Purpose of the Informed Consent Process
Informed consent is understood as an on-going process which starts with the initial presentation of a research activity to a prospective subject by the investigator and continues through the research activities until the subject ends his/her participation or the study closes. The initial phase of the consenting process commonly begins with the first contact between the subject and the investigator when the potential subject is first informed about the study. Many subjects make their decision regarding whether to participate in research during this initial contact. As a result, the greatest potential for misunderstanding exists in the initial consent process. Researchers must provide sufficient time for a potential subject to reflect on the nature of participation during the important initial presentation of a research activity. When subjects are presented with numerous research and clinical options, the consent process must include a clear description of the possible known ramifications resulting from each option presented. Subjects must also be made aware of the possibility of unforeseen risks resulting from participation in the research project. The presentation must not include specific “leading” information about whether to participate in any particular project.
By providing a potential subject with information, understandable to the subject in an initial session regarding complex research issues, potential subjects should have an improved comprehension of the elements within the consent form and provide a more informed consent for participation in the research.
The second step in the consent process is the presentation of the consent form(s) to the subject.
- Consent forms should be presented with consideration to environment. Distractions and noise should be limited. Privacy should be protected when possible.
- In biomedical research the investigator should separate the research consent form from any other clinical information or hospital admission forms. Subjects should not be asked to sign hospital admission paperwork or hospital consent documents for clinically indicated procedures at the same time as the presentation of the research consent form. If this must occur, the study team should make it very clear what is being done for research and what is being done as part of medical care.
- Individuals who have already received pre-op medication or anesthesia should not be asked to sign a consent to participate in a research study. The presentation of the research consent form should be a separate process. The principal investigator or a member of the research team should ensure that the subject or their legally authorized representative (LAR) reads the consent form or has it read to them. After the subject or LAR reads the consent form or has it read to them, the principal investigator or member of the research team should use open ended questions to determine if the subject or their LAR understands the information presented to them. Please note that the IRB must approve the use of an LAR or surrogate prior to obtaining their consent.
The IRB ensures that informed consent will be sought from each prospective subject or the subjects legally authorized representative, in accordance with, and to the extent required by 45 CFR 46.116 and 21 CFR 50.20. In addition, the IRB ensures that informed consent will be appropriately documented, in accordance with, and to the extent required by 45 CFR 46.117 and 21 CFR 50.27. The IRB ensures, as part of its review, that the information in the consent document and process is consistent with the research.
To ensure an effective informed consent process, the Institutional Review Board (IRB) and investigators comply with all applicable federal regulations (e.g., 21 CFR 50, 45 CFR 46.116, 117, and 38 CFR 16.116, 117). These regulations mandate the inclusion of eight basic informed consent elements (described below). Six additional elements may be required, depending on the nature of the research. IRB policy also specifies the information to include in the consent process.
The informed consent template included in the full and expedited IRB applications outlines the required elements of informed consent. The investigator may use a short form if approved by the IRB in accord with applicable federal requirements.
Informed Consent: Informed consent is an ongoing educational process that takes place between the investigator and prospective subject, allowing the investigator and the participant to exchange information and ask questions
Consent: Consent is the act of agreement and is only valid if the person providing consent has been fully informed, possesses the cognitive ability to understand what is being agreed to and also possesses the ability to self determine and is of the legal age or disposition to do so. The term is also used to refer to the consent form itself.
Assent is defined as affirmative agreement of a child or an individual with impaired consent capacity to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent.
Permission is defined as the agreement of parent(s) or guardian to the participation of their child or ward in research or clinical investigation. Permission includes the element of consent set forth in federal regulations and outlined in the informed consent template included in the IRB expedited and full review applications.
In Virginia, the terms child or children refer to all individuals under 18 years of age unless the individual(s) is legally emancipated. (See section Emancipated Individuals for details of Virginia state law.) Individuals under 18 years of age who are not emancipated meet the federal definition for child [e.g., Department of Health and Human Services (DHHS), Food and Drug Administration (FDA), and U.S. Department of Education].
Legally Authorized Representative (LAR) is an individual who has the authority to make research participation decisions on behalf of another. In accord with state law and federal regulation, individuals who can serve as legally authorized representatives are as follows:
Consent by an LAR should involve all the same considerations that informed consent from a competent subject involves.
