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Bottom of Form * Main Menu * My Profiles * My CEUs * My Reports * Support * Main Menu › VA Human Subjects Protection › Informed Consent Informed Consent
Content Author * Diane Paul, M.S., RN
National Comprehensive Cancer Network
Introduction
It is important to understand that informed consent is a process that begins with the recruitment and screening of a subject and the signing of the consent document, continues throughout the subject's involvement in the research, and continues beyond study termination. It includes: * Recruitment efforts encompassing the means of first creating awareness or contact and spanning everything from medical record review to advertisements and other recruitment materials. * Providing specific information and answering questions about the study to subjects in a way that is understandable to them while giving subjects adequate time to consider participation. * Obtaining the voluntary agreement of subjects to take part in the study. While the subject may agree to participate in the study, subjects may withdraw at any time. Part of the ongoing nature of the consent process is verifying the subject's continued interest in participating in the study. * Making plans for the provision of new information to be shared with former subjects, even after the study ends.
There is consensus regarding the importance of informed consent. Informed consent is a demonstration of how investigators and those involved in human subjects research show respect to research subjects, and it is mandated by the Department of Health and Human Services (HHS) at 45 CFR 46 and the Food and Drug Administration at 21 CFR 50*. The regulation was developed to: * Protect human subjects/volunteers. * Ensure that potential study subjects clearly understand the benefits and risks associated with their participation in a study. * Provide the potential study subjects with all information needed to reach a decision on whether or not to participate in a research study.
*The Code of Federal Regulations (CFR) is published in the Federal Register, a publication of the Federal Government that codifies the general and permanent rules of executive departments and agencies. There are 50 titles that represent broad areas subject to federal regulation. The CFR is updated once each calendar year and is issued on a quarterly basis.
The purpose of this module is to provide a basic understanding of informed consent and the process of obtaining informed consent.
Learning Objectives
By the end of this module, you should be able to: * Describe the requirements for complying with informed consent regulations. * Describe the process for obtaining informed consent. * Define vulnerable populations. * Describe the regulations for waiving informed consent.
Informed Consent Requirements
General Requirements
The framework for informed consent can be found at 45 CFR 46.116(a) and 21 CFR Part 50.25(a). Legally appropriate informed consent will include the following elements: 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 and that notes the possibility that the Food and Drug Administration may inspect the records. 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. 8. A statement that participation is voluntary, that refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and that the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.
Additional Requirements
In addition, if relevant to the research, legally effective informed consent will also include the following elements, outlined in The Code of Federal Regulations 45 CFR 46.116(b) and 21 CFR 50.25(b): 1. 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. 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. 6. The approximate number of subjects involved in the study.
ClinicalTrials.Gov Requirement
The FDA also issued an addition to the elements of informed consent adding a new requirement that went into effect March 2012. When seeking informed consent for applicable clinical trials, as defined in 42 U.S.C. 282(j)(1)(A), the following statement shall be provided to each clinical trial subject in informed consent documents and processes. This will notify the clinical trial subject that clinical trial information has been or will be submitted for inclusion in the clinical trial registry databank under paragraph (j) of section 402 of the Public Health Service Act. The statement is: * "A description of this clinical trial will be available here, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time."
In February 2012, the FDA also issued Guidance for Sponsors, Investigators, and Institutional Review Boards - Questions and Answers on Informed Consent Elements, 21 CFR 50.25(c)
Regulatory Groups
Compliance with informed consent regulations is regulated by the: * FDA, 21 CFR 50 - see FDA-Regulated Research module * HHS, 45 CFR 46 - through OHRP * Applicable Institutional Review Boards (IRBs)
Obtaining Informed Consent
Obtaining informed consent involves: * Providing information to the subject. * Answering questions the subject may have to improve his/her comprehension * Obtaining the voluntary agreement of the subject to participate in the study.
Providing Information
Guidelines for providing information include: * Advertising may be the first information about research seen by subjects and is most often used in recruitment. It cannot be coercive or make false promises or claims. The process of informed consent is often conceptualized to begin at the recruitment stage. Additionally, some areas to consider with respect to recruitment include: * Laws, guidelines, or institutional policies that govern advertising for study subjects, particularly in multi-site research; * Whether compensation for study volunteers is allowed where the research is proposed, and how it will be noted in recruitment materials; * What the "norms" for recruiting are in the particular location where recruitment will occur and with the proposed population. * Procedures to screen potential subjects for eligibility must protect the rights and welfare of prospective subjects. * The information should be communicated in a manner and language that is clear and understandable, be communicated in an organized fashion, and allow for questions the subject may have to be answered. * The information communicated should not use exculpatory language either in the written consent or in discussions about the research. "No informed consent, whether oral or written, may include any exculpatory language through which the subject 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". --- 45 CFR 46.116
Improving Understanding
Guidelines for improving understanding include: * Providing consent in a language that is understandable to the subject or his/her representative. * Providing non-English speaking subjects a translated informed consent document that is accurate as determined by the IRB. * If a translator is used, providing a written translation of the consent document is still required. Some IRBs allow use of a short form translation of the IRB consent document, see 45 CFR 46.117 (b)(2). * Giving the person enough time to think about his/her participation in the research before giving consent.
