Informed consent

Excerpt of U.S. Code of Federal Regulations (CFR) Title 45, Part 46, Subpart A, Section 46.116 General requirements for informed consent

Informed consent, as used in human subject research or healthcare, refers to an active decision of a subject/patient to agree to a certain action (participate as a subject in research, receive a medical treatment, allow release of personal information, etc.) on the basis of having sufficient knowledge to understand the implications of such a decision. Informed consent assumes that the person has full autonomy to be able to agree, is presented adequate information about what is involved, and has the ability to understand what is presented. Often the subject/patient is asked to sign or acknowledge this consent in an informed consent document or consent form.

Examples of informed consent would be an adult, competent subject agreeing to participate in a study of the efficacy and side-effects of a vaccine after being informed of the purpose of the study, the potential benefit of the study for the subject or society at large, the risks to the subject (physical, emotional, financial, etc.), sources of research funding, the ability to withdraw consent at any time, and so forth. Another example would be an adult, capable patient consenting to a particular surgical medical procedure after being informed of the risks of the procedure, the risks of not having the procedure, the likelihood and magnitude of benefits, and so forth.

A valid informed consent requires that the subject/patient has the autonomy to be able to freely agree or not agree to the action, is provided adequate information to inform the decision, and is competent to be able to understand what is presented about the implication of the action. When someone lacks full autonomy or the capacity to give consent (very young, prisoners, those suffering from advanced dementia, etc.), then special protections need to be in place to assure that their right to informed consent is protected. Some of the major ethical failings of human subject research have been because of the failure of the research subject to have full autonomy to consent (eg., Nazi human experimentation) or there was a lack of accurate information about what they were consenting to (eg., Tuskegee Syphilis Study).

Definition

The three basic elements in informed consent are: (1) the subject/patient is presented with adequate information to made a decision on whether or not to allow or participate in a certain action; (2) the subject/patient is able to comprehend the information presented; and (3) the subject/patient has the autonomy to be able to freely agree to the action.

The Belmont Report, issued in 1978, is a milestone reference and guidance document in terms of identifying guiding ethical principles and corresponding applications for research with human subjects. Its first section dealing with applying its three core ethical principles — respect for persons, beneficence, and justice — is titled "Informed Consent." Here it states, "there is widespread agreement that the consent process can be analyzed as containing three elements: information, comprehension and voluntariness." The following are brief excerpts from that section:

• Information. Most codes of research establish specific items for disclosure intended to assure that subjects are given sufficient information.
• 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 subjects 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.
• Voluntariness. An agreement to participate in research constitutes a valid consent only if voluntarily given. The element of informed consent requires conditions free of coercion and undue influence.

The Declaration of Helsinki is another cornerstone document that outlines ethical principles for conducting medical research with human subjects. The Declaration of Helsinki captures the essence of these three basic elements in its extensive section on informed consent. The following are some excerpts from that section:

• 25. Participation by individuals capable of giving informed consent as subjects in medical research must be voluntary. Although it may be appropriate to consult family members or community leaders, no individual capable of giving informed consent may be enrolled in a research study unless he or she freely agrees.
• 26. In medical research involving human subjects capable of giving informed consent, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest... anticipated benefits and potential risks...The potential subject must be informed of the right to refuse to participate in the study or to withdraw consent to participate at any time without reprisal...Special attention should be given to the specific information needs of individual potential subjects as well as to the methods used to deliver the information.

The U.S. Code of Federal Regulations captures the essence of these three elements in 45 CFR Part 46.116 (5):

• (2) An investigator shall seek informed consent only under circumstances that provide the prospective subject or the legally authorized representative sufficient opportunity to discuss and consider whether or not to participate and that minimize the possibility of coercion or undue influence.

• (3) The information that is given to the subject or the legally authorized representative shall be in language understandable to the subject or the legally authorized representative.

• (4) The prospective subject or the legally authorized representative must be provided with the information that a reasonable person would want to have in order to make an informed decision about whether to participate, and an opportunity to discuss that information.

• (5) Informed consent must begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject or legally authorized representative in understanding the reasons why one might or might not want to participate in the research. This part of the informed consent must be organized and presented in a way that facilitates comprehension.

