The IRB has and follows written policies and procedures to evaluate the consent process and to require that the Researcher appropriately document the consent process. (AAHRPP Element II.3.F)

Informed consent is a continuing process whereby the investigator and research participant have an on-going dialogue about all aspects of a research study that might inform a participant’s decision to take part in the study and their decision to continue their involvement as a participant. The purpose of the consent process is to assure knowledgeable decision-making and voluntary participation.

 This process generally includes:

1.      Bringing the research study to the notice of potential participants;

2.      Presentation and explanation of the study activities to the participant or their legally authorized representative (LAR);

3.      Documentation of the informed consent via a signed and dated written consent document; 

4.      Ongoing discussions between the investigator and the participant regarding continued participation in the study.

The consent process must:

1.      Provide sufficient opportunity for the participant, or the participant’s legally authorized representative (LAR), to consider whether to participate;

2.      Minimize the possibility of coercion or undue influence;

3.      Be free of exculpatory language; and

4.      Be in language understandable to the participant or their representative.

The IRB also requires that the circumstances of the consent process be culturally and linguistically appropriate for the intended participants.

This Chapter addresses:

12.1    Requirements for Informed Consent

12.2    Consent Procedures for Research Involving Vulnerable and Other Special Populations Including Consent by a Legally Authorized Representative

12.3    IRB Review of the Consent Process, including Consent Documents

12.4    Documentation of Informed Consent – Signature Requirements

12.5    Waiver or Alteration of Informed Consent Requirements

            12.6    Exceptions to Informed Consent in Emergency Situations

12.7    Observation of the Consent Process

Refer also to Chapter 14.6 for more information on the consent document, and protocol director responsibilities in the informed consent process.

12.1   Requirements for Informed Consent

Section revised: 12/7/2015

The IRB has and follows written policies and procedures to evaluate the consent process and to require that the Researcher appropriately document the consent process. (AAHRPP Element II.3.F

Unless waived by the IRB, legally effective informed consent must be obtained from participants or their LARs as a condition for protocol approval.  All relevant requirements in OHRP in 45 CFR 46.111 and 46.116, and in the FDA regulations in 21 CFR 50.20, 50.25, 50.27 and 56.111 that are applicable to the consent process and the consent document must be satisfied.

IRB Evaluation of Compliance with Informed Consent Requirements

The evaluation of compliance is achieved by:

1.      IRB review of the informed consent process information and document(s) provided by the PD.

2.      Periodic consent form reviews comparing signed and dated consent forms with the IRB approved versions.

3.      Observation of the consent process, performed either as a periodic review function of the HRPP Compliance Manager, or as requested by the convened IRB. See Chapter 12.7.

12.1.1. Elements of Informed Consent

Legally effective informed consent includes the eight basic required elements and the six additional elements specified in 45 CFR 46.116 and 21 CFR 50.25.

Informed consent requirements for vulnerable and other special populations are addressed in Chapter 12.2.

12.1.2. Additional Consent Requirements

STANFORD has and follows written policies and procedures that identify applicable laws in the localities where it conducts human research, takes them into account in the review and conduct of research, and resolves differences between federal or national law and local laws. (AAHRPP I.1.G)

The legal counsel to the IRB, who is a non-voting member of the IRB, can provide assistance to investigators and the IRB in resolving any conflicts among applicable laws.

      1.            California Law

      2.            VA-Specific

      3.            HIPAA

      4.            HIV Testing or Research on AIDS

      5.            Genetic Testing

      6.            Data and Tissue Repositories

      7.            Xenotransplantation

      8.            International research

      9.            Stem Cell

  10.            Other Federal Agencies

 

1.  California Law 

Under California Law, there are additional requirements regarding the informed consent process when certain procedures are involved.

Experimental Subject’s Bill of Rights: In addition to the basic and additional elements of informed consent described above, the IRB requires that participants be given a list of their rights if participating in a “medical experiment” under California law as specified in CA Health and Safety Code 24172. The California Experimental Subject’s Bill of Rights is included in the STANFORD informed consent templates for medical research. 

Additional California requirements can be found in sections of this chapter that address specific consent requirements.

2.  VA-Specific

For VA research, additional consent requirements might apply – refer to VHA Handbook 1200.05.  Additional requirements include:

        i.            Payment by Veteran Participants for Treatment:  Informed consent information must include a statement that veteran-participants shall not be required to pay for treatment received as a participant in a research program.  Investigators should note, however, that veterans in the "discretionary work load" category are subject to co-payments, if so indicated by a means test.  The IRB suggests that this co-payment requirement be described in the consent document. See the VA Sample Consent template for suggested language.

      ii.            Required Signatures:  The informed consent document must be signed and dated by:

·   the participant or the participant’s legally authorized representative,

·   the person obtaining consent, and

·   if required by the IRB, a witness to the participant or the legally authorized representative’s signature (not as a witness to the consent process).  The witness cannot be the person obtaining consent, but may be another member of the study team or may be a family member.

   Note: If the sponsor or IRB requires a witness to the consenting process in addition to the witness to the participant’s signature and if the same person needs to serve both capacities, a note to that effect will be placed under the witness’s signature line.

    iii.            A copy of the signed and dated consent document will be given to the person signing the consent document.

    iv.            Adequate opportunity:  The investigator will give either the participant or the participant’s legally authorized representative adequate opportunity to read the consent document before it is signed.

3.  Health Insurance Portability and Accountability Act (HIPAA)

If the protocol involves protected health information (PHI) as defined by HIPAA (refer to the Stanford University HIPAA Policy H-13 Research and Patient Privacy), then HIPAA authorization may be included in the consent process. HIPAA authorization is an authorization to use or disclose PHI, and must be executed by a separate signature.

