Informed Consent Requirements

THESE CHANGES APPLY TO NON-EXEMPT RESEARCH.

Some of the most substantial changes with the revised Common Rule involve the informed consent process.

General Requirements for Informed Consent

  • General Requirements for Informed Consent

    "General. 

    General requirements for informed consent, whether written or oral, are set forth in this paragraph and apply to consent obtained in accordance with the requirements set forth in paragraphs (b) through (d) of this section. Broad consent may be obtained in lieu of informed consent obtained in accordance with paragraphs (b) and (c) of this section only with respect to the storage, maintenance, and secondary research uses of identifiable private information and identifiable biospecimens. Waiver or alteration of consent in research involving public benefit and service programs conducted by or subject to the approval of state or local officials is described in paragraph (e) of this section. General waiver or alteration of informed consent is described in paragraph (f) of this section. Except as provided elsewhere in this policy:

    (1) 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.

    (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) Except for broad consent obtained in accordance with paragraph (d) of this section:

    (i) 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.

    (ii) Informed consent as a whole must present information in sufficient detail relating to the research, and must be organized and presented in a way that does not merely provide lists of isolated facts, but rather facilitates the prospective subject's or legally authorized representative's understanding of the reasons why one might or might not want to participate.

    (6) 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." 45 CFR 46.116(a)(2018 requirements)

  • Summary of Changes

    The revised Common Rule include clarifying changes:

    • Alter the structure of this section so that the requirements are numbered.
    • Add a summary of the provisions added.
    • Include slight revisions to clarify existing requirements.
    • Clarify that all of the general requirements apply to written or oral consent.

     

    There are also substantive changes:

    • Emphasize the requirement that subjects be given an opportunity to discuss the informed consent.
    • New requirement that information that a reasonable person would want must be provided.
    • New requirement that the informed consent begin with a concise and focused presentation of key information.
    • New requirement on how consent as a whole must be presented.

     

    The following section provide more detailed information about the substantive changes.

  • More Information About Providing Sufficient Opportunity to Discuss and Consider

    Regulatory Text

    "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." 45 CFR 46.116(a)(2)(2018 requirements)

    More Information

    • This requirement was revised to add the requirement that a subject be given sufficient opportunity to discuss whether or not to participate.
    • Consider including a question after the summary that asks subjects if they have any questions or what are their concerns.
  • More Information About Providing Information that a Reasonable Person Would Want

    Regulatory Text

    "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." 45 CFR 46.116(a)(4)

    More Information

    • This requirement is new and requires that the subject or legally authorized representative must be provided with information that a reasonable person would want to have in order to make an informed decision about whether to participate.
    • The requirement also adds the requirement that the subject must have an opportunity to discuss that information.
  • More Information About Providing a Concise and Focused Presentation of Key Information

    Regulatory Text

    "Except for broad consent obtained in accordance with paragraph (d) of this section:

    (i) 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.

    (ii) Informed consent as a whole must present information in sufficient detail relating to the research, and must be organized and presented in a way that does not merely provide lists of isolated facts, but rather facilitates the prospective subject's or legally authorized representative's understanding of the reasons why one might or might not want to participate." 45 CFR 46.116(a)(5)(2018 requirements)

    More Information

    Content

    In general, the beginning of an informed consent would include a concise and brief explanation of the following:

    1. The fact that consent is being sought for research and that participation is voluntary;
    2. The purposes of the research, the expected duration of the prospective subject’s participation, and the procedures to be followed in the research;
    3. Any reasonably foreseeable risks or discomforts to the prospective subject;
    4. Any benefits to the prospective subject or to others that may reasonably be expected from the research; and
    5. Appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the prospective subject.

     

    As a general matter, a brief description of these five factors would encompass the key information most likely to assist a reasonable person (or legally authorized representative) in understanding the reasons why one might or might not want to participate in research.

    This section of the consent could, in appropriate circumstances, include a summary of relevant pieces of information that are explained in greater detail later in the consent form.

    NOTE: this determination by the IRB is necessarily project and fact specific; the IRBs may require that somewhat different (or additional) information be presented at the beginning of an informed consent to satisfy the requirement for a concise and focused presentation of key information.

    Length and Format

    The initial presentation of the key pieces of information must be relatively short.

    While lists and charts may be used to facilitate comprehension and understanding, the informed consent must be organized and presented in a way that does not merely provide lists of isolated facts, but rather facilitates the prospective subject's or legally authorized representative's understanding of the reasons why one might or might not want to participate.

    Repetition of Information

    If information is included at the beginning of the informed consent, the information included at the beginning typically need not be repeated later in the body of the informed consent.

    Relatively Simple Studies

    For some relatively simple research studies with limited risks or benefits, the entire informed consent document may be relatively brief and still satisfy the informed consent requirements. The informed consent document could include the concise and focused presentation at the beginning of the informed consent document, followed by limited additional information.

