Chapter 13 - Informed Consent and Documentation

General Overview of Informed Consent

Informed consent is one of the primary ethical requirements underpinning research involving humans; it reflects the basic principle of respect for persons. It should always be remembered that informed consent is an ongoing process, not a single event, designed to provide potential research subjects with all of the relevant information they need to make a fully informed, autonomous decision as to whether they wish to participate in a research study.

To assist investigators and coordinators who are conducting research, information regarding the informed consent process is provided on the HRPO website. Examples and instructions are available, including guidelines for the informed consent process and sample language for the informed consent document.

IRB Review of Informed Consent Process

During its review of the informed consent process as described in the protocol, the IRB requires that:

  • Adequate opportunity is provided to the subject or the subject’s legally authorized representative to read the consent document and ask questions regarding the study before the informed consent document is signed.
  • The consent process minimizes the possibility of coercion or undue influence. The consent discussion is in language understandable to the subject or the subject’s legally authorized representative.
  • The information communicated to the subject or the subject’s legally authorized representative during the consent process does not include any exculpatory language that waives or appears to waive any legal rights that the subject may have, or releases or appears to release the investigator, the sponsor, the institution or its agents from liability for harm caused by their negligence.

In addition, the IRB requires that the consent document include all of the basic elements of consent set forth in 45 CFR 46.116 and, if applicable, 21 CFR 50.25, except those which can be waived, or altered, according to regulation. The IRB may also require that additional elements or information be given to the prospective subjects when, in the IRB’s judgment, the information would meaningfully add to the protection of the rights and welfare of the research subject.

Basic Elements of Informed Consent

45 CFR 46.116 (a) or 21 CFR 50.25(a) include:

  • A statement that the study involves research;
  • A description of any reasonably foreseeable risks or discomforts to the subject;
  • A description of benefits to the subject or others that may be reasonably expected from the research;
  • The disclosure of appropriate alternative procedures or course of treatment, if any, that might be advantageous to the subject;
  • A statement describing the extent to which confidentiality of records identifying the subject will be maintained;
  • For medical research involving more than minimal risk, an explanation as to whether or not any compensation or any medical treatments are available if injury occurs during study participation;
  • The identification of an individual who can be contacted by the subject for answers to questions related to the research, research-related injury, or their rights as a research subject;
  • 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 s/he is otherwise entitled.

Additional Elements of Informed Consent

45 CFR 46.116 (b) or 21 CFR 50.25(b) that should be addressed, as appropriate include:

  • A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable;
  • Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent;
  • Any additional costs to the subject that may result from participation in the research;
  • The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;
  • 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;
  • The approximate number of subjects involved in the study.

Consent Form Addendum

When subjects need to be informed of specific changes in the risk or benefit of study participation, an addendum consent, which focuses on the new information, may be more appropriate than a modified consent document.  A consent form addendum may also be used to inform enrolled subjects about significant new findings that may have a bearing on their willingness to continue participation in the study.

 

Waivers

Waiver of the Requirement to Obtain a Signed Informed Consent

Regulatory Requirements

Following expedited or full-board review, the IRB may waive the requirement to obtain a signed consent form for some or all subjects if it finds that either:

  1. 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 (i.e., see 45 CFR 46.117 (c) (2); 21 CFR 56.109 (c) (1)) or
  2. the only record linking the subject and the research would be the informed consent document and the principal risk would be potential harm resulting from a breach of confidentiality (i.e., see 45 CFR 46.117 (c) (1))
    • Subject to granting a waiver of the requirement to obtain a signed informed consent based on this criterion, the IRB will require the principal investigator to ask each subject whether s/he wants documentation linking him/her to the research, and the subject’s wishes will govern.

The IRB will not waive the requirement to document informed consent based on criterion #2 if the research study is subject to the FDA regulations (21 CFR Parts 50, 56) governing human subject protections.

Upon granting a waiver of the requirement for obtaining a signed informed consent, the IRB reviews and approves the information that will be provided to potential subjects to obtain their verbal consent for study participation, and the procedure(s) that will be used by the investigators to document obtaining verbal consent.