Consent templates incorporating HIPAA authorization, and separate HIPAA authorization language are provided on the Human Subjects Research website. 

4.  HIV Testing; Research on AIDS

Public Health System (PHS) Funded Research

If the protocol is supported by funding from the Department of Health and Human Services and includes testing for HIV, the consent documentation must state that identifiable participants will be informed of their results and provided with the opportunity for counseling.  The IRB requires this except in cases where it is not required by PHS policy.

 

HIV testing and disclosure: (CA Health & Safety Code Section 121080)

Individually identifiable research records generated by AIDS-related research are confidential and may only be disclosed with the prior written consent of the participant.

Any disclosure authorized by a research subject shall be accompanied by a written statement containing substantially the following language:

"This information has been disclosed to you from a confidential research record, the confidentiality of which is protected by state law and any further disclosure of it without  specific prior written consent of the person to whom it pertains is prohibited.”   

5.   Genetic Testing

If a protocol includes genetic testing, the IRB requires that the informed consent information disclose the risks specific to this type of testing.  Genetic testing includes research that studies the characteristics, genes, and gene versions that are transmitted by parents to offspring.  This may include many types of information, such as personal appearance and biochemistry, gene sequences, genetic landmarks, individual or family medical histories, reactions to medication, and responses to treatment.  The IRB includes detailed provisions and issues in its informed consent template that should be considered by the protocol director when the research includes genetic testing.  The template is also used by IRB staff and members as a guide for their review of such a consent document. 

6.   Data and Tissue Repositories

The NIH guidance on Data and Tissue Repositories is of interest to investigators who collect data or tissues of participants for repositories, and IRB staff and members who review such protocols.

When such repositories collect individually identifiable health information of participants, the HIPAA privacy regulations in 45 CFR Parts 160 and 164 must also be satisfied.  This may require either a written HIPAA authorization from the participants or a waiver of authorization by the IRB.  These requirements are discussed in Chapter 11

VA research: See  VA Handbook 1200.12, Use of Data and Data Repositories in VHA Research

7.   Xenotransplantation

Xenotransplantation: Any procedure that involves the transplantation, implantation, or infusion into a human recipient of either (A) live cells, tissues, or organs from a nonhuman animal source or (B) human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues, or organs.

In reviewing protocols and informed consent involving xenotransplantation, the IRB acts in accordance with the Guideline on Infectious Diseases Issues in Xenotransplantation issued by the federal Public Health Service (PHS) on January 19, 2001.  The PHS Guidelines require that various other administrative panels (e.g., Biosafety Committee) review such protocols, in addition to the IRB. The PD should consult the PHS Guideline prior to drafting the consent document, since they contain detailed guidance about the content of the informed consent information provided to potential xenotransplantation product recipients.  For example, they must be informed of the importance of complying with long-term or life-long surveillance necessitating routine physical evaluations and the archiving of tissue or body fluid specimens.

8.   International Research

When conducting research in certain communities or social contexts, whether in the U.S. or abroad, it may be inappropriate to document consent by using the standard written and signed consent document.  Other consent procedures may be more culturally or socially sensitive and may afford better protection to participants.  See Chapter 1.4.1.

Investigators may ask the IRB to consider a waiver or alteration of some of the mandatory elements of consent [45 CFR 46.116(d)], or a waiver of documentation of consent [45 CFR 46.117(c); 21 CFR 56.109(c)]. See Chapter 12.5.

Consult Legal Counsel If Necessary:  PDs should contact the legal advisor to the IRBs in the Office of the General Counsel to assist in determining who under local law may serve as a legally authorized representative, if children or adults who are unable to consent may be enrolled as participants. 

9.   Stem Cell Research

At Stanford University, the conduct of research involving human stem cells is governed by federal, State of California, and CIRM regulations, and must be reviewed by the combined IRB/SCRO (Institutional Review Board/Stem Cell Research Oversight) Panel.

See:

·         Stanford University Research Policy Handbook RPH 5.8 Human Stem Cell Research

·         Stem Cell Research Oversight website.

10.  Requirements - Other Federal Agencies

Additional requirements might apply, depending on the source of support/funding (e.g., Department of Defense, Department of the Navy, Department of Justice): see Other Federal Agencies - Additional Requirements [GUI-42].

12.1.3.   Consent Templates and Glossary of Lay Terms

The Human Subjects Website provides consent form templates, including VA specific templates, which address the required elements of informed consent, as well as providing language for other situations, (e.g., related to MRI, tissue banking), in which certain additional information may need to be provided to participants.  For research involving children, an Assent Template is also provided.

To assist PDs in preparing consent documents comprehensible to lay persons (i.e., at approximately 8th grade level) a glossary of lay terms is also available on the website.

12.1.4. Short Form Consent Process

Federal regulations permit the use of a short form consent process (45 CFR 46.117(b)(2)) with the prior approval of the IRB.  However, the IRB encourages the use of a full consent form translated into the participant’s language whenever possible.  The IRB may require that a participant be re-consented using a fully translated consent in the participant’s language within 30-days of enrollment for certain studies (e.g., first-in-human, high risk).

The short form consent process may be approved by the IRB, on a protocol-specific basis, for use with participants who are non-English speaking.  The IRB considers the study complexity and the amount and duration of participant involvement when determining if using the short form consent process is appropriate and can be approved.  

For use of the short form of consent documentation, the IRB determines:

·         The consent document states that the elements of disclosure required by regulations have been presented orally to the participant or the participant’s legally authorized representative.

·         A written summary embodies the basic and appropriate additional elements of disclosure.