    Complicated Clinical Trials Studies

    For most complicated clinical trials involving cancer patients with long (e.g., 20- to 25- page) consent documents, the expectation is that the concise and focused presentation would be no more than a few pages, and would provide the key pieces of information about the trial in such a manner that facilitates a person’s comprehension of why they might or might not want to participate in the research. In such cases, for example, would not consider a 10-page description of elements such as potential risks, accompanied by lengthy and complex charts and graphs, to satisfy the ‘‘concise and focused’’ requirement.

    With regard to risks in the type of cancer trial mentioned above, for example, instead of needing to mention every reasonably foreseeable risk in the summary, this beginning section of the consent form should identify the most important risks, similar to the information that a doctor might deliver in the clinical context in telling a patient how sick the chemotherapy drugs will make them, but with a particular emphasis on how those risks are changed by participating in the study.

    The most important reasonably foreseeable risks to subjects would be summarized at the beginning of the informed consent as part of the concise and focused presentation, but a more comprehensive and detailed description of reasonably foreseeable risks to subjects would be included later in the body of the informed consent.

    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. Consider including a question after the summary that asks subjects if they have any questions or what are their concerns.

A guidance document for the concise and focused presentation of key information is available on the Consent Templates webpage.

New Elements of Informed Consent

  • New Elements of Informed Consent

    Basic elements of informed consent. 

    "Except as provided in paragraph (d), (e), or (f) of this section, in seeking informed consent the following information shall be provided to each subject or the legally authorized representative:

    (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." 45 CFR 46.116(b)(2018 requirements)

    Additional elements of informed consent. 

    "Except as provided in paragraph (d), (e), or (f) of this section, one or more of the following elements of information, when appropriate, shall also be provided to each subject or the legally authorized representative:

    (7) 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;

    (8) A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions; and

    (9) For research involving biospecimens, whether the research will (if known) or might include whole genome sequencing (i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen)." 45 CFR 46.116(c)(2018 requirements)

  • Summary of Changes

    One new basic element of consent is now required for any research that involves the collection of identifiable private information or identifiable biospecimens. The new element requires disclosure about the possibility of future research.

    Three new additional elements of consent have been added. Two new elements require additional information be provided to subjects when the research involves biospecimens, and the other new element of consent requires that additional information be provided when the research may involve clinically relevant research results.

    See the following sections for more information.

  • More Information about Informed Consent Element: Research Involves Collection of Identifiable Private Information or Identifiable Biospecimens

    Regulatory Text

    (b) Basic elements of informed consent. Except as provided in paragraph (d), (e), or (f) of this section, in seeking informed consent the following information shall be provided to each subject or the legally authorized representative:

    (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.

    More Information

    One of the two statements above must now be included in consent documents when research involves the collection of identifiable private information or identifiable biospecimens. This requires researchers inform potential subjects about the possible use of their identifiable information.

    If a specific technology or technique determined to be capable of generating identifiable private information or identifiable biospecimens will be used, that information should be included in the description of the research procedures to be followed.

  • More Information About Additional Element of Consent: Research Involving Biospecimens

    Regulatory Text

    "Additional elements of informed consent. Except as provided in paragraph (d), (e), or (f) of this section, one or more of the following elements of information, when appropriate, shall also be provided to each subject or the legally authorized representative:

    (7) 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;

    (9) For research involving biospecimens, whether the research will (if known) or might include whole genome sequencing (i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen)." 45 CFR 46.116(c)

    More Information

    Commercial Profit

    Investigators, when appropriate, should inform prospective subjects about whether they might or might not benefit commercially from future products resulting from the research.

    Whole Genome Sequencing

    Given the unique implications of the information that can be developed through whole genome sequencing, if it is either known that a specific research study will include this technique, or might include it, this aspect of the research must be disclosed to prospective subjects as part of the informed consent process.

  • More Information About Additional Element of Consent Research Involving Clinically Relevant Research Results

    Regulatory Text

    "Additional elements of informed consent. Except as provided in paragraph (d), (e), or (f) of this section, one or more of the following elements of information, when appropriate, shall also be provided to each subject or the legally authorized representative:

    (8) A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions;" 45 CFR 46.116(c)

    More Information

    • Subjects should be aware of the possibility that they might not receive research results, as well as the possibility that they might, so that they can factor that information into their decision about whether to consent to research.
    • This provision is intended to pertain to all clinically relevant research results, including general or aggregate research findings and individual research results.

New Requirement for Waiver of Informed Consent Criteria

  • General Waiver or Alteration of Consent Criteria (2018)

    "General waiver or alteration of consent—

    (1) Waiver. An IRB may waive the requirement to obtain informed consent for research under paragraphs (a) through (c) of this section, provided the IRB satisfies the requirements of paragraph (f)(3) of this section. If an individual was asked to provide broad consent for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens in accordance with the requirements at paragraph (d) of this section, and refused to consent, an IRB cannot waive consent for the storage, maintenance, or secondary research use of the identifiable private information or identifiable biospecimens.

