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THE COMMITTEE ON HUMAN RESEARCH

UCSF GUIDANCE ON RESEARCH TOPICS AND ISSUES

RECRUITMENT AND CONSENT PROCESS

Consent Guidelines (Revised February 2005, November 2006, March 2008)

• Brief Overview
• Consent Process and Documentation
• Federal Requirements for Informed Consent
• CHR Consent Form Standards
  • General Information
  • Section by Section Discussion
• Sample Consent and Assent Forms
• Other IRBs’ Consent Form Requirements
• Consent by Surrogates/Legally Authorized Representatives
• Waiver of All Consent
  • Minimal Risk Studies
  • Example of Approvable Waiver of Consent
  • Waiving Consent vs. Obtaining Consent from Surrogates/Legally Authorized Representatives
  • Consent for Continuing or Followup Procedures after Initial Waiver of Consent
  • Providing Additional Pertinent Information
  • Research in Emergency Settings – More than Minimal Risk
  • Public Benefit/Service Program Studies
• Waiver of Signed Consent/Obtaining Verbal or Implied Consent
  • Examples of Approvable Waiver of Signed Consent
  • Verbal Consent
  • Information Sheets
  • Implied Consent
• Short Form plus Summary Consent with Non-English Speakers
• Consent in Vulnerable Subject Populations
  • Children and Minors
  • Those Who Are Cognitively Impaired
  • Pregnant Women, Fetuses, and Neonates
  • Prisoners
  • Those Who Do Not Speak, Read, or Understand English
• Useful Links and References

Brief Overview

With few exceptions, researchers must obtain and document consent from the prospective research subject before initiating any screening or study procedures. Any exceptions must be reviewed and approved by the CHR beforehand.

Based on the governing principles of human research outlined in "The Belmont Report" — respect for persons, beneficence, and justice—research investigators have key responsibility for ensuring voluntary participation of research subjects. The recruitment plan, consent process and consent documents to be used with prospective subjects must be carefully designed so that subjects’ consent will be well-informed and freely given.

The Office for Human Research Protections (OHRP) and the Food and Drug Administration (FDA) enforce federal regulations covering informed consent in research involving human subjects.

• Title 45-Code of Federal Regulations (CFR)-Part 46, Section 46.116 and 46.117 applies to human research conducted or funded in whole or part by the Department of Health and Human Services (DHHS).



• Title 21 CFR-Part 50 applies to research involving products regulated by the FDA.

These regulations are applied to all human research at UCSF.

The purpose of these guidelines is to assist investigators in planning the consent process and consent documents to be used in their research studies, in accord with federal regulations and UCSF standards.

Consent Process and Documentation

Informed consent: Any individual (or their legally authorized representative) who is asked to take part in a research study should be able to understand as completely as possible what procedures, risks, benefits, alternatives, and rights are involved, and make the choice about being in the study without pressure or undue inducement to participate.

Ongoing process: Free and informed consent is not one event but an ongoing process. Throughout the study, participants must be told about changes in the study, feel free to ask questions, and be allowed to withdraw from the study at any time for any reason, or even for no reason.

Documentation of informed consent: Federal and state regulations direct that informed consent be documented, in general, with a written consent form incorporating the required elements of consent. The participant or his/her legally authorized representative reads, signs and dates the consent form. The person obtaining consent also signs and dates the consent form. A signed copy of the consent form is given to the participant or, when appropriate, to his/her legally authorized representative.

For further details of federal and UCSF requirements for consent documentation, see 45 CFR 46.117, 21 CFR 50, CHR Consent Form Standards and Sample Consent and Assent Forms.

Exceptions to informed consent requirements: As discussed in detail below, the CHR may approve exceptions to the general rule for informed consent, including waiver of all consent, use of surrogate consenters, use of verbal consent, or use of a short-form process for subjects who cannot read English. Investigators must justify any of these exceptions in their CHR applications.

Purpose of consent document: The form is one part of the entire consent process. It serves as a written summary of the information that was presented to prospective subjects before their agreement to participate in a study, and thus provides a useful reference for both the subject and the investigator.

Contacting prospective subjects: See UCSF Subject Recruitment guidelines for more information on this topic.

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Federal Requirements for Informed Consent

Federal regulations on informed consent (45 CFR 46.116) describe general requirements for informed consent as follows:

Except as provided elsewhere in this policy, no investigator may involve a human being as a subject in research covered by this policy unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence. The information that is given to the subject or the representative shall be in language understandable to the subject or the representative. No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the investigator, the sponsor, the institution or its agents from liability for negligence.

They then stipulate eight basic required elements of informed consent, and six additional elements which may be added to a consent form when appropriate.