·         There will be a witness to the oral presentation. The witness may be the interpreter (including the hospital interpreter), staff, a family member, or other person.

·         For participants who did not speak English, the witness will be conversant in both English and the language of the participant.

·         The participant or the participant’s legally authorized representative will sign and date the consent document:

·         The witness will sign and date both the short form and a copy of the summary:

·         The person actually obtaining consent will sign and date a copy of the summary.

·         A copy of the signed and dated short form will be given to the participant or the participant’s legally authorized representative.

·         A copy of the summary will be given to the participant or the participant’s legally authorized representative.

Information on the requirements for use of a short form consent process is available on the website.

12.2     Consent Procedures for Vulnerable and Other Special Populations Including Consent by a Legally Authorized Representative

Section revised: 7/15/2015  

Surrogate” and “legally authorized representative” have the same meaning when used in this Chapter 12 and the HRPP.

The IRB has and follows written policies and procedures requiring appropriate protections for prospective participants who cannot give consent or whose decision-making capacity is in question. (AAHRPP Element II.4.B)

(Also addresses portions of AAHRPP Element II.4.A)

When considering approval of research, the IRB considers issues such as the selection of participants, privacy and confidentiality, coercion and undue influence, and risk-benefit analysis.  Decisions are guided by the ethical principles underlying human research as set forth in the Belmont Report.

Special consideration is given to protecting the welfare of vulnerable participants, such as children, prisoners, pregnant women, fetuses, and mentally disabled persons, handicapped persons, or economically or educationally disadvantaged persons (45 CFR 46.111(b) and 21 CFR 56.111(b)). There are specific regulatory provisions for research involving pregnant women, fetuses, and neonates (45 CFR 46, Subpart B), prisoners (45 CFR 46, Subpart C), and children (45 CFR 46, Subpart D and 21 CFR 50 Subpart D).  Special considerations for providing legally effective informed consent for these participants are discussed below:

12.2.1. Adults with Impaired Decision-Making Capacity

VA Research – Additional Requirements

12.2.2. Pregnant Women, Fetuses and Neonates

12.2.3. Children and Consenting Minors

12.2.4. Illiterate Participants

12.2.5. Non-English Speaking Participants

12.2.6. Prisoners

Also see Chapter 9.3 concerning determination of the risks to vulnerable populations as defined in applicable federal regulations, and specifically for determining the required risk categories in protocols involving children and prisoners.

Additional Requirements

Depending on the type of research project, or the source of support/funding for the study or institution at which the study will be conducted (e.g., Department of Education), other additional requirements might apply. See Other Federal Agencies - Additional Requirements [GUI-42].

12.2.1.   Adults with Impaired Decision-Making Capacity – “Decisionally impaired”

The IRB has and follows written policies and procedures requiring appropriate protections for prospective participants who cannot give consent or whose decision-making capacity is in question. (AAHRPP Element II.4.B)

(Also addresses portions of AAHRPP Element II.4.A)

Decisionally impaired individuals are those with diminished capacity for judgment and reasoning due to a psychiatric, organic, developmental, or other disorder that affects cognitive or emotional functions.  Other individuals may be considered decisionally impaired or have limited decision-making ability because they are under the influence of or dependent on drugs or alcohol, suffering from degenerative diseases affecting the brain, are terminally ill, or have severely disabling physical handicaps.

The IRB must determine whether such participants should be recruited or whether support mechanisms, such as surrogate consent, are appropriate. 

IRB considerations include:

·         Can the person or their legally authorized representative understand the information?

·         Can the person or their legally authorized representative retain enough of the information to think the question through?

·         Is the person legally able to give consent?

·         If not, should the person be involved in the discussion anyway?

·         What are the alternatives to participation for the person? Does the person believe that those alternatives are real?

·         What are the pressures on the person to consent or refuse?  If surrogate permission is necessary, what are the pressures on the legally authorized representative to consent or refuse?

·         Is the selection of participants equitable, particularly given the special considerations raised by research involving vulnerable populations?

Criteria for Inclusion in Research

The IRB considers and evaluates the following criteria before approving research involving adult participants with impaired decision-making capacity:

·         The research must relate to the cognitive impairment, lack of capacity, or serious or life-threatening diseases and conditions of research participants [CA Health & Safety Code 24178(b)]

·         The research is either minimal risk, more than minimal risk with a prospect of direct benefit, or more than minimal risk without a prospect of direct benefit, but of importance to the vulnerable population.

·         Adequate provisions are made for obtaining consent from the participant or the participant’s legally authorized representative.

·         Whether assent of the participants is a requirement, and, if so, whether the plan for assent is adequate.

·         The protocol must have an adequate plan for the assessment of the capacity to consent.

The IRB may consider additional safeguards to protect participants, such as:

·         Requiring the involvement of participant advocates

·         Requiring independent monitoring

·         Requiring waiting periods

·         Appointing a monitor to supervise the informed consent process.

Such decisions may be based on the amount of risk involved in the research and the likelihood that participants will derive health benefits from their participation. 

Assessment and Determination of Incompetence

If it is believed that the prospective participant is not competent to consent for him or herself, competency must be determined by a physician (generally an investigator on the protocol).  A determination of incompetence shall be made after an appropriate medical evaluation that concludes there is little or no likelihood that the participant will regain competence in a reasonable period of time, or as established by legal determination.  This definition of incompetence is not limited to the legal definition but also may be a clinical judgment that a person lacks the capacity to understand the circumstances of participating in research and to make an autonomous decision to take part.

Competency should be evaluated on an individual basis to avoid incorrect assumptions as to an individual’s ability to make decisions.  Criteria for determining competence might vary according to the degree of risk or discomfort presented by the research procedures and the extent to which therapeutic gain can be anticipated.

