Monitoring & Compliance FAQs

The CARs Committee is comprised of the IRB Chair, the IRB Regulatory Affairs Specialist, the ECS-HSR Director and staff, the Deputy Director, Office of Research Protections, and staff members. The CARs meetings are conducted monthly to review compliance activity reports and other compliance events to determine if a review by the convened IRB Executive Committee is warranted. The CARs meeting minutes are provided to the IRB Executive Committee and are voted for approval at a convened meeting. The outcome of a CARs review is not documented in the PittPRO application history. A principal investigator is only notified of a CARs determination by email if there are significant concerns or if additional information is required to complete a review.  

The purpose of a compliance activity is to ensure the protection of human subjects, verify compliance with regulatory and institutional review board (IRB) policies and ensure the research was conducted within Good Clinical Practices (GCPs). ECS-HSR compliance activities include Research Investigator Start-up Education (RISE) reviews, monitoring visits and audits.

RISE reviews

RISE reviews are conducted by the ECS-HSR to foster human subject protection and regulatory compliance of study teams with newly IRB approved protocols. The following are topics that may be reviewed during a one-time 60 to 90-minute interview:

• Protocol-specific guidance,
• Study documentation tools,
• Logistics of implementing study procedures,
• Review of Good Clinical Practice (GCP) guidelines, and
• Instructions on submitting reportable new information to IRB.

If subjects are enrolled at the time of the RISE, some of the research records may be reviewed to assess for compliance.

For more information, visit RISE Reviews.

Monitoring

Monitoring visits are conducted by the ECS-HSR to review the ongoing progress of the study and to confirm the following requirements are met:

• The rights and well-being of human subjects are protected,
• Original source documentation is maintained for research participants,
• The study is conducted in accordance with the protocol and applicable regulatory requirements,
• There is accurate and timely reporting of adverse events and serious adverse events,
• Protocol deviations/ noncompliance are addressed and properly reported,
• A regulatory file is maintained and contains up-to-date essential documents, and
• Study product storage is appropriate, and the study product accountability are accurate, as applicable.

For more information, visit Monitoring Services.

Audits

Audits are conducted by the ECS-HSR at the request of the IRB and other institutional offices.  The following are examples of reasons an audit may be requested:

• Concerns with a modification, continuing review or reportable new information submission,
• Complaint filed by an employee or research subject, and
• Verification of the informed consent process

The reason for an audit dictates the extent of the review such as the number of subject records and specific data points. This decision is made on a case-by-case basis and may change as the audit progresses.

For more information, visit Audits.

Relax! The best way to prepare for the RISE review is to be familiar with the IRB approved study application, the methods to implement and document study procedures and the IRB’s requirements.  If subjects have been enrolled, the ECS-HSR may review 1-2 of the subject research records to assess for compliance, offer suggestions to improve documentation and provide instruction on submitting reportable new information to the IRB, as needed.  Questions that may be asked during the RISE review include:

• Who will be responsible for conducting specific study tasks?
• How are potential subjects identified and/or recruited?
• What is the process for obtaining and documenting informed consent?
• How is eligibility assessed and documented? 
• What are the methods to review, assess and document adverse events, protocol deviations and instances of noncompliance?
• How will study specific protocol training be documented?

To prepare for an audit, you should be familiar with the IRB approved study application, the methods to implement and document study procedures and the IRB’s requirements. Research records should be organized by subject and in order of enrollment, if possible. Arrange for a quiet workspace for ECS-HSR to review the records; if enrollment numbers are high, the audit may take several days. The following documents and/or access to electronic data may be requested:

• Enrollment/Screening/Randomization logs,
• Informed consent documents for enrolled subjects,
• Original source documents such as:
  • Medical records (e.g., lab results, x-rays, MRI reports, clinical and office notes, etc.)
  • Case report forms
  • Electronic research data (e.g., downloaded data from a mobile/wearable device, etc.),
• Study product accountability records,
• Regulatory file(s) including correspondence with funding agencies/sponsors, and
• Departmental Standard Operating Procedures (SOPs).

The ECO-HSR office is available to perform a review of subject records and regulatory files prior to an FDA inspection or regulatory audit, for studies under the jurisdiction of the University of Pittsburgh IRB.  These are performed if time permits.  Please notify the ECS-HSR at ECS-HSR@pitt.edu immediately if you have been informed of a regulatory audit/inspection. Guidance documents available include:

FDA Inspection Checklist
FDA Inspection Helpful Hints

For more information, visit the Human Research Protection Office.  

Deviations/noncompliance are often identified when preparing for a compliance activity. The deviation/noncompliance should be recorded on a noncompliance log. The principal investigator should review the deviation/noncompliance to determine if it meets the reporting requirements outlined in the IRB Policies and Procedures, Chapter 17, and funding agency’s requirements/the event should be reported accordingly to the IRB and or the study sponsor. In addition, the study team should review and amend SOPs to follow corrective and preventative action plans, if applicable. 

Corrective and Preventative Action (CAPA) is a systematic approach that includes actions needed to correct, avoid re-occurrence of and eliminate the cause of potential problems.  A quality CAPA plan includes the following:

• An analysis of the root cause,
• Identification of actions that need to be taken (research solutions),
• Documentation of corrective and preventive action activities (act),
• Implementation of solutions (prevent), and
• Steps to verify the solution was effective works (prevent).

