Revised on: 2/02/2022
Investigators are required to obtain informed consent as a legal and ethical obligation. This chapter discusses the process of consent, the elements of consent, and legal requirements involved when obtaining informed consent from subjects.
No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or to 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.
Informed consent is more than a form; it is a process. Information must be presented to participants so that they can voluntarily decide whether or not to participate in research. Prospective subjects must be provided with the information that a “reasonable person” would want to have in order to make an informed decision and subjects must be provided the opportunity to discuss that information. The informed consent form must be written in “lay language” to ensure participants can understand its content. The amount of information contained in the consent and the manner of presentation is related to the complexity and risk involved in the study. The consent form serves to document the basis for consent and also serves as future reference for study subjects.
While the informed consent process is prospective and takes place before research activities are conducted, consent should also be an ongoing interaction between the investigator and the research subject for the duration of the study. Subjects must be informed about significant new information or findings that develop during the course of the study that may affect their willingness to continue participation. Refer to Section 9.17 – Significant New Information/Findings (SNIF) to Participants for more information.
The informed consent form must be signed before any study procedures begin. The investigator or research staff verbally explains the purpose and procedures involved in the study. The research staff answers questions and provides information to allow the subject to make an informed decision with ample time to consider participation. Thus, investigators should consider whether obtaining consent on the same day that study procedures begin provides participants enough time to consider participation.
The consent process must be free of coercion or undue influence. If an investigator has a relationship with potential subjects (physician-patient, instructor-student, employer- employee), care should be taken to avoid recruitment methods that may be seen as coercive due to the special relationship between the parties.
The consent document should be revised when new information becomes available or when the study changes. Any proposed changes to an IRB-approved informed consent form must be reviewed and approved by the IRB before changes are implemented (unless the change is necessary to avoid immediate harm to subjects or others). Refer to Section 8.1 – Amendments – Changes to Research after Approval for additional information.
Consent and Assent
Only competent adults can give legally effective informed consent to participate in research.
Minors and those individuals who are not competent to give consent should be asked for their assent to take part in the research. Assent is the agreement of a minor or cognitively impaired adult to participate in a research project.
Adequate provisions should be made for soliciting the independent, non-coerced assent from minors/children or cognitively impaired persons who are capable of knowledgeable agreement. In general, the IRB recommends that children ages seven and older and most cognitively impaired adults be given the opportunity to assent. In cases where assent is obtained from a minor or cognitively impaired subject, permission must also be obtained from a legally authorized representative. The legally authorized representative may be a parent, a court-appointed guardian, or the court.
Special attention must be given to state law regarding attaining the age of majority (18 years of age) and situations involving emancipated minor subjects. Refer to Section 9.16 – Child Assent Special Requirements for more information.
When the study subject population includes people who do not understand English, and the investigator or the IRB anticipates that consent interviews are likely to be conducted in a language other than English, the IRB will require translation of the IRB-approved consent documents into those languages.
Informed Consent Translation
It is the responsibility of the investigator or study sponsor to provide translation of an IRB approved Informed Consent Form (ICF). For studies that are greater than minimal risk (Full Board), one of the following is required a) A Certificate of Translation by a) a professional certified translator/translation company , or b) documentation that the translation has undergone quality review by an entity such as an NIH Regulatory Support Center or the NIH Translation Unit. The translated ICF and appropriate documentation must be sent to the IRB via “Send Message to IRB.” The translated consent form with IRB stamp will be uploaded into the iStar application. Investigators will receive email notification that the translated consent form is ready for use. A letter of IRB approval will not be issued for the translated consent document.
Minimal risk studies (Exempt or Expedited) do not require a Certificate of Translation to be submitted.
The USC IRB no longer provides translation services.
For OHRP and FDA guidelines on obtaining consent from subjects who do not speak English.
The California Experimental Subject’s Bill of Rights is a document that is legally required for all studies involving a medical experimentation* in the state of California. The goal is to provide subjects with a clear statement of their rights as study subjects.
California law requires that the Experimental Subject’s Bill of Rights should remain a separate document from the informed consent form. It must be attached to the front of the informed consent form as illustrated in the Informed Consent Template and Instructions available on the OPRS websites. In addition, the copy is to be dated and signed by the subject or the subject’s legally authorized representative. The subject or subject’s legally authorized representative is given a copy of the Experimental Subject’s Bill of Rights before giving consent to participate in any medical experiment.
The California Experimental Subject’s Bill of Rights must be provided to the subject or subject’s legally authorized representative in his or her language during the consent process. This also applies when a Short Form is used in the consent process. The Bill of Rights and Short Form consents are available in various languages on the OPRS websites.
* A medical experiment is defined under section 24174 of the California Health and Safety Code as follows: “(a) The severance or penetration or damaging of tissues of a human subject or the use of a drug or device, as defined in Section 109920 or 109925, electromagnetic radiation, heat or cold, or a biological substance or organism, in or upon a human subject in the practice or research of medicine in a manner not reasonably related to maintaining or improving the health of the subject or otherwise directly benefiting the subject; (b) The investigational use of a drug or device as provided in Sections 111590 and 111595; (c) Withholding medical treatment from a human subject for any purpose other than maintenance or improvement of the health of the subject.”
