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*NEW* The Unanticipated Problem and Adverse Event (AE) Reporting policy & form have been replaced with a new Reportable New Information policy and form.

  • The new policy eliminates the requirement to report on site SAEs that do NOT meet the criteria for an “unanticipated problem” (UP = unexpected, & related/possibly related, & places subjects or others at greater risk of harm)
  • The form better instructs Investigators and research teams about what items need to be reported to the IRB quickly (within 5 business days)
  • The form defines reportable deviations as “Failure to follow the protocol that harmed a subject or placed subject at risk of harm.

Reportable New Information

During the course of a research study, unanticipated problems involving risk to subjects or others, non-compliances, and other events may occur that need to be reported to the IRB in accordance with 45 CFR.46.103(b)(5) and 21 CFR 56.108(b). The list below is intended to help ensure that the reporting and review of these events occur in a timely, meaningful way so that research participants can be protected from avoidable harms.

IRB Forms

  1. Reportable New Information (HRP-214)

Report the information items that fall into one or more of the following categories to the IRB within 5 business days using the Reportable New Information (HRP-214) form. For any questions or clarifications on the below, please call the IRB office at 617-636-7512:

Information that does not fall under any of the categories does not require reporting to the IRB.

  1. Harm experienced by a subject or other individual, which in the opinion of the investigator is unexpected and related/possibly related to the research procedures.
    1. A harm is “unexpected” when its specificity and/or severity is inconsistent with risk information previously reviewed and approved by the IRB in terms of nature, severity, frequency, and characteristics of the study population.
    2. A harm “possibly related” when there is a reasonable likelihood that the incident, experience, or outcome may have been caused by the procedures involved in the research.
  2. Information that indicates a new or increased risk, or a new safety issue. For example:
    1. New information (e.g., an interim analysis, safety monitoring report, publication in the literature, sponsor report, or investigator finding) indicates an increase in the frequency or magnitude of a previously known risk, or uncovers a new risk or greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.
    2. 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
    3. Withdrawal, restriction, or modification of a marketed approval of a drug, device, or biologic used in a research protocol
    4. Complaint of a subject that indicates subjects or others might be at increased risk of harm or at risk of a new harm
    5. Any changes or new information adversely affecting the conduct of the research (that indicates a new or increased risk, or a new safety issue)
  3. 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
  4. Audit, inspection, or inquiry by a federal agency and any resulting reports (e.g. FDA Form 483)
  5. Any site monitoring or other audit report finding that directly and materially affects subject safety or their willingness to continue participation
  6. Failure to follow the protocol that harmed a subject or placed subject at risk of harm (for example, missed study test or visit (or out of window) that could affect subject safety, enrollment of a subject who did not meet all eligibility criteria, failure to follow safety monitoring plan. These examples are intended as a guide and are not all-inclusive.)
  7. Breach of confidentiality
  8. Change to the protocol taken without prior IRB review to eliminate an apparent immediate hazard to a subject
  9. Incarceration of a subject in a study not approved by the IRB to involve prisoners
  10. Complaint of a subject that indicates that the rights, welfare, or safety of the subject have been adversely affected or a subject complaint that cannot be resolved by the research team
  11. Premature suspension or termination of the protocol by the sponsor, investigator, or institution
  12. State medical board actions against any member of the research team
  13. Unanticipated adverse device effect (any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, 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 that relates to the rights, safety, or welfare of subjects.)
  14. Information that, per the sponsor, requires prompt reporting to the IRB

Reminder about removing identifiers (name, MR#, etc.)

Do not include subject identifiers when submitting reportable new information to the IRB, unless identifying the subject is absolutely necessary (for example, if the IRB will need to contact the subject).

In general, when submitting reportable new information, redact subject identifiers by doing the following:

  • Make a copy of the document
  • Using a black marker, black out the subject’s name and any other subject identifiers, then
  • Photocopy this redacted (blacked out) copy so the identifiers cannot be read through the black marker

When corresponding by e-mail, re-read your e-mail to double check that the e-mail and any e-mails in the chain do not include subject identifiers.

Useful Definitions

Adverse Event: Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research (modified from the definition of adverse events in the 1996 International Conference on Harmonization E-6 Guidelines for Good Clinical Practice).

External Adverse Event: From the perspective of one particular institution engaged in a multicenter clinical trial, external adverse events are those adverse events experienced by subjects enrolled by investigators at other institutions engaged in the clinical trial.

Internal Adverse Event: From the perspective of one particular institution engaged in a multicenter clinical trial, internal adverse events are those adverse events experienced by subjects enrolled by the investigator(s) at that institution. In the context of a single-center clinical trial, all adverse events would be considered internal adverse events.

Possibly Related to the Research: There is a reasonable possibility that the adverse event, incident, experience or outcome may have been caused by the procedures involved in the research (modified from the definition of associated with use of the drug in FDA regulations at 21 CFR 312.32(a)).

Serious Adverse Event: Any adverse event temporally associated with the subject’s participation in research that meets any of the following criteria:

  1. results in death;
  2. is life-threatening (places the subject at immediate risk of death from the event as it occurred);
  3. requires inpatient hospitalization or prolongation of existing hospitalization;
  4. results in a persistent or significant disability/incapacity;
  5. results in a congenital anomaly/birth defect; or
  6. any other adverse event that, based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (examples of such events include allergic bronchospasm requiring intensive treatment in the emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse).
    (Modified from the definition of serious adverse drug experience in FDA regulations at 21 CFR 312.32(a).)

Unanticipated problem involving risks to subjects or others: Any information, including any incident, experience, or outcome that meets ALL of the following conditions:

  1. Unexpected (in terms of nature, severity, or frequency) given the procedures described in the research protocol documents (e.g., the IRB-approved research protocol and informed consent document) and the characteristics of the human subject population being studied;
  2. Related or possibly related to participation in the research (“possibly related” means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
  3. Suggests that the research places human subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized, even if no harm has actually occurred.

Unexpected adverse event: Any adverse event occurring in one or more subjects in a research protocol, the nature, severity, or frequency of which is not consistent with either:

  1. the known or foreseeable risk of adverse events associated with the procedures involved in the research that are described in (a) the protocol–related documents, such as the IRB-approved research protocol, any applicable investigator brochure, and the current IRB-approved informed consent document, and (b) other relevant sources of information, such as product labeling and package inserts; or
  2. the expected natural progression of any underlying disease, disorder, or condition of the subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the adverse event.
    (Modified from the definition of unexpected adverse drug experience in FDA regulations at 21 CFR 312.32(a).)

Guidance:

OHRP Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events from January 15, 2007

OHRP Glossary of key terms and examples

FDA Guidance for Clinical Investigators, Sponsors, and IRBs Adverse Event Reporting to IRBs — Improving Human Subject Protection from January, 2009