14 Informed Consent

14.1Informed Consent Process

No investigator may involve a human being as a subject in research without obtaining the legally effective informed consent of the subject or the subject’s legally authorized representative unless a waiver of consent has been approved by the COMIRB. In general, the COMIRB considers individuals who are unable to consent for their own clinical care to be unable to consent for research participation. Tools or instruments such as the Mini Mental Exam can also be used to determine capability to consent.

Investigators must obtain consent prior to entering a subject into a study and/or conducting any procedures required by the protocol, unless consent is waived by the COMIRB.

Consent must always be sought under circumstances that:

Provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate; and

Minimize the possibility of coercion or undue influence.

The COMIRB will consider where the consent process will take place and the individual who will be obtaining consent (e.g. the investigator, collaborator, or qualified designee) in its determination regarding the appropriateness of the consent process. When the potential participant’s understanding of the research may be impaired due to the timing, location, or individuals participating in the proposed consent process, the COMIRB will require an alternative process.

The information that is given to the subject or the representative must be in language understandable to the subject or the representative.

No informed consent, whether oral or written, may include exculpatory language which the subject or the representative is made to waive or appear to waive any of the subject’s legal rights.

No informed consent, whether oral or written, may include exculpatory language through which releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.

A person knowledgeable about the consenting process and the research (i.e., a member of the project’s research team) to be conducted must obtain the informed consent.

If someone other than the investigator conducts the interview and obtains consent, the investigator needs to formally delegate this responsibility and the person so delegated must have received appropriate training to perform this activity.

14.2Basic Elements of Informed Consent

Informed consent must be sought from each potential subject or the subject’s legally authorized representative, in accordance with, and to the extent required by 45 CFR 46.116 and 21 CFR 50.25.

14.2.1Basic Elements

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

 A description of any benefits to the subject or to others which may reasonably be expected from the research;

 A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject (for biomedical research);

 A statement describing the extent, if any, to which confidentiality of records identifying the subject must be maintained;

 For applicable FDA-regulated studies information about ClinicalTrials.gov.

Applicable studies include:

Phase 2 – 4 Interventional studies;

Studies involving drugs, biologics, or medical devices regulated by FDA;

Studies that have at least one site in the US or is conducted under an IND or IDE; and

Studies initiated or ongoing as of September 27, 2007 or later

 For biomedical research involving more than minimal risk, an explanation as to the availability of medical treatment in the case of research-related injury, including who will pay for the treatment and whether other financial compensation is available;

 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;

 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;

 For FDA-regulated studies, the possibility that the Food and Drug Administration may inspect the records needs to be included in the statement regarding subject confidentiality.

 An explanation of whom to contact to voice concerns or complaints about the research.

 Contact information for the COMIRB to obtain answers to questions about the research; to voice concerns or complaints about the research; to obtain answers to questions about their rights as a research participant; in the event the research staff could not be reached; and in the event the subject wishes to talk to someone other than the research staff.

14.2.2Additional Elements

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 (For example: Include when the research involves investigational test articles or other procedures in which the risks to subjects is not well known.);
Anticipated circumstances under which the subject’s participation may be terminated by the investigator without regard to the subject’s consent (For example: Include when there are anticipated circumstances under which the investigator may terminate participation of a subject.);
Any additional costs to the subject that may result from participation in the research (For example: Include when it is anticipated that subjects may have additional costs.);
The consequences of a subject’s decision to withdraw from the research and procedures for orderly termination of participation by the subject (For example: Include when withdrawal from the research is associated with adverse consequences);
A statement that significant new findings developed during the course of the research which may relate to the subject’s willingness to continue participation must be provided to the subject (For example: Include when the research is long term and interim information is likely to be developed during the conduct of the research.);
The approximate number of subjects involved in the study (For example: Include when the research involves more than minimal risk).