The National Comprehensive Cancer Network (NCCN) provides a free online database for researchers and IRB members that contains standardized lay language descriptions of risks and events associated with clinical research. (NCCN 2015) This resource aims to help increase subject understanding by providing lay language terms approved by academic IRB's that can be used in consent forms for clinical terms (for example, the term "acuity reduced" could be replaced with the lay term "blurry vision").
Obtaining Voluntary Agreement to Participate
Legally effective informed consent shall: * Be obtained from the subject or the subject's legally authorized representative. * Be obtained under circumstances that provide the subject with an opportunity to consider whether or not to participate and that minimize coercive influences. Coercive tactics such as inappropriate financial compensation or other rewards cannot be used. * Not include any language through which the subject is made to waive or appear to waive any of his/her legal rights or any language that releases the investigator, sponsor, or institution from liability for negligence. * Illiterate English-speaking subjects can "make their mark" on the informed consent document, as long as it is consistent with applicable state laws.
Special Challenges
Language Issues
The consent process should be conducted in the language spoken by the subject, and the consent form should be translated into that language. An IRB may require independent confirmation of the accuracy of the translation. Subjects who are not literate in their language must have an interpreter present to explain the study to the subject and translate questions and answers between the subject and the person obtaining consent.
Cultural Issues
Issues other than literacy may affect comprehension. For example, in some cultures it may be considered rude to ask questions of an investigator researcher, or rude to decline what is perceived of as a request for a favor. In these circumstances, the questions of who conducts the consent process and how it is explained become even more important.
Vulnerable Populations
The concept of subject vulnerability is important to research ethics and to regulatory compliance. FDA regulation 21 CFR 56.111(b) requires that "when some or all of the subjects are likely to be vulnerable to coercion or undue influence, additional safeguards have been included in the study to protect the rights and welfare of these subjects." These regulations do not provide a definition of vulnerable subjects or an explanation of the causes of vulnerability, but they do provide the following list of examples of vulnerable subjects: "children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons." Other examples include: * Patients in emergency situations * Subjects who are marginalized in society (for example, Gay/Lesbian/Bisexual/Transgender individuals, undocumented workers) * Members of a group with a hierarchical structure, such as students in medicine, pharmacy, dental, and nursing subordinate hospital and laboratory personnel, and members of the armed forces * Patients with fatal or incurable diseases * The elderly * Persons in nursing homes * Unemployed or impoverished persons * Ethnic minority groups * Homeless persons, nomads, refugees
While vulnerability is not a term clearly defined in the regulations, thinking of vulnerability as a limitation on autonomy provides a valuable tool for considering whether there are sufficient safeguards in a given research project to protect the rights and welfare of these subjects.
Regulations for Waiving Informed Consent
Sometimes, under specific circumstances with IRB approval, informed consent can be waived.
HHS Regulations for Waivers
The HHS (45 CFR 46.116) allows an IRB to waive or change the requirements for informed consent under two sets of circumstances:
1) Government Projects and 2) General Waivers and Alterations.
Government Projects
If the research/project is approved and/or conducted by state or local government and is meant to study/evaluate: * A program to benefit the public. * Procedures under those programs. * Alternatives to those programs or procedures. * Changes in payment methods or levels for the services of those programs. * The research could not practicably be carried out without the waiver.
General Waivers and Alterations are permissible if the IRB determines that: * The research involves no more than minimal risk to 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. * Whenever appropriate, the subjects will be provided with additional pertinent information after participation.
Special Considertaions for NIH Funded Research:
NIH funded research using newborn dried blood spots collected on or after March 18, 2015, is considered research on human subjects (which requires the informed consent of the subject) according to the Newborn Screening Saves Lives Reauthorization Act of 2014. The Act also eliminates the ability of an IRB to waive informed consent requirements for research on newborn dried blood spots. This means that researchers would need parental permission to use the dried blood spots. NIH-funded research with non-identifiable dried blood spots collected before March 18, 2015, is considered non-human subjects research and is exempt from the regulations.
FDA Regulations for Exceptions from Informed Consent Requirements
The FDA 21 CFR 50.23 and 21 CFR 50.24 provide exceptions to the requirement for informed consent under the following circumstances: * In situations where requirements for exception from informed consent are met for emergency research (21 CFR 50.24). * In life-threatening conditions involving an individual subject where requirements for an exception from informed consent are met and include documentation of all of the following: * The investigator, with the concurrence of another physician, believes the situation necessitates the use of a test article (an investigational drug, device, or biologic). * The subject and/or legally authorized representative is unable to communicate consent
(FDA definition of Legally Authorized Representative: 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). * There is insufficient time to obtain consent. * No alternative exists that will provide an equal or better chance of saving the subject's life.