Amdur and Bankert (2022), in their book Institutional Review Board: Member Handbook, also defined the term in terms of human subject research: "Informed consent means the subjects understand the important implications of the decision to participate in research, and they actively agree to such participation." They further noted the importance that researchers not confuse the term with the corresponding document: "Use the term consent document or consent form instead of informed consent. Informed consent indicates an action — an ongoing process of communication between the subject and research staff — is occurring. Informed consent is not a document, and presenting subjects with information in a document does not constitute informed consent on their part."

Of course, the same three elements apply not only to human subject research, but also medical procedures and information.

A unique situation is what to do when the second and third elements above are not possible, when the subject/patient is unable to comprehend the information presented or the subject/patient lacks the autonomy to be able to freely agree to the action. For example, a prospective candidate may lack the mental capacity to understand the information presented or a prisoner may lack the autonomy to freely make a decision. These special cases are considered below in the section Cases where patient/subject is incapable of giving informed consent.

History of informed consent

Vollman and Winau (1996), who examined the history of informed consent in Germany prior to 1933, when Nazi human experimentation began, noted some statements referencing aspects of this concept as far back as the end of the nineteenth century. The authors wrote that in 1891 the Prussian minister of the interior issued a directive dealing with voluntary consent in terms of the use of tuberculin for treatment of tuberculosis in prisons, stating it "must in no case be used against the patient's will." But the authors in particular stressed the important developments in informed consent related to the Neisser case, which led to the "first detailed regulations about non-therapeutic research in Western medicine."

The Neisser case involved clinical trials conducted by Albert Neisser. His research involved injecting cell-free serum from patients with syphilis into patients admitted for other medical issues, hoping this might act as a vaccination against syphilis. None of the subjects were informed about the experiments or were asked for consent. Some of the subjects subsequently contracted syphilis, although Nessler argued that because most of his patients were prostitutes, they probably contracted the disease independent of his serum injections. In 1898, Albert Neisser published the results of his clinical trials on serum therapy (Vollmann and Winau 1996).

The Neisser case led to public, legal, and legislative concern. An important figure in bringing Neisser's work to public attention was Albert Moll, a private-practice psychiatrist in Berlin. In his Physicians' Ethics, Moll had presented 600 cases of what he considered unethical, non-therapeutic research on humans, in which he emphasized the need for informed consent. Moll considered Neisser's work to be another example of unethical research. A public prosecutor investigated the case in 1898 as well, and Neisser was fined by the Royal Disciplinary Court, which according to the summary of Vollmann and Winau (1996), found that "though Neisser as a well known medical authority may have been convinced that the trials were harmless, he should have sought the patients' consent." The authors reiterated that it was "not questionable science but lack of patients' consent" that "was the main principle for the legal judgment."

Based on the Neisser case, and a request from the Prussian parliament, the minister for religious, educational, and medical affairs asked for a report from the Scientific Medical Office of Health, which concluded, as summarized by Vollmann and Winau (1996), "a physician who recognised that an injected serum might cause infection had no right to inject such a serum. In any case, both informing the subject and obtaining the subject's consent were preconditions to experimentation." The minister further sought legal advise from lawyers, who advised, again summarized by Vollmann and Winau (1996), that "conducting non-therapeutic research on a subject without consent fulfilled the criteria for causing physical injury in criminal law. The scientific validity of the experiment did not serve as mitigation. Informed consent was a mandatory precondition for any non-therapeutic research."

On this basis, the minister for religious, educational, and medical affairs issued, in 1900, a directive to all hospitals and clinics. According to Vollman and Winau (1996), this directive required that "all medical interventions other than for diagnosis, healing, and immunization were excluded under all circumstances if 'the human subject was a minor or not competent for other reasons' or if the subject had not given his or her 'unambiguous consent' after a 'proper explanation of the possible negative consequences' of the intervention."

Bazzano et al., in their 2021 article, "A modern history of informed consent and the role of key information," examined the history of informed consent in the United States. According to Bazzano et al. (2021), the history of informed consent begins with four court cases in the early twentieth century:

The concept of informed consent has a relatively short history, beginning with a series of 4 judicial decisions in the early 20th century that laid the foundation for the principle of patient autonomy. These legal decisions began in 1905, with the cases of Mohr v Williams and Pratt v Davis. Subsequently, 2 additional cases, Rolater v Strain and Schloendorff v Society of New York Hospital, established and solidified the principle of patient autonomy that ultimately formed the basis of the requirement for informed consent in medicine and research.