For research involving protected health information (PHI), a current Health Insurance Portability and Accountability Act (HIPAA) research authorization form must be signed. The subject or legally authorized representative must sign and date the authorization form. If the subject is a minor (under 18 years old), a parent will sign the HIPAA authorization form. The HIPAA authorization form must be a separate form per California Civil Code – Civ. Code 56.11(b) An authorization for the release of medical information by a provider shall be valid if it: (b) Is clearly separate from any other language present on the same page and is executed by a signature which serves no other purpose than to execute the authorization. HIPAA authorization templates can be downloaded from the following website: HIPAA. The HIPAA authorization form must be a separate form per California Civil Code – Civ. Code 56.11(b) An authorization for the release of medical information by a provider shall be valid if it: (b) Is clearly separate from any other language present on the same page and is executed by a signature which serves no other purpose than to execute the authorization.
Investigators should refer to “Instructions for Completing HIPAA Research Authorization Forms” provided by the USC Office of Compliance. This instruction sheet explains what sections can and cannot be changed. If additional changes to language in the HIPAA Authorization are required, these changes must be submitted to the Office of Compliance for approval before they are used. For additional information regarding HIPAA Privacy Regulations, refer to the Office of Compliance at HIPAA Privacy Regulations.
California Law requires the HIPAA Authorization to remain as a separate document from the informed consent form.
The General Data Protection Regulation (GDPR) effective 5/25/2018 has been designed to harmonize data privacy laws across the European Union (EU). These regulations have the potential to affect clinical research and other scientific research activities conducted by USC. Investigators should be aware that research involving “personal data” about individuals in the EU/EEA (European Economic Area) must comply with the GDPR.
In addition to entities established in the EU/EEA, the GDPR applies to the processing of “personal data” by a controller or processor who is not physically established in the EU/EEA when the processing is related to (a) the monitoring of behavior of research subjects who are in the EU/EEA, or (b) offering goods or services to research subjects in the EU/EEA. The U.S.-based use and processing of “personal data” that has been collected in the EU/EEA, for clinical or other research purposes is subject to the GDPR. The regulations also apply to “Personal data” collected for clinical or other research purposes, from research subjects who have relocated to reside in the EU/EEA.
GDPR defines “Personal Data” as “any information relating to an identified or identifiable natural person” who is in the EU/EEA, regardless of the individual’s EU/EEA citizenship status. EU/EEA data protection authorities deem data to be de-identified if there is no reasonable means through which someone who has access to the data could use the data to re-identify an individual who is the subject of the data.
Individually identifiable data collected from an EU/EEA citizen at a location in the United States will be subject to United States law and not GDPR, unless the data was solicited from an individual while in the EU/EEA, or the organization continues to monitor the EU/EEA citizen after the citizen returns to the EU/EEA. More information is available on the OPRS website.IRB will assure that proper consent appears on GDPR qualified studies:
A valid consent to process an individual’s Personal Data for research purposes under GDPR must be freely given, specific, informed and unambiguous agreement to the processing. GDPR permits an organization to rely upon consent from research subjects as a lawful basis for processing Personal Data for research purposes.
The USC GDPR Consent Addendum can be found at the OPRS website.
The required information includes:
- The period for which the data will be stored.
- Any projected future use of the data.
- The fact that consent may be withdrawn, and data will be deleted.
Primary investigators are responsible for discerning whether their study data collection demands adherence to the General Data Protection Regulation (GDPR). For guidance refer to: NIH Recommendations: https://www.hhs.gov/ohrp/sachrp- committee/recommendations/attachment-b-implementation-of-the-european-unions- general-data-protection-regulation-and-its-impact-on-human-subjects- research/index.html.
Informed consent templates provide sample language, instructions, and guidance. The templates include the Informed Consent Template which is to be used when there is no model template provided by an industry sponsor or cooperative group. The Informed Consent Form Instructions for Industry Sponsor, Cooperative Group, or External IRB Studies is to be used when a model consent form is provided by an industry sponsor, cooperative group or external IRB. The use of the latter template should require less editing and allow for a more expedient processing for industry sponsored studies.
Federal regulations (45 CFR 46.116 and 21 CFR 50.25) specify basic required elements and additional elements of informed consent described below.
The informed consent requirements are not intended to preempt any applicable Federal, state, or local laws (including tribal laws passed by the official governing body of an American Indian or Alaska Native tribe) that require additional information to be disclosed in order for informed consent to be legally effective.
Emergency Medical Care
Nothing in this policy is intended to limit the authority of a physician to provide emergency medical care, to the extent the physician is permitted to do so under applicable Federal, state, or local law (including tribal law passed by the official governing body of an American Indian or Alaska Native tribe).
Key Information in Consent
The 2018 changes to the Common Rule (45 CFR 46) require that consent forms “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.” Below is guidance for key elements that should be addressed as appropriate to the study – modify accordingly.
- Being in this research study is voluntary – it is your choice.
- You are being asked to take part in this study because [Specify condition,
situation, circumstances or other reason for recruitment]. The purpose of this
study is [INSERT brief description of purpose].
- Your participation in this study will last for about [INSERT timeframe, e.g.,
- Procedures will include [INSERT primary activities]. Some of these procedures
may be optional.
- There are risks from participating.
- The most common risk is [INSERT].
- One of the most serious risks is [INSERT].
See the “Risks of Participation” section in this consent form for more information.
You should discuss these risks in detail with the study team.
- You will not benefit from being in this study. -OR- You might not benefit from being in this research study. The potential benefit to you might be…
- If you do not want to take part in this study [discuss appropriate alternative procedures or courses of treatment that might be advantageous to the subject (e.g., standard treatment, no treatment, comfort care or participation in another study)] [Delete if no alternatives]
For studies with simple designs, the consent form itself may be just a few pages (less than 5 pages), meeting the requirements for being clear, concise and also containing key information in an appropriate format.
