165. Problems in VA Research: Reporting, Review, and Notification

Updated Oct. 4, 2019

This section addresses IRB reporting requirements for VA Research per VHA Handbook 1058.01, the VHA Decision Chart: Reporting Local Deaths, Local Serious Adverse Events (SAEs), and Serious Problems In VA Research, and the following ORO guidance documents:

NOTE: Sponsor reporting requirements differ from IRB reporting requirements.

When a local death or serious adverse event (SAE), possible noncompliance, or serious problem is bothunanticipated or unexpected and related to the research, members of the VA research community must notify the IRB of the death, event, or incident.

  • Unanticipated/unexpected means the incident is new or the nature, severity, or frequency is greater than previously known or expected given the procedures described in the protocol documents and the characteristics of the study population.
  • Related means the incident is reasonably regarded as caused by or probably caused by the research.

Serious unanticipated problems involving risks to participants or others include:

  • Interruptions of participant enrollments or other research activities due to concerns about the safety, rights, or welfare of human research participants, research staff, or others.
  • Any work-related injury to personnel involved in human research, or any research-related injury to any other person, that requires more than minor medical intervention (i.e., basic first aid), requires extended surveillance of the affected individuals, or leads to serious complications or death.
  • Any VA National Pharmacy Benefits Management (PBM) Bulletins or Communications (sometimes referred to as PBM Safety Alerts) relevant to one or more of the VA facility’s research projects.
  • Any data monitoring committee, data and safety monitoring board or data and safety monitoring committee report describing a safety problem.
  • Any sponsor analysis describing a safety problem for which action at the VA facility might be warranted.
  • Any unanticipated problem involving substantive harm, or a genuine risk of substantive harm, to the safety, rights, or welfare of human research participants, research staff, or others.
  • Any problem reflecting a deficiency that substantively compromises the effectiveness of the VA facility’s Human Research Protection Program (HRPP).

VA principal investigators must comply with the University IRB policy for reporting problems and VHA Handbook 1058.01 and are therefore responsible for notifying the IRB in writing of serious unanticipated problems involving risks to participants or others, local unanticipated serious adverse events, apparent serious or continuing noncompliance, any termination or suspension of research by the sponsor, PI, or authority other than the IRB; and privacy or information security incidents when these are related or possibly related to VA research. These reporting requirements apply to inappropriate access, loss, or theft of PHI; noncompliant storage, transmission, removal, or destruction of PHI; or theft, loss, or noncompliant destruction of equipment containing PHI. As specified in the IRB policy for reporting problems, VA researchers use IRBNet and the problem reporting form for such written notifications.

NOTE: The requirement for written notification to the IRB is in addition to the requirement for immediate oral notification for unanticipated and related local death, as specified below; and other applicable reporting requirements such as to the sponsor or FDA.

Local Research Deaths in VA Research

VA personnel must notify the IRB orally, immediately (i.e., within one hour) after becoming aware of a local death that is both unanticipated and related to the research. Within five business days of the oral notification, a written report of the death must be submitted to the IRB, via IRBNet.

Within five business days of the oral notification, the IRB Chair or other qualified IRB member reviews the report to determine and document if actions are necessary to eliminate apparent immediate hazards to participants.

The report of local death is reviewed at the next convened IRB meeting. The IRB makes and documents one of three determinations:

  1. The death was both unanticipated and related to the research; or
  2. There is insufficient information to determine whether the death was both unanticipated and related to the research; or
  3. The death was not unanticipated and/or the death was not related to the research.

The convened IRB also determines if protocol or informed consent modifications are warranted. If changes are warranted, the IRB determines if the investigator must notify enrolled participants and if so, when and how participant notification will occur. If the IRB determines renewed or revised consent should be obtained from participants, the IRB will specify how the renewed/revised consent will be documented.

Information about notification of the Associate Chief of Staff for Research (ACOS/R), Facility Director, and ORO are described at the end of this policy.

Local Serious Adverse Events and Serious Problems in VA Research

Within five business days of learning of an unexpected and related SAE or serious problem, VA personnel must submit a written report of the SAE/problem via IRBNet.

  • SAE: an untoward occurrence in human research that results in death, a life-threatening experience, inpatient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly, or birth defect, or that requires medical, surgical, behavioral, social, or other intervention to prevent such an outcome.
  • S erious problem: a problem in human research or research information security that may reasonably be regarded as (1) presenting a genuine risk of substantive harm, to the safety, rights, or welfare of human research subjects, research personnel, or others, including their rights to privacy and confidentiality of identifiable private information; or (2) substantively compromising a facility’s HRPP or research information security program.

Within five business days of receiving the written report, the IRB Chair or qualified IRB member will review the package to determine and document if actions are necessary to eliminate immediate hazards to participants.

The problem report is reviewed at the next convened IRB meeting. The IRB makes and documents one of three determinations:

  1. The incident was serious and unanticipated and related to the research; or
  2. There is insufficient information to determine the incident was serious and unanticipated and related to the research; or
  3. The incident was not serious, and/or not unanticipated and/or not related to the research.

The convened IRB also determines if protocol or informed consent modifications are warranted. If changes are warranted, the IRB determines if the investigator must notify enrolled participants and if so, when and how participant notification will occur. If the IRB determines renewed or revised consent should be obtained from participants, the IRB will specify how the renewed/revised consent will be documented.

Information about notification of the ACOS/R, Facility Director, and ORO are described at the end of this policy.

Additional information can be found in IRB policy for adverse events and unanticipated problems involving risks to participants or others.

Apparent Serious or Continuing Noncompliance in VA Research

Within five business days of learning of apparent serious or continuing noncompliance in VA research, VA personnel including the Research Compliance Officer (RCO) following an audit, must submit a written report of the noncompliance via IRBNet.

