What is the purpose of the Office of Human Research Protection (OHRP) audit program? 

The purpose of the Office of Human Research Protection (OHRP) Auditing and Compliance (A&C) program is to improve the quality of the human research subjects’ protections program.  The program strives to increase the awareness of regulatory compliance and improve the ethical conduct of research. 

An institution that holds an approved Department of Health and Human Services (DHHS) Office for Human Research Protections Federal Wide Assurance (FWA) is required to assure it has procedures that “include formal mechanisms for monitoring compliance with human research subject protection requirements”.  Research audit programs provide one mechanism for ensuring compliance with this requirement.

The program is intended to be proactive, non-punitive, and focused on educating investigators and research staff about their ethical and regulatory responsibilities in the conduct of research. 

In summary, the auditing and compliance program is used to:

• Determine that the rights and safety of subjects participating in clinical studies are properly protected
• Determine adherence to Federal Regulations and Good Clinical Practice Guidelines
• Determine adherence to the Human Assurance Committee (HAC) Policies and Procedures, Chesapeake Research Review, Inc. (CRRI) and the institutional policies and procedures of MCG and MCG Health Inc.
• Determine educational and training needs of research professionals

What is a Medical Record Audit?

The Office of Human Research Protection (OHRP) conducts random audits of research subjects’ medical records on a periodic basis to obtain a sampling of the quality of research compliance.  It is not a complete audit of the study itself, but another key component of our institution’s program for the protection of human research subjects. 

Any subject participating in a HAC or Chesapeake Research Review, Inc. (CRRI) approved clinical trial conducted at the Medical College of Georgia Health Inc., may be randomly selected by the Investigational Pharmacist for audit. 

The MCG Health Inc., (MCGHI) Investigational Pharmacist will randomly select medical records of research subjects enrolled in studies approved by HAC or CRRI for a medical record audit.

The audit is conducted by the Clinical Trials Auditors or the Director or Assistant Director of the Office of Human Research Protection. Compliance with the policies and procedures of  Medical College of Georgia and Medical College of Georgia Health Inc., HAC, Chesapeake Research Review, Inc. (CRRI), The Joint Commission on Accreditation of Healthcare Organizations, Food and Drug Administration (FDA) and DHHS Office for Human Research Protections Regulations (OHRP) and International Conference on Harmonization (ICH)  Good Clinical Practices (GCP) Guidelines are assessed using the following criteria: 

1. Study Alert located in the medical record (available at http://hi.mcg.edu/aboutus/policies/PDFPolicies/16_51.pdf) per MCGHI Policy I.6.0
2. Signed copy of the Informed Consent and/ or Children’s Assent Document located in the subject’s medical record per current OHRP SOPs and MCGHI Policy No. I.6.0 (available at http://www.hi.mcg.edu/hcapp/i60.htm) and FDA GCP guidelines.
3. Documentation of subject’s voluntary participation in the progress notes prior to the initiation of any study specific procedures OHRP SOPs per current OHRP SOPs  and FDA GCP guidelines.
4. Documentation of study visits reported as such in the progress reports per current OHRP SOPs and FDA/GCP guidelines.
5. Documentation of subject’s continuing Informed Consent at each and every study visit as per current OHRP SOPs and FDA GCP guidelines.

After the audit, a report is issued to the investigator and study coordinator.  The report is distributed via email and will list both positive findings as well as areas that may need improvement.  The investigator may be requested to provide clarifications in writing to any questions raised and develop a plan of corrective actions to eliminate future recurrences. The report is not intended to be punitive but educational in nature.
 

What is a Study Alert? 

The Study Alert is a required document (per MCGHI Policy I.6.0 http://hi.mcg.edu/hcapp/i60.htm) in the medical record of all research subjects who fit any or all of the following criteria:

• The subject is receiving study drug
• The subject is involved in the use of an investigational medical device
• The subject has more than one study visit or is hospitalized as part of the study
• The subject is a patient of MCGHI

The Study Alert immediately identifies the patient as a research subject and informs medical personnel reviewing the record of this status and the appropriate contact persons.

The form can be obtained at http://hi.mcg.edu/hcapp/pdf/i60a.pdf.
 

What is a “For Cause” audit? 

A For Cause Audit is an in-depth examination of all components of a research study including, but not limited to all records and documents, observations of processes, and interviews with investigators, research staff members, and participants for the purpose of determining if the rights and welfare of participants are being upheld according to federal regulatory , IRB and institutional requirements.

For cause audits are conducted in response to: 

	Requests from the Institutional Review Board (IRB)
	Subject complaints – this may include family members or legally authorized representatives (LAR’s)
	Sponsor complaints
	Requests from institutional officials or other institutional contacts
	Requests/concerns from government agencies (e.g., FDA, NIH, DHHS OHRP

What is a “Random” audit?

Random audits are also referred as study-oriented and are conducted:

• routinely as a part of the Human Research Protection Program (HRPP) 
• to maintain consistency and evaluate reports submitted as part of the IRB and other institutional processes

How are protocols randomly selected for an audit?

Protocols are randomly selected for an audit by performing a query of the IRB database.  Fields included in the query are:

• Source of funding
• Level of review
• Number of subjects enrolled to date
• IRB  file number    
   

What is a “Rotational” Audit?

This type of audit is ususally conducted every 4-6 weeks for each division of Oncology (Adult, Pediatric, Women’s Health, and Prevention).  Oncology studies are selected randomly by a query of the IRB database.
 

What studies can be audited?

All studies reviewed and approved by the IRB can be audited.
 

What information is reviewed during an audit?