IRB Documentation of Concurrence

Documentation of concurrence that a request for waiver to obtain written informed consent meets with the applicable regulatory requirements (45 CFR 46.117 (c), 21 CFR 56.109 (c)) is required of the IRB reviewer(s). The IRB reviewer utilizes the "Waiver to Obtain a Signed Consent" form found on the OSIRIS website. For full board protocols, the Full Board Research Review Coordinator documents that the applicable criteria have been met in the minutes. For expedited reviews, the Exempt/Expedite Research Review Coordinator documents that the applicable criteria have been met via electronic notification to the Vice Chair.

Waiver (or Alteration) of Informed Consent
 

Regulatory Requirements

The IRB requires that informed consent be sought from each prospective subject or the subject’s legally authorized representative prior to participation in research activities, with the following exceptions.

  1. The IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent, or
  2. The IRB may waive the requirement to obtain informed consent if it finds and documents that the research activity meets the criteria for a waiver of consent as addressed under 45 CFR 46.116(d) as follows:
    • The research involves no more than minimal risk to the subjects;
    • The waiver or alteration will not adversely affect the rights and welfare of the subjects;
    • The research could not practicably be carried out without the waiver or alteration; and
    • Whenever appropriate, the subjects will be provided with additional pertinent information after participation.
  3. The IRB may also waive the requirement to obtain informed consent if it finds and documents that the research activity meets the criteria for a waiver of consent as addressed under 45 CFR 46.116 (c) This IRB does not typically receive requests of this type. If investigators wish to request this waiver, they should contact the IRB for further guidance.

The IRB does not waive the requirement to obtain informed consent if the research study is subject to the FDA regulations (21 CFR Parts 50, 56) governing human subject protections except for planned emergency research 21 CFR 50.24 see Chapter 16.

IRB Documentation of Concurrence

Documentation of concurrence that a request for waiver of informed consent meets with the applicable regulatory requirements (45 CFR 46.116)  is required of the IRB reviewer(s). The IRB reviewer utilizes the "Waiver of Informed Consent" form found on the OSIRIS website. For full board protocols, the Full Board Research Review Coordinator documents that the applicable criteria have been met in the minutes. For expedited reviews, the Exempt/Expedite Research Review Coordinator documents that the applicable criteria have been met via electronic notification to the Vice Chair.

Waiver of Consent for Planned Emergency Research

The IRB (subsequent to full-board review) may approve a research study without requiring that informed consent of all research subjects be obtained if it finds and documents that the research activity meets the criteria for an exception to the requirement to obtain informed consent for emergency research as addressed under planned emergency research regulations found at 21 CFR 50.24. See Chapter 16.

Waiver of Parental Consent for Abused or Neglected Children

The IRB may waive the requirement for parental consent if it determines that the research study is designated for conditions or for a subject population (e.g., neglected or abused children) for which parental or guardian permission is not a reasonable requirement to protect the subjects (see Chapter 14 and also refer to 45 CFR 46.408).

Other Considerations

Assent

For information on assent, please refer to Chapter 14.

Proxy Consent

For research involving subjects who are or may be decisionally impaired such that the subject is not capable of giving informed consent, the IRB approves the research only if it finds that proxy consent is appropriate.  For more information on how this is handled in this subject population, see Chapter 14.

Non-English Speaking Participants

Federal regulations require that informed consent information must be presented in a language understandable to the subject and, in most situations, that informed consent be documented in writing (45 CFR 46.116 and 46.117).  All required elements necessary for legally effective informed consent must be present in the consent document in the language spoken by the research subjects.  Investigators should submit the proposed consent document in English, with a certified translation in the language which will be used with subjects.  This process should be utilized any time a research study is actively recruiting non-English speaking participants.

There is an alternative approach available to investigators in the event that the study is not designed to recruit non-English speaking participants. If a potential subject otherwise meets inclusion criteria, a short form written consent document can be utilized. Guidance on this approach as well as translations of the short form in several different languages are available on the IRB website.
 

Obtaining Consent

Responsibility for Obtaining Consent

The principal investigator of the research study is ultimately accountable for assuring that all aspects of the study are at all times in compliance with applicable research regulations and IRB policies. This includes the entire informed consent process and the instruction and oversight of individuals who may be involved in this process. The IRB application must include a detailed plan for informed consent process and include the individuals who will actually be conducting the consent process.

Studies Involving Drug, Device, or Surgical Procedures

The University requires that the PI or a Co-Investigator who is a licensed physician obtain informed consent. This does not mean the study coordinator cannot introduce the study and answer preliminary questions about the research. The final process of obtaining the written informed consent must be conducted by a physician investigator who must sign the Investigator's Certification statement at the time of this involvement.