Basic Elements of Informed Consent
The following information shall be provided to each subject or the legally authorized representative.
- 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;
- 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; and
- 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.
Nine additional elements of informed consent may apply, depending on the nature of the study [45 CFR 46.116(c)]. When appropriate, informed consent forms must also include one or more of the following 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) 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).
Other Information to be Included in Consent
The informed consent form should describe any compensation available to subjects. This may include payment for participation and reimbursement for expenses such as parking fees, travel expenses, and childcare incurred during the study. The consent form should explain how and when subjects will receive payment. In alignment with Food and Drug Administration (FDA) recommendation, USC encourages the adoption of a pro-rated payment system whenever possible. The nature, amount, and method of payment must not constitute undue inducement to participate.
If subjects will receive more than $600 per year for taking part in one or more research studies, the consent form should explain that subjects may receive an Internal Revenue Service (IRS) Form 1099. The $600 per year amount does not include reimbursements for expenses.
If payment will be in the form of academic credit that will be awarded for research participation, the amount and type of credit should be clearly stated as well as any required conditions for credit.
Sponsor or Funding Agency Identification
If applicable, subjects should be told what entity is funding the research (such as the drug company, device manufacturer, federal agency, or foundation).
Conflict of Interest
The research team must disclose all financial or other personal considerations that compromise, or have the appearance of compromising, professional judgment in proposing, conducting, supervising, or reporting research. Conflicts include financial, non-financial and institutional interests.
Disclosure of Incidental Findings
The consent form must clarify whether or not subjects will be informed about information obtained but not sought as part of the research project.
Pregnant Partners of Research Subjects
When males are enrolled in clinical studies, researchers are often interested in evaluating whether the investigational drugs, devices, or procedures have effects on their pregnant female partners and their fetuses. Pregnant partners who are not participants in the research should be consented for this purpose.
When a pregnancy occurs in the partner of a research subject, the IRB should be notified, and the information recorded in iStar. The following provides the process for obtaining data from the pregnant partner of the research subject when it is requested by the researcher or study sponsor.
The USC IRB considers the pregnant partner, fetus, and child to be research subjects because the researcher is collecting identifiable private information (under HHS) and the partner, fetus and/or child is participating in the investigation by allowing the collection of information about his/her (indirect) receipt of the test article (under FDA).
Under HHS per 45 CFR 46.102:
(d) Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge
(f) Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains:
(1) Data through intervention or interaction with the individual, or
(2) Identifiable private information.
Under FDA per 21 CFR 50.3:
(c) Clinical investigation means any experiment that involves a test article and one or more human subjects…
(g) Human subject means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient.
(j) Test article means any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act …
Process for Obtaining Pregnant Partner’s Informed Consent
Written consent/HIPAA from the pregnant partner is required if data and information relating to the pregnancy will be collected from identifiable records. Obtaining consent requires talking with the male subject about the desire to obtain the information about the pregnant partner and the subsequent birth if applicable. No information regarding the partner’s pregnancy (accompanied with identifiers) should be recorded by the study team or the sponsor until the partner has given permission and signed the consent/HIPAA form.
It is important to preserve the professional relationship that exists between the subject and the study team so the initial approach for permission from the partner must be via the subject (with his permission) and the USC study team.
A consent form for the pregnant partner must include the required USC language and HIPAA. The purpose listed on the consent should be the collection of information about the pregnant partner, fetus and/or child, not the purpose of the research in which the male partner is participating. A complete Authorization for Use/Disclosure of Health Information Authorization Form, (or a Release of Medical Records Form) is required to permit the release of specific medical information from the pregnant partners personal physician(s) about the pregnancy and the health of the baby. This authorization form describes the information that will be collected and with whom it will be shared (the study sponsor, or the study sponsor and site study team). The form will be provided by the study team.
The pregnant partner consent/HIPAA form should be submitted before any data is collected on a pregnant partner, fetus and/or child. It may be submitted with the initial study documents or at a later date when data collection is imminent, as long as enough time is allowed for IRB review and approval before its anticipated use.
There needs to be the ability for a pregnant partner to “opt out” of additional data collection on his or her child. It is also important to specify in the consent form the time period requested for continued access to records regarding the pregnancy and birth. The time should not be open ended. Children have several steps of increasing autonomy which should correspond with decisions about use of their data. Providing parental permission to access their data in infancy requires defining the time frame. If there is long term follow up, reasonable expectations might include re-consenting the family at age 10- 12 so that the developing autonomy of the child may be taken into consideration.
Please consult with the IRB as needed for study specific issues or situations not outlined in this policy.
Who may conduct the informed consent process is determined by institutional policy and the risks and nature of the study. The following is the USC policy on who can conduct the informed consent process for human research studies:
- Individuals who are knowledgeable about the protocol must obtain consent from subjects for participation in a study. Specifically, they must be able to describe the purpose, procedures, benefits, risks, and alternatives to participation in the study. They must be able to answer subjects’ questions about the protocol and about risks of the research procedures and alternatives.
- All individuals who participate in the informed consent process must first successfully complete the online USC Human Subjects Education Program through the Collaborative IRB Training Initiative (CITI). More information on CITI is available at the following website: CITI.