- Permission and/or authorization by a legally authorized representative for children: Consistent with Virginia health care decision statutes for choosing an LAR for children, the following responsible parties in the order of priority listed shall be authorized to make research participation decisions on behalf of the child: (a) the judicially appointed guardian of the person, if the guardian has been appointed and if the decisions to be made under the consent are within the scope of the guardianship; (b) the parent of the child.
- Permission and/or authorization by a legally authorized representative for individuals with impaired consent capacity: Consistent with Virginia health care decision statutes for choosing a legally authorized representative for adult subjects unable to consent, one of the following responsible parties, in the following order of priority (if no individual in a prior class is reasonably available, willing, and competent to act), is authorized to make research participation decisions on behalf of the person: (a) the judicially appointed guardian of the person, if the guardian has been appointed and if the decisions to be made under the consent are within the scope of the guardianship; (b) the attorney-in-fact named in a durable power of attorney, if the durable power of attorney specifically includes authority for the decisions to be made under the consent; (c) the spouse of the person; (d) an adult child of the person, or if the person has more than one (1) child, the majority of the adult children who are reasonably available for consultation; (e) the parents of the subject; (f) the nearest living relative, or if more than one of the same relation, a majority of the nearest living relatives.
In Virginia, a guardian is an individual who may serve as an LAR as defined above. These individuals meet the federal definitions for guardian.
In order to obtain true informed consent requires that the potential subject understands the information shared with them about the research study and is able to make a decision based on what is best for themselves.
The Teach-back method is a proven method to verify the subject understands the information about the study before enrolling.
Principal Investigators are responsible for maintaining original copies of consent/authorization forms signed by subjects, in a secure location, along with the study records until completion of the research and longer, in accordance with state and federal regulations for record retention and the funding source or sponsor requirements. Please reach out to UVA Records and Information Management for current storage requirement on research record retention timeframes. Additionally, the UVA Records and Information Management office must approve the destruction of study records prior to implementation.
If the study might affect the clinical care of the subject a copy of the informed consent document must be placed in the subject's medical record in accordance with Virginia state and local government regulations.
In cases where Principal Investigators transfer their research programs to other institutions, the disposition of consent/authorization forms must be discussed with the IRB administrative staff.
Consider the experience of the participant:
Are the participants aware that they are participating in a research study?
If not, then consent has been waived.
The Common Rule (45CFR46) allows the IRB to approve a waiver, or an alteration, of the requirement for informed consent to the research if the proposed protocol meets the following specific criteria found at 45 CFR § 46.116(d):
1. The research involves no more than minimal risk to the privacy of the subjects.
2. The research could not practicably be carried out without the waiver or alteration.
3. The research could not practicably be conducted without access to and use of this identifiable protected health information.
4. Whenever appropriate (generally, when there is a health justification), the subjects will be provided with additional pertinent information after participation.
Additional HIPAA Criteria
The protocol must include, at a minimum, the following elements:
a) An adequate plan to protect identifiers from improper use and disclosure.
b) An adequate plan to destroy the identifiers at the earliest opportunity consistent with conduct of the research, unless there is a health or research justification for retaining the identifiers or such retention is otherwise required by law and
c) Adequate written assurances that the protected health information will not be reused or disclosed to any other person or entity, except as required by law, for authorized oversight of the research study, or for the research for which the use or disclosure of protected health information would be permitted.
Note: If the study is regulated by the FDA (involves use of food, drug, biologics or devices), the IRB cannot grant a waiver of consent. The only exception is for emergency use of a test article FDA 21 CFR 50.23, or planned emergency research FDA 21 CFR 50.24.
Consider the experience of the participant:
If the participant is given all the relevant information, but a written consent document is not signed, then this is an example of a study design where the documentation of consent has been waived by the IRB. In these cases, where consent is obtained without a signature, the participant has been asked for consent verbally or to demonstrate that they give their consent through action, like clicking forward on an online survey.
Background
If you propose to obtain informed consent for the research activity without obtaining the subject’s signature on a consent form you are requesting a waiver of documentation of consent. Waiving the requirement for a written form does not eliminate the requirement for informed consent. Subjects must be informed of the nature of the research, and their consent (or the consent of their legal representatives) must be obtained whenever appropriate. This type of waiver is useful for some telephone or internet surveys, questionnaires, or when signing the consent document could have a negative consequence for the subject.
