On January 21, 2019 new federal regulations regarding human subjects’ research took effect. The most significant revisions are intended to “modernize, strengthen, and make more effective” the current system of oversight. The revisions propose to better protect human subjects, expedite research, and reduce regulatory burden.These new regulations concern all new studies and the Loyola IRB is obligated to institute them.
Please note: Studies approved before January 21, 2019 must continue to comply with the terms under which they were authorized.
Most definitions remain the same; however, there are some important changes. Some important terms are undefined in the regulations, but are clarified in the Final Rule’s preamble. The most significant definition revisions are highlighted below:
Vulnerable: The term has been updated, but not defined in the Final Rule, to reflect that research subject vulnerability should be considered a function of the possibility of coercion or undue influence. IRBs should focus on vulnerability to coercion or undue influence in reference to the subject’s ability to make a decision to participate in research.
Human Subject: Rationale; the definition was revised to replace the reference to “data” with “information or biospecimens.” It also clarifies that an investigator is not conducting human subjects research by merely gathering information or biospecimens but instead when he/she “uses, studies, analyzes, or generates” identifiable private information or “identifiable biospecimens.”
- A living individual about whom an investigator (whether professional or student) conducting research (i) obtains information·or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens, or (ii) obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.
Clinical Trial: This is a new term, as the pre-2018 rule did not include a definition.
- A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes.
Research: The definition did not change; however, four categories of activities were removed from the definition to make clear that they are NOT within the Rule’s jurisdiction, as follows:
- Scholarly or journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship) that focus directly on the specific individuals about whom information are collected
- Public health surveillance activities (collecting, analyzing, and using data to target public health and disease prevention)
- Authorized operational activities for national security missions
- Data collection and analysis that enables the conduct of certain activities carried out as part of the criminal justice system
The final rule contains several major revisions to the requirements for informed consent. The changes are specifically intended to make informed consent more meaningful so that research subjects have the necessary information to make informed decisions, as follows:
Key Information in Consent Forms
New requirements relating to the content, organization, and presentation of information included in the consent form and process to facilitate a prospective subject’s decision about whether to participate in research. The informed consent documents/process 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. This provision further requires that this beginning portion of the informed consent must be organized and presented in a way that facilitates comprehension. Please see Informed Consent for sample consent documents.
Elements of Informed Consent
Additional items have been added to the elements of informed consent. These new elements will need to be included in consent forms approved after January 21, 2019. The new language includes a basic element of consent that addresses the future use of identifiable private information or specimens. Additional elements of consent have been added (when applicable) that relate to commercialization of biospecimens, return of results, and whole genome sequencing. [§46.116(b)(c)] Some key elements are explained below:
- Projects that collect identifiable private information or biospecimens must include a statement that expressly states whether identifiers may be removed, and if the de-information or biopspecimens may or may not be used for future research or shared with other investigators [46.116 (b)(9)]
Projects with clinically relevant research results must include a statement regarding whether the clinically relevant research results, including individual research results, will be disclosed to subjects, and if so under which conditions [46.116 (c)(8)]
- Projects that use biospecimens must include 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 the commercial profit [46.116 (c)(7)]
- Projects that involve whole genome sequencing must include a statement indicating that the research will (if known) or might include whole genome sequencing [46.116 (c)(9)]
Waiver or Alteration of Informed Consent
An additional criterion has been added that requires investigators to justify the use of identifiable private information or identifiable biospecimens. In addition to the existing requirements for a waiver the following information must be provided.
- If the research involves using identifiable private information or biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format [§46.116(f)(2)(iii)]
A waiver of informed consent is no longer necessary for screening, recruitment, or determining eligibility. This is based on the IRBs determination that there are adequate privacy and confidentiality safeguards in place for the information obtained by investigators. This aligns with the HIPAA regulations. In order for the IRB to approve this, the procedures need to be listed as a part of the protocol and one of the following conditions must be met:
- The investigator will obtain information through oral or written communication with the prospective subject or legally authorized representative, or
- The investigator will obtain identifiable private information or biospecimens by accessing records or stored identifiable biospecimens. [§46.116(g)]
Posting of Clinical Trial Consent Forms
Federally funded clinical trials must post a copy of the consent form on a “publicly available Federal Web site” (TBD) after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject. Currently there is no instruction from DHHS on the federal website to be used. The website will be updated as information becomes available.