14.2.3Additional Elements Required by the VA

When appropriate, VA requires one or more of the following elements of information be provided to the subject:

Commercial Product: If applicable, that the investigator believes that the human biologic specimens obtained could be part of, or lead to the development of, commercially valuable products.
Future Use of Specimens: if the specimens are to be retained after the end of the study for future research, where the specimens will be retained, who will have access to them, and how long they will be retained.
Future Use of Data: If any of the data will be retained after the study for future research, where the data will be stored, and who will have access to the data.

Re-Contact: if the subject will be re-contacted for future research whether within the VA or outside the VA.

Payment for Participating in the Study: If appropriate, a statement regarding any payment the subject is to receive for participating in the study and how the payment is to be made.
Disclosure of Results: If the subject will receive a report of the aggregate results or any results specific to the subject.

14.3Documentation of Informed Consent

Informed consent must be appropriately documented, in accordance with, and to the extent required by 45 CFR 46.117 or 21 CFR 50.27.

Informed consent is documented by the use of a written consent form approved by the COMIRB and signed and dated by the subject or the subject’s legally authorized representative at the time of consent.

A copy of the signed and dated consent form must be given to the person signing the form.

The consent form may be either of the following:

a.A written consent document that embodies the elements of informed consent may be read to the subject or the subject’s legally authorized representative, but the subject or representative must be given adequate opportunity to read it before it is signed;

If use of facsimile is approved by the IRB, the subject may submit the signed and dated informed consent form to the investigator or designee by facsimile.

b.A short form written consent document detailing the elements of informed consent is presented / translated orally to the subject or the subject’s legally authorized representative. When this method is used:

1)There must be a witness to the oral presentation; and

2)The COMIRB must approve a written summary (usually the full consent form) of what is to be signed by the subject or representative; and

3)The witness must sign both the short form and a copy of the summary; and

4)The person actually obtaining consent must sign a copy of the summary; and

5) A copy of the summary must be given to the subject or representative, in addition to a copy of the short form.

Note: The HIPAA B form in English (unless the Spanish translation is being used) must also be translated by the interpreter as part of the summary and the HIPAA B form must be signed and dated by the subject or representative.

14.3.1Documentation of the Consent Process

The informed consent form must be signed and dated by:

1)The subject or the subject’s legally authorized representative;

2)The person obtaining the informed consent, and

3)A witness, if required by COMIRB (e.g., the COMIRB may require a witness if the study involves an invasive intervention or an investigational drug or device). A witness is always required when a short form consent is employed to enroll non-English speaking or non-reading subjects.

4)The PI should sign and date the consent document as part of his or her

oversight of the study especially for FDA regulated research. This signature and date may be later than the other required signatures detailed above but should be within 30 days of the subject signature, unless a shorter time frame is specifically directed by COMIRB or COMIRB may determine that a PI signature line is not required for the particular study.

Note: the witness is required to witness only the subject’s or subjects’ LAR ‘s signature not the informed consent process unless the sponsor or COMIRB requires the witness to witness the informed consent process.

The witness cannot be the potential subject or the person who obtained informed consent from the subject, but may be another member of the study team, a translator, or may be a family member.

Withdrawal:

When a participant withdraws from a study, the data collected on the participant to the point of withdrawal remains part of the study database and may not be removed. A researcher may ask a participant who is withdrawing whether the participant wishes to provide continued follow-up and further data collection subsequent to their withdrawal from the interventional portion of the study. It must be clear to subjects what was considered study-related intervention and what is continued follow-up. The researcher must obtain the participant’s sent for this limited participation in the must if it was not clearly delineated in the original consent and COMIRB must prospectively approve the consent form. If a participant withdraws and does not want to continue follow-up the researcher cannot access records for purposes related to the study. However, the research may review study data prior to the participant’s withdrawal and may consult public records such as those establishing survival status.

