Source: https://www.hhs.gov/ohrp/regulations-and-policy/guidance/faq/informed-consent/index.html
Timestamp: 2020-04-02 11:53:38
Document Index: 786916429

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Informed Consent FAQs | HHS.gov
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The HHS regulations at 45 CFR part 46 for the protection of human subjects in research require that an investigator obtain the legally effective informed consent of the subject or the subject’s legally authorized representative, unless (1) the research is exempt under 45 CFR 46.101(b); (2) the IRB finds and documents that informed consent can be waived (45 CFR 46.116(c) or (d)); or (3) the IRB finds and documents that the research meets the requirements of the HHS Secretarial waiver under 45 CFR 46.101(i) that permits a waiver of the general requirements for obtaining informed consent in a limited class of research in emergency settings. When informed consent is required, it must be sought prospectively, and documented to the extent required under HHS regulations at 45 CFR 46.117. [Food and Drug Administration (FDA) regulations at 21 CFR part 50 may also apply if the research involves a clinical investigation regulated by FDA.]
The requirement to obtain the legally effective informed consent of individuals before involving them in research is one of the central protections provided for under the HHS regulations at 45 CFR part 46. This requirement is founded on the principle of respect for persons, one of the three ethical principles governing human subjects research described in the Belmont Report. The principle of respect for persons requires that individuals be treated as autonomous agents and that the rights and welfare of persons with diminished autonomy be appropriately protected. The Belmont Report states that an autonomous agent is “an individual capable of deliberation about personal goals and of acting under the direction of such deliberation.” Respect for persons requires that prospective research subjects “be given the opportunity to choose what shall or shall not happen to them” and thus necessitates adequate standards for informed consent.
The informed consent process involves three key features: (1) disclosing to potential research subjects information needed to make an informed decision; (2) facilitating the understanding of what has been disclosed; and (3) promoting the voluntariness of the decision about whether or not to participate in the research. Informed consent must be legally effective and prospectively obtained. HHS regulations at 45 CFR 46.116 and 45 CFR 46.117 describe the informed consent requirements.
The informed consent process is the critical communication link between the prospective human subject and an investigator, beginning with the initial approach of an investigator to the potential subject (e.g., through a flyer, brochure, or any advertisement regarding the research study) and continuing until the completion of the research study. For the purposes of the HHS regulations at 45 CFR part 46, “investigators” are individuals who conduct human subjects research projects, including individuals directly involved in seeking the voluntary informed consent of potential subjects. Investigators can include physicians, scientists, nurses, administrative staff, teachers, and students, among others.
The informed consent process should be an active process of sharing information between the investigator and the prospective subject. The exchange of information between the investigator and prospective subjects can occur via one or more of the following modes of communication, among others: face-to-face contact; mail; telephone; video; or fax. Prospective subjects should be provided with ample opportunity to ask questions and seek clarification from the investigator. The prospective subjects should be in a position to freely decide whether to initially enroll in the research, or later, to withdraw or continue participating in the research. The informed consent process should ensure that all critical information about a study is completely disclosed, and that prospective subjects or their legally authorized representatives adequately understand the research so that they can make informed choices.
The procedures used in seeking and obtaining informed consent should be designed to communicate with the subject population in terms that they can understand. Information about a research project must be presented in such a way that enables each person to voluntarily decide whether or not to participate as a research subject. Thus, the information must be conveyed in language understandable to those being asked to participate as subjects in the research (45 CFR 46.116).
The consent process and its documentation should be revised when deficiencies in its accuracy or completeness are noted, when new information about reasonably foreseeable risks and potential benefits becomes available, or when other additional information becomes known that will improve the consent process. Such revisions must be reviewed and approved by an IRB prior to the revised consent being utilized except when necessary to eliminate apparent immediate hazards to subjects (45 CFR 46.103(b)(4)).
Is it possible to obtain legally effective informed consent to research in an urgent or emergency care setting?
