or devices in emergency conditions may be carried out without the consent of the patient-subjects or the permission of their representatives. In such protocols either consent or permission must be obtained within a reasonable period of time after the initiation of the research; this entails authorization of the research participation already completed as well as the continuing participation of the subject in the research (Biros et al.).

The therapeutic-privilege exception to the informed-consent rule permits the doctor to withhold information when, in her judgment, disclosure would be detrimental to the patient's interests or well-being (Levine). Most commentators agree that invoking the doctrine of therapeutic privilege to assure a subject's cooperation in a research project is almost never appropriate; it gives the investigator entirely too much license to serve vested interests by withholding information that might be material to a prospective subject's decision. U.S. federal regulations do not explicitly endorse the use of the therapeutic-privilege exception in research, although some authors have suggested that they could be interpreted as an implicit endorsement (Levine).

The success of some research activities is contingent upon withholding from the subjects information about the purposes or procedures of the activities or, in some cases, upon deliberate deception (providing false information). U.S. federal regulations permit waivers and alterations of consent requirements if there is no more than minimal risk; if the waiver or alteration will not adversely affect subjects' rights or welfare; if without the waiver or alteration the research "could not practicably be carried out"; and if the subjects will be debriefed (given a full and accurate explanation afterward) when appropriate ("General Requirements," pt. 46.116d).

There are some categories of research which, until recently, have been customarily carried out without individual informed consent; waiver of the requirement for informed consent in these categories was generally considered justified according to the waivers and alterations provisions of the regulations. Such activities included most research involving medical records and "leftover" specimens of tissues and body fluids obtained for either clinical or research purposes. Institutional patient information brochures generally contained notices of such routine research activities (Levine). Such routine uses of medical records without consent have had to be reconsidered in the light of the requirements of the Health Insurance Portability and Accountability Act of 1996 (DHHS). Similarly, routine use by researchers of specimens of tissue, without informed consent, have had to be reevaluated in the light of rapidly evolving standards (Clayton et al.); there is general agreement that such research is permissible without informed consent if the specimens are anonymous.

In a 1979 article, Diana Baumrind expressed her opposition to deceptive practices, arguing not only that they violate the principle of respect for persons but also that in the long run they will invalidate research on scientific grounds. Various proposals have been made to minimize the need for and harmful effects of deceptive practices: Subjects might be invited to consent to incomplete disclosure with a promise of full disclosure at the termination of the research; subjects might be told as much as possible and asked to consent for specified limits of time and risk; or approval of the plans to withhold information from or to deceive subjects might be sought from surrogate populations that resemble the actual intended subject populations in relevant respects (Levine).

"Secondary" Research Subjects

U.S. federal regulations define a human subject as "a living individual about whom an investigator … conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information." (45 CFR 46.102f). Until 1999 it was generally assumed that this definition applied only to those individuals who were the targets of the researcher's interest and that part (2) of the definition was intended to cover the use of records and specimens of tissue and body fluids. In 2000, however, the federal Office for Protection from Research Risks (now the Office for Human Research Protections, part of the Department of Health and Human Services) issued a novel interpretation: Questions asked of research subjects calling upon them to report on private information of their relatives, friends, or associates had the effect of turning these friends, relatives, and associates into secondary research subjects. If the private information solicited could be considered sensitive, then it would be required that the informed consent of the secondary subjects be obtained. This is a highly controversial matter, a full discussion of which is beyond the scope of this entry (Botkin).

Conclusions

The use of a person as a research subject can be justified only if that person, or one authorized to speak on the person's behalf, consents to such use. The legal and ethical requirement for consent is grounded in fundamental tenets of the Judeo-Christian religious tradition as well as in basic ethical principles that create the universal obligation to treat persons as ends and not merely as means to another's end. The consent requirement also reflects the perspective that competent persons are generally the best protectors of their own well-being. Most major disagreements over the form and substance of the consent requirement derive from conflicting interpretations of one or more of the basic principles.

A widespread tendency among researchers to focus on consent forms seems to reflect an assumption that the consent form is an appropriate instrumentality through which they might fulfill their obligation not to treat persons merely as means. Most commentators on informed consent disagree, however, seeing consent as a continuing process rather than a single event consummated by the signing of a form. Moreover, whereas the primary purposes of informed consent are to foster self-determination and to empower prospective subjects to protect their own well-being and other interests, the primary purpose of its written documentation is to protect the investigator, the institution, and the research sponsor from legal liability.

robert j. levine (1995)

revised by author

SEE ALSO: Children: Healthcare and Research Issues; Competence; Coercion; Holocaust; Human Rights; Information Disclosure, Ethical Issues of; Minorities as Research Subjects; Placebo; Race and Racism; Research Policy: Risk and Vulnerable Groups;Students and Research Subjects; and other Informed Consent subentries

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INTERNET RESOURCE

U. S. Code of Federal Regulations, Protection of Human Subjects. 45 CFR 46. 2003. Available from <http://ohrp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm/>