Informed Consent Guidance

Informed Consent Process

Obtaining informed consent is a basic ethical obligation and a legal requirement for researchers, unless the IRB waives this requirement.  The requirement for informed consent is one of the central protections defined by:

  • Department of Health & Human Services (HHS) regulations at 45 CFR part 46
  • Food and Drug Administration (FDA) regulations at 21 CFR part 50

This section describes:

Informed Consent Process

Your protocol and/or application must describe your process for obtaining informed consent from potential participants. This process must comply with IRB Standard Operating Procedure HRP-090, but the procedures for obtaining consent will depend on the research setting and your participant population.

Obtaining consent is an ongoing process that involves much more than providing a document to a prospective participant and obtaining a signature. The requirement for consent is based 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 independent agents who must be allowed to choose what will happen to them. According to the Belmont Report, there is widespread agreement that the consent process can be analyzed as containing three elements:

  1. Information

Researchers must provide adequate information about the research. This topic will be covered more in the section Requirements for Consent Documents.

  1. Comprehension

Researchers must ensure that potential participants understand the information provided to them before obtaining consent. The information provided during the consent process must be in a language the participant can understand.  For more information on including non-English speaking participants click here.  Researchers should carefully review the language to ensure that it is understandable and that scientific or other complex phrases are explained.  During the consent process, the person obtaining consent should assess the participant’s understanding by asking the participant open-ended questions such as:

  • Are we offering you your usual medical care or are we asking you to be in a research study?
  • What is the purpose of the study?
  • Tell me what will happen to you in this study.
  • Tell me about the risks you will face if you join this study.
  • Tell me about any benefits you could receive if you join this study.
  • What will happen to you if you decide not to be in this study?
  • Suppose you want to drop out of the study – when can you drop out?

It is the researcher’s responsibility to provide sufficient information so the subject can correctly answer questions similar to those listed above.

  1. Voluntariness

Participants’ agreement must be voluntary and free of coercion and/or undue influence.  The consent process should be conducted by an individual not in an authority position over the potential participant because the potential participant might feel intimidated or coerced into participation. Likewise, the participant should not be made to feel threatened if he or she does not agree to participate.

To avoid undue influence, information must be provided in an unbiased manner without emphasis on potential benefits or compensation.  The consent process should include no claims that an investigational drug or device is safe or effective for the purposes under investigation, or that the test article is equivalent or superior to any other drug, biologic or device. Participants must not feel unduly influenced into agreeing to participate or staying in a study when the participant does not want to continue.

Requirements for Consent Documents

UC Davis has a template consent document (HRP-502) that can be used to create a consent document that includes all of the information required by regulations and UC Davis policies for human subject research that is not exempt.  Unless the IRB waives one or more elements, the following information must be included in the information provided to potential subjects:

  1. For research involving a “medical experiment” (Health and Safety Code
  2. Section 24174), the California Bill of Rights must be included (see template consent form (HRP-502))
  3. A statement that the study involves research
  4. An explanation of the purposes of the research
  5. The expected duration of the subject’s participation
  6. A description of the procedures to be followed
  7. Identification of any procedures which are experimental or investigational
  8. A clear description of any reasonably foreseeable discomforts or risks which the subject might encounter during participation in the research
  9. A clear description of any benefits to the subject or to which may reasonably be expected from the research
    Note – compensation should not be included as a benefit
  10. A statement describing how confidentiality of records identifying the subject will be maintained
    Note – if the research is subject to FDA jurisdiction, this section must include a statement that the FDA may inspect the records
  11. A statement that participation is voluntary and that the participant will not be penalized or lose benefits for refusing to participate
  12. A statement that the participant may withdraw or discontinue participation at any time without penalty or loss of benefit
  13. Where this is appropriate (usually where the experimental procedure involves treatment of some type), the consent form must include information about alternative procedures that would be of advantage to the subject
  14. For research involving more than minimal risk, an explanation as to whether any compensation or medical treatment is available if injury occurs
  15. An explanation about whom to contact for answers to questions about the research (Include individual’s title, email address and phone number)
  16. A statement that participants should call the IRB for questions about their rights as participants (Include IRB email address and phone number)
  17. An explanation about whom to contact if a research-related injury occurs to the subject  (Include individual’s title, email address and phone number)
  18. If the research is a clinical trial that requires posting on clinicaltrials.gov, this statement must be included on the consent document:  “A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.”