The IRB will require the use of an Information Sheet to be given to the potential subject or an oral script to be read to the potential subject. Investigators will use the information sheet or script to guide them through the informed consent discussion/process. You will not need to obtain the subject’s signature on a consent form. The script or information statement must be provided to the IRB at the time of original protocol submission for review and approval. The PI and/or research staff will document the participant's consent, as well as date, and the name of the person conducting consent in the study files.
In addition to describing the study, the script or information sheet must contain the basic elements of informed consent, as referenced in 45CFR46.116(a) and 21CFR50.25.
The script or information sheet should include the following information:
· State that the study involves research
· Explain the purposes of the research and the expected duration of the subject's participation
· If applicable: describe any foreseeable risk or discomforts to the subject
· If applicable: describe any benefits to subjects or to others that may reasonably be expected from the research.
· If applicable: disclose alternatives
· Describe the extent to which confidentiality of records identifying subjects will be maintained, where the records will be stored and who will have access to them.
· Provide contact information for answers to pertinent questions about the research, and participants' rights.
· Include that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which participants are otherwise entitled, and also that participants may discontinue participation at any time without penalty or loss of benefits to which they are otherwise entitled.
According to 45 CFR 46.117(c), an IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either:
· Research presents no more than minimal risk*
AND
· Research involves procedures that do not require written consent when performed outside of a research setting
45 CFR 46.117(c)(2)
*Definition of Minimal Risk
An individual is considered to be at more than minimal risk if exposed to the possibility of harm -- physical, psychological, social, legal, or other -- as a consequence of participation as a human subject in any research activity which departs from the performance of routine physical or psychological examinations and tests, or which departs from established and accepted procedures necessary to meet the individual's needs, or which increases the probability or magnitude of risks ordinarily encountered in daily life.
OR
45 CFR 46.117(c)(1)
· Principal risks are those associated with a breach of confidentiality concerning the subject’s participation in the research
AND
· Consent document is the only record linking the subject with the research.
AND
· Each participant will be asked whether the participant wants documentation linking the participant with the research, and the participants wishes will govern.
For each clinical trial* regulated under the 2018 Common Rule and conducted or supported by a Federal department or agency, one IRB approved informed consent form used to enroll subjects must be posted to Clinicaltrials.gov or regulations.gov after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject, as required by the protocol 45CFR46.116(h).
*Clinical Trial is defined as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes.
TIPS:
• A consent must be posted for any study regulated by the 2018 Common Rule that is federally funded or FDA regulated.
• Posting the consent form is usually done by the sponsor or overall PI.
Use of Electronic Informed Consent (e-Consent)
Federal guidance on how to implement e-Consent in clinical research
The purpose of this document is to provide guidance on documenting consent other than by obtaining a physical inked signature on paper.
Electronic informed consent (e-Consent) refers to using electronic methods to obtain consent and can apply to either the process of consenting, the documentation of consent, or both. Electronic documentation of consent may be used when researchers conduct the consent process with subjects in person, as well as when potential subjects are not physically present during the consent process. In either situation, the consent process itself should still be designed to ensure that subjects are adequately informed about the research, can easily ask, and get answers to questions, and recognize that participation is voluntary.
When the IRB reviews the study, it will consider how the electronic signature is being created, whether the signature can be shown to be legitimate (confirm the subject or LAR identity using 2 forms of identification), and how the research team plans to provide a version of the consent form to the potential subject for their review and retention. Subjects must still be provided with the ability to access a written version of the consent form that they can retain for their records. All elements of informed consent are required by HHS or FDA regardless of the platform used. Regulations require IRBs to maintain the version of any web-based information containing the study-related information that the IRB has reviewed and approved. This includes text-based information as well as information provided via video, infographics, hyperlinks to external resources and other multimedia sources. If properly obtained, an electronic signature can be considered an ‘original’ for the purposes of recordkeeping. In other words, it would satisfy requirements in case of an audit.
Methods for e-Consenting
- In-person e-Consenting using an electronic device such as a tablet or a computer when subjects are on-site with study personnel present.
E.g., The subject meets study personnel on-site for a discussion. Comprehensive materials and the ability to sign may be provided through a device such as a tablet.
- Remote e-Consenting takes place without the researcher witnessing any or all the consent process in settings such as the subject’s home. Note: The study team must provide adequate justification for requesting remote e-Consent.
E.g., The subject is screened remotely by study personnel through a WebEx or Zoom conference and receive a REDCap/DocuSign/Qualtrics link that allows them to read comprehensive materials and sign electronically (remotely) on a personal computer.
