1. Preparing for and Handling Monitoring Visits and Audits
Subtitle: Why You Have to Tolerate Monitors
Shari Lawler, MSN, FNP

2. I have no real or apparent conflicts of interest to report.
Shari L. Lawler, MSN
I have no real or apparent conflicts of interest to report.

3. Disclosure
Presenter has no financial interest in anything except sheep and cattle.
Good Morning! I hope everyone is as well-caffeinated as I am this morning. I’d like to thank Dr. Ron Waksman for adding Research to CRT.
I work for the CRI as a Consultant CRA monitoring IIT. I’ve been a monitor for 12 years and prior to that I was a coordinator.

4. Key Point to Remember
Effectively communicating and working with the Monitor is one of the best ways to prepare your site for an FDA Audit.
If you remember nothing else I say, please remember this…effectively communicating and working with the Monitor is one of the best ways to prepare your site for an FDA audit. PIs and CRCs often dread monitoring visits which is counter-productive. View monitoring as a valuable extension of your research program. This is the person that is going to make sure you are audit

5. Purpose of Monitoring Visits
Protection of human subjects
Accuracy of data
Compliance with protocol, GCP, and FDA regulations
Verify that rights and well-being of subjects are protected
Verify that reported data are accurate, complete, and verifiable from source documents
Verify complain with approved protocol, CGP guidelines, and all applicable regulatory requirements

6. Administration to qualified subjects
CRA
Communication:
Data Center
Sponsor
Site
CRO
Verify Compliance:
Federal Regs
Protocol
GCPs
IP Accountability:
Storage
Administration to qualified subjects
Documentation of receipt, use, return
Disposition of unused drug or device
Source Documentation
PD/AE/SAE Reporting
Query Resolution
Verify Accuracy:
CRF/EDC

7. Types of Monitoring Visits
Pre-Study Site Visit
Site Initiation Visit
Interim Monitoring Visit
Close-Out Visit
We’ve talked about why the monitor comes to your site, now let’s talk about when they come.

8. Pre-Study Site Visit Monitor will visit the site to discuss:
Suitability of Investigator, Site & Staff
Regulatory requirements
Sponsor’s expectations
Not all studies require a PSSV. These are usually conducted by the Sponsor when choosing sites that they have not worked with in the past. Be realistic when making patient population claims and enrollment projections. You don’t want to take on a study you can’t enroll in.

9. Site Initiation Visit Monitor will: Review protocol Review regulatory
Review data submission
Perform IP inventory
Verify shipment of study supplies
Review PD/AE/SAE/UADE reporting
During the SIV the monitor will explain the study and what is required of you, the site. Take notes! This is your opportunity to ask lots of questions.
The monitor will: 1) review the protocol and study requirements – be familiar with the protocol so you can ask questions. 2) review regulatory binder 3) review data handling guidelines and source documentation requirements which means access to original medical records, not shadow charts 4) perform investigational product inventory – accountability for study drug or device 5) verify receipt of study supplies, if you haven’t received lab supplies or CRF binders, etc. – let the monitor know 6) review requirements for reporting adverse events, serious adverse events or unanticipated adverse device effects

10. Site Initiation Visit Cont’d
Discuss GCP, FDA regulations, and Sponsor requirements
Discuss study staff roles & responsibilities
Review CRF completion/EDC training
Discuss recruitment strategies & enrollment expectations
Review monitoring procedures
These are the activities that the monitor will perform during the SIV. Your role as the site is to have dedicated space available for the visit, make sure study staff are present for the protocol review, pre-arrange Pharmacy visit if they are responsible for the study drug. Be familiar with the protocol so that you can ask questions at the SIV.

11. Preparation for IMV
Clinical Research Coordinator (CRC) should arrange for:
Area for monitoring
Internet connection/telephone
Access to medical records/EMR
Time to meet with PI, Pharmacy, Regulatory Coordinator, etc.
Time for addressing issues/making corrections

12. Preparation for IMV Cont’d
Assure that documentation is available and up-to-date:
Drug or device accountability log
Subject screening/enrollment logs
Serious adverse event reporting
Protocol deviation reporting
Data entry completed prior to visit
Queries resolved
Regulatory binder current
These are the activities that the monitor will perform during the SIV. Your role as the site is to have dedicated space available for the visit, make sure study staff are present for the protocol review, pre-arrange Pharmacy visit if they are responsible for the study drug. Be familiar with the protocol so that you can ask questions at the SIV.

