Routine Review Procedure

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Overview

A Routine Audit is one which is conducted only due to a protocol selection process, not for a particular cause.

Review Process

How is a protocol selected?

In order to schedule a routine audit, an HSPP analyst will obtain a list of all ongoing, IRB-approved human subjects research from eIRB and the IRB database, which includes studies on each of the three Rutgers campuses of Newark Health Sciences, New Brunswick Health Sciences, and New Brunswick Arts and Sciences. A representative number of studies will be scheduled for routine audit on each campus based on the current total of IRB-approved studies. All studies will be categorized by the type of research involved and the general risk to the safety, welfare, or rights of study subjects.

Each HSPP analyst selects a minimum of two (2) and a maximum of four (4) protocols a month to audit. All active human subject protocols are eligible for audit, including those protocols sponsored by the National Cancer Institute (NCI), pharmaceutical industry, or other sponsors. 

When selecting a protocol to audit, these are some of the issues we consider:

  • What is the study's risk level?
  • Which studies involve an FDA-regulated product (e.g., drug, device, or biologic)?
  • Who initiated the study (Investigator, Sponsor)?
  • When was the last time PI's schools/departments/performance site was selected for a routine audit?
  • Does this study involve vulenerable populations?
  • Has this study had any issues with enrollment (i.e., not enrolling, over enrolling, under enrolling)?
  • Was the protocol approved with any stipulations?
  • What is the source of funding?
  • How many studies is currently conducted by this Principal Investigator?
  • Does the study's Principal Investigator hold an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application?
  • Did the Principal Investigator choose not to use the University's Research Pharmacy?
  • Does the PI need a follow up to a for-cause review to confirm that the correction action plan is being followed?

Audit Preparation

How is a routine audit scheduled?

The HSPP analyst will notify the Principal Investigator by sending a formal “Notification of a Routine Review via Rutgers email. The Senior Analyst allows the Principal Investigator a maximum of ten (10) business days to respond to the routine review request.  If there is no response, the HSPP staff will begin a correspondence log to track the efforts of scheduling an initial visit. If the HSPP team is unsuccessful with arranging the routine review, they will seek the support from the Chief/Executive Director.

When the investigator is reached by phone or email, the Senior Analyst and Principal Investigator arrange a mutually convenient time for review of all appropriate research records including

  • regulatory files
  • subject research/medical records, as necessary
  • electronic data, where applicable

Audit checklists are available upon request and are offered by the HSPP staff at the time they are scheduling the review.

One or two days before the audit, the Senior Analyst will contact a member of the study team to confirm details (i.e., date, time and place) and to answer any final questions.   This communication is followed up by an email to confirm the conversation.

What are the responsibilities of the HSPP Team?

An HSPP analyst shall prepare for the routine review of each study with a review of the full IRB protocol file including initial and continuing review submissions and approvals, amendments, and all correspondence to and from the Principal Investigator, sponsor, and IRB.  This review of documents will be written in chronological order and will later be compared to the Principal Investigator’s IRB protocol file.

The protocol will be reviewed for adherence to 45CFR and 21CFR, ICH GCP (if applicable), Rutgers policies and procedures, state and local institutional policies, and research site standard operating procedures.

The HSPP analyst will review the eIRB or paper file to verify completion of the following items:

  • initial submission, with IRB approval letter
  • protocol and amendments/modifications, with IRB approval letters
  • consents and amendments/modifications, with IRB approval letters 
  • advertisements, with IRB approval letters
  • continuing reviews, with IRB approval letters
  • reported adverse events
  • correspondence (e.g., IRB debriefing letters, investigator responses to the IRB, emails)
  • IRB approval from any collaborating institutions
  • training and education of staff related to the study 

If applicable, the HSPP analysts will contact the research pharmacist to review all records regarding the dispensation of investigational/study drugs.

In addition, the Medical Records Department may need notification from the Chief/Executive Director to gain access to the particular set of subject records associated with the source documents that support the conduct of the study.  

What are the responsibilities of the Principal Investigator and the Study Team?

Prior to the audit, the Principal Investigator and study team are responsible for the following items:

  • ensuring the regulatory binder is complete and up-to-date  
  • gathering original eligibility checklists, ICFs, and off-study forms for the selected subjects 
  • gathering completed case report forms (CRFs) and research files for the selected subjects
  • gathering all source documentation for the selected subjects
  • flagging or organizing the required elements of the protocol in the selected subjects’ charts

It is preferred that all eIRB screen shots and electronic source documentation are printed in preparation for the routine review.

Audit Visit

What happens during the initial interview?

The on-site review of the requested protocol begins with an initial interview. The Principal Investigator is encouraged to invite his/her co-investigator(s), study coordinator(s), and any other personnel named on the protocol.