The eight required elements of consent are:

1. “a statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject’s participation, a description of the procedures to be followed, and identification of any procedures which are experimental;



2. a description of any reasonably foreseeable risks or discomforts to the subject;



3. a description of any benefits to the subject or to others which may reasonably be expected from the research;



4. a disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;



5. a statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;



6. for research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;



7. an explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject; and



8. a statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.”

The six additional elements which may be added to a consent form when appropriate are:

1. “a statement that the particular treatment or procedures may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable;



2. anticipated circumstances under which the subject’s participation may be terminated by the investigator without regard to the subject’s consent;



3. any additional costs to the subject that may result from participation in the research;



4. the consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;



5. a statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject; and



6. the approximate number of subjects involved in the study.”

In addition, DHHS provides guidance regarding possible conflict of interest in research, including consent form recommendations. Investigator Conflicts of Interest and CHR Review should be consulted for UCSF guidance in this regard.

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CHR Consent Form Standards

In preparing any UCSF consent form or information sheet, the researcher should follow the CHR standard format, adapting as necessary and appropriate.

The goal of the CHR standard format is to create a document that satisfies federal and institutional consent requirements, and presents all needed information in a way that is as clear and easily readable as possible to the prospective subject.

The CHR standard format incorporates OHRP and FDA regulations. The CHR Standard Format was updated in 2004 to reflect consent form recommendations by the National Cancer Institute (NCI).

General information and a section-by-section discussion of CHR’s standard format are provided below. Also see Sample Consent and Assent Forms for examples.

General Information

• Eighth grade reading level: The consent document should be written at the most likely level of understanding of the subject population—in general, an eighth grade reading level is recommended. Everyday vocabulary and simple sentence structure should be used throughout. Researchers always have the option of describing the study in more detail or more scientific language during the consent process (if appropriate). But the initial written description of the study should be simple and straightforward, so that subjects will have an easily understood consent form to take home and refer to.



• Using lay language instead of medical terminology: Unless the subjects are themselves medical professionals, scientific or technical terms should be replaced with or defined in lay language (e.g., "blood draw" is preferable to "venipuncture," "x-ray" to "radiographs," "upset stomach" to "GI upset”).



• Avoiding legalistic language: Legal-sounding language such as "You hereby agree," "You certify that," "You, the undersigned, do acknowledge that," or “You understand that” is unnecessary and should not be used.



• Person of the form: The NCI recommends a “Q&A” format, with the section headings written as questions from the subject’s viewpoint (first person–“I”), and answers/other information written from the investigator’s viewpoint addressing the subject (second person–“you”). This format is preferred for all adult consent forms. Minors’ assent forms may be written entirely in the second person of the subject. In either case, the chosen format should be consistent throughout the form.



• Avoiding “you/your child” format: Using wording like “you/your child” throughout a consent form (in order to use the same form with adult subjects and parents giving permission for their children to be subjects) is confusing and should be avoided. See CHR guidance on consent for children and Sample Consent and Assent Forms for better ways to approach this problem.

Section by Section Discussion

For detailed guidance about information and wording which the CHR prefers in each section of the consent form, see CHR Consent Form Standards – Section by Section Discussion.

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Sample Consent and Assent Forms

For additional wording, see Sample Consent and Assent Forms.

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Other IRBs’ Consent Form Requirements

A UCSF investigator may wish to conduct research at another study site where the institutional review board has different standards for consent documentation. In such cases, the CHR will consider a request to approve use of the other IRB's approved consent form or information sheet, as long as it satisfies the federal requirements for informed consent. The request and the explanation for this should be included in the cover letter of the application.

See Working with Other Institutions and Units for additional information.

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Consent by Surrogates/Legally Authorized Representatives

In general, participation in research should be limited to individuals who can give informed consent for themselves. In special cases where this is not possible, federal and state regulations provide that consent may be given by the subject’s surrogate or legally authorized representative.

For more detailed information on relevant federal, state, and University of California requirements, see Surrogate Consent.

NOTE: Parents’ or legal guardians’ consent (permission) for children to participate in research is covered separately under Minors in Research.

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Waiver of All Consent

NOTE: For chart on regulations pertaining to this and the next section, see 45 CFR 46.116 and 46.117; 21 CFR 50.23 and 50.24; 21 CFR 56.109: Waiver of Consent vs. Waiver of Signed Consent.

In certain cases, federal regulations allow the CHR to approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent, or to waive the requirement to obtain any informed consent. Most complete waivers of consent involve studies in which there are minimal risks to subjects, but complete waivers are also possible in emergency care and a few other circumstances.

NOTE: FDA regulations (21 CFR 50 and 56) differ from DHHS regulations (21 CFR 46) and are generally more restrictive. The differences are noted below.

Minimal Risk Studies

Federal regulation 45 CFR 46.116(d) establishes four criteria for waiving consent or altering the elements of consent in minimal risk studies. There are no corresponding provisions in FDA regulations, and these criteria may not be used to waive or alter the elements of consent in FDA-regulated studies:

1. The research involves no more than minimal risk;



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, the subjects will be provided with additional pertinent information after participation.
   