14.4Waiver of Informed Consent

The COMIRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth above, or waive the requirement for informed consent provided the COMIRB finds and documents that:

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, the subjects must be provided with additional pertinent information after participation;

1.The research or demonstration 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:

public benefit or service programs;

procedures for obtaining benefits or services under those programs;

possible changes in or alternatives to those programs or procedures; or

possible changes in methods or levels of payment for benefits or services under those programs; (Exempt Category 5) and

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

Note: Informed Consent cannot be waived for research involving FDA-regulated products. Exceptions from the FDA requirements for informed consent may be waived for emergency situations (21 CFR 50.23) or for emergency research (21 CFR 50.24).

For VA regulated research only: The investigator must maintain a master list of all subjects from whom informed consent has been obtained whether or not COMIRB granted a waiver of documentation of informed consent. If COMIRB waives the requirement to maintain such a master list, COMIRB must provide written documentation in the COMIRB minutes or COMIRB protocol file justifying the waiver.

14.5Waiver of Documentation of Informed Consent(Waiver of Signed Consent)

The COMIRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it determines that the research meets the criteria described below.

In cases in which the documentation requirement is waived, the COMIRB requires the investigator to provide in the application materials a written summary of the information to be communicated to the subject, and the COMIRB will consider whether to require the investigator to provide subjects with a written statement regarding the research.

14.5.1For Studies that are NOT Regulated by the FDA

The COMIRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either that the:

1.Only record linking the subject and the research would be the consent document and the principle risk would be potential harm resulting from a breach of confidentiality.

Note: Subjects must be asked whether they want documentation linking them with the research, and their wishes must govern.

(Example: domestic violence research where the primary risk is discovery by the abuser that the subject is talking to researchers.)

2.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. Procedures such as non-sensitive surveys, questionnaires and interviews generally do not require written consent when conducted by non-researchers.

COMIRB can waive the requirement for the investigator to maintain a master list for a given study if both of the following conditions are met:

a)There is a waiver of documentation of consent; and

b)The COMIRB determines that including the subjects on such a master list poses a potential risk to the subjects from a breach of confidentiality.

14.5.2For Studies that ARE Regulated by the FDA

For studies that involve items regulated under the FDA Regulations, the COMIRB, at its discretion, may waive the requirement for the PI to obtain a signed consent document if:

The Research presents no more than Minimal Risk of harm to the Human Subjects and involves no procedures for which written consent is normally required outside the Research context; or

The requirements for an exception from informed consent for Emergency Research are met.

14.6Review and Approval of the Informed Consent Form

The COMIRB is responsible for the review and approval of the informed consent form prepared by the investigator. The wording on the informed consent form must contain all of the required elements and meet all other requirements as described in this section. If the wording of the informed consent has been initially prepared by an external entity (e.g., a pharmaceutical company or a cooperative study group, including National Cancer Institute (NCI) groups) other than by a University Principal Investigator, the COMIRB needs to ensure that the wording of the consent meets all the requirements of, or has been reviewed by, the appropriate University committees and subcommittees such as the Institutional Biosafety Committee.

COMIRB approval of the wording of the consent must be documented through the use of a certification stamp on the front page that indicates the date of the most recent COMIRB approval of the document and the expiration date. If the consent form is amended during the protocol approval period, the form must have the approval date of the amendment rather than the date of the approved protocol.

For research conducted at the Eastern Colorado Health Care System, the VA Form 10-1086, Research Consent Form, must be used. COMIRB approval of the wording of the consent must be documented through the use of a certification stamp on each page that indicates the date of the most recent COMIRB approval of the document and the expiration date. The consent form must also be approved by the R&D committee indicated with the R&D committee stamp. If the consent form is amended during the protocol approval period, the form must bear the approval date of the amendment rather than the date of the approved protocol. The amended consent form must also be approved by the R&D committee indicated with the R&D committee stamp.

14.7Consent Monitoring

In reviewing the adequacy of informed consent procedures for proposed research, the COMIRB may on occasion determine that special monitoring of the consent process by an impartial observer (consent monitor) is required in order to reduce the possibility of coercion and undue influence, ensure that the approved consent process is being followed, or ensure that subjects are truly giving informed consent.