The first case mentioned above, Mohr v. Williams, dealt with the plaintiff consenting to an operation on her right ear, but, after anesthetized, the physician altered the plan and operated on the left ear, impacting her hearing. The Supreme Court of Minnesota determined that "the surgeon should have obtained consent before performing surgery on the opposite ear" (Bazzano et al. 2021). In the second case, Pratt v Davis, the physician had obtained consent for a particular operation but not for a second procedure, a hysterectomy. The surgeon admitted intentionally misleading the patient, but claimed she was not competent to give her consent due to her suffering from epilepsy. The 1905 Illinois appellate decision was also in favor of the patient. In the third case mentioned above, Rolater v Strain, the surgeon removed a bone from the patient's foot during an operation intended for another purpose. The patient had given consent for only the original purpose and had stated her wish that the surgeon not remove any bones of her foot. The Supreme Court of Oklahoma ruled in favor of the plaintiff (the patient) because the surgeon "had not performed the procedure in the manner agreed upon between the physician and patient" (Bazzano et al. 2021). The final case was the 1914 case of Scholendorff v Society of New York Hospital. The patient had been subjected to a hysterectomy without her consent and had "explicitly stated her wish not to undergo surgery." The judge found for the plaintiff, stating, "Every human being of adult years and sound mind has a right to determine what shall be done with his own body; and a surgeon who performs an operation without his patient's consent commits an assault, for which he is liable in damages" (Bazzano et al. 2021).

In 1931 in Germany, the Reich minister of the interior issued detailed "guidelines for new therapy and human experimentation" that addressed the concept of informed consent (Vollmann and Winau 1996). This Reich Circular on Human Experimentation of February 28, 1931, included the regulation that "innovative therapy may be carried out only after the subject or his legal representative has unambiguously consented to the procedure in light of relevant information provided in advance" (Weindling 2011).

Based on the 1931 Circular, Vollman and Winau (1996) note: "For the first time in history informed consent, the research process, and explicit clarification of personal responsibility for the experiment were required to be included in the medical record." Based on their review of German policy, Vollman and Winau (1996) concluded that "at the turn of the century informed consent was already a legal doctrine in medical experimentation in Germany, being based on "unambiguous consent" of the subject after "proper" information had been given by the doctor, including negative consequences and side effects," and "the basic concept of informed consent was developed long before the second world war and before Nazi crimes in Germany, not on the initiative of the medical profession or research community but as a legal doctrine by government authorities."

Bazzano et al. (2021) claim the term "informed consent" in the United States only became named and legally binding in 1957:

The principle of "informed consent" remained nameless and not legally binding until the term was first publicly recorded in the court documents for the 1957 case Salgo v Leland Stanford Jr University Board of Trustees.

This case had to do with the plaintiff undergoing a translumbar procedure that resulted in permanent paralysis of his lower limbs. The plaintiff sued on the basis that the potential risk had not been disclosed. The California appellate court ruled that "each physician must exercise practical insight in completely divulging potential procedure hazards and that physicians are liable for failing to disclose information that a patient would need to make an informed decision regarding medical procedures" (Bazzano et al. 2021). Bazzano et al. (2021) further claim that "this legal ruling was the first to identify and focus attention on the need to provide the patient with information about the potential benefits and the risks of any medical procedures."

However, there was a judges' verdict ten years earlier that garnered a great deal more public attention, and greater influence, regarding the importance of one of the elements of informed consent, that being voluntary consent. This was the verdict in August 1947 of the American judges of the International Military Trial in Nuremberg known as the Doctor's Trial. The Nuremberg Trials were a series of trials held in Nuremberg, Germany, after World War II, for individuals being charged as war criminals. The best known of these is the one held for major war criminals before the International Military Tribunal (IMT). The “Doctors’ Trial” was one of the subsequent ones held before an American military tribunal (U.S. Nuremberg Military Tribunal or NMT) under Control Council Law No. 10. The Doctors’ Trial involved twenty-three defendants, most of who were medical doctors and were being accused of criminal human experimentation. The trial began on December 9, 1946, and concluded on August 20, 1947.

