the guidance provides sponsors of drugs, biologics, and medical devices, as well as investigators and institutional review boards (IRBs), with recommendations on how to provide concise and easy-to-understand language to help prospective participants decide whether to participate in a given study.HHS seeks comments on the draft guidance through April 30, 2024.The draft guidance provides recommendations on how to present key information at the start of an informed consent process, which should include topics that are generally important for clinical trial participants to understand, including: the purpose of the research, the possible risks and benefits of the study, and the study’s length and procedures. The recommendations apply to FDA-regulated clinical investigations of drugs, devices, and biologics, as well as to HHS-supported or -conducted nonexempt human subjects research. Notably, the recommendations also apply to consent documents developed for emergency research studies, under 21 CFR 50.24, that are not subject to the general informed consent requirements, and to expanded access studies.According to HHS, the recommendations in the draft guidance align with the Federal Policy for the Protection of Human Subjects, known as the “Common Rule,” revisions to which came into effect in 2018. Specifically, the guidance provides research sponsors, investigators, and IRBs with recommendations on how to implement two requirements in FDA’s September 2022 proposed rules on harmonizing human subject research regulations with the revised Common Rule, including that informed consent:begin with key information about the research presented in a clear and concise manner; and,is presented in a way that facilitates understanding of the reasons why someone might or might not want to participate in the research.FDA’s 2022 proposed rules have yet to be finalized, and are titled “Protection of Human Subjects and Institutional Review Boards” and “Institutional Review Boards; Cooperative Research.

ommittee (DMC) for trial monitoring. It also provides recommended procedures and other considerations for DMCs. Once the Draft Guidance is finalized, it will supersede FDA’s March 2006 guidance entitled Establishment and Operation of Clinical Trial Data Monitoring Committees.IN DEPTHBACKGROUND ON DMCsA DMC (often referred to as a data safety monitoring committee) is a group of individuals with relevant clinical, scientific, statistical or other expertise. This group regularly reviews human-subject data accumulating from a clinical trial and provides recommendations to the sponsor on whether to continue, modify or suspend the clinical trial. In certain circumstances, a DMC may also provide recommendations regarding operational matters based on noncomparative safety and efficacy data.Even though sponsors are required to use DMCs only for certain emergency research, the use of DMCs has increased in many areas beyond the historic norm of diseases involving serious morbidity or mortality. (21 CFR 50.24(a)(7)(iv) sets forth the exception for the requirement to obtain informed consent for a clinical trial in an emergency setting. One condition for such exception is the establishment of an independent DMC to oversee the clinical trial.) FDA notes that DMCs are now being used for modest-sized trials, to implement certain adaptive clinical trial designs, and to oversee entire clinical development programs (as opposed to single clinical trials). In part, the Draft Guidance appears to be an effort by FDA to update its recommendations for DMCs given the significant changes in the use of DMCs that have occurred since FDA released its 2006 guidance.Relationship Between DMCs and Other Oversight GroupsThe Draft Guidance addresses the specific relationships DMCs have with other groups that may be involved in a clinical trial, including an institutional review board, a clinical trial steering committee, an endpoint assessment/adjudication committee, clinical site monitors, entities reviewing safety reporti

f increasingly complex adaptive trial designs in which the DMC may make major recommendations regarding changes to the conduct of the trial based on emerging evidence of futility or substantive benefit. Further, sponsors should ensure that DMC recommendations pertaining to comparative interim assessments of safety signals between the treatment and control arms are evaluated for potential reportability to FDA.1See FDA, Draft Guidance, Use of Data Monitoring Committees in Clinical Trials (Feb. 2024), https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-data-monitoring-committees-clinical-trials.2A data monitoring committee (DMC) may also be known as a data and safety monitoring board (DSMB), a data and safety monitoring committee (DSMC) or an independent data monitoring committee (IDMC).3See FDA, Guidance for Clinical Trial Sponsors, Establishment and Operation of Clinical Trial Data Monitoring Committees (Mar. 2006), https://www.fda.gov/media/75398/download.4See 21 C.F.R. § 50.24(a)(7)(iv).