Note: The study teams can use Zoom or Webex for a consent discussion.
To document e-Consent using a verifiable electronic signature AND use an application that meets the required UVA Data Security standards see (Docusign, UVA RedCap) & (Qualtrics) for completion of surveys).
NOTE: The UVA REDCap system is NOT 21 CFR Part 11 compliant. This means that it should NOT be used IF:
- your study is FDA regulated AND the data will be submitted as part of a marketing approval application OR
- your study is FDA regulated AND the study involves eConsent
When providing electronic consent, there are several ways in which an e-signature might be documented.
Some examples include:
- Typing one’s name with an accompanying check box and statement noting an intent to affix a legal signature (e.g., “By checking this box and typing my name below, I am electronically signing this consent form”); or
- Signing with a stylus in an electronic document. In-person e-Consenting versus remote e-Consenting
Researchers should have methods in place to ensure that the e-Consent process provides the opportunity to consider whether to participate, and to ask questions about the study before they sign consent, as well as at any time during the subject’s involvement in the research study. This may be accomplished by a discussion between study personnel and the subject, whether it is in-person, a telephone call, or a video conference. When video conferencing is used during the e-Consent process, study personnel should remind subjects to conduct the e- Consent discussion in a private location. Additionally, the signed documentation of consent from the subject, returned electronically or a digital form with electronic signature, must be obtained.
The electronic informed consent process must include the same information contained within the written ‘paper’ informed consent document; include methods to verbally discuss the consent form; evaluate the subject’s comprehension; and document the subject’s or LAR’s consent. The e-Consent must also contain all elements of informed consent required by federal regulations (45 CFR 46.116 and 21 CFR 50.25). The information must be in language understandable to the potential subject or the subject’s LAR and conveyed in a manner that minimizes the possibility of coercion or undue influence regarding the subject’s decision to participate in a study. The device, system, or platform used to obtain informed consent must allow enough time for completion, the ability to navigate forwards and backwards, and the option to stop and resume later. Electronic methods of communication should allow the subject to contact the researcher again at any point in the process to ask additional questions.
The IRB must review all forms (electronic and paper) and other informational materials, including any videos and Web-based presentations, which the subject will receive and view during e-Consenting. The IRB will also review any optional questions or methods used to gauge subject comprehension of key study elements. During its review, the IRB will review the proposed e-Consent process to determine the usability of the e-Consent materials. If the program uses hyperlinks to convey study-related information, the IRB will review the online materials to ensure that the study-related information is accurate and appropriate.
Additional information:
• Subjects must be instructed how and when they will receive answers to questions, and they must be provided information on how to contact an appropriate individual for pertinent questions about the research and their rights and whom to contact in the event that they sustain a research-related injury.
• Subjects may have difficulty navigating or using electronic systems because of a lack of familiarity with electronic systems, poor eyesight, or impaired motor skills. In such cases, e-Consenting processes should be ADA compliant to meet the needs of these subjects. A paper-based informed consent should be also available to subjects.
• The e-Consent may use interactive electronic-based technology, which may include diagrams, images, graphics, videos, hyperlinks, and narration. The e-Consent should be appropriate for the intended audience, taking into consideration the subject’s age, language, and comprehension level.
• Regulations require identity verification before study personnel establishes, assigns, certifies, or otherwise sanctions an individual’s electronic signature.
• The e-Consent process can be used to obtain assent from pediatric subjects (when applicable) and parental permission from their parent(s) or guardian as well as consent from a Legally Authorized Representative (LAR).
• Subjects should receive a copy of their e-Consent and have easy access to the materials and information presented to them during the consenting process with the ability to ask questions at any time.
• The electronic system used in e-Consent must be secure with restricted access and should include methods to ensure confidentiality regarding the subject’s identity, study participation, and personal information after informed consent has been obtained. Depending on the electronic system, additional clearance from UVA Information Security (INFOSEC) may be needed before IRB approval can be granted.
• Stand-alone HIPAA authorizations may be obtained electronically, provided that the signature of the subject (or the subject’s LAR) is a valid electronic signature under applicable laws and regulations.
• Any changes to the e-Consent materials and processes require submission of a modification to the IRB and subsequent IRB approval prior to their use.
For more information see the Learning Shot on The Informed Consent Process for Clinical Research