Planning and Surviving An Audit/Monitoring visitCarmen B. Jacobs, BS, RN,OCN, CCRP
U.T. MD Anderson Cancer Center
Houston, Texas U.S.A
Objectives
• Sponsor’s role or responsibilities• Difference between monitoring and auditing• Preparing for monitor/audit visits• Consequences of an audit with poor results• Suggestions to prevent non-compliance
Sponsor’s Role
• According to 21CFR Part 312.50)– Select investigators and sites– Inform investigators of increased subject risk– Ensure proper monitoring– Ensure the investigation is conducted per the
protocol– Maintain and retain records– Ensure the return or disposition of unused
investigational drug supplies
Monitoring and Auditing
• Necessary to assure:
1. Rights and safety of patients are protected.
2. Reported trial data are accurate, complete, and verifiable from source documents.
3. Conduct of trial is in compliance with protocol, good clinical practice (GCP) and applicable regulatory requirements.
MONITORING
Monitoring
• Monitoring: act of overseeing the progress of a clinical trial, of ensuring that is conducted, recorded and reported in accordance with the protocol, standard operating procedures (SOPs), GCP, and all applicable regulatory requirements.
Data safety and monitoring plan DSMB/DSMC
• Visits are routine and expected. May be conducted by the sponsor or CRO.
• Key to success visit: Preparation and Planning
Preparation and Planning
General Considerations:Request medical records to be reviewed Inform pharmacy of visit and schedule appointmentCheck availability of PI, CTN, othersArrange for a quiet room
Preparing for a Regulatory Review
All protocol versions and approvals All Investigator Brochure versions Lab certifications and normal ranges All versions of Form 1572 CVs, licenses and Financial Disclosures for all investigators All IRB correspondence All Sponsor correspondence Signature and Delegation of Responsibilities Log
Preparing for a Source Document Review
Assure medical records contain (obtain missing information or document why unobtainable): All laboratory and radiology reports Progress notes (physician’s notes, nursing notes) All AEs reviewed and attribution assigned by the
investigator Drug compliance/administration notes including stop and
start times/dates Procedures documenting study parameters All original signed and dated consents Informed consent process documentation
Preparing for a Source Document Review
Make sure laboratory reports and procedure reports are reviewed and signed by PI (if required per sponsor SOP).
Review research/shadow chart to make sure that documents not allowed in the medical record (e.g., QOL survey, PK worksheets) are available.
Preparing for a Case Report Form (CRF) Review
Assure CRFs are complete, accurate, up to date. Focus on:
Adverse events Concomitant medications Study drug administration
Preparing for a Pharmacy/Drug Dispensing Review
Pharmacy or responsible individual should review drug dispensing records prior to visit to assure drug count is accurate
Will help if able to check the Drug Accountability Record Form (DARF) and actual drug count before visit
Inform PI of discrepancies
Common deficiencies found at a monitoring visit
Failure to follow the protocol Failure to keep adequate and accurate recordsProblems with the informed consent form Failure to report adverse events Failure to account for the disposition of study drugs Source document to support eligibility criteria is not
located Source documents are not signed/datedCorrections are not initialed /dated
Important factors to keep in mind If the Investigator fails to comply with the protocol, prompt
action is necessary to secure compliance. When attempts to reach compliance remain an issue, the
Sponsor may terminate the contractual agreement. Completion of CRFs and query resolution may be tied to
financial payment for the clinical trial Successful monitoring visit:
Adequate preparation Organization Staying on top of documentation, CRFs completion,
answering queries in a timely manner and documentation of circumstances for non-adherence to the protocol.
AUDITING
Auditing
• Auditing: systematic and independent examination of the trial related activities and documents to determine whether the evaluated trial related activities were conducted, the data recorded accurately, analyzed and appropriately reported, according to the protocol, sponsor’s SOPs, GCP, and all applicable regulatory requirements.
Audits may be conducted during or after a study is completed.
Audit Goals
Review, inspect and verify: The ethical conduct of human subject
research Integrity of previously reported data Adherence to the study protocol Applicable institutional, state and federal
regulations and guidance
Audit Types
Federal audits Sponsor
audits Cooperative
group audits Internal site
audits IRB audits
Routine For-cause
Audits
Routine inspections sites with high
subject enrollment
sites with data that significantly differs from others
representative “sample”
For-cause inspections issues with the
quality or/and integrity of the data
rights of subjects may have been infringed
“complaint” from someone
Opening Interview
Who should be present principal investigator
to determine his/her oversight of study activities
other individuals directly involved in the study to answer questions, especially if the P.I.
was not closely involved in study activities Others that the inspector may ask to speak to:
sub-investigators, study coordinators, pharmacist, lab personnel, regulatory personnel
Source Documents
Documents to be inspected should be: accurate up to date readily available organized
SHOULD BE ABLE TO RECONSTRUCT THE TRIAL
Most often reviewed informed consent forms documentation of the informed consent
process reported data adverse events regulatory records source documentation to ensure protocol
compliance drug shipping records drug dispensing records
Most often reviewed
Auditors may also request to review the site’s internal SOPs for conducting human subjects research, the research team credentials and documentation of training.
Answering the inspector questions
make sure you understand the question before responding, ask for clarification if necessary. answer honestly, succinctly. do not be evasive. do not interpret questions (i.e., “Do you
mean……?”). do not give false or misleading information. do not trust your memory. Refer to
documentation if necessary.
Exit meeting
• inspector will present the results of the inspection and discuss them with you.
Consequences of an audit with poor results
investigator may be prevented from conducting further studies.
investigator may be penalized in other ways. agency (i.e., FDA) may require the sponsor to
remove the data from the marketing application
Suggestions to prevent non-compliance
create standard operating procedures for the research being conducted at your site
document delegation of responsibilities develop plan for organizing records promptly report protocol violations to IRB and
sponsor work with monitors correct small problems before they grow
Ensure Quality Data
A Attributable - Is it obvious who wrote it?
L Legible - Can it be read?
C Contemporaneous - Is the information current and in the correct time frame?
O Original - Is it a copy? Has it been altered?
A Accurate - Are conflicting data recorded elsewhere?
Points to remember
Most importantly: preparation for an audit should begin before
the study starts organize create SOPs educate collect ensure quality data
“There is no wisdom equal to that which comes after the event.”- Geraldine Jewsbury