Informed consent is a core element of subject recruitment in clinical trials. It is not merely just obtaining a subject’s signature, but rather it involves an active conversation between the investigator and the participant.
Informed Consent Defined
Informed consent is a legal document containing specific, required information about the clinical trial. It must have the patient’s formal authorization to participate in the trial as well as be written in the language that a patient understands so they are able to understand the information and ask questions as needed.
As per federal regulations, the process of informed consent must meet the following criteria:
- Providing potential subjects with adequate information to allow for an informed decision to participate in the study
- Facilitating potential subject’s comprehension of the information
- Providing adequate opportunity for potential subjects to feel comfortable enough to ask questions.
- Continuing to keep the subject informed as the clinical investigation proceeds. The informed consent process goes beyond the initial conversation, it must continue for as long as the participant is part of the clinical trial.
Purpose of Informed Consent
The purpose of an informed consent that meets all the federal requirements include:
- Protection of subject rights.
- Proves that the subject and research team have an ongoing relationship.
- Provides an opportunity to update and reinforce the process as needed.
- Gives subjects an opportunity to actively voice their concerns and reassess participation.
- Promotes informed, independent decision making between the patient and investigator.
For more information regarding informed consent, please continue reading below. For more detailed information, visit the following https://research.rutgers.edu/researcher-support/research-compliance/human-subjects-protection-program-irbs/hspp-guidance-topics
Who Can Obtain Informed Consent?
Only IRB (Institutional Review Board) approved research staff that are delegated by a Principal Investigator are authorized to obtain informed consent from participants. Individuals obtaining informed consent must have proper training, education, and experience. The individual must be knowledgeable about the clinical investigation in order to effectively communicate information about the protocol as well as potential risks. Even if the task is delegated to another IRB approved research staff, the principal investigator must be responsible that informed consent is being conducted per federal regulations. (21 CFR 312.60 and 21 CFR 812.100).
Informed Consent Regulations and Requirements
There are several code federal regulations (21 CFR 50) and 45 CFR 46 for informed consent set in place to ensure the protection of human subjects. Requirements of this subpart include:
- Investigators shall obtain consent only when the prospective subjects have the opportunity to consider whether or not to participate.
- Information must be given in a language that the participant or representative understands.
- Some local IRBs may have Short Forms available for use. These Short Forms are written in the participant’s native language and is essentially a consent form with the participant stating that the consent was verbally translated to them and that they have full understanding of their voluntary participation in the research study. These Short Forms are not permitted to be used regularly and if the study population includes persons who speak a specific language, the investigator should make plans to translate the informed consent into the subject’s language.
- Informed consents can not have exculpatory language under any capacity, meaning it can not appear to waive any of the subject’s legal rights.
- Compliance with 21 CFR 50.20 No investigator may involve a human being in research unless the investigator has obtained legally effective informed consent of the subject or the subject’s legally authorized representative-this means that no research specific procedures can begin until informed consent is fully executed (eCFR).
- Investigators shall only obtain consent in a setting that provides prospective subjects an opportunity to make an informed, independent decision about participating. This includes having a private setting where the potential subject is not reluctant to ask questions without having judgment from others that may be watching. It is also a breach of confidentiality if potential subjects are sharing personal health sensitive data in a public setting such as a waiting room. Participants must also be given appropriate time to make the decision and should not be rushed in any circumstance.
- Information must be given in a language that the potential subject can understand. Inclusion/Exclusion Criteria outlines if non-English speaking participants can enroll in the study. If they are able to participate, there are two ways to obtain informed consent.
- If the IRB has an approved consent form that is translated into the participant’s language, the investigator must use it.
- If there is no IRB approved translated consent form, investigators may use a Short Form. These forms are only to be used a limited number of times. It is also important to ensure that the investigative team has a certified or institutionally recognized translator. Investigators should make plans to have their consent forms fully translated if anticipating frequent use of the Short Form.
Both 45 CFR 46 and 21 CFR 50 must be met if the investigation is conducted or supported by the Department of Health and Human Studies (DHHS) and involves an FDA regulated product. If there is a difference among the regulations, the regulation offering greater protection for human subjects should be followed.
Elements of Informed Consent
In order to be compliant with 21 CFR 50, the following information must be provided to the subject when obtaining informed consent:
- Research Description: Statement that the study involves research, explanation of research purposes, expected duration of subject’s participation, description of procedures, and identification of experimental procedures.