The following additional information must be provided to prospective participants, when applicable:

  1. For research investigating risks of a drug, device or procedure: 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) which are unforeseeable.
  2. If participants may be withdrawn from the research: Anticipated circumstances under which participation may be terminated by the investigator without regard to the participant’s consent.
  3. If participants will incur any costs if they participate: A description of the costs to the participant that may result from participation in the research.
  4. If participants will face risk when they withdraw from participation: The consequences of a subject’s decision to withdraw from the research and procedures for orderly termination of participation by the subject (i.e. the need to taper study drug, etc.)
  5. A statement that significant new findings obtained during the research which may relate to the subject’s willingness to continue participation will be provided to the subject.
  6. For most research: The approximate number of subjects involved in the study.

Important Information about Consent Documents

  1. The consent document must include accurate information. Compare the consent document to the protocol (and investigators brochure, when applicable) to ensure that procedures, risks and other information are correct and complete.
  2. The IRB must approve your consent form before you use it. Approved consent forms will have an approval stamp (similar to the example below) in the right bottom corner of each page:

IRB Stamp

  1. If you make revisions to your protocol or if new information, such as risk information, is obtained you may need to revise the consent document so it is accurate and complete. According to Office for Human Research Protections (OHRP) Guidance, you cannot enroll participants into a study if the consent document is inaccurate or incomplete.
  2. Whenever you revise the consent document, you must submit the revised version to the IRB as a modification and the IRB must approve the new version before the version can be used.
  3. Unless otherwise instructed by the IRB in writing, you must use the most current approved version of the consent document when enrolling participants.

Documenting Consent

Unless the IRB waives the requirement for a signed consent form, consent must be documented in the following manner:

Handwritten signature:

  1. The participant (or the participant’s legally authorized representative (LAR)) personally signs and dates the consent form.
  2. The individual obtaining consent personally signs and dates the consent form.
  3. A copy of the signed and dated consent document is provided to the participant or the LAR.
  4. The original signed and dated consent document must be maintained in the research files.
  5. When applicable, place a copy of the signed and dated consent document in the participant’s EMR.
  6. These statements should be included in the research record:
    • A statement indicating that informed consent took place;
    • The participant (or LAR) apparently understood the information and voluntarily agreed to participate;
    • A copy of the signed and dated consent document was provided to the participant or LAR;
    • The time and date the process took place.

Electronic Signature

Federal regulations allow electronic signatures when the documentation process is approved by the IRB. UC Davis IRB will approve the use of a secure system for electronic or digital signature when the system provides an encrypted identifiable “signature” compliant with federal regulations.

DocuSign, is one mechanism for obtaining electronic signatures in a compliant manner and UCOP has a Business Associate Agreement with DocuSign that allows researchers to use this vendor to obtain electronic signatures whenever the consent language includes health information. California law also includes requirements for digital signatures.  One requirement is that the vendor used to certify the authenticity of the signature must be approved by the state.  Here is the website the lists the approved vendors.

As with handwritten signatures, both the participant/LAR and the individual obtaining consent must provide an electronic signature.

A paper or electronic copy of the consent must be provided to the participant. The electronic copy can be provided on an electronic storage device, through a document sharing program or via email.  However, only secure email should be used when the consent document includes identifiable health information or other sensitive information. DocuSign automatically provides a copy of the signed and dated document to participants.

If the electronic consent document includes one or more hyperlinks to information on the Internet, the hyperlinks should be maintained and information should be accessible to participants until study completion. If the hyperlinks or other web sites or podcasts convey information specifically related to the informed consent process, the information in these hyperlinks must be included in any printed paper copy, if one is provided.

Whether using handwritten or electronic signatures, IRB Administration recommends that you document the steps completed during the consent process in the research record as outlined above.

HIPAA Authorization

If the research includes access to or use of identifiable health information, you might also need to obtain the individual’s HIPAA authorization.  Sometimes the IRB can waive the requirement for a signed authorization form.

For more information on HIPAA, click here.

HIPAA Authorization for Research form, click here.