Some approaches to this assessment include:

·         A post-consent quiz documenting the participants’ knowledge of critical elements in the informed consent document - i.e., nature of the illness being studied, voluntary nature of participation, ability to withdraw at any time, consequences of withdrawing, possible risks and benefits of participation, procedures involved, time required, confidentiality, and whom to call with any questions.

·         The study investigators may ask a physician/psychologist outside the research team to evaluate the potential participant's decisional capacity.

The IRB may consider additional safeguards to protect participants, such as:

·         Requiring the involvement of participant advocates

·         Requiring independent monitoring

·         Requiring waiting periods

·         Appointing a monitor to supervise the informed consent process.

Such decisions may be based on the amount of risk involved in the research and the likelihood that participants will derive health benefits from their participation. 

Obtaining Consent from a Legally Authorized Representative

The IRB, consistent with state and federal human subjects regulations, requires that consent for research be obtained from the participant’s legally authorized representative, if the subject lacks the capacity to consent (e.g., OHRP 45 CFR 46.116, FDA 21 CFR 50.20, CA Health & Safety Code 24178).  Section 24178 of the California Health and Safety Code specifies the legally authorized representative of the participant in most (but not all) research situations for California and its requirements must be met before a surrogate may be used under its provisions.

See guidance Research Surrogate Decision-Makers - Section 24178 of the California Health and Safety Code. 

Participants in Psychiatric Units or Mental Health Facilities: Special Rules

Surrogates for an inpatient on a psychiatric unit or in a mental health facility or a patient on a psychiatric hold may not be able to consent for research under different California laws, particularly if the research participant has been adjudicated to lack the capacity to consent and a conservator appointed.  An investigator who proposes to involve such participants with the possible need for surrogate decision makers should discuss the situation with the IRB staff or the IRB legal advisor in the Office of the General Counsel. 

 

VA Research – Additional Requirements

Criteria for Decision-Making Capacity

   See VHA Handbook 1200.05.

 

Criteria for enrolment

      1.            Individuals who lack decision-making capacity may be enrolled in protocols if:

The proposed research entails:

(a) No greater than minimal risk to the subject as determined by the IRB;

or

(b) If the research presents some probability of harm, there must be at least a greater probability of direct benefit to the subject;

or

(c) Greater than minimal risk and no prospect of direct benefit to individual subjects, but is likely to yield generalizable knowledge about the subject’s disorder or condition that is of vital importance for the understanding or amelioration of the subject’s disorder or condition.

      2.            The disorder (e.g., Alzheimer’s) leading to the individual’s lack of decision-making capacity is being studied, whether or not the lack of decision-making itself is being evaluated (e.g., an individual who lacks decision-making capacity as the result of a stroke can participate in a study of cardiovascular effects of a stroke), but only if the study cannot be performed with only persons who have decision-making capability 

      3.            The subject of the study is not directly related to the individual’s lack of decision-making capacity, but the investigator can make a compelling argument for including individuals who lack decision-making capacity in the study (e.g., transmission of methicillin-resistant Staphylococcus aureus (MRSA) infections in a nursing home where both individuals with, and those without, decision-making capacity are affected). 

 

IRB Determination

If the criteria for enrolment are met, the IRB may approve the inclusion of individuals who lack decision-making capacity in research studies on the basis of informed consent from LARs as defined VHA Handbook 1200.05.

Before approving the study, the IRB must:

(a)    Ensure the study includes appropriate procedures for respecting dissent;

(b)   Consider whether or not the study needs to include procedures for obtaining assent; and

(c)    Determine whether any additional safeguards need to be used (e.g., consent monitoring).

 

Where consistent with state law, VA policy recognizes as legally authorized representatives:

      1.            Persons appointed as health care agents under Durable Powers of Attorney for Health Care (DPAHC)

      2.             Court appointed guardians

      3.            Next of kin in the following order of priority: spouse, adult child, parent, adult sibling, grandparent or adult grandchild.

See checklist Research Involving VA Studies.

12.2.2. Pregnant Women, Fetuses and Neonates

The IRB has and follows written policies and procedures requiring appropriate protections for prospective participants who cannot give consent or whose decision-making capacity is in question. (AAHRPP Element II.4.B)

 

In accordance with OHRP, the IRB requires that additional protections be provided to pregnant women, fetuses and neonates involved in research.  General considerations related to research involving pregnant women, fetuses and neonates are set out in Chapter 9.  The special informed consent requirements are specified in 45 CFR 46, Subpart B (OHRP) and are summarized in the guidance Research Involving Pregnant Women, Fetuses, and Neonates.  

Pregnant Children

If the pregnant person is under the age of 18 and is not emancipated, the IRB generally requires, consistent with OHRP, that parental permission and child assent be obtained.  If the research is therapeutic, and the PD believes that the child’s participation in the research falls into one of the categories under California law where an unemancipated minor is permitted to consent to her own medical care, the PD should confirm this with IRB staff or the IRB legal advisor in the Office of the General Counsel.

Nonviable Neonates

Consent may not be obtained from a legally authorized representative of either or both of the parents of a nonviable neonate.  The IRB will not permit elements of the informed consent process to be altered or waived in research involving nonviable neonates, even if the general requirements for waiver are satisfied. 

When it has been determined that the neonate is viable, the neonate is considered a child and the consent requirements laid out below apply.

12.2.3. Children and Consenting Minors

The IRB has and follows written policies and procedures requiring appropriate protections for prospective participants who cannot give consent or whose decision-making capacity is in question. (AAHRPP Element II.4.B)

The IRB imposes additional protections on research involving children, in accordance with 45 CFR 46, Subpart D and 21 CFR 50, Subpart D.