Waiver of Signed Consent/Use of Oral Consent
Signed consent may be waived and oral consent used under the following circumstances:
FDA
The U.S. FDA allows waiver of documented informed consent (21 CFR 56.109(c)[1]) when study participation presents minimal risk to the subject and the research involves no procedures requiring consent outside the context of participation in a research study. The IRB may require the investigator to provide the subject with written materials about the research.
HHS
According to HHS (45 CFR 46.117), an IRB may allow waiver of a signed consent document in either of the following circumstances: * The consent would be the only link between the research and the subject and the principal risk to the subject would be due to a breach of confidentiality, and each subject will be asked if they want consent to be documented. * Study participation presents minimal risk of harm to the subject and the research involves no procedures requiring consent outside the context of participation in a research study. * The investigator may be required by the IRB to provide a written summary about the research to the subject if either of these methods is used.
Appendix - Internet Resources and References
Is Telephone Consent From a Legally Authorized Representative Appropriate?
FDA
Verbal approval does not satisfy the 21 CFR 56.109(c) requirement for a signed consent document, as outlined in 21 CFR 50.27(a). However, according to FDA guidance it is acceptable to send the informed consent document to the legally authorized representative (LAR) by facsimile and conduct the consent interview by telephone when the LAR can read the consent as it is discussed. If the LAR agrees, he/she can sign the consent and return the signed document to the clinical investigator by facsimile.
HHS
Documentation of informed consent is required by HHS 45 CFR 46 unless a waiver of documentation is granted by the IRB. The regulations dictate that the signature must be the subject's or the subject's legally authorized representative. HHS guidance regarding informed consent can be found at OHRP's FAQs. HHS does allow the exchange of consent information to take place face-to-face or by mail, telephone, fax or video. Informed ConsentA researcher proposes a randomized trial of an investigational drug in patients about to undergo surgery for acute appendicitis. The investigational drug (or placebo, depending on which arm the subject is assigned to) is administered immediately prior to the surgery. If the investigational drug works it will mean less pain and maybe less need for other pain medicines like morphine. The investigator who is also the surgeon performing the operation, proposes to have a nurse explain the research in the "pre-op" area. The nurse will explain the research while the patient is being prepared for the operation and having an IV started, as well as blood pressure and other measurements taken. The surgeon will then arrive, get consent for the operation and get the patient's signature on the research consent form. If the patient does not speak English, an interpreter will answer the patient's questions. The patient will sign the English language consent form. * Is the proposed consent process appropriate for this situation? The consent process is flawed in several aspects. First, the federal regulations mandate that investigators, in this case the surgeon, provide subjects or their representatives, sufficient time to consider whether to participate or not. Obtaining consent in the "pre-op" area immediately before an emergency operation, and while other clinical procedures are being performed, is not conducive to thoughtful deliberation or decision-making.Second, investigators also must obtain consent under circumstances that minimize the possibility of coercion or undue influence. In this case, the patient's surgeon is obtaining consent for research immediately before performing a potentially lifesaving procedure. The patient may be under undue influence, or possibly coercion, to participate in the research even though it may be against his actual wishes. In addition, the aspect of this participant being vulnerable must be considered. In this stressful situation, how can one access the participant's ability to comprehend information and make sound decisions?Third, obtaining consent at the same time for both performing the operation (a clinical indicated procedure), and for participating in the research might confuse the patient. It may be difficult for the patient to understand which procedures are standard care and which are part of the research. Finally, investigators must present information about the research in a language understandable to the subject or the representative. Having an interpreter available only to answer questions and not present for the explanation, and using a consent form written in English, rather than a subject's native language, does not fulfill this requirement.As a final point, obtaining informed consent in this setting (particularly as concerning the first two points above) may be nearly impossible. It would be more appropriate to choose a different subject population, for example, patients undergoing elective procedures, where consent can be obtained well in advance of the research and participants will have time to ask questions and demonstrate understanding.Close Case Study |
References & Resources * Code of Federal Regulations for the Protection of Human Subjects in Research, U.S. Department of Health and Human Services, 1998, 21 CFR Part 50 and 45 CFR Part 46. * U.S. Food and Drug Administration, Information Sheets [Online] Guidance for Institutional Review Boards and Clinical Investigators, 1998. * National Cancer Institute (NCI), Informed Consent [Online]. * National Cancer Institute (NCI). Cancer Diagnosis Program Offers an Educational Video on Cancer Treatment and Tissue Dontation. 2015. "Donating Your Tissue for Research." Accessed December 3. * NCCN Informed Consent Language (ICL) Database [Online]. 2015. Accessed August 7. * Klimaszewski, A.D., Anderson, S., Good, M. (2000). Informed Consent. Manual for Clinical Trials Nursing. 213-219.
Original Release: July 2003
Last Updated: April 2016

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