TRTO (Translational Research Trials Office) Training Standard Operating Procedures for Good Clinical Practice at the Investigative Site Section: SUBJECT MANAGEMENT – Informed Consent

TRTO 4.0 – Informed Consent Development and Implementation Purpose: To describe the steps for fulfilling the regulatory and ethical requirements for developing the informed consent document and for appropriately obtaining the subject’s informed consent. This SOP applies to the activities involved in preparing the informed consent form, submitting it for IRB approval, and for obtaining informed consent from research subjects who participate in clinical trials. It applies to obtaining consent under routine circumstances as well as specialized procedures for obtaining informed consent from non-English speaking persons and from those who cannot be physically present for the consenting discussion.

TRTO 4.0 – Informed Consent Development and Implementation Importance: The ethical conduct of clinical investigations is based upon the voluntary consent of the subject who has been appropriately informed about a study’s risks and benefits. It is the responsibility of the investigator to ensure that all federal and state regulations have been met through the language of the informed consent document, and that informed consent itself has been properly obtained from the subject or the subject’s legal representative. Documentation of the informed consent process is required to establish that the subject was accurately and adequately informed.

TRTO 4.0 – Informed Consent Development and Implementation Definitions: Assent: Even though children cannot “consent”, because true consent implies full understanding, they are now routinely asked whether they agree (assent) or do not agree (dissent) to participate. Informed Consent: A process by which a subject voluntarily confirms his/her willingness to participate in a particular trail, after having been informed of all aspects of the trial that are relevant to the subject’s decision to participate. Informed consent is documented by means of a written, signed, and dated informed consent form. Legally Acceptable Representative: An individual or juridicial or other body authorized under law to consent, on behalf of a prospective subject, to the subject’s participation in the clinical trial. Vulnerable Subjects: Populations considered vulnerable to coercion or undue influence

TRTO 4.0 – Informed Consent Development and Implementation Drafting or Adapting the written informed consent form: Write draft of informed consent based upon the protocol and sample consent (if available). Use the CCHMC IRB informed consent template located at the CCHMC IRB website. Job aid! CCHMC IRB Informed Consent Template A second member of the TRTO must review the informed consent form to verify all required elements and CCHMC IRB-required text are included. Job aid! Informed Consent Checklist

TRTO 4.0 – Informed Consent Development and Implementation Drafting or Adapting the written informed consent form (cont): Submit the informed consent form to the IRB for review and approval along with the other IRB-required documents. If modifications are requested by the IRB, do so in consultation with the PI, Sponsor, and TRTO leadership. After the consent form document has been approved by the IRB, file the original IRB approval letter and informed consent form document in the study regulatory binder.

TRTO 4.0 – Informed Consent Development and Implementation Obtaining written consent from the subject (or legal representative): Ensure the most recent version of the IRB-approved consent form is used. Review the informed consent form with the subject/parent/legal guardian by discussing all of the elements: overview of the study, purpose, procedures, potential risks and benefits, drug and comparative agent, alternatives, research-related procedures, etc. Job aid! Guidelines for Obtaining Informed Consent

TRTO 4.0 – Informed Consent Development and Implementation Obtaining written consent from the subject (or legal representative) (cont.): Allow the subject/parent/legal guardian time to read the document and ask questions. Obtain assent for study participants as required by the IRB. Check your IRB approval notice.

TRTO 4.0 – Informed Consent Development and Implementation Obtaining written consent from the subject (or legal representative) (cont.): After consenting, ensure that the subject (if assent required), parent/legal guardian(s), person obtaining consent, and the PI sign and date the document. For all therapeutic trials, use the Informed Consent Process form to document the process by which consent was obtained. Job aid! Informed Consent Process Form

TRTO 4.0 – Informed Consent Development and Implementation Distribution of Signed Informed Consent Form: Patient’s medical record (HIM record) and research shadow chart (if applicable): copies of informed consent form and Informed consent process form. Patient’s study file: original informed consent form and Informed Consent process form Patient or Parent/Guardian: copy of informed consent form

TRTO 4.0 – Informed Consent Development and Implementation Revisions to the informed consent form: Review changes to the 1) protocol, 2) investigator’s brochure, and 3) IND safety reports, to assess the need for revising the informed consent form. Review according to informed consent procedures discussed earlier. Submit the revised informed consent to the IRB for approval. If appropriate, contact currently enrolled subjects to request that they sign the new informed consent form. (The IRB or sponsor should advise if this is required.)