By regulatory definition, “children” are persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted.  In California, a person under 18 years old is considered a “child,” and may not legally give consent, although there are certain exceptions for emancipated and self-sufficient minors. 

Since children cannot legally give consent, informed consent must be obtained from parents (“parental permission”), or the legally appointed guardian. The IRB requires the investigator to obtain the permission of a child's parent(s) or guardian before enrolling the child in a study.  See guidance Parental Permission.

Assent

When, in the judgment of the IRB, the children are capable of providing assent the IRB may determine that assent is required, that adequate provisions are made for soliciting the assent of the children, and whether and how assent must be documented. Generally, children aged 7 and above may be asked to give their assent to participation.

When Minors, Including Emancipated Minors, may Consent as Adults

In accordance with California law, there are certain situations in which the IRBs permit minors to consent to participation in research as adults without parental permission.  If the protocol director is not familiar with such laws, he or she may need to consult with IRB staff or the IRB legal advisor in the Office of the General Counsel prior to enrolling a minor in a research study without parental permission, to ensure that the applicable legal requirements are met.  The criteria under which a waiver of parental permission may be granted are discussed in the guidance Consent for Protocols Involving Children and Consenting Minors.

See guidances:

·         Consent for Protocols Involving Children and Consenting Minors

·         Parental Permission

·         Chapter 12.4 for information on documentation of informed consent, and assent.

12.2.4. Illiterate Participants

The IRB has and follows written policies and procedures to evaluate the consent process and to require that the Researcher appropriately document the consent process. (AAHRPP Element II.3.F)

The IRB has and follows written policies and procedures requiring appropriate protections for prospective participants who cannot give consent or whose decision-making capacity is in question. (AAHRPP Element II.4.B)

The IRB allows individuals who speak and understand English, but who cannot read the consent materials due to illiteracy, to enroll in a study by “making their mark” (e.g., signing or marking an “X”) on the consent document, after going through the informed consent process.

If a participant, or their LAR, is illiterate:

·         Information in the consent materials should be presented orally, including the California Experimental Subject’s Bill of Rights (as appropriate, and for clinical investigations)

·         Sufficient time should be allowed for questions to be asked and answered, both by the participant, and by the person obtaining consent to ensure the participant comprehends the consent information.

Additionally, FDA guidance on Illiterate English Speaking Subjects contains recommendations for documenting the consent process when a participant is competent and understands and comprehends spoken English, but is physically unable to talk or write, but can indicate approval or disapproval by other means:  

·         An impartial witness, present during the entire informed consent discussion, signs and dates the consent document,

·         Videotaping the consent discussion might be considered,

·         The person obtaining consent (POC) might document on the consent form the method used for communication with the prospective subject and the specific means by which the prospective subject communicated agreement to participate.

Participants (or their LARs) must be given a copy of the signed consent document(s), and any other written information provided to participants.

12.2.5. Non-English Speaking Participants

The IRB has and follows written policies and procedures requiring appropriate protections for prospective participants who cannot give consent or whose decision-making capacity is in question. (AAHRPP Element II.4.B)

Stanford University is located in a culturally diverse region of California.  Investigators are encouraged to recruit and include all segments of the community in research, including individuals whose primary language is not English.

Participants who do not speak English should be presented with a consent document written in a language understandable to them, and which embody all the elements necessary for legally effective informed consent. 

The Stanford HRPP and OHRP strongly encourage the use of a full consent form translated into the participant’s language whenever possible. When all of the participants in a study (i.e., the target population) are anticipated to be non-English speaking, a full translated consent is required.  Refer to the Human Subjects Website for information on translating consent forms.

When a full-length form embodying all elements of consent is required by the IRB to document consent, the IRB requires that appropriately translated consent documents be submitted to the IRB for review and approval prior to their use in enrolling participants. 

Investigators may use language translators or interpreter services to obtain consent in a language understandable to the participant or the participant's legally authorized representative.  The IRB may utilize expedited review procedures in approving such documents if the English language consent document has already been approved. 

Short Form Consent Process

Federal regulations permit the use of a short form consent process (45 CFR 46.117(b)(2) and 21 CFR 50.27(b)(2)) with the prior approval of the IRB; for more information see Chapter 12.1.4 above, and the Human Subjects Website.

12.2.6. Prisoners

The IRB has and follows written policies and procedures requiring appropriate protections for prospective participants who cannot give consent or whose decision-making capacity is in question. (AAHRPP Element II.4.B)

The IRB considers prisoners to be a vulnerable population because both their incarceration and the constraints imposed on them during their incarceration may render them unable to make a truly informed and voluntary decision regarding whether to participate in research.  The IRB imposes additional protections pertaining to biomedical and behavioral research involving prisoners, limits the types of research that can be approved, and requires special consent information as specified in OHRP in 45 CFR 46 (Subpart C) and Sections 3521-3522 of the California Penal Code. Guidance Involvement of Prisoners in Research is provided.  (See Chapter 9 for an explanation of these additional safeguards.)  If the Protocol Director (PD) is not familiar with these legal requirements, the PD who proposes to involve prisoners in research should contact IRB staff or the IRB legal adviser in the Office of General Counsel prior to submission of the protocol and consent document to the IRB for review.

As required by California law regarding prisoner research, the IRB evaluates the consent process and the consent document to ensure that the information disclosed to the participant covers the requirements of California Penal Code Sections 3521-3522. These California consent requirements duplicate requirements already covered by OHRP, except for the requirement that the prisoner participant be informed of the expected recovery time after completion of the experiment.

