This section of the Investigator Manual outlines reporting requirements for UW and VA studies, what does not require reporting, changes to eliminate immediate hazards to subjects, corrective action plans, study suspension or termination, and IRB reporting requirements.


Reporting Requirements

Information items that fall into one or more of the categories listed below must be reported to the IRB. These information items will be reviewed by the IRB to determine if they represent noncompliance, unanticipated problems involving risks to subjects or others, and/or result in suspension or termination of IRB approval. For more information, see the How to Submit a Reportable Event page. Do not include any identifiable information related to subjects in the submission or supporting materials. Maintain electronic copies of all information submitted to the IRB.

  • What to Report in 1 business day (Report the information items that fall into one or more of the following categories to the via phone call to the IRB Chair and Director within 1 business day):
    • Events that occur in studies involving drugs or biologics and are:
      • Probably caused by or associated with study participation; and
      • Unexpected; and
      • Immediately life-threatening or severely debilitating to current subjects or others not participating in the study
    • Events that occur in studies involving testing of devices and are:
      • Not previously identified in nature, severity, or frequency in IRB documentation (e.g., protocol, consent documents) OR relates to subjects’ rights, welfare, or safety; and
      • Immediately life-threatening or severely debilitating to current subjects.
  • What to Report in 10 Business Days (Only for Studies Involving Testing of Investigational Device):
    • An event must be reported within 10 business days if the event was caused by/associated with the device and not previously identified in nature, severity or frequency in any IRB documents (or relates to the rights, safety and welfare of subjects).
  • What to Report Within 14 Business Days (Report the information items that fall into one or more of the following categories to the IRB within 14 business days):
    • Information that indicates a new or increased risk, or a new safety issue. For example:
      • 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.
      • 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, if revised study documents will be received by the study team within 14 business days of learning of the new information, ONLY a change of protocol would need to be submitted. If revised study documents are not expected to be received in time to submit a change of protocol within 14 days, a new information report should be submitted as a placeholder.
      • 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
      • Complaint of a subject that indicates subjects or others might be at increased risk of harm or at risk of a new harm
      • Any changes significantly affecting the conduct of the research
    • 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.
    • Noncompliance with the federal regulations governing human research or with the requirements or determinations of the IRB, or an allegation of such noncompliance.
    • Audit, inspection, or inquiry by a federal agency that result in reportable findings (e.g., FDA Form 483.)
    • Written reports of study monitors that result in reportable findings (e.g., noncompliance with the IRB approved protocol)
    • Failure to follow the protocol due to the action or inaction of the investigator or research staff. (see Guidance for What Does Not Require Reporting to the IRB below)
    • Breach of confidentiality. Note that breaches that involve PHI must be reported to the HIPAA privacy officer.
    • Incarceration of a subject in a study not approved by the IRB to involve prisoners.
    • Complaint of a subject that cannot be resolved by the research team.
    • Premature or unexpected suspension or termination of the protocol by the sponsor, investigator, or institution that appears to impact subject safety and/or the ability of the study to meet its original aims (e.g., halt to enrollment due to equipment malfunction or drug supply issues). NOTE: This does not include meeting enrollment goals earlier than planned or a temporary suspension due to a planned interim analysis.

Reporting Requirements for VA Studies

VA reporting requirements generally parallel reporting requirements for non-VA studies, with the timeframe for report. Any event that occurs on a study under Madison VA purview that meets UW unanticipated problem or noncompliance reporting requirements must be reported to the IRB and Associate Chief of Staff within 5 business days of the local research team becoming aware of the event.

Any local research death that is both unanticipated AND related to the research must be orally reported to the IRB immediately after the local research team becomes aware of the death. Written notification of the death must be received by the IRB within 5 business days of the local research team becoming aware of the death.

Guidance on what does not need to be reported

Described below are cases of minor protocol non-compliance that generally do not need to be reported to the IRB to the extent that the event does not adversely affect subject safety, rights, or welfare, decrease potential benefits, or compromise data integrity.

This guidance is specific to unintended events that have already occurred and NOT to intended exceptions or deviations from the protocol, such as exceptions made to eligibility criteria for a single patient. Intended exceptions or deviations must be submitted to and reviewed by the IRB as a change of protocol prior to implementation unless necessary to eliminate an apparent immediate hazard to subjects (see corresponding section).

In order to be considered protocol non-compliance that does not require reporting to the IRB, the event must meet ALL of the following criteria:

  • The event did not affect nor did it have the potential to affect the subject’s rights, safety or welfare*;
  • The event did not result in a change to the participant’s clinical or emotional condition or status;
  • The event did not affect the integrity, accuracy and/or reliability of the research data; and
  • The event did not result from willful or knowing misconduct on the part of the study team.

