Human Research Routine Review & Education Program

A: Routine Reviews are not-for-cause, initiated by the review team, and are equally distributed among types of research, taking into account criteria that include:

• Studies which are federally funded
• Investigator initiated studies
• Studies enrolling vulnerable populations
• Studies with high participant enrollment
• Studies with large numbers of reported deviations and adverse events
• Phase I or Phase II clinical trials
• Studies utilizing the WCM Data and Safety Monitoring Board (DSMB)
• Studies involving international research

Written reports detailing the findings of a Routine Review are only shared with the PI, research team and Routine Review team, unless a finding indicates possible serious or continuing noncompliance, or a possible unanticipated problem involving risks to subjects or others, in which case the report is also shared with the IRB. 

For‐Cause audits are those that are requested by the IRB, Department Chair, the Institutional Official, Research Integrity Officer, or Executive Leadership, and may be conducted in response to any of the following:

• Indication of an increased risk to participants
• Participant/family member complaint
• Follow‐up from an external inspection, such as FDA, OHRP, or NYSDO
• Studies in progress that are outside the investigator’s field of specialty
• Lack of or unreported adverse events and/or DSMB reports
• Absence of reporting to the IRB, including failure to obtain continuing review approval
• Employee concern or complaint about the research
• Clinical trials involving an IND or IDE when a safety warning has been issued by the FDA, or when there has been a change in labeling that indicates an increase in risk
• Issue or allegation of non‐compliance
• Suspected research misconduct

Written reports detailing the findings of a For‐Cause audit are always shared with the IRB. 

Apart from how they are initiated, and to whom the written reports with findings are disseminated, For‐Cause audits and Routine Reviews are the same. 

A: Yes.  You may request assistance with preparation for an external audit by the FDA or other regulatory body by emailing researchaudit@med.cornell.edu.

A: Depending of the scope of the evaluation, the Routine Review or For-Cause audit may take anywhere from a few hours to several days.  

A: A given audit or Routine Review involves interviews and comprehensive regulatory and participant documentation review.

The PI is always interviewed twice – once to start the audit/Routine Review and a second time to discuss findings – and members of the study team and/or participants are interviewed as needed. The PI’s first interview occurs at the beginning of the audit/Routine Review, whereas the PI exit interview occurs within 3 days of completion of the evaluation. 

The Routine Review team will evaluate regulatory documentation, including IRB documentation, study team credentials and participant documentation, such as informed consent(s), assent(s), and medical record, in detail. During this time, a member of the study team able to answer questions should be made available.

When applicable, the Routine Review team will also tour the research facility to verify control, storage, and accountability of investigational new test articles and/or to confirm availability of related research equipment.

The Routine Review team may also view the study team conducting the informed consent process.

A: The interview is a discussion guided by the individual’s role on the protocol and may include:

• Grasp of regulatory obligations
• Training prior to assuming protocol responsibilities
• Informed consent process
• Reporting to the IRB and other regulatory bodies
• Data storage and procedures for maintaining research participant privacy
• Study team communication regarding ongoing protocol management
• Questions about the research facility

A: For all audits, regulatory documentation, including but not limited to:

• Protocol
• Investigator’s Brochure (if applicable)
• Logs (Screening/Enrollment/Delegation/Deviation/Monitoring Visits/Training)
• Records of retained tissue or fluid samples
• Laboratory certifications and lab normal ranges (when applicable)
• Correspondence
• Investigational product labeling, accountability, receipt, storage, dispensing, and destruction logs (if applicable)
• FDA correspondence and annual reports
• All IRB approved documents and correspondences, including:
• IRB initial applications, renewals, amendments with associated Modifications Required letters, Deferral letters, and Approval letters from the IRB
• Recruitment material (e.g., flyers, advertisements, newsletters, letters, e‐mail) with documented IRB and sponsor approvals
• Safety Report submissions and associated acknowledgments
• DSMB Report submissions and associated acknowledgments
• Filed IRB correspondences, including approval letters
• All stamped approved revised versions of the Informed Consent document, assents, and short form for non‐English speaking subjects
• All stamped approved HIPAA Authorization Forms
• Documentation demonstrating timely reporting of adverse events and protocol deviations according to the Immediate Reporting Policy, including Further Information Required and Acknowledgment letters from the IRB
• Exception Requests and associated IRB approvals

A review of study team credentials and training such as:

• Required Human Subjects Training
• Protocol‐specific training
• Conflicts of interest
• Updated CV and Licenses
• Appropriate certification, when required

A review of participant source documentation, consisting of the following:

• Evaluation of signature, date, and time (where applicable) on informed consent(s), assent(s), and HIPAA Authorization documents, including copy in the medical chart
• Confirmation of participants’ eligibility
• Study visit assessment
• Assessment of participant adherence to protocol: drug accountability, deviations, etc.
• Adverse events (AEs and SAEs) assessments and reporting
• Concomitant medication documentation
• Medical History documentation
• In the case of Investigator‐Initiated Trials, the research record and informed consent form will be reviewed for the first participant to have been enrolled and received study treatment
• In the case of Investigator Requested audits, the auditor will select a sample of at least 20% of participants, but no less than 5.  The participant’s research record, informed consent, and other related documents will be reviewed. The Principal Investigator or study team may request additional records to be reviewed.
• In the case of External Audit and Inspection Preparation, the auditor will select a sample of at least 20% of participants, but no less than 5. The participant’s research record, informed consent, and other related documents will be reviewed.

A: In the case of Routine Reviews, only the PI, research team, and Routine Review team see the report, unless findings indicate possible serious or continuing noncompliance, or a possible unanticipated problem involving risks to subjects or others, in which case the report is shared with the IRB. Otherwise, the report stays with the PI, research team, and Routine Review team.

In the case of a For‐Cause audit, at a minimum, the IRB, Assistant Dean of Human Research Compliance, Associate Dean of Clinical Research, department chair, and division chief will also view the report. Other relevant and key stakeholders may view it as necessary.

A: If this occurs, the Principal Investigator is required to implement a corrective action plan commensurate with the degree of noncompliance. In some cases, the written report you receive will guide you as to what corrective actions might best fit your circumstances in the opinion of the Human Research Routine Review & Education Program. If this happens, the principal investigator can choose to follow these prescribed corrective actions or implement his or her own. In either case, corrective actions must be detailed in the principal investigator’s response to the written report so that, in the case of a For‐Cause audit, they can be presented to the IRB by the audit team at a convened meeting. 

A: If you disagree with the accuracy of a For‐Cause audit finding, notify researchaudit@med.cornell.edu of the request to appeal with a signed memo 2 weeks prior to the IRB meeting at which the findings are to be discussed. The audit findings and appeal will both be presented at an IRB meeting by the audit team.