Prisoners at VA Facilities

The IRB, consistent with VA policy, prohibits research on prisoners conducted by VA investigators while on official duty, or at VA facilities unless a waiver has been granted by the Chief Research and Development Officer.  (VHA Handbook 1200.05).  If the waiver is granted, the research must be conducted in accordance with the general IRB policies and procedures specified above.

12.3   IRB Review of the Consent Process, including Consent Documents

Section revised: 04/15/16  

 The IRB has and follows written policies and procedures to evaluate the consent process and to require that the Researcher appropriately document the consent process. (AAHRPP Element II.3.F)

Protocol Directors (PDs) should refer to Chapter 14.6 for information regarding the development of an informed consent process and method of documentation appropriate to the type of research and the study population. 

 PDs must submit for IRB review any consent document(s) and explanation of the circumstances under which informed consent will be sought for new protocols, at continuing review, and whenever a modification to the consent process or documents is requested.

The Protocol Application solicits the information necessary for the IRB to evaluate whether the informed consent process will be appropriately conducted given the protocol-specific circumstances (e.g., level of risk, inclusion of special participant populations) and adequately protects participants, considering issues such as whether:

      1.            Participants have sufficient time to discuss concerns and decide whether to participate in the research;

      2.            The possibility of coercion and undue influence is minimized;

      3.            Communications to the participant or their LAR  are in a language understandable to them; and

      4.            Consent process communications do not include any exculpatory language through which the participant or their LAR is made to waive, or appear to waive, any of the participant’s legal rights, or which releases or appears to release the investigator, sponsor, institution, or agents from liability for negligence.

The same evaluation criteria apply to review and approval of the consent process and consent document(s) when reviewed by the expedited process, as by regular review.

The IRB staff review the consent document(s) and consent process information (see Informed Consent Checklist.)  For continuing review or modifications, any new information that could impact participants’ risks (e.g., adverse events) or procedure changes are also examined to ensure the consent document is appropriately updated.  Re-consent may be required.  Examples of when re-consent might be required include when there is new information (e.g., risks, procedures, etc.) that could impact participants’ willingness to participate, or any other time the IRB determines it is necessary.  Consent process requirements are discussed in Chapter 12.1 above.

The IRB considers the relationship between the person(s) who will solicit, obtain consent, and explain the consent document and the potential participant.  The IRB requires that the circumstances of the consent process be culturally and linguistically appropriate for the intended participants, and protects participants by minimizing the possibility of coercion and undue influence and allowing adequate time for them to discuss and decide whether to participate in the research. 

The IRB also reviews any direct advertising (e.g., newspaper, TV or radio ads, posters, flyers, letters or postcards, emails, postings on bulletin boards/ internet/ web), since it is considered by the FDA “to be the start of the informed consent and subject selection process.” In order to approve advertisements, the IRB must determine that the direct advertising is not unduly coercive and does not promise a certainty of cure or favorable outcome or other benefits beyond what is outlined in the consent and the protocol. (See Chapter 10.)   See guidance Advertisements: Appropriate Language for Recruitment Material.

Consideration at an IRB Convened Meeting

The IRB determines that all basic, and all additional elements appropriate to the research, are included in the consent process.  All the relevant requirements in OHRP in 45 CFR 46.109(b) and 46.116, and in the FDA regulations in 21 CFR 56.109(b), 50.20 and 50.25, that are applicable to the consent process and the consent document, must be satisfied for IRB approval.  

The IRB may require revisions to the consent document as a condition for approval. If the revisions are minor and can be dictated verbatim at the meeting, the protocol may be approved contingent upon the revisions being made.  The Panel will determine if a member or IRB staff can confirm that the revisions have been implemented as specified before the contingency can be removed. If revisions are greater than minor or cannot be dictated verbatim at the convened meeting, the protocol is tabled, and the consent document is referred back to the PD for the drafting of the revisions and submission at a future convened meeting.  If the PD disagrees with the verbatim revisions specified by the IRB, the protocol is tabled and the PD must submit a revised consent document for future consideration.

The approval date and the expiration date must be added to the consent document(s).  (See Chapter 14.6).

Additional Requirements

See Other Federal Agencies - Additional Requirements [GUI-42].

 

12.4   Documentation of Informed Consent – Signature Requirements

Section revised: 3/13/13  

The IRB has and follows written policies and procedures to evaluate the consent process and to require that the Researcher appropriately document the consent process. (AAHRPP Element II.3.F)

Documentation of informed consent refers to a participant, or their legally authorized representative (LAR), signing and dating an IRB-approved, dated consent document, which includes the eight basic elements of informed consent and the six additional elements of informed consent, when appropriate (45 CFR 46.116; 21 CFR 50.25(a),(b)).

When a person agrees to be a participant in a research study, signing the consent document indicates that they have participated in the consent process, and understand the information provided to them.

Documentation requirements for informed consent are specified in OHRP in 45 CFR 46.117(a),(b) and FDA 21 CFR 50.27(a),(b). 

In order to approve research, the IRB must determine that informed consent will be appropriately documented, unless the IRB waives documentation under OHRP or FDA regulations (see Chapter 12.5.2.).  If a participant lacks the capacity to consent, then consent for research must be obtained from their LAR.  See Chapter 12.2 above, and guidance Research Surrogate Decision-Makers - Section 24178 of the California Health and Safety Code.

Consent is documented through use of a written consent document signed and dated by the participant or their legally authorized representative that embodies all of the required elements of informed consent (see Chapter 12.1).  Only the IRB approved informed consent document may be used, and unless the requirement is waived by the IRB, the document must be signed by the participant (or the participant’s LAR), and a copy must be given to the person signing the form.  FDA regulations require that the signature be dated.