    (2) Alteration. An IRB may approve a consent procedure that omits some, or alters some or all, of the elements of informed consent set forth in paragraphs (b) and (c) of this section provided the IRB satisfies the requirements of paragraph (f)(3) of this section. An IRB may not omit or alter any of the requirements described in paragraph (a) of this section. If a broad consent procedure is used, an IRB may not omit or alter any of the elements required under paragraph (d) of this section.

    (3) Requirements for waiver and alteration. In order for an IRB to waive or alter consent as described in this subsection, the IRB must find and document that:

    (i) The research involves no more than minimal risk to the subjects;
    (ii) The research could not practicably be carried out without the requested waiver or alteration;
    (iii) If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format;
    (iv) The waiver or alteration will not adversely affect the rights and welfare of the subjects; and
    (v) Whenever appropriate, the subjects or legally authorized representatives will be provided with additional pertinent information after participation." 45 CFR 46.116(f)(2018 requirements)
  • Summary of Changes

    Overall, the format and organization in the 2018 requirements are different that the pre-2018 rule. The changes were made to provide clarity regarding the requirements. 

    Waiver of Consent

    The 2018 requirements:

    • Prohibit an IRB from waiving consent for the storage, maintenance, or secondary research uses of identifiable private biospecimens or identifiable private information if an individual was asked to provide broad consent for such purposes and refused to provide such consent.
    • Adopt a new waiver criterion which now mandates that for research involving access to or use of identifiable private information or identifiable biospecimens, the requirements of informed consent can be waived or altered only if the research could not practicably be carried out without using such information or biospecimens in an identifiable format.
    • The IRB also cannot waive broad consent (a requirement to meet a limited IRB review exemption criteria). 

    Alteration of Consent

    The revised rule does not allow an IRB to omit or alter any of the general requirements for informed consent. The IRB also cannot alter broad consent.

    Note: these changes are also reflected in the waiver criteria applicable to research involving public benefit and service programs conducted by or subject to the approval of state or local officials. See 45 CFR 46.116(e)(2018 requirements) for the specific criteria.

New Criteria to Waive the Requirement for a Signed Consent Document

  • Waiver of the Requirement to Obtain a Signed Informed Consent Form

    "(1) An IRB may waive the requirement for the investigator to obtain a signed informed consent form for some or all subjects if it finds any of the following:

    (i) That the only record linking the subject and the research would be the informed consent form and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject (or legally authorized representative) will be asked whether the subject wants documentation linking the subject with the research, and the subject's wishes will govern;

    (ii) That the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context; or

    (iii) If the subjects or legally authorized representatives are members of a distinct cultural group or community in which signing forms is not the norm, that the research presents no more than minimal risk of harm to subjects and provided there is an appropriate alternative mechanism for documenting that informed consent was obtained.

    (2) In cases in which the documentation requirement is waived, the IRB may require the investigator to provide subjects or legally authorized representatives with a written statement regarding the research." 45 CFR 46.117(c)(2018 requirements)

  • Summary of Changes

    The 2018 requirements add a new provision allowing a waiver of the requirement for a signed consent form if the subjects are members of a distinct cultural group or community for whom signing documents is not the norm, provided that the research presents no more than minimal risk of harm to subjects and there is an appropriate alternative method for documenting that informed consent was obtained.

    The criteria also includes a reference to the subject’s legally authorized representative to clarify that this provision applies when a subject has a legally authorized representative who is a member of a distinct cultural group or community in which signing forms is not the norm.

New Exception for Screening, Recruiting, or Determining Eligibility

  • Exception for screening, Recruiting, or Determining Eligibility

    "Screening, recruiting, or determining eligibility. An IRB may approve a research proposal in which an investigator will obtain information or biospecimens for the purpose of screening, recruiting, or determining the eligibility of prospective subjects without the informed consent of the prospective subject or the subject's legally authorized representative, if either of the following conditions are met:

    (1) The investigator will obtain information through oral or written communication with the prospective subject or legally authorized representative, or

    (2) The investigator will obtain identifiable private information or identifiable biospecimens by accessing records or stored identifiable biospecimens." 45 CFR 46.116(g)(2018 requirements)

  • Summary of Changes

    The exception is new and clarifies the circumstances in which the IRB may approve the investigator’s proposal to obtain information directly from a prospective subject, or to obtain already collected identifiable private information or identifiable biospecimens by accessing records or stored biospecimens, for purposes of screening, recruiting, or eligibility assessment, without the informed consent of the prospective subject or the subject’s legally authorized representative. 

    This change addresses concerns that the pre-2018 regulations required an IRB to waive informed consent before investigators could record identifiable private information for the purpose of identifying and contacting prospective subjects for a research study. The change is intended to address these concerns by eliminating the requirement for the IRB to waive informed consent for these activities and clarifying that this is not a waiver of the consent requirement but rather an exception to the requirement.

    As part of its review and approval of the research, the IRB must determine that there are adequate privacy and confidentiality safeguards for information obtained by investigators for these preparatory-to-research activities.

Revised Common Rule