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Site Monitoring Reports

It’s More than the Follow-up Letter!

Initially Presented at ACRP Meeting 2008 by

• Andrea Favalora, Director-Research Development, Benchmark Research

• Kathy Dickinson, Clinical Research Manager, Neurotech

• Alicia Pouncey, Managing Director, Aureus Research

• We’ll discuss lots of scenarios… and may not always see “eye to eye”…

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Did You Know…There Were Two Items Generated by the Monitor/CRA after Routine Monitoring Visits?

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Sponsor/Monitor/CRO InspectionsCommon Deficiencies

0%

5%

10%

15%

20%

25%Failure to adequatelymonitor study

Failure to documentmonitoring visits

Failure to have orfollow SOPs

Failure to maintaindrug acct. records

Failure to selectqualified monitors

Failure to assure IRBapproval of study

23%21%

18%

15%13%

10%

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Remember, Sponsors are“Responsible”for Monitoring

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What about ICH?

• ICH 5.18 Purpose of Monitoring

• Ensure the rights of subjects are protected

• Ensure accurate and verifiable data

• Ensure trial conduct is compliant

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The Only ICH-Statement About Site Monitor-Visit Reports

ICH Guidelines, E6

Current Practices in Documenting Site Monitoring Visits

• Report written by monitor post-visit, submitted to Sponsor/CRO

• Correspondence (Letter) to Investigator

• Electronic clinical trial management systems

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Items Often Tracked or Reported by Sponsors…

• “Visit Demography”– Who, what, when,

• Enrollment and subject-progress

• Regulatory items• Supply/equipment issues• Drug/device accountability

• Subject-specific info• Protocol compliance

• Screening activities• Staff changes or availability• Protocol clarifications

• SAEs Reporting• Data entry progress

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“Accuracy of Monitoring Reports”from FDA Warning Letter to a Sponsor…

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Where Monitors Spend Time…

• More time in reviewing paperthan communicating with site staff

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101520253035404550

% Time on Task

Source DocumentVerificationRegulatory BinderReviewCommunication w/CRCCRF ConsistencyCheckDrug Accountability

Communication w/PI

C. Breslauer, 2006. Monitor Survey: Utilization of Time While on Site n=21

The Site’s Perspective

Do We Know the Difference between the Follow-Up Letter and Monitoring Report?

Friendly chat or routine monitoring visit???

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Follow-Up Letters: Some Actual Site Experiences

1. Letter Written that PI not available Site: Monitor was in a hurry and could not meet with the doctor. Amendment to Follow-up Letter Requested.

2. Letter states that the records were not complete d for monitoring visitSite: The monitor had cancelled the visit and was not at the site at all, yet, still sent a Follow-up Letter. Amendment to Letter Requested

3. Letter notes drug accountability not performed Site: Drug was in research unit and monitor was working in administrative office and chose not to do accountability. Letter noted that the CRC did not want the monitor to do drug accountability. Amendment to Letter Requested.

Summarizing “Quotes” from SitesRegarding CRA Follow-up Letters…• “Mixed Feelings”

• “If it does not contain the same information as the Monitoring Report, is it really helpful or honest?”

• “Follow-up Letter just Created from a template”

• “Some FU Letters contain a list of matters that could have easily been addressed or explained at the time of the visit”

• “Some information just never happened”

The Sponsor Perspective…

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From the Perspective of a Sponsor

1. Monitoring reports are a critical tool2. Report should provide a clear impression

of the site3. The Follow-Up Letter is confirmatory4. Both items are read and filed5. Information is very, very “Time sensitive”

From the Perspective of a Sponsor

From the Perspective of a Sponsor

*RMV Reports provide:

1.Update on enrollment, staffing2.ICF’s, AE’s, ConMeds3.Accounting of Regulatory Status

4.Is the site following protocol?5.Have deviations occurred? If so, documented?

Trends, corrective action?

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An Example of a Poorly Written Report...and Suspect for Inadequate Monitoring

Monitoring Visit Report: Regulatory Binder Reviewed at this visit Yes X No X

Follow-up letter: “… The Regulatory Documents Binder was reviewed at this visit. Please ensure that the following items, noted at this visit, are completed and available….”