13. During the IMV PI available to discuss findings
CRC available to make corrections and address action items
Resolve as many outstanding action items during the visit as possible

14. Preparing for Audits
Who
What
AUDIT
When

15. Type of Audits Internal Audit Sponsor Audit Research Compliance Audit
Federal Agency Audit

16. An FDA Audit: What the Investigator Needs to Know
Notify the Sponsor, IRB, and study team of impending audit
Have available:
All study documents
Person knowledgeable about the study
A place to review records
Access to a photocopier

17. FDA Audit: What Is Reviewed
Administrative
Protocol/Informed consent forms
Amendments to protocol/consents
Drug/device accountability records
Sponsor/IRB correspondence
IRB Approvals/Progress reports/AE reports
1572/Investigator Agreement

18. FDA Audit: What Is Reviewed
Case Report Forms
How data is recorded/corrected
Compared to source documents
Supporting Files(Source Documentation)
Hospital Chart
Clinic Chart
Research Chart

19. FDA Audit: What Is Reviewed
Informed Consent Forms
Are all required elements included
Are additional elements relevant
Was it approved by the IRB
Were they signed and dated by subjects
Does FDA have current version

20. FDA Audit: What Is Inspected
Interview study staff
Test article storage area
Data Audit
Examine case report forms and compare with source documents
Compare sponsor tabulations with source documents and case report forms

21. FDA Audit: Critical Issues
Is study entry recorded?
Did subject meet inclusion/exclusion criteria?
Is IP administration documented?
Is there study raw data?
Did an IRB approve all significant stages?
Did each subject provide proper informed consent prior to study entry?

22. FDA Audit: Critical Issues
Were all screened subjects entered?
Does amount of test article used coincide with number of subjects treated?
Was test article properly disposed of?
Was blind maintained?
Was randomization scheme followed?

23. FDA Audit: Common Deficiencies
Protocol non-adherence
Failure to report concomitant therapy
Inadequate and inaccurate records
Failure to report adverse events
Inadequate drug or device accountability
IRB problems
Informed consent

24. FDA Audit: What Goes Wrong
Most commonly observed deficiencies in these areas include:
Failure to follow the protocol
Violation of inclusion/exclusion criteria
Failure to perform required tests
Failure to maintain adequate and accurate records
absence of supporting source documents
inaccurate or incomplete source documents

25. FDA Audit: Exit Interview
Discuss inspection findings
May issue an 483
Represents deviations from federal regulations for clinical investigators
Verbal response to 483

26. Tips for A Successful Study: Understand Responsibilities
Read the following before you sign-on
ICH GCP Consolidated Guideline
FDA GCP Regulations
FDA Information Sheets for IRB’s and Clinical Investigators:
21 CFR Part 312 / 21 CRF Part

27. Tips for a Successful Study: Enhancing Protocol Adherence
Fully understand protocol limits and the importance of strict compliance
Is there latitude with concomitant therapy?
Is it ok to skip procedures that are not medically necessary (lab tests, PEs, biopsies)?
Which protocol procedures can be performed by non-physician study support staff?

28. Tips for a Successful Study: Enhancing Record Quality
Clearly understand what records are to be maintained and how they should be completed
Original source data for critical study endpoints
Use your site’s indigenous record-keeping system to the maximum extent possible, discuss this with the sponsor up front

29. Tips for a Successful Study: Enhancing Record Quality
All records should meet the ALCOA test:
Attributable
Legible
Contemporaneous
Original
Accurate

30. Tips for a Successful Study: Enhancing Record Quality
Minimize the need for transcription
Don’t throw anything away especially originals
Expect the worst
FDA will be inspecting the records

31. Tips for A Successful Study: Communicate
With the IRB
Protocol changes
Continuing review
With sponsor and monitors
Openly address problems
With regulatory authorities
Understand expectations
Honor reporting obligations