remote monitoring - nchicacentralized/remote monitoring •with transition to electronic health...

Remote Monitoring

NCHICA AMC Conference

June 27, 2016

Clinical Trial Monitoring

• Sponsors are required to provide oversight of studies to ensure adequate protection of rights, welfare, and safety of human subjects AND the qualify of the clinical trial data submitted to the FDA

• Oversight provided through monitoring of study – Opportunity to identify and correct potential problems

• The way a sponsor monitors a study is not specified in the regulations – Approach may vary by type of study, resources

available, physical location, etc.

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM269919.pdf

Traditional Monitoring

• Reviewing paper-based or electronic records

• On-site

• Frequent visits by sponsors every several weeks

Centralized/Remote Monitoring

• With transition to electronic health records and other electronic data capture methods, there is expanded monitoring capabilities

• Centralized/remote monitoring – Ability to review data off-site – Missing or insufficient data as well as

outliers can be more readily identified through electronic means and statistical models

– Potential cost savings by not having to monitor on-site as frequently

Privacy Officer Stages of Acceptance Stage 1

Remote Monitoring: Site Perspective

• Pre-Epic implementation:

– On-site only

– Date-limited access to eBrowser (EHR) for selected participants


• Post-Epic implementation on-site process

– Period of using Release to Inspector (static PDF report)

– Currently using Duke MedLink (Epic CareLink)

– Electronic access (monitor provided unique login)

– Access must be requested at least 10 days prior to visit

• Requested by coordinator via REDCap survey

• System automatically sends notifications and required confidentiality agreement

– Monitor must sign separate confidentiality agreement

– No ability to restrict date range (may not be necessary for many studies)


• Post-Epic implementation remote process – Using Duke MedLink (Epic CareLink) – Sponsors must sign study-specific Access

Agreement. Includes: • Access terms and conditions • Background check form to be completed by monitor

annually • Confidentiality agreement • Contact information of sponsor’s privacy officer

– Access agreement is non-negotiable (has prevented some sponsors from accepting)

– Provide log-in and password to monitor and have “live check-in” via WebEx when monitoring is to begin to verify identity


REDCap Access Request

Duke MedLink

Challenges to Remote Monitoring • Security implications

– Where will they be monitoring? Office? Home? Starbucks? – Less accountability than on-location where coordinator is

within eyesight • Reporting/Audit implications

– How will we audit? How frequently? Which group (Health System or School)?

– If monitor intentionally accesses information that he/she shouldn’t, what are the implications for future remote monitoring for that sponsor?

• Burden/Cost shifting – Depending on processes put in place and sponsor

requirements, may require additional work from site’s coordinators

– Will need to recover these costs in budget negotiated with sponsor

University of North Carolina

• Site perspective

• UNC and UNC Health Care two separate entities

• Both entities take patient privacy very seriously



• Pre-Epic implementation:

– On-site only

– If given access to WebCis, the reviewer was not limited to selected research subjects

– Monitor sometimes “looked over the shoulder”

– Printed paper records


• Printing records

– Certification of the printed record

– Monitor request

– Coordinator preference

– How would the sponsor know if something was left out?


• Post-Epic implementation on-site process

– Strongly discourage printing of the medical record

– Electronic access (monitor provided unique login)

– Access must be requested at least 5 days prior to visit

– Monitor must sign separate confidentiality agreement

– Can only access from on-site computers

– Access restricted to only those subjects on the IRB approved study

– “Clean-up” required after the monitor leaves


• We do not allow remote access to Epic records for study monitors

• We discourage the printing of the medical record, but…

• Many print and scan or fax applicable parts of the medical record to the CRO or sponsor

Using Electronic Health Records in Clinical Investigations:

A Sponsor’s Perspective

20

Sandra SAM Sather, MS, BSN, CCRA, CCRC

Clinical Pathways, LLC

[email protected]

mailto:[email protected]

Sponsors Worry About

• Data Integrity

• Data Access

• Missed Eligibility and AEs (and more)

• Not having access to same info as the FDA

• Audit Risk, incomplete and inaccurate data

What should the sponsor do when working with a site that does not allow access to original source documents found within a subject’s EHR?

A. Predicate Rules: -Is this noncompliance to FDA CFR?

B. Pre-study Assessments Documentation: -Was there clear expectations established prior to accepting the site? -Was there adequate training for sites and monitors on the requirements?

C. Enforceable Agreements: -What are the enforceable agreements that support access to the pertinent source within the subject’s EMR?

