Informed Consent

 

Content Author

 

Diane Paul MS, RN

National Comprehensive Cancer Network.

 

 

Internet Resources and References:

•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 ( http://www.access.gpo.gov/nara/cfr/waisidx_98/21cfr50_98.html) and 45 CFR Part 46 (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.htm).

•U.S. Food and Drug Administration, Information Sheets [Online] Guidance for Institutional Review Boards and Clinical Investigators, 1998. (www.fda.gov/oc/ohrt/irbs/faqs.html)

•National Cancer Institute, Informed Consent [Online]. Available: http://cancertrials.nci.nih.gov.

•Klimaszewski, A.D., Anderson, S., Good, M. (2000). Informed Consent. Manual for Clinical Trials Nursing. 213-219.

 

Introduction

There is consensus regarding the importance of informed consent. Informed consent is how you show respect to research subjects, and it is mandated by the *Code of Federal Regulations (CFR) 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. By the end of the module you will be able to:

 

•Describe the requirements for complying with informed consent regulations.

•Describe the process for obtaining informed consent.

•Describe the regulations for waiving informed consent.

 

Informed Consent Requirements

General Requirements

The framework for informed consent can be found in The Code of Federal Regulations 45 CFR 46.116(a) and 21 CFR Part 50.25(a). Legally appropriate informed consent will include the following elements:

 

•Information that the study involves research.

oAn explanation of the purposes of the research.

oThe expected duration of the subject's participation.

oA description of the procedures to be followed.

oIdentification of any procedures that are experimental.

•A clear description of the risks or discomforts to the subject. Such description must:

oBe accurate and reasonable.

oReview any risks related to procedures and tests relating solely to research and any tests that carry a risk of morbidity/mortality.

oInform the subject of previously reported adverse events.

•A description of the benefits to the subject or to others.

•A disclosure of any alternative procedures or treatments that may be advantageous to the subject, thus giving the subject a full range of available options. When appropriate, a statement that supportive care with no additional disease specific treatment is an alternative.

•A description explaining how the institution/investigator will maintain confidentiality of records. Statement should include full disclosure and description of approved agencies (i.e., FDA, OHRP) and/or other designated parties that may access the records.

•For research involving more than minimal risk, an explanation should describe:

oWhether there will be any compensation.

oWhether there will be any medical treatment offered and who will bear the financial responsibility for treatment if injury occurs, and, if so, how and to what extent.

oWhere the subject may obtain further information.

•The specific office, name, and telephone number (s) of whom to contact for further information regarding the research subjects' rights, the research study, or for research-related injury.

•A statement that participation is voluntary, that refusal to participate involves no penalty or loss of benefits to which the person is otherwise entitled, and that the subject may discontinue at any time.

 

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):

 

•A statement that the procedure may involve unforeseeable risks.

•When appropriate, include a statement that the research could involve unforeseeable risks to the embryo or fetus or to the subject if the subject is or becomes pregnant.

•A description of circumstances under which the subject's participation may be terminated by the investigator without the subject's consent.

•A description of any additional costs to the subject that may result from participation in the research.

•A clear statement of the consequences of a subject's decision to withdraw from the research, and, if so, how to withdraw safely.

•A statement that significant new findings developed during research which may relate to the subject's willingness to continue will be provided to the subject. Also describe the process whereby subjects will be notified of significant new findings.

•A description of the approximate number of subjects that will be involved in the study.

 

Regulatory Groups

Compliance with informed consent regulations is regulated by the:

 

•Food and Drug Administration (FDA), Title 21, Code of Federal Regulation, Part 50 (21CFR50)—see Module 12.

•Office for Human Research Protections, Title 45, Code of Federal Regulations, Part 46 (45CFR46).

•Study institution's Institutional Review Board.

 

Obtaining Informed Consent

Obtaining informed consent involves:

 

•Providing information to the subject.

•Ensuring the subject understands by answering questions the subject may have.

•Obtaining the voluntary agreement of the subject to participate in the study.

 

Providing Information

Guidelines for providing information include:

 

•Advertising cannot be coercive or make false promises or claims.

•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

•Procedures to screen potential subjects for eligibility must protect the rights and welfare of prospective subjects.

 

Ensuring Understanding

Guidelines for ensuring understanding include:

 

•Proving 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 their research before consenting to research study participation

 

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.

•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.

 

Coercive tactics such as inappropriate financial or other rewards cannot be used. 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 investigator.

 

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.

 

Regulations for Waiving Informed Consent

Sometimes, under specific circumstances with IRB approval, informed consent can be waived.

 

DHHS Regulations for Waivers

The DHHS (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.

 

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:

oThe investigator, with the concurrence of another physician, believes the situation necessitates the use of a test article (i.e., an investigational drug, device, or biologic).

oThe 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).

oThere is insufficient time to obtain consent.

oNo 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 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.

 

When obtaining consent from a legally authorized representative (LAR) who is not able to provide signed consent in person, it is acceptable to send the informed consent document to the 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.

 

DHHS

According to DHHS (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.

 

See 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 in21 CFR 50.27(a). However, 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.

 

See the for links to FDA information about informed consent.

 

DHHS

See 45 CFR 46.117