- The PI must identify all individuals who will obtain consent and attest that they fit the above criteria. The PI is ultimately responsible for ensuring that ethically and legally valid consent is obtained from all research subjects.
- The investigator or other person obtaining informed consent must sign the study consent document(s) on the signature line labeled “Person Obtaining Informed Consent”.
Legally Authorized Representative (LAR) means 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 procedures involved in research. California law specifies who can be the Legally Authorized Representative and provide consent when a subject is not able to provide informed consent.
For studies involving cognitively-impaired adults, consent guidelines and the use of legally authorized representatives are governed by California Health and Safety Code Section 24175. For more information, refer Section 13.4 – Cognitively-Impaired Persons. If studies relate to the subject’s cognitive impairment, lack of capacity, or serious or life- threatening diseases and conditions, consent must be sought from the LAR based on the order defined in California Law CA Health and Safety Code 24178.
If the person from whom assent is sought refuses, the person should not be enrolled, even if the LAR gives permission. Alternatively, if the person from whom assent is sought agrees to participate, the person may not be enrolled if the parent or authorized representative does not give permission.
For Child Assent see Section 9.16
The purpose of an informed consent form is to provide subjects with a written source of information for future reference and to document the fact that the process of informed consent occurred prior to the subject’s participation. The form generally serves as a basis for the initial presentation of the study to the potential subject. Typically, informed consent is documented by using the IRB-approved, written informed consent form which is signed and dated by the subject, or the subject’s legally authorized representative, at the time of consent. The consent form may be read to the subject or the subject’s legally authorized representative. A copy of the informed consent form must be given to the subject. Unless the investigator has requested a waiver of documentation of consent, the subject’s signature on an informed consent form is required prior to beginning any study procedures. Information given to the subject or the representative must be in a language understandable to the subject or representative.
When the research is not exempt, and deception is used as a technique, there should be a prompt and complete debriefing of the subjects. Debriefing may include explaining the research, and if possible, providing the opportunity for withdrawal of personal responses or withdrawal from participation in the study. A debriefing statement for IRB review should be submitted along with the informed consent form.
The informed consent form (or electronic consent) signed by a study subject, or the subject’s legally authorized representative, must be the version currently approved by the IRB that bears the date stamp of the IRB. One copy must be given to the subject and the original consent with the original signature must be maintained by the investigator. Another copy of the informed consent form must be maintained in the subject’s research chart, medical record, or equivalent file in medical research studies.
One version of the informed consent form must be posted on one of two publicly available websites – ClinicalTrials.gov or Regulations.gov (search: docket folder Docket ID: HHS-OPHS-2018-0021). The ICF must be posted after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject. The ICF posted must have been used in enrolling participants. The responsibility for posting is the Principal Investigator, awardee or the federal department or agency component conducting the study.
Electronic consents (eConsent) and electronic signatures may be used if the procedures for obtaining them, and the vendor, are approved by the IRB, and the risk of breach of confidentiality is minimized. The IRB will consider vendor security confidentiality issues – such as how a copy of the consent document may be provided for review if requested by the subject. Per FDA/OHRP guidance, “If properly obtained, an electronic signature can be considered ‘original’ for the purposes of recordkeeping.” * This includes electronic signature to documents in the research record.
The subject must agree to use the electronic format and must be provided a written copy of the informed consent in non-electronic form, and be provided description of any procedures that must be followed to withdraw their agreement to use an electronic record.
Vendors producing electronic consents will also need to comply with established FDA regulations. “Electronic” documents would be subject to a specialized set of requirements found at 21 CFR Part 11. Compliance with these standards is used to assure that electronic records are “trustworthy, reliable, and generally the equivalent to paper records and handwritten signatures executed on paper.” Investigators are responsible for ensuring compliance with 21 CFR Part 11. This regulation requires that the electronic system capture the record date that the subject or subject’s LAR provides consent.
The following consideration should be given when using eConsent technologies:
- The ability or individuals to access or use the technology, especially individuals with poor eyesight or impaired motor skills
- The ability of the study team to verify the identity of the individual using the technology
- the availability of the study team to answer questions of study participants; and
- Security measures to ensure the privacy and confidentiality of information collected with the electronic technology.
- All IRB-approved versions of an eConsent must be archived and easily retrievable. All procedures must be in compliance with FDA regulations for electronic records (Part 11, Electronic Records; Electronic Signatures – Scope and Application).
Amendments to an eConsent may be provided in an electronic or paper format. Either is acceptable to convey and transmit updated information to the subject. OPRS and FDA regulations permit the flexibility of using electronic and paper informed consent methods independently or in combination throughout the course of the study.
For studies that involve social media websites, investigators must ensure informed consent language does not conflict with terms of service agreements from those websites (such as Facebook, Twitter).
*The definition of “written” or “in writing has been determined to mean writing on a tangible medium (i.e. paper), or in an electronic format.
A short form consent document attests that the elements of informed consent, as required by DHHS and the FDA, have been presented orally to either the participant or the participant’s legally authorized representative (LAR). The OPRS website has Short Form Consent Templates available in English and other languages – Forms and Templates. If the language you need is not available on the website, you must have the English short form translated into the appropriate language prior to submitting your request to the IRB.
The short form process may be used twice for a particular language in a study. After the second use of the short form consent process, the informed consent document must be translated into that particular language as it can be anticipated you will encounter additional potential participants that understand that language.