Yes, in certain circumstances it is possible to obtain legally effective informed consent in an urgent or emergency care setting. For a particular research study, the answer depends on (1) the expected medical condition of the prospective subject population; (2) the nature of the research; (3) whether there is sufficient time for the potential subjects or their legally authorized representatives to consider participation; and (4) whether the circumstances for obtaining informed consent appropriately minimize the possibility of coercion or undue influence. The Institutional Review Board (IRB) and investigator(s) would have to consider several variables. For example, what is the likely health and emotional condition of the patient population being considered for the proposed research (e.g., conscious but receiving emergency care, undergoing preparation prior to surgery)? What is the likely ability of this population during the consent process to process information, ask questions, and consider the risk involved? What is the timing of the consent process and is it so close to the receipt of care that the patient might blur the distinction between treatment and research?
Because individuals receiving urgent or emergent medical care frequently may be vulnerable to coercion or undue influence, even if temporarily, additional protections may be required to ensure the subject's consent to participate in research is truly voluntary and sought under circumstances that minimize the possibility of coercion or undue influence (45 CFR 46.111(b), (45 CFR 46.116). In addition, in some cases, it might be possible to obtain consent from a legally authorized representative (e.g., in the case of decisionally incapacitated individuals). In certain emergency circumstances, the Secretarial waiver of informed consent under 45 CFR 46.101(i) may be applicable. It should be noted that if the research is regulated by FDA, the Secretarial waiver permits the research to be conducted under a comparable provision.
See the Office for Human Research Protections' (OHRP) guidance; and HHS policy (PDF - 22KB).
The basic required elements of informed consent can be found in the HHS regulations at 45 CFR 46.116(a). Also see OHRP Informed Consent Tips.
Additional elements are described at 45 CFR 46.116(b)
What additional information might be appropriate to provide during the consent process?
When determined to be appropriate by the Institutional Review Board (IRB), subjects must be provided with one or more of the following additional elements of information during the informed consent process (see 45 CFR 46.116(b)):
It is up to the IRB to determine in a particular instance whether some or all of the above additional elements must be included as part of the informed consent process for a particular study. The IRB should make this determination based on the nature of the research and its knowledge of the local research context. If the IRB determines that additional elements are appropriate to the research study, this additional information should be considered just as essential as the eight basic elements of informed consent described in the HHS regulations at 45 CFR 46.116(a).
Furthermore, an IRB may require that additional information beyond the basic and additional elements be given to subjects during the informed consent process, when in the IRB’s judgment the additional information would meaningfully add to the protection of the rights and welfare of the subjects 45 CFR 46.109(b).
Can consent or parental permission ever be "passive" or "implied?"
Terms such as “passive” or “implied” consent are not referenced in the HHS regulations. However, OHRP is aware that these terms are sometimes used by investigators or IRBs to describe a process in which consent or parental permission requirements have been altered or waived, or for which the requirement to document consent or parental permission has been waived.
HHS regulations at 45 CFR 46.116 state that no investigator may involve a human being as a subject unless the investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative. However, under conditions specified in the regulations at 45 CFR 46.116(c) or (d) an IRB may approve a consent procedure that does not include, or that alters some or all of the elements of informed consent set forth in 45 CFR 46.116. In some cases, an IRB also can waive the requirement to obtain consent (45 CFR 46.116(c) and (d)). In addition, under conditions specified in the regulations at 45 CFR 46.117, an IRB may also waive the requirement for documentation of informed consent. (Note that the regulations at 45 CFR 46.408(c) also permit an IRB to waive parental permission.)
For example, a researcher conducting a survey (that does not qualify for an exemption under 45 CFR 46.101(b) mails a survey questionnaire to a random sample of adults. The survey materials clearly state that by responding to the questions and mailing the survey back, the recipients have agreed to participate in the research. However, the materials accompanying the questionnaire do not include all of the elements of consent listed at 45 CFR 46.116(a) and do not require that the subject sign a consent form. If the IRB has approved this alteration of the consent process and has waived the need for documentation of consent, then such procedures are permissible under the regulations. By sending back a completed survey the recipient has implied that he or she consents to participate but has not signed an informed consent document. Although some might call this “implied informed consent,” OHRP would consider this to be a permissible informed consent process if the IRB has approved the informed consent alteration and waived the requirement for documentation of informed consent.
