802. Directed On-Site Review

Updated July 19, 2021

One of the goals of the Quality Improvement Program (QIP) is to educate researchers on the mechanisms by which human participants are protected. A directed review is performed when concerns regarding compliance, protocol adherence, or participant safety are brought to the attention of the Research Integrity or the IRB. This is considered a full review. This type of review may occur more than once in a twelve month period if concerns about the protocol were brought to the attention of the IRB on multiple occasions. Additional reviews or continued monitoring may result from a review in which corrective actions were prescribed by the IRB.

The Research Compliance Officer (RCO) conducts directed on-site reviews at the request of the IRB, the Vice President for Research Innovation (VPRI), or Research Integrity Director due to unusual circumstances, significant risks to participants, routine failure on the part of an investigator to comply with federal and/or institutional requirements, or allegations or concerns about the conduct of the study. The IRB, VPRI, or the Research Integrity Director may also request periodic reviews to evaluate whether investigators meet their responsibilities within specific areas of research (e.g., investigators conducting research using an investigational device). If appropriate, directed reviews also encompass elements of informed consent evaluation. The IRB may request measures to monitor the consent process to determine whether procedures for administration of informed consent are proper. The RCO may review IRB records to determine accuracy and consistency with the investigator’s research records and to verify that the investigator made no material changes to the protocol.

Areas Reviewed During the Site Visit

• Recruitment & Compensation
• Participant Population
• Participant Enrollment
• Informed Consent (Content and Process)
• Data Collection, Storage, Transmittal, Destruction, and Security
• Data and Safety Monitoring Board (DSMB) and Plan (DSMP)
• Adverse Events
• Project Personnel (Qualifications and IRB Training)
• Continuing Review
• Amendments
• Protocol Adherence (Violations/Deviations)
• Other areas as determined by the review

Arranging for a Directed Review of Research Team Files and Activities

• Written notification of pending review will be sent from the Research Compliance Officer. It is the responsibility of the RCO to schedule the visit as soon as possible. The RCO may use the following criteria to identify protocol(s) for inspection: federal, state, or industry-funded projects; currently approved and active for two years; level of risk to participants; or participants currently enrolled in study.
• The RCO may review the initial review meeting minutes, IRB records, and database to become familiar with the protocol(s) and to identify issues to address.
• The RCO may also request a tour of the facilities to verify control, storage, and accountability of investigational new test articles and/or to confirm availability of related research equipment, and/or to verify secure storage of research records.

Reviews may include, but are not limited to the following activities:

• Interviews of the Principal Investigator (PI), co-investigators and/or research staff
• Review of randomly selected participant files to:
• Determine whether the approved inclusion/exclusion criteria were met
• Determine that participants were not enrolled until after all appropriate approvals were obtained
• Determine whether the correct informed consent document(s) was utilized and that informed consent was obtained in the manner approved by the IRB
• Determine whether the approved dose ranges of the study drug were administered
• Review of study files to:
• Determine whether all the amendments were reported before changes were implemented unless it was necessary to eliminate apparent immediate hazard
• Determine whether adverse events and unanticipated problems were reported in a timely manner
• Determine if the advertisements and other recruiting materials in use are the versions approved by the IRB
• Determine whether the informed consent document complies with federal regulations
• Determine whether IRB (Research Integrity) and VA R&D administrative file(s) contain all modifications and adverse events submitted by the investigator
• Determine whether IRB review was timely
• Review projects to verify from sources other than the researcher that no unapproved changes have occurred since previous review
• Monitor conflict of interest concerns to assure the consent documents include the appropriate information and disclosures
• Determine if continuing reviews were completed within one year (or more often if appropriate)
• Observe the consent process as determined necessary by the convened IRB (i.e., considered when a complaint is received regarding the informed consent process, or when investigator veracity is doubted)
• Conduct any other monitoring or review activities as deemed appropriate by the IRB
• Confirm completion of compliance education for PI and research staff
• Compare list of participants (# enrolled/accrued) provided by the Investigator with continuation review report for consistency

The RCO offers to conduct an optional entrance interview. The RCO conducts an exit interview with the PI at the conclusion of the review. The IRB Chair/IRB member may participate in these interviews. At the PI’s discretion, select study personnel may also attend. The RCO may use this time to explain the goals of the Directed Review/QIP and the impetus behind the directed review. It also allows the PI/study personnel an opportunity to explain what the protocol entails, respond to the issues which instigated the directed review, and answer any questions arising from the RCO’s review of the IRB protocol records.

Outcome of Reviews

The RCO and/or IRB Chair/IRB member conducts the exit interview after the RCO completes a review of the PI’s records and may request clarification regarding the protocol or research procedures at that time. The RCO and/or IRB Chair/IRB member provides the investigator with a verbal summary of the findings and explains the remaining procedures for conclusion of the directed on-site review.

Following completion of the review, the RCO will prepare a written report for the PI. The report may include recommendations for aligning the research protocol, if necessary, with institutional policies and regulatory requirements and/or specify corrective actions, if any.

• If the directed review identifies a need for revision of the research protocol or informed consent processes, the PI is responsible for submitting an amendment/modification to the current approved protocol in accordance with IRB requirements.
• If the directed review identifies serious or continuing noncompliance, the PI will adhere to established processes of the investigation, correction and reporting of any material noncompliance, as may be required or appropriate.

The RCO sends the written report to the PI with a requested response date determined on a case-by-case basis. Typically, the PI has two to three weeks to submit his/her/their response to the recommendations and/or comments on the report. Upon receipt of the PI’s response, the RCO schedules a review with the IRB at a convened meeting.

Reportable to the IRB and Institutional Official

Significant deficiencies in research participant protections (including, but not limited to):

• A major protocol deviation
• Unanticipated problem involving risks to participants or others which has not been previously reported to the IRB
• Serious or continuing noncompliance

Not necessarily reportable to the IRB and/or Institutional Official

• Unintentional administrative/management errors which do not impact participant safety, do not substantially alter risks to participants, or do not affect data integrity
• Unintentional deviations that are largely outside of the reasonable control of the PI (e.g., missed appointments, misinformation by participant regarding eligibility and exceeding the number of participants in survey research with a link, etc.)
• Intentional changing of the order of procedures without risk to participants for the convenience of the participant

IRB Review and Vote

IRB members vote for one of the following actions:

• Approved – No further action is required. The RCO sends the PI a letter describing the outcome of IRB review.
• Revisions/additional information requested – The IRB withholds approval pending submission of revisions/additional information. The IRB may give the individual chairing the meeting the authority to approve non-substantial revisions/additional information or require review of substantial revisions/additional information at a convened meeting. If the IRB request necessitates further review, the RCO acts accordingly and processes any additional findings/information for review based on the IRB’s determination at the convened meeting (either gives them to the individual who chaired the IRB meeting or assigns them to a convened IRB meeting for review). If the IRB request necessitates a response from the PI, the RCO sends the PI a letter describing the IRB’s request. When the PI responds to the IRB’s request in writing, the RCO processes the response based on the IRB’s determination at the convened meeting (either gives it to the individual who chaired the IRB meeting or assigns it to a convened IRB meeting for review). If the individual who chaired the meeting is the IRB’s designated reviewer, he/she/they may decide to forward the response to the entire IRB for additional review, request additional information, or approve.
• Suspension or termination of the research. The RCO sends the PI a letter describing the outcome of the IRB review. A copy of this letter is sent to the VPRI, individual chairing the meeting and the RI Director. Additional copies of the letter will be sent as described in the policy regarding IRB notification requirements for reportable events.