   Minimal risk is defined in 45 CFR 46.102 as “the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”
   

(Above example adapted from Institutional Review Board: Management and Function, R. Amdur and E. Bankert, Chap. 6-6, "Research without Consent or Documentation Thereof," M. M. Elliott.)

Waiving consent versus obtaining consent from a surrogate/legally authorized representative: When prospective research participants in minimal risk studies cannot consent for themselves because they are incapacitated in some way, the researcher must decide whether to request a waiver of all consent or use of a surrogate consenter/legally authorized representative.

• Ethically, it is usually preferable to use a surrogate who knows the subject’s wishes rather than waive consent entirely. However, these concerns are less serious for studies with minimal risks. Consent can be waived completely if the study is not practicable without the waiver.



• If surrogates will be asked to give consent, even for studies involving minimal risk, the standard procedures for identifying a legally authorized representative and obtaining surrogate consent must be followed (see Surrogate Consent and UCOP Guidance on Surrogate Consent for Research). It may not be practicable to follow this process for some minimal risk studies, in which case a waiver of all consent should be requested.
  
  NOTE: When Surrogate Consent is used in a study, there are strict requirements for obtaining additional consent when the subject becomes competent, especially if there are any continuing or followup procedures.

Consent for continuing or followup procedures after initial waiver of consent: In occasional minimal risk studies, the CHR may waive consent when subjects initially cannot consent for themselves, but require consent for later procedures when subjects recover their capacity to consent.

• Examples where followup consent might be required: The CHR approves waiver of consent for a minimal risk blood draw from patients arriving unconscious at the emergency room. But if the researchers want any procedures (e.g., blood draws, tests, collection of information from records) to continue after subjects become competent to consent, or want the subjects to participate in follow-up procedures (e.g., interviews, office visits, or additional tests or medical record review), then the CHR would probably require that signed consent be obtained before research on that participant could continue.



• Contents of followup consent: The consent form should clearly describe what procedures occurred without the subject’s consent, why they were performed, and what additionally will be done if consent is given to continue the subject in the study. The subject must also be given the option of refusing to allow the researchers to use the data already collected.

Providing additional pertinent information: One requirement when consent is waived in minimal risk studies is that “Whenever appropriate, the subjects will be provided with additional pertinent information after participation” [45 CFR 46.116(d)].

• There are no strict rules for deciding when it is “appropriate” to provide additional pertinent information; but the CHR will apply some general standards, as below, in considering such requests.



• If consent is waived because it is not practicable to obtain consent from large numbers of patients for a retrospective chart review study, generally it also will not be appropriate to attempt to contact those patients to tell them about the study retrospectively.



• If consent is waived because subjects are temporarily incapacitated, it may well be appropriate to provide them with information later, and even, as noted above, to obtain consent for ongoing research.
  
  APPLICATION NOTE: Investigators should specifically address arguments for waiver of standard consent procedures in the CHR Application, Part 8- Consent Process and in the form Appendix: Request for Waiver of Consent/ Authorization for Minimal Risk Research or for Screening for Recruitment.

Research in Emergency Settings – More than Minimal Risk

Federal regulations (21 CFR 50.24; see also OPRR Reports 10/31/96) allow for waiver of consent in situations where there is more than minimal risk to participants, provided there is a prospect of direct benefit to participants and a number of other conditions are met. This waiver applies to both FDA- and DHHS-regulated studies. The conditions include the following:

• The study could not practicably be carried out without the waiver.
• Consultation with community representatives occurs before the study starts.
• Public disclosure is made before and after the study.
• A therapeutic window is defined, and the researcher commits to trying to locate a surrogate/legally authorized representative who can give consent within that window before proceeding to waive consent.

Meeting all of the conditions for waiver under these regulations is arduous, but the regulations do allow research that otherwise could not be approved. It may be worthwhile to consider this process for research in circumstances where treatment must be provided quickly, patients are incapacitated, and a legally authorized representative is not readily available. Examples include research on cardiac arrest, stroke, head trauma, spinal cord injury, gunshot wounds, and poisoning.

For more information on this type of waiver, see the CHR application supplement Emergency Medical Research: Waiver of Informed Consent and the extended discussion in Research in Emergency Settings.

IMPORTANT NOTE: Emergency and Compassionate Use of Experimental Drugs and Devices is usually distinct from planned research in emergency settings. Planned research in emergency settings involving a waiver of informed consent requires compliance with the conditions discussed in this section. Most emergency and compassionate use does not involve waiver of consent and usually, when provided to a single patient, is not considered research by DHHS and is considered research but is exempted from prior CHR approval by the FDA. Physicians should consult with the CHR prior to such use if at all possible, and are required to report to the CHR after any such use. For more information on this topic, follow the link given above.