Use of an Impartial Witness

ICH Good Clinical Practice (GCP) defines an Impartial Witness as “a person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject or the subject’s legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject.” This definition contains four parts, all of which must be met. Here they are presented separately for emphasis and analysis:

  • “Who is independent of the trial:” This could be a person who is a family member. It would not be a member of the site staff involved with the study.
  • “Who cannot be unfairly influenced by people involved with the trial:” This would be a person free from potential coercion or undue influence or conflicted interest.
  • “Who attends the informed consent process if the subject or the subject’s legally acceptable representative cannot read:” This emphasizes the participation of the witness throughout the consent process, not just when the subject signs. A robust informed consent process will likely result, on the part of the person obtaining consent.
  • “Who reads the informed consent form and any other written information supplied to the subject:” This responsibility has the witness confirming the subject was presented sufficient information to assure truly informed consent of the subject.

Use of an Legally Authorized Representatives (Surrogate Consent Guidance)

This guidance provides investigators with information on the measures that need to be taken and the required documentation when they plan to enroll prospective research participants who cannot consent on their own behalf. Federal regulations permit investigators to obtain consent from a legally authorized representative. California law (Health & Safety Code 24178) and UC Guidance on Surrogate Consent for Research define the categories of individuals who are allowed to provide surrogate consent for research. This guidance applies to the following groups:

  • Individuals whose medical condition may render them temporarily unable to provide informed consent as a consequence of severe pain, confusion, or impaired consciousness due to events such as life-threatening illness or trauma, and
  • Individuals who have cognitive impairments such as intellectual disabilities, dementia, or psychosis that are enduring or that may worsen with time

There are separate informed consent guidelines for planned research in emergency settings and for research involving children and minors and are described in separate documents.

NOTE: More detailed information about legally authorized representatives and surrogate consent policies and procedures can be found here

Including participants who cannot Read

When a prospective participant is competent but cannot read because of blindness or other reason, you should:

  1. Ensure an impartial witness is present during the consent process
  2. Read the entire consent document to the prospective participant
  3. Answer all of the participant’s questions
  4. Ask the participant questions to assess comprehension
  5. Obtain agreement from the participant only after assessing that the participant comprehends the information in the consent document
  6. Obtain the signature (or mark) and date from the participant
  7. Obtain a signature and date from the witness
  8. Sign and date the consent document as the individual obtaining consent
  9. These statements should be included in the research record:
    • A statement indicating that informed consent took place;
    • A statement indicating the participant (or LAR) could not read the consent document and the document was read to the participant in the presence of an impartial witness;
    • The participant (or LAR) apparently understood the information and voluntarily agreed to participate;
    • A copy of the signed and dated consent document was provided to the participant or LAR;
    • The time and date the process took place.

Including participants who cannot read English

When preparing your Initial Review Application for IRB approval, consider whether you will enroll individuals who cannot read the English consent document because their native language is not English. If it is apparent that some or all of the participants will not be able to read the English version, then the consent document should be translated into the participants’ native language so you will have a document ready for the consent process.  The translation must be submitted to the IRB and approved before use.

During the consent process, an interpreter should be present to help with explanations and answers to the participant’s questions.  You should also plan for interpretation during the participant’s study visits and for emergencies, if applicable.

Sometimes an individual who cannot read English might qualify for your study and you do not have a translated consent document available. When such an event occurs, consider the options carefully. If there is sufficient time to obtain a translated consent document for the individual, you should not enroll this person until you obtain the translated document and obtain IRB approval.  If there is insufficient time to obtain a translated consent document for this individual, enrollment should depend upon the risk benefit analysis. For example, if participation involves significant risk, then the participant should not be enrolled in the study unless there is a significant potential for benefit that would not otherwise be available to the individual.

If you decide to enroll an individual who cannot read the English version of the consent document, you should:

  1. Check your IRB application to see if you indicated you would enroll individuals who cannot read English. If you did not, you must submit a modification requesting approval to enroll the individual.  If you submitted an electronic application, you will need to revise the application when you submit the modification.
  2. Check the IRB’s website to see if a HRP-507 Short Form exists in a language the participant can read. Download the form. If there is not a Short Form available in a language the individual can read, contact the IRB Office.
  3. Ensure that the information in the consent document is accurately translated orally into a language the individual can understand. You should also ensure that you will have an ability to adequately communicate with the individual during study visits and for emergencies.
  4. You will need to obtain an impartial witness to observe the consent process.
  5. With the witness present, the consent form should be presented (read) orally to the individual in a language the individual understands. The individual’s questions should be answered and the person obtaining consent should ask questions of the individual through the translator to assess the individual’s comprehension.
  6. When you are certain the individual has adequate comprehension and is voluntarily agreeing to be in the study you must:
    1. Obtain the participant’s (or the participant’s LAR) signature and date on the Short Form;
    2. Obtain the witness’s signature (and date) on the Short Form and a copy of the consent document;
    3. You, as the person obtaining consent, must sign the consent document;
    4. Provide a copy of the Short Form and the consent document to the participant or the participant’s LAR;
    5. Document the following in the research record:
      1. A statement indicating that informed consent took place by using the Short Form consent process;
      2. A qualified translator was available during the process;
      3. An impartial witness observed the consent process;
      4. The participant (or LAR) apparently understood the information and voluntarily agreed to participate;
      5. A copy of the Short Form and consent document were provided to the participant and LAR;
      6. The time and date the process took place.

Including Participants who cannot Consent for themselves

If you intend to enroll participants who cannot personally consent, you must include this information in your Initial Review Application. The IRB will determine whether it is appropriate to include these vulnerable participants.

Unless the requirement for consent is waived, you cannot include a participant in your research if you do not have legally effective informed consent.  “Legally effective” means the person providing consent has the capacity to consent – if the participant has legal capacity to consent, you must obtain consent from the participant. If the participant does not have capacity, you must obtain consent from an individual who has legal authority to provide consent on behalf of the participant. You must check the credentials of the individual providing consent to ensure the individual has the required authority.  You should also document how you ascertained whether the individual giving consent had the required authority.

The individual providing consent must act in the best interest of the participant and if the participant is capable, s/he should sign and date the consent document indicating assent (agreement) to participate.

If the participant regains capacity to consent while participating in the research, you must obtain informed consent directly from the participant before involving the participant in any additional research procedures.

For more information on surrogate consent, click here.

For information on including children in research, click here.

Including Participants who cannot physically sign and date the Consent Document

In rare instances, a potential participant may be competent to provide consent but may not be able to sign and date the consent document because of a physical impairment.  In these instances, you should conduct the consent process in the presence of an impartial witness who will attest that the participant comprehended the information and agreed to participate but was unable to sign and date the consent document.  You should also document the consent process and include a statement indicating the reason for the participant’s inability to sign the document and a statement that an impartial witness was present during the process.

Waiver of Documentation of Consent (aka Verbal or Online consent)

 

The IRB may waive the requirement for a signature on a consent document when the following criteria are met:

  1. The research involves only minimal risk; and
  2. The research involves no procedures for which consent is usually required.

When research is not under FDA jurisdiction, the IRB also may waive the requirement for a signature on a consent document when these criteria are met:

  1. The main risk to the research is breach of confidentiality; and
  2. The only document linking the participant to the research is the consent document; and
  3. The participant does not want to sign a consent document.

Requests to waive the requirement for a signature should be included in the electronic Initial Review Application Form.

When the requirement for a signature is waived, the individual obtaining consent must ensure that the participant obtains all of the consent information, comprehends the information and voluntarily agrees to participate in the research.  Usually the IRB will require the research to provide written information to potential participants in an Information Sheet, email invitation or as introductory language for a survey.

Waiver or Alteration of the Requirements for Informed Consent for Minimal Risk Research

The IRB may waive the requirement for informed consent or waive the requirement to include specific information in the consent document or process when these criteria are met:

  1. The research involves only minimal risk to participants;
  2. The waiver will not adversely affect the participants’ rights; and
  3. The research cannot be conducted unless the waiver is approved.

The third requirement is met when (1) it will not be possible to obtain informed consent from participants because the research is not engaging in interactions or interventions with participants and it is not possible to obtain consent through other means; or (2) in the rare circumstances when bias will be introduced into the results unless data about all eligible participants is required.

Researchers may request a waiver of consent when completing the Initial Review Application.

Waiver of Consent for FDA regulated research

In addition to the waiver of consent allowed for minimal risk research, the FDA regulations allow research involving humans to take place under the following conditions:

  1. Planned research in emergency situations when there is no time to obtain informed consent – Emergency Exemption from Prospective IRB approval for Investigational Drug, Biologics, and Devices (for more information click here)
  2. Unplanned use of an investigational drug, device or biologic in an emergency (for more information click here)