the human subjects. The rule, which implements a 2016 amendment to the Federal Food, Drug, and Cosmetic Act (FD&C Act) authorizing FDA to permit an exception from informed consent for certain minimal risk clinical investigations,2 modifies 21 C.F.R. Parts 50, 312, and 812. It affects sponsors, investigators, IRBs, and healthcare institutions that sponsor or conduct clinical research.The rule is effective January 22, 2024.In part, the rule harmonizes FDA regulations with the criteria for IRB waiver or alteration of informed consent for minimal risk clinical investigations outlined in the Common Rule (i.e., the “Federal Policy for the Protection of Human Subjects”) that became effective January 19, 2017. Prior to this new rule, FDA regulations permitted an exception from the requirements for informed consent only in a life-threatening situation or under Presidential waiver related to a military operation (21 C.F.R. § 50.23), or in accordance with the requirements for emergency research (21 C.F.R. § 50.24). On July 15, 2017, FDA released guidance informing sponsors, investigators, and IRBs that FDA “did not object” to IRB waiver or alteration of informed consent for certain minimal risk clinical investigations,3 and the agency issued a proposed rule on November 15, 2018.4FIVE CRITERIA FOR EXCEPTION FROM OR MODIFICATION OF INFORMED CONSENTTo waive or alter informed consent, IRBs must identify and document that each of the following five criteria are met:The clinical investigation involves no more than minimal risk to human subjects. It is important to appreciate that the meaning of “minimal risk” is very different from the term “significant risk”5 that is applicable to investigational devices. In the preamble, FDA clarifies that it relies on the definition of “minimal risk” in 21 C.F.R. § 50.3 that states: “Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in dail

Informed Consent. FDA requirements for informed consent (21 CFR part 50) for particular clinical trials (e.g., emergency research under 21 CFR 50.24, or clinical investigations involving pediatric subjects under subpart D) are more extensive than ICH E6 with respect to IRB responsibilities. The revised guidance notes that its “experience has not revealed that this difference has caused a conflict, but in the event of one,” the agency “would be willing to discuss a resolution with the sponsor on a case-by-case basis.”

FDA expects its evaluation of potential violations to be risk‑based, with a focus on:Responsible parties who have failed to submit required clinical trial registration and/or results information for applicable clinical trials of products that potentially may pose a higher risk to human subjects, or applicable clinical trials of products intended to address significant public health need. Examples may include trials of a drug, biological, or medical device product not previously approved, licensed, or cleared and intended to treat a serious and/or life-threatening disease or condition; or applicable clinical trials involving vulnerable populations (such as pediatrics), rare diseases, or emergency research conducted without informed consent under 21 C.F.R. 50.24;Responsible parties or submitters who have a pattern of previous noncompliance with requirements for the submission of clinical trial information and/or required certifications; andApplicable clinical trials for which noncompliance exists in conjunction with other noncompliance pertaining to conduct of the trial (e.g., failure to retain clinical trial records, failure to obtain informed consent).RECOMMENDATIONS: Responsible Parties And Submitters Must Inventory Studies And Submissions And Confirm Compliance, Adjust Policies and Procedures As NecessarySome responsible parties historically submitted basic results for applicable clinical trials of all approved drug, biological, or medical device products.

FDA strongly advises consultation for complex investigational products (e.g. cellular therapy and gene therapy products) where potentially altered storage and handling conditions could adversely affect product stability.If researchers need to obtain informed consent from patients in COVID-19 isolation, the guidance provides for alternative methods of obtaining consent and documenting that consent, without risking the health or safety of study staff. Procedures for consent remain available under 21 CFR 50.23 (for life-threatening situations) or 21 CFR 50.24 (for emergency research). For electronic consent, 21 C.F.R. Part 11 requirements also need to be considered.

[ii]” Currently, FDA regulations only allow an exception from the informed consent requirements in life-threatening situations (21 CFR 50.23) or for emergency research (21 CFR 50.24). Thus, FDA intends to publish regulations to reflect this statutory change, including any appropriate human subject protection safeguards.

The bill, which was already passed by the House in September, was presented to the President for approval on November 25, 2014. A copy of H.R. 4067 is available by clicking here.FDA Updates Manual on Review of INDs Seeking Exception from Informed Consent for Emergency Research Under 21 C.F.R. § 50.24 – On November 17, 2014, the U.S. Food and Drug Administration published a revised version of its internal review procedures and policies for Investigational New Drug applications (INDs) that implicate the exception to the requirement to obtain informed consent from research subjects for emergency research. This exception from informed consent for the use of investigational drugs in emergency research could be sought for public health situations where potential research subjects are incapacitated, in a life-threatening clinical situation, and unable to immediately give consent (e.g., community outbreaks of Ebola virus infection).

This exception from informed consent for the use of investigational drugs in emergency research could be sought for public health situations where potential research subjects are incapacitated, in a life-threatening clinical situation, and unable to immediately give consent (e.g., community outbreaks of Ebola virus infection).Background -The exception from informed consent for emergency research, provided under 21 C.F.R. § 50.24, is intended to ensure stringent protections in circumstances where, due to the emergency nature of medical care under research, subjects who are to be enrolled in an IND or Investigational Device Exemption (IDE) protocol are anticipated to be incapacitated and largely unable to provide informed consent. It is typically used to enable research of investigational drugs and medical devices regulated by FDA on conditions such as traumatic brain injury or stroke.Please see full alert below for more information.