The term “passive consent” is sometimes used in research with children to describe situations in which the investigator can assume that a parent is permitting a child to participate. For example, researchers collecting survey and behavioral data from children at school provide parents with information regarding the study by mail and ask the parent(s) to return a form if they do not want their child to participate. Sometimes this practice is referred to as an opt out procedure, which is not consistent with the regulatory requirement for seeking and obtaining parental permission. If the IRB determines that the conditions for waiver of parental permission can be met, then the IRB could waive the requirement for parental permission under 45 CFR 46.408(c) or 45 CFR 46.116(c) or (d). Even though not required by the regulations, an IRB may require that parents be given the opportunity to refuse permission even when the IRB has waived the regulatory requirement to obtain parental permission.
Paying research subjects in exchange for their participation is a common and, in general, acceptable practice. However, difficult questions must be addressed by the IRB. For example, how much money should research subjects receive, and for what should subjects receive payment -- their time, inconvenience, discomfort, or some other consideration -- IRBs must be sensitive to whether any aspect of the proposed remuneration will be an undue influence, thus interfering with the potential subjects’ ability to give voluntary informed consent.
Remuneration for participation in research should be just and fair. However, the specifics of each protocol will influence how those determinations are made. Both researchers and IRBs need to be familiar with the study population and the context of the research in order to make reasonable judgments about how compensation might affect participation. Wherever the remuneration is set, it will influence the decisions of some more than others. In particular, it will be more important to those for whom it will make a significant financial difference. Thus, IRBs should be cautious that payments are not so high that they create an “undue influence” or offer undue inducement that could compromise a prospective subject’s examination and evaluation of the risks or affect the voluntariness of his or her choices.
Information submitted to IRBs should indicate and justify proposed levels and purposes of remuneration, which also should be clearly stated in the accompanying consent forms.
The above principles would apply to remuneration offered to parents whose children are prospective subjects.
[Note: The previous version of the response to this FAQ included the following sentences. “In no case should remuneration be viewed as a way of offsetting risks; that is, it should not be considered a benefit to be weighed against study risks. The level of remuneration should not be so high as to cause a prospective subject to accept risks that he or she would not accept in the absence of the remuneration.” The first sentence has been struck because this FAQ focuses on potential undue influence in the consent process (45 CFR 46.116) rather than on IRB considerations under 45 CFR 46.111. However, OHRP continues to assert that IRBs should not consider remuneration as a way of offsetting risks. The second sentence has been deleted to clarify that remuneration to subjects may include compensation for risks associated with their participation in research and that compensation may be an acceptable motive for agreeing to participate in research. In addition, the previous version contained the following sentence, which has been struck because it is focused on IRB considerations under 45 CFR 46. 111 rather than informed consent, and was misplaced in this FAQ: “IRBs may need to request of the investigator some plan for monitoring subject recruitment to ensure that such inducements do not result in inequitable subject recruitment (e.g., recruiting only economically disadvantaged individuals).”]
The regulations require that the investigator seek consent only under circumstances that minimize the possibility of coercion or undue influence (45 CFR 46.116). The Office for Human Research Protections (OHRP) recommends that institutions have policies in place that clarify for students and faculty that any participation of students in research must be voluntary. Reasonable levels of extra credit or rewards may be offered for participating in research. If extra credit or rewards are offered for participation, students must be provided with and informed of non-research alternatives involving comparable time and effort to obtain the extra credit in order for the possibility of undue influence to be minimized. However, if participation in research is a course requirement, students must be informed of non-research alternatives involving comparable time and effort to fulfill those requirements in order for the possibility of undue influence to be minimized. Moreover, students must not be penalized for refusing to participate in research (45 CFR 46.116(a)(8)).
In addition, some research institutions use a so-called “student subject pool” to identify students who might be willing to participate in research, even when the exact nature of the research to be conducted has not yet been determined. Extra credits or other rewards are often offered as an incentive to encourage participation. Students who sign up for such pools have not legally consented to participate in a research study since they have not been provided with sufficient information concerning the exact study in which they would participate. Thus, signing up to be in a subject pool is only a first and preliminary step by which individuals can indicate their willingness to be considered for research participation. The student must also provide informed consent, unless the consent requirement is waived by an IRB once he or she is being considered for a specific study (45 CFR 46.116). Furthermore, individuals in the pool must be free to decline participation in any available research projects without penalty (45 CFR 46.116(a)(8)).
The issues involving employees as research subjects are essentially identical to those involving students as research subjects: that is, investigators and IRBs must be cautious about the potential for coercion or undue influence and the need to protect confidentiality.
Employee participation raises questions about the ability of employees to exercise free choice, for example, because of the possibility that a decision to participate could affect performance evaluations or job advancement, even if it is only the employee’s perception that this is the case. In the case of coercion, refusal to participate might result in a loss of benefits (e.g., salary increases, time off). In the case of undue influence, a decision to participate could result in a job promotion. Employees are likely to view their employers as authority figures to whom they must show deference, which could undermine the freedom of their choice.
Should the initial consent or parental permission procedure ever be repeated or supplemented?
Yes, in some circumstances. The HHS regulations require that an investigator obtain legally effective informed consent from subjects or a legally authorized representative before the subjects may be involved in research (45 CFR 46.116), unless this requirement has been waived by an IRB. Likewise, for research involving children, permission of the potential subjects' parents or guardians must be obtained (45 CFR46.408(c)), unless an IRB has waived this requirement. Ensuring an adequate consent or parental permission process may require repeating or supplementing the initial consent procedure. The regulations also stipulate that “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 minimizes the possibility of coercion or undue influence” (45 CFR 46.116). This requirement also might necessitate repeating or supplementing the initial consent procedure.
Informed consent and parental permission should be viewed as an ongoing process. The regulations do not explicitly describe all of the circumstances that might require repeating or supplementing the informed consent process. However, they do require that potential subjects be provided, when appropriate, with a “statement that significant new findings developed during the course of the research which may relate to the subject’s willingness to continue participation will be provided to the subject” (45 CFR 46.116(b)(5)). Thus, to ensure that consent remains legally effective -- for example, if the protocol design or risks have changed, or if a substantial period of time has elapsed between the time consent was obtained and the study begins -- it might be necessary to ensure that subjects still want to participate in the research. For example, the prospective subject may no longer be interested in participating, may no longer meet the eligibility criteria, may no longer find the risks acceptable, or may no longer have the time to complete all study-related activities.
The IRB must review and approve any changes in the approved consent procedure, including alterations of the content, as described in the elements listed at 45 CFR 46.116, or in its timing, and may consider whether there is a need to reiterate the process (45 CFR 46.103(b)(4)). The IRB should take into account whether the changes could potentially affect a subject’s understanding of the nature of the study or potentially affect a subject’s willingness to participate. If so, such changes need to be made in the informed consent document. Even without significant changes to a protocol or informed consent document, periodic reiteration or affirmation of consent is often a good idea, especially if the study takes place over a long period of time or is particularly complex. Minor changes, such as correcting nonsubstantive typographical errors in the consent document, would not generally rise to a level requiring repeating the consent process.
How far in advance of research participation can consent be obtained?
The HHS regulations at 45 CFR part 46 do not specify how far in advance of study entry a subject can provide consent. The amount of time required by a subject to make a decision would presumably depend on the nature of the study, taking into account, among other factors, the degree of risk, potential benefits, alternatives, and desire to consult with family members or others. However, if a prolonged period of time elapses from the date of consent to the date of entry into the study even if there have been no changes in the study design or no new significant findings affecting the study it might be prudent to review the information contained in the consent form with the subject prior to initiating any research procedures with the subject.
How can the consent and parental permission processes be designed to facilitate understanding?
The procedures used in obtaining informed consent and parental permission should be designed to inform the subject population or the parents of the subject population about the research in terms that they can understand. Therefore, informed consent and parental permission language and its documentation in the accompanying forms (especially explanation of the study’s purpose, duration, experimental procedures, alternatives, risks, and benefits) should be provided in language that is understandable and culturally sensitive to those being asked to participate or provide permission for their child’s participation.