One of the issues before the tribunal was what constituted acceptable medical experimentation involving human subjects. Some of the Nazi doctors argued that their experiments differed little from those conducted by American and German researchers in the past, and that there was no international law or even informal statements that differentiated illegal from legal human experimentation. For this reason, there was a need for the prosecution to demonstrate how the defendants' experiments had deviated from fundamental ethical principles that should govern research in civilized society. Two doctors who were working with the prosecution during the trial, Dr. Andrew Ivy and Dr. Leo Alexander, drew up six points delineating legitimate research principles, and they submitted this memorandum on April 17, 1947, to the U.S. Counsel for War Crimes. When the August 19, 1947, verdict was issued, these six points had been revised into ten points and issued as part of the verdict. These ten points became known as the Nuremberg Code (United States Holocaust Memorial Museum).

The very first of the ten principles of the Nuremberg Code dealt with a key aspect of informed consent:

1. The voluntary consent of the human subject is absolutely essential.

Another major development in terms of informed consent was the Declaration of Helsinki. This document outlines ethical principles for conducting medical research with human subjects. Originally adopted in Helsinki, Finland in June 1964, it has undergone several revisions, the most recent being the 2013 version. The Declaration of Helsinki is produced by the World Medical Association (WMA), an international body representing physicians since its founding in 1947.

The Declaration of Helsinki has an entire section, composed of eight separate numbered points (paragraphs 25 to 32), dealing with informed consent. It is the most extensive section of the Declaration, involving over one-quarter of the statement. Among topics treated are the voluntary consent of the research subjects, adequately informing the research subject regarding the research, issues of undue pressure to participate, and those subjects incapable of giving informed consent. Also included is informed consent in terms of "collection, storage and/or reuse" of "identifiable human material or data."

The following are some excerpts from this section:

• 25. Participation by individuals capable of giving informed consent as subjects in medical research must be voluntary...
• 26. .. each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest... anticipated benefits and potential risks...The potential subject must be informed of the right to refuse to participate in the study or to withdraw consent to participate at any time without reprisal...
• 28. For a potential research subject who is incapable of giving informed consent, the physician must seek informed consent from the legally authorized representative.

Another major cornerstone document is the Belmont Report. The Belmont Report was issued in 1978 by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report recognizes informed consent as deriving from its principle of respect for persons, stating, "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."

Standards for information to be conveyed

An individual's autonomy to actively decide whether or not to participate in a research study or allow a particular medical procedure or release of personal information is only one of the basic elements in informed consent. The other two elements are that the individual be presented with adequate information to make the decision and that the individual is able to comprehend the information presented. Various guidelines address these later two points.

The Belmont Report notes:

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.

The Declaration of Helsinki addresses this issue as follows:

• In medical research involving human subjects capable of giving informed consent, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail, post-study provisions and any other relevant aspects of the study. The potential subject must be informed of the right to refuse to participate in the study or to withdraw consent to participate at any time without reprisal. Special attention should be given to the specific information needs of individual potential subjects as well as to the methods used to deliver the information.
• After ensuring that the potential subject has understood the information, the physician or another appropriately qualified individual must then seek the potential subject’s freely-given informed consent, preferably in writing. If the consent cannot be expressed in writing, the non-written consent must be formally documented and witnessed.
• All medical research subjects should be given the option of being informed about the general outcome and results of the study.

One of the most thorough listing in terms of information to be conveyed is found in the U.S. Federal Policy, detailed below.

U.S. Federal Regulations on Informed Consent

The U.S. Federal Policy for the Protection of Human Subjects, or Common Rule, regulates the treatment of human subjects in research as adopted by numerous departments and agencies. This federal policy is codified in the Code of Federal Regulations (CFR), with each of the diverse departments/agencies utilizing identical language in its particular chapter of the CFR. For the HHS regulations, the Common Rule constitutes subpart A, 45 CFR, part 46.

The Code of Federal Regulations detail requirements for informed consent, including general requirements, essential elements of informed consents, documentation of informed consent, and obtaining waivers. For example, under general requirements for informed consent (46 CFR 46.116), it is noted that:

• Before involving a human subject in research covered by this policy, an investigator shall obtain the legally effective informed consent of the subject or the subject's legally authorized representative.
• An investigator shall seek informed consent only under circumstances that provide the prospective subject or the legally authorized representative sufficient opportunity to discuss and 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 legally authorized representative shall be in language understandable to the subject or the legally authorized representative.
• The prospective subject or the legally authorized representative must be provided with the information that a reasonable person would want to have in order to make an informed decision about whether to participate, and an opportunity to discuss that information.