Use of short form consent is an option for any kind of research. When using the short form to document consent, the informed consent must begin with a concise and focused presentation of the key information to assist a prospective subject in understanding the reasons why one might or might not want to participate in the research. The informed consent must be organized and presented in a way that facilitates comprehension.
Regulations do not limit the use of short form consent to translations only.
If informed consent is obtained using the Short Form method (oral translation of the consent form in a language understood by the participant supplemented with the written Short Form in the participant’s language), the subject, or the subject’s legally authorized representative, and an impartial witness must sign and date the informed consent. The consent form may be read to the subject or the subject’s legally authorized representative. If applicable, the subject or legally authorized representative must also sign the California Bill of Rights translated into a language understood by the subject.
The signature of an impartial witness is required by federal regulations in very limited circumstances. It can also be required by the IRB to assure an adequate informed consent process for some research studies. The witness signature means that the requirements for consent have been satisfied, and that consent is voluntary and freely given by the subject or legally authorized representative.
One who signs as a witness to the consent process must be an adult who is not a member of the research team and is able to understand the consent, for example an interpreter, a member of the clinic staff or a family member. The witness must be fluent in both languages if translation is required.
When an investigator anticipates enrollment of non-English speaking subjects, the IRB-approved informed consent form must be translated into each anticipated language. When a study includes unanticipated non-English-speaking subjects, the investigator must provide short form consent to the subject or legally authorized representative (LAR).
If there is occasional and unexpected need to enroll subjects who are not fluent in English, a written short form informed consent must be used in conjunction with the written IRB-approved English version of the consent. The short form consent includes the basic and possible additional elements of disclosure. The short form is available in English and many languages on the OPRS websites. Investigators can download the short form and fill in the blanks as appropriate. The language has already been approved by the IRB.
The process for enrolling subjects with the short form is outlined below. Substitute “Legally Authorized Representative (LAR)” for “subject” when a LAR is involved in the process. Please refer to “Impartial Witness of Informed Consent Process” for requirements. All of the following requirements must be completed:
- A translator must orally translate the entire IRB-approved English version of the consent form to the subject in a language understandable to him/her, and the subject must be given a copy of the translated “short form” consent document to read
- The entire consent process must include an impartial witness to the oral presentation
- The IRB-approved English version of the consent form must be signed by the individual authorized by the IRB to obtain consent and signed by the impartial witness to the consent process. The translated short form must be signed by the subject and the witness to the consent process
- The California Bill of Rights must be provided to the subject for studies that involve a “medical experiment” as defined by California law. The Bill of Rights is available in the same languages as the short form and available on the OPRS website – Forms and Templates. The subject must sign and date the form, AND
- The subject must be given copies of the IRB-approved English version of the consent form and the translated versions of the short form consent document and California Bill of Rights.
Additional protections are needed for subjects who cannot see, hear, or speak or who cannot read or sign consent forms. The consent process must be conducted in a language or manner understandable to the subject and must allow the subject to communicate his or her willingness to participate. The informed consent must begin with a concise and focused presentation of the key information to assist a prospective subject in understanding the reasons why one might or might not want to participate in the research. The informed consent must be organized and presented in a way that facilitates comprehension. The study team must ensure that the subject is adequately informed and properly document the consent process. Guidance_Consenting Participants With Physical Impairment 6.04.2020
When consenting the following subjects – an impartial witness is required to observe and sign the informed consent (per OHRP, FDA, ICH).
- Subjects who cannot read, write, or hear
- Non-English-speaking subjects consented with a Short Form consent
- Cognitively Impaired subjects at the discretion of the IRB
- Any subjects at the discretion of the IRB
An impartial witness must be present during the consent process and must sign the consent form. Subjects who are unable to sign the consent form can consent to participate in the research by “making their mark” (providing an alternative form of signature) on the signature line. The name of the subject, date, and time (if applicable) can be completed for the subject by either the witness or the person obtaining consent. A note must be included in the research record stating the method used for communicating with the subject and the means by which the subject communicated agreement.
For non-English speaking subjects who cannot see, read, or write, the process described above should be used. The study team must use a consent form or short form translated into a language the subject understands.
People who can read but cannot physically write can give verbal consent. An impartial witness must be present during the consent process and must sign the consent form. The name of the subject, date, and time (if applicable) can be completed for the subject by either the witness or the person obtaining consent. Documentation in the research record must include the method used for communicating with the subject and the means by which the subject communicated agreement.
For people who can read and write but cannot hear or speak, sign language or specialized oral interpreters should be used to enhance communication with the study team. An impartial witness* must be present during the consent process and must sign the consent form. Documentation in the research record must include the method used for communicating with the subject and the means by which the subject communicated agreement.
When consent is obtained from a Legally Authorized Representative (LAR), follow the procedures above substituting LAR for subject as applicable.
* Please refer to “Impartial Witness of Informed Consent Process” for requirements.
Broad consent is an option for secondary research use, storage, and maintenance of identifiable private information and identifiable biospecimens. Broad consent is only used for secondary research. The use of broad consent is optional, and alternatively, investigators can continue to use biospecimens that are coded or seek waiver of consent for use of biospecimens with identifiers if broad consent has not been declined. The IRB cannot waive consent if an individual refuses broad consent.
The researcher and institution are required to track impermissible uses of the data collected with broad consent. The challenge of developing and maintaining such a tracking system is not feasible at this time, therefore the use of broad consent is not available at USC
See Section 14.3 on Secondary Data Analysis
Waiver of Requirements of Informed Consent
In some situations, the IRB may waive the requirement for obtaining a signed informed consent 45 CFR 46.117(c). Investigators may request the IRB waive some or all of the requirement for informed consent. The following describe the requirement for the approval of waiver.