There are circumstances when the IRB may permit, with an appropriate justification, that the consent process to be conducted by a licensed health care professional who is listed as a Co-Investigator. This individual must have the appropriate expertise and credentials to perform this duty.

Greater Than Minimal Risk Study

For greater than minimal risk research studies which do not involve the use of a drug, device, or surgical procedure; the PI or listed Co-Investigator must be involved in the informed consent process and must sign the Investigator's Certification statement at the time of this involvement.

Minimal Risk Study

The IRB may approve an exception to the rule requiring the PI or Co-Investigator’s to obtain consent with appropriate justification. If a waiver is requested, the individual who will be involved in the informed consent process and who will sign the Investigator’s Certification must be identified by name or position.

Informed Consent Process

Note that verbal or telephone consent is not acceptable unless the IRB has specifically waived the requirement for a signed consent form. Deferred consent (i.e., obtaining consent after the initiation of study procedures) is also prohibited.

The investigator must seek informed consent under circumstances that give the individual sufficient opportunity to consider whether to participate in the research study, and that minimize possible coercion or undue influence.

Informed consent to participate in a research study should be sought at a time separate from obtaining informed consent for procedures performed for the medical management of the patient (i.e., non-research procedures).For certain research studies (e.g., studies involving questionnaires, surveys) it may be practical and acceptable to mail the informed consent document to the potential subject and to have the signed document returned by mail. If this approach is taken, there must also be provisions for a telephone interaction between the potential subject and investigators to ensure that the informed consent process has been appropriately addressed. The cover letter accompanying the mailed informed consent document and survey or questionnaire materials must clearly address this telephone interaction. The procedures for ensuring an appropriate informed consent process when the consent form is mailed to potential research subjects should be addressed in the Questions 4.11, 4.12, and 4.13 of the OSIRIS application.

The Principal Investigator must retain the original signed informed consent document in his/her research records. A copy of the informed consent document must be provided to the subject. For hospital inpatients, a separate copy of the informed consent document should be incorporated into the patient’s medical record.

In addition to obtaining the signed, written informed consent document, it is recommended that a narrative note be written in the subject’s research records documenting the informed consent process. This documentation may depend on the risk of the study and could include information such as:

  • Who was present during the informed consent discussion;
  • The fact that risks were presented;
  • A notation, if applicable, that significant issues of concern to the subject were addressed;
  • A statement that all questions were answered to the satisfaction of the subject.

The narrative note should also indicate the date and time that the subject signed the informed consent document and be signed by individual responsible for the documentation. Noting the time of consent, in addition to the date, is especially important if any research procedures will be performed on the same day that informed consent was obtained. Note that this is a requirement for any research study involving the evaluation of a research intervention which falls under the jurisdiction of the FDA.

HIPAA Authorization

The IRB requires that written HIPAA authorization be sought from each subject or the subject’s authorized representative prior to participation in any research activity that involves the use of the subject’s protected health information (i.e., identifiable medical record information) maintained by a covered entity (i.e., health care provider, health care plan, health care clearinghouse). See sample HIPAA authorization, found on the IRB website. HIPAA authorization must also be obtained for the placement of research data into the subject’s medical record information maintained by the covered entity.

When protected health information (PHI) will be accessed, used and/or disclosed for research purposes, the research consent may include all the necessary elements under HIPAA thereby alleviating the need for a separate HIPAA Authorization.

Regulatory Requirements

The necessary HIPAA elements include the following:

  • A specific description of PHI that will be collected for research and the purpose of collecting this information;
  • A specific description of any research-derived information that will be placed in the individual’s medical record;
  • The person or class of persons who may use or disclose the PHI collected for research;
  • The person or class of persons to whom PHI collected for research may be re-disclosed and the purpose of such re-disclosure;
  • The expiration date of the authorization;
  • Consequences to the individual of a refusal to sign the authorization;
  • The individual’s right to revoke authorization and consequences of such revocation.

