The team, the procedures, the monitor

and the Sponsor

Lucy H H Parker
Clinical Research Governance Manager

Joint Research & Enterprise Office Training

 The Team

CI and PIs Research Pharmacy

Monitor Archivist
Regulatory Assurance Manager Finance
Stats. Support Departments
?RN/CTA/DM IT - eCRF

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 How are the studies set up?

Lots of meetings!

Site selection

Risk Assessment (26 point risk assessment)

Major issues identified and minimised

Monitoring plan – agreed with all parties even if external monitor

Standard RG processes – initiation, routine, close out

Safety reporting

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 Sponsor

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 Sponsor

• Sponsor takes on overall responsibility for initiation, management and/or

financing of study
• All clinical trials must have a designated sponsor
– Must be named in the protocol
• Not necessarily the funder
– Typically CI employer
• Can delegate responsibilities to investigators

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 Sponsor Responsibilities

• Confirmation of Review by REC

• Quality Assurance (audits)
• Information on IMP
• Quality Control (monitoring)
• Manufacturing, Packaging, Labelling, and Coding
• Contracts & Agreements of IMP
• Medical Expertise • Supplying and Handling of IMP
• Trial Design • Record Access
• Trial Management, Data Handling, and Record • Safety Information
Keeping
• Safety Reporting
• Investigator Selection
• Non-compliance
• Allocation of Responsibilities
• Premature Termination or Suspension of a Trial
• Compensation to Subjects and Investigators
• Clinical Trial/Study Reports
• Financing
• Multi-centre Trials
• Submission to Regulatory Authorities
ICH GCP Section 5

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 Quality Assurance (QA) versus Quality Control (QC)

• QC = Quality Control = monitoring

– Member of trial team
– Ongoing

• QA = Quality Assurance = auditing

– Independent
– Planned and systematic

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 Monitoring

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 What is monitoring?

“The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted,
recorded, and reported in accordance with the protocol, SOPs, GCP, and any regulatory
requirements”

ICH GCP Section 5.18

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 Purpose of Monitoring?

• Protection of rights and wellbeing of human participants

– Ensure consent in place for record access

• Trial data are accurate, complete and verifiable from source documents

• Conduct of trial is in compliance with the currently approved protocol, GCP, and all
applicable regulatory requirements

ICH GCP Section 5.18.1

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 Qualities of a Good Monitor?

• Appropriately trained
• Adequate scientific and/or clinical knowledge
– Documented with training logs and CVs
• Thoroughly familiar with:
– IMP
– Protocol
– Consent form
– Sponsor & trial SOPs
– GCP
• Knowledge of local laws, regulations, customs & local language

ICH GCP Section 5.18.2

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 Extent and Nature of monitoring

• Monitoring should be proportionate to:

– Objective
– Purpose
– Design
– Blinding
– Size and complexity
– Outcome measures
– Risks
ICH GCP Section 5.18.3

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 Types Of Monitoring (1)

• Coordinating centre / day-to-day monitoring

– Data collected are consistent with protocol
– CRFs are being completed by authorised staff
– No key data is missing
– Data appears to be valid
– Review of recruitment rate, withdrawals and losses to f/up

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 Types Of Monitoring (2)

• Central monitoring
– Determination of key eligibility criteria through collection of:
• Consent forms (with agreement by participant)
• Scans
• Pathology reports
– Statistics
• Unusual patterns of data

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 Types Of Monitoring (3)

• On-site monitoring
– Staff training
– Access to necessary documents
– Confirm pharmacy and lab resources in place
• Count study drugs
– Adherence to protocol and GCP
– Check medical records
• Consent forms
• Eligibility
• SAEs, SADRs, SUSARs etc
– Source Data Verification (SDV)

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Data Management & Processing
Data entry Double data
checks entry
EDC system
OCR
CRF Completion Data Entry

Training Investigators Data cleaning &

Validation

Monitoring visits Post entry

& SDV checks

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 Common queries and checks

• Most common checks to identify discrepancies:

– Missing values
– Range checks, including lab values and normals
– Logical date sequence
– Header information consistent
– Missing visits or pages
– Visits in compliance with protocol
– Inclusion/exclusion criteria met
– Procedures performed in proper order
– Fraud

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 Post
Post Entry Checks 1. Data manager cleans & validates
database
8. Corrections entered in 2. Problems such as missing values or
database inconsistencies

No
7. Query forms with resolution sent
back to data manager
Yes
Data validated

6. Monitor checks query

3.Queries addressed to the PI via paper
resolutions
query forms

5. Query resolutions put on 4. PI resolves

query form queries

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 Ensuring the Quality of the Data

MONITORIN
G & AUDITS
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