The most common compliance activity findings are:

• Incomplete regulatory files (e.g., failure to document protocol specific training, incomplete DALs, etc.),
• Inadequate subject records,
• Incomplete deviation/noncompliance logs,
• Failure to report deviations/noncompliance that meet the IRB’s reporting requirements, and
• Informed consent deficiencies (e.g., failure to use currently approved version, date/signature errors, etc.)

The PI is ultimately accountable for the conduct of the study. Although the PI may delegate trial related tasks to appropriately qualified and trained staff, the IRB and the FDA hold the PI responsible for the conduct of the study. PI responsibilities are outlined in the IRB Policy and Procedures, Chapter 4, and as outlined below:

1 CFR 312.50: General Responsibilities of Investigators
21 CFR 812.100: Responsibilities of Investigators: Biologics
21 CFR 812.110: Responsibilities of Investigators: Devices
DHHS: Office of Human Research Protections (OHRP): Frequently Asked Questions

The term delegation of authority log is not mentioned in the federal regulations.  The International Council of Harmonization (ICH), which is the gold standard for Good Clinical Practice (GCP), outlines in Section 4.1.5 that the principal investigator (PI) should maintain a list of appropriately qualified persons to whom the PI has delegated significant trial-related duties.

Although the PI is ultimately accountable for the conduct of the study, they may delegate trial-related tasks to appropriately qualified and trained staff.  The DAL is a means of documenting which study team members (study staff, investigators, clinical research coordinators, etc.) have been delegated significant trial-related duties from the PI.  All staff delegated to significant study related duties must show evidence of education and training appropriate to the role to confirm that they are qualified to perform the delegated task. 

The DAL should be maintained for studies that meet the definition of an NIH Clinical Trial and is considered a best practice for all studies. View an example of a DAL.

As outlined in Section 4.1.5 of the ICH Guideline, the principal investigator (PI) should maintain a list of appropriately qualified persons to whom the PI has delegated significant trial-related duties. While the term significant is not defined, this is interpreted as being any duty/task that could have significant impact on subject safety, protocol compliance, and the quality and integrity of the study data.

Non-research staff who perform only research specific procedures in connection with the protocol and which follow the scope of practice assigned to their specific role (e.g., Phlebotomists, EKG Technicians, Lab Technicians, Interventional Radiologists, Infusion Center Nursing Staff, Medical Assistants, etc.) are not required to be listed on the DAL.  Per the ICH GCP Guidelines in section 4.1.5, these individuals are not performing significant trial-related duties and do not require study specific training to perform these procedures. Additionally, for in-patient trials, Hospitalists, Nurse Practitioners, Residents, or Fellows who only provide ancillary or intermittent care for the study patients, but do not make a direct or significant contribution to the clinical data (i.e., evaluate AEs, sign drug order forms, consent study patients, etc.) are not required to be listed on the DAL.

In cases where a unit is responsible for a trial related task (e.g., the Clinical Translational Research Center or Investigational Drug Service), it is acceptable for the manager responsible for the unit to sign the DAL on behalf of his or her staff.   However, the PI in conjunction with the manager must ensure that staff are appropriately credentialed, trained and informed of the study procedures. 

Yes. The ECS-HSR created a document titled, University of Pittsburgh Guideline: Study Documentation for FDA Regulated Research and Clinical Trials.  This document also can be found in the Good Clinical Practice Toolbox. 

SOPs are written processes that describe in detail how to perform a task(s) specific to your study. Documenting standards properly allows study teams to comply with regulatory and quality standards, ensure subject safety, train future staff more effectively, ensure tasks are performed consistently and enable a culture of continuous improvement.

Study-specific training should be performed, prior to the enrollment of subjects, to ensure that members of the study team are aware of the study aims and procedures as well as who on the study team is responsible for tasks associated with the conduct of the study. Members of the study team should be provided with, at a minimum, a copy of the IRB-approved protocol and consent document(s). Other documentation that should be disseminated to the study team, as applicable, include the FDA clinical protocol, data collection tools, manual of procedures, standard operating procedures, safety training, etc. 

Training can be accomplished by holding an implementation meeting where study team members meet for a review of relevant issues associated with the conduct of the study. Consider creating a slide deck to guide the discussion and address areas of the study that are of most significance. Documentation of training should be maintained including the date of training, attendees, the name of the person(s) conducting training and the material covered.  Members of the study team, who are unable to attend in person, can join the meeting by phone or teleconferencing.  An email containing documents reviewed during the implementation meeting should be sent to those who are unable to attend; recipients should be asked to provide written confirmation of their receipt and review of training materials.

Documentation of study-specific training should be maintained with the regulatory documents.

Other considerations:

• Generate a sign-in sheet for attendees to sign documenting their attendance. The sign-in sheet should contain the study title and the date of training; a copy of the agenda can be attached prior to filing with the regulatory documents.
• If feasible, have a Signature and Delegation of Authority Log at the implementation meeting for study team members to sign and document their assigned tasks.
• Training is an ongoing process; study team members should be apprised when the protocol and/or consent document has been modified. This training should also be documented.
• For new research staff, documentation of training should be in place prior to engaging in research procedures.

Contact our experienced Information Disclosure Administrator at CTgov@pitt.edu if you have questions or need to establish an account.