An IRB may approve a consent procedure that does not include, or that alters, some or all of the elements of informed consent set forth above; or waive the requirements to obtain informed consent, provided the IRB finds and documents that:
- The research involves no more than minimal risk to the subjects;
- The research could not practicably be carried out without the requested waiver or alteration;
- If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format;
- The waiver or alteration will not adversely affect the rights and welfare of the subjects; and
- Whenever appropriate, the subjects or legally authorized representatives will be provided with additional pertinent information after participation.
An IRB may approve a consent procedure that does not include, or that alters, some or all of the elements of informed consent set forth above; or waive the requirements to obtain informed consent, provided the IRB finds and documents that:
- The clinical investigation involves no more than minimal risk (as defined in 21 CFR 50.3(k) or 56.102(i)) to the subjects;
- The waiver or alteration will not adversely affect the rights and welfare of the subjects;
- The clinical investigation could not practicably be carried out without the waiver or alteration; and
- Whenever appropriate, the subjects will be provided with additional pertinent information after participation.
FDA does not object to a sponsor initiating, or an investigator conducting, a minimal risk clinical investigation for which an IRB waives or alters the informed consent requirements as described above.
IRB Waiver or Alteration of Informed Consent for Clinical Investigations Involving No More than Minimal Risk to Human Subjects (July 24, 2017)
Waiver of Documentation of Informed Consent
The IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds that the:
- Only record linking the subject and the research would be the informed consent form and the principal risk would be potential harm resulting from a breach of confidentiality;
Note 1: Subjects must be asked whether they want documentation linking them with the research, and their wishes must govern. (Example: domestic violence research where the primary risk is discovery by the abuser that the subject is talking to researchers.)
Note 2: In order to waive written documentation of consent where the only record linking the participant and the research would be the consent document, the IRB has to determine that the research is not FDA-regulated.
- The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context. Procedures such as non-sensitive surveys, questionnaires and interviews generally do not require written consent when conducted by non- researchers; or
In cases in which the documentation requirement is waived, the IRB requires the investigator to provide in the application materials a written summary of the information to be communicated to the subject, and the IRB will consider whether to require the investigator to provide subjects with a written statement regarding the research.
- The research presents no more than minimal risk of harm to subjects and which signing forms is not the cultural norm.
- Only record linking the subject and the research would be the informed consent form and the principal risk would be potential harm resulting from a breach of confidentiality;
Waiver of Elements of Consent or Consent Itself
Some research projects would not be possible if obtaining consent from subjects was required. The IRB may consider waiving the requirement for some or all of the elements of informed consent. The regulations state that informed consent may be waived in full or in part if the IRB determines that all 4 conditions below are met
- The research involves no more than minimal risk to the subjects and
- The research could not practicably* be carried out without the requested waiver or alteration:
- The waiver or alteration will not adversely affect the rights and welfare of the subjects; and
For research involving the use of identifiable private information or identifiable biospecimens, a waiver of consent may be granted if it is determined that the research could not practicably be carried out without using such information or biospecimens in an identifiable format.
*For the purposes of this policy, practicably means reasonably capable of being accomplished; feasible. The investigator must provide justification as to why the research cannot “practicably” be carried out without a waiver or alteration of consent.
A waiver may consist of a waiver of the entire consent or waiver of some element of the consent as justified.
In emergency situations, an exception to the informed consent process may be justified. Refer to Section 16.8 – Planned Emergency Research with Exception from Informed Consent.
*OHRP Human Subject Regulations Decision Chart 11 provides more information.
Consent not required for screening, recruiting, or determining study eligibility
The IRB may approve a research proposal in which an investigator will obtain information or biospecimens for the purpose of screening, recruiting, or determining eligibility of prospective subjects without the informed consent of the prospective participant or the participant’s legally authorized representative, if either of the following conditions are met ((45 CFR 46.116(g)):
- the information will be obtained through oral or written communication with the prospective subject, or
- by accessing records or stored biospecimens
A partial waiver of HIPAA authorization for screening and recruitment is required to
access medical records.
This regulation does not apply to FDA regulated research (21CFR50).
Waivers for public benefit and service programs
The IRB may waive informed consent requirements or the need to obtain informed consent for research involving public benefit and service programs that require approval by state or local officials (45 CFR 46.116(a))
Waiver Due to Cultural Norm
Waiver of informed consent is granted if the subjects or legally authorized representative (LAR) are members of a distinct cultural group or community in which signing forms is not the norm, and the research presents no more than minimal risk of harm to subjects and provided there is an appropriate alternative mechanism for documenting the informed consent obtained.
Special informed consent procedures and forms are required when children participate in research. Children have not attained the legal age to consent to research treatments or procedures. Assent is a child’s affirmative agreement to participate in research. Investigators must obtain permission from parents and agreement (assent) from children. Additional information about research involving children as subjects is found in Section 13.1 – Protection of Children Involved as Subjects in Research.
Requirements for Parental Consent
Subpart D of the federal regulations (45 CFR 46 Subpart D) addresses permissible research with children and consent requirements. Some situations require permission from one parent, while other situations require permission from both parents. In other cases, waiving the requirement to obtain consent may be necessary (See Section 13.1 – Protection of Children Involved as Subjects in Research for more about Subpart D).