Basic elements of informed consent

These federal regulations delineate eight essential elements of informed consent (which, since the first element has four points, yields fourteen items). These are listed below, with subtitles added in this article to facilitate organization. These are taken from 46 CFR 46.116 (b) Basic Elements of Informed Consent, and introduced as "in seeking informed consent the following information shall be provided to each subject or the legally authorized representative":

Research purpose, duration, basic procedures

(1) A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures that are experimental;

Reasonably foreseeable risks

(2) A description of any reasonably foreseeable risks or discomforts to the subject;

Potential benefits

(3) A description of any benefits to the subject or to others that may reasonably be expected from the research;

Alternative procedures/treatments

(4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;

Confidentiality

(5) A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;

Compensation and treatment of injury

(6) For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;

Contact information

(7) An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject;

Voluntary and right to withdraw without penalty

(8) A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.

There is a ninth required element of informed consent when dealing specifically with identifiable private information or identifiable biospecimens:

(9) One of the following statements about any research that involves the collection of identifiable private information or identifiable biospecimens:

(i) A statement that identifiers might be removed from the identifiable private information or identifiable biospecimens and that, after such removal, the information or biospecimens could be used for future research studies or distributed to another investigator for future research studies without additional informed consent from the subject or the legally authorized representative, if this might be a possibility; or

(ii) A statement that the subject's information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies.

Additional points

Section (c) of 46 CFR 46.116 adds some of the other "elements of information" that, "when appropriate, shall also be provided to each subject or the legally authorized representative." Below is are some of these points:

• A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) that are currently unforeseeable;

• Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's or the legally authorized representative's consent;

• Any additional costs to the subject that may result from participation in the research;

• The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;

• A statement that significant new findings developed during the course of the research that may relate to the subject's willingness to continue participation will be provided to the subject;

• A statement that the subject's biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit;

• A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions.

The Code of Federal Regulations also provides for cases where an Institutional Review Board (IRB) may waive the requirement for informed consent, such as projects conducted to evaluate a public benefit or service program, or the research involves no more than minimal risk to the subject and could not be practically carried out without the waiver. The Code also details the requirement that informed consent be documented and how it should be documented, but likewise notes conditions where this requirement can be waived, such as the documentation being the only record linking the subject and the research and would compromise confidentiality.

The Code of Federal Regulations also makes explicit that informed consent is not to include exculpatory language that would waive legal rights or liability for negligence.

No informed consent may include any exculpatory language through which the subject or the legally authorized 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.

Cases where patient/subject is incapable of giving informed consent

Informed consent requires that the subject/patient has the autonomy to be able to freely decide what to do and is able to comprehend the information given. However, there are cases where a potential subject/patient lacks one or both of these elements. As noted in the Belmont Report, "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." Examples of individuals with a diminished ability to consent include the immature (infants and young children) and prisoners, the first because of their intellectual development and legal status and the second because they have forfeited certain liberties. Others may be considered to have diminished autonomy if they lack the capacity to understand their situation well enough to decide whether or not to participate in a research study or undergo a medical procedure.

In the case of prisoners, the Belmont Report notes:

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.

Well-known codes of ethics uniformly agree that individuals with impaired or potentially compromised decision-making capacity (e.g., infants, young children, prisoners, mentally disabled patients, the comatose, etc.) deserve special protection to prevent exploitation and to make sure their best interests are advanced. The Belmont Report notes, "respect for the immature and the incapacitated may require protecting them as they mature or while they are incapacitated," and that this principle of respect for persons "includes the conviction that those individuals with diminished autonomy are to be accorded extra protection." A U.S. Department of Energy publication (CDOEIRB 2015, p. 34) notes that there needs to be "special additional protections for research involving prisoners who, because of their incarceration, may have a limited ability to make truly voluntary and uncoerced decisions about whether or not to participate as subjects in research."

However, the inclusion of such individuals in research or as candidates for medical procedures may be important, such as the need to surgically repair a damaged organ or testing of a treatment for a childhood disorder. How then can the requirement for informed consent be applied when the individuals lack the capacity to freely give their consent or understand the information provided?