D. Risk Analysis and Action Plan: -What are the threats related to restricted access to source? -How will the sponsor manage the risk?

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FAQ #1


A. Predicate Rules: Is this noncompliance?

• Be sure the sponsor and regulators have access to things that support the investigator’s regulatory requirements.

• Define what is pertinent and identify anywhere this will be located, even if duplicated.

Good Documentation Practices: DO NOT document something twice. • Increased risk of not agreeing • If these are pertinent source, BOTH should be maintained as

part of case histories by the investigator, AND if reviewed, disclosed to monitors and auditors.

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FAQ #1 A

A. Predicate Rules: Is this noncompliance? [cont.] • What are the requirements of the FDA fields investigators

related to source documentation enforcement at sites?

• What would the FDA have access to during a site inspection?

Supporting Source Data Categories (reference: 2010 FDA Information Sheet: Inspections of Clinical Investigators)

• Predated information • For this study what would be pertinent source that is

prior to ICF? How will the sponsor monitors and / or auditors access the data?

• During the study • Study Specific Procedure Documentation and where

will this be documented? • Non-study related (e.g., between study visits

treatments)

• Post-study participation data 24

FAQ #1

A. Predicate Rules [cont.] • 21 CFR 312.62(b) Case Histories

Investigator required to prepare and maintain adequate and accurate case histories

Record all observations and other data pertinent to the investigation on each individual . . .

Include case report forms and supporting data including, • signed and dated consent forms and medical records

including, for example, o progress notes of the physician, the individual's

hospital chart(s), and the nurses' notes. [*No matter the type of source (e.g., electronic or paper)]

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FAQ #1

A. Predicate Rules [cont.]

• 21 CFR 812.140(a) Investigator Records

Maintain the following accurate, complete, and current records relating to the investigator's participation in an investigation:

(3) Records of each subject's case history and exposure to the device.

• Include the case report forms and supporting data including,

o for example, signed and dated consent forms and medical records including: progress notes of the physician, the individual's hospital chart(s), and the nurses' notes.

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FAQ #1

A. Predicate Rules: ICF and case histories [cont.]

• 21 CFR 50.20 General requirements for informed consent – …investigator has obtained the legally effective informed consent of

the subject or the subject's …representative. –…under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence.

• 21 CFR 312.62(b) Investigator recordkeeping and record retention

–The case history for each individual shall document that informed consent was obtained prior to participation in the study.

• 21 CFR 812.140(a)Investigator Records

–The case history for each individual shall document that informed consent was obtained prior to participation in the study.

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FAQ #1

A. Predicate Rules [cont.]

– Guidance Documents

– Topics:

• CRF Source Document Verification

• Availability of Trial Related Materials

• Access to Source

• Verifying Source Data

• Monitor AEs Recorded

• Maintenance of Essential Documents 28

FAQ #1


B. Pre-study Assessments Documentation: set expectation, assess capabilities, develop action plan.

• Qualification visit – Identify where pertinent source generation – Identify how the pertinent source will be monitored/audited – Assess quality systems (e.g., SOPs) – Post related action items – Document

• Monitoring Plan – requirements and clear expectations for monitoring and disclose

pertinent info to sites

• SIV reinforcement training – Verify if plan still adequate – Document

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FAQ #1 B


C. Enforceable Agreements

– Protocol

– Clinical Trial Agreement (CTA)

– Regulations (investigator obligations) – Part 11? 2013 eSource Guidance – no But yes to ALCOA

– Refer to tool

– Others?

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FAQ #1 C


D. Risk Analysis and Action Plan

– Threats (HSP, DI)

– Vulnerability

– Likelihood to occur

– Impact if were to occur

– Mitigate by acting vs. avoiding, transfer, accept

– Action plan

• May affect the monitoring plan for one or multiple sites

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FAQ #1 D


A. Predicate Rules: ✔ – Is this noncompliance to FDA CFR?

B. Pre-study Assessments Documentation: ✔ – Was there clear expectations established prior to accepting the site? Was

there adequate training for sites and monitors on the requirements?

C. Enforceable Agreements: ✔ – What are the enforceable agreements that support access to the

pertinent source within the subject’s EMR?

D. Risk Analysis and Action Plan: ✔ – What are the threats related to restricted access to source? How will the

sponsor manage the risk? 32

Review for FAQ #1

How do we apply ALCOA to electronic source data and supporting source? How is ALCOA supported differently for paper and electronic source?

2008 FDA CPGM Clinical Investigator, Part III

• “. . . an important principle to understand when evaluating clinical research data is that the regulatory requirements for the clinical data do not change whether clinical data are captured on paper, electronically, or using a hybrid approach.