Permission of One Parent
The IRB may find that the permission of one parent is sufficient for research to be conducted under §46.404 (research not involving greater than minimal risk) or §46.405 (research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects).
Permission of Both Parents
Where research is covered by §46.406 (referring to research involving greater than minimal risk and no prospect of direct benefit) and §46.407 (specific requirements of IRB members to ensure the safeguard of vulnerable subjects), permission is to be obtained from both parents, unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child.
Waiver of Consent Requirements
If the IRB determines that a research protocol is designed for conditions or for a subject population for which parental or guardian permission is not a reasonable requirement to protect the subjects (for example, neglected or abused children), it may waive the consent requirements in 45 CFR 46 Subpart A and 45 CFR 46.408(b), provided an appropriate mechanism for protecting the children who will participate as subjects in the research is substituted, and provided further that the waiver is not inconsistent with federal, state or local law.
Additionally, Public Demonstration Projects may obtain a waiver of parental permission if the IRB finds that all criteria below are satisfied:
- The research is to be conducted by or subject to the approval of state or local government officials, and
- The research is designed to study, evaluate or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs, and
- The research could not practicably be carried out without the waiver or alteration, and
- The research is not FDA-regulated.
Research participants must be provided with significant new information/findings that arise during the course of the research and may affect their willingness to continue participating [45 CFR 46.116(b)(5) and 21CFR50.25(b)(5)]. Subjects will be informed of SNIF using an updated consent. Examples of situations that require the investigator to provide an updated:
- Changes to the procedures
- Identification of new risks or that risks previously described are known to occur
with greater frequency or severity than previously reported
- New investigator conflict of interest
- Notification of significant findings from related studies
Providing Significant New Information/Findings (SNIF) to Participants
If an apparent, immediate hazard to participants is identified, participants must be notified, and corrective actions implemented as soon as possible. The IRB must be informed and the investigator must submit a Reportable Event in iStar – “Protocol Change Initiated to Eliminate Immediate Hazard” promptly (within 10 days). (Please see “Investigator Reporting of Internal Adverse Events to the USC IRB Subsequently, an amendment with revised study documents (such as an updated consent form, and updated protocol) must be submitted to the IRB within 30 days. The Principal Investigator must notify the sponsor as required by the sponsor or FDA.
When investigators must contact participants immediately, notification can be made in writing or verbally. However, study files must document when participants were notified, how they were notified (in person, by phone, or by email or letter), what information was provided to them, and who contacted them.
Significant New Information that Does Not Involve an Apparent Immediate Hazard
If significant new information/findings do not warrant immediate notification of participants, the investigator must inform participants of the new information/findings using a consent document. The consent document requires prior IRB review and approval. The study participant will be asked to sign a new informed consent form that will include the significant new information. This will document the participant’s decision to remain in the study (“re-consent”)
Recruitment of subjects is considered to be the beginning of the informed consent process. Recruitment is one of the most challenging aspects of research involving human subjects. Recruitment is often conducted by use of posters and brochures displayed in public spaces that include hospitals, clinics and laboratories. Traditional radio and television announcements, along with websites and social media are also often used.
The pressure to enroll subjects raises ethical challenges for investigators and research staff. Recruitment of subjects must be equitable and include racial, ethnic, educational, socioeconomic, and gender diversity appropriate to the condition being studied. All recruitment efforts must respect personal rights to privacy and confidentiality and be compliant with FDA, OHRP, and HIPAA regulations, as applicable.
The IRB will not review recruitment and/or consent documents for studies determined to qualify for exemption.
For additional guidance, refer to:
Guidance and Requirements for Recruitment Letters and Emails for Potential Human Subjects Identified from Electronic Health Records – USC OPRS
FDA Information Sheet “Recruiting Study Subjects”
All recruitment materials under local control, including advertising and marketing materials, for non-exempt studies must be reviewed by the IRB. Any recruitment materials generated by USC investigators or research personnel must be submitted to the IRB for review before they can be used. The IRB does not stamp recruitment materials.
The following information may be included in recruitment materials developed by sponsors or locally:
- Accurate description of the research purpose
- Name and address of the investigator or facility (including university affiliation
- Condition under study or purpose of the research
- Eligibility criteria
- Time commitments required
- Location of the research
- Person to contact for further information
The following information should NOT be used in recruitment materials:
- Coercive and or persuasive language
- Claims that a device or drug is safe and effective
- The words “new treatment,” “new medication,” or “new drug” if the test article is
- Promises of “free medical treatment”
- The word “free” should not be used
- Compensation should not be excessive relative to the nature of the project and should not stand out from the surrounding text
- Statements or implications assuring favorable outcome or other benefits beyond what is outlined in the consent document and protocol
- Claims, either explicitly or implicitly, that the test article is known to be equivalent or superior to any other drug, biologic, or device
- Exculpatory language
If you have questions, contact the IRB for more information.
National Recruitment Materials Not Reviewed by the IRB
Industry sponsors often produce recruitment materials that are used on a national basis and that cannot be modified by local sites. Examples include websites, radio or television advertisements, and call center scripts. Recruitment materials that cannot be modified by USC investigators should not be submitted to the USC IRB. These materials should not be attached in the iStar application.
Screening procedures to determine eligibility are considered part of the subject selection and recruitment process, and therefore, require IRB oversight. An example is the need for consent prior to medical testing necessary to determine eligibility.