Stanford Hospital and Clinics (SHC), the Lucile Packard Children’s Hospital (LPCH) and Stanford University policies stipulate that the signed consent document must be scanned into the participant's medical record.  The VA has a similar requirement.

Short Form Consent Process – Additional Signature Requirements 

Subject to prior approval of the IRB, consent may be documented through use of a short form written consent document with the requirements and process specified in OHRP 45 CFR 46.117(b)(2) and the FDA regulations in 21 CFR 50.27(b)(2).  The short form consent process is generally applicable to situations involving non-English participants. If the participant agrees to take part in the study, the following signatures are required:

On the short form consent document (translated): 

                                i.            Participant or the participant's legally authorized representative [LAR] 

                              ii.            Witness (the interpreter may act as the witness)

On the summary form (English):  

                                i.            Person obtaining consent 

                              ii.            Witness (the interpreter may act as the witness)

For information on using the short form consent process see Chapter 12.1.4 above and the Human Subjects Website.

Children Participants, Documentation of Informed Consent, and Assent

Since children cannot legally give consent, informed consent must be obtained from parents (“parental permission”), or the legally appointed guardian. For information on the requirements for documentation of consent for children participants, see guidances Consent for Protocols Involving Children and Consenting Minors and Parental Permission.

When, in the judgment of the IRB, the children are capable of providing assent, the IRB may determine whether and how assent must be documented.  See the Assent Template and Chapter 12.2.3.

12.5   Waiver or Alteration of Informed Consent Requirements

Section revised: 6/1/13  

The IRB has and follows written policies and procedures for approving waivers or alterations of the consent process and waivers of consent documentation. (AAHRPP Element II.3.G)

·         Waiver or alteration of the consent process

·         Waiver of documentation of informed consent – (“waiver of signature”)

12.5.1. Waiver or Alteration of the Consent Process

Under OHRP 45 CFR 46.116(c) (d), and (e), IRBs have authority to alter or waive the requirement to obtain informed consent. 

FDA regulations do not provide for a waiver or alteration of the informed consent process; the only exceptions to the informed consent requirements are for clearly defined circumstances of emergency use of a test article (see Chapter 5.8), and waivers granted for planned emergency research (see Chapter 12.6). Thus, the information below in this Chapter 12.5.1 applies only to non-FDA-regulated research.

The IRB may approve an investigator’s request to waive or alter the requirement to obtain informed consent if the investigator demonstrates with specificity that the criteria under 45 CFR 46.116(c) or 46.116(d) are met.  To approve such a request under 46.116(d), the IRB must find and document the following:

      1.            The research involves no more than minimal risk to the subjects;

      2.            The waiver or alteration will not adversely affect the rights and welfare of the subjects;

      3.            The research could not practicably be carried out without the waiver or alteration; and

      4.            Whenever appropriate, subjects will be provided with additional pertinent information after participation.

Also, under 45 CFR 46.116(c) the IRB may waive or alter the consent process; however this is rarely applicable.

To request a waiver or alteration of the informed consent process the investigator must demonstrate that each of the criteria under Section 46.116(c) or (d) is met for the given protocol.  (See Protocol Application). 

To approve a waiver or alteration of the informed consent process the IRB must find and document that all regulatory criteria under 45 CFR 46.116(d) (OHRP) are met and that the research is not subject to FDA regulations.

Special Considerations for Research Involving Deception

In research involving deception, the investigator may, with protocol-specific justification, request an alteration of the consent process.  The IRB may approve the research, including the request to alter the requirement for informed consent if the investigator demonstrates that deception or incomplete disclosure is necessary and addresses concerns relating to participant protection; e.g., debriefing.   

Research Involving Children: Waiver of Parental Permission/Guardian Consent 

Research regulated by the FDA is not eligible for waiver of parental permission, except for the use of an FDA test article meeting the emergency exception (see Chapter 12.6). 

 The IRB will often consider a request for a waiver or partial waiver of parental permission for minimal risk research to be conducted in a classroom. 

The IRB may waive parental permission by determining that the criteria for waivers or alterations are met. However, research is ordinarily not suitable for a waiver of parental permission if it involves any of the following issues:

      1.            Parental political affiliations or beliefs

      2.            Mental or psychological problems

      3.            Sexual behavior or attitudes

      4.            Illegal, antisocial, or self-incriminating behavior

      5.            Appraisals of other individuals with whom the minor has a familial relationship

      6.            Relationships legally recognized as privileged (lawyers, doctors, clergy), and

      7.            Religious affiliations or beliefs.

If the IRB waives the requirement for parental permission, it may require an alternative mechanism to protect the child participants (e.g., appoint a qualified child advocate).

Additional Requirements - Other Federal Agencies

Additional requirements might apply, depending on the source of support/funding (e.g., Department of Defense, Department of the Navy, and Department of Education (such as compliance with Family Educational Rights and Privacy Act (FERPA)): see Other Federal Agencies - Additional Requirements [GUI-42].

12.5.2. Waiver of Documentation of Consent – (“waiver of signature”)

As allowed by OHRP (45 CFR 46.117 (c)) and FDA regulations (21 CFR 56.109(c)), the IRB may waive the requirement to obtain written documentation of informed consent.  This provision can be used only for the waiver of documentation of consent, not for waiver or alteration of the consent process itself.  A waiver of documentation of consent does not mean that requirements of the consent process are removed.

 

Even if a waiver of documentation is granted by the IRB, permitting the investigator to forego obtaining the participant’s signature on a written consent document, the investigator still must provide the participant with all of the information described in Chapter 12.1 required to constitute a complete and appropriate consent process, through an information sheet, or through an oral script in a language understandable to the participants.  In all cases in which the requirement for documentation of consent is waived, the IRB may require the PD to provide participants with the written consent document with an option to sign the consent document, or with a written statement regarding the research. 