If the prospective subjects include, for example, persons whose primary language is not English, or populations with low literacy levels, the IRB should take special care to ensure that both oral presentations and consent or permission forms are comprehensible to all subjects or the parents of subjects who are children. Subjects who do not speak English should be presented with a consent or permission document written in a language understandable to them. OHRP strongly encourages the use of such a document whenever possible. (See OHRP guidance on this topic at http://www.hhs.gov/ohrp/regulations-and-policy/guidance/obtaining-and-documenting-infomed-consent-non-english-speakers/index.html; for information about requirements for child assent, see FAQs regarding research with children.)
In general, ordinary language should replace technical terms (e.g., upper extremities are better referred to as arms, venipuncture as taking blood from your arm with a needle, and so forth).
Some IRBs find that their lay members (e.g., community or non-scientist members) are particularly helpful in suggesting necessary modifications to language. Others ask members of the proposed subject population (e.g., clinic patients) to review consent or permission forms and indicate which parts they do not understand.
Yes, if it is more convenient for the subjects or parents of children who are subjects to fax a signed copy of the consent or permission form to the investigator, the research subjects or parents may fax the signed form. The subjects or parents need not provide the investigator with the original signed consent or parental permission documents.
Who must sign the informed consent or parental permission document?
When a written consent or parental permission form is used that embodies some or all of the elements of informed consent required by the regulations at 45 CFR 46.116, the regulations only require that the informed consent or parental permission document be signed by the subjects or the subjects' legally authorized representatives or by the parents of children who are subjects (45 CFR 46.117(a)) and 45 CFR 46.408(d)). Only in situations where a short form is used, stating that the elements of informed consent required by 45 CFR 46.116 have been presented orally to the subject or the subject’s legally authorized representative or to the parent(s) of a child who is a subject, are there additional requirements for signatures (45 CFR 46.117(b)(2)).
For the consent or parental permission process using the short form, the regulations state that there must be a witness to the oral presentation, who then signs both the short form and a copy of the IRB-approved written summary of what is to be said to the subject or the subject's legally authorized representative or to the parent(s) of a child who is a subject. The subject or the subject’s legally authorized representative or the parent(s) must sign the short form, and the person actually obtaining the consent must sign the copy of the summary (45 CFR 46.117(b)(2)). Thus, three types of persons are involved in this specific consent process -- the subject or legally authorized representative or parent(s) of a child who is a subject, the person obtaining consent, and the witness.
Do signatures on consent forms have to be dated?
Although the HHS regulations at 45 CFR 46.117 do not require the consent form to be dated at the time it is signed, OHRP recommends that it be dated so that the IRB and others can document that informed consent was obtained prior to a subject’s participation in the research.
Who can be a legally authorized representative (LAR) for the purpose of providing consent on behalf of a prospective subject?
Legally authorized representative (LAR) 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 (45 CFR 46.102(c)). The regulations state that “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” (45 CFR 46.116). The issue as to who can be an LAR is determined by the laws of the jurisdiction in which the research is conducted (e.g., local or state law). Some states have statutes, regulations, or common law that specifically address consent by someone other than the subject for participation in research. Most states have no law specifically addressing the issue of consent in the research context. In these states, law that addresses who is authorized to give consent on behalf of another person to specific medical procedures or generally to medical treatment may be relevant if the research involves those medical procedures or medical treatment.
When the laws of the jurisdiction in which the research is being conducted provide a reasonable basis for authorizing an individual to consent on behalf of a prospective subject to their participation in the research procedure(s), OHRP would consider such an individual to be an LAR as defined by HHS regulations at 45 CFR 46.102(c). IRBs may wish to consult with legal counsel when deciding who can serve as an LAR for subjects of proposed research.
In answering this question, the HHS regulations at 45 CFR part 46 should be consulted in addition to the laws of the jurisdiction in which the research is conducted. As a general matter, if an adult lacks capacity to consent, for example, as a result of trauma, mental retardation, some forms of mental illness, or dementia - whether temporary, progressive, or permanent - only a legally authorized representative for that adult can give consent for participation in the research, unless the requirement to obtain informed consent is waived by the IRB in accordance with the requirements at 45 CFR 46.116(c)(d), or in accordance with the provisions for emergency waiver, which are permitted under the authority of the HHS Secretary at 45 CFR 46.101(i).