*All study drug dosing errors (under- or over-dosing) and any events related to failure to obtain valid informed consent require reporting to the IRB.

A study team member not listed on the IRB application or whose role is not accurately reflected on the Study Team Roles page does not require reporting if ALL of the following are true:

  • The study team member is internal to the UW (e.g. a UW-Madison/UWHC employee);
  • The study team member has completed all required human subjects/GCP/HIPAA trainings and none are expired;
  • The study team member has no financial conflicts of interest related to the study;
  • The study team member has the appropriate expertise and training to conduct study
    procedures.

If the event meets the criteria above, the event does not require reporting to the IRB, but should still be documented in the study records.

If the study team has multiple (i.e., two or more) occurrences of the same kind of protocol non-compliance that is not otherwise reportable to the IRB (e.g., missed questionnaire, sample collection), please consult with the IRB Office to determine whether reporting is required.

Subject Deviations from the Study Protocol

Protocol deviations that are the result of subjects’ behavior do not require reporting to the IRB unless they meet ANY of the following criteria:

  • The incident(s) suggest that a subject’s safety is being affected, or
  • The incident(s) adversely impinge upon the integrity, accuracy and/or reliability of the research data from the subject, or
  • A pattern of protocol deviations occurs that indicate a need for changes in the protocol or informed consent document(s).

When an individual subject demonstrates a pattern of repeated noncompliance with the study protocol, the research team should consider withdrawing the participant from the study and/or revising the protocol. If the subject deviation requires reporting to the IRB an unanticipated problem report should be submitted.

Changes to eliminate an apparent immediate hazard to subjects

Changes in approved research initiated without prior IRB review and approval are allowed under both the Common Rule and FDA regulations ONLY to eliminate apparent immediate hazards to subjects. These changes are expected to be rare. Any such changes made must be reported to the IRB within fourteen (14) business days of implementation as both an unanticipated problem and a change of protocol.

  • In the unanticipated problem report, the investigator must give an overview of the situation including what changes were implemented prior to IRB approval and why these changes needed implementation prior to IRB approval to prevent immediate hazard to study subjects.
  • In the change of protocol, the investigator needs to specifically explain any changes to the protocol and study documents (e.g., informed consent documents) that are required.

If a change of protocol is implemented prior to IRB approval and the IRB determines that the change was not necessary to eliminate apparent immediate hazards to a subject, the investigator’s action may be considered to represent noncompliance with the regulations governing human subjects research and result in additional action by the IRB.

Corrective Action Plans

When a deviation/noncompliance event is discovered, immediate measures (also referred to as corrections) to mitigate risk and protect rights, safety, and welfare of the subject(s) and others should be taken. This may be in the form of a phone call or an office/clinic visit between the subject and a member of the research team, or other tests and procedures to ensure the subject’s safety. Corrections alone may resolve minor deviations, but they will not effectively resolve more significant or systematic noncompliance, which generally also require corrective and preventive action.

Corrective and Preventive Actions (CAPA) are developed and implemented for more significant or systematic noncompliance, once the root cause is known. CAPA are implemented to prevent the occurrence and recurrence of an event. For more information on CAPAs, see the Post-Approval Monitoring Program’s website.

Study Suspension or Termination

If the IRB suspends or terminates your human research, the IRB will provide a written determination that includes the reasons for suspension or termination of IRB approval.

For suspension, the IRB will indicate whether some or all the human research activities have been suspended. If, for example, the suspension applies only to the enrollment of new subjects, the IRB will indicate this specifically.

For terminations, you must immediately cease all research activities and work with theIRB to develop a plan for safely removing subjects from the research as applicable.

IRB Reporting Obligations

Federal regulations (HHS and FDA) require that institutions have written procedures to ensure that the following determinations are promptly reported:

  • Any unanticipated problems involving risks to subjects or others;
  • Any serious or continuing noncompliance with FDA or HHS regulations or the requirements or determinations of the IRB; and
  • Any suspension or termination of IRB approval.

You will be notified of these determinations in writing. In addition, the following officials and entities may be notified: funding agency, Department Head, Dean, Institutional Officials, and others. When reporting to regulatory entities (e.g., FDA and/or OHRP) is required, the IRB will make every effort to notify the study team in writing, by phone, or in person prior to forwarding the report to the regulatory entity.

See HRP 052-SOP-Post Review for more information regarding the IRB’s obligations to report this information to regulatory and university officials and department leadership.