At the initial interview, the HSPP analysts will address the following questions.  This is not a comprehensive list, as the questions may vary according to specific protocol details:

  • How is your study conducted?
  • How are subjects recruited?
  • What is the informed consent process?
  • What staff is involved in study activities, and what are their roles and qualifications?
  • How many subjects were approved by the IRB?
  • How many subjects are currently enrolled?
  • What source documents are available to support the conduct of the study?
  • Is this the only performance site?
  • Where are the original signed and dated consent forms stored?
  • Have there been any serious adverse events or unanticipated events, and have they been reported to the local IRB and sponsor (if applicable)?
  • Where are study medications/investigational drugs/investigational devices stored and dispensed (if applicable)?
  • Has there been a lapse in IRB approval?  If so, why?

What happens during the tour of the facility?

The HSPP team will request a tour of the facility to observe where the research is being conducted. The Principal Investigator, co-investigator, or study coordinator should be able to answer the following questions:

  • Where are the ICFs locked and stored?
  • Where does the consent process take place?
  • Where are physical exams and/or study procedures conducted (if applicable)?
  • Where are study medications/investigational drugs/investigational devices stored and dispensed (if applicable)?
  • Are there any temperature logs regarding storage of the study medications/investigational drugs/investigational devices?
  • Where is the study equipment located?
  • Where are the computer stations located?  Is the area private and secure?
  • Where are the source documents stored?

What study documents will be reviewed?

The Principal Investigator shall be asked to provide a space for the Senior Analysts to review research records and arrange for research staff to be available during the routine review to assist and provide answers to questions regarding the conduct of the selected study. 

The following items will be reviewed:

  • Regulatory Files
    • initial submission, with IRB approval letter
    • protocol and amendments/modifications, with IRB approval letters
    • consents and amendments/modifications, with IRB approval letters  
    • advertisements, with IRB approval letters
    • continuing reviews, with IRB approval letters
    • reported adverse events
    • correspondence (e.g., IRB debriefing letters, investigator responses to the IRB, emails)
    • training and education of staff related to the study 
  • ICFs
    • location (i.e., confidentiality, limited access, separate from study data)
    • appropriate recruitment of subjects with respect to protocol-specific inclusion/exclusion criteria (i.e., enrollment and screening logs)
    • signed consents equal the number of enrolled subjects
    • content of signed consents corresponds to IRB-approved versions
    • proper execution of each informed consent (i.e., signed before study activities)
    • documentation of the consent process
    • determination of any enrollment during lapse in IRB approval 
  • Data
    • location (i.e., confidentiality, limited access)
    • compliant with HIPAA
    • source documentation of protocol-specific study procedures, interventions, study visits, follow-up, adverse events, and unanticipated problems (e.g., CRFs, computer generated study visit forms)

If the audit identifies non-compliance, such as lack of oversight, deliberate falsification or omission, failure to comply with the requirements and determinations of the IRB, or significant and/or frequent protocol violations or deviations, the Senior Analysts will immediately notify the Chief/Executive Director who will review the findings and make a determination to notify the Institutional Official and federal agencies of oversight.

Please refer to the audit checklists for a more detailed description of the documents that will be reviewed.

What happens during the exit interview?

The exit interview will ideally occur within 72 working hours of the completion of the audit. The Principal Investigator is required to be present during the exit interview. The co-investigator and/or study team members are also strongly recommended to attend.

The HSPP analyst presents the audit findings and responds to any questions from the Principal Investigator and study team.  It is important at this point to discuss all questionable issues and provide opportunities for clarification.  Any missing, incomplete, or incorrect data should be given to the HSPP analyst within ten (10) business days of the exit interview.  If no communication is received regarding the missing, incomplete, or incorrect data, then the deviation will be cited in the final report.

What is included in the final audit report?

The HSPP analysts will complete the final audit report within two (2) to four (4) weeks of the exit interview.  The final audit report lists the specific details of the audit, including the dates of the audit, a detailed list of significant findings, and minor additional observations and findings.

The HSPP Senior Analysts will electronically send a final report to the IRB administrator of the IRB of record, who will place it on the next IRB Executive Committee agenda.

How can the IRB Executive Committee respond to the final audit report?

If there were no significant findings, the routine review is attached to the IRB Executive Committee agenda to be reviewed and accepted.

If there are any significant findings, then the routine audit report is placed on the agenda, and the HSPP analysts will present a verbal report to the IRB Executive Committee.

No formal written response will be required if the audit of the protocol is deemed “accepted with no further action” by the IRB Executive Committee.

However, a formal written response signed by the Principal Investigator is required if the audited protocol requires a corrective action plan or clarification by the IRB Executive Committee.

The IRB Executive Committee Chair has the opportunity at this point to take immediate action, including suspension of the protocol and/or recommendation of closure to the IRB, if deemed necessary.  Immediate action by the Chief/Executive Director and notification of the Institutional Official would take place in the event of suspected subject safety risks, possible research misconduct, or an extremely deficient audit.