To approve a waiver of documentation, the IRB must find that the protocol-specific justification for waiving documentation satisfies regulatory criteria.  Specifically, the IRB must determine the regulatory basis for the waiver as one of the following (note that a) does not apply for FDA-regulated research):

(a)    Under OHRP (45 CFR 46.117(c)(1) the IRB must find and document either: 

                    i.            the only record linking the participants and the research would be the consent document, and the principal risk would be potential harm resulting from a breach of confidentiality. Each participant will be asked whether he/she wants documentation linking the participant with the research, and the participant’s wishes will govern; or

                  ii.            the research presents no more than minimal risk of harm to participants and involves no procedures for which written consent is normally required outside of the research context;

or

(b)   For research subject to OHRP and FDA regulations, the IRB must find and document that the research involves no more than minimal risk to participants and involves no procedures for which written consent is normally required outside of the research context. (45 CFR 46.117(c)(2), 21 CFR 56.109(c)(1)).

Guidance Findings for Waiver or Alteration of Consent Requirements and Findings for Waiver of Documentation (Including Signature) of Consent is available to IRB members and on the Human Subjects Research website.

Waiver or Alteration of HIPAA Authorization

In order to waive or alter an authorization, the investigator must provide sufficient information on which the IRB may make the following three findings specified by the Privacy Rule (45 CFR 164.512(i)(2)(ii):

A.    The use or disclosure of protected health information (PHI) involves no more than minimal risk to the privacy of individuals based on;

1.      An adequate plan to protect the identifiers from improper use and disclosure;

2.      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

3.      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 project, or for other research for which the use or disclosure of protected health information would be permitted by the Privacy Rule;

B.     The research could not be practically conducted without the waiver or alteration; and

C.     The research could not be practically conducted without access to and use of the protected health information.

See Stanford University HIPAA Policy H-13 Research and Patient Privacy, Appendix A.

12.6   Exceptions to Informed Consent in Emergency Situations

Section revised: 7/15/2015  

The IRB has and follows written policies and procedures for making exceptions to consent requirements for planned emergency research and reviews such exceptions according to applicable laws, regulations, codes, and guidance. (AAHRPP Element II.4.C)

Note: “Planned emergency research” is not synonymous with “emergency use of a test article”, which is addressed in Chapter 5.8.

Planned emergency research refers to research planned for emergency settings, including the planned use of a test article.

Planned emergency research involves an extensive approval process, including FDA approval, prospective IRB review, and approval and consultation with representatives of the communities where the research will be conducted and from where participants will be drawn. Investigators must submit a protocol application including a description of the informed consent process or a request to waive informed consent; often in emergency settings it is not possible to obtain informed consent from a potential participant when there is insufficient time and a legally authorized representative (LAR) is not available. 

 The IRB may waive the requirement for informed consent in accordance with an exception under 21 CFR 50.24 (FDA) or 45 CFR 46.101(i) or 45 CFR 46.116(f) (OHRP), depending on whether or not the research is subject to FDA regulation, given that all required IRB determinations under these provisions can be made.  Under these regulations, the IRB may permit planned research in an emergency setting without the informed consent of the participants or their legally authorized representatives in a limited class of emergent situations where the participant is in need of an emergency experimental intervention, but cannot give informed consent due to a life-threatening medical condition and there is not sufficient time to obtain consent from the participant’s legally authorized representative. (This does not apply to VA research – see below.)

In addition, advance notice of such planned emergency research protocols will be provided to the Office for Human Research Protections pursuant to 45 CFR 46.101(i).

See also:

·         Informed Consent Requirements in Emergency Research [OHRP]

·         Exception from Informed Consent for Studies Conducted in Emergency Settings [FDA]

 

VA Research

Planned emergency research cannot be conducted by the VA.  See VHA Handbook 1200.05.

Additional Requirements - Other Federal Agencies

Additional requirements might apply, depending on the source of support/funding (e.g., Department of Defense, Department of the Navy (such as who may grant waivers of the consent process and human research protections policy requirements): see Other Federal Agencies - Additional Requirements [GUI-42].

12.7   Observation of the Consent Process

Section revised: 3/13/13  

 STANFORD has and follows written policies and procedures that allow the Institutional Review Board to function independently of other organizational entities in protecting research participants. (AAHRPP Element I.1.C)

See the Charges by the Vice Provost and Dean of Research to:

·         The Administrative Panel on Human Subjects in Medical Research – IRB

·         The Administrative Panel on Human Subjects in Medical Research – IRB/SCRO

·         The Administrative Panel on Human Subjects in Nonmedical Research.

As part of the IRB oversight options, the IRB may require that a staff member or an outside third party observe the consenting of research participants to determine:

·         Whether the informed consent process has been appropriately completed and documented;

·         Whether the participant has had sufficient time to consider study participation, that no coercion has been used by the consenting staff; and

·         That the information presented to the participant reflects the content of the consent form and is conveyed in understandable language.

The IRB may require that one or more informed consent process situations be observed for selected protocols.  IRB considerations used to choose such protocols include:

·         High risk studies

·         Studies that involve particularly complicated procedures or interventions

·         Studies involving potentially vulnerable populations (e.g., ICU patients, children)

·         Studies involving study staff with minimal experience in administering consent to potential study participants, or

·         Situations when the IRB has concerns that the consent process is not proceeding well.

See:

·         Procedure for Observation of the Consenting Process [PRO-C2]

·         Consent Observation Checklist [CHK-C15].