• The informed consent document (ICD) and/or children’s assent document (CAD)
• Adherence to the inclusion/exclusion criteria
• Adherence to study procedures
• Occurrence and reporting of adverse events and protocol deviations/violations
• The regulatory binder and affiliated study correspondence
• Financial documents (if applicable)
• All Sponsor/CRO correspondence (if applicable)
• Drug and device accountability (if applicable)
• IND safety reports (if applicable)
• Medical record (if applicable)
• Research record
• HIPAA

What should I do if I identify problems when preparing for the audit?

If any errors or omissions are identified while preparing for the audit, please contact OHRP for guidance at x11478 and document the occurrence of the event by placing a signed and dated note to file in the appropriate research file or binder.  A report describing this event should also be submitted to the IRB along with a plan of corrective actions that will be taken to eliminate future occurrences.
 

Do I need to be present during the entire audit?

No, you do not need to be present during the entire audit. However, the research team may be asked to be available or to check in periodically to answer any questions that may arise.
 

How long will the audit take? 

The length of time an audit takes will depend on several factors:

• The complexity of the study
• The number of subjects enrolled and the number selected for audit
• Length of time the study has been active
• Organization of the regulatory files and study charts
• Site preparation for the audit
• Study subject

How many research records are audited?

If there are less than 10 subjects enrolled, all 10 will be audited.  If greater than 100 subjects are enrolled, approximately 5-10% will be audited.

Prior to conducting the audit, the research team will be asked to provide a list of the study subjects (study or IDs only) along with their date of study enrollment.  From this list, a random selection of subjects is made and the research team will be informed in advance of what records will be audited. 
 

What materials should I have available for the audit?

The following information should be available for the audit: 

• Signed and dated Informed Consent Documents (ICD) and/or Children’s Assent Documents for all subjects enrolled in study regardless of their current status
• The subjects research records, medical records (if applicable), and shadow charts
• Source documentation, case report forms, and any data capture forms
• The regulatory binder including protocol, amendments and general correspondence
• Financial documents, budgets, and contracts

What is a regulatory binder?

A regulatory binders contains the essential documents for the conduct of a study.  These documents exhibit the compliance the compliance of the institution, investigators, sponsors, and monitors with regulatory requirements.  All investigators are expected to maintain regulatory binders that contain all vital study documentation. 
 

What are the most frequently identified issues found during an audit? 

• Disorganized and/or incomplete study records and regulatory files
• Informed Consent Document (ICD) not signed and dated by the IRB approved investigator
• ICD not signed and dated by a witness
• Utilization of an outdated ICD
• Subject did not initial all pages of the ICD to verify the entire document was read by the subject
• Poor, or no, documentation of the informed consent process and/or continuing informed consent process
• Curriculum Vitae of research team members not filed in regulatory documents
• Medical licenses of licensed research team members not filed in regulatory documents
• Study Alert not placed in subject’(s) medical record where applicable
• IRB Membership Rosters not kept current or not on file in regulatory documents
• Individuals not approved by the IRB obtained informed consent and/ or conducted research related activities
• The investigator deviated from the protocol without obtaining permission from the HAC or CRRI
• Education and/or training not current

What are the most serious issues found during an audit? 

• Lost or missing informed consent documents
• ICD signed after the implementation of research procedures
• ICD utilized without the IRB approved stamp
• ICD not signed by subject
• Modification of the ICD, i.e. a change made to the document by the investigator without the approval of the IRB
• Child assent not obtained, i.e. child did not sign a child assent document
• Failure to report adverse events and protocol deviation/ violations
• Failure to follow the protocol

Who receives the audit report?

The audit report is provided to the principal investigator (PI), the study coordinator (SC), the PI's department/division chair, the Vice President of Research, Associate Vice President for Clinical Research (if School of Medicine), the HAC Chairman or CRRI representative.  If the PI is a department chair, the audit findings will be sent to the Dean of the School. 

The report will list both positive findings as well as areas that may need improvement.  The investigator may be requested to provide clarifications in writing to any questions raised and to develop a plan of corrective actions to eliminate future reoccurrences of the problem.

In cases where major deficiencies are identified, a meeting with the Principal Investigator, the study coordinator, the HAC Chairman or CRRI contact, the OHRP Director, and the Clinical Trials Auditor (CTA), will be called.  At the meeting, the PI and SC will be given an opportunity to clarify discrepancies and deficiencies.
 

What is research non-compliance?

Research non-compliance is any action or activity associated with the conduct or oversight of research involving human subjects that fails to comply with federal or state regulations or institutional policies governing such research.  Noncompliance actions may range from minor to serious, be unintentional or willful, and may occur only once or several times. The degree of noncompliance is evaluated on a case by case basis and will take into account such considerations as to what degree subjects were harmed or placed at an increased risk of harm and willfulness of the noncompliance.  Please see Rules and Procedures for Responding to Allegations of Research Misconduct.
 

How is research non-compliance addressed?

Research noncompliance may result in the following, which could include, but is not limited to:

• Clinical trial suspension until all areas of noncompliance are addressed
• Data generated by the clinical trial may be determined ineligible for use
• Clinical trial termination
• Referral to the Scientific Misconduct Committee
• Food and Drug Administration (FDA) notification
• Notification of the VHA
• DHHS Office for Human Research Protections (OHRP) notification
• The site will be required to develop study-specific Standard Operating Procedures, and site-specific Standard Operating Procedures.
• Studies being conducted at the site will be audited again for future compliance and to help identify and correct any other problems.
• The site staff will be required to complete additional clinical research training and courses.  The site will be required to notify the Office of Human Research Protection (OHRP) upon successful completion of additional training.
• The site staff will be required to develop and maintain a training file to document completion of any additional clinical research training. 

How can I report research noncompliance?

Please contact the Office of Human Research Protection (OHRP) at ohrp@mcg.edu or 706.721.1478.