Page 2 of Monitoring Visit Report:

Yes No NA Have Study Staff changes occurred since the last visit? (If X □ □ Yes, list staff changes in comments section below)

Page 3 of Monitoring Visit Report:

Comments:“No study staff changes have occurred since last monitor visit”

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1. “Cut-and-Paste” from report to report is an obvious issue

2. Report sometimes says as much about the monitor as about the site

3. Sites are at a disadvantage since you never “see” the report

From the Perspective of a Sponsor – Case Study

Monitoring Visit Report :(Two page narrative of conversation held with PI as documented in report)“… monitor discussed the issue of [certified study equipment] being removed on

[date] … monitor asked [PI] if he could appeal keeping [equipment] as [sponsor] does not want any changes in the [equipment used to collect primary outcomes data]…[PI] states it is out of his hands and will not get involved as it has nothing to do with him and there is nothing he can do … He states he is a separate entity from the main research group and has no say as to when machines come in”

Follow-Up Letter:[Not mentioned]

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Monitoring Visit Report (October):(Two page narrative of conversation held with PI)

“… subject had an SAE … [2 months ago] which has still not been reported. [PI] did not see the relevance of reporting this because it has nothing to do with the study. I informed him that this again is the definition of an SAE, especially if the patient was hospitalized, and it needs to be within 24 hours as this is way overdue. I told him again this is patient safety, anything that happens to any subject while they are in the study is relevant… Per [SC] I told her she needs to report this immediately, any information that she can. She has not been able to reach the subject…”

“The Report’s” Follow-Up Letter (December):“Please be sure to report the SAE … that occurred [*2 months ago] to the IRB as well as [CRO] as soon as possible. Please be sure to obtain hospital records as well.”

(which was actually 4 months, as of the time of the follow-up letter)

• CRC/Investigator and CRA: allow time to “debrief” prior to end of monitoring visit; if no time “at end”, ensure a short t-conference scheduled within 1 week of visit

• Goal of both the Monitoring Visit Report and the Follow-Up Letter should be effective, complete and accurate communication

– If inaccurate, sites should request corrections to the follow-up letter OR– Respond in writing to Sponsor/CRO, with copy to IRB if applicable

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So How Can We Improve?

Each has a responsibility…

• Sponsors/CRO Directors and Managers

• CRC/Site Managers

• CRA

• Investigator

• Auditors and Regulatory agencies

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MONITORING REPORTS

• Should Be:– To provide summary-level data of observations made

– Reports should contain (per ICH Guidelines):• Proper identifiers• Summary of what was reviewed• Monitoring statement of findings/facts, deviations,

deficiencies• Action taken or to be taken to secure compliance

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AnInformative Follow-up Letter

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Communicating Corrective Action…

What Else Can We Do?

Be Proactive• Coordinators, Site Managers, and Investigators should meet

with CRAs to find out if there were any significant issues

• Ensure site personnel and monitors are available to discuss problems

– Matters could easily be addressed and some written-issues avoided

• Sites need to consider use of a “Site Monitor Checkout Form”

• Look at CRCs, CRAs, CROs, Sponsors as “team players” – Focus on outcomes of a successful study

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More About the “Visit Check Out” Form

• Some Sites Use a Check Out form routinely– Lists issues identified during visit; encourages immediate-

discussion and potential resolution– Site personnel and monitor sign/date the document.

• Monitor and Investigator/CRC discuss items of concern to clear up any matters before the end of the visit

More About the “Visit Check Out” Form

• Later compare Form to Follow-up letter

• Consider including an area to provide “feedback to the monitor”– E.g., requests monitor schedule 3-day visits (vs. 2) to ensure all

areas are addressed

Summary• Visit reports and follow-up letters are primary

methods for documenting the details of site monitoring visits

• All of us have responsibility in ensuring accuracy and follow-up

• Prompt-feedback (check-out form) may be immediate method to improve this process