- Risks: Disclosure of potential risks and discomforts the participant may encounter during the study.
- Benefits: Disclosure of potential benefits the participant may encounter during the study.
- Alternatives: Disclosure of possible alternative procedures that may be advantageous to the subject.
- Confidentiality: Statement that describes the procedure for securing records that identify the subject or their private health information. There must also be a disclosure that the FDA may inspect the record.
- Compensation or Treatment due to Injury: For research studies that involve greater than minimal risk and have been approved by a full board IRB (Institutional Review Board) Review, medical treatment options must be disclosed. There must also be explanations as to what the medical treatment consists of in the case of injury.
- Contacts: A contact for answering patient questions about the research. Participants must also provide an emergency contact in the case of injury.
- Voluntary Participation and Withdrawal: Statement that expresses that participation is voluntary and that the subject will not have a penalty if they refuse to participate. Investigators must also disclose that participants can choose to withdraw from the study at any time without any penalty.
- The investigator must disclose if the participant will be made aware of the results of their study.
When appropriate, 21 CFR 50.25 requires disclosure of the following information to participants:
- Statement that details the risk of the treatment or procedure to the embryo or fetus if the subject becomes pregnant. It can also refer to general risks that are currently unforeseeable.
- Anticipated circumstances where the subject’s participation may be terminated by the investigator when considering the subject’s best interest. This may include pregnancy or if the subject is experiencing adverse events.
- Additional costs incurred by the subject as a result of their participation in the study. This may include insurance costs due to additional visits and imaging.
- Consequences of the subject’s withdrawal from the study.
- Statement relaying that new findings gained from the study may contribute to the subject’s willingness to participate.
- The appropriate number of participants involved in the study.
Best Practices While Conducting an Informed Consent
- The entire consent form must be reviewed with the participant prior to signing. The investigator must go over every section and allow patients to ask questions throughout.
- Each person involved in the informed consent process (investigators, participants, physicians, translators) must sign, print, and date for themselves. Pre-population of any part of the informed consent form is prohibited.
- The consent form must be completed in its entirety in order to be considered active. Even if one section is lacking a signature or acknowledgement, it is considered invalid.
Assent refers to a child’s affirmative agreement to participate in a research study. The assent must be written in a language that the child recognizes. For the child to make an informed decision, they do not need to comprehend the entirety of the study and it’s scientific background. Rather, they just need to be informed of the interventions and the general procedure. The age of assent can vary based on the study’s level of complexity as well as the child’s ability to understand. Assents can be written for different age ranges. For example, there may be a separate form for ages 7-13 and an assent form with more advanced language for ages 14-17.
Consult with the IRB if you believe the intervention involved in the research study provides medical benefit to the participant to see if you qualify for a waiver of assent.
A HIPAA authorization refers to consent obtained to use or disclose an individual’s protected health information. Usually, sharing of such information would not be permitted under the HIPAA Privacy Rule. The authorization must be in writing in order to be valid. Investigators may opt to include HIPAAAuthorization within the main consent form. Depending on the site, in which you are conducting clinical research, you may have a separate institutional authorization form. The HIPAAAuthorization will list all of the relevant parties that will have access to the data such as investigators, sponsors, CROs, IRBs, and other involved parties. It will also outline the time and length the HIPAAAuthorization is valid and applicable.
Certificate of Confidentiality (CoC)
CoC is important for protecting the privacy of research participants and includes the following elements:
- Must be issued by the NIH to protect identifiable research information in order to prevent forced disclosure.
- Allows investigators to refuse access to disclosing identifying information in any civil, criminal, administrative, legislative, or other proceeding.
- Guaranteeing protection of sensitive health and confidential information to promote research study participation and retention. If applicable, a CoC will likely be granted for your NIH funded study and you are to include the language in your informed consent form.
An enrollment note refers to legal documentation of the appropriate, properly conducted informed consent. Elements of an acceptable enrollment note include:
- Date and time the note is written and the consent was conducted.
- Identify the protocol that the subject is being enrolled to.
- Statement verifying that subject meets the inclusion criteria and none of the exclusion criteria.
- Statement that the proper informed consent was obtained prior to beginning any of the study procedures.
- Statement disclosing that the participant (or legal representative) had the opportunity to ask questions and communicate their concerns.
- Statement that ensures the participant had full understanding of their voluntary participation.
- Signature and date of the IRB approved investigator.