Category Archives: Regulatory Intelligence

NIMH Guidance on Risk-Based Monitoring

The National Institute of Mental Health (NIMH) requires enhanced monitoring for NIMH-supported human subjects research that is more than minimal risk (as defined in federal regulations at 45 CFR 46.102(i) and 21 CFR 50.3(k)). The purpose of this guidance document is to clarify risk level definitions and the NIMH’s monitoring expectations to mitigate those risks. Read more at NIMH…

US Patient Informed Consent: Final Rule

CITI offers a guide to explain the US Patient Informed Consent with compliance expected of 21 January 2018 as stipulated in the Federal Policy for the Protection of Human Subjects (45 CFR 46). The Final Rule is intended to add flexibility and to reduce regulatory burden. Final Rule.

Revised Human Subjects Research Definitions

  • The definition of “human subject” has been changed to include “identifiable biospecimens” as well as how data and/or biospecimens have been collected or will be used.
  • The definition of “research” has been expanded to list activities that are specifically deemed not to be research, i.e., oral history, journalism, public health surveillance, criminal justice or criminal investigative activities, and activities in support of intelligence, homeland security, defense, or other national security missions.

New and Revised Exemption Categories

  • Category #1: Includes a statement that the research cannot “adversely impact students’ opportunity to learn required educational content or the assessment of educators who provide instruction.”
  • Category #2: Includes a clarification that the data may involve visual or audio recording. This category also allows for the collection of sensitive, identifiable data to be collected as long as “limited review” is conducted by the IRB.
  • New! Category #3: Includes research with benign behavior interventions, i.e., interventions that are brief in duration, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on the subjects; subjects not likely to perceive them as offensive or embarrassing.
  • Category #4: Includes mention of biospecimens. It also removes the pre-2018 requirement that information and biospecimens must be pre-existing.
  • Category #5: Requires Federal department or agency conducting or supporting the research to publicly post research prior to commencement.
  • Category #6: Unchanged (taste and food quality evaluation; consumer acceptance studies).
  • New! Category #7: Includes storage or maintenance of identifiable private information or identifiable biospecimens. Requires “limited review” and broad consent.
  • New! Category #8: Includes research involving the use of identifiable private information or identifiable biospecimens for secondary research use. Requires “limited review” and broad consent.

Limited IRB Review

Limited IRB Review is a new concept introduced by the Final Rule that is designed to ensure adequate privacy and confidentiality safeguards for identifiable private information and identifiable biospecimens. Limited review involves the IRB making and documenting a determination that adequate provisions are in place for protecting privacy and maintaining confidentiality. Limited review is required for exempt categories #2, 3, 7, and 8.

Broad Consent

Broad consent is a new term introduced by the Final Rule that allows an investigator to seek prospective consent to unspecified future research. It’s intended for “secondary research use” of private identifiable information and identifiable biospecimens. Broad consent is required for exempt categories 7 and 8. Harvard University has decided not to implement Broad Consent.

Continuing Review

Continuing review is no longer required under the following circumstances:

  • Research complies with 2018 regulatory requirements.
  • Research eligible for expedited review.
  • Research reviewed by the IRB in accordance with the limited IRB review.
  • Research that has progressed to the point that it only involves (a) data analysis, including analysis of identifiable private information or identifiable biospecimens, and/or (b) accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care.

Of note, investigators are still responsible for submitting modifications for review/approval prior to implementation; reporting new information within 5 business days, and closing human research protocols, as appropriate.

Informed Consent Requirements

According to the Final Rule, the consent process (document/discussion) must first include a presentation of “key information,” i.e., information most likely to assist in understanding why to participate (or not) in the research. As per the Final Rule preamble, Key Information is understood to include the following:

  • The fact that consent is being sought for research and that participation is voluntary
  • The purpose(s), the expected duration of participation, and the procedures to be followed
  • The reasonably foreseeable risks or discomforts to the prospective subject
  • The benefits to subjects or others that may reasonably be expected
  • Appropriate alternatives, if any, that might be advantageous

New Basic and Additional Elements of Consent

  • If the research involves the collection of identifiable private information or identifiable biospecimens, a statement on whether the identifiers might be removed and information or biospecimens could be used for future research without additional informed consent.
  • When applicable:
    • A statement that 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 about whether clinically relevant research results, including individual research results, will be disclosed to subjects.
    • A statement about whether the research project might include whole genome sequencing.

Single IRB Review

When more than one institution is involved in a research study, the regulations define this as a “cooperative research project.” The Final Rule requires the use of one IRB for cooperative research (“Single IRB” or “sIRB”).  Of note, the effective date for this change isn’t until January 19, 2020; however, the NIH Policy on sIRB, which requires a single IRB for NIH-funded human research, went into effect January 25, 2018. 

EU Medical Device Regulations (MDR)

The European Union Medical Device Regulation (Council Regulation 2017/745 of 5 April 2017 concerning medical devices, OJ No L 117/1 of 2017-05-05) (MDR) repeals the existing directives on medical devices: Medical Devices Directive (MDD) [93/42/EEC] and Active Implantable Medical Device Directive [90/385/EEC]. The regulation was published on 26 May 2017 and comes into force on 25 May 2020. Currently approved medical devices have a transition time of three years/36 months (until 26 May 2020) to meet the new MDR requirements. The life-cycle approach is based on US FDA and International Standards to improve clinical safety and market access. Read more…..

IRB Organization

Under FDA regulations, an IRB is an appropriately constituted group that has been formally designated to review and monitor biomedical research involving human subjects. In accordance with FDA regulations, an IRB has the authority to approve, require modifications in (to secure approval), or disapprove research. This group review serves an important role in the protection of the rights and welfare of human research subjects.

The purpose of IRB review is to assure, both in advance and by periodic review, that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in the research. To accomplish this purpose, IRBs use a group process to review research protocols and related materials (e.g., informed consent documents and investigator brochures) to ensure protection of the rights and welfare of human subjects of research. The following link to US FDA Guidances contains answers to frequently asked IRB questions:

From this site, one interesting IRB procedure:

26. If an IRB disapproves a study submitted to it, and it is subsequently sent to another IRB for review, should the second IRB be told of the disapproval?

Yes. When an IRB disapproves a study, it must provide a written statement of the reasons for its decision to the investigator and the institution [21 CFR 56.109(e)]. If the study is submitted to a second IRB, a copy of this written statement should be included with the study documentation so that it can make an informed decision about the study. 21 CFR 56.109(a) requires an IRB to “… review … all research activities [emphasis added] ….” The FDA regulations do not prohibit submission of a study to another IRB following disapproval. However, all pertinent information about the study should be provided to the second IRB.