Wavier of HIPAA Authorization - For UPMC Facilities Only

The IRB also serves as the Privacy Board for UPMC facilities and may approve a HIPAA authorization process for studies taking place in UPMC facilities which does not include, or which alters some or all of the elements of a valid written authorization (as specified under 45 CFR 164.508(c)), or waives the requirement for written HIPAA authorization if the IRB finds and documents that the use of the subjects’ protected health information meets the criteria for a waiver as addressed under 45 CFR 164.512 (i)(2)(ii).  In granting an alteration or waiver of HIPAA authorization, the IRB must determine that the alteration or waiver, in whole or in part satisfies each of the following criteria:

  1. The use or disclosure of protected health information involves no more than minimal risk to the privacy of individuals, based on, at least, the presence of the following elements:
  • an adequate plan to protect the identifiers from improper use and disclosure;
  • an adequate plan to destroy the identifiers at the earliest opportunity consistent with the 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
  • an adequate written assurance 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 other research for which the use or disclosure of protected health information would be permitted (i.e., under the HIPAA regulations).The research could not practicably be conducted without the waiver or alteration.

   2. The research could not practicably be conducted without access to the use of the protected health information.

Documentation of Approval Concurrence

Documentation of the IRB’s approval of an alteration or waiver of HIPAA authorization must include:

  • a statement that the alteration or waiver of authorization has been reviewed under either full-board or expedited review procedures;
  • a statement that the IRB has determined that the alteration or waiver, in whole or in part, of the authorization satisfies each of the waiver criteria under 45 CFR 164.512(i)(2)(ii);
  • a statement identifying the date on which the alteration or waiver of authorization was approved;
  • a brief description of the protected health information for which use or access has been determined to be necessary by the IRB; and the documentation of the alternation or waiver of authorization must be signed by the IRB Chair or other IRB member, as designated by the IRB Chair.

The IRB reviewer utilizes the Waiver of HIPAA Authorization form found at (http://www.osiris.pitt.edu)and documents in the minutes (if full board) or in a note to Vice Chair (if expedited) that the applicable criteria have been met.  Note that the IRB cannot approve alteration or waiver of HIPAA authorization for protected health information from covered entities other than UPMC.
 

Use Preparatory to Research Within UPMC

UPMC has established a policy whereby researchers may access protected health information held by UPMC solely for use preparatory to research. Following is an excerpt from the policy.  The policy in its entirety can be found on the IRB website, and researchers should directly contact the appropriate offices within UPMC for further information.

For reviews of PHI preparatory to research (hypothesis/protocol work), HIPAA permits UPMC to make available the PHI to a researcher based solely on the researchers written representations that no PHI shall be recorded for the purpose of research and/or removed from the provider entity and that the PHI reviewed by the researcher shall be limited to that necessary to prepare a research protocol. UPMC shall permit researchers to review PHI, held by a UPMC entity, for the purpose of preparing a research hypothesis and research protocol.

UPMC has a template agreement that is available to the researcher (from the IRB or UPMC) for this HIPAA-permitted activity. The researcher must provide requested information and attest/sign and submit this agreement to the director of the entity’s health information management department or an individual designated by the entity to receive such information in order to access the records/PHI.

Research on Deceased Individuals

Research involving deceased individuals is not human subjects research according to 45 CFR 46.102(f) and does not require IRB oversight unless the research involves both living and deceased individuals.  At the University of Pittsburgh, the Committee for Oversight in Research Involving Decedents (CORID), under the Office of Oversight of Anatomic Specimens, conducts reviews of projects that involve deceased individuals exclusively.

UPMC polices address access to the PHI of deceased individuals as outlined below and found on the IRB website.

UPMC may grant access to and permit researchers to record the PHI of deceased individuals, held by a UPMC entity, under the following conditions:

  • if the information is de-identified by an honest broker service; or,
  • if pursuant to a valid research authorization signed by the administrator or executor of the deceased individual’s estate or the person who is listed as next of kin.

HIV Consent

For studies involving HIV testing a separate consent can be used by investigators to address unique issues under state law. This consent notifies subjects that their information will be handled in compliance with the Pennsylvania law on HIV-related confidential information, that they will be notified of the testing results and that counseling will be available to them prior to and after HIV testing.

Sponsor Contract Language

The University of Pittsburgh Office of Research will provide the IRB with the sponsor’s contract language related to subject injury. The language will be reviewed for consistency with the IRB application and informed consent document. If the language is not consistent, the IRB will contact the research team through OSIRIS and request that a modification be submitted.