An exception to the requirement for informed consent to obtain information or biospecimens for the purpose of screening/recruitment/determination of eligibility, may be granted under certain conditions if one of the two conditions are met:
- the information will be obtained through oral or written communication with the prospective subject, or
- by accessing records or stored biospecimens.
Interactions or interventions performed as part of the practice of medicine and which would be done whether or not study entry was contemplated, such as for diagnosis or treatment of a disease or medical condition, may be performed and the results subsequently used for determining study eligibility without first obtaining consent. However, a partial waiver of HIPAA authorization for screening and recruitment is required to access medical records.
Depending on the nature of the research, consent may be required before any screening procedures are performed. There are several potential options for obtaining consent for screening procedures.
Examples of screening procedures that can be performed without consent:
- When no data is kept, and no medical or psychological intervention occurs
- When screening activities generally pertain to non-medical minimal risk research
- When screening involves a procedure for which written consent is normally NOT required outside the research context
Screening procedures that require a separate consent form for screening:
- When requested by sponsor / IRB
- When screening involves a medical/psychological interaction or intervention that is greater that minimal risk or involves a procedure for which written consent is normally required
- When screening data are kept
- When impractical or not feasible to enroll a subject immediately after screening
Compensation takes many forms such as school supplies, gift certificates, parking reimbursements, meal coupons, nominal gifts, lotteries or cash.
The plan for compensating subjects must be submitted to the IRB in the study application. In addition, the form of compensation, or remuneration must be described in the informed consent document (such as cash, gift card, or chance to win a gift) as well as a description of the conditions under which a subject would receive partial or no payment.
For participation in an FDA regulated, sponsored trial, compensation may not be offered in the form of a discount coupon on the purchase price of the product after it has been approved for marketing.
Guidelines for Compensating Research Participants:
- Payment for participation in research should not be offered as a means of coercion. Rather, it should be a form of recognition for the investment of the subject’s time, loss of wages, or other inconvenience incurred. Compensation may not be withheld contingent on the subject’s completion of the study.
- In cases involving ongoing participation, compensation should be given on a reasonable, prompt, and prorated basis to avoid possible coercion. The payment should be made throughout the course of the study, contingent on participation as described in the protocol.
- The Principal Investigator and IRB should consider the risk, duration of participation, effort required, and local economy when determining appropriate compensation for a study population. Economically disadvantaged subjects are especially vulnerable to undue influence from excessively high levels of compensation.
- It is acceptable to provide entry into a drawing to receive a gift as a form of compensation in lieu of providing cash or other remuneration. The “thank you” gift is commonly used by student investigators with limited funds. Examples of gifts include a chance to win a “thank you” item such as an MP3 player, cellular phone, or gift-card.
Compensation for U.S. Military Personnel for Department of Defense (DOD) Sponsored Research
When a USC investigator conducts Department of Defense-sponsored research on US military personnel, the following limitations on dual compensation for US military personnel apply:
- Prohibits an individual from receiving pay from more than one position for more than 40 hours of work in one calendar week. (Includes temporary, part-time and intermittent appointments.)
The Army allows research compensation when military personnel are ‘off-duty’ or on ‘official leave’. If the research is greater than minimal risk the Commanding Officer must give permission for the military personnel to enroll. DOD allows compensation for military personnel up to $50 per blood draws whether on or off duty.
USC policy does not allow any finder’s fees. Investigators, or any other member of the research team, may not receive or offer payment to subjects (prospective, previously enrolled, or currently enrolled) for enrolling, or referring for enrollment their friends, family member, or other individuals. Finder’s fees may not be offered to other investigators, clinicians, researchers, or any other individual or group for referring potential subjects.
Social network-based sampling and intervention studies that involve peer referral, social contact referral, or near peers information is not subject to the finder’s fee policy prohibition. Respondent driven or chain referral/snowball sampling recruitment procedures for network (including dyadic) intervention studies, that employ modest incentives for peer referral for study enrollment are acceptable. The offer of finder’s fees as a recruitment incentive for sponsored biomedical research is prohibited.
Incidental Findings in research are results obtained/uncovered about an individual research subject, for which there is a potential health importance but is beyond the aims of the study. It may arise in collecting or analyzing research data/images or part of establishing eligibility or for purposes of the study itself (samples, eligibility, screening).
The research proposal should delineate how incidental findings will be managed in the research. The informed consent should be consistent with this plan. In general, it is contemplated that the health care provider/investigator will disclose the relevant information and ensure appropriate referral or care are recommended or provided.
Recommendations for Incidental Findings
- Researchers should develop a plan to manage anticipatable incidental findings, including but not limited to those findings known to be significant and clinically actionable (and, when relevant, analytically valid and clinically valid). The plan should be reviewed and approved by the Institutional Review Board.
- Researchers should develop a process for evaluating and managing unanticipated findings. Researchers who discover an unanticipated incidental finding of concern should assess its significance, consulting with experts as appropriate.
USC Dornsife Imaging Center (DNI) Policy and process for handling Incidental Findings
The Dornsife Imaging Center (DNI) is a research facility that is part of the College of Letters, Arts & Sciences and is not affiliated with the Keck School of Medicine or the University Hospital.
This DNI policy does not apply to biomedical researchers who conduct research at HSC. They are subject to additional internal policies established by their home division/department.
Researchers using or planning to use DNI services must familiarize themselves with the Dornsife Imaging Center policies. The policies are accessible online here.
The DNI policy includes mandatory informed consent language, consent for neuroimaging consult and subject eligibility. PI and research staff adherence to policy.