Basically, informed consent for those with diminished capacity for consent requires that another individual, who is capable and has the best interests of the potential subject/patient in mind, provides the informed consent. Regarding research, Amdur and Bankert (2022) note that "conducting research based on the permission from someone other than the research subject is based on the concept of substituted judgement, which basically means that the person making the decision knows what the subject would want to do in that situation."

The Declaration of Helsinki, likewise, states:

• For a potential research subject who is incapable of giving informed consent, the physician must seek informed consent from the legally authorised representative. These individuals must not be included in a research study that has no likelihood of benefit for them unless it is intended to promote the health of the group represented by the potential subject, the research cannot instead be performed with persons capable of providing informed consent, and the research entails only minimal risk and minimal burden.
• Research involving subjects who are physically or mentally incapable of giving consent, for example, unconscious patients, may be done only if the physical or mental condition that prevents giving informed consent is a necessary characteristic of the research group. In such circumstances the physician must seek informed consent from the legally authorised representative. If no such representative is available and if the research cannot be delayed, the study may proceed without informed consent provided that the specific reasons for involving subjects with a condition that renders them unable to give informed consent have been stated in the research protocol and the study has been approved by a research ethics committee. Consent to remain in the research must be obtained as soon as possible from the subject or a legally authorised representative.

The Belmont Report similarly states:

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.

The U.S. Code of Federal Regulations defines this position as follows (45 CFR Part 46, Subpart A):

Legally authorized representative means an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject's participation in the procedure(s) involved in the research. If there is no applicable law addressing this issue, legally authorized representative means an individual recognized by institutional policy as acceptable for providing consent in the nonresearch context on behalf of the prospective subject to the subject's participation in the procedure(s) involved in the research.

The U.S. Code of Federal Regulations includes special sections for dealing with protections for pregnant woman, human fetus, neonates (subpart B), prisoners (subpart C), and children (subpart D).

See also

• Belmont Report
• Common Rule
• Declaration of Helsinki
• Human subject research
• Nuremberg Code
• Tuskegee Syphilis Study

References

ISBN links support NWE through referral fees

• Amdur, Robert J., and Elizabeth A. Bankert. 2022. Institutional Review Book: Member Handbook, 4th Edition. Burlington, MA: Jones & Bardett Learning.
• Bazzano, Lydia A., Jaquail Durant, and Paula Rhode Brantley. 2021. A modern history of informed consent and the role of key information. Ochsner Journal 21:81-85. Retrieved September 20, 2021.
• Hautala-Bateman, C., and L. White. May 14, 2019. Changes to the Common Rule. PowerPoint Presentation to the Central Department of Energy Institutional Review Board Meeting of May 14, 2019.
• National Commission for the Protection of Human Subjects of Biomedical and Behavior Research. April 18, 1979. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Retrieved July 23, 2021.
• The Nuremberg Code. From: Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10. Vol. 2, pp. 181-182. Washington, DC: U.S. Government Printing Office, 1949.
• United States Department of Energy, Central DOE Institutional Review Board (CDOEIRB). 2015. Standard Operating Procedure. December 2015. Department of Energy.
• United States Department of Health and Human Services (HHS). 2021a. Federal Policy for the Protection of Human Subjects ('Common Rule'). Retrieved July 23, 2021.
• United States Department of Health and Human Services (HHS), Office of the Assistant Secretary of Health, Office for Human Research Protections (HHS). 2021b. Subpart A of 45 CFR Part 46: Basic HHS Policy for Protection of Human Subjects. PDF version. Official HTML version Retrieved July 23, 2021.
• United States Holocaust Memorial Museum. n.d. Nuremberg Code. [United States Holocaust Memorial Museum note]. Retrieved July 25, 2021.
• Vollman, J., and R. Winau. 1996. Informed consent in human experimentation before the Nuremberg code. British Medical Journal 313(7070): 1445-9. PMID: 8973233
• Weindling, Paul J. 2011. The Nazi Medical Experiments. Chapter 2, pages 18-30 in Ezekiel J. Emanuel, Christine C. Grady, Robert A. Crouch, Reidar k. Lie, Franklin G. Miller, and David D Wendler (Eds.), The Oxford Textbook of Clinical Research Ethics. New York: Oxford University Press. ISBN: 9780199721665.
• World Medical Association (WMA). 2018. WMA Declaration of Helsinki - Ethical Principles For Medical Research Involving Human Subjects. Retrieved August 4, 2021.

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