Given the large number of active clinical research projects at UCSF, it is not possible for the QIU to review each study. QIU on-site review activities will focus primarily on studies that do not undergo some degree of formal routine on-site monitoring.
The QIU selects studies for review or investigation based on either “Routine” or “Directed” criteria.
Routine Site Visits (RSVs): The QIU conducts routine, proactive, educational, on-site reviews. The RSV review/report template outlines the areas of review.
Verify that subjects' rights and safety are being protected: The QIU staff will verify this generally through study team member interviews and a review of the study records.
Improve/ensure compliance: The QIU staff will help the study team improve/ensure compliance with the protocol and related procedures approved by the IRB; federal and state regulations; Good Clinical Practice (GCP); University guidelines; IRB policies and guidance; and other applicable regulations, guidelines or policies.
Educate research staff: The QIU will educate research staff on areas that need improvement, areas about which research staff have questions, resources available for education and training, and best practices (i.e., GCP).
The QIU identifies studies at the time of continuing review using the following criteria:
- Studies may involve an IND or IDE, or be investigator-initiated, department-sponsored, industry-sponsored, and do not have provision for on-site monitoring.
- Studies are greater than minimal risk, have been active for less than 5 years, and are currently enrolling or actively following participants.
- Studies may involve a vulnerable subject population (i.e., surrogate consent, minors, etc.) or the study design has a potential for increased risk to study volunteers (i.e., phase I trial, gene therapy, etc.)
Formal on-site study monitoring involves overseeing the progress of a research study via regular, ongoing site-level quality checks that are conducted by an appropriately qualified individual (i.e., the investigator, designated study staff, an outside group, or the study sponsor or their surrogate).
In contrast, auditing is most often a one-time, targeted, independent examination of a research study by an external entity (e.g., FDA).
Study monitors should be appropriately trained and should have the scientific and/or clinical knowledge needed to monitor the study adequately. Monitors should be thoroughly familiar with the investigational product(s), the protocol, the informed consent form(s) (and any other written information to be provided to study participants), the sponsor’s standard operating procedures (SOPs), Good Clinical Practice (GCP) guidelines and other applicable regulatory requirements.
What might formal on-site monitoring include? Investigators should specify who, with what frequency, how and to whom monitoring staff will report. On-site study monitors should physically check the conduct and documentation of study activities to ensure that:
- All necessary approvals are in place prior to commencement of recruitment, screening or enrollment activities
- All necessary approvals remain in place throughout the duration of research activities
- Recruitment, screening, enrollment and the informed consent process are being conducted per conditions of IRB approval
- Documentation is on file demonstrating that all participants met all inclusion and no exclusion criteria
- Documentation is on file demonstrating protocol adherence (and documentation when protocol adherence was not met)
- No changes are made to the IRB approved study protocol or consent form unless immediate changes are required to protect the safety of study participants
- Adverse events and pertinent safety information is being captured, assessed, reported and followed as required by IRB, sponsor and/or regulatory agencies
- Any other unanticipated problems (including violations, incidents and/or research-related concerns or complaints) are reported as required by IRB
RSVs are scheduled 1-6 months in advance. If a study is selected, the RSV is mandatory, although the QIU will schedule at a time that accommodates the PI.
Prior to the RSV, the QIU Analyst will provide you with details about the visit and send you the RSV review/report template. The QIU also has prepared the QIU RSV Findings presentation, which describes common findings from RSVs and provides more information on the process.
Directed (for-cause) Investigations: The QIU conducts directed investigations at the request of the IRB for a number of reasons including, but not limited to:
- Investigator has history of poor adherence to IRB policies and procedures.
- The HRPP receives an internal complaint or concern (i.e., from a research participant or family member, UCSF personnel or other UCSF entity).
- The HRPP receives an external complaint (i.e., from OHRP, the FDA or a sponsor) of potential protocol violation or regulatory noncompliance.
QIU personnel generally conduct the on-site reviews. The QIU is a multidisciplinary team comprised of professionals who have experience in conducting, managing and/or monitoring clinical research studies. Rarely, other HRPP staff or IRB members may be involved.
No, the study PI does not need to be present during the entire RSV or directed investigation. However, we usually request that the PI meet with the QIU staff at the start and end of the review or investigation for an interview. The PI also may be asked to be available via pager or to check in periodically with QIU staff during the visit to answer any questions that may arise.
The scope of review or investigation may vary depending on a number of factors. All site reviews or investigations will be preceded by a notification from the QIU that includes specific details about the precise scope of review.
The scope of review may include some or all of the following items:
- The approved research protocol/application and all IRB correspondence
- The informed consent documents and the informed consent process documentation
- Recruitment, screening and enrollment process and procedures
- The regulatory binder and affiliated study correspondence
- Adherence to the inclusion/exclusion criteria
- Adherence to study procedures
- Occurrence and reporting of adverse events, protocol violations or research-related incidents
- Drug and device accountability tracking forms/logs (if applicable)
If you identify any errors, omissions or other problems while preparing for an on-site review, please notify a QIU coordinator for guidance. The most frequent advice when errors or omissions are discovered is to document the event in the participant’s medical record and place a signed dated memo regarding the event in the research file (known as “note to file”). Also submit a report describing this event to the IRB, along with a plan of corrective action to be taken to eliminate future occurrence of this problem.
What information should be available for an on-site visit?
- Informed consent documents for all persons screened and/or enrolled
- Screening/enrollment logs
- Each research participant’s study binder/file
- The regulatory file/binder, which should include all correspondence involving the investigator, IRB, regulatory entities, sponsor and DSMB activities/reports
- Drug and device accountability documentation, if applicable
On completion of a RSV or directed investigation, the QIU staff will draft a report of their findings and send it to the PI and the Co-PI.
For routine site reviews in which no serious or reportable problems are found, the report of findings is sent only to the study PI/Co-PI and other leading site staff; the findings are not shared with the IRB panel overseeing the protocol review.
For other types of review (i.e., directed investigations) or if there are serious or reportable findings from a routine on-site review, reports are shared with the IRB panel overseeing the research project and copies of the report may be distributed to some or all of the following individuals and agencies:
- Department Chair
- Appropriate University officials
- Regulatory and/or funding agency
The QIU has prepared the RSV Findings presentation, which describes common findings. Some of these problems include the following:
- Failure to follow the approved procedures/protocol
- Problems with the consent form, documentation of informed consent or the informed consent process
- Incomplete and/or inaccurate records
- Key Study Personnel lacking CITI training
- Implementing changes to the study without prior IRB approval
- Failure to report protocol violations or adverse events