Under the current regulations, secondary research use of identifiable data/biospecimens is permissible through study-specific consent, by obtaining an IRB waiver of consent, or by removal of identifiers. In the Revised Common Rule, "Broad Consent" is an (optional) alternative consent process for use only for the storage, maintenance, and secondary use identifiable private information or biospecimens for future, yet-to-be-specified research. [§46.116(d)]
Loyola will not be adopting the use of Broad Consent on an institutional level as the tracking requirement may be burdensome. Exemption categories 7 and 8, which are specific to Broad Consent, will not be utilized. The issues of Broad Consent may be entertained in the future pending further guidance from OHRP.
The new provision for limited IRB review allows certain research to be categories as exempt, even when the identifiable information might be sensitive or potentially harmful if disclosed. In order to qualify for exemption, the study must meet the standards of the limited IRB review. If the information is both identifiable and sensitive or potentially harmful, the safeguards offered by the limited IRB review may allow an exemption determination to be made.
Limited IRB review is required in the following circumstances:
- Exempt category 2 (educational tests, surveys, interview or observations of public behavior). When the information is recorded by the investigator in an identifiable manner and disclosure of the subject’s responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement or reputation.
- Exempt category 3 (benign behavioral interventions). When the information is recorded by the investigator in an identifiable manner and disclosure of the subject’s responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement or reputation.
When reviewing the exempt categories 2 and 3, the limited IRB review assures adequate protections for the privacy of subjects and adequate plans to maintain the confidentiality of the data.
Limited IRB review must be performed by an IRB committee member. The review can occur on an expedited basis and does not require consideration by a convened board. The reviewer may require modifications to the proposal prior to approval. Disapprovals must be made by the convened board. If the limited IRB review does not result in approval under the exempt categories, then the IRB can evaluate whether or not approval is appropriate under the expedited categories. Expedited research must meet all the approval criteria under 45 CFR 46.111, including either informed consent or waiver of consent.
The revised common rule significantly impacts how minimal risk research is reviewed and as such, the categories of research that qualify for exemption have been expanded and revised. New categories were added and new processes created. Please review Categories of Review for a detailed list of the revised categories.
The Final Rule eliminates continuing review for many minimal risk studies. Unless an IRB determines otherwise, continuing review of research is not required if:
- The research was initially approved under expedited review;
- The research is reviewed by the IRB in accordance with the limited IRB review procedure described in several of the exemption categories (specifically 2 and 3 at Loyola); or
- The research was initially approved by a convened IRB and has progressed to the point that it involves only one or both of the following activities:
- Data analysis (including analysis of identifiable information or identifiable biospecimens), or
- Access to follow-up clinical data from procedures that subjects would undergo as part of clinical care.
If an IRB chooses to conduct continuing review even when these conditions are met, the rationale for doing so must be documented.
If the IRB determines that these regulations can be applied, IRB approval will not expire and continuing review applications will no longer be required. However modifications and reportable events should still be submitted. Additionally, any modifications to the protocol must be submitted for approval by the committee before they can be implemented. Failure to do so will result in protocol noncompliance.
If you have a currently active study that was approved prior to January 21, 2019, you should continue to operate under the old common rule regulations. At the time of your next continuing review, the IRB committee will determine if the new regulations can be applied. Your IRB approval letter will then include an expiration date or a notice that continuing review is no longer required.
Most federally funded collaborative research projects located in the U.S. will be required to use a single IRB (commercial, academic, or hospital-based) starting January 20, 2020. The IRB overseeing the research must be approved by the funding agency. Loyola's plans for sIRB will be developed in the coming months.