Informed Consent Writing Tip Sheet

Informed consent is one of the central protections the regulations provide to research subjects. This tip sheet outlines the regulatory requirements for research informed consent forms (ICFs).  The regulatory requirements for informed consent will vary depending upon which regulations apply to the conduct of a particular study.

Note: Individual institutional review boards (IRBs) may have their own specific policies regarding how ICFs should be formatted, how to address certain regulatory criteria, and other considerations. Always check with your IRB of record to confirm you understand its requirements.

Part C of the Belmont Report notes that respect for persons requires subjects be given the opportunity to choose what will or will not happen to them. The informed consent plays a key role in this respect and should adhere to three main elements:

• Information
  • Provide information to help potential subjects understand the study’s risks and benefits to help them decide whether they wish to participate in the research
• Comprehension
  • Provide information in a way that is meaningful to potential subjects. Investigators should be able to make certain the potential subject truly understands the presented information
• Voluntariness
  • Consent to participate in research is valid only if given voluntarily. To facilitate this, avoid coercion (i.e., threat of harm) and undue influence (i.e., excessive, improper, and/or inappropriate reward) when informing potential subjects about the study

Language and Reading Level

Ensure the ICF is written in a way that will make sense to the study’s specific subject population. U.S. regulatory agencies recommend written ICFs contain easy-to-read and understandable information so a lay person can make an informed decision about participating in a study.

Generally, the aim is for a sixth to eighth grade reading level; however, it is recognized that some consent forms require technical language which will make this level unreachable.  Before proceeding with a specific approach, make sure it is appropriate for your study. Flesh-Kincaid readability tools can help with grade level assessments.

The consent form cannot include any exculpatory language. Exculpatory language is that which has the general effect of waiving or appearing to waive a subject’s legal rights, or releases or appears to release the investigator, the sponsor, the institution or its agents from liability from negligence. The Food and Drug Administration (FDA) website has guidance titled Exculpatory Language in Informed Consent, which includes examples.

If you are targeting a community that includes a sizable number of non-English speakers:  Have translated ICFs available when English is not a potential subject’s first language. Whenever possible, have translated ICFs available ahead of time so you don’t have to wait to have the consent conversation with a potential subject.

Should an unexpected non-English speaking subject arrive before a translated study ICF is available, the regulations permit providing an oral presentation of the informed consent information along with a short form consent document and a written summary of the oral presentation. To access Advarra’s translated short forms in over 20 languages, login to the Advarra CIRBI Platform and select “Reference Materials.”

If your study will enroll children younger than the legal age of majority in in your area: Consider whether assent documents are appropriate (in addition to the standard ICF) and/or whether it may be suitable to add an assent signature line to the standard ICF. Most IRBs identify age ranges when assent may be necessary, so check with your IRB regarding their standards.

Advarra’s IRB requires an assent statement (separate signature block in the standard ICF) for subjects who are minors and old enough to understand the ICF as written (approximately 14-17 years old). An assent form is needed when younger subjects (approximately 7-13 years old) need the information presented in age-appropriate language. The IRB doesn’t typically require subjects 6 years old or younger to sign an assent statement or assent form.

Basic Elements of Informed Consent

The regulations are very specific regarding what to include in the ICF and what to exclude. The basic elements of informed consent are mandated by the Common Rule (i.e., Department of Health and Human Services [DHHS] Office of Human Research Protections [OHRP] regulations) and FDA regulations at 45 CFR 46.116 and 21 CFR 50.25 respectively.

To remain compliant with the International Council of Harmonization’s good clinical practice guidelines (ICH-GCP) for studies conducted outside the U.S., also consider the ICH basic elements. Note that many (though not all) ICH elements are well-aligned with U.S. requirements.

Remember that it is only necessary to include the regulatory elements applicable for a given study. For example, an FDA regulated study would not need to comply with the Common Rule unless there is also DHHS funding involved.

