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