  • Noncompliance is any failure to adhere to the requirements for conducting VA research.
  • Serious noncompliance is any failure to adhere to requirements for conducting VA research that may reasonably be regarded as (1) presenting a genuine risk of substantive harm to the safety, rights, or welfare of human research participants, research personnel, or others (including their rights to privacy and confidentially of identifiable private information); or (2) substantively compromising the effectiveness of a VA facility’s HRPP. The unfounded classification of a serious adverse event as “anticipated” constitutes serious non-compliance.
  • Continuing noncompliance is the persistent failure to adhere to the legal and policy requirements governing human research.

Individuals may wish to review the ORO guidance Examples and a Brief Guide for Reporting Apparently Serious or Apparently Continuing Noncompliance… for examples of serious and continuing noncompliance.

Problem reports that are assessed and determined to possibly constitute serious or continuing noncompliance are reviewed by the convened IRB at the earliest practicable opportunity, but no later than 30 business days after receipt of the notification. The IRB determines and documents, within 30-45 days after receiving a report of apparent non-compliance, whether or not serious or continuing noncompliance occurred. Prior to review by the convened IRB, the IRB Chair may take interim action as needed to eliminate apparent immediate hazards to participants.

If the convened IRB determines serious or continuing noncompliance occurred, the IRB will specify and document any requirements for remedial actions to ensure present or future compliance.

For apparent serious or continuing noncompliance that was identified by an RCO audit, within 5 business days after review by the convened IRB, the IRB will notify the RCO of its determination (regardless of outcome).

IRBNet maintains an electronic record of problem reports, including apparent or continuing noncompliance. Additional tracking and reporting for the VA facility Director Certification are the responsibility of the VASNHCS Research office.

Information about notification of the ACOS/R, Facility Director, and ORO are described at the end of this policy.

Both the IRB and the VASNHCS Medical Center Director will notify relevant Federal agencies (e.g., OHRP, FDA, DoD) within 30 days of an IRB determination of serious or continuing noncompliance. The sponsor will be notified as specified in the contract.

Timeline for Researchers to Complete IRB-Requested Remedial Actions

Remedial actions must be completed within 120 days after the IRB’s determination unless remediation requires substantial renovation, fiscal expenditure, hiring, legal negotiations, or other extenuating circumstances that preclude completion of the actions within 120 days. In the latter case, the VASNHCS is responsible notifying ORO as required.

Systemic Deficiencies

VA personnel, including WOC and IPA appointees, and the IRB must notify the VA facility’s R&D Committee within 5 business days after becoming aware of any apparent systemic deficiency.

  • Systemic Deficiency is a fundamental, underlying problem that jeopardizes the effectiveness of the VA facility’s HRPP.

Research Information Security Incidents

Information security incidents must be immediately reported (within one hour) to the ACOS/R, the Information Security Officer (ISO), the Privacy Officer (PO), and relevant investigators.

Within 5 business days of discovery of the incident, the following requirements for written notification must be completed.

  • If the immediate notification was not in writing, written notification of the incident must be provided to the ACOS/R.
  • Information security problems involving human research must be reported to the IRB via the problem reporting form.

The VASNHCS is responsible for ensuring the required notifications are completed as specified in Handbook 1058.01 and the related ORO examples and brief guide for reporting and decision chart.

Problem reports of information security incidents are reviewed by the convened IRB at the earliest practicable opportunity, but no later than 30 business days after receipt of the notification. During its review, the IRB will consider the examples and questions in section A of the ORO guidance: Examples and a Brief Guide for Reporting Apparently Serious Research Information Security Problems …

The IRB will document the following determinations:

  1. Whether or not the incident constitutes a serious problem; and
  2. In conjunction with the ISO and/or PO as applicable, remedial actions to be completed by the facility or the relevant investigators (if warranted).

If the IRB determines the incident constitutes a serious problem or serious noncompliance, the additional requirements apply for IRB review and documentation, and notification of the ACOS/R and ORO.

Associate Chief of Staff, ORO, and Other Notifications

Notification of Local Deaths

Immediately after receiving oral notification of an unanticipated, related local death, the IRB will notify the VASNHCS Research Office either orally or via email. The VASNHCS is responsible for notifying ORO of same within two business days of the IRB notification.

Notification of IRB Determinations

Following review of a problem report by the convened IRB, the IRB notifies the VASNHCS ACOS/R and the Facility Director within five business days of the following IRB determinations:

  1. Local death, regardless of IRB determination;
  2. Actions necessary to eliminate apparent immediate hazards to participants; including related modifications to protocol or informed consent processes/document;
  3. Serious, unanticipated, and related problem/event or information was insufficient for determination of serious, unanticipated, and related problem/event;
  4. Serious or continuing noncompliance;
  5. Following report of RCO finding of apparent serious/continuing noncompliance regardless of outcome; or
  6. Suspension or termination of IRB approval.

The agreement between the VASNHCS and the University identifies the VASNHCS as the party responsible for notifying ORO of Reportable Events.

Following notification from the IRB of any of the above-specified determinations, the VASNHCS ACOS/R is responsible for the following additional (prompt) notifications and under the applicable conditions:

  • Research and Development Committee;
  • Privacy Office for problems involving unauthorized use, loss, or disclosure of individually identifiable patient information; and
  • Information Security Officer for problems involving violations of VA information security requirements.

Notifications for Safety-Related Suspensions/Terminations of Research

When a party other than the IRB suspends or terminates research due to concerns about the safety, rights, or welfare of research participants, the ACOS/R is responsible for notifying the Facility Director; Research and Development Committee; and other relevant research review committees (including the IRB if not previously notified by the PI). The Research and Development Committee and the Facility Director have the authority to suspend or terminate their approval of research.