Research Resources / Dartmouth Health Human Research Protection Program

Reports of New Information

What is a Report of New Information?

A Report of New Information (“RNI”) is a one size fits all submission to let the IRB know of events that are “new” to the study.  These new events might be a new risk that has been identified, a protocol violation, or a monitor’s report, among other things.

The RNI is important as it provides the IRB with information that was not known (or considered) at the time the study was initially approved.

During the conduct of the study, it is the responsibility of the study team to let the IRB know when something unexpected happens. By doing so, the study team keeps the IRB apprised on whether a reevaluation of risks is needed.

All RNIs should be submitted within five business days of when the study team learns of the event.

When do I need to submit a RNI to the IRB?

There are many events that might happen during the conduct of a study however not all things require reporting to the IRB within five business days.

  RISKS

Events that are UNEXPECTED, PROBABLY RELATED TO THE STUDY, may ADVERSELY AFFECT the SAFETY, RIGHTS, and WELFARE of the SUBJECT, and may ADVERSELY affect the SCIENTIFIC VALIDITY of the RESEARCH

  • Information that indicates a new or increased risk, or a new safety issue.

For example, this might include:

    • New information (e.g., an interim analysis, safety monitoring report, publication in the literature, sponsor report, or investigator finding) indicating an increase in the frequency or magnitude of a previously known risk, or uncovers a new risk.
    • An investigator brochure, package insert, or device labeling is revised to indicate an increase in the frequency or magnitude of a previously known risk, or describe a new risk. Note. Submission of an IB, package insert, or device labeling as a RNI does not prevent this new information from being submitted as a modification to the existing study. In this case, a RNI and a modification to the study would be required. For these situations, indicate in the RNI that a separate modification will be submitted to the study.
    • Withdrawal, restriction, or modification of a marketed approval of a drug, device, or biologic used in a research protocol.
    • Protocol violation that harmed subjects or others or that indicates subjects or others might be at increased risk of harm.
    • Any changes significantly affecting the conduct of the research.
    • Note!  FDA considers the occurrence of any SAE in an IND-exempt Bioavailability (BA)/Bioequivalence (BE) study, regardless of whether the event is considered to be drug related, to be an unanticipated problem involving risk to human participants (UPIRTSO) or others that must be reported to the IRB (§56.108(b)(1)).
    • Certain events may not meet the criteria for reporting in an IND safety report or as a BA/BE study premarket SAE, but still must be reported to the IRB because they represent unanticipated problems involving risk to human participants or others:
      i. Such events may occur at the participant, site, and/or study level and may include serious and unexpected adverse events that occur prior to test article administration, during a washout period, or that are attributable to a screening procedure.
      ii. Other examples may include reports of medication errors (such as receipt of wrong dose or contaminated study medication), breach of privacy/confidentiality (such as disclosure of personally identifiable information), untimely destruction of study records, and other scenarios.
      iii. See FDA Guidance Investigator Responsibilities — Safety Reporting for Investigational Drugs and Devices: https://www.fda.gov/media/152530/download
  • Harm experienced by a subject or other individual, which in the opinion of the investigator are unexpected and probably related to the research procedures.
    • A harm is “unexpected” when its specificity or severity are inconsistent with risk information previously reviewed and approved by the IRB in terms of nature, severity, frequency, and characteristics of the study population.
    • A harm is “probably related” to the research procedures if in the opinion of the investigator, the research procedures more likely than not caused the harm (including physical, psychological, economic, or social harm) related to the research than was previously known or recognized.

This may include an unanticipated adverse device effect or unanticipated adverse drug effect (any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device or drug, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device or drug that relates to the rights, safety, or welfare of subjects). It may also include any unanticipated adverse effect by any other study procedure.

You may find the following Venn Diagram helpful in determining what to report in this instance:

  • Breach of confidentiality. Such as a lost computer, a breach of PHI, or other accidental disclosure of information.
  • Change to the protocol taken without prior IRB review to eliminate an apparent immediate hazard to a subject. These actions are intentional and are done in reaction to a perceived hazard to the subject.
  • Incarceration of a subject in a study not approved by the IRB to involve prisoners.
  • Premature suspension or termination of the protocol by the sponsor, investigator, or institution

NON-COMPLIANCE

Events that may involve potential NON-COMPLIANCE

  • As these events may adversely affect the safety, rights, and welfare of the subject, and may adversely affect the scientific validity of the research, the IRB must decide whether the event constitutes non-compliance.
  • Non-compliance with the federal regulations governing human research or with the requirements or determinations of the IRB, or an allegation of such non-compliance. This may include changing a study procedure for convenience, a whistle-blower report, or including a new measure without the IRBs approval.
  • Reports such as:
    • An audit, inspection, or inquiry by a federal agency and any resulting reports (e.g., FDA Form 483.). Submit any and all of these to the IRB within five days.
    • Written reports of study monitors. If the report does not include any findings, the report may be submitted at the time of continuing review. For those reports that do include findings, these must be submitted to the IRB within five business days.
  • Failure to follow the protocol due to the action of the investigator or research staff.This may include intentional protocol violations such as enrolling a subject that did not meet study criteria or shortening the wash-out period for a subject because of their planned vacation.
  • Failure to follow the protocol due to the inaction or inaction of the investigator or research staff. There may also be unintentional protocol deviations that occur such as an accidental failure to perform a protocol-required blood test or correctly administer a test agent. These types of unintentional protocol violations should only be reported as an RNI if there is the possibility that the action may cause a new or increased risk, a new safety issue, or affect the scientific validity of the research.

COMPLAINTS

Events that involve COMPLAINTS (regardless of risk, harm, or data integrity issues)

  • Complaint of a subject that cannot be resolved by the research team.
  • Complaint of a subject that indicates subjects or others might be at increased risk of harm or at risk of a new harm.

If any of these events occur, you are required to complete a Report of New Information to the IRB within five business days.

Know that the above events are required to be reported to the IRB. A study Sponsor, federal agency, and others have additional reporting requirements.

What about OTHER events that occur during a study?

Events in which the study team is absolutely certain that ALL OF THE FOLLOWING ARE TRUE:

  • ARE NOT unexpected
  • ARE NOT probably related to the study
  • DO NOT adversely affect the safety, rights, and welfare of the subject
  • DO NOT ADVERSELY affect the scientific validity of the research

…are to be reported as part of the continuing review submission for studies that require a continuing review.  Note that for studies that do not have a continuing review requirement, only events that require RNI reporting are mandated.

The above material was adapted from the following guidance: