August 2023 FDA Guidance – eICF Focus
On August 16, 2023, the Food and Drug Administration (“FDA”) announced that the final guidance for industry entitled “Informed Consent: Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors” is now available. This Guidance was issued on August 15, 2023, and it aims to assist Institutional Review Boards (IRBs), clinical investigators, and Sponsors to comply with regulatory requirements for clinical investigations – FDA`s informed consent requirements.
The afore mentioned Guidance replaces FDA’s guidance entitled “A Guide to Informed Consent,” issued in September 1998, and finalizes FDA’s draft guidance entitled “Informed Consent Information Sheet,” issued in July 2014.
As a structure, this Guidance starts with presenting general guidance on FDA’s regulatory requirements for informed consent and explains the roles of IRBs, clinical investigators, sponsors, and FDA as regards informed consent, and last, FDA presents an analysis of frequently asked questions.
Some of the main changes implied by the new guidelines are listed below:
A. As regards general informed consent requirements, e.g., FDA:
• identifies exceptions to the requirement for informed consent,
• provides considerations to minimize the possibility of coercion or undue influence,
• explains the need for information to be understandable by a prospective subject or the legally authorized representative,
• discusses the prohibition on exculpatory language in the consent process,
• highlights the basic elements of informed consent: (i) a description the clinical investigation and the extent of the prospective subject’s participation, (ii) potential risks and discomforts, (iii) explanation of benefits, disclosing alternatives and maintaining confidentiality, (iv) description of injury compensation, (v) providing information on whom to contact with questions and (vi) stating that participation is voluntary.
• mentions that notification during the informed consent process to participants that information has been/will be submitted for inclusion in the clinical trial registry databank under paragraph (j) of Section 402 of the Public Health Service Act.
B. As regards ICF requirements in conjunction with IRBs responsibilities,
• The Guidance provides that FDA “does not consider reimbursement for reasonable travel expenses to and from the clinical trial site (e.g., airfare, gas, tolls), and associated costs such as parking and lodging, to raise issues related to coercion and undue influence”. In other words, a change consists in inserting new language on examples of coercion and undue influences.
• Also, the FDA explains that “reimbursement for other expenses may be considered by an IRB on a case-by-case basis, and IRBs should consider whether the proposed remuneration could be an undue influence. Payment for participation in research should be just and fair”. Therefore, FDA advises IRBs that in their revisions of proposed remuneration to reimburse other expenses, to seek for justness and fairness.
• The guidance also contains additional responsibilities of the IRBs regarding financial arrangements. For example, FDA provides that “although the clinical investigators should consider these issues regarding financial relationships and interest, IRBs have the final responsibility of determining whether subjects should be provided with information regarding the source of funding, funding arrangement, or financial interests of parties involved in the clinical investigations as part of the informed consent process”.
C. As regards, FAQ section detailed in the Guidance, the novelties consist in information such as:
• Considerations for enrolling children in a clinical investigation.
• Whether additional protections are required when enrolling children who are wards of the state.
• Considerations for enrolling non-English speaking subjects.
• Enrolling subjects with low literacy and numeracy.
• Enrolling subject with physical or sensory disabilities.
• Considerations for enrolling subjects with impaired consent capacity.
• Who can serve as a legally authorized representative.
• Obtaining informed consent through electronic means.
• Whether subjects should be informed of aggregate study results at the conclusion of trials.
• Whether a subject can participate in more than one clinical investigation simultaneously.
• Whether informed consent is required to review patient records.
• The manner subjects will be informed of new information that may affect their willingness to continue participation in the research.
As a conclusion, although this Guidance contains non-binding recommendations, we are to believe that it will certainly represent a valuable tool for the subjects to whom it is addressed, adding a more uniform approach to the management of delicate/ambiguous situations for clinical trials.
Focus on electronic consent –> guidance regarding eICF
Food and Drug Administration (FDA) has prepared, jointly with the Department of Health and Human Services (HHS) Office for Human Research Protections, (OHRP) this guidance which is intended for institutional review boards (IRBs), investigators, and sponsors engaged in or responsible for oversight of human subject research under HHS and/or FDA regulations.
The Guidance was enacted in 2016 and provides detailed recommendations on the use of electronic systems and processes that may employ multiple electronic media to obtain informed consent for both HHS-regulated human subject research and FDA-regulated clinical investigations of medical products, including human drug and biological products, medical devices, and combinations thereof.
We also mention that the FDA requirements which underlie the afore mentioned Guidance on electronic records/electronic signatures, informed consent, and IRBs are set forth in 21 CFR (Code of Federal Regulations) parts 11, 50, and 56, respectively HHS requirements regarding the protection of human subjects are set forth in 45 CFR part 46.
As for the Guidance`s (on use of electronic informed consent) structure it has a practical approach therefore, it contains questions and answers. For example, it states about how the information in the eIC should be presented to subject, information about the use of electronic signatures, IRB`s responsibilities in the eIC process and others.
Coming back to the present reform, in conjunction with the latest Guidance released by FDA regarding “Informed consent. Guidance for IRBs, clinical investigators, and Sponsors” earlier this month, on August 15, we also mention that as regards it`s third part – Frequently asked questions – the question no. 10 refers to “How can informed consent be obtained through electronic methods?”
In short, FDA informs that supports the use of electronic processes to obtain informed consent. Also, this latest Guidance states that electronic media are being used to provide information usually contained within a paper informed consent form, to evaluate the subject’s comprehension of the information presented, and to document the consent of the subject or the participant`s legally authorized representative (“LAR”).
Moreover, FDA adds that electronic processes to obtain informed consent may use an interactive interface for the informed consent process, which may facilitate the subject’s ability to retain and comprehend the information. Another advantage of using electronic processes to collect informed consent of clinical trial participants is that it may also promote timely entry of any electronic informed consent into a study database and facilitate collection of the subject’s informed consent from remote locations.
In terms of signatures, the document must be maintained as part of the subject’s case history required under 21 CFR 312.62(b) and 812.140(a)(3).
Yet, there are exceptions to this requirement. In cases where the signed ICF cannot be retrieved for filing in the study records (e.g., because the subject is in strict isolation due to a highly transmissible infectious disease), and electronic consent is not available, it is acceptable to retain for the study records a photographic image of the signed consent form along with an attestation by the person entering the photograph into the study records that states how the photograph was obtained and that it is a photograph of the informed consent form signed by the subject.
Thus, FDA not only agrees with the use of eICF, but its use is also supported, being identified its many advantages.
Sources:
https://www.fda.gov/media/88915/download;