Informed Consent General Requirements Obtaining informed consent is a basic ethical obligation and a legal requirement for researchers unless the IRB issues a waiver of informed consent. The requirement for informed consent is one of the central protections of human subjects, defined by: Department of Health & Human Services (HHS) regulations at 45 CFR part 46 Food and Drug Administration (FDA) regulations at 21 CFR part 50 Definitions Informed Consent means a research subject’s voluntary agreement to participate in research. Informed Consent Form (ICF) is a written document that provides research subjects with all necessary information to make an informed choice regarding participation in research. Legally Authorized Representative (LAR) is an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the research. What Is the Requirement? 45 CFR 46.111 (4) Informed consent will be sought from each prospective subject or the subject’s legally authorized representative, in accordance with, and to the extent required by, §46.116 General requirements for informed consent. How Do I Comply With This Requirement? General Requirements for informed consent, whether oral or written: Before involving a human subject in research, an investigator shall obtain the legally effective informed consent of the subject or the subject's legally authorized representative, unless the requirement for informed consent has been waived by the IRB. An investigator shall seek informed consent only under circumstances that provide the prospective subject or the legally authorized representative sufficient opportunity to discuss and 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 legally authorized representative shall be in language understandable to the subject or the legally authorized representative. The prospective subject or the legally authorized representative must be provided with the information that a reasonable person would want to have in order to make an informed decision about whether to participate, and an opportunity to discuss that information. Informed consent must begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject or legally authorized representative in understanding the reasons why one might or might not want to participate in the research. This part of the informed consent must be organized and presented in a way that facilitates comprehension. Informed consent as a whole must present information in sufficient detail relating to the research, and must be organized and presented in a way that does not merely provide lists of isolated facts, but rather facilitates the prospective subject's or legally authorized representative's understanding of the reasons why one might or might not want to participate. No informed consent may include any exculpatory language through which the subject or the legally authorized 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. Elements of Informed Consent Basic Elements of Informed Consent Unless the IRB waives one or more elements, the following information must be included in the informed consent document: 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 that 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 that 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; A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained; 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; Informed Consent Guidelines 23 November 2020 OHRA-GDL-2020-004 3 ©2020 Albert Einstein College of Medicine 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; One of the following statements about any research that involves the collection of identifiable private information or identifiable biospecimens: A statement that identifiers might be removed from the identifiable private information or identifiable biospecimens and that, after such removal, the information or biospecimens could be used for future research studies or distributed to another investigator for future research studies without additional informed consent from the subject or the legally authorized representative, if this might be a possibility; or A statement that the subject's information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies. Additional Elements of Informed Consent 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) that are currently unforeseeable Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's or the legally authorized representative'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 that 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; A statement that the subject's biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit; A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions; and For research involving biospecimens, whether the research will (if known) or might include whole genome sequencing (i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen). Elements of broad consent for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens. A general description of the types of research that may be conducted with the identifiable private information or identifiable biospecimens. This description must include sufficient information such that a reasonable person would expect that the broad consent would permit the types of research conducted; A description of the identifiable private information or identifiable biospecimens that might be used in research, whether sharing of identifiable private information or identifiable biospecimens might occur, and the types of institutions or researchers that might conduct research with the identifiable private information or identifiable biospecimens; A description of the period of time that the identifiable private information or identifiable biospecimens may be stored and maintained (which period of time could be indefinite), and a description of the period of time that the identifiable private information or identifiable biospecimens may be used for research purposes (which period of time could be indefinite); Unless the subject or legally authorized representative will be provided details about specific research studies, a statement that they will not be informed of the details of any specific research studies that might be conducted using the subject's identifiable private information or identifiable biospecimens, including the purposes of the research, and that they might have chosen not to consent to some of those specific research studies; Unless it is known that clinically relevant research results, including individual research results, will be disclosed to the subject in all circumstances, a statement that such results may not be disclosed to the subject; and An explanation of whom to contact for answers to questions about the subject's rights and about storage and use of the subject's identifiable private information or identifiable biospecimens, and whom to contact in the event of a research-related harm. Readability The potential research subjects must be able to understand the information presented in the consent document. Follow these guidelines to improve the readability of the consent document: Write at or below an 8th grade reading level Use short sentences; < 15 words Use the active form (first person) Use 12 point font Avoid jargon and acronyms Format information to improve visual understanding by using: Tables Bulleted lists White space Additional Resources US Government Plain Language Checklist KP Washing Program for Readability in Science & Medicine (PRISM) Presenting Information for Effective Communication (Video, PDF) OHRP: What’s New in Informed Consent: Revisions to the Common Rule (26:50) IRB Review of Consent Documents The consent document must include accurate information. Compare the consent document to the protocol (and investigators brochure, when applicable) to ensure that procedures, risks and other information are correct, complete and consistent throughout all documents. The IRB must approve your consent form before you use it. A stamped version of the approved consent forms will be provided in Reviews section of iRIS. If you make revisions to your protocol or if new risk information is obtained, you may need to revise the consent document so it is accurate and complete. According to Office for Human Research Protections (OHRP) Guidance, you cannot enroll participants into a study if the consent document is inaccurate or incomplete. Whenever you revise the consent document, you must submit the revised version to the IRB as a modification and the IRB must approve the new version before the version can be used. Unless otherwise instructed by the IRB in writing, you must use the most current approved version of the consent document when enrolling participants. Ethical Considerations Freely given informed consent must be obtained from every decisionally capable, potential adult subject before any research procedures begin, unless the IRB has waived some or all of the consent requirements. Informed consent is not just a form or a signature, but a process of information exchange that takes place between the prospective subject and the investigator before, during, and sometimes after the study, which includes subject recruitment materials, verbal instructions, written materials, question and answer sessions, and agreement documented by signature. Who May Consent/Enroll Subjects? The Principal Investigator is required to submit to the IRB for each protocol the names of the individuals authorized to obtain informed consent from the subjects in the study. All of these individuals must be knowledgeable about the study and must have completed the CITI training program required by Einstein and MMC. The PI must obtain the IRB’s approval prior to adding additional individuals to the authorized list. The PI remains responsible for ensuring that adequate informed consent is obtained from each subject enrolled in the study protocol.