(See the Federal Register notice of this waiver.) Should the subject regain or develop the capacity to consent, then his or her consent must be obtained for any further research, as the consent of the legally authorized representative is no longer valid.
The HHS regulations are silent on the consent procedures specific to subjects with impaired decision-making capacity, for example, as a result of trauma, mental retardation, some forms of mental illness, or dementia, whether temporary, progressive, or permanent. The regulations do require that the IRB ensure that “additional safeguards have been included in the study to protect the rights and welfare” of all subjects that are “likely to be vulnerable to coercion or undue influence.” The regulations include “mentally disabled persons” in this category (45 CFR 46.111(b)).
In research involving adult subjects with mental illnesses or cognitive impairments, the IRB and investigator(s) must be knowledgeable about the condition and any level of impairment that is likely to be present in the subject population. The regulations do speak to the fact that the IRB must possess “the professional competence necessary to review specific research activities” (45 CFR 46.107(a)). This is achieved either by having members with the appropriate experience and expertise or inviting consultants with competence in the special area to assist in the review of issues that require expertise beyond or in addition to that available on the IRB (45 CFR 46.107(a) and (f)). Ensuring such expertise on the IRB improves its ability to make determinations about subject recruitment, enrollment, and informed consent requirements that best match the needs of the subjects.
In some research, such as longitudinal studies involving progressive disorders or aging populations, enrolled subjects may be competent to consent on their own behalf at the outset, yet may experience effects of progressive or intermittent disorders that lead to decisional impairment during the course of the study. In these situations IRBs and investigators should consider the need to discuss with the prospective subjects whether they should designate someone to serve as a legally authorized representative at the outset of the study, consistent with all applicable laws. Even if a subject has consented on his or her own accord, a designated representative would be ready to step in as the legally authorized representative if the subject’s ability to assess his or her own needs and interests becomes compromised during the study.
May the requirement for obtaining informed consent or parental permission be altered or waived?
Waiver or alteration of the requirements for obtaining informed consent from adult subjects can occur under any of the following three provisions:
Research in emergency settings: an IRB may also waive the requirement for obtaining informed consent if it finds and documents that the research meets the requirements of the HHS Secretarial waiver under 45 CFR 46.101(i) that permits a waiver of the general requirements for obtaining informed consent in a limited class of research in emergency settings (PDF) (23KB).
For research involving children, an IRB may waive the requirements for obtaining parental or guardian permission under any of the following four provisions:
The IRB makes and documents the required findings under 45 CFR 46.116(c) as described above.
The IRB makes and documents the required findings under 45 CFR 46.116(d) as described above.
The IRB finds and documents that the research meets the requirements of the HHS Secretarial waiver under 45 CFR 46.101(i) that permits a waiver of the general requirements for obtaining informed consent in a limited class of research in emergency settings (PDF) (23KB).
What is the definition of guardian in the context of obtaining consent for research involving children?
The term guardian means “an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care” (45 CFR 46.402(e)) The role of a guardian in the context of research involving a child who is a ward is to provide permission, in lieu of a child’s biological or adoptive parents, for the ward to participate in the research (45 CFR 46.402(c)). For a more extensive discussion see FAQs on Research with Children.
What are the regulatory bases for waiving or altering some or all of the required elements of informed consent or parental permission?
At 45 CFR 46.116(c), the regulations identify when IRBs may waive or approve an alteration of informed consent in some research examining state or local public benefit or service programs, or certain features of those programs.
At 45 CFR 46.116(d) the regulations identify when IRBs may waive or approve an alteration of informed consent in research that meets four specified criteria.
At 45 CFR 46.408(c), the regulations identify when IRBs may approve waiver of parental permission in certain research involving children.
Under the provisions of 45 CFR 46.101(i), the Secretary, HHS, has waived the general requirements for obtaining informed consent in a limited class of research in emergency settings.