Public Benefit or Service Program Studies

Federal regulation 45 CFR 46.116(c) provides for waiving consent in the following circumstances. (Note: To date, the CHR has never seen a study that satisfies these requirements; these provisions do not apply to FDA-regulated studies).

1. The project is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs; and



2. The research could not practicably be carried out without the waiver or alteration.

Waiver of Signed Consent/Obtaining Verbal or Implied Consent

NOTE: For chart on regulations pertaining to this and the previous section, see 45 CFR 46.116 and 46.117; 21 CFR 50.23 and 50.24; 21 CFR 56.109: Waiver of Consent vs. Waiver of Signed Consent.

Federal regulations [45 CFR 46.117(c)] allow the CHR to waive the requirement for obtaining signed consent if it finds that either:

1. The only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality (These criteria cannot be used for FDA-regulated studies),
   
   or



2. The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context. This paragraph only also applies to FDA-regulated studies per 21 CFR 56.109(c)(1).

The CHR can also waive signed consent in studies that meet the requirements for waiving all consent. The CHR will usually approve a request for waiver of signed consent in the following situations; in most cases, however, verbal consent (often with use of an information sheet) or implied consent will still be required.

Verbal Consent

Investigators may wish to replace signed consent with verbal consent. The CHR will consider approving such requests in limited circumstances, and will usually require use of an information sheet. If this is not feasible (for example, the only contact is by phone), the CHR may ask to see a script of what would be said to prospective subjects to evaluate the consent process.

Information Sheets

As the regulations state, "in cases where the documentation requirement is waived, the IRB may require the investigator to provide subjects with a written statement regarding the research." In such cases, the CHR will usually call for use of an information sheet that includes most or all of the elements of a consent form but not the subject’s signature.

CONSENT NOTE: Consent forms and information sheets should be written using the CHR Standard Format and Sample Consent and Assent Forms.

Implied Consent

Investigators may wish to replace signed consent with implied consent (e.g., a prospective subject is informed about a study where participation consists only of filling out an anonymous questionnaire; the person completes the questionnaire and, by doing so, agrees to participate in the research). The CHR will consider approving such requests in limited circumstances, based on appropriate justification and information regarding the consent process.

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Short Form plus Summary Consent with Non-English Speakers

In addition to the standard “written consent document that embodies the elements of informed consent required by §46.116,” federal regulation 45 CFR 46.117(as well as identical provisions in 21 CFR 50.27 for FDA-regulated studies) provides for use of an alternative form of consent documentation as follows:

A short form written consent document stating that the elements of informed consent required by §46.116 have been presented orally to the subject or the subject's legally authorized representative. When this method is used, there shall be a witness to the oral presentation. Also, the IRB shall approve a written summary of what is to be said to the subject or the representative. Only the short form itself is to be signed by the subject or the representative. However, the witness shall sign both the short form and a copy of the summary, and the person actually obtaining consent shall sign a copy of the summary. A [signed] copy of the summary shall be given to the subject or the representative, in addition to a [signed] copy of the short form. [Bracketed words are additions to comply with California requirements.]

The CHR will consider a request to use this type of consent documentation for the occasional and unanticipated non-English-speaking prospective subject (see Informed Consent for Research Subjects Who Do Not Read, Speak or Understand English). However, the CHR discourages any other use of this method.

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Consent in Vulnerable Subject Populations

The CHR must exercise special care when considering subjects whose ability to give free and informed consent is compromised in any way.

Some studies propose to involve individuals who cannot give signed or even verbal consent for themselves (e.g., young children, cognitively impaired persons, unconscious patients), or people in other special circumstances (e.g., pregnant women, prisoners).

For further details on consent/assent requirements for such subjects, see:
Vulnerable Subject Populations

• Children and Minors


• Those with Cognitive Impairments


• Pregnant Women, Fetuses, and Neonates


• Prisoners


• Those Who Do Not Speak, Read, or Understand English.

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Useful Links and References

U.S. Department of Health and Human Services (DHHS), Code of Federal Regulations, Title 45 Public Welfare, DHHS, National Institutes of Health, Office for Protection from Research Risks, Part 46, Protection of Human Subjects. http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm, especially Sections 46.116 and 46.117.

Food and Drug Administration (FDA), Department of Health and Human Services, Part 50 – Protection of Human Subjects (21 CFR 50). http://www.access.gpo.gov/nara/cfr/waisidx_98/21cfr50_98.html.

Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htm.

International Conference on Harmonisation, "Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance," April 1996. http://www.fda.gov/cder/guidance/959fnl.pdf.

National Cancer Institute (NCI), US National Institutes of Health (NIH), "Simplification of Informed Consent Documents." http://www.cancer.gov/clinicaltrials/understanding/simplification-of-informed-consent-docs/.

DHHS Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subjects Protection