• Data must be reliable and usable for evaluating the safety and/or effectiveness of FDA-regulated products.” [ALCOA]

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FAQ #2

2007 Final Guidance Computerized Systems Used in Clinical Investigations

• Source data and source documentation must meet certain fundamental elements of data quality that are expected of paper records:

– attributable = distinguishable – legible – contemporaneous – original – Accurate

• FDA's acceptance of data depends on FDA's ability to verify the quality and integrity of the data during FDA onsite inspections and audits.

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FAQ #2

35

Paper Source vs. EMR: • Requirements and expectations of paper records will

usually also apply to electronic records, but may be implemented differently.

• CRFs as original Data • Promoted within RBM and draft e-Source guidance • ICH, ISO, CPGMs

2007 Final Guidance Computerized Systems Used in Clinical Investigations

FAQ #2

36

ALCOA Standard

Paper

EMR

A: Attributable

Can link the data or supporting source with unique subject and the author. Paper record with delegation log, and subject other subject source. Predated, during, post pertinent information

Same. Common to have a combination of paper and electronic records.

L: Legible

Can you read the handwriting of the author / subject?

Is the information encrypted and if so can you read on the screen and does the data print legibly and does it support attributable-ness?

C: Contemporan-eous

Things are written at the time they occur. If the records are converted from paper to electronic, does it support attributable and Does the system date-time-stamp; audit trail to be sure can verify timing to support predicate rule and also protocol compliance.

O: Original

Pertinent info is documented first. If copied and supplied as source, confirmation that exact copy with all the same attributes as the original. Some call this “certification” process. Not the same as a “shadow file”, unless specified differently = unverified. If something is located in a medical chart and the sight also writes it in a study source document, both are source. Duplication of documentation is not a good practice.

Same as paper, but pertinent info may be documented first in an electronic record, (EMR or eSource for the study). If printouts are supplied by the site, these are like shadow files and need to be confirmed as a copy with all the same attributes as the original.

A: Accurate

Source should accurately support the CRFs, and various source should not contradict one another.

Same. Also, some EMRs are prepopulated with past information or demographics about the subject. Caution, some records prepopulate past vital signs and other info that may not be contemporaneous and conflict with other data.

How do we apply ALCOA to electronic source data and supporting source? How is ALCOA supported differently for paper and electronic source?

• Questions?

• Discussion

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Review for FAQ #2

What are acceptable methods of monitoring pertinent source at a site where there is an EMR that contains pertinent source?

• FDA does require sponsors to adequately monitor.

– Per enforceable standards (e.g., SOPs, MP). – RBM encourages focus on critical study parameters. – Electronic ICF?

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FAQ #3

#1. Directly Monitor the Original Pertinent Data in the EMR • Site provides the monitor with a temporary User Name & Password • Authority & Access are limited

– Read only – Only certain subjects, not access to all patients – Audit trail intact – Remote Access (PDFs, remote sign-in?)

#2. Certified Copy provided to the Monitor • Site should have SOPs for certified copies and documented training for those

that perform the activity. • How to deal with certified copies of EMR that have electronic signatures? • ALCOA

#3. Monitor a Copy Generated from a Report From the EMR • EMR may be able to print a date/time stamped report per patient. • Documentation in MVR and f/U letter.

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Monitoring EMRs FAQ #3

#4. Monitor certain data 100% from original by sitting with the Coordinator

• Critical Study Parameters

• Ensuring proper AE reporting

– Challenges of AE SDV with this method

#5. Monitor a %’age of subjects or data or sites

• Based on rationale from risk analysis and supported in monitoring plan

Not Monitor a shadow copy / printed, unverified, copy of EMR

• Are you following the requirements?

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Monitoring EMRs FAQ #3

-What are conditions where the monitor can directly access and monitor a subject’s supporting source data within a site EMR? -What are acceptable methods of monitoring pertinent source at a site where there is an EMR that contains pertinent source?

• Questions?

• Discussion

41

Review for FAQ

What are the implications of the FDA draft guidance related to Use of EHRs in Clinical Trials?

• Purpose

• Scope

• Interchangeability

• ALCOA

• Informed Consent

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FAQ #4

What are the implications of the FDA draft guidance related to Use of EHRs in Clinical Trials?

• Questions?

• Discussion?

43

FAQ #4

Thank you!

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Sandra SAM Sather, MS, BSN, CCRA, CCRC

Clinical Pathways, LLC

[email protected]

mailto:[email protected]