TRTO 4.0 – Informed Consent Development and Implementation Verbal Informed Consent using a short form and summary sheet for subjects whose primary language is not English: Develop two documents: A “short form” in the subject’s language that captures the elements of informed consent . Job aid! Short Form of Informed Consent for Spanish Speakers A summary sheet of the information that is to be presented verbally to the subject/parent or the legal representative. The institutional IRB-approved English language informed consent document may serve as this summary. Both documents must be approved by the IRB.

TRTO 4.0 – Informed Consent Development and Implementation Verbal Informed Consent using a short form and summary sheet for subjects whose primary language is not English (cont.): To administer informed Consent: The transcriber’s/interpreter’s credentials must be verified and documented prior to involvement with the informed consent process. The contents of the informed consent should be explained by the person consenting and translated orally by the interpreter. The person authorized to obtain consent signs the summary. A witness, who is fluent in both English and the language spoken by the family should be present during the oral translation of the informed consent document. The translator may serve as the witness. The witness must sign both the short form consent and the summary. Distribute and file as described earlier.

TRTO 4.0 – Informed Consent Development and Implementation Waiver of Informed Consent in emergency situations: A study Investigator and a second Physician not listed as an Investigator of the study must establish that informed consent CANNOT be obtained from the subject for ALL of the following reasons: The subject is in a life-threatening situation requiring the use of the test article (drug or device). Informed consent cannot be obtained from the subject. There is insufficient time to seek consent from the subject’s legal representative. No appropriate alternative therapy is available or recognized as being effective.

TRTO 4.0 – Informed Consent Development and Implementation Waiver of Informed Consent in emergency situations (cont.): If time does not permit the independent judgment of a second physician and the life of the subject is at stake, the Investigator may administer the test article. Later, a second physician not involved with the study must review and evaluate the event. Within 5 working days of the emergency use of the test article, send documentation from the Investigator and the second physician to the IRB. Notify the sponsor as soon as possible.

TRTO 4.0 – Informed Consent Development and Implementation Obtaining consent from those who cannot be physically present for the consenting discussion: The consent discussion(s) may occur via speakerphone, as a last resort, if the subject/ parent/legal guardian cannot be physically present. This is acceptable provided the following process is strictly followed: The most recent version of the IRB-approved consent form is either mailed or faxed to the subject/parent/legal guardian prior to the discussion. At least 2 CCHMC witnesses (other than the treatment team) are present for the entire discussion. The consent form is reviewed in the same level of detail as a face-to-face consent discussion.

TRTO 4.0 – Informed Consent Development and Implementation Obtaining consent from those who cannot be physically present for the consenting discussion (cont.): Sufficient time and opportunity is given for the subject/parent/ legal guardian to express concerns and ask questions. This may require a follow-up discussion. If the subject/parent/legal guardian verbally agrees to consent (and assent, if applicable), arrangements must be made to obtain signatures on the consent form. This could include: Fax Expedited shipping (e.g. FedEx) Regular mail Obtaining signatures at the next visit to CCHMC

TRTO 4.0 – Informed Consent Development and Implementation Obtaining consent from those who cannot be physically present for the consenting discussion (cont.): Once received, the signed consent form must be signed by the consenting physician. The consenting physician must also complete the Informed Consent Process Form describing the methods used to satisfy the above requirements, along with listing the witnesses present during the consenting discussion. No study procedures and no enrollment on the study may occur until the completed, signed consent form is received by CCHMC

Quiz time! TRTO SOPs – Informed Consent Quiz