FDA and Common Rule Elements of Informed Consent

• For research regulated by the Common Rule: ICF should begin with a concise and focused presentation of the key information most likely to assist a prospective subject in understanding the reasons why one might/might not want to participate in the research
• Purpose of Research:
  • A statement that the study involves research
  • An explanation of the purposes of the research
  • The expected duration of the individual’s participation
  • A description of the procedures to be followed
  • Identification of any experimental procedures
• Risks and Discomforts: A description of any reasonably foreseeable risks or discomforts to the subject
  • Cross-reference ICF language with risks in the protocol document and product information (i.e., Investigator’s Brochure)
• Benefits: A description of any benefits to the subject (or to others) which may reasonably be expected from the research
• Alternatives: Disclosure of appropriate alternative procedures or courses of treatment (if any) that might be advantageous to the subject
• Confidentiality: A statement describing the extent (if any) to which confidentiality of records identifying the subject will be maintained
  • If applicable, this section should also include a statement noting the possibility that the FDA may inspect the records
• Compensation for Injury: Only required for research involving more than minimal risk: An explanation as to whether any compensation and/or any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained
• Research Questions: 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
• Voluntary Participation: 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
• ClinicalTrial.gov information: Applicable for Phase 2 and later studies, must be verbatim as follows: A description of this clinical trial will be available on http://www.ClinicalTrials.gov, 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.

ICH-GCP Elements of Informed Consent

• The trial involves research
• The trial’s purpose
• The trial treatment(s) and the probability for random assignment to each treatment
• The trial procedures to be followed, including all invasive procedures
• The participant’s responsibilities
• The experimental aspects of the trial
• The reasonably foreseeable risks or inconveniences to the participant and, when applicable, to an embryo, fetus, or nursing infant
• The reasonably expected benefits (when there is no intended clinical benefit to the participant, the participant should be made aware of this)
• The alternative procedure(s) or course(s) of treatment that may be available to the participant and their important potential benefits and risks
• The compensation and/or treatment available to the participant in the event of trial-related injury
• The anticipated prorated payment, if any, to the participant for participating in the trial
• The anticipated expenses, if any, to the participant for participating in the trial
• The individual’s participation in the trial is voluntary, and the participant may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the participant is otherwise entitled
• The monitor(s), the auditor(s), the IRB/institutional ethics committee (IEC), and the regulatory authority(ies) will be granted direct access to the participant’s original medical records for verification of clinical trial procedures and/or data, without violating the participant’s confidentiality, to the extent permitted by the applicable laws and regulations and that, by signing a written informed consent form, the participant or the participant’s legally acceptable representative is authorizing such access
• Identifying participant records will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available; if the results of the trial are published, the participant’s identity will remain confidential
• The participant or the participant’s legally acceptable representative will be informed in a timely manner if information becomes available that may be relevant to the participant’s willingness to continue participation in the trialThe person(s) to contact for further information regarding the trial and the rights of trial participants, and whom to contact in the event of trial-related injury
• The foreseeable circumstances and/or reasons under which the individual’s participation in the trial may be terminated
• The expected duration of the participant’s participation in the trial
• The approximate number of participants involved in the trial

Additional Elements of Informed Consent

Note: These elements are instance-specific, and their applicability is at the IRB’s discretion. To help streamline the review process, sponsors and sites should communicate with the IRB regarding the circumstances informing the addition or omission of these 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
• Anticipated circumstances under which the subject’s participation may be terminated by the investigator without regard to the subject’s consent
• Any additional costs to the subject that may result from research participation
• 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 which 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
• For all NIH-funded research, and any other research for which a Certificate of Confidentiality (CoC) has been issued, a description of the CoC.
• If genetic testing results will be returned to the site and/or the subject, include information about the Genetic Information Nondiscrimination Act (GINA)
• If infectious diseases will be tested for (i.e., tuberculosis (TB), HIV, hepatitis (B, C), COVID-19), a statement that results may be required by law to be reported to local health authorities
• For research regulated by the Common Rule: For research with identifiable private information or identifiable biospecimens, a statement that identifiers might be removed from the identifiable private information or identifiable biospecimens and the information or biospecimens could then be used for future research studies or distributed to another investigator for future research studies without additional informed consent
  • 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
• For research regulated by the Common Rule: A statement that the subject’s biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will/will not share in this commercial profit
• For research regulated by the Common Rule: A statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions
• For research regulated by the Common Rule: For research involving biospecimens, whether the research will (if known) or might include whole genome sequencing

For more information on informed consent, review: 21 CFR 50.20, 21 CFR 50.25, 45 CFR 46.116, 45 CFR 46.117, ICH Good Clinical Practice (GCP), FDA Information Sheet: Informed Consent, OHRP Informed Consent FAQs, Belmont Report, PlainLanguage.gov, NCCN Informed Consent Language Database

Still not sure how to write that ICF? Advarra can help craft a comprehensive, easy-to-read ICF that meets IRB review requirements in as little as 3-5 days. Visit advarra.com/ICF-writing for more information.

Note: This article was originally published April 14, 2022, and has been updated to include new and clarifying information. 

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