What are the criteria under 45 CFR 46.116(c) for waiving or altering some or all of the required elements of informed consent or parental permission?
Under 45 CFR 46.116(c), an IRB may waive the requirement for obtaining informed consent or parental permission or approve a consent or parental permission procedure that leaves out or alters some or all of the elements of informed consent, provided that the IRB finds and documents that the following two criteria are satisfied:
possible changes in methods or levels of payment for benefits or services under those programs; 45 CFR 46.116(c)(1).
Note that this criterion means that only public benefit or service program research activities that are under state or local authority meet this criterion; similar research conducted under federal authority would not qualify here and is treated elsewhere in the regulations. Research conducted by or subject to the approval of only a private entity also would not qualify.
the research could not practicably be carried out without the waiver or alteration (45 CFR 46.116(c)(2)).
This criterion means that the practical circumstances of the research are such that the research is not feasible if the informed consent of the subjects must be obtained. For example, a study of identifiable private information about program benefit recipients using 20-year-old records might meet this criterion, if current contact information for those recipients is not available.
What are the criteria under 45 CFR 46.116(d) for waiving or altering some or all of the required elements of informed consent or parental permission?
Is it possible to waive the informed consent requirement when conducting research in an emergency setting?
In 1996, the HHS Secretary announced, under 45 CFR 46.101(i), a waiver of the applicability of the regulatory requirement for obtaining and documenting informed consent for a strictly limited class of research, that is, research that may be carried out in human subjects who are in need of emergency therapy and for whom, because of the subjects’ medical condition and the unavailability of legally authorized representatives of the subjects, no legally effective informed consent can be obtained. This waiver applies to research involving adults or children, but does not apply to research involving pregnant women, human fetuses, neonates of uncertain viability, and nonviable neonates, or prisoners.
For more detailed information, see OHRP’s guidance on Emergency Research Consent Waiver. It should be noted that FDA also has a comparable provision for a waiver of informed consent for emergency research at 21 CFR 50.24.
When an Institutional Review Board (IRB) has not waived the requirement for seeking prospective informed consent of the subjects or the parental permission of children who are subjects, under the HHS regulations at 45 CFR 46.117(c), it may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either:
Some subjects might refuse a copy of the consent form once signed out of concern that their possession of the form could compromise their privacy. This is fully consistent with the idea behind one of the bases for a waiver of the requirements for documentation of informed consent - that harm would result to the subject if his/her identity were compromised by the documentation itself. The investigator may document that the subject refused a copy of the informed consent document and still include the subject in the study.
Can parental or guardian permission for research involving children be waived?
Yes, under certain circumstances. An IRB may waive the requirements for obtaining parental or guardian permission if either of the following two conditions is met:
The IRB makes and documents the required findings under either 45 CFR 46.116(c) or (d); or
The choice of an appropriate substitute mechanism (for example, appointing a child advocate or an assent monitor) for protecting children participating in research would depend on the nature and purpose of the activities described in the protocol, the risk and anticipated benefit to the research subjects, and the child’s age, maturity, status, and condition (45 CFR 46.408(c)).
Note that an IRB may waive the requirement for obtaining parental or guardian permission under 45 CFR 46.408(c) even if the research involves more than minimal risk to the child subjects.
Is child assent always required when research involves children?
No, the IRB is responsible for deciding whether child assent is required in proposed research activities. Assent means a child’s affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent (45 CFR 46.402(b)). Child assent is required, except in the following three circumstances described at 45 CFR 46.408(a):
How should child assent be documented?
The HHS regulations do not require documentation of assent. The IRB has the discretion to determine the appropriate manner, if any, of documenting child assent. Based on such considerations as the child’s age, maturity, and degree of literacy, the IRB should decide what form of documentation, if any, is most appropriate. If adolescents are involved in research where a consent form would have been used if the subjects were adults, it would generally be appropriate to use a similar form to document an adolescent’s assent.
If young children are involved who are as yet unable to read, documentation should take a form that is appropriate for the purpose of recording that assent took place. The IRB may also decide that documentation of assent is not